SYNTHESIS and CHARACTERIZATION of NEW UNSYMMETRICAL DIGLYCOLAMIDES for TRIVALENT LANTHANIDE METAL EXTRACTION by BENJAMIN GEORGE

SYNTHESIS AND CHARACTERIZATION OF NEW UNSYMMETRICAL

DIGLYCOLAMIDES FOR TRIVALENT LANTHANIDE

METAL EXTRACTION

BENJAMIN GEORGE TOKHEIM

A dissertation submitted in partial fulfillment of the requirements for the degree of

DOCTOR OF PHILOSOPHY

WASHINGTON STATE UNIVERSITY Department of Chemistry

JULY 2016

To the Faculty of Washington State University:

The members of the Committee appointed to examine the dissertation of

BENJAMIN GEORGE TOKHEIM find it satisfactory and recommend that it be accepted.

______Kenneth L. Nash, Ph.D., Chair

______Robert C. Ronald, Ph.D.

______Scot E. Wherland, Ph.D.

______Mark P. Jensen, Ph.D.

ACKNOWLEDGEMENTS

I would like to thank my advisor, Ken Nash, for teaching me how to find patterns in the seemingly inexplicable and how to persevere through repeated failures.

I would like to thank my mentor, Rob Ronald, for imparting a portion of his vast wisdom to me and for showing me how to delight in everyday experiences.

I would like to thank my professor, Scot Wherland, for introducing me to the world of inorganic chemistry and for sharing his passion for teaching with me.

I would like to thank my undergraduate assistant, Shane Kelly, for helping with the difficult task of synthesizing and purifying many new compounds.

I would like to thank the Nash group post-doctoral associate, Joey Lapka, for sharing an office and sharing his knowledge.

I would like to thank Yuji Sasaki of the Japan Atomic Energy Agency for his generous gift of TODGA.

I would like to thank Gerhard Munske of the WSU Molecular Biology and Genomics Core for helping to elucidate structures with his HRMS expertise.

I would like to thank Greg Helms and Bill Hiscox of the WSU Center for NMR

Spectroscopy for many hours of assistance and sage advice.

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I would like to thank my fellow graduate students for their assistance and support, especially Guy Dutech, Ashleigh Kimberlin, Ian Hobbs, Jeff Berry, Bess O’Leary, Adam Burn,

Jeff Johnston, Jessica Drader, and Colt Heathman.

I would like to thank all my wonderful professors (Jim Togeas, Nancy Carpenter,

Jennifer Goodnough, Rob Rossi, George Shuffelton, Steve Kennedy, and Rick Penning) and teachers (Vern Stevens, Deanna Jordahl, Maury Ferden, Butch Halterman, Teresa Goddard,

Darwin Tebeest, and Dan Hampton) from whom I have learned so much and owe my passion for continued learning.

I would like to thank my father, Gene Tokheim, who always says that I am a success, even after apparent failures.

I would like to thank my brother, Sam Tokheim, who provides excellent advice and comic relief for every situation.

I would like to thank my brother, Luke Tokheim, who always shares some of his positive outlook and creates fun wherever he goes.

Lastly, I would like to thank my mother, Lucy O’Laughlin, who always listens and sees the beauty in everything.

SYNTHESIS AND CHARACTERIZATION OF NEW UNSYMMETRICAL

DIGLYCOLAMIDES FOR TRIVALENT LANTHANIDE

METAL EXTRACTION

Abstract

by Benjamin George Tokheim, Ph.D. Washington State University July 2016

Chair: Kenneth L. Nash

Twelve new unsymmetrical diglycolamide (UDGA) ligands have been synthesized as solvent extraction reagents for trivalent lanthanide ions from highly acidic nitrate media. The asymmetry in the extractant design arises from attaching nonpolar alkyl chains (hexyl, octyl,

2-ethylhexyl, 3,7-dimethyloctyl) to one amide group and smaller, more compact, cyclic alkyl groups (pyrrolidinyl, piperidinyl, morpholino) to the other amide moiety. This structural variant of a well-known cation receptor reduces the interfacial footprint of the extractant and is designed to increase the rate of phase transfer of the target cations. The partitioning of 152,154Eu(III) between aqueous phases of varying nitric acid concentrations (0.01-3 M) and a 0.05 M UDGA in

5% v/v 1-octanol/n-dodecane organic phase was measured radiometrically and compared to the symmetrical diglycolamide, N,N,N′,N′-tetraoctyldiglycolamide (TODGA). All twelve UDGA ligands quantitatively extracted trivalent Eu(III) cations from 1 M nitric acid. Separate solvent extraction slope analysis experiments were used to determine the stoichiometry and conditional

extraction equilibrium constant (K'ex) of the extracted Eu-UDGA complex in

5% v/v 1-octanol/n-dodecane. The metal-ligand complex stoichiometry in the extracted species was found to be approximately 1:3 for the UDGA ligands and TODGA while the conditional extraction equilibrium constants (K'ex) decreased with increasing ligand size and alkyl chain branching. Luminescence spectroscopy investigations established the relative stability and stoichiometry of the complexes in acetonitrile. The overall trends in the conditional extraction equilibrium constant (K'ex) and the 1:3 conditional stability constant (β103) followed a similar pattern, indicating a correlation between complex stability and ligand structural features.

TABLE OF CONTENTS

Page

ACKNOWLEDGEMENTS ...... iii

ABSTRACT ...... v

LIST OF TABLES ...... x

LIST OF FIGURES ...... xii

CHAPTER ONE: INTRODUCTION

1. THE ATOMIC AGE ...... 1

2. SOLVENT EXTRACTION COMPLEXANT DEVELOPMENT ...... 13

3. REFERENCES ...... 33

CHAPTER TWO: SYNTHESIS AND CHARACTERIZATION OF NEW UNSYMMETRICAL DIGLYCOLAMIDES

1. INTRODUCTION ...... 40

2. MATERIALS ...... 46

3. METHODS ...... 47

4. SYNTHETIC DESIGN OBJECTIVES ...... 49

5. SYNTHESIS AND PURIFICATION OF LIGANDS 1-9...... 51

Flash Chromatography: CombiFlash® Rf+ Lumen™...... 58

6. SYNTHESIS AND PURIFICATION OF LIGANDS 10-12...... 63

Flash Chromatography: MPLC #3 ...... 71

7. CONCLUSIONS...... 73

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8. REFERENCES ...... 75

CHAPTER THREE: TRIVALENT LANTHANIDE METAL EXTRACTION BEHAVIOR BY NEW UNSYMMETRICAL DIGLYCOLAMIDES

1. ABSTRACT ...... 77

2. INTRODUCTION ...... 77

3. MATERIALS ...... 81

4. METHODS ...... 83

Radiotracer 152,154Eu Experiments ...... 84

ICP-MS Ln Experiments...... 86

5. EQUILIBRATION TIME ...... 87

6. THIRD PHASE FORMATION ...... 90

7. LIGAND SOLUBILITY ...... 92

8. NITRIC ACID EXTRACTION ...... 95

9. EU(III)-UDGA COORDINATION COMPLEXES ...... 100

10. NITRIC ACID DEPENDENCE EXTRACTIONS ...... 113

11. NITRATE DEPENDENCE EXTRACTION ...... 124

12. LANTHANIDE SERIES EXTRACTIONS ...... 125

13. CONCLUSIONS...... 135

14. FURTHER WORK ...... 136

15. REFERENCES ...... 137

CHAPTER FOUR: PROBING THE EUROPIUM-UNSYMMETRICAL DIGLYCOLAMIDE COMPLEX USING LUMINESCENCE SPECTROSCOPY

1. INTRODUCTION ...... 141

2. MATERIALS ...... 146

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3. METHODS ...... 147

4. LUMINESCENCE LIFETIMES FOR EU(III)-UDGA COMPLEXES ...... 148

5. LUMINESCENCE EMISSION SPECTROSCOPY FOR EU(III)-UDGA COMPLEXES ...... 154

6. CONCLUSIONS...... 172

7. REFERENCES ...... 173

CHAPTER FIVE: CONCLUSIONS

1. PROJECT GOALS ...... 175

2. ORGANIC SYNTHESIS ...... 176

3. SOLVENT EXTRACTION STUDIES ...... 176

4. LUMINESCENCE SPECTROSCOPY ...... 178

5. FUTURE WORK ...... 178

LIST OF TABLES

Table 1.1. Neutron capture cross sections (σγ), half-lives (t1/2), and decay energies for radioisotopes involved in one pathway for plutonium-239 production...... 3

Table 1.2. Neutron capture cross sections (thermal and above thermal resonance integral) and isobar (138-160) fission yields for the stable lanthanide nuclides...... 12

Table 1.3. Distribution ratios for U(VI), Pu(IV), and Np(VI) extraction by varying trialkyl phosphates (1.09 M in n-dodecane) from 3.0 M HNO3 at 30°C...... 14

Table 1.4. Relative dielectric constants (εr) for liquids relevant to solvent extraction processes...... 27

Table 2.3. Names, molecular weights, and overall percent yields for unsymmetrical diglycolamide ligands 1-9...... 59

Table 2.4. Evaporative distillation temperature ranges (ev, °C) and pressures (P, mm Hg) for bis(3,7-dimethyloctyl) pyrrolidinyl and piperidinyl ligands 10 and 11. Mass and percent yields for the second amidation reaction are also listed. The bis(3,7-dimethyloctyl) morpholino ligand (12) was purified via flash chromatography instead of evaporative distillation...... 71

Table 2.5. Names, molecular weights, and overall percent yields for unsymmetrical diglycolamide ligands 10-12...... 72

Table 3.1. UDGA ligand solvent extraction experiments with varying diluent mixtures...... 94

Table 3.2. The extraction of nitric acid by the diglycolamide ligand DMOmorDGA (L = DMOmorDGA, aqueous phase = 3.018 ± 0.006 M HNO3; diluent = 5.0% v/v 1-octanol/n-dodecane)...... 97

Table 3.3. The results of solvent extraction experiments performed by Sasaki et al. to ascertain the ligand to metal ratio for Eu(III) in various diluents. The dielectric constants for each diluent are also listed...... 107

Table 4.1. The stability constants (log β) and thermodynamic data (ΔG, ΔH, and ΔS) for the 1:1, 1:2, and 1:3 complexes of Nd(III) and N,N,N',N'-tetramethyldiglycolamide (TMDGA) and diglycolic acid (ODA). Data were taken from work by Tian et al...... 143

Table 4.2. Physical and thermodynamic data for water, ethanol, and acetonitrile. Data taken from the CRC Handbook of Chemistry and Physics (2004)...... 145

Table 4.3. Luminescence lifetimes (τobs) and inner-sphere hydration numbers 3+ (NH2O) for 1.00 mM Eu in 0.0981, 0.961, and 3.01 M HNO3...... 151

Table 4.4. Luminescence lifetimes (τobs) and inner-sphere hydration numbers

(NH2O) for the terminal Eu(III)-L complex (L = UDGA ligands 1-12 and TODGA)...... 153

LIST OF FIGURES

Figure 1.1. The actinyl (An) linear dioxo cation with coordinating ligands (L) in n+ n+ the equatorial plane. Coordination number (CN) is six for NpO2 and PuO2 , n+ while UO2 can accommodate several different coordination numbers (CN = 2, 4, 6, 7, 8)...... 4

Figure 1.2. The typical coordination around Bi(III) in monazite-type BiPO4. Bi = fuchsia sphere; O = teal sphere; P = yellow sphere. Bi-O bond distances are shown in angstroms...... 5

Figure 1.3. Structure of methyl isobutyl ketone (MIBK)...... 6

Figure 1.4. Structure of tributyl phosphate (TBP)...... 7

Figure 1.5. The radiotoxicity (sieverts/metric ton natural uranium) of typical spent nuclear fuel from a pressurized water reactor over time...... 9

Figure 1.6. The fission product yields (kg/tonne initial heavy metal) of typical spent nuclear fuel from a pressurized water reactor...... 10

Figure 1.7. Structure of diphenyl phosphoric acid (HDφP)...... 15

Figure 1.8. Structure of di-(2-ethylhexyl)phosphoric acid (HDEHP)...... 15

Figure 1.9. Structure of mono-(2-ethylhexyl)phenylphosphonic acid (HEH[φP])...... 16

Figure 1.10. Structure of diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA)...... 16

Figure 1.11. Structure of lactic acid...... 17

Figure 1.12. Structure of 1,4-diisopropylbenzene (DIPB)...... 17

Figure 1.13. Structure of dihexyl-N,N-diethylcarbamoylmethylphosphonate (DHDECMP or CMP)...... 17

Figure 1.14. Structure of octyl(phenyl)- N,N-diisobutylcarbamoylmethylphosphine oxide (OφD[IB]CMPO or CMPO)...... 17

Figure 1.15. Structure of oxalic acid...... 18

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Figure 1.16. Generic structure of the monoamides...... 19

Figure 1.17. Structure of N,N-dibutylhexanamide (DBHA)...... 19

Figure 1.18. Structure of N,N,N',N'-tetrabutylmalonamide (TBMA)...... 19

Figure 1.19. Generic structure of the malonamides...... 20

Figure 1.20. Structure of N,N'-dimethyldibutyltetradecylmalonamide (DMDBTDMA)...... 21

Figure 1.21. Structure of N,N'-dimethyl-N,N'-dioctyl-2-hexylethoxymalonamide (DMDOHEMA)...... 21

Figure 1.22. Structure of diglycolic acid...... 21

Figure 1.23. Structure of N,N'-dimethyl-N,N'-dihexyldiglycolamide (DMDHDGA)...... 22

Figure 1.24. Structure of N,N,N',N'-tetraoctyldiglycolamide (TODGA)...... 22

Figure 1.25. Thermal ellipsoid plot (at 50% probability level) of the solid-state IV structure of [Pu (TMDGA)3](NO3)4. Non-coordinating nitrate anions and H atoms have been omitted for clarity. Structure taken from Reilly et al. Chem. Commun. 2012, 48 (78), 9732...... 25

Figure 1.26. Structure of N,N-dihexyloctanamide (DHOA)...... 27

Figure 1.27. Structure of N,N,N',N'-tetra(2-ethylhexyl)diglycolamide (TEHDGA)...... 29

Figure 1.28. Structure of N,N-di(2-ethylhexyl)-N',N'-dioctyldiglycolamide (DEHDODGA)...... 30

Figure 1.29. Structure of N,N-didodecyl-N',N'-dioctyldiglycolamide (D3DODGA)...... 30

Figure 2.1. Structure of tributyl phosphate (TBP)...... 43

Figure 2.2. Structure of octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO)...... 43

Figure 2.3. Structure of N,N'-dimethyl-N,N'-dioctyl-2-hexylethoxymalonamide (DMDOHEMA)...... 44

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Figure 2.4. Structure of N,N,Nʹ,Nʹ-tetraoctyldiglycolamide (TODGA) coordinated to generic metal cation (M)...... 45

Figure 2.5. Structure of N,N-didodecyl-N',N'-dioctyldiglycolamide (D3DODGA)...... 46

Figure 2.6. Structures of the secondary dialkylamines: dihexylamine, dioctylamine, and di-(2-ethylhexyl)amine...... 52

Figure 2.7. Structures of N,N-dihexyldiglycolamic acid methyl ester (A), N,N-dioctyldiglycolamic acid methyl ester (B), and N,N-di-2-ethylhexyldiglycolamic acid methyl ester (C)...... 54

Figure 2.8. Structures of the cyclic secondary amines: pyrrolidine, piperidine, and morpholine...... 56

Figure 2.9. Structures of newly synthesized unsymmetrical diglycolamides (1-9) with acronyms provided (DH = di-hexyl, DO = di-octyl, DEH = di-2-ethylhexyl, pyr = pyrrolidinyl, pip = piperidinyl, mor = morpholino, DGA = diglycolamide)...... 59

Figure 2.10. Stereochemical structures of the three different isomers of bis(3,7-dimethyloctyl)amine (d, l, and meso)...... 66

Figure 2.11. Structure of N,N-bis(3,7-dimethyloctyl)diglycolamic acid methyl ester (D)...... 69

Figure 3.1. Structure of tributyl phosphate (TBP)...... 79

Figure 3.2. Structure of octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO)...... 79

Figure 3.3. Structure of N,N,N',N'-tetraoctyldiglycolamide (TODGA)...... 80

Figure 3.4. Structure of diglycolic acid...... 80

Figure 3.5. Generic structure for the symmetrical diglycolamides including N,N,N′,N′-tetrabutyldiglycolamide (TBDGA, R = butyl) N,N,N′,N′-tetraamyldiglycolamide (TADGA, R = amyl), and N,N,N′,N′-tetrahexyldiglycolamide (THDGA, R = hexyl)...... 88

Figure 3.6. Structure of N,N-di-2-ethylhexyl-N',N'-dioctyldiglycolamide (DEHDODGA)...... 89

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Figure 3.7. The extraction of Eu(III) from 0.985 M HNO3 by N,N-dihexyl- N'-pyrrolidinyldiglycolamide (DHpyrDGA) with varying equilibration times. Organic phases were all pre-equilibrated with metal-free aqueous phase for 30 minutes...... 90

Figure 3.8. Structures of newly synthesized unsymmetrical diglycolamides (1-12) with acronyms provided (DH = dihexyl, DO = dioctyl, DEH = di-2-ethylhexyl, DMO = bis(3,7-dimethyloctyl), pyr = pyrrolidinyl, pip = piperidinyl, mor = morpholino, DGA = diglycolamide)...... 93

Figure 3.9. Possible hydrogen bonding interaction between a nitric acid molecule and the diglycolamide ligand N,N-bis(3,7-dimethyloctyl)-N'-morpholinodiglycolamide (DMOmorDGA)...... 99

Figure 3.10. Structure of N,N,N',N'-tetra-isobutyldiglycolamide (TiBDGA)...... 100

Figure 3.11. Nine-coordinate tricapped trigonal prismatic structure of 3+ La(TiBDGA)3 (R = isobutyl)...... 101

Figure 3.12. The partitioning of Eu(III) metal between 1.004 M HNO3 and varying [DHpyrDGA] in 5.0% v/v 1-octanol/n-dodecane. Distribution ratios were corrected for nitrate complexation. Triplicate data points are plotted...... 106

152,154 Figure 3.13. The distribution ratios (DEu) for radiotracer Eu(III) between a 10 mM diglycolamide (ligands 1-12 and TODGA(T)) in 5.0% v/v 1-octanol/n-dodecane organic phase and a 1.0 M HNO3 aqueous phase...... 110

Figure 3.14. Generic structures of di-2-ethylhexyl diglycolamides (left) and the bis(3,7-dimethyloctyl) diglycolamides (right). Three-dimensional structures were created using the program Avogadro 1.1.1. Hydrogen atoms were included in the optimization process but omitted in the final structure for ease of viewing. The structures are shown from the front with a quarter bias (C = grey, O = red, N = blue)...... 111

Figure 3.15. Resonance structures for the pyrrolidinyl amide (R = hexyl, octyl, 2-ethylhexyl, 3,7-dimethyloctyl...... 112

Figure 3.16. The extraction of 152,154Eu(III) by N,N,N',N'-tetraoctyl-diglycolamide (TODGA) from varying concentrations of nitric acid. The 0.1 M TODGA in n- dodecane data was digitized from published work by Sasaki et al...... 115

Figure 3.17. The extraction of 152,154Eu(III) by the dihexyl derivatives (1-3) from varying concentrations of nitric acid...... 117

Figure 3.18. The extraction of 152,154Eu(III) by the dioctyl derivatives (4-6) from varying concentrations of nitric acid...... 119

Figure 3.19. The extraction of 152,154Eu(III) by the di-2-ethylhexyl derivatives (7-9) from varying concentrations of nitric acid...... 121

Figure 3.20. The extraction of 152,154Eu(III) by the bis(3,7-dimethyloctyl) derivatives (10-12) from varying concentrations of nitric acid...... 123

Figure 3.21. The log β103 values for the tris-diglycolate complexes with La(III)-Lu(III) (μ = 1.00 M NaClO4, T = 20.0°C) from work by Grenthe and Tobiasson. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon...... 126

Figure 3.22. The extraction of La(III)-Lu(III) by N,N,N',N'-tetraoctyldiglycolamide (TODGA) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon...... 127

Figure 3.23. The extraction of La(III)-Lu(III) by the dihexyl derivatives (1-3) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon...... 129

Figure 3.24. The extraction of La(III)-Lu(III) by the dioctyl derivatives (4-6) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon...... 131

Figure 3.25. The extraction of La(III)-Lu(III) by the di-2-ethylhexyl derivatives (7-9) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon...... 133

Figure 3.26. The extraction of La(III)-Lu(III) by the bis(3,7-dimethyloctyl) derivatives (10-12) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon...... 134

Figure 4.1. Structure of N,N,N',N'-tetraoctyldiglycolamide (TODGA)...... 141

Figure 4.2. Nine-coordinate tri-capped trigonal prismatic structure of Nd(III)- (TMDGA)3...... 142

Figure 4.3. Structures of unsymmetrical diglycolamides (1-12) with acronyms provided (DH = dihexyl, DO = dioctyl, DEH = di-2-ethylhexyl, DMO = bis(3,7-dimethyloctyl), pyr = pyrrolidinyl, pip = piperidinyl, mor = morpholino, DGA = diglycolamide)...... 144

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Figure 4.4. Luminescence of Eu3+ ligand complexes with a quenching pathway through water molecule vibrational energy transfers (νOH). Graphic taken from Cotton, S. Lanthanide and actinide chemistry; Wiley: Chichester, 2006...... 149

Figure 4.5. Emission spectra of 1.00 mM Eu(NO3)3 in 0.0981, 0.961, and 3.01 M HNO3...... 150

Figure 4.6. Emission spectra of Eu(III) with increasing amounts of the ligand N,N-bis(3,7-dimethyloctyl)-N'-piperidinyldiglycolamide (DMOpipDGA). Inset of 608-624 nm included to show the peak splitting toward the end of the titration (black line = beginning; red line = end)...... 154

Figure 4.7. Emission spectra of Eu(III) with increasing amounts of the ligand N,N-bis(3,7-dimethyloctyl)-N'-morpholinodiglycolamide (DMOmorDGA). Inset of 608-624 nm included to show the small amount of peak splitting toward the end of the titration (black line = beginning; red line = end)...... 156

Figure 4.8. Corrected fluorescence intensity spectra for Eu(III)-DMOpipDGA complexes in 0.3 mM HNO3/0.2 M H2O/99.7% MeCN...... 159

Figure 4.9. Corrected fluorescence intensity spectra for Eu(III)-DMOmorDGA complexes in 0.3 mM HNO3/0.2 M H2O/99.7% MeCN...... 160

Figure 4.10. Stepwise stability constants (log K) calculated from Table 4.5 for the UDGA ligands (average of data from ligands 3-12), TODGA, and diglycolic acid...... 164

Figure 4.11. Comparison of log K'ex values (obtained from previous radiotracer 152,154 Eu(III) solvent extraction ligand dependence data in Table 3.4) and log β103 values (obtained from Eu(III) luminescence spectroscopy titrations in Table 4.5) for the unsymmetrical diglycolamides (1-12) and TODGA (T)...... 166

Figure 4.12. Possible square antiprismatic structure (#1, 5-membered chelate rings) for the 8-coordinate Eu(III)-pyrDGA metal-ligand complex (R = hexyl, octyl, 2-ethylhexyl, 3,7-dimethyloctyl)...... 170

Figure 4.13. Possible square antiprismatic structure (#2, 8-membered chelate rings) for the 8-coordinate Eu(III)-pyrDGA metal-ligand complex (R = hexyl, octyl, 2-ethylhexyl, 3,7-dimethyloctyl)...... 171

Figure 5.1. Structure of N,N-bis(3,7,11-trimethyldodecyl)-N′-piperidinyldiglycolamide (TMDpipDGA)...... 180

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Chapter 1

INTRODUCTION

1.1. The Atomic Age

The first controlled nuclear chain reaction was housed inside a stack of graphite bricks with wooden timbers as support beams. Small “eggs” of uranium were embedded in the graphite until the number of neutrons produced exceeded the number of neutrons absorbed. This was the first nuclear reactor and it was housed safely on the campus of the University of Chicago, in the middle of a huge metropolitan area.1 This feat was accomplished in 1942 by Enrico Fermi and dozens of other scientists and workers involved with the Manhattan Project. The first commercial nuclear reactor did not come online until twelve years later in Obninsk, Russia.2 Two years later the first pressurized light water reactor (PWR) began producing power in Shippingport, Pennsylvania.3

Over the next few decades the number of electricity-producing nuclear reactors in the United States steadily increased until reaching a maximum of 110 in 1990.

A partial meltdown of a reactor at Three Mile Island in 1979 and a reactor explosion at

Chernobyl in 1986 led to a slowdown in nuclear power plant construction throughout the late 1980s to early 2000s. However, concern over climate change and the emission of greenhouse gases such as carbon dioxide fueled renewed interest in nuclear power at the beginning of this decade. In

2011, a tsunami hit the coast of Japan and knocked out power to the cooling systems at the

Fukushima Daiichi nuclear power plant, which led to the meltdown of three reactor cores. Japan halted nuclear energy production and the debate over the construction of new nuclear reactors

continued in the United States and the European Union. In 2015, there were a total of 438 nuclear power reactors in operation worldwide with 70 new reactors under construction, most in the developing world. The United States generated 20% of all domestic electricity using 99 operational nuclear reactors with five new reactors under construction.4

The use of hydraulic fracturing to extract natural gas from oil shales has driven down the price of this fossil fuel, which has overtaken coal as the largest producer of electricity in the United

States.5 Nevertheless, burning fossil fuels releases greenhouse gases (e.g., carbon dioxide) and contributes to climate change. Concerns about the potential impact of climate change, particularly the connection between climate instability, population growth, and fossil carbon combustion have framed the discussion in the first two decades of the 21st century. Given the need for near zero carbon primary power to ameliorate the effects of fossil carbon combustion, it is increasingly likely that nuclear power must be an integral part of any energy plan for the future. After more than 50 years of steadily increasing performance and safety, it is clear that this resource can be further improved through research on next generation reactors and used nuclear fuel recycling.

The first application of nuclear energy was the production of the atomic bomb. The Fat

Man design used the radioisotope plutonium-239 as the fissile material. The plutonium was produced by irradiating natural uranium (99.3% uranium-238, 0.7% uranium-235, trace uranium-234)6 in the B, D, and F reactors at the Hanford Site in central Washington State.7 The main B reactor was a larger version of Fermi’s original Chicago Pile-1 (CP-1) with the added benefit of water cooling from the Columbia River. The uranium metal slugs were canned in aluminum-silicon cladding (later Zircaloy-2) and fed into one of 2,004 horizontal process channels drilled through a wall of graphite blocks.8 The high-purity graphite (carbon atoms) slowed down the neutrons released from the fission of uranium-235, which increased the probability of

subsequent neutron interactions with uranium nuclei.9 One pathway for plutonium-239 production is shown below in Equation 1.1,

-- 238U n,γ 239 U  β 239 Np  β 239 Pu (1.1)

Table 1.1 shows the relevant neutron capture cross sections (σ), radioisotope half-lives

(t1/2), and decay energies for the nuclides shown in Equation 1.1. The neutron capture cross section

(σ) represents the probability that a given nucleus will interact with an incoming neutron and undergo one of several different reactions with neutrons. The most common neutron capture reaction (σγ), seen in the first step of Equation 1.1, is accompanied by a high-energy gamma-ray emission. The two different values give for (σγ) represent the thermal and above thermal neutron capture cross sections.

Table 1.1. Neutron capture cross sections (σγ), half-lives (t1/2), and decay energies for radioisotopes involved in one pathway for plutonium-239 production.9 -24 2 Nuclide Half-life (t1/2) Decay Modes (Energies) σγ (barns = 10 cm ) U-238 4.47×109 yr α (4.20, 4.15 MeV) 2.68, 277 γ (49.6 keV) U-239 23.5 min β- (1.21, 1.28 MeV) 22 γ (74.7,43.5 keV) Np-239 2.356 d β- (0.438, 0.341 MeV) (30 + 30) γ (106.1, 277.6, 228.2 keV) Pu-239 2.41×104 yr α (5.16, 5.14, 5.11 MeV) 271, 200 γ (51.6 keV)

Fissile radioisotopes such as 235U and 239Pu will also undergo fission with thermal neutrons

(0.025 eV) and produce a multitude of fission products: gallium through erbium.10 These fission products include two elements from the alkali metals, alkaline earth metals, boron group, carbon

group, pnictides, chalcogenides, halides, and noble gases, as well as the entire second row of the transition metals. Most of the lanthanide series is also included in the fission products.11 As such, the chemistry of the fission products is as diverse as the periodic table itself.

The combination of uranium, transuranics (Np, Pu, Am, Cm), and fission products in the irradiated fuel pellets make the separation of plutonium a challenge. Uranium, neptunium, and plutonium, like most of the early actinides, exist in a variety of oxidation states. Each of these oxidation states has its own unique chemistry, which complicates the separation but can also be exploited. Neptunium and plutonium both have five accessible oxidation states: III, IV, V, VI, and

VII. In typical acidic aqueous solutions, neptunium is found predominately as the redox stable

Np(V) while plutonium displays the anomalous behavior of existing in four different oxidation states (III-VI) in acidic solutions. Uranium can be found in oxidation states from trivalent to hexavalent but is most redox stable as U(VI). All three of these actinides exist as linear dioxo cations in both the pentavalent and hexavalent oxidation states. The axial oxygen atoms are substitution inert so ligand interaction takes place in the equatorial plane (Figure 1.1).

Figure 1.1. The actinyl (An) linear dioxo cation with coordinating ligands (L) in the equatorial n+ n+ n+ plane. Coordination number (CN) is six for NpO2 and PuO2 , while UO2 can accommodate several different coordination numbers (CN = 2, 4, 6, 7, 8).12

The first process to separate plutonium from the irradiated uranium used a co-precipitation

13 method with bismuth phosphate (BiPO4, Figure 1.2). After irradiation in a reactor, the used fuel pellets were dissolved in 6-8 M HNO3, which oxidized U and Np to the hexavalent state and Pu to the tetravalent state. Plutonium can also exist in the trivalent and hexavalent oxidation states in highly acidic media so a small amount of oxalic acid was added to stabilize Pu(IV).14 Bismuth nitrate and phosphoric acid were then added to create bismuth phosphate.8 The bismuth phosphate acted as a carrier for the co-precipitation of Pu(IV) but also brought along other trivalent cations

(e.g., lanthanides).12,15

Figure 1.2. The typical coordination around Bi(III) in monazite-type BiPO4. Bi = fuchsia sphere; O = teal sphere; P = yellow sphere. Bi-O bond distances are shown in angstroms.

The precipitate was centrifuged and separated from the liquid phase. The plutonium-rich precipitate was then dissolved in nitric acid and the Pu(IV) was oxidized to Pu(VI) using sodium bismuthate.8 The Pu(VI) stayed in solution while the bismuth phosphate co-precipitated the trivalent lanthanides, Ln(III), and trivalent actinides, Am(III) and Cm(III).16 This process succeeded in producing kilogram quantities of plutonium-239 that were used in the Trinity atomic bomb test17 and Fat Man atomic bomb dropped on Nagasaki, Japan at the end of World War II.18

The second process implemented at the Hanford site used a liquid-liquid solvent extraction system to increase throughput to meet the rising demand for plutonium in the 1950s. The REDOX

(reduction oxidation) process used methyl isobutyl ketone (MIBK, Figure 1.3) as a neat organic

2+ 2+ solvent and extractant. MIBK forms weak adducts with PuO2 and UO2 while rejecting the

+ fission products and NpO2 .

Figure 1.3. Structure of methyl isobutyl ketone (MIBK).

The goal of solvent extraction is to partition solutes from one phase to another. Polar solutes

(e.g., metal cations) will not partition from an aqueous phase into an organic diluent such as n-dodecane without achieving charge neutrality and increased ligand complexation. MIBK is a solvating extractant so two nitrate anions must extract with the uranyl or plutonyl cation.

Glueckauf and McKay determined that the uranyl-MIBK complex contained an average of three

MIBK ligands.19,20

The extraction reaction for uranyl-MIBK is shown below in Equation 1.2,

UO (NO ) (H O) 3MIBK UO (NO ) (MIBK) 6H O (1.2)  23226aq org 232 3 org 2aq

MIBK is a weak extractant so this reaction required either high HNO3 concentrations

(e.g., 8 M) or a salting-out agent (e.g., NH4NO3, Al(NO3)3) to reduce the amount of free water available to hydrate the uranyl-nitrato complex. High concentrations of HNO3 caused the chemical degradation of MIBK so the most effective salt, aluminum nitrate, was used to facilitate U(VI) and

21 Pu(VI) extraction. Unfortunately, the excess Al(NO3)3 increased the amount of waste and further complicated the REDOX process.8

The PUREX (Plutonium Uranium Reduction EXtraction) process (introduced at Hanford and the Savannah River Plant in the mid-1950s) used the extractant tributyl phosphate (TBP,

Figure 1.4) to form adducts with the actinide nitrates but did not require aluminum nitrate as a salting-out agent. Instead, the nitric acid was distilled off and reused continuously.22

Unlike MIBK, TBP extracts uranyl nitrate in the absence of Figure 1.4. Structure of tributyl phosphate (TBP). coordinated waters. This provides a large entropic benefit for the extraction of U(VI) since six waters are liberated and only two TBP ligands replace them.

The extraction reaction for uranyl-TBP is shown below in Equation 1.3,

UO (NO ) (H O) 2TBP UO (NO ) (TBP) 6H O (1.3)  2 3226aq org 2 32 2 org 2aq

TBP selectively extracts Pu(IV) and U(VI) over the fission products and the minor actinides (MA): neptunium, americium, and curium.23 The strength of extraction by TBP is

4+ 2+ 3+ + governed by the effective charges of the metal cations: Pu (4) > UO2 (3.3) > An (3) > NpO2

24,25 2+ 26 (2.2). The PUREX process can also be modified to extract NpO2 along with U and Pu. The

TBP extractant has been shown to degrade into dibutyl phosphate (DBP) and monobutyl phosphate

(MBP) but a solvent wash step can remove these undesirable products.27 The PUREX process is still used today in countries where reprocessing is a reality and remains the industry standard for the recovery of plutonium and uranium from used nuclear fuel.10

The PUREX process is only the first step in nuclear fuel reprocessing, effectively a means of separating U and Pu from the fission “waste” byproducts. The plutonium and uranium can be recycled in a special mixed oxide (PuO2/UO2 – MOX) fuel but a large amount of long-lived radioisotopes remain in the PUREX waste stream. These radioisotopes include two of the minor actinides (MA), americium and curium, which account for much of the long-lived radiotoxicity in high level liquid waste (HLLW). Without further reprocessing, the HLLW would need to be isolated for over 10,000 years to reach the radiotoxicity of natural uranium ore. The removal and transmutation of the minor actinides can reduce this time to less than 500 years, which makes geological repository siting a much easier task. Salvatores and Palmiotti created the graph below

(Figure 1.5) which represents the long-term radiotoxicity of spent nuclear fuel components.28

The process to remove these minor actinides (Am, Cm) from spent nuclear fuel is called partitioning and transmutation (P&T). The partitioning portion refers to the chemical separation of long-lived radioisotopes such as the minor actinides from the other constituents in the HLLW.

The transmutation portion refers to the bombardment of the long-lived radioisotopes with neutrons to produce short-lived or stable isotopes.29 The chemical separation of uranium, plutonium, and neptunium takes advantage of the redox chemistry available to each of these actinides in acidic media. The minor actinide americium also has multiple available oxidation states in aqueous

3+ 4+ + 2+ media: Am , Am , AmO2 , and AmO2 . All four of these oxidation states can coexist in alkaline

3+ 2+ 30 solutions while only the trivalent Am and hexavalent AmO2 ions are stable in acidic solutions.

Am(III) is the most stable oxidation state in aqueous media, however, so the trivalent americium cation is the most important species concerning solvent extraction systems.

Figure 1.5. The radiotoxicity (sieverts/metric ton natural uranium) of typical spent nuclear fuel from a pressurized water reactor over time.

Moreover, the chemically analogous lanthanides, Ln(III), are present in the HLLW at far greater concentrations (ca. 150 mM) than the minor actinides (ca. 2.4 mM).10 The complicated nature of fission includes the asymmetrical splitting of the nucleus into two different fragments

235 150 82 1 9 and the release of 2.5 neutrons on average (e.g. 92U  60 Nd + 32 Ge + 3 0 n ). The light lanthanide metals (atomic numbers 57-64) are overrepresented in the fission products because of this asymmetry. Figure 1.6 shows the fission product yields for typical used PWR fuel after ten years of cooling.11

Fission Product Yields for Typical Spent PWR Fuel 104 Calculated composition after 10 years cooling of 1 tonne U as 3.2% enriched UO2 fuel 103 with 33 MWd/kg U burnup at a mean flux of 3.24 × 1018 n m-2 s-1 in a typical PWR* 102 101 100 10-1 10-2 10-3 10-4 10-5 10-6 10-7

10-8 Fission Yield (kg/tonne IHM) (kg/tonne Yield Fission 10-9 10-10 10-11 25 30 35 40 45 50 55 60 65 70 75 Atomic Number *Data taken from Choppin, G.; Liljenzin, J.-O.; Rydberg, J, Radiochemistry and Nuclear Chemistry; Butterworth-Heinemann: Kundli, India, 2002, p. 593.

Figure 1.6. The fission product yields (kg/tonne initial heavy metal) of typical spent nuclear fuel from a pressurized water reactor.

Most of the fission products quickly β- decay into stable nuclides including a large number of lanthanide metals. Isobars 138-160 account for over 56% of the fission yield from uranium-235 and include the elements lanthanum through terbium. The lanthanides share the trivalent oxidation state with the minor actinides and have similar ionic radii. These similarities make it difficult to achieve separation of these two groups of metals. The eventual separation is necessary because

151 3 many of the lanthanides have large neutron capture cross sections (e.g., Eu: σγ = 5.9 × 10 barns

{thermal}; 4.0 × 103 barns {resonance}). These large neutron capture cross sections absorb the neutrons meant for the transmutation of the minor actinides into stable or short-lived nuclides.

Table 1.2 shows the neutron capture cross sections and isobar fission yields for the stable lanthanide nuclides. Neodymium and samarium have large isobar fission yields (24% combined) with moderate neutron capture cross sections (average = 2.4 × 103 barns (1 barn = 1 × 10-24 cm2)).

Europium and gadolinium make up a small percentage of the isobar fission yields

(< 1% combined) but have very large neutron capture cross sections (average = 2.4 × 104 barns).9

Table 1.2. Neutron capture cross sections (thermal and above thermal resonance integral) and isobar (138-160) fission yields for the stable lanthanide nuclides. Thermal Neutron Stable Nuclide Capture Cross Sections Resonance Integral Isobar Fission Yield (barns) (barns) from 235U (%) Cerium-138 1.0 × 100 5 × 100 6.77 Lanthanum-139 9.0 × 100 1.2 × 101 6.41 Cerium-140 5.8 × 10-1 4.8 × 10-1 6.22 Praseodymium-141 7.5 × 100 1.41 × 101 5.80 Cerium-142 9.7 × 10-1 1.3 × 100 5.85 Neodymium-143 3.3 × 102 1.3 × 102 5.96 Neodymium-144 3.6 × 100 3.9 × 100 5.50 Neodymium-145 4.5 × 101 2.4 × 102 3.93 Neodymium-146 1.4 × 100 2.8 × 100 3.00 Samarium-147 5.7 × 101 7.0 × 102 2.25 Neodymium-148 2.5 × 100 1.4 × 101 1.67 Samarium-149 4.0 × 104 3.1 × 103 1.08 Neodymium-150 1.0 × 100 1.4 × 101 0.653 Europium-151 5.9 × 103 4.0 × 103 0.419 Samarium-152 2.1 × 102 3.0 × 103 0.267 Europium-153 3.5 × 102 1.5 × 103 0.158 Samarium-154 7 × 100 3.0 × 101 0.074 Gadolinium-155 6.1 × 104 1.54 × 103 0.032 Gadolinium-156 2 × 100 1.0 × 102 0.0149 Gadolinium-157 2.55 × 105 8.0 × 102 0.0062 Gadolinium-158 2.4 × 100 7 × 101 0.0033 Terbium-159 2.32 × 101 4.3 × 102 0.0010 Gadolinium-160 1 × 100 8 × 100 0.0003

There is a slight increase in the covalency of the minor actinides over the trivalent lanthanides, which does allow for some separation using ligands with “softer” donor atoms

(e.g., nitrogen and sulfur). Several solvent extraction processes (e.g., TALSPEAK31 and ALSEP32)

have been developed that take advantage of this difference in covalency by using a nitrogen-donor aqueous complexant. The separation of f-elements traces back to plutonium production in the

Manhattan Project and has steadily developed over the last seventy years.

1.2. Solvent Extraction Complexant Development

The early success of the PUREX tributyl phosphate (TBP) extraction process emphasized the importance of the phosphoryl group (P=O) in forming adducts with U(VI), Pu(IV), and Np(VI).

Libman et al. studied the extraction of U(VI), Pu(IV), and Np(VI) by phosphate esters with different alkyl chains.33 Ligand design for solvent extraction processes is always a balance between complexation strength (achieved with smaller alkyl groups) and organic phase compatibility

(achieved with larger alkyl groups). The trialkyl phosphates have a relatively small molecular footprint where the phosphoryl group coordinates to the metal of choice and the alkyl groups interact with the surrounding aliphatic diluent (e.g., n-dodecane). In this case, the n-butyl group derivative achieves sufficient organic phase solubility because the alkyl groups are closely spaced and can dissolve in a longer chain diluent such as n-dodecane. TBP was favored for the PUREX process over the n-pentyl, n-hexyl, and n-octyl derivatives because of the slightly higher distribution ratio (Equation 1.4) for Pu(IV) and the lower viscosity compared to solutions prepared with phosphate esters containing the longer alkyl chains.

M D = org (1.4) M M  aq

Table 1.3 shows the distribution ratios of U(VI), Pu(IV), and Np(VI) for the four different alkyl (R) groups.34

Table 1.3. Distribution ratios for U(VI), Pu(IV), and Np(VI) extraction by varying trialkyl phosphates (1.09 M in n-dodecane) from 3.0 M HNO3 at 30°C.

Distribution Ratio (DM) R Group U(VI) Pu(IV) Np(VI) n-butyl 26 16.1 15.6 n-pentyl 32 15.6 19.3 n-hexyl 38 15.6 20.0 n-octyl 33 15.3 15.7

Ligand design for the selective co-extraction of An(III) and Ln(III) built on these early findings and introduced modifications to suit this different set of f-elements. Successful extractants

(solvent extraction ligands) must be amphiphilic (i.e., interfacially active) and strong complexing agents for the metal solute of interest. Shorter alkyl chains generally make stronger complexing agents with more interfacial activity. Longer alkyl chains are beneficial for adequate extractant solubility in the organic phase; extractants that exhibit notable solubility in both phases of a biphasic system create opportunities for the undesirable formation of microemulsions. Ideally, the ligand must have good solubility in diluents with sufficiently high boiling points/flash points

(e.g., n-dodecane: fp 74°C bp 216.3°C; 1-octanol: fp 81°C bp 195.1°C) to reduce the risk of solvent combustion.35 High solubility in saturated aliphatic diluents (e.g., n-dodecane) is also desirable due to the insolubility of long-chain aliphatic diluents in the aqueous phase.21 The ideal ligand is able to extract millimolar quantities of An(III) and Ln(III) into the organic phase without forming a heavy organic phase, or third phase, enriched with the metal-ligand complexes. The ligand must also allow the metal cations to be stripped back into the aqueous phase in a subsequent step,

preferably via a change in the concentration of acid or neutral supporting electrolyte in the aqueous phase or as a result of changing the oxidation state of the extracted metal ion. TBP meets these criteria for the separation of U and Pu, so early research on ligands focused on this class of monofunctional organophosphorus extractant.

Working at Argonne National Laboratory in Lemont, Illinois in the late 1950s, Peppard et al. demonstrated the ability of diphenylphosphoric acid (HDφP, Figure 1.7) to extract Y(III) from 12 M HCl (DY = 7.0). They also used di-(2-ethylhexyl)phosphoric acid (HDEHP, Figure 1.8)

36 to extract Am(III) from 0.23 M HCl (DAm = 2.1).

Figure 1.7. Structure of diphenyl Figure 1.8. Structure of di-(2-ethylhexyl)phosphoric phosphoric acid (HDφP). acid (HDEHP).

These two ligands represent a second type of extractant called a cation exchanger. As opposed to the previous solvating extractants TBP and MIBK, cation exchangers do not need to

- extract counter ions (e.g., NO3 ) along with the positively charged metal cation. The ionizable proton on the phosphate group is lost to the aqueous phase and replaced with a coordinated metal cation. Equation 1.5 shows the generic extraction reaction for HA (cation exchanger) and M (metal cation),

+- M(NO3 ) x (H 2 O) y,aq + x(HA) 2,org M(AHA) x,org + xH aq + xNO 3 aq + yH 2 O aq (1.5)

Five years later Weaver and Kappelmann utilized HDEHP and mono(2-ethylhexyl) phenylphosphonic acid (HEH[φP], Figure 1.9) to selectively extract the Ln(III) while using the complexant, diethylenetriaminepentaacetic acid (DTPA, Figure 1.10), to maintain the An(III) in the aqueous phase.31

Figure 1.9. Structure of mono- Figure 1.10. Structure of diethylenetriamine- (2-ethylhexyl)phenylphosphonic N,N,N',N'',N''-pentaacetic acid (DTPA). acid (HEH[φP]).

This process was named TALSPEAK (Trivalent Actinide-Lanthanide Separations by

Phosphorus reagent Extraction from Aqueous Komplexes). TALSPEAK required the use of 1 M lactic acid (Figure 1.11) as a buffer and solubilizing agent for DTPA. Diisopropylbenzene (DIPB,

Figure 1.12) was favored over n-dodecane due to the improved Eu/Am separation factors.

TALSPEAK only achieves high separation factors at certain pH conditions and phase transfer kinetics have proven to be too slow for a large-scale solvent extraction process. The addition of a carboxylic acid buffer such as lactic acid can maintain pH and improve metal extraction kinetics but also adds to the complexity of the system and the eventual waste stream.37

Figure 1.11. Structure of lactic acid. Figure 1.12. Structure of 1,4-diisopropylbenzene (DIPB).

In the early 1980s, Horwitz et al. developed the TRUEX (TRansUranic EXtraction) process at Argonne National Laboratory. This process started with the PUREX solvent (30% TBP in normal paraffinic hydrocarbons (NPH), C10-C14) and added a purpose-specific bifunctional organophosphorus reagent (DHDECMP or OφD[IB]CMPO, Figures 1.13 and 1.14).

Figure 1.13. Structure of dihexyl- Figure 1.14. Structure of octyl(phenyl)- N,N-diethylcarbamoylmethylphosphonate N,N-diisobutylcarbamoylmethylphosphine (DHDECMP or CMP). oxide (OφD[IB]CMPO or CMPO).

These bifunctional extractants contain both a phosphoryl and amide group and can effectively extract U, Np, Pu, Am, and Ln(III) from 3-4 M nitric acid in one step while rejecting most other fission products. Non-lanthanide transition metal fission products were held back in the aqueous phase with oxalic acid (Figure 1.15). TBP was shown to act as a phase modifier in this system and also facilitated the extraction of metals by the bifunctional extractants at high acid concentrations (e.g., 1 M HNO3) and the stripping of metals at low acid concentrations

(e.g., 0.01 M HNO3). The absence of TBP led to the formation of a heavy organic phase, or third phase, at high acid or metal concentrations.38

Figure 1.15. Structure of oxalic acid.

Organophosphorus extractants (e.g., TBP, HDEHP, CMPO) dominated the first half century of solvent extraction processes for spent nuclear fuel separations. In the late 1980s,

Musikas et al. suggested the monoamides (Figure 1.16) as a possible replacement for the industry standard extractant, TBP.39 The monoamides contain only carbon, hydrogen, oxygen, and nitrogen, which makes them completely incinerable (CHON principle40). This feature is seen as a desirable approach to minimizing the volume of secondary wastes from reprocessing activities. The phosphorus in TBP is not fully combustible and remains in the final solid waste product; the resulting phosphate suffers limited compatibility with typical vitrified waste forms.41 The radiolytic and hydrolytic degradation products of the monoamides (i.e., carboxylates and amines) are significantly weaker complexing agents than the monoamide extractants. Thus, the monoamide degradation products do not interfere with the stripping of the extracted metals. TBP degrades into dibutylphosphate (HDBP) and monobutylphosphate (H2MBP), which complex more strongly than

TBP at low acid concentrations, which prevents the stripping of the extracted metals into the aqueous phase.42 Degradation products of TBP and the monoamides must be converted to the salt form and scrubbed from the organic phase using sodium hydroxide or sodium carbonate solutions before the extractants can be reused effectively.43

Figure 1.16. Generic structure of the monoamides.

Bifunctional versions of ligands are generally stronger complexing agents/extractants than their monofunctional counterparts (e.g., N,N-dibutylhexanamide (DBHA, Figure 1.17) vs.

N,N,N',N'-tetrabutylmalonamide (TBMA, Figure 1.18)) due to the chelate effect. The chelate effect is based on a favorable increase in entropy that results when one chelating ligand displaces two or more weaker ligands from a metal complex.44 For example, Mowafy and Aly studied the partitioning of uranyl nitrate between an acidic aqueous phase (DBHA: 3.5 M HNO3; TBMA:

3 M HNO3) and an amidic extractant organic phase (0.5 M DBHA in toluene; 0.1 M TBMA in benzene). The distribution ratio (DU) was 2.43 for the monoamide N,N-dibutylhexanamide

(DBHA)45 and 15.3 for the diamide N,N,N',N'-tetrabutylmalonamide (TBMA)46.

Figure 1.17. Structure of N,N-dibutyl Figure 1.18. Structure of N,N,N',N'-tetra- hexanamide (DBHA). butylmalonamide (TBMA).

In the late 1980s, Musikas et al.47,48 aimed to eliminate phosphorus from the solvent extraction system by using amidic extractants and take advantage of the chelate effect by

synthesizing diamide ligands. A natural bifunctional analog of the monoamides are the malonamides, structurally similar to CMP (Figure 1.13) or CMPO (Figure 1.14). Madic et al. synthesized thirty different substituted malonamides (Figure 1.19) and rated each one in terms of

An(III) and Ln(III) metal extractability and third phase formation properties.49 Some of these malonamide extractants included an alkyl group (R'') off the bridging methylene group between the two amidic carbonyl groups. This extra alkyl group was useful for increasing the solubility of the extractant in organic diluents with minimal interference with metal complexation.

Figure 1.19. Generic structure of the malonamides.

The asymmetric ligands with R = methyl decreased the steric hindrance near the binding pocket and increased An(III) and Ln(III) metal extraction. The chain length of the other two alkyl groups (R' and R'') was also varied to achieve the optimal solubility in aliphatic diluents. The top two extractant candidates (N,N'-dimethyldibutyltetradecylmalonamide, DMDBTDMA,

Figure 1.20 and N,N'-dimethyl-N,N'-dioctyl-2-hexylethoxymalonamide, DMDOHEMA,

Figure 1.21) from the preliminary experiments were studied in further detail, including the extraction of transition metals (e.g., ruthenium). DMDOHEMA was found to have higher decontamination factors (percentage of unwanted solute removed) for Fe(III), Mo(VI), and Ru than DMDBTDMA and was chosen as the extractant for the DIAMEX (DIAMide EXtraction)

process.50 The DIAMEX process was developed in concert with the SANEX (Selective ActiNide

EXtraction) process to eventually isolate the An(III) for transmutation.51

Figure 1.20. Structure of N,N'-dimethyldibutyltetradecylmalonamide (DMDBTDMA).

Figure 1.21. Structure of N,N'-dimethyl-N,N'-dioctyl-2-hexylethoxymalonamide (DMDOHEMA).

In the early 1990s, Stephan et al. synthesized a series of diamide ligands from the precursor diglycolic acid (Figure 1.22).52 Diglycolic acid has two methylene groups and an etheric oxygen in between the two amide groups. This allows the diamide ligands to be tridentate with the etheric oxygen participating in the metal coordination.53

Soon after, Sasaki et al. applied this new category Figure 1.22. Structure of diglycolic acid. of ligands to An(III) and Ln(III) metal extraction studies.54 One of the first ligands synthesized

(DMDHDGA, Figure 1.23) was inspired by the malonamides with methyl and hexyl groups attached to the amide moieties. DMDHDGA was shown to form 3:1 complexes with Eu(III) and

Am(III) and was slightly selective for Eu(III) over Am(III) from nitric acid media.55

Figure 1.23. Structure of N,N'-dimethyl-N,N'-dihexyldiglycolamide (DMDHDGA).

Further iterations of the diglycolamides (DGAs) led to the extractant N,N,N',N'-tetraoctyldiglycolamide (TODGA, Figure 1.24). TODGA was shown to quantitatively extract both

56 Eu(III) and Am(III) from ≥ 1 M HNO3.

Figure 1.24. Structure of N,N,N',N'-tetraoctyldiglycolamide (TODGA).

Sasaki et al. used radiotracer (152,154Eu and 241Am) solvent extraction experiments to develop log DM vs. log [TODGA] plots. These plots used the relationship between the extraction reaction, extraction constant, and the distribution ratio to calculate the number of TODGA molecules associated with each metal cation in the organic phase. TODGA is a solvating

extractant, akin to TBP and the malonamides, so the extraction reaction includes bringing nitrates into the organic phase along with the metal-ligand complex (Equation 1.6).

Mx+ + xNO - + yTODGA M(TODGA) (NO ) (1.6) aq 3 aq org y 3 x org

The extraction equilibrium constant (Kex) is given in Equation 1.7,

M(TODGA) (NO ) y 3 x org Kex = xy (1.7) Mx+   NO -   TODGA   aq 3  aq   org

The distribution ratio (DM) for this extraction is shown in Equation 1.8,

 M(TODGA)y (NO 3 ) x D = org (1.8) M Mx+ aq

The substitution of Equation 1.8 into Equation 1.7 yields Equation 1.9,

DM Kex = xy (1.9) NO-   TODGA  3 aq   org

Equation 1.9 can be converted into the logarithmic form and rearranged to Equation 1.10,

log DK = y log TODGA + x log NO- + log (1.10) M org  3aq ex

Sasaki et al. varied the concentration of the ligand while maintaining the aqueous phase at

56 a constant 1 M HNO3. The logarithm of one is equal to zero so under this set of conditions the final expression can be written as Equation 1.11,

log DK = y log TODGA + log (1.11) M org ex

Therefore, the log DM vs. log [TODGA] plot in principle yields a slope that is equal to y, or the number of TODGA ligands associated with each metal center, and a y-intercept that is equal to the log Kex. By this method, the reported ligand to metal ratio for the TODGA-Eu system was shown to be 4.10 ± 0.05 in n-dodecane and 2.48 ± 0.07 in 1-octanol.57 Neither of these ligand to metal ratios fits with the expected Ln(III) coordination number of eight or nine58; three tridentate

DGA ligands would provide a 9-coordinate environment around the metal center. The ligand to metal ratio of 2.48 in TODGA/1-octanol system could be rationalized as a mixture of dimer and trimer DGA complexes, with three monodentate nitrate ions complexed in the inner-sphere of the dimer and three nitrate ions forced into the secondary coordination sphere for the trimer DGA

IV complex. It has been shown that the crystal structure of [Pu (TMDGA)3](NO3)4 forms a homoleptic complex with the nitrate anions in the outer coordination sphere (Figure 1.25).59

TMDGA is the acronym for the aqueous soluble N,N,N',N'-tetramethyldiglycolamide.

Figure 1.25. Thermal ellipsoid plot (at 50% probability level) of the solid-state structure of IV [Pu (TMDGA)3](NO3)4. Non-coordinating nitrate anions and H atoms have been omitted for clarity. Structure taken from Reilly et al. Chem. Commun. 2012, 48 (78), 9732.59

The ligand to metal ratio of 4.10 in the TODGA/n-dodecane system suggests the predominance of a four TODGA molecules around a single Eu(III) metal center. Assuming that all the TODGA molecules are coordinated to the metal, this would represent a 12-coordinate environment. Although possible, 12-coordinate complexes with Eu3+ are rare and involve small multidentate ligands that take up very little space in the coordination sphere (e.g., nitrate).60 Jensen et al. have studied the TODGA/n-octane system using small-angle neutron scattering (SANS) and vapor pressure osmometry (VPO) and found evidence that TODGA starts forming small reverse

61 micelles (n = 4) at the critical micelle acidity of 0.7 M HNO3. These TODGA tetramers contain extracted nitric acid ([HNO3]org = 10 mM) and water ([H2O]org = 21 mM) and form with or without

Ln(III) metal present. This may suggest that the Ln(III) metal is only partially coordinated to the

TODGA ligands inside the tetrameric reverse micelle.

Unfortunately, these TODGA aggregates are susceptible to third phase formation wherein a second organic phase enriched in extractant molecule, nitric acid, water, and metal cations

(if present) separates from the bulk organic phase – formally a metastable triphasic system involving three distinct liquids and two liquid-liquid interfaces.62 A third phase can be dangerous in a solvent extraction process that contains radioactive and fissile materials. A certain mass and geometry of fissile materials (e.g., 239Pu: critical mass = 2.6 kg metal, 0.22 kg aqueous solution) can lead to an accidental criticality where a fission chain reaction becomes self-sustaining.63 The formation of a third phase has the potential to concentrate fissile radioisotopes into a geometry that is favorable for criticality. The addition of a phase modifier or an increase in temperature are two methods for eliminating a third phase.43 Increasing the temperature adds more energy to the system, which can disrupt weaker intermolecular interactions (e.g., dipole-dipole and London dispersion forces) between extractant molecules that contribute to third phase formation.64 Several solvent extraction systems, including the TRUEX process, can be run at elevated temperatures

(e.g., 40°C) to hinder third phase formation.38

Phase modifiers (often surface-active long-chain alcohols or similar weakly solvating species that do not compete with the primary extractant for the target metal ions) can be added to a system to increase the polarity of the solvent and thereby maintain a homogeneous organic phase.

Magnusson et al. added the solvating extractant TBP to a TODGA-hydrogenated tetrapropylene

(TPH) solvent and achieved quantitative extraction of An(III) and Ln(III) from a genuine PUREX raffinate.65 Sasaki et al. added the monoamide dihexyloctanamide (DHOA, Figure 1.26) to a

TODGA-n-dodecane solvent and were able to saturate the organic phase with Nd(III) following the theoretical 3:1 ligand-metal ratio.66

Figure 1.26. Structure of N,N-dihexyloctanamide (DHOA).

Polar organic diluents (e.g., 1-octanol) have also been used to suppress third phase formation because the higher dielectric constant supports more electrical charge in the organic phase. The dielectric constant is a measure of the ability of an insulating medium to reduce the electric field between two charges.67 Metal cations have positive electric charges, which are more easily shielded in a medium with a higher dielectric constant (e.g., H2O). Table 1.4 shows the dielectric constants for reprocessing relevant liquids.68

Table 1.4. Relative dielectric constants (εr) for liquids relevant to solvent extraction processes. Liquid Dielectric Constant (εr) Temp. (°C) n-dodecane 2.0120 20 tributyl phosphate 8.34 20 1-octanol 10.30 20 methyl isobutyl ketone 13.11 20 N,N-dibutylacetamide 19.1 20 water 80.100 20

The difference between the dielectric constants of the aqueous phase (εr (water) = 80.1) and the organic phase (εr (n-dodecane) = 2.01) is large and makes it impossible for bare cations to spontaneously partition into the organic phase. The amphiphilic nature of the extractant molecule provides a polar core for the metal cation, which allows the charged cation to move into a nonpolar solvent. At high metal loading of the organic phase, it can become necessary to add a phase

modifier that increases the polarity of the medium. Ansari et al. extracted Nd(III) from 3 M HNO3 with 0.1 M TODGA in both n-dodecane and 1-octanol and found an increase in the limiting organic concentration (LOC) of Nd(III) from n-dodecane (8 mM Nd) to 1-octanol (49 mM Nd).69 The limiting organic concentration is the maximum amount of metal that can be extracted into an organic phase before a third phase forms. Assuming a 3:1 TODGA-Nd complex in n-dodecane, the maximum organic concentration of Nd would be 33.3 mM for 100 mM TODGA. The experimental LOC was only 8 mM Nd, which means that organic solvent is only 24% loaded. This value is the lower limit, as the calculation does not take into account the HNO3 that is extracted by

TODGA, which reduces the free ligand concentration.

An extensive study by Sasaki et al. showed that TODGA also extracts fission products, including Zr(IV) and Sr(II).70 Further studies using the branched alkyl group derivative

N,N,N',N'-tetra(2-ethylhexyl)diglycolamide (TEHDGA, Figure 1.27) demonstrated a suppression of the extraction of fission products (e.g., Sr(II)) compared to TODGA.71 Branched alkyl groups add steric hindrance near the binding pocket, which leads to a decrease in metal extraction. The branching also disrupts reverse micelle formation, which can lead to third phase formation. As expected, TEHDGA has lower partitioning coefficients than TODGA for all metal cations under similar conditions. TEHDGA also has a much lower LOC for Nd(III) than TODGA, however, which does not support the branched alkyl group third phase disruption theory.72 The addition of the phase modifier DHOA to both TODGA and TEHDGA solvents led to a significant increase in the LOC for Nd(III) for both ligands that corresponded to a saturated 3:1 ligand-metal ratio.

Figure 1.27. Structure of N,N,N',N'-tetra(2-ethylhexyl)diglycolamide (TEHDGA).

Recently, Ravi et al. synthesized an unsymmetrical diglycolamide (UDGA) ligand using both n-octyl and 2-ethylhexyl alkyl groups.73 DEHDODGA (Figure 1.28) was still prone to third phase formation at high nitric acid concentration (i.e., 3 M) and had consistently lower LOC values than TODGA with the addition of the phase modifier DHOA.74 Seeking to eliminate the need for a phase modifier, Ravi et al. synthesized a series of UDGA ligands with different alkyl groups

(e.g., n-hexyl, n-decyl, n-dodecyl) replacing the 2-ethylhexyl group.75,76 The authors found that the n-dodecyl derivative (D3DODGA, Figure 1.29) had a much higher LOC value for Nd(III) than

TODGA and did not require a phase modifier to extract minor actinides from a simulated high-level liquid waste (SHLLW).77

Figure 1.28. Structure of N,N-di(2-ethylhexyl)-N',N'-dioctyldiglycolamide (DEHDODGA).

Figure 1.29. Structure of N,N-didodecyl-N',N'-dioctyldiglycolamide (D3DODGA).

The goal of the work described here is to further explore the characteristics of unsymmetrical diglycolamides in solvent extraction systems. This is a multifaceted objective because the design of effective extractant molecules demands both the creation of a cation-compatible binding pocket in a geometry that is also amphiphilic (having both polar and non-polar constituents and thus interfacially active). Investigating this concept will demand a combination of organic synthesis, inorganic coordination chemistry, and separation science. Based on this examination of the literature, the desire for phosphorus-free reagents and the comparative

ease of synthesis, the target polar functional group will be the unsymmetrical dialkyl diglycolamides.

One of the advantages of the diglycolamides is their ability to quantitatively extract metals at high nitric acid concentration (e.g., 3 M) and also allow metals to be stripped into a dilute nitric acid medium (e.g., 0.01 M). Solvent extraction studies using radiotracer 152,154Eu were performed to evaluate the dependence of nitric acid concentration on metal extraction by the UDGA ligands.

Phase transfer kinetics were determined by monitoring the distribution of the metal as a function of time and/or agitation. The ligand concentration was also varied to determine the stoichiometry of the metal-ligand complexes.

Conditional stability constants of the metal-ligand complexes were determined using luminescence spectroscopy. Each ligand was titrated into a solution of europium and the peaks at

5 7 5 7 590 nm ( D0 → F1, magnetic dipole) and 618 nm ( D0 → F2, hypersensitive peak) were monitored for changes. The spectra were fit using the program HypSpec78 and stability constants were obtained for the various metal-ligand complexes.

One obstacle to the use of diglycolamides in nuclear fuel processing is their tendency towards third phase formation at either high nitric acid concentration or high metal loading.

Appropriately-configured unsymmetrical diglycolamides could possibly maintain the favorable nitric acid dependence while suppressing the aggregation of ligand molecules in the organic phase.

Metal loading experiments were done to test the limiting organic concentration of Eu(III) for selected ligands. Separate experiments were also performed to determine the extraction of nitric acid by the UDGA ligands and allow for a calculation of an equilibrium constant for HNO3 extraction and thus the concentration of the free ligand.

Twelve new UDGA ligands have been synthesized using a variety of alkyl groups, with one end of the molecule being more polar (e.g., pyrrolidinyl, piperidinyl, morpholino) and the other end being nonpolar (e.g., hexyl, octyl, 2-ethylhexyl, 3,7-dimethyloctyl). These ligands are truly unsymmetrical in the sense of polarity and their behavior at the interface or in the bulk organic phase is dictated by that asymmetry. This project investigates UDGA ligand behavior using various solvent extraction experiments and further probes the metal-ligand complexes using optical spectroscopy.

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Chapter 2

SYNTHESIS AND CHARACTERIZATION OF NEW UNSYMMETRICAL

DIGLYCOLAMIDES

2.1. Introduction

Nuclear energy provides 20% of the electricity used in the United States.1 This source of electricity relies on the radioactive properties of the actinide element uranium. Natural uranium that is mined from the Earth contains two different uranium isotopes: 235U (0.7%) and 238U

(99.3%). Uranium-235 is fissile, which means it is capable of sustaining a fission chain reaction by itself. On the other hand, uranium-238 is fissionable, which means it has the ability to fission but not maintain a chain reaction by itself. Natural uranium does not contain enough of the fissile isotope 235U to achieve the fission chain reaction that supplies the heat necessary to create steam to drive turbines and make electricity. The uranium dioxide fuel rods (10 × 4000 mm) used in most nuclear power plants are composed of about 3% 235U and 97% 238U, or 30 kg of 235U per metric ton of uranium oxide. Neutron capture by U-238 in the reactor core (ca. 40,000 fuel rods) leads to the formation of the transuranic elements neptunium, plutonium, americium, and curium.2 The asymmetric fission of the actinide nuclei also leads to the formation of the 36 elements from germanium to holmium. One metric ton of used nuclear fuel typically contains 35 kilograms of these fission products and 11 kilograms of the transuranic elements upon discharge from the reactor.3 In a closed nuclear fuel cycle, the uranium and plutonium are removed and recycled from the used fuel for continued use. This leaves behind the fission products, neptunium, and transplutonium elements as nuclear waste. In an effort to reduce the long-term radioactive hazard

associated with nuclear waste, many research groups are focused on developing processes to further separate various components of the waste for eventual disposal and storage or transmutation.

Most of the processes for used nuclear fuel separations employ liquid-liquid solvent extraction. Solvent extraction is the distribution of a solute between two immiscible liquid phase.4

The two immiscible liquid phases usually include an aqueous phase and an organic phase. The aqueous phase in used nuclear fuel reprocessing is determined by the initial decladding and leaching processes for the used fuel rods. High concentrations (e.g., 8 M) of nitric acid are sufficient for the dissolution of the uranium dioxide fuel pellets.5 Most of the fission products and transuranics are also soluble under these highly acidic conditions. This nitric acid based aqueous phase contains over forty different elements from every group in the periodic table. The organic phase solvent, or diluent, must be immiscible with the aqueous phase and should preferably be less dense than the aqueous phase. The organic phase for nuclear fuel reprocessing schemes can be designed to selectively extract certain metals of interest. Most solvent extraction systems contain an extractant, which is an interfacially-active amphiphilic molecule that forms complexes with metal solutes at the liquid-liquid interface and partitions the metal solute into the organic phase.4

Amphiphilic extractants have a polar region (usually containing oxygen, nitrogen, or sulfur donor atoms) for complexing with the metal cations and a nonpolar region (e.g., alkyl groups) to allow the metal-extractant complex to dissolve in the organic phase. Extractant design is a balance between increasing the solubility of the metal-extractant complex (e.g., larger or more alkyl groups) and increasing the metal complexation strength (e.g., more polar donor atoms). Several different processes with various extractants have been developed over the last 70 years for used

nuclear fuel separations. A selection of those processes will be presented as a foundation for this work.

The PUREX (Plutonium Uranium Reduction EXtraction) process achieves the separation of uranium and plutonium from the fission products and minor actinides through the use of tributyl phosphate (TBP, Figure 2.1) in a solvent extraction process.6 This process can also be adjusted to allow co-extraction of neptunium (UREX, NPEX processes).7,8 TBP will not extract trivalent actinides (e.g., Am(III)) or lanthanides (e.g., Eu(III)) from the nitric acid dissolver solution. The

Am(III) and Cm(III) present in the PUREX raffinate (aqueous phase depleted of Pu, U, and possibly Np) contribute significantly to the long-term radiotoxicity of the used nuclear fuel reprocessing residues, making repository development a challenging task. Solvent extraction processes have been developed to remove trivalent actinides from PUREX/UREX/NPEX residues but the problem presents itself in the form of the trivalent lanthanides. The chemistry of the trivalent actinides, An(III), and the trivalent lanthanides, Ln(III), is similar and separating the two groups of metals proves to be difficult. The separation of fission product lanthanides from transplutonium actinides is needed because of the large neutron capture cross-sections of several important lanthanide fission products, whose presence reduces the effectiveness of the transmutation of the minor actinides in fast breeder reactors (FBR) or controlled thermonuclear reactors (CTR).3 Both of these advanced reactor designs use above thermal neutron fluxes that can destroy the minor actinides through the process of fission. Many research groups around the world are focused on developing solvent extraction processes that address this specific issue.

Figure 2.1. Structure of tributyl phosphate (TBP).

Processes have also been developed to separate the byproducts of nuclear fission to isolate the f-elements from the 4d-transition, alkali, alkaline earth, and main group fission products. The

TRUEX (TRansUranic EXtraction) process uses the extractant octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO, Figure 2.2) to co-extract the An(III) and Ln(III) from the fission products in the PUREX raffinate.9 Tributyl phosphate is used alongside CMPO as a phase modifier to prevent third phase formation at high metal or acid concentrations. The TRUEX solvent can remove 99.99% of trivalent americium from simulated waste solutions.10 However, both CMPO and TBP also contain the element phosphorus, which is not completely incinerable and can complicate the eventual disposal process. To remove this extra complication, all nuclear separations should be based on reagents that leave no solid residue after incineration.

Figure 2.2. Structure of octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO).

The DIAMEX (DIAMide EXtraction) process avoids the phosphorus-based compounds and adheres to the CHON (Carbon Hydrogen Oxygen Nitrogen) principle. These four elements are completely incinerable which can simplify the eventual disposal process. The DIAMEX process uses N,Nʹ-dimethyl-N,Nʹ-dioctyl-2-hexylethoxymalonamide (DMDOHEMA) to extract the An(III) and Ln(III) from the PUREX raffinate (Figure 2.3).11 Unfortunately, DMDOHEMA also extracts certain transition metals (e.g., Zr, Mo, Pd). This has been shown to result in third

12 phase formation under some conditions (e.g., > 3 M HNO3).

Figure 2.3. Structure of N,N'-dimethyl-N,N'-dioctyl-2-hexylethoxymalonamide (DMDOHEMA).

Sasaki et al. developed a diglycolamide extractant called N,N,Nʹ,Nʹ-tetraoctyldiglycolamide (TODGA).13 TODGA is a diamide version of the water-soluble complexant, diglycolic acid. TODGA is a tridentate ligand as opposed to the bidentate diamide from the

DIAMEX process. The two amidic carbonyl oxygens are linked by an ether oxygen atom to strengthen the metal binding (Figure 2.4). TODGA has been shown to quantitatively extract both actinides and lanthanides from the fission products in highly acidic HNO3 solutions. Nevertheless,

TODGA also tends to form a problematic third phase at high HNO3 concentration. Testard and co-workers observed that the third phase formation is caused by the self-aggregation of the polar

TODGA cores into reverse micelles.14 Addition of tributyl phosphate increases the metal loading

capacity of the extractant which inhibits third-phase formation but reintroduces the phosphorus atom into the waste stream.15

Figure 2.4. Structure of N,N,Nʹ,Nʹ-tetraoctyldiglycolamide (TODGA) coordinated to generic metal cation (M).

The overall goal of this work was to design and synthesize a class of ligands that would allow partitioning of both trivalent lanthanides and trivalent actinides from used nuclear fuel. This would be followed by the separation of the Ln(III) and An(III) and the eventual transmutation of

Am(III) and Cm(III). This project also responded to the CHON principle while still providing pragmatic solutions to the handling and possible recycling of used nuclear fuel. The basis for the organic phase extractant design focused on the ability of the ligand to selectively extract the f-elements from the fission products and avoid third-phase formation. All synthesized ligands incorporated the diglycolamide binding site, which has already been shown to complex strongly with Ln(III) and An(III). The new approach in diglycolamide ligand design came in the form of asymmetry. Ravi et al. have synthesized a series of unsymmetrical diglycolamides with varying long-chain alkyl groups on either side of the molecule. The authors found that the dodecyl/octyl derivative (D3DODGA, Figure 2.5) had higher metal loading than TODGA and did not require a phase modifier to extract minor actinides from a simulated high-level liquid waste (SHLLW).16

Figure 2.5. Structure of N,N-didodecyl-N',N'-dioctyldiglycolamide (D3DODGA).

This work focused on polar/nonpolar asymmetry with one end of the molecule being a five- or six-membered ring and the other end being a hexyl or octyl group with optional branching. In this exploration of size-property relationships of this class of extractants, novel unsymmetrical diglycolamide ligands were synthesized and characterized using NMR and IR spectroscopy. The purpose of this study was to determine whether the more compact geometry provided by the asymmetric alkyl groups favorably impacted the phase transfer/compatibility properties of this type of reagent.

2.2. Materials

The diglycolic anhydride starting material was obtained from Alfa Aesar (97%) and used without further purification. All commercially available amines were obtained from

Sigma-Aldrich (reagent grade) and distilled out of calcium hydride before use. The branched C20 bis(3,7-dimethyloctyl)amine was prepared in a separate synthesis from (±)-citronellal (Alfa Aesar,

96%). 4-(dimethylamino)pyridine (DMAP) was obtained from Sigma-Aldrich (99%) and used

without further purification. All organic solvents were ACS reagent grade and used without further purification. Dimethyl sulfate was obtained from Sigma-Aldrich (99+%) and used without further purification. The filter aids diatomaceous earth (Celite® 521/546), activated charcoal (Norit®), and silica gel (technical grade, pore size 60 Å, 230-400 mesh particle size, 40-63 μm particle size) were obtained from Sigma-Aldrich. The drying reagent anhydrous magnesium sulfate was obtained from J.T. Baker (99%). Sulfuric acid and sodium hydroxide solutions were made using

ACS reagent grade chemicals with deionized water. Deuterated chloroform (CDCl3) was obtained from Cambridge Isotope Laboratories (99.8% D).

2.3. Methods

The amidation of diglycolic anhydride (Step 1) was adapted from a previous work by

Ramirez et al.17 The methylation of the diglycolamic acid (Step 2) was adapted from a fundamental work by Stodola.18 The amidation of the diglycolamic acid methyl ester (Step 3) was adapted from a review on amide bond formation by Montalbetti and Falque.19 All steps were performed under ambient atmospheric conditions. The amine synthesis from the starting material citronellal used a reductive amination reaction under a pressurized hydrogen atmosphere. The reaction was run in a saturated solution of anhydrous ammonia (NH3) in ethanol (EtOH). The saturated solution was made by bubbling NH3 gas into a stoppered graduated cylinder containing 15 mL of absolute EtOH for 10 minutes. A saturated solution of NH3 in absolute EtOH at 25°C is ca. 16% w/w NH3/EtOH

20 so the volume of EtOH determined the moles of NH3 dissolved.

Small amounts of platinum(IV) dioxide (Sigma-Aldrich, 99.5%) and rhodium

(Sigma-Aldrich, 5 wt% on carbon) were added as reaction catalysts. Crude products were purified by evaporative distillation using a Kugelrohr apparatus (Büchi). Further purification was completed using either a Teledyne Isco CombiFlash® Rf+ Lumen™ flash chromatography system or a custom-made medium-pressure liquid chromatography (MPLC#3) system fitted with a main column of ca. 100mL volume (ca. 125g 40-60 μm silica gel; 25 mm i.d., Ace Adjust-a-Chrom™ column) and a fore-column about 10 cm long containing about 16g of 40-60 μm silica gel.

Infrared (IR) spectroscopy data were collected using either a Thermo Electron Corporation

Nicolet™ 6700 or a Thermo Scientific Nicolet™ iS10 FT-IR spectrometer set up for transmission.

Reaction mixture samples and purified products were spotted directly onto NaCl plates for IR spectroscopic analysis. All spectra were collected from 4000 to 400 cm-1 using at least 16 scans and 4 cm-1 resolution. A background spectrum of air was taken before each sample was run.

Nuclear magnetic resonance (NMR) spectra were obtained using either a Varian Mercury

Vx 300 MHz spectrometer or a Varian/Agilent 400 MHz spectrometer. All samples were run in a

Wilmad-LabGlass 528-PP-7 5 mm thin wall precision NMR sample tube (7” L, 500 MHz). 1H and

13C NMR spectra were used to verify the structure of the products. Approximately 2-3 mg of purified product were dissolved in deuterated chloroform (CDCl3, Cambridge Isotope

Laboratories, 99.8% D) for 1H NMR spectra while ca. 15-20 mg of product were dissolved in

13 1 CDCl3 for C NMR spectra. H NMR spectra were run for at least 64 scans (nt) with a relaxation delay (d1) of 3 seconds. 13C NMR spectra were run for at least 512 scans (nt). Raw free induction decay (FID) data were digitized and Fourier transformed using the NMR processing program

MestReNova (Mestrelab Research, Version 10.0). All chemical shifts were referenced to the

21 CDCl3 peak at 7.260 ppm. All nuclear magnetic resonance (NMR) spectroscopy chemical shifts

(δ) are reported in ppm and coupling constants (J) in Hz.

High accuracy mass spectra were collected on a Sciex 4800 MALDI TOF/TOF Analyzer run in positive reflector mode using methods supplied by the manufacturer. Samples were mixed

1:1 with α-cyano-4-hydroxycinnamic acid (CHCA, Sigma-Aldrich) at 10 mg/mL in a

50% acetonitrile/0.1% trifluoroacetic acid solution. The sample with matrix were spotted onto a

384 plate, allowed to dry, and then loaded onto the instrument. Spectra were collected as the average of 400 shots and then internally calibrated using matrix peaks for the low mass range and

GluFib peptide for the high mass. When GluFib was included for internal calibration 2 μL of the

GluFib solution and 2 μL of the sample were mixed with 4 μL of matrix solution. Concentrations were adjusted to give similar peak heights for the sample and calibration peaks.

2.4. Synthetic Design Objectives

The diglycolamide backbone (see TODGA, Figure 2.4) has been shown to preferentially

13 extract Ln(III) and An(III) over tetravalent cations from highly acidic media (e.g., 1 M HNO3).

Symmetrical diglycolamides (e.g., TODGA) have two long-chain alkyl groups attached to each amidic nitrogen atom. These alkyl groups help to solubilize the ligand in organic diluents

(e.g., n-dodecane). These same alkyl groups can make it more difficult for the ligand to interact with metal cations dissolved in the aqueous phase of a biphasic solvent extraction system. TODGA has also been shown to form aggregates (four extractant molecules arranged in a reverse micelle in the n-dodecane) when in contact with high concentrations of nitric acid or metal.14 These

aggregates can lead to the formation of a second, more dense organic phase, which is problematic in solvent extraction systems where clean phase disengagement is key to metal separations.

This series of unsymmetrical diglycolamides was designed such that one of the amides maintained the long-chain alkyl groups and the other amide was replaced with a 5- or 6-membered ring. The ring structure is smaller and should have some aqueous solubility, allowing the ligand to interact more easily with metal cations dissolved in acidic media. This could lead to faster phase-transfer kinetics for metal extraction and stronger overall metal-ligand complexes in the organic phase. The asymmetry of the ligands could also limit the aggregation of the ligand molecules in the organic phase because of a decrease in the intermolecular forces between the ligands. The pyrrolidinyl (5-membered) and piperidinyl (6-membered) rings were incorporated into eight different ligands and compared based upon the differences in the ring size and orientation in space (e.g., pyrrolidine is in a staggered configuration while piperidine is in a bulkier chair configuration). The morpholino (6-membered, oxygen atom in the 4-position) ring was also used in the synthesis of four more ligands. The morpholino ligands can be directly compared to the piperidinyl ligands and the effect of an additional oxygen atom in the ligand can be used to draw conclusions about increasing the polarity of the amide ring structure.

The long-chain dialkylamide group was varied in both chain length (hexyl and octyl) and chain branching (2-ethylhexyl and 3,7-dimethyloctyl). The hexyl and octyl groups were used to draw a comparison between varying alkyl chain length, where the hexyl would be expected to increase metal complexation and the octyl would be expected to increase ligand solubility in the organic phase. The branched alkyl chain 2-ethylhexyl can be compared directly to the octyl group in terms of total number of carbons (8) and how the different isomers affect both the metal extraction and ligand solubility in n-dodecane. The doubly-branched alkyl chain 3,7-dimethyloctyl

was added as a comparison to the branching in the 2-position in the 2-ethylhexyl chains and the unbranched octyl chain. The 3,7-dimethyloctyl derivatives have the largest masses and would be expected to have higher solubility in the organic phase than the smaller hexyl, octyl, and

2-ethylhexyl derivatives.

2.5. Synthesis and Purification of Ligands 1-9

The synthetic approach for ligands 1-9 (names and structures provided in Table 2.3 and

Figure 2.9, respectively) started with a one-pot amidation and methylation reaction to yield three different diglycolamic acid methyl esters. These half methyl esters were then converted to the diamide in a second amidation reaction to yield nine different unsymmetrical diglycolamides.

The first step was the amidation of diglycolic anhydride with a long-chain secondary amine

(e.g., dihexylamine, dioctylamine, di-(2-ethylhexyl)amine). The reaction was conducted in a

50 mL two-necked round-bottom flask fitted with a pressure equalizing addition funnel and an air- cooled reflux condenser sealed with rubber septum. The system was vented with a plastic syringe needle in the septum. The diglycolic anhydride (1 equiv.) starting material and

4-(dimethylamino)pyridine (DMAP, 0.02 equiv.) acylation catalyst were weighed into the round- bottom flask and dissolved in dichloromethane (8 parts). The reaction was stirred constantly using a magnetic stir bar. The non-nucleophilic proton scavenger N,N-diisopropylethylamine (DIPEA

1.1 equiv.) was added directly into the reaction mixture using a glass syringe fitted with a stainless steel needle. The round-bottom flask was placed in an ice bath to slow down the highly exothermic reaction and avoid unwanted side reactions. The secondary amine (1 equivalent of dihexylamine,

dioctylamine, or di-(2-ethylhexyl)amine, Figure 2.6) was added to the pressure equalizing addition funnel using a glass syringe fitted with a stainless steel needle. The secondary amine was also dissolved in dichloromethane (3 parts) to dilute the reagent and moderate the exothermic reaction.

The secondary amine solution was added dropwise (ca. 10 drops/min) over a period of 20 minutes.

The reaction was stirred for an additional 30 minutes at 0°C after which a small sample was taken for analysis using infrared spectroscopy (IR). The disappearance of the diglycolic anhydride carbonyl stretch peaks at 1820 and 1770 cm-1 was taken to indicate that the reaction was complete.

A sample of the reaction mixture was also spotted on a thin-layer chromatography (TLC) plate next to the starting materials to confirm the reaction progress. The intermediate product, a

N,N-diisopropylethylammonium diglycolamate salt, showed up with carbonyl peaks around

1650 cm-1 for the amide group and 1610 cm-1 for the carboxylate group. The first step of the reaction is shown in Scheme 2.1.

Figure 2.6. Structures of the secondary dialkylamines: dihexylamine, dioctylamine, and di-(2-ethylhexyl)amine.

Scheme 2.1. Amidation of diglycolic anhydride with various secondary amines (R = hexyl, octyl, or 2-ethylhexyl).

The second step in this one-pot sequence was done without any purification of the intermediate diglycolamate salt. The alkylating agent dimethyl sulfate (Me2SO4, 1.3 equiv.) was charged into the addition funnel and diluted with dichloromethane (3 parts). The Me2SO4 solution was added dropwise (ca. 1 drop/sec) over a period of two minutes. The reaction mixture was stirred in the ice bath for 30 minutes and then allowed to stir at room temperature for 2-3 days. The reaction was monitored using IR spectroscopy. The ingrowth of the methyl ester carbonyl stretch peak at 1750 cm-1 and the disappearance of the carboxylate carbonyl stretch peak at 1620 cm-1 signified the reaction progress. The reaction was deemed complete when the carboxylate carbonyl stretch peak at 1620 cm-1 was absent from the IR spectrum. A sample of the reaction mixture was also spotted on a thin-layer chromatography plate next to the starting materials to confirm the reaction progress. The second step of the reaction is shown in Scheme 2.2.

Scheme 2.2. Alkylation of dialkyl diglycolamate with dimethyl sulfate (R = hexyl, octyl, or 2-ethylhexyl).

NaCl solution (brine). The organic phase was dried over anhydrous MgSO4 and filtered through a layer of Celite® 546 diatomaceous earth and activated charcoal to clarify the solution. The solution was then concentrated to a pale, orange oil using a rotary evaporator at reduced pressure and ca. 40°C. The crude methyl ester products were obtained as oils and evaporatively distilled using a Kugelrohr apparatus: N,N-dihexyldiglycolamic acid methyl ester (A) = ev 162–168°C, 0.100 mm Hg, 2.66 g (84%); N,N-dioctyldiglycolamic acid methyl ester (B) = ev 176–182°C, 0.050 mm Hg, 4.41 g (79%); N,N-di-2-ethylhexyldiglycolamic acid methyl ester (C) = ev 156–162°C,

0.050 mm Hg, 4.64 g (83%). The structures of the three different methyl esters are shown in

Figure 2.7.

Figure 2.7. Structures of N,N-dihexyldiglycolamic acid methyl ester (A), N,N-dioctyldiglycolamic acid methyl ester (B), and N,N-di-2-ethylhexyldiglycolamic acid methyl ester (C).

A small sample of the evaporatively distilled compounds was taken for IR and NMR spectroscopic analysis. IR spectroscopy showed the methyl ester peaks at 1753 ± 1 cm-1 for each compound. 1H-NMR spectroscopy showed the methyl ester peaks at 3.75 ± 0.01 ppm for each compound. NMR and IR spectroscopic data for compounds A-C are listed:

1 (A): H-NMR (300 MHz, CDCl3, δ): 4.28 (s, 2H), 4.26 (s, 2H), 3.75 (s, 3H), 3.29 (m, 2H), 3.19

-1 (m, 2H), 1.53 (br m, 4H), 1.28 (br m, 12H), 0.88 (br m, 6H). IR (NaCl, film) νmax (cm ): 2953

(s, CH, aliphatic), 2930 (s, CH, aliphatic), 2857 (s, CH, aliphatic), 1753 (s, C=O), 1647 (s, C=O),

1467 (m, C-N), 1439 (m, C-N), 1132 (m, C-O). Yield = 84%.

1 (B): H-NMR (400 MHz, CDCl3, δ): 4.28 (s, 2H), 4.26 (s, 2H), 3.76 (s, 3H), 3.29 (t, J = 7.7 Hz,

2H), 3.19 (t, J = 8.0 Hz, 2H), 1.53 (br m, 4H), 1.28 (br m, 20H), 0.88 (br m, 6H). IR (NaCl, film)

-1 νmax (cm ): 2953 (s, CH, aliphatic), 2927 (s, CH, aliphatic), 2854 (s, CH, aliphatic), 1754 (s, C=O),

1650 (s, C=O), 1465 (m, C-N), 1437 (m, C-N), 1131 (m, C-O). Yield = 79%.

1 (C): H-NMR (400 MHz, CDCl3, δ): 4.31 (s, 2H), 4.26 (s, 2H), 3.75 (s, 3H), 3.28 (qd, J1 = 13.6 Hz,

J2 = 7.4 Hz, 2H), 3.11 (d, J = 7.5 Hz, 2H), 1.67 (m, 1H), 1.57 (m, 1H), 1.27 (br m, 16H), 0.88

-1 (br m, 12H). IR (NaCl, film) νmax (cm ): 2958 (s, CH, aliphatic), 2921 (s, CH, aliphatic), 2872

(s, CH, aliphatic), 2856 (s, CH, aliphatic), 1753 (s, C=O), 1646 (s, C=O), 1458 (m, C-N), 1434

(m, C-N), 1123 (m, C-O). Yield = 83%.

The purified compounds were then used in the third step of this reaction scheme: an amidation using cyclic secondary amines. Each dialkyl diglycolamic methyl ester compound

(1 equiv.) was weighed into a small, tared round-bottom flask. The cyclic secondary amines

(pyrrolidine, piperidine, morpholine; Figure 2.8) were added in excess (3 equiv.) using a glass

syringe fitted with a stainless steel needle. The reaction was run without additional solvent. The reaction mixture was stirred constantly. An air-cooled reflux condenser was fitted into the round- bottom flask and sealed with a rubber septum. The system was vented with a plastic syringe needle in the septum. The solution was heated at 90°C using an oil bath to boil off the methanol byproduct.

The reaction was heated and stirred for 1-2 days and monitored using IR spectroscopy. The reaction was judged to be complete when the methyl ester carbonyl stretch peak at ca. 1750 cm-1 was no longer visible in the IR spectrum. A sample of the reaction mixture was also spotted on a thin-layer chromatography plate next to the starting materials to confirm the reaction progress. The reaction is shown in Scheme 2.3.

Figure 2.8. Structures of the cyclic secondary amines: pyrrolidine, piperidine, and morpholine.

The excess cyclic amine was removed using rotary evaporation to yield an orange oil in each system. The crude diglycolamide product was either evaporatively distilled using a Kugelrohr apparatus (pyrrolidinyl and piperidinyl derivatives) or flash chromatographed (morpholino derivatives) to yield a yellowish orange oil. The evaporative distillation conditions along with the yields for the pyrrolidinyl and piperidinyl derivatives are shown in Table 2.1.

Scheme 2.3. Amidation of dialkyl diglycolamic methyl esters (R = hexyl, octyl, or 2-ethylhexyl) with three different cyclic secondary amines (pyrrolidine, piperidine, and morpholine).

Table 2.1. Evaporative distillation temperature ranges (ev, °C) and pressures (P, mm Hg) for pyrrolidinyl and piperidinyl ligands 1, 2, 4, 5, 7, and 8. Mass and percent yields for the second amidation reaction are also listed. Morpholino ligands (3, 6 and 9) were purified via flash chromatography instead of evaporative distillation. Ligand # ev (°C) P (mm Hg) Yield (g) Yield (%) 1 170-175 0.100 1.05 93 2 179-185 0.100 1.10 90 4 200-205 0.100 1.50 90 5 193-200 0.050 1.51 88 7 184-189 0.050 1.56 94 8 167-172 0.050 1.55 90

Flash Chromatography: CombiFlash® Rf+ Lumen™

The three morpholine derivatives (3, 6, and 9) were purified using a Teledyne Isco

CombiFlash® Rf+ Lumen™ flash chromatography system. A solid loading sample cartridge (25 g capacity) was first loaded with ca. 5 g of silica gel (40-63 μm particle size) to act as a guard column to keep polar impurities from reaching the main column. The crude morpholino ligand was then dissolved in dichloromethane in a 50 mL round-bottom flask. Silica gel (40-63 μm particle size) was weighed into the same flask at a ratio of 2:1 silica gel to crude sample. A few drops of methanol

(MeOH) were added to the flask to evenly disperse the compound onto the silica gel. The solvent was removed via rotary evaporation to produce a free-flowing off-white silica gel. The solid sample was added to the same solid loading cartridge and packed tightly using a circular glass frit and a Teflon™ cylinder. The sample was run on a 40 g RediSep® Rf silica gel (40-60 μm particle size) flash column with a flow rate of 40 mL/min. Eluent A was hexanes and eluent B was 5% v/v methanol (MeOH) in ethyl acetate (EtOAc). The solvent gradient was and elution times were adjusted to maximize peak separation. Thin-layer chromatography was used check selected fractions for compound purity. Fractions with identical retention factors (Rf) were combined and concentrated to a clear and nearly colorless oil. The flash chromatography conditions along with the yields for the morpholine derivatives are shown in Table 2.2.

Table 2.2. Flash chromatography elution times and solvent gradients for morpholino ligands 3, 6, and 9. Mass and percent yields for the second amidation reaction are also listed (Solvent A = hexanes, Solvent B = 5% v/v MeOH/EtOAc). Ligand # Elution Time (min) Solvent B Gradient (%) Yield (g) Yield (%) 3 39 0-59 2.04 39 6 34 0-58 1.60 68 9 31 0-55 1.43 51

The full names (following Sasaki et al.22 and not IUPAC nomenclature), molecular weights

(MW), and overall percent yields for ligands 1-9 are shown below in Table 2.3. The structures for ligands 1-9 are shown in Figure 2.9.

Table 2.3. Names, molecular weights, and overall percent yields for unsymmetrical diglycolamide ligands 1-9. # Unsymmetrical Diglycolamide Ligand MW (g/mol) Overall Yield (%) 1 N,N-dihexyl-N'-pyrrolidinyldiglycolamide 354.535 79 2 N,N-dihexyl-N'-piperidinyldiglycolamide 368.562 80 3 N,N-dihexyl-N'-morpholinodiglycolamide 370.534 32 4 N,N-dioctyl-N'-pyrrolidinyldiglycolamide 410.643 71 5 N,N-dioctyl-N'-piperidinyldiglycolamide 424.670 69 6 N,N-dioctyl-N'-morpholinodiglycolamide 426.642 45 7 N,N-di-2-ethylhexyl-N'-pyrrolidinyldiglycolamide 410.643 78 8 N,N-di-2-ethylhexyl-N'-piperidinyldiglycolamide 424.670 75 9 N,N-di-2-ethylhexyl-N'-morpholinodiglycolamide 426.642 32

Small samples were taken of each purified compound and analyzed using 1H and 13C NMR spectroscopy, IR spectroscopy, and high resolution mass spectrometry. Data for ligands 1-9 are shown below:

1 DHpyrDGA(1): H-NMR (400 MHz, CDCl3, δ): 4.32 (s, 2H), 4.26 (s, 2H), 3.49 (t, J = 6.9 Hz,

2H), 3.41 (t, J = 6.8 Hz, 2H), 3.29 (m, 2H), 3.19 (m, 2H), 1.94 (p, J = 6.8 Hz, 2H), 1.83

(p, J = 6.5 Hz, 2H), 1.51 (br m, 4H), 1.27 (br m, 12H), 0.87 (br m, 6H). 13C-NMR (101 MHz,

CDCl3, δ): 168.46, 167.81, 69.94, 69.33, 47.10, 46.01, 45.93, 45.70, 31.73, 31.67, 29.04, 27.68,

-1 26.84, 26.64, 26.32, 24.05, 22.73, 22.71, 14.17, 14.12. IR (NaCl, film) νmax (cm ): 2955 (s, CH, aliphatic), 2928 (s, CH, aliphatic), 2869 (s, CH, aliphatic), 2857 (s, CH, aliphatic), 1651 (s, C=O),

1451 (m, C-N), 1431 (m, C-N), 1131 (m, C-O). HRMS-MALDI TOF/TOF (m/z): [M + H]+(calc.)

= 355.29614; [M + H]+(exp.) = 355.29568. Overall yield = 79%.

1 DHpipDGA(2): H-NMR (400 MHz, CDCl3, δ): 4.29 (s, 2H), 4.26 (s, 2H), 3.52 (t, J = 5.5 Hz,

2H), 3.39 (t, J = 5.4 Hz, 2H), 3.28 (t, J = 7.7 Hz, 2H), 3.15 (t, J = 7.6 Hz, 2H), 1.61 (br m, 2H),

13 1.53 (br m, 8 H), 1.27 (br m, 12H), 0.87 (br m, 6H). C-NMR (101 MHz, CDCl3, δ): 168.44,

167.24, 69.96, 69.27, 47.00, 46.07, 45.86, 42.95, 31.70, 31.63, 29.00, 27.66, 26.80, 26.60, 26.52,

-1 25.67, 24.58, 22.70, 22.67, 14.14, 14.09. IR (NaCl, film) νmax (cm ): 2929 (s, CH, aliphatic), 2854

(s, CH, aliphatic), 1650 (s, C=O), 1466 (m, C-N), 1443 (m, C-N), 1119 (m, C-O). HRMS-MALDI

TOF/TOF (m/z): [M + H]+(calc.) = 369.31184; [M + H]+(exp.) = 369.31253. Overall yield = 80%.

1 DHmorDGA(3): H-NMR (400 MHz, CDCl3, δ): 4.28 (s, 2H), 4.23 (s, 2H), 3.65 (t, J = 4.6 Hz,

4H), 3.58 (t, J = 4.7 Hz, 4H), 3.26 (m, 2H), 3.11 (m, 2H), 1.49 (m, 4H), 1.26 (m, 12H), 0.86

13 (m, 6H). C-NMR (101 MHz, CDCl3, δ): 168.15, 167.55, 70.27, 68.99, 66.92, 66.90, 46.89, 45.88,

45.70, 42.17, 31.66, 31.57, 28.94, 27.64, 26.76, 26.57, 22.67, 22.63, 14.11, 14.07. IR (NaCl, film)

-1 νmax (cm ): 2954 (s, CH, aliphatic), 2928 (s, CH, aliphatic), 2867 (s, CH, aliphatic), 1655 (s, C=O),

1465 (m, C-N), 1434 (m, C-N), 1116 (m, C-O). HRMS-MALDI TOF/TOF (m/z): [M + H]+(calc.)

= 371.29043; [M + H]+(exp.) = 371.29205. Overall yield = 32%.

1 DOpyrDGA(4): H-NMR (400 MHz, CDCl3, δ): 4.31 (s, 2H), 4.25 (s, 2H), 3.49 (t, J = 6.9 Hz,

2H), 3.41 (t, J = 6.8 Hz, 2H), 3.29 (m, 2H), 3.18 (m, 2H), 1.94 (p, J = 6.9 Hz, 2H), 1.84

(p, J = 6.7 Hz, 2H), 1.52 (br m, 4H), 1.27 (br m, 20H), 0.87 (dt, J1 = 3.5 Hz, J2 = 6.8 Hz, 6H).

13 C-NMR (101 MHz, CDCl3, δ): 168.47, 167.66, 69.83 69.24, 47.00, 45.90, 45.82, 45.59, 31.86,

31.80, 29.42, 29.38, 27.65, 27.10, 26.89, 26.25, 23.97, 22.69, 22.67, 14.14. IR (NaCl, film)

-1 νmax (cm ): 2956 (s, CH, aliphatic), 2927 (s, CH, aliphatic), 2871 (s, CH, aliphatic), 2854 (s, CH, aliphatic), 1652 (s, C=O), 1451 (m, C-N), 1129 (m, C-O). HRMS-MALDI TOF/TOF (m/z):

[M + H]+(calc.) = 411.35874; [M + H]+(exp.) = 411.35913. Overall yield = 71%.

1 DOpipDGA(5): H-NMR (400 MHz, CDCl3, δ): 4.34 (s, 2H), 4.30 (s, 2H), 3.54 (m, 2H), 3.41

(m, 2H), 3.29 (m, 2H), 3.17 (m, 2H), 1.63 (br m, 2H), 1.54 (br m, 8H), 1.27 (br m, 20H), 0.87

13 (m, 6H). C-NMR (101 MHz, CDCl3, δ): 168.51, 167.32, 77.16, 70.01, 69.32, 47.05, 46.11, 45.92,

43.00, 31.94, 31.89, 29.51, 29.46, 29.38, 29.34, 29.07, 27.73, 27.18, 26.98, 26.56, 25.70, 24.61,

-1 22.78, 22.75, 14.22. IR (NaCl, film) νmax (cm ): 2929 (s, CH, aliphatic), 2854 (s, CH, aliphatic),

1652 (s, C=O), 1467 (m, C-N), 1443 (m, C-N), 1119 (m, C-O). HRMS-MALDI TOF/TOF (m/z):

[M + H]+(calc.) = 425.37444; [M + H]+(exp.) = 425.37344. Overall yield = 69%.

1 DOmorDGA(6): H-NMR (400 MHz, CDCl3, δ): 4.31 (s, 2H), 4.26 (s, 2H), 3.68 (m, 4H), 3.62

(m, 4H), 3.29 (m, 2H), 3.13 (m, 2H), 1.52 (br m, 4H), 1.27 (br m, 20H), 0.88 (dt, J1 = 3.3 Hz,

13 J2 = 6.9 Hz, 6H). C-NMR (101 MHz, CDCl3, δ): 168.25, 167.64, 70.35, 69.06, 66.98, 66.96,

46.99, 45.98, 45.78, 42.25, 31.92, 31.87, 29.49, 29.42, 29.37, 29.32, 29.04, 27.74, 27.17, 26.98,

-1 22.76, 22.74, 14.21. IR (NaCl, film) νmax (cm ): 2956 (s, CH, aliphatic), 2929 (s, CH, aliphatic),

2859 (s, CH, aliphatic), 1658 (s, C=O), 1469 (m, C-N), 1431 (m, C-N), 1112 (m, C-O).

HRMS-MALDI TOF/TOF (m/z): [M + H]+(calc.) = 427.35374; [M + H]+(exp.) = 427.35483.

Overall yield = 45%.

1 DEHpyrDGA(7): H-NMR (300 MHz, CDCl3, δ): 4.38 (s, 2H), 4.29 (s, 2H), 3.49 (t, J = 6.8 Hz,

2H), 3.41 (t, J = 6.7 Hz, 2H), 3.28 (m, 2H), 3.10 (d, J = 7.5 Hz, 2H), 1.94 (p, J = 6.4 Hz, 2H), 1.85

(p, J = 6.2 Hz, 2H), 1.67 (m, 1H), 1.57 (m, 1H), 1.25 (br m, 16H), 0.87 (br m, 12H). 13C-NMR

(151 MHz, CDCl3, δ): 169.60, 167.73, 69.86, 69.41, 50.24, 48.09, 45.97, 45.67, 38.08, 36.82,

30.69, 30.63, 28.97, 28.96, 28.84, 28.83, 26.32, 24.04, 23.97, 23.93, 23.21, 23.14, 14.20, 14.15,

-1 11.09, 10.78, 10.77. IR (NaCl, film) νmax (cm ): 2959 (s, CH, aliphatic), 2929 (s, CH, aliphatic),

2871 (s, CH, aliphatic), 2859 (s, CH, aliphatic), 1654 (s, C=O), 1455 (m, C-N), 1422 (m, C-N),

1123 (m, C-O). HRMS-MALDI TOF/TOF (m/z): [M + H]+(calc.) = 411.35874; [M + H]+(exp.) =

411.35913. Overall yield = 78%.

1 DEHpipDGA(8): H-NMR (300 MHz, CDCl3, δ): 4.33 (s, 2H), 4.33 (s, 2H), 3.54 (m, 2H), 3.41

(m, 2H), 3.29 (m, 2H), 3.08 (d, J = 7.5 Hz, 2H), 1.63 (br m, 4H), 1.56 (br m, 4H), 1.25 (br m,

13 16H), 0.88 (m, 12H). C-NMR (101 MHz, CDCl3, δ): 169.46, 167.24, 69.93, 69.39, 50.16, 48.06,

46.07, 42.97, 38.07, 36.79, 30.66, 30.62, 28.96, 28.82, 26.53, 25.69, 24.60, 23.93, 23.20, 23.13,

-1 14.20, 14.15, 11.08, 10.76. IR (NaCl, film) νmax (cm ): 2957 (s, CH, aliphatic), 2931 (s, CH, aliphatic), 2870 (s, CH, aliphatic), 2856 (s, CH, aliphatic), 1653 (s, C=O), 1461 (m, C-N), 1443

(m, C-N), 1119 (m, C-O). HRMS-MALDI TOF/TOF (m/z): [M + H]+(calc.) = 425.37444;

[M + H]+(exp.) = 425.37466. Overall yield = 75%.

1 DEHmorDGA(9): H-NMR (300 MHz, CDCl3, δ): 4.31 (s, 2H), 4.29 (s, 2H), 3.68 (m, 4H), 3.61

(m, 4H), 3.27 (m, 2H), 3.05 (d, J = 7.5 Hz, 2H), 1.66 (m, 1H), 1.56 (m, 1H), 1.27 (m, 16H), 0.88

13 (m, 12H). C-NMR (101 MHz, CDCl3, δ): 169.23, 167.63, 70.30, 69.22, 66.98, 50.15, 48.20,

45.77, 42.25, 38.12, 36.81, 30.67, 28.94, 28.80, 23.95, 23.22, 23.14, 14.21, 14.17, 11.07, 10.81.

-1 IR (NaCl, film) νmax (cm ): 2957 (s, CH, aliphatic), 2924 (s, CH, aliphatic), 2868 (s, CH, aliphatic),

2854 (s, CH, aliphatic), 1653 (s, C=O), 1457 (m, C-N), 1438 (m, C-N), 1108 (m, C-O).

HRMS-MALDI TOF/TOF (m/z): [M + H]+(calc.) = 427.35374; [M + H]+(exp.) = 427.35373.

Overall yield = 32%.

2.6. Synthesis and Purification of Ligands 10-12

The synthetic approach for ligands 10-12 started with the reductive amination of the commercially available unsaturated, branched aldehyde, citronellal, with ammonia (NH3) in absolute ethanol (EtOH) using a platinum catalyst. The platinum(IV) oxide catalyst (0.01 equiv.) was suspended in EtOH (0.5 parts) and pre-reduced to platinum(0), “platinum black”, in a small

Ace-Thred™ pressure tube (length = 20 cm, width = 2.5 cm, ca. 35 mL capacity, 150 psi max.) with a #15 nylon threaded cap attached to a pressure gauge and needle valve. A ball valve was plumbed between the pressure tube and the hydrogen gas feed/house vacuum for gas evacuating and repressurization. The pressure tube was evacuated via a vacuum line and repressurized with

40 psi of hydrogen gas three times to charge the tube with a hydrogen atmosphere. The reaction was stirring continuously and allowed to react for 10 minutes to reduce the Pt(IV) to Pt(0).

The citronellal (1 equiv.) was weighed into a large Ace-Thred™ pressure tube (length =

34 cm, width = 2.5 cm, ca. 60 mL capacity, 150 psi max.) with a #15 nylon threaded cap attached to a pressure gauge and needle valve. The aldehyde was dissolved in EtOH (3 parts) and stirred continuously using a magnetic stir bar. A saturated solution of ammonia (ca. 7 M NH3, 2.1 equiv.) in absolute ethanol (ca. 15 mL) was made and added to the large pressure tube.20 The reduced platinum catalyst solution was then added to the large pressure tube and the reaction mixture was pressurized to 40 psi of H2, following the same procedure from above. The reaction vessel was refilled with hydrogen gas periodically until the H2 pressure remained constant. The reductive amination step is shown in Scheme 2.4.

Scheme 2.4. Reductive amination of citronellal with NH3, PtO2, and H2 in absolute ethanol.

The secondary amine was the main product of this reaction with the Pt catalyst, however, typically only about 50% of the double bonds were reduced (as determined by integration of relevant peaks in 1H NMR spectrum). The residual double bonds were reduced by adding a pre-reduced 5 wt% rhodium on carbon (Rh/C) catalyst. The 5 wt% Rh/C catalyst (0.013 equiv.) was pre-reduced using the same procedure as described for the Pt catalyst. The activated 5 wt%

Rh/C catalyst was then added to the large pressure tube containing the previous reaction mixture

(see Scheme 2.4). The pressure tube was charged with 40 psi of H2 and monitored for any loss of pressure. The reaction vessel was refilled with hydrogen gas periodically until the H2 pressure remained constant. The hydrogenation of the partially reduced secondary amine is shown in

Scheme 2.5.

Scheme 2.5. Hydrogenation of partially reduced N-(3,7-dimethyloctyl)- 3,7-dimethyloct-6-en-1-amine with 5 wt% Rh/C under H2 atmosphere (NH3 and PtO2 still present in reaction mixture).

The crude product was purified by two different routes: recrystallization and evaporative distillation. The hydrochloride salt of bis(3,7-dimethyloctyl)amine was made by adding concentrated hydrochloric acid to the reaction mixture. The reaction mixture was then filtered through a pad of Celite® 521 (to remove catalyst) to give a white solid. The bis(3,7-dimethyloctyl)amine hydrochloride salt was then recrystallized from isopropyl ether

(containing a small amount of ethanol) to give a white solid (mp 138-141°C, 4.45 g, 82% yield).

A separate reaction mixture was filtered through a pad of anhydrous MgSO4 (to remove catalyst) and was concentrated at reduced pressure to afford a clear, colorless oil. The crude product was evaporatively distilled, which resulted in a clear, colorless oil with some crystalline material at the bottom of the distillate flask (ev 115-123°C, 0.050 mm Hg, 6.98 g, 93% yield). The complete saturation of the amine was supported by the absence of an alkene C-H peak (5.1 ppm) on the

1H NMR spectrum. The identity of the amine was also confirmed using high resolution mass spectrometry on samples of the bulk oil (2A) and crystal phases (2B). Both samples were found to contain only the secondary amine: [M + H]+(calc.) = 298.34683 m/z; (2A) [M + H]+(exp.) =

298.34875 m/z; (2B): [M + H]+(exp.) = 298.34842 m/z. The difference in crystallinity between the two samples of secondary amine is likely due to the presence of meso and dl stereoisomers. Each branched alkyl chain of the amine contains one stereocenter so there are theoretically four different stereoisomers for this compound (maximum number of stereoisomers = 2n, where n = number of stereocenters).23 Since two of these stereoisomers are meso and therefore identical, there are three different stereoisomers for bis(3,7-dimethyloctyl)amine shown in Figure 2.10.

Figure 2.10. Stereochemical structures of the three different isomers of bis(3,7-dimethyloctyl)amine (d, l, and meso).

The newly synthesized bis(3,7-dimethyloctyl)amine (1 equiv.) was then reacted with excess diglycolic anhydride (2.59 equiv.) in the presence of the acylation catalyst, DMAP

(0.032 equiv.), and the proton scavenger, DIPEA (1.16 equiv.). The limiting reagent in this reaction scheme is the valuable secondary amine, as opposed to Scheme 2.1 where the limiting reagent is diglycolic anhydride. This revised method ensures that all of the amine reacts with the anhydride to form the desired intermediate salt. The reaction was monitored by IR spectroscopy

and was judged to be complete when there was unreacted diglycolic anhydride remaining in the reaction mixture (i.e., peaks present at 1820 and 1770 cm-1 in the IR spectrum). Carbonyl peaks were also observed at 1650 cm-1 for the amide group and 1610-1620 cm-1 for the carboxylate group. This method of reaction monitoring is likely better than the reverse where the disappearance of the anhydride peaks is observed. Diglycolic anhydride is susceptible to nucleophilic attack from not only the 4-(dimethylamino)pyridine (DMAP) and bis(3,7-dimethyloctyl)amine (DMOA) nitrogen atoms but also from water. This small side reaction can lead to the formation of diglycolic acid, which will not form the desired half-amide compound. A sample of the reaction mixture was also spotted on a thin-layer chromatography plate next to the starting materials to confirm the reaction progress. The reaction of bis(3,7-dimethyloctyl)amine with diglycolic anhydride is shown in Scheme 2.6.

Scheme 2.6. Amidation of diglycolic anhydride with bis(3,7-dimethyloctyl)amine.

The next step for this synthesis was completed in the same round-bottom flask as the last step without any purification of the intermediate diglycolamate salt. The alkylating agent dimethyl sulfate (Me2SO4, 2.85 equiv.) was charged into the addition funnel and diluted with dichloromethane (4.5 parts). The Me2SO4 solution was added dropwise (ca. 1 drop/sec) over a period of two minutes. The reaction mixture was stirred in the ice bath for 30 minutes and then

allowed to stir at room temperature for two days. The reaction was monitored using IR spectroscopy. The ingrowth of the methyl ester carbonyl stretch peak at 1750 cm-1 and the disappearance of the carboxylate carbonyl stretch peak at 1620 cm-1 signified the reaction progress.

The reaction was deemed complete when the carboxylate carbonyl stretch peak at 1620 cm-1 was completely absent from the IR spectrum. After 1-2 days, the reaction was quenched with triethylamine (TEA, 2.9 equiv.) to react with any Me2SO4 remaining and prevent unwanted side reactions. The alkylation reaction is shown in Scheme 2.7.

Scheme 2.7. The alkylation of N,N-diisopropylethylammonium-N,N-bis(3,7-dimethyloctyl)- diglycolamate using dimethyl sulfate.

The reaction mixture was poured into a separatory funnel and deionized water was added until two distinct phases were observed. Hexanes were then added to the funnel until the organic phase rested on top of the aqueous phase. The organic layer was washed with small portions of deionized water until the aqueous phase was nearly colorless. The organic layer was then washed with 0.5 M H2SO4 repeatedly until the aqueous phase remained colorless. The organic extract was washed once with 15% NaOH, two times with deionized water, and once with saturated NaCl solution (brine). The organic phase was dried over anhydrous MgSO4 and silica gel and filtered through a layer of Celite® 546 diatomaceous earth and activated charcoal to clarify the solution.

The solution was then concentrated to a yellow-orange oil using rotary evaporation at reduced pressure and ca. 40°C. The crude methyl ester product was then evaporatively distilled using a

Kugelrohr apparatus and yielded a pale, yellow oil (N,N-bis(3,7-dimethyloctyl)diglycolamic acid methyl ester (D) = ev 170–180°C, 0.050 mm Hg, 2.42 g (76% yield)). The structure of

N,N-bis(3,7-dimethyloctyl)diglycolamic acid methyl ester is shown in Figure 2.11.

Figure 2.11. Structure of N,N-bis(3,7-dimethyloctyl)diglycolamic acid methyl ester (D).

A small sample of the evaporatively distilled compound was taken for IR and NMR spectroscopic analysis. IR spectroscopy showed the methyl ester peak at 1755 cm-1 and 1H-NMR spectroscopy showed the methyl ester peak at 3.75 ppm, which is consistent with previously synthesized methyl ester compounds A-C. NMR and IR spectroscopic data for compound D are listed below:

1 (D): H-NMR (400 MHz, CDCl3, δ): 4.29 (s, 2H), 4.27 (s, 2H), 3.75 (s, 3H), 3.31 (m, 2H), 3.20

(m, 2H), 1.52 (m, 4H), 1.40 (m, 4H), 1.29 (br m, 6H), 1.14 (br m, 6H), 0.90 (d, J = 6.4 Hz, 6H),

13 0.86 (d, J = 6.6 Hz, 12H). C-NMR (101 MHz, CDCl3, δ): 170.68, 168.02, 69.42, 68.18, 51.99,

45.43, 44.33, 39.33, 37.24, 36.16, 35.58, 34.67, 31.12, 29.94, 28.09, 24.80, 22.83, 22.74, 19.71.

-1 IR (NaCl, film) νmax (cm ): 2952 (s, CH, aliphatic), 2926 (s, CH, aliphatic), 2868 (s, CH, aliphatic),

1755 (s, C=O), 1646 (s, C=O), 1462(m, C-N), 1436 (m, C-N), 1133 (m, C-O). Yield = 76%.

The purified N,N-bis(3,7-dimethyloctyl)diglycolamic acid methyl ester was then used in the last step of this reaction scheme: an amidation using cyclic secondary amines. The amidation

followed the same protocol used in Scheme 2.3 with an excess of the cyclic secondary amine

(pyrrolidine, piperidine, or morpholine) added neat to the reaction vessel and heated at 90°C for

1-2 days. The reaction was monitored using IR spectroscopy. The complete disappearance of the methyl ester carbonyl stretch peak at ca. 1750 cm-1 signaled the end of the reaction. A sample of the reaction mixture was also spotted on a thin-layer chromatography plate next to the starting materials to confirm the reaction progress. The reaction is shown in Scheme 2.8. The excess cyclic amine was removed using rotary evaporation to yield an orange oil. The crude diglycolamide product was either evaporatively distilled using a Kugelrohr apparatus (ligands 10 and 11) or flash chromatographed (ligand 12) to yield a yellow-orange oil. Table 2.4 shows the evaporative distillation conditions along with the yields for this amidation reaction (ligands 10-12).

Scheme 2.8. Amidation of N,N-bis(3,7-dimethyloctyl)diglycolamic acid methyl ester with different cyclic secondary amines (pyrrolidine, piperidine, and morpholine).

Flash Chromatography: MPLC#3

The morpholine derivative (ligand 12) was purified using a custom-built medium-pressure liquid chromatography (MPLC#3) system. The MPLC#3 was fitted with a 125 g (silica gel,

40-60 μm) main column (25 mm i.d., Ace Adjust-a-Chrom™ column, bed volume = 100 mL) and a 16 g fore-column. The crude sample (10.43 g, 94%) was evaporated onto 20 g of silica gel

(40-60 μm) and poured into a loading column (30 cm × 1.5 cm i.d.). The remaining volume was filled with fresh, dry silica gel (40-60 μm). Diethyl ether (Et2O) was used as the solvent to elute the material off the loading column. Once all the desired material was completely eluted from the loading column (checked frequently via TLC), the loading column was disconnected and the main column was eluted using a stepwise gradient of 100 mL portions of MeOH-Et2O beginning with

1% MeOH and moving up to 10% MeOH. Thin-layer chromatography was used check selected fractions for compound purity. Fractions with identical retention factors (Rf) were combined and concentrated to a clear, light-yellow oil (9.26 g, 84%).

The full names (following Sasaki et al.22 and not IUPAC nomenclature), molecular weights

(MW), and overall percent yields for ligands 10-12 are shown below in Table 2.5.

Table 2.5. Names, molecular weights, and overall percent yields for unsymmetrical diglycolamide ligands 10-12. MW Overall Yield # Unsymmetrical Diglycolamide Ligand (g/mol) (%) 10 N,N-bis(3,7-dimethyloctyl)-N'-pyrrolidinyldiglycolamide 466.751 66 11 N,N-bis(3,7-dimethyloctyl)-N'-piperidinyldiglycolamide 480.778 55 12 N,N-bis(3,7-dimethyloctyl)-N'-morpholinodiglycolamide 482.750 62

A small sample of each purified compound (ligands 10–12) was taken and analyzed using

1H and 13C NMR spectroscopy, IR spectroscopy, and high resolution mass spectrometry. Data for ligands 10–12 are shown below (DMO = 3,7-dimethyloctyl):

1 DMOpyrDGA(10): H-NMR (400 MHz, CDCl3, δ): 4.31 (s, 2H), 4.26 (s, 2H), 3.49 (t, J = 6.8 Hz,

2H), 3.41 (t, J = 6.7 Hz, 2H), 3.31 (m, 2H), 3.18 (m, 2H), 1.93 (p, J = 6.4 Hz, 2H), 1.85

(p, J = 6.3 Hz, 2H), 1.51 (br m, 4H), 1.37 (br m, 4H), 1.28 (br m, 6H), 1.14 (br m, 6H), 0.90

(d, J = 6.2 Hz, 6H), 0.87 (d, J = 2.3 Hz, 6H), 0.85 (d, J = 2.3 Hz, 6H). 13C-NMR

(101 MHz, CDCl3, δ): 168.34, 167.65, 69.85, 69.14, 45.91, 45.61, 45.20, 44.12, 39.31, 39.23,

37.23, 37.16, 36.10, 34.62, 31.05, 30.97, 28.00, 26.26, 24.72, 23.99, 22.77, 22.68, 22.66, 19.64.

-1 IR (NaCl, film) νmax (cm ): 2962 (s, CH, aliphatic), 2921 (s, CH, aliphatic), 2871 (s, CH, aliphatic),

2856 (s, CH, aliphatic), 1653 (s, C=O), 1449 (m, C-N), 1136 (m, C-O). HRMS-MALDI TOF/TOF

(m/z): [M + H]+(calc.) = 467.42134; [M + H]+(exp.) = 467.42172. Overall yield = 66%.

1 DMOpipDGA(11): H-NMR (400 MHz, CDCl3, δ): 4.32 (s, 2H), 4.26z (s, 2H), 3.54 (m, 2H),

3.41 (m, 2H), 3.32 (m, 2H), 3.17 (m, 2H), 1.54 (br m, 10H), 1.27 (br m, 10H), 1.15 (br m, 6H),

0.90 (d, J = 6.1 Hz, 6H), 0.87 (d, J = 2.4 Hz, 6H), 0.85 (d, J = 2.4 Hz, 6H). 13C-NMR (101 MHz,

CDCl3, δ): 168.35, 167.27, 70.05, 69.26, 46.12, 45.25, 44.21, 42.99, 39.39, 39.31, 37.30, 37.23,

36.19, 34.71, 31.14, 31.05, 28.08, 26.56, 25.70, 24.79, 24.62, 22.83, 22.74, 22.72, 19.70. IR (NaCl,

-1 film) νmax (cm ): 2948 (s, CH, aliphatic), 2926 (s, CH, aliphatic), 2859 (s, CH, aliphatic), 1652

(s, C=O), 1458 (m, C-N), 1115 (m, C-O). HRMS-MALDI TOF/TOF (m/z): [M + H]+(calc.) =

481.43637; [M + H]+(exp.) = 481.43475. Overall yield = 55%.

1 DMOmorDGA(12): H-NMR (400 MHz, CDCl3, δ): 4.34 (s, 2H), 4.28 (s, 2H), 3.69 (m, 4H), 3.61

(m, 4H), 3.32 (m, 2H), 3.14 (m, 2H), 1.53 (br m, 4H), 1.39 (br m, 4H), 1.28 (br m, 6H), 1.14

(br m, 6H), 0.91 (d, J = 6.4 Hz, 6H), 0.88 (d, J = 3.7 Hz, 6H), 0.86 (d, J = 3.7 Hz, 6H). 13C-NMR

(101 MHz, CDCl3, δ): 168.09, 167.61, 70.39, 69.04, 66.97, 45.80, 45.16, 44.25, 42.25, 39.38,

39.31, 37.27, 37.21, 36.15, 34.73, 31.15, 31.06, 28.08, 24.78, 22.82, 22.72, 19.70. IR (NaCl, film)

-1 νmax (cm ): 2956 (s, CH, aliphatic), 2929 (s, CH, aliphatic), 2864 (s, CH, aliphatic), 1653 (s, C=O),

1462 (m, C-N), 1439 (m, C-N), 1113 (m, C-O). HRMS-MALDI TOF/TOF (m/z): [M + H]+(calc.)

= 483.41634; [M + H]+(exp.) = 483.41568. Overall yield = 62%.

2.7. Conclusions

Ligands 1-12 were transferred to small, screwcap vials for storage before eventual use in liquid-liquid solvent extraction and optical spectroscopy studies. There was no visible degradation of the ligands after up to two years in storage. The two-step ligand synthesis was designed with the idea of scaling-up in mind. All of the reagents (with the exception of the bis(3,7-dimethyloctyl)amine) are commercially available and relatively inexpensive. The large-scale purification of these materials would likely require a distillation set-up, as column chromatography would be prohibitively expensive. The synthesis scheme was also designed to be

environmentally friendly with the only major byproducts being sulfate, methanol and diisopropylethylamine salts. This simple synthetic approach can be used to yield several different unsymmetrical diglycolamides with varying characteristics.

The twelve ligands in this report were designed to extract trivalent lanthanides and trivalent actinides at high nitric acid concentrations (e.g., 1 M HNO3). The ligand design also incorporated amphiphilic alkyl groups with one end preferring the aqueous phase (e.g., pyrrolidinyl, piperidinyl, and morpholino groups) and the other end preferring the organic phase (e.g., hexyl, octyl,

2-ethylhexyl, 3,7-dimethyloctyl). These features were included to change the phase-transfer kinetics and mechanism of the metal extraction reaction. The asymmetry may also affect the aggregation of ligands in the presence of high nitric acid concentrations or high metal loading.

Studies of the extraction chemistry and coordination chemistry of these systems are the subject matter for the next chapter of this document.

2.8. References

(1) IAEA. Reference Data Series No. 2, 2015 Edition: Nuclear Power Reactors in the World; 2015.

(2) Choppin, G. R.; Rydberg, J. Nuclear Chain Reactions. In Nuclear Chemistry: Theory and Applications; Pergamon Press: Oxford, 1980; pp 441–501.

(3) Choppin, G. R.; Liljenzin, J.-O.; Rydberg, J. The Nuclear Fuel Cycle. In Radiochemistry and Nuclear Chemistry; Butterworth-Heinemann: Kundli, India, 2002; pp 585–641.

(4) Cox, M.; Rydberg, J. Introduction to Solvent Extraction. In Solvent Extraction Principles and Practices; Rydberg, J., Cox, M., Musikas, C., Choppin, G. R., eds.; Marcel Dekker: New York, 2004; pp 1–25.

(5) Long, J. T. Spent-Fuel Dissolution. In Engineering for Nuclear Fuel Reprocessing; Gordon and Breach Science Publishers: New York, 1967; pp 273–325.

(6) Lanham, W. B.; Runion, T. C. PUREX Process for Plutonium and Uranium Recovery. Oak Ridge Natl. Lab. 1949, 479 (October), 1–12.

(7) Nunez, L.; Vandegrift, G. F. Evaluation of Hydroxamic Acid in Uranium Extraction Process: Literature Review. Argonne National Laboratory. 2001, pp 1–11.

(8) Nash, K. L.; Braley, J. C. Challenges for Actinide Separations in Advanced Nuclear Fuel Cycles. In ACS Symposium Series; Oxford University Press, 2010; Vol. 1046, pp 19–38.

(9) Vandegrift, G. F.; Leonard, R. A.; Steindler, M. J.; Horwitz, E. P.; Basile, L. J.; Diamond, H.; Kalina, D. G. Transuranic Decontamination of Nitric Acid Solutions by the TRUEX Solvent Extraction Process -- Preliminary Development Studies. Argonne Natl. Lab. 1984, No. ANL-84-45, 1–125.

(10) Paiva, A. P.; Malik, P. Recent Advances on the Chemistry of Solvent Extraction Applied to the Reprocessing of Spent Nuclear Fuels and Radioactive Wastes. J. Radioanal. Nucl. Chem. 2004, 261(2), 485–496.

(11) Berthon, L.; Morel, J. M.; Zorz, N.; Nicol, C.; Virelizier, H.; Madic, C. Diamex Process for Minor Actinide Partitioning: Hydrolytic and Radiolytic Degradations of Malonamide Extractants. Sep. Sci. Technol. 2001, 36(5-6), 709–728.

(12) Modolo, G.; Wilden, A.; Geist, A.; Magnusson, D.; Malmbeck, R. A Review of the Demonstration of Innovative Solvent Extraction Processes for the Recovery of Trivalent Minor Actinides from PUREX Raffinate. Radiochim. Acta 2012, 100(8-9), 715–725.

(13) Sasaki, Y.; Sugo, Y.; Suzuki, S.; Tachimori, S. The Novel Extractants, Diglycolamides, for the Extraction of Lanthanides and Actinides in HNO3-n-dodecane System. Solvent Extr. Ion Exch. 2001, 19(1), 91–103.

(14) Nave, S.; Modolo, G.; Madic, C.; Testard, F. Aggregation Properties of N,N,N',N'- tetraoctyl-3-oxapentane (TODGA) in n-Dodecane. Solvent Extr. Ion Exch. 2004, 22(4), 527–551.

(15) Magnusson, D.; Christiansen, B.; Glatz, J.; Malmbeck, R.; Modolo, G.; Serrano‐Purroy, D.; Sorel, C. Demonstration of a TODGA Based Extraction Process for the Partitioning of Minor Actinides from a PUREX Raffinate. Solvent Extr. Ion Exch. 2009, 27(1), 26–35.

(16) Ravi, J.; Venkatesan, K. A.; Antony, M. P.; Srinivasan, T. G.; Vasudeva Rao, P. R. Feasibility of Using Di-dodecyl-di-octyl Diglycolamide for Partitioning of Minor Actinides from Fast Reactor High-Level Liquid Waste. Solvent Extr. Ion Exch. 2014, 32 (4), 424–436.

(17) Ramírez, F. D. M.; Charbonnière, L.; Muller, G.; Scopelliti, R.; Bünzli, J.-C. G. A p-tert- Butylcalix[4]arene Functionalised at Its Lower Rim with Ether-amide Pendant Arms Acts as an Inorganic–Organic Receptor: Structural and Photophysical Properties of Its Lanthanide Complexes. J. Chem. Soc. Dalt. Trans. 2001, No. 21, 3205.

(18) Stodola, F. H. Base-Catalyzed Preparation of Methyl and Ethyl Esters of Carboxylic Acids. J. Org. Chem. 1964, 29(8), 2490–2491.

(19) Montalbetti, C. A. G. N.; Falque, V. Amide Bond Formation and Peptide Coupling. Tetrahedron 2005, pp 10827–10852.

(20) Seidell, A. Solubility of Ammonia in Ethyl Alcohol. In Solubilities of Inorganic and Organic Compounds; D. Van Nostrand Company: New York, 1919; p 33.

(21) Fulmer, G. R.; Miller, A. J. M.; Sherden, N. H.; Gottlieb, H. E.; Nudelman, A.; Stoltz, B. M.; Bercaw, J. E.; Goldberg, K. I. NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist. Organometallics 2010, 29(9), 2176–2179.

(22) Sasaki, Y.; Rapold, P.; Arisaka, M.; Hirata, M.; Kimura, T.; Hill, C.; Cote, G. An Additional Insight into the Correlation between the Distribution Ratios and the Aqueous Acidity of the TODGA System. Solvent Extr. Ion Exch. 2007, 25(2), 187–204.

(23) Branch, G. E. K.; Hill, T. L. Calculation of the Number of Stereoisomers in Carbon Chain Compounds. J. Org. Chem. 1940, 5(2), 86–99.

Chapter 3

TRIVALENT LANTHANIDE METAL EXTRACTION BEHAVIOR BY NEW

UNSYMMETRICAL DIGLYCOLAMIDES

3.1. Abstract

Twelve different unsymmetrical diglycolamide (UDGA) extractants having seven different

N-alkyl groups (R1 = hexyl, R2 = octyl, R3 = 2-ethylhexyl, R4 = 3,7-dimethyloctyl,

R5 = pyrrolidinyl, R6 = piperidinyl, R7 = morpholino) were synthesized and compared based on

Ln(III) metal extraction and phase compatibility at high nitric acid concentrations (e.g., 3 M). All twelve UDGA ligands were shown to quantitatively extract trivalent Eu(III) cations from 1 M nitric acid. The stoichiometry of the extracted Eu-UDGA complex in 5% v/v 1-octanol/n-dodecane was found to be approximately 1:3 for the UDGA ligands. The dependence of Eu(III) extraction on [HNO3] and the lanthanide series extraction pattern were determined for the UDGA ligands.

The R1 = hexyl derivatives were prone to phase incompatibility (third phase formation) at 3 M

HNO3 and the R4 = 3,7-dimethyloctyl derivatives were shown to be stronger Eu(III) extractants than the R3 = 2-ethylhexyl derivatives, which runs counter to most extraction trends with increasing alkyl group size.

3.2. Introduction

The steady increase in atmospheric carbon dioxide concentrations (from 280 ppm in 1750 to 379 ppm in 2005) can be strongly correlated with the increased burning of fossil fuels such as coal, oil, and natural gas.1 There have been global measures taken to reduce the emission of carbon

dioxide and other greenhouse gases (e.g., Kyoto Protocol (1992), Paris Agreement (2015)) but the increasing worldwide energy demand requires alternative sources for electricity production.2

Nuclear reactors fueled by low-enriched uranium produce almost 20% of the electricity used in the United States every year and have zero carbon dioxide emissions.3 The irradiation of this uranium fuel does lead to the creation of many other elements including radioactive plutonium

(8.7 kg per metric ton of U fuel) and americium (0.6 kg per metric ton of U fuel) and the neutron poisons cerium (2.4 kg per metric ton of U fuel) and neodymium (4.0 kg per metric ton of U fuel).4

These neutron poisons decrease the efficiency of the reactor core by absorbing the neutrons necessary to maintain the nuclear chain reaction. This requires that 20-25% of used fuel rods be removed from the reactor core and replaced by fresh fuel rods every year. This used nuclear fuel currently stays in large cooling pools on site with no plans for disposal. The used nuclear fuel is still mostly uranium (956 kg per metric ton of U fuel) and plutonium, which can be recycled and combined to form a mixed uranium-plutonium oxide (MOX) fuel for further irradiation and power generation.4 The first challenge is the separation of uranium and plutonium from the other forty elements present in the used fuel pellets. The second challenge is the separation of the other radioactive transuranic elements (Np, Am, Cm) from the fission products (including the trivalent lanthanides). Overcoming both of these challenges would allow used nuclear fuel to be recycled multiple times and would decrease the overall volume of highly radioactive waste.

One method for large-scale metal separations is liquid-liquid solvent extraction. Solvent extraction systems generally include two immiscible phases in contact with one another with a solute of interest partitioning between the two phases. In used nuclear fuel reprocessing, the lower phase is a highly acidic aqueous phase containing the dissolved metal nitrates. The upper phase is generally an aliphatic diluent (e.g., n-dodecane) containing a reagent, or extractant, meant to form

extractable complexes with the metal solute of interest.5 The extractant tributyl phosphate (TBP,

Figure 3.1) has been used in the PUREX (Plutonium Uranium Reduction EXtraction) process to extract U and Pu from used nuclear fuel.6

Figure 3.1. Structure of tributyl phosphate (TBP).

Advanced PUREX processes have also been developed to separate Np along with the U and Pu.7 The minor actinides (Am and Cm, or An(III)) are both trivalent metals and have the added challenge of being chemically similar to the trivalent lanthanides (Ln(III)), which are present in greater concentrations. The TRUEX (TRansUranic EXtraction) process added the bifunctional organophosphorus extractant octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide

(CMPO, Figure 3.2) to the TBP solvent and was able to co-extract U, Np, Pu, Am, Cm, and Ln(III)

8 from highly acidic media (e.g., 3-4 M HNO3) while rejecting most other fission products.

Figure 3.2. Structure of octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO).

Other processes (including the DIAMide EXtraction process, DIAMEX) were developed containing only carbon, hydrogen, oxygen, and nitrogen in the extractant molecules to allow for complete combustion of the reprocessing waste stream.9 The diglycolamide (DGA) ligand

N,N,N',N'-tetraoctyldiglycolamide (TODGA, Figure 3.3) derived from oxydiacetic acid, or diglycolic acid (Figure 3.4), was shown to preferentially extract Ln(III) and An(III) over Pu(IV)

10 and U(VI) from highly acidic media (1 M HNO3).

Figure 3.3. Structure of N,N,N',N'-tetraoctyl- Figure 3.4. Structure of diglycolic acid. diglycolamide (TODGA).

This project seeks to expand on the diglycolamide class of extractants by introducing different alkyl groups on the two amide groups. Twelve new unsymmetrical diglycolamide

(UDGA) ligands were designed and synthesized to co-extract trivalent lanthanides and trivalent actinides at high nitric acid concentrations (e.g., 1 M HNO3). The ligand design, based on the nominally tridentate oxydiacetic acid amides, or diglycolamides, incorporates alkyl groups so that one end of the extractant molecule (e.g., pyrrolidinyl, piperidinyl, and morpholino groups) will prefer the aqueous phase and the other more lipophilic end (e.g., hexyl, octyl, 2-ethylhexyl,

3,7-dimethyloctyl) will interact more strongly with the organic solvent. This asymmetry in the amidic alkyl groups further enhances the amphiphilic behavior of the extractant molecule and could allow for greater metal-ligand interactions at the liquid-liquid interface. These features were investigated with the objective of improving the phase-transfer kinetics and perhaps altering the mechanism of the metal extraction reaction while maintaining the general conformation of the

cation coordination moiety. It was also postulated that the ligand asymmetry could also affect the aggregation of ligands in an organic phase in contact with aqueous media of high nitric acid or metal concentrations. The Ln(III) metal extraction by these twelve unsymmetrical diglycolamides was probed using radiometric and ICP-MS techniques.

Preliminary experiments looked at the solubility of the UDGA ligands in different diluent mixtures and the amount of time needed to reach biphasic equilibrium. The metal-ligand stoichiometry was deduced using slope analysis experiments and nitric acid dependence profiles were created for each ligand. Exploratory experiments addressed nitric acid extraction and sodium nitrate extraction dependence. The final group of experiments tested the biphasic partitioning of the entire lanthanide series and compared the trends seen between each ligand. All ligands were compared to the most widely studied representative of this class of extractants,

N,N,N',N'-tetraoctyldiglycolamide (TODGA) when possible.

3.3. Materials

Aqueous nitric acid solutions were prepared using EMD Millipore OmniTrace® nitric acid

(67-70%) and 18 MΩ·cm deionized water. All nitric acid solutions were titrated with sodium hydroxide to determine accurate concentrations using a Mettler Toledo DL50 titrator. Sodium nitrate solutions were made using recrystallized sodium nitrate (Alfa Aesar, 99.0% min., ACS, crystalline). The sodium nitrate solution was standardized for [Na+] using ion-exchange chromatography (Dowex 50x beads, H+ form) and potentiometry.

The radiotracer europium-152/154 was produced through the neutron activation of Eu2O3

(Arris International Corp., 99.999%) in the 1 MW Teaching Research Isotopes General Atomics

(TRIGA) nuclear reactor at the Washington State University Nuclear Radiation Center

(WSUNRC). Europium-152/154 radiotracer working solutions were made in dilute nitric acid

(e.g., 0.011 M). A europium nitrate stock solution was prepared by the addition of concentrated nitric acid to Eu2O3 (Arris International Corp., 99.999%). The solution of europium and concentrated HNO3 was then evaporated to near dryness. The solid was redissolved in concentrated HNO3 and evaporated again. This process was repeated until no solid (Eu2O3) remained in homogeneous aqueous solution. The solution was standardized for [Eu3+] and [H+] using ion-exchange chromatography (Dowex 50x beads, H+ form). The extraction chemistry of the entire lanthanide (Ln) series (excluding promethium) was studied using an inductively-coupled plasma mass spectrometry (ICP-MS) standard solution. The ICP-MS Multielement Standard B

(High Purity Standards, ISO certified) contained 10.0 ± 0.1 μg/mL of each Ln(III) in 2% HNO3.

Organic diluents n-octane, 1-octanol, and n-dodecane were obtained from Acros Organics

(99%), Sigma-Aldrich (99%), and Alfa Aesar (99%), respectively, and used without further purification. Synthesized unsymmetrical diglycolamide ligands were purified by Kugelrohr distillation or flash chromatography and were characterized using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and high resolution mass spectrometry

(HRMS). The symmetrical diglycolamide N,N,N',N'-tetraoctyldiglycolamide (TODGA, >99% purity) was generously donated by Dr. Yuji Sasaki from the Japan Atomic Energy Research

Institute in Tokai, Ibaraki, Japan.

3.4. Methods

All solvent extraction experiments were performed at room temperature (22 ± 1°C) unless otherwise indicated. All organic solutions were prepared by mass of both the ligand and the diluent.

Each organic phase was prepared fresh for each new experiment. This method minimized ligand waste, which was necessary for dealing with small amounts of total synthesized ligand (e.g., 1 g).

The volume of the ligand was excluded from the total volume calculation of the organic phase.

Mixed organic diluents (e.g., 5.0 ± 0.1 or 10.0 ± 0.2% v/v 1-octanol in n-dodecane) were made in larger batches to maintain consistency in the diluent makeup. Organic phase samples were stored in glass containers with PTFE- or PP-lined caps to prevent any contamination. Standardized nitric acid aqueous phases were added by volume using a pipette (Thermo Scientific™ Finnpipette™).

Sodium nitrate solutions were made by mass from a more concentrated stock solution

(4.926 ± 0.046 mol NaNO3/kg solution) and then diluted with water in a volumetric flask. All organic and aqueous solution concentrations were determined to at least three significant figures of precision. All Thermo Scientific™ Finnpipette™ pipettes were calibrated regularly at the maximum (< 0.6% accuracy, < 0.5% precision) and minimum (< 3.0% accuracy, < 2.5% precision) dispense volumes. Pipettes were used to dispense the maximum volume when possible.

The organic phase (2000 ± 6 μL) was pre-equilibrated with a metal-free aqueous phase

(2000 ± 6 μL) for 30 minutes in a 4 mL screw-cap glass vial using a Fisher Scientific™ Analog

Vortex Mixer on level 9 (ca. 2850 rpm). This equilibration procedure was adequate to bring the biphasic system to thermodynamic equilibrium. The samples were then centrifuged for 5 minutes to achieve complete phase separation. Three aliquots (500 ± 2 μL) of fresh aqueous phase were pipetted into three different 2 mL glass, screw-cap vials. Three aliquots (500 ± 2 μL) of the pre-

equilibrated organic phase were taken and transferred to the same 2 mL screw-cap glass vials. All experiments were run in triplicate.

Radiotracer 152,154Eu Experiments

For radiotracer experiments, a 5.00 ± 0.03 μL aliquot of radioactive europium-152/154 was spiked into each individual 2 mL vial containing both phases. Each 5.00 ± 0.03 μL 152,154Eu(III) spike contained ca. 20,000 counts per minute (cpm) gamma decays as indicated by an automatic gamma counting system (Packard COBRA II). The volume (5.00 ± 0.03 μL) and acidity

(0.011 M HNO3) were ignored in all experimental calculations. The spiked phases were then contacted for at least 30 minutes using a Vortex mixer. The samples were centrifuged again to separate the two phases completely prior to sampling for radiometric analysis.

A 200.0 ± 0.6 μL sample was taken from the organic phase of each vial and deposited in a plastic tube for gamma counting. A disposable plastic transfer pipette was used to carefully remove the remaining organic phase from the glass vial. The aqueous phase was then removed from the screw-cap glass vial and transferred to a 2 mL glass shell vial using another plastic pipette.

A 200.0 ± 0.6 μL sample was then taken from the aqueous phase and deposited in a plastic tube for gamma counting. This “shell vial” method was employed to reduce the cross-contamination of the organic and aqueous phases.

The plastic gamma tube samples were then counted on a COBRA II gamma counter with a window set from 15 to 2000 keV to include the wide spectrum of gamma energies for 152Eu and

154Eu. Each sample was counted for 15 minutes or until the counting percent error reached 1%, whichever came first. The counting error was propagated throughout the subsequent calculations.

The counts per minute (cpm) in each phase represent the partitioning of the europium metal from

the aqueous phase into the organic phase. The distribution ratio (DEu) was determined by this relationship seen in Equation 3.1.

cpm (org. phase) D = (3.1) Eu cpm (aq. phase)

A plastic gamma tube containing the 5.00 ± 0.03 μL 152,154Eu(III) spike was counted with each experiment to safeguard against counter errors or loss of radioactivity. The cpm in each original phase was calculated from the experimental data and the total cpm was compared to the activity of the 152,154Eu(III) spike by itself. This method also proved invaluable for the identification of any samples that experienced third phase formation (separation of the normal biphasic system into a triphasic system – aqueous/dense organic/light organic). This “phase splitting” was readily recognized during the counting of the aqueous and organic samples, since a loss of cpm in each bulk phase was easily tracked. Any data point with a 10% or greater loss of cpm overall was thrown out due to the possibility of third phase formation. Three plastic gamma tubes containing 200.0 ± 0.6 μL of water were also counted with each experiment to determine the average background activity. This background was subtracted from the experimental cpm values before the distribution ratios were calculated. The background subtraction was crucial for the determination of quantitative metal extraction, where essentially all of the metal has partitioned to the organic phase and a distribution ratio becomes meaningless. Any data point with less than

5 cpm in the aqueous phase was considered to have quantitative extraction for Eu(III). The error associated with each distribution ratio was a combination of the standard deviation of three data points and the propagated counting error. The vast majority of reported distribution ratios have less than 10% uncertainty.

ICP-MS Ln Experiments

For ICP-MS experiments, the organic phase was prepared as previously stated. The organic phase was also pre-equilibrated with a metal-free aqueous phase as before and centrifuged to achieve phase separation. The initial aqueous phase was prepared in a large batch

(e.g., 50.00 ± 0.05 mL) using an ICP-MS multielement standard solution containing 10.0 ± 0.1

μg/mL of each lanthanide metal plus scandium, yttrium, and thorium in 2% HNO3. The ICP-MS multielement standard solution was diluted to 50.00 ± 0.05 mL in a Class A volumetric flask with

1.935 ± 0.007 M HNO3 to lower the concentration of each metal to 1 μg/mL. A 200.0 ± 0.6 μL aliquot of this initial aqueous phase was taken before contacting with the organic phase to determine the initial metal concentration in the aqueous phase accurately. The 200.0 ± 0.6 μL aliquot of initial aqueous phase was diluted to 10.0 ± 0.1 mL with 2% HNO3. The final concentration of each metal was ca. 20 ng/mL or 20 ppb, which is within the desired concentration range for ICP-MS analysis.

Three aliquots (500 ± 2 μL) of fresh initial aqueous phase were pipetted into three different

2 mL glass, screw-cap vials. Three aliquots (500 ± 2 μL) of the pre-equilibrated organic phase were taken and pipetted on top of the fresh aqueous phase in the same three glass vials. Both phases were equilibrated for 30 minutes using a Vortex mixer and then centrifuged for five minutes. A plastic transfer pipette was used to remove the metal-loaded organic phase. A 200.0 ± 0.6 μL aliquot of the final aqueous phase was taken post-contact with the organic phase to determine the final metal concentration in the aqueous phase accurately. This aliquot was also diluted to

10.0 ± 0.1 mL using 2% HNO3. The final concentration (< 20 ppb) of each metal in the aqueous phase was dependent on the distribution ratio for each ligand and each metal, which varied with the identity of the lanthanide cation.

Samples were counted on an Agilent 7700 ICP-MS instrument. The counts per second (cps) at the appropriate mass for the major isotope of each element represent the metal concentrations in the initial and final aqueous phases. The organic phase metal concentration was determined by finding the difference between these two concentrations, or cps in this case (Equation 3.2).

cps (aq. phase, initial) - cps (aq. phase, final) = cps (org. phase) (3.2)

Assuming that the counts per second represent the individual metal concentrations, a distribution ratio can be written as Equation 3.3,

cps (org. phase) D = (3.3) M cps (aq. phase, final)

The uncertainty associated with each distribution ratio was a combination of the standard deviation between the triplicate points and residual standard deviation associated with the cps measurement. Uncertainties were generally below 10% for all distribution ratios with the exception coming at DM < 0.1. The errors become larger at low distribution ratios because both the initial and final aqueous phases result in similar counts per second.

3.5. Equilibration Time

Short chain diglycolamides (DGA) like N,N,N′,N′-tetrabutyldiglycolamide (TBDGA,

Figure 3.5) have been shown by Sasaki et al. to have some solubility in water (e.g., 2.3 mM

11 TBDGA in H2O determined by total organic carbon (TOC) analysis). It is likely that the unsymmetrical diglycolamide N,N-dihexyl-N'-pyrrolidinyldiglycolamide (DHpyrDGA), which has the same number of carbons as TBDGA, has similar solubility in water. The solubility of DGA

ligands in water drops off quickly at N,N,N′,N′-tetraamyldiglycolamide ([TADGA]aq = 0.27 mM,

Figure 3.5) and N,N,N′,N′-tetrahexyldiglycolamide ([THDGA]aq = 0.11 mM, Figure 3.5), which have the same number of carbons as N,N-dioctyl-N'-pyrrolidinyldiglycolamide (DOpyrDGA) and

N,N-bis-(3,7-dimethyloctyl)-N'-pyrrolidinyldiglycolamide (DMOpyrDGA), respectively. The partitioning of ligand into the aqueous phase could affect the free concentration of ligand in the organic phase, which would suppress the overall distribution of metal into the organic solvent. The aqueous phase was not pre-equilibrated with an organic phase, however, due to limited amounts of ligand.

Figure 3.5. Generic structure for the symmetrical diglycolamides including N,N,N′,N′-tetrabutyldiglycolamide (TBDGA, R = butyl) N,N,N′,N′-tetraamyldiglycolamide (TADGA, R = amyl), and N,N,N′,N′-tetrahexyldiglycolamide (THDGA, R = hexyl).

The diglycolamides are also known to extract water and nitric acid in the absence of metal cations.12 All organic phases containing diglycolamide ligands were pre-equilibrated with a metal-free aqueous phase before the main experiment. This pre-equilibration step was done to saturate the organic phase with water and nitric acid before the metal contact. Furthermore, there is yet another equilibrium shift when the metal itself is added to the system. These complex reactions require thorough mixing of phases and enough time to come to dynamic equilibrium.

Previous work with N,N,N',N'-tetraoctyldiglycolamide (TODGA)10 equilibrated both phases for two hours while work on the unsymmetrical diglycolamides (e.g., N,N-di-2-ethylhexyl-

N',N'-dioctyldiglycolamide, DEHDODGA, Figure 3.6)13 equilibrated for one hour to reach thermodynamic equilibrium.

Figure 3.6. Structure of N,N-di-2-ethylhexyl-N',N'-dioctyldiglycolamide (DEHDODGA).

One of the first experiments performed with the unsymmetrical diglycolamide (UDGA) ligand 1 (N,N-dihexyl-N'-pyrrolidinyldiglycolamide, DHpyrDGA) monitored the distribution ratio

(DEu) over a period of time. These new unsymmetrical diglycolamide (UDGA) ligands have shorter alkyl chains and less steric bulk around the binding pocket. It was expected that the required equilibration times would be shorter than those used for TODGA and DEHDODGA. The results are shown in Figure 3.7. The distribution ratio (DEu) quickly came to equilibrium (ca. 400) and levelled off after only ca. 2 minutes of equilibration on a Vortex mixer. Other experiments with larger UDGA ligands (e.g., N,N-bis(3,7-dimethyloctyl)-N'-pyrrolidinyldiglycolamide) also found

30 minutes to be a sufficient contact time to achieve equilibrium. All solvent extraction experiments henceforth use this contact time unless otherwise stated.

103

102

101 DEu

100 org: 0.100 M DHpyrDGA in 5% 1-octanol/n-octane 152,154 aq: 10.0 mM Eu(NO3)3 in 0.985 M HNO3 ( Eu(III) spike also present) 30 min pre-contact with metal-free aqueous phase 10-1 0 5 10 15 20 25 30 Equilibration Time (min)

3.6. Third Phase Formation

A phenomenon called third phase formation can occur when two seemingly immiscible phases are equilibrated. A third phase usually forms at the interface between the organic and aqueous phases and contains much higher concentrations of ligand and metal (or other extractable species) than the bulk organic phase. This third phase is more dense than the bulk organic phase

and generally less dense than the aqueous phase. Under some conditions, the third phase can take the form of an amorphous solid. Third phase formation is undesirable in a solvent extraction process because it can interfere with phase disengagement and complicate the metal separations.

A third phase could be potentially catastrophic in a spent nuclear fuel reprocessing plant where fissile materials (e.g., plutonium-239) could be concentrated into a geometry favorable for accidental criticality. Third phase formation occurs when too much metal or nitric acid or other polar solute is extracted into the nonpolar organic phase, thus exceeding its solubility in the organic phase; at the extremely dilute lanthanide concentrations of these experiments, when third phase formation is detected, it is necessarily the result of unfavorable interactions between the extractant and nitric acid. The amphiphilic extractant has the task of solvating these polar metal solutes

(e.g., Eu(III)) while simultaneously dissolving into the nonpolar diluent (e.g., n-dodecane). All solvating extractants can be expected to form a third phase at some concentration of metal or acid.

This category of extractant can still be used as long as the process conditions do not exceed concentrations of solutes under which third phase occurs.

Another method for combating third phase formation is the addition of a phase modifier.

A phase modifier is generally an amphiphilic molecule itself, which has good solubility in the bulk organic phase but is itself more polar than the bulk organic phase. An example of a phase modifier is the long-chain alcohol 1-octanol. The n-octyl group readily dissolves in aliphatic diluents such as n-octane while the hydroxyl group increases the polarity of bulk organic phase. Phase modifiers allow more polar solutes to be extracted into the organic phase but will not necessarily prevent third phase formation at any solute concentration.

3.7. Ligand Solubility

Twelve new, unsymmetrical diglycolamides (UDGAs, 1-12) were synthesized for use in a solvent extraction system. All of the ligands were found to exhibit good solubility in dichloromethane, hexanes, and deuterated chloroform during the course of the syntheses. The structures of all twelve synthesized ligands are shown in Figure 3.8.

Initial solvent extraction experiments were performed with n-octane as the organic phase solvent, or diluent. The first two dihexyl derivatives (1 and 2) exhibited a third phase when an organic phase of 0.107 M DHpyrDGA or 0.103 M DHpipDGA in n-octane was contacted with a

152,154 0.985 M HNO3 aqueous phase spiked with radiotracer Eu(III). A second experiment looked at 0.099 M DHpyrDGA in n-octane contacted with a 10.0 mM Eu(NO3)3 in 0.985 M HNO3 aqueous phase. A third phase was immediately observed in this high metal loading system. Small aliquots of the phase modifier 1-octanol were added to slowly increase the polarity of the organic phase. The third phase was no longer observed at ca. 5% v/v 1-octanol/n-octane. The sample was then spiked with radiotracer 152,154Eu(III) and counted on a gamma counter. The counts per minute in both phases added up to the total counts per minute in the spike, which confirmed the absence of a third phase after the addition of ca. 5% 1-octanol. These initial experiments with the most polar ligands (except 3) showed that 1-octanol was an effective phase modifier in this solvent extraction system and 5% by volume was a sufficient amount to add to the organic diluent. The main diluent was later changed from n-octane (fp 13°C) to n-dodecane (fp 74°C)13 because a flashpoint below room temperature is potentially dangerous in an industrial scale solvent extraction process.

Notwithstanding the initial results in n-octane, the remaining ligands (except the morpholino derivatives 3, 6, and 9) were all tested in aliphatic diluents (n-octane or n-dodecane) to better understand the consequences of each structural change (e.g., dihexyl vs. dioctyl or piperidinyl vs. morpholino). The first ligand to not form a third phase in n-octane was the dioctyl- piperidinyl derivative, DOpipDGA (5). The dioctyl groups increased the ability of the extractant to dissolve in the aliphatic diluent but the piperidinyl group was also necessary since the analogous dioctyl-pyrrolidinyl derivative, DOpyrDGA (4), formed a third phase under identical conditions.

The di-2-ethylhexyl derivatives (7-9) behaved similarly to the dioctyl derivatives with slightly suppressed distribution ratios. DEHpipDGA (8) did not form a third phase in n-octane but did form a third phase in n-dodecane (at differing ligand concentrations). The first ligand to not form a third phase in n-dodecane was the bis(3,7-dimethyloctyl)-morpholino derivative, DMOmorDGA (12),

but this only occurred at a higher ligand concentration (25 mM). Results of the various diluent experiments for ligands 1-12 are shown in Table 3.1.

Table 3.1. UDGA ligand solvent extraction experiments with varying diluent mixtures.

[UDGA] [HNO ] # Ligand Name Diluent 3 D (mM) (M) Eu

DHpyrDGA 99.0 n-octane 0.985 third phase 1 DHpyrDGA 10.4 5.0% 1-octanol/n-octane 0.985 10.9 ± 0.9 DHpyrDGA 107 30% 1-octanol/n-octane 0.985 quantitative DHpipDGA 103 n-octane 0.985 third phase 2 DHpipDGA 11.3 5.0% 1-octanol/n-octane 0.985 20.1 ± 2.6 DHpipDGA 122 30% 1-octanol/n-octane 0.985 178 ± 28 DHmorDGA 50.1 5.0% 1-octanol/n-dodecane 0.985 quantitative 3 DHmorDGA 49.9 10% 1-octanol/n-dodecane 0.985 113 ± 12 DOpyrDGA 101 n-octane 0.985 third phase 4 DOpyrDGA 10.3 5.0% 1-octanol/n-octane 0.985 7.0 ± 0.7 DOpyrDGA 50.0 5.0% 1-octanol/n-dodecane 0.985 415 ± 29 DOpipDGA 10.0 n-octane 0.985 third phase DOpipDGA 99.9 n-octane 0.985 85.6 ± 8.9 5 DOpipDGA 11.9 5.0% 1-octanol/n-octane 0.985 0.90 ± 0.09 DOpipDGA 49.3 5.0% 1-octanol/n-dodecane 0.985 195 ± 28 6 DOmorDGA 49.7 5.0% 1-octanol/n-dodecane 0.985 115 ± 16 DEHpyrDGA 100. n-octane 0.985 third phase 7 DEHpyrDGA 10.3 5.0% 1-octanol/n-octane 0.985 1.8 ± 0.2 DEHpyrDGA 50.0 5.0% 1-octanol/n-dodecane 0.985 647 ± 257 DEHpipDGA 10.0 n-octane 0.985 third phase DEHpipDGA 101 n-octane 0.985 80.1 ± 7.5 DEHpipDGA 10.4 n-dodecane 0.985 third phase 8 DEHpipDGA 10.9 5.0% 1-octanol/n-octane 0.985 0.18 ± 0.02 DEHpipDGA 50.3 5.0% 1-octanol/n-octane 0.985 23.1 ± 2.4 DEHpipDGA 50.1 5.0% 1-octanol/n-dodecane 0.985 26.2 ± 0.9 9 DEHmorDGA 50.1 5.0% 1-octanol/n-dodecane 0.985 40.2 ± 5.9 DMOpyrDGA 10.0 n-dodecane 3.01 third phase 10 DMOpyrDGA 50.0 5.0% 1-octanol/n-dodecane 0.985 quantitative

DMOpipDGA 11.0 n-octane 1.004 0.27 ± 0.05 DMOpipDGA 9.62 5.0% 1-octanol/n-octane 1.004 0.14 ± 0.01 11 DMOpipDGA 10.0 n-dodecane 1.004 third phase DMOpipDGA 50.0 5.0% 1-octanol/n-dodecane 1.004 81.7 ± 2.5 DMOmorDGA 10.0 n-dodecane 3.01 third phase 12 DMOmorDGA 25.4 n-dodecane 3.01 quantitative DMOmorDGA 50.0 5.0% 1-octanol/n-dodecane 0.961 57.9 ± 9.2

The data in Table 3.1 demonstrate that there is a decrease in the tendency toward third phase formation as the size of the ligands increases. The concentration of the unsymmetrical diglycolamide (UDGA) ligand is also an important factor as seen in experiments with

DOpipDGA (5), DEHpipDGA (8), and DMOmorDGA (12). All three ligands formed a third phase at 10 mM UDGA in either n-octane or n-dodecane but did not form a third phase when the concentration was increased to either 100 mM (for 5 and 8) or 25 mM (for 12). Since all the experiments in Table 3.1 were done with radiotracer 152,154Eu(III), where the [Eu] = 10-5 M, it is safe to say that the third phase formation is primarily the result of nitric acid extraction, which is at 0.985 M or greater in all of the experiments. The increase in ligand concentration may extract the same percentage of nitric acid while leaving more total free ligand for the important job of metal complexation and solvation in the organic phase.

3.8. Nitric Acid Extraction

Nitric acid extraction is an issue for all solvating extractants because of the strong dipole-dipole interactions between the partial negative charge (δ-) on the carbonyl (or phosphoryl) oxygen on the extractant and the partial positive charge (δ+) on the hydrogen on the nitric acid.14

This type of dipole-dipole interaction is called hydrogen bonding and accounts for the extraction of both nitric acid and water from the aqueous phase. The present work did not quantify the amount

of water extracted into the organic phase but did look at nitric acid extraction. The ligand concentration (5.1, 10.2, 20.3 and 40.7 mM DMOmorDGA in 5% v/v 1-octanol/n-dodecane) was varied while the acid concentration (3.018 ± 0.006 M HNO3) was held constant for this experiment.

Each organic phase was contacted with the 3.018 ± 0.006 M HNO3 for 30 minutes and then centrifuged to separate the phases. The nitric acid loaded organic phase was then removed and transferred to a vial containing water only. The two phases were contacted for 10 minutes and centrifuged. The organic phase was again removed and transferred to a new vial containing another measure of water. The mixing and centrifugation was repeated. Both aqueous phases containing the stripped nitric acid were combined and titrated to determine the moles of [H+] present in the organic phase.

The extraction of nitric acid by the phase modifier 1-octanol has also been evaluated in a study by Geist.15 The equilibrium model for the extraction of nitric acid by 1-octanol is shown in

Equation 3.4. Overlined species are in the organic phase.

H+  NO  2  C H OH HNO C H OH (3.4) 3 8 17 3 8 17 2

The equilibrium constant (KH) was determined for several different 1-octanol concentrations, including 5% v/v (or 0.316 M) 1-octanol (C8H17OH) in hydrogenated tetrapropylene (TPH). The equilibrium constant (KH) for 5% 1-octanol in TPH is defined in

Equation 3.5.

HNO C H OH  3 8 17 2 KH =2  0.019 H+   NO   C H OH (3.5)   3   8 17

The theoretical equilibrium concentration of extracted nitric acid can be calculated by plugging in values for the [HNO3] (3.018 M) and [1-octanol] (0.316 M) in Equation 3.6.

HNO HNO C H OH  0.019 3.018 3.018 0.3162  0.017 M (3.6) 3 3 8 17 2     

The organic phase concentrations of nitric acid were corrected for the extraction by

1-octanol by subtracting 17 mM from the experimental data. The results for the nitric acid extraction using DMOmorDGA are shown in Table 3.2. (left off - fix Table 3.2)

Table 3.2. The extraction of nitric acid by the diglycolamide ligand DMOmorDGA (L = DMOmorDGA, aqueous phase = 3.018 ± 0.006 M HNO3; diluent = 5.0% v/v 1-octanol/ n-dodecane).

[L]tot (mM) [HNO3]org,tot (mM) [HNO3]org,L (mM)* [HNO3]org,L:[L]tot 5.1 13.5 ± 0.6 0 0 10.2 19.1 ± 0.3 1.82 0.178 20.3 32.2 ± 0.1 14.9 0.734 40.7 68.8 ± 2.1 51.5 1.27

*Assuming [HNO3]org,L = [HNO3]org,tot - 0.017 M

The nitric acid extraction equilibrium for the DMOmorDGA in 5.0% v/v

1-octanol/n-dodecane system can be expressed by Equation 3.7. Overlined species are in the organic phase.

2H+  2NO  2  C H OH n DMOmorDGA HNO C H OH  HNO DMOmorDGA 3 8 17 3 8 172  3  n

(3.7)

The HNO3 extraction equilibrium constant (KH) for the DMOmorDGA in 5.0% v/v

1-octanol/n-dodecane system is thus expressed by Equation 3.8.

HNO C H OH   HNO DMOmorDGA   3 8 172   3  n  KH  4 2 n HNO C H OH   DMOmorDGA  3 8 17    or (3.8) HNO  3  KH  4 2 n HNO C H OH   DMOmorDGA  3 8 17   

Taking the logarithm of both sides and rearranging gives Equation 3.9,

log HNO  4log HNO  logKn  2  log  C H OH    log  DMOmorDGA  (3.9) 3  3  H  8 17   

Plotting log HNO 4log HNO versus log DMOmorDGA can give values for both 33   log (KH) and the HNO3-DMOmorDGA complex ratio (n). Unfortunately, the data listed in

Table 3.2 are not internally consistent and do not yield reasonable numbers for either of these values.

Further experiments with more data points need to be performed to calculate accurate values for n and KH. A better experiment would also eliminate the phase modifier 1-octanol to simplify the extraction equilibrium. The determination of the nitric acid extraction equilibrium constant (KH) is important because it quantifies the strength of the HNO3-UDGA complexes in the organic phase. The HNO3 extraction is in competition with the Eu(NO3)3 extraction and, as such, can reduce the concentration of ligand available for complex formation. The metal extraction equilibrium constant (Kex) is much larger than KH but the high concentrations of nitric acid

(e.g., 3.0 M) compared to Eu3+ (e.g., 10-5 M for radiotracer studies) can lead to millimolar quantities of extracted nitric acid.

Nitric acid extraction into a TODGA/n-dodecane solvent has been studied extensively and much of the data at 1 M HNO3 support a 1:1 ratio between the extracted HNO3 and TODGA ligand.16–19 However, Modolo et al. found that the ratio was 2:1 at for a 0.1 M TODGA in

20 hydrogenated tetrapropylene (TPH) contacted with 6 M HNO3. The data shown previously in

Table 3.2 support a primarily 1:1 HNO3-DMOmorDGA complex in the organic phase. These results can be explained by the hydrogen bonding interactions between the electronegative amidic oxygens in the DMOmorDGA molecule and the proton in HNO3 (Figure 3.9).

Figure 3.9. Possible hydrogen bonding between a nitric acid molecule and the diglycolamide ligand N,N-bis(3,7-dimethyloctyl)-N'-morpholinodiglycolamide (DMOmorDGA).

Further nitric acid extraction studies would need to be performed to confirm the predominance of the 1:1 HNO3-DMOmorDGA complex and to calculate a value for the nitric acid extraction equilibrium constant (KH).

3.9. Eu(III)-UDGA Coordination Complexes

As previously stated, the diglycolamides are tridentate ligands with the two amidic oxygens and the central etheric oxygen coordinating to the metal cation. The amidic oxygens are more strongly coordinating than the etheric oxygen, as is evidenced by x-ray crystallographic data.

Kannan et al. synthesized a lanthanum(III)-tetra-isobutyldiglycolamide (TiBDGA, Figure 3.10) coordination complex and reported La–O bond lengths of 2.496(3) and 2.501(3) Å for the amidic oxygens and 2.580(3) Å for the etheric oxygen.21

Figure 3.10. Structure of N,N,N',N'-tetra-isobutyldiglycolamide (TiBDGA).

The overall structure of the La(III)-TiBDGA complex is a triple-stranded helical arrangement of three tridentate ligands coordinated around the metal center. The complex adapts the tricapped trigonal prismatic structure with the etheric oxygens representing the caps and the amidic oxygens representing the vertices of the prism. Figure 3.11 shows the approximate structure from above.

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3+ Figure 3.11. Nine-coordinate tricapped trigonal prismatic structure of La(TiBDGA)3 (R = isobutyl).

The light lanthanides (La-Eu) are generally nine-coordinate while the heavy lanthanides

(Gd-Lu) are eight-coordinate.23 The change in coordination number stems from the decrease in ionic radii across the lanthanide series, which decreases the distance between the metal center and donor atoms on the surroundings ligands. This is generally a steric effect because there is less available space for ligands in the smaller coordination sphere. Since the valence 4f orbitals of the lanthanides are submerged in the core, they typically do not participate strongly in the bonding interactions of these ions; structural features of lanthanide coordination compounds are most often determined by ligand structural features and the balance of cation-ligand attraction and ligand-ligand repulsion effects.

The unsymmetrical diglycolamides (UDGAs, 1-12) synthesized for this work are designed for enhanced asymmetry and so do not form crystals readily. Thus, an alternative method for determining ligand-to-metal ratios was necessary. Solvent extraction experiments offer a representation of the coordination complex in a realistic organic phase

(e.g., 5.0% v/v 1 octanol/n dodecane). The partially simplified extraction of Eu(III) by a UDGA is

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represented by the reaction shown in Equation 3.10. The extraction of water has been neglected in this representation. The overlined species are in the organic phase.

3+ - Eu(free) + 3NO 3 + xn HNO 3 + UDGA Eu(UDGA)nx (NO 3 ) 3 (HNO 3 ) (3.10)

The conditional equilibrium constant for this extraction reaction can then be written as

Equation 3.11,

Eu(UDGA)nx (NO3 ) 3 (HNO 3 ) K'   ex 3 x n (3.11) Eu3+   NO -   HNO   UDGA  (free) 33    

Equation 3.11 almost contains the distribution ratio expression for Eu(III), which is the concentration of Eu(III) in the organic phase divided by the concentration of Eu(III) in the aqueous phase. The aqueous metal concentration given in Equation 3.11, however, is the free concentration of Eu(III) because some of the metal is bound by the weak complexant, nitrate. There are stability constants in the literature for 1:1 and 1:2 europium-nitrate complexes so the total aqueous metal concentration would be represented by Equation 3.12,

2+ + Eu3+  =  Eu 3+  +  Eu NO  +  Eu NO   (3.12)  (tot)   (free) 33  2 

The stability constants (β1 and β2) for the europium nitrate complexes (μ = 5 M NaNO3,

22°C) are given in Equations 3.13 and 3.14.24

2+ Eu NO3    1.. 86  0 04 (3.13) 1 Eu3+   NO -   (free) 3 

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Eu NO + 3 2 2 2 0.. 43  0 02 (3.14) Eu3+   NO -   (free) 3 

Equations 3.13 and 3.14 can also be rearranged to Equations 3.15 and 3.16

2+ Eu NO    Eu3+   NO -  (3.15) 3 1 (free)  3 

2 Eu NO+    Eu3+   NO -  (3.16) 32 2 (free)  3 

Substituting Equations 3.15 and 3.16 into Equation 3.12, a new total aqueous metal concentration expression containing β1 and β2 emerges in Equation 3.17,

2 Eu3+ = Eu 3+ +   Eu 3+ NO - + Eu 3+ NO - (3.17) (tot) (free)1  (free) 3 2 (free) 3

Equation 3.17 can be simplified to Equation 3.18,

2 Eu3+  =  Eu 3+  1+   NO -  +  NO -  (3.18)  (tot)   (free)  1  3  2  3  

The distribution ratio for Eu(III) in this particular system is given in Equation 3.19,

Eu(UDGA)nx (NO3 ) 3 (HNO 3 ) D   (3.19) Eu Eu3+ (tot)

Substituting Equation 3.18 into Equation 3.19, a new distribution ratio expression containing β1 and β2 emerges in Equation 3.20,

Eu(UDGA)nx (NO3 ) 3 (HNO 3 ) D   Eu 2 (3.20) Eu3+  1+   NO -  +  NO -   (free)  1  3  2  3  

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Equation 3.20 can be rearranged to Equation 3.21,

2 Eu(UDGA)nx (NO3 ) 3 (HNO 3 ) D 1+  NO--  +  NO    (3.21) Eu 1 3  2  3   Eu3+ (free)

Equation 3.21 can then be substituted into the original K'ex Equation 3.11 to give an expression containing both K'ex and DEu (Equation 3.22).

2 D 1+  NO--  +  NO  Eu 1 3  2  3   K'ex  3 x n (3.22) NO-   HNO   UDGA 33    

Equation 3.22 can be converted into a logarithmic form and rearranged to give Equation 3.23,

2 logD 1+  NO---  +  NO  log K'  3  log  NO   x  log  HNO   n  log UDGA  Eu 1 3  2  3  ex  3   3  

(3.23)

Equation 3.23 can be simplified if the concentration of nitric acid is fixed at 1.004 M. The log of 1.004 is equal to -0.00173, which can be neglected, so two terms (concentrations of nitric acid and nitrate) disappear from the right side of the equation. The values of β1 and β2 can also be plugged in to Equation 3.23 to yield Equation 3.24,

log 3. 49 D  log K'  n  log UDGA (3.24)  Eu ex 

Equation 3.24 can be represented by the slope of a straight line (y = mx + b) where y = log(3.49⋅DEu), m = n (the average number of ligands associated with each metal center),

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x = log[UDGA]org, and b = log K'ex. This mathematical relationship can help to obtain both the ligand-to-metal ratio (n) in the organic phase and an average extraction equilibrium constant (K'ex).

A series of solvent extraction experiments were run in which the concentration of the

UDGA ligand was varied while the concentration of HNO3 was held constant at 1.004 ± 0.006 M.

The metal partitioning was measured radiometrically by introducing a 152,154Eu(III) spike (10-5 M) to the biphasic system and measuring the counts per minute in each separated phase. The diluent

5.0% v/v 1-octanol/n-dodecane was used throughout to prevent third phase formation and allow for clean phase disengagement. Two of the smaller morpholino ligands (DHmorDGA and

DOmorDGA) displayed some third phase formation with the 5.0% 1-octanol diluent so the experiments were repeated with 10.0% v/v 1-octanol/n-dodecane. The additional phase modifier did prevent third phase formation but also made it difficult to compare the two ligands to the larger group. The concentration range for each UDGA ligand varied depending on metal extraction strength (e.g., 5.0, 10.0, 20.0, and 40.0 mM DHpyrDGA) and used at least four triplicate data points for the linear fitting in OriginPro® 2015. Every triplicate data point was plotted individually instead of plotting y-axis ±error to avoid any weighting of data points. Distribution ratios (DEu) were multiplied by a factor of 3.49 (see Equation 3.24) to account for the nitrate complexation in the aqueous phase.

The concentration of UDGA ligand was plotted vs. the nitrate-corrected distribution ratios on a logarithmic scale to utilize Equation 3.24. An example of the graphed data for DHpyrDGA is shown in Figure 3.12.

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105 org: 5.0, 10.0, 20.0, and 40.0 mM DHpyrDGA in 5.0% 1-octanol/n-dodecane

152,154 aq: Eu(III) radiotracer in 1.004 M HNO3 4 10 (org. phase pre-contacted w/ 1.004 M HNO3 for 30 min)

(org. phase contacted w/ spiked 1.004 M HNO3 for 30 min)

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2 DEu 10

1 10 Equation log(D) = n*log[UDGA] + log(K'ex) Weight No Weighting Residual Sum 0.03308 of Squares 0.99867 0 Pearson's r 10 Adj. R-Square 0.99707 Value Standard Error log(K'ex) = Intercept 7.81836 0.09274 n = Slope 3.01795 0.04933 10-1 1E-3 0.01 0.1 [DHpyrDGA] (M)

The slope (n) of the line fit through all twelve graphed points was 3.02 ± 0.05, which represents a 3:1 ligand to metal center ratio. This result is supported by the crystal structure previously referenced21 and by similar solvent extraction experiments using other unsymmetrical diglycolamides.12 Sasaki et al. also performed these ligand concentration dependence experiments with TODGA in various diluents.16 The numbers of ligands associated with each metal center in the organic phase increased with the decreasing dielectric constant of the diluent used. Table 3.3 shows the slopes (n) for each experiment with Eu(III).

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Table 3.3. The results of solvent extraction experiments performed by Sasaki et al.16 to ascertain the ligand to metal ratio for Eu(III) in various diluents. The dielectric constants for each diluent are also listed. Diluent εr TODGA:Eu (n) 1,2-dichloroethane 10.42 2.20 ± 0.06 1-octanol 10.30 2.48 ± 0.07 chloroform 4.8069 2.60 ± 0.09 toluene 2.379 3.58 ± 0.12 n-dodecane 2.0120 4.10 ± 0.05

Dielectric constants (ε) taken from the CRC Handbook of Chemistry and Physics.25

The increase in the stoichiometry of the extracted metal-ligand complex with decreasing polarity (dielectric constant) of the diluent can be attributed to the ability of the metal-ligand complex to dissolve in the diluent. A more polar diluent (e.g., 1,2-dichloroethane or 1-octanol) only requires two TODGA ligands (eight total octyl groups) to solvate the metal cation while nonpolar diluents (e.g., toluene and n-dodecane) require 3-4 TODGA ligands (12-16 octyl groups) to solvate the metal cation.15 The unsymmetrical diglycolamides (UDGA) ligands have fewer carbons in their alkyl chains than TODGA, which may theoretically require four or more ligands for each metal cation in an aliphatic diluent (e.g., n-dodecane). This requirement makes it impossible for the ligands to coordinate in either a tridentate or bidentate fashion (assuming a metal coordination number of 8 or 9), which could partially explain formation of a third phase for the majority of the UDGA ligands in aliphatic diluents. The addition of the phase modifier 1-octanol increases the polarity of the diluent and lowers the required number of ligands needed to solvate the metal cation from four or greater to three. It is also possible that the more polar 1-octanol molecules are selectively solvating the metal-ligand complexes, which would only increase the solvent polarity locally around the metal-ligand complexes. Nevertheless, the addition of 5.0%

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1-octanol to the n-dodecane diluent gives a stoichiometry of 1:3 for the Eu-UDGA complex

(Table 3.4).

Table 3.4. Conditional equilibrium constants (log K'ex) and metal-ligand complex stoichiometry (n) for unsymmetrical diglycolamide ligands (1-12) and TODGA in 5.0 or 10.0% v/v 1-octanol/n-dodecane in contact with radiotracer 152,154 Eu(III) in 1.004 M HNO3. # Diglycolamide Ligand log K'ex (Eu) n (ligand:metal) 5% 1-octanol/n-dodecane 1 DHpyrDGA 7.82 ± 0.09 3.02 ± 0.05 2 DHpipDGA 6.9 ± 0.2 3.0 ± 0.1 3 DHmorDGA third phase third phase 4 DOpyrDGA 7.9 ± 0.1 3.14 ± 0.07 5 DOpipDGA 6.7 ± 0.2 3.0 ± 0.1 6 DOmorDGA third phase third phase 7 DEHpyrDGA 7.4 ± 0.2 3.22 ± 0.09 8 DEHpipDGA 6.35 ± 0.04 3.27 ± 0.02 9 DEHmorDGA 5.5 ± 0.2 3.1 ± 0.1 10 DMOpyrDGA 8.3 ± 0.1 3.25 ± 0.07 11 DMOpipDGA 6.6 ± 0.1 3.08 ± 0.08 12 DMOmorDGA 5.1 ± 0.3 3.0 ± 0.1 - TODGA 6.24 ± 0.02 2.92 ± 0.01 10% 1-octanol/n-dodecane 3 DHmorDGA 6.41 ± 0.08 3.11 ± 0.04 6 DOmorDGA 6.83 ± 0.09 3.33 ± 0.05

The second result of each variable ligand experiment was a conditional equilibrium constant for the extraction of the metal from a nitric acid aqueous phase. This conditional equilibrium constant (log K'ex) was defined by Equation 3.23 to be equal to the y-intercept from the log-log plot seen in Figure 3.11. The log K'ex value for the DHpyrDGA experiment was

7.82 ± 0.09. The conditional equilibrium constants (log K'ex) and metal-ligand complex stoichiometry (n) are shown below in Table 3.4. The equilibrium constants generally became

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smaller as the ligand alkyl groups increased in size or branching. This trend follows the general

Eu(III) extraction trend seen in other solvent extraction experiments.

The ligand to metal ratios for the Eu-DGA complexes fall in between the Sasaki et al. literature values seen in Table 3.3 (4.10 ± 0.05 in n-dodecane and 2.48 ± 0.07 in 1-octanol).16 The combination of both diluents brings the ligand:metal ratio to an average of about 3:1. An experiment was run using TODGA in 5.0% v/v 1-octanol/n-dodecane to confirm these results and the 3:1 stoichiometry was verified. A digitized version of a graph from the same article by Sasaki et al. was used to estimate the conditional stability constants for the Eu-TODGA complexes (6.4 in n-dodecane and 4.8 in 1-octanol). These values also agree with the range of values seen in this work and the relative extraction strength of the ligands. Figure 3.13 shows the extraction of Eu(III) from 1.0 M HNO3 by ligands 1-12 and TODGA in 5% v/v 1-octanol/n-dodecane.

The dihexyl group of DGA extractants (black squares, 1-3) behaves quite similarly to the dioctyl group (red circles, 4-6) with a very slight decrease in distribution ratios from the hexyl to octyl derivatives. Within these families, extraction is seen to decrease from the “pyr” to “pip” to

“mor” for the smaller, more clearly polar side of the DGA extractants. Substitution of the branched

2-ethylhexyl group for the n-octyl group results in a ten-fold decrease in partitioning strength, as has been reported for the symmetrical diglycolamides TODGA and TEHDGA.26 The most amphiphilic family (DMO) exhibits the greatest sensitivity to the polarity of the cyclic amide functional group, decreasing by a factor of 103 from the “pyr” to the “mor” derivatives. The trend of decreasing metal distribution ratios with increasing alkyl group size has been reported in the earlier DGA literature with both symmetrical diglycolamides (tetraoctyl DGA vs. tetradecyl DGA)10 and unsymmetrical diglycolamides (di-decyl di-octyl DGA vs. di-dodecyl di-octyl DGA).12 The increase in alkyl chain length improves ligand solubility in n-dodecane, but

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also increases the steric hindrance around the binding pocket. This crowding of the binding pocket leads to a decrease in the metal distribution ratios.

104 org: 10 mM DGA ligand in 5% v/v 1-octanol/n-dodecane

152,154 aq: Eu(III) spike in 1.0 M HNO3 3 10 (30 min. pre-contact of org. phase with metal-free aq. phase) (30 min. contact of spiked org./aq. phases) 102

101

DEu 100

10-1 dihexyl UDGA dioctyl UDGA

-2 di-2-ethylhexyl UDGA 10 bis(3,7-dimethyloctyl) UDGA tetraoctyl DGA 10-3 1 2 3 4 5 6 7 8 9 10 11 12 T Diglycolamide Ligand

The branched di-2-ethylhexyl group (DEH, 7-9) and bis(3,7-dimethyloctyl) group (DMO,

10-12) display an opposite trend where the larger alkyl chain (DMO = C10) ligands actually have higher distribution ratios than the smaller alkyl chain (DEH = C8) ligands, with the exception of

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the DMO and DEH morpholino ligands, which have nearly similar DEu values. The branched

2-ethylhexyl group has been shown to have lower distribution ratios than straight-chain derivatives

(e.g., hexyl, octyl, decyl, dodecyl) for the symmetrical diglycolamides.27 It is possible that the ethyl group on the 2-position of the alkyl chain is positioned in a manner that could hinder access of the metal ion to the tridentate binding pocket. This hypothesis is supported by the higher metal extraction results with the 3,7-dimethyloctyl group. The shorter methyl groups on the 3- and

7-positions of the alkyl chain likely interfere less with metal binding while still increasing the ligand solubility in the organic phase. Figure 3.14 shows the optimized structures of generic di-2-ethylhexyl diglycolamides and the bis(3,7-dimethyloctyl) diglycolamides.

Figure 3.14. Generic structures of di-2-ethylhexyl diglycolamides (left) and the bis(3,7-dimethyloctyl) diglycolamides (right). Three-dimensional structures were created using the program Avogadro 1.1.1.28 Hydrogen atoms were included in the optimization process but omitted in the final structure for ease of viewing. The structures are shown from the front with a quarter bias (C = grey, O = red, N = blue).

In these structures, the di-2-ethylhexyl alkyl chains do appear to extend into a region relatively close to the binding pocket. The ethyl group on the 2-position also forces the alkyl groups farther apart, which may increase the steric hindrance around the binding pocket even more. The

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bis(3,7-dimethyloctyl) branched alkyl chains behave almost like a straight C8 chain with the only steric hindrance occurring between the two alkyl groups themselves.

The pyrrolidinyl group (pyr: 1, 4, 7, and 10) has the highest distribution ratios of all the ligands. The five-member pyrrolidine ring has the smallest footprint of all the alkyl groups and a five-membered ring (rather than six) attached at the amide moiety. All of the rings (pyr, pip, mor) lack free rotation due to the double-bond nature introduced into the C-N amide bond. The resonance structures for the cyclic amides (pyr used as an example) are shown in Figure 3.15.

Figure 3.15. Resonance structures for the pyrrolidinyl amide (R = hexyl, octyl, 2-ethylhexyl, 3,7-dimethyloctyl.

The confined pyrrolidinyl group does not interfere with metal complexation in the binding pocket (an area in the plane of the three oxygens directly above the central etheric oxygen at a distance of ca. 1.5 Å). The structures of the piperidinyl (2, 5, 8, and 11) and morpholino

(3, 6, 9, and 12) amides include a sixth atom (C or O) projected out of the plane of the ring in the chair formation. These extractants are considerably weaker than their pyrrolidinyl counterparts with the piperidinyl groups having slightly stronger extraction than the morpholino groups. It is possible that the oxygen in the morpholine ring withdraws enough electron density from the amide to weaken the complexation of metal cations in the binding pocket. The large increase in extraction with the pyrrolidinyl group is likely based upon a decrease in steric hindrance.

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Solvent extraction slope analysis studies offer a fairly simple way to characterize the metal-ligand complex in the organic phase. The conditional extraction equilibrium constants and average ligand-to-metal ratios allow different extractant molecules to be compared under similar conditions. Nevertheless, the true identity of the metal-ligand complex is much more difficult to elucidate. The denticity of each ligand and location of nitrate, nitric acid, and water molecules further complicate the inner and outer coordination spheres of the metal center. As previously seen, crystal structures of Ln(III)-diglycolamide complexes show three tridentate ligands perfectly arranged around the metal.21 Unfortunately these solvent extraction systems involve two immiscible phases with the metal-ligand complex solvated in the organic phase. Alternative techniques such as vapor pressure osmometry (VPO) and small-angle neutron scattering (SANS) can be used to confirm ligand aggregation numbers in the organic phase, while optical spectroscopy can offer some illumination on the location of nitrate and water molecules.

3.10. Nitric Acid Dependence Extractions

152,154 Investigation of the extraction of Eu(III) from 1 M HNO3 was important for establishing the relative strength of metal-ligand complexes (log K'ex) and metal-ligand complex stoichiometry (n). Examining the metal extraction from a broader range of [HNO3] is important for the overall evaluation of the newly synthesized unsymmetrical diglycolamides. The relative partitioning of metal cations into an organic phase containing solvating extractants is greatly affected by the concentration of nitric acid (or nitrate ion) in the aqueous phase. At low

- concentrations of HNO3 (e.g., 0.01 M), solvating extractants lack sufficient NO3 counter anions to drive the extraction of trivalent metal cations and the metal cations are strongly solvated by water molecules. At high concentrations of HNO3 (e.g., 1 M), there is a large excess of available

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- NO3 anion to drive the extraction of the neutral metal-ligand complex and the metal cations are more weakly hydrated due to the decrease in available water (salting-out effect).29 A generic extraction equilibrium equation is shown in Equation 3.25 for a solvating extractant (L) and a trivalent metal (M3+). Organic phase species are overlined.

3+ - M(H2 O)y + 3NO 3 + x HNO 3 + n L Eu(L) n (NO 3 ) 3 (HNO 3 ) x  y H 2 O (3.25)

As previously stated, solvating extractants (e.g., TODGA) are known to also extract water into the organic phase but that has been neglected in Equation 3.24.30 The equilibrium is more significantly affected by the dehydration of the metal cation and the release of water molecules

(an entropic effect). This equilibrium shifts to the right when the amount of free water is decreased and the amount of nitrate anion is increased. The number of nitrate anions extracted is fixed at three because of the necessity to extract a neutral metal-nitrato complex into the nonpolar organic phase. The number of nitric acid molecules extracted is not fixed, however, as was suggested in the previous section dealing with nitric acid extraction.

Sasaki et al.10,16 and Yaita et al.31 have performed experiments with TODGA

(in n-dodecane) where the concentration of ligand is fixed and the concentration of HNO3 is varied.

The results have shown that at high HNO3 concentrations (e.g., 1 M) there is a hyperstoichiometric nitrate dependence (i.e., >3). Since only three nitrate anions are required to neutralize each trivalent metal ion that is extracted, the extra nitrate is most likely extracted in the form of neutral

HNO3. In the TODGA system, this hyperstoichiometric nitrate dependence coincides with an exponential increase in trivalent lanthanide and trivalent actinide metal extraction at these high acidities. This behavior can be seen in Figure 3.16.

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104 0.1 M TODGA in n-dodecane‡ 0.0500 M TODGA in 5.0% v/v 1-octanol/n-dodecane* 103

102

101

0.2 DEu 0 10 0.2

slope = 3.4

slope = 2.1 10-1 0.1

slope = 2.1 10-2

*quantitative metal extraction at 2.97 M HNO3

‡TODGA in n-dodecane data digitized from Sasaki et al. Solvent Extr. Ion Exch. 2007, 25, 187-204. 10-3 1E-3 0.01 0.1 1 10

[HNO3] (M)

Figure 3.16. The extraction of 152,154Eu(III) by N,N,N',N'-tetraoctyldiglycolamide (TODGA) from varying concentrations of nitric acid. The 0.1 M TODGA in n-dodecane data was digitized from published work by Sasaki et al.16

The nitric acid dependence (slope = 2.1 ± 0.2) for the 0.0500 M TODGA in 5.0% v/v

1-octanol/n-dodecane differs from the n-dodecane data where two distinct regions are observed

(slope1 = 2.1 ± 0.1; slope2 = 3.4 ± 0.2). The extracted complex must contain three nitrate ions to balance the +3 charge on the metal cation so the theoretical nitric acid dependence slope should always be 3.0. However, there are several competing equilibria involved in the extraction reaction so the theoretical value is rarely achieved. The aqueous complexation of nitrate to Eu3+ increases with increasing [HNO3], which could reduce metal partitioning into the organic phase (i.e., lower

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distribution ratio). It is also known that the diglycolamides (and all solvating extractants) also extract HNO3, which decreases the amount of free ligand in the organic phase available to extract metal-nitrato complexes. This decrease in metal extraction will also depress the distribution ratios as [HNO3] increases, which is a second factor lowering the nitric acid dependence slope.

The hyperstoichiometric region (slope2 = 3.4 ± 0.2) in the TODGA-n-dodecane system is likely due to a change in the extracted complexes at high acidity (e.g., ≥ 0.5 M HNO3). Jensen et al. found that “tetrameric” (TODGA)4 complexes formed in n-octane when in contact with aqueous phase acidities greater than 0.7 M HNO3 in the absence of metal. These quaternary TODGA

3+ 32 complexes were also shown to form with Nd present at aqueous phase acidities ≥ 0.5 M HNO3.

The tetramers are described as reverse-micelles with a polar core containing the extracted metal cations, nitrates, nitric acid, and water molecules. These (TODGA)4 reverse-micelles preferentially extract Ln(III) and An(III) cations over Pu(IV) and U(VI)10 while also extracting hyperstoichiometric quantities of nitrate.

It has been seen earlier in this work (see Tables 3.3 and 3.4) that the addition of the phase modifier 1-octanol changes the extracted Eu-TODGA complex from the tetrameric 1:4 complex32 to the 1:3 extracted species. The 1:3 extracted species has not been shown to be a reverse-micelle and will likely not have the ability to extract nitric acid and metal into the same (TODGA)3 complex. Nevertheless, the unsymmetrical diglycolamides require the diluent 5.0% v/v

1-octanol/n-dodecane to prevent third phase formation at high acidity (e.g., ≥1 M HNO3). The

UDGAs (1-12) were each evaluated for nitric acid dependence profiles using the radiotracer

152,154Eu(III) as the partitioned metal. Figure 3.17 shows the extraction data for the first three

UDGAs (DHpyrDGA, DHpipDGA, DHmorDGA).

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104 org: 50 M UDGA in 5.0% v/v 1-octanol/n-dodecane 152,154 aq: Eu(III) spike in 0.0097, 0.097, 0.99, and 3.0 M HNO3 103 (org. pre-contacted with metal-free aq. for 30 min.) (spiked org./aq. phases contacted for 30 min.)

102

1 0.2 10 slope = 1.8 DEu slope = 1.5 0 10 slope = 0.4 0.1

10-1 slope = 2.5 DHpyrDGA(1)† 10-2 DHpipDGA(2)† DHmorDGA(3)† †third phase formation occurs at 3 M HNO3 10-3 1E-3 0.01 0.1 1 10

[HNO3] (M)

Figure 3.17. The extraction of 152,154Eu(III) by the dihexyl derivatives (1-3) from varying concentrations of nitric acid.

The dihexyl derivatives (1-3) are the strongest extractants in this current suite of ligands, which is perhaps not surprising based on a low steric hindrance argument. The C6 alkyl chains are less likely to interfere with the metal coordinating at the binding pocket than the longer or more branched C8 (n-octyl or 2-ethylhexyl) or C10 (3,7-dimethyloctyl) alkyl chains. The shorter C6 alkyl chains also reduce the solubility of the HNO3-UDGA ligand complex in the organic phase, which is seen in the data points at 3.0 M HNO3 where third phase formation was observed. DHpyrDGA(1) and DHpipDGA(2) both have a distribution ratio of about 1 at 0.0097 M HNO3, which would not

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be sufficient for stripping extracted Ln(III) from a loaded organic phase with this medium.

DHpyrDGA(1) and DHpipDGA(2) also have a flatter nitric acid dependence at low acidity and only a slightly higher dependence (slope ~ 2) at higher acidity. DHmorDGA(3) appears to maintain a slope of 2.5 throughout the nitric acid concentration range Evidence for the appearance of a third phase at 3.0 M HNO3 limited the potential utility of this series and so plans for further slope analysis investigations were dropped.

The second group of extractants studied was the dioctyl derivatives (4-6). These derivatives contain the n-octyl groups that are considered optimal for use with the symmetrical diglycolamides

(i.e., TODGA). The straight chain C8 groups increase the lipophilicity of the aliphatic extractant

“tails” relative to the C6 groups and should exhibit improved solubility in aliphatic diluents such as n-octane and n-dodecane. The C8 groups are also preferable to C10 groups or greater because they have demonstrated stronger metal extraction than the longer, more sterically hindering alkyl groups in solvent extraction studies by Sasaki et al.10 A more detailed nitric acid dependence is shown in Figure 3.18 for ligands 4-6 (DOpyrDGA, DOpipDGA, DOmorDGA). The dioctyl derivatives are comparable in metal extraction strength to their dihexyl counterparts (1-3). This is supported by previous extraction results in this work (see Table 3.4 and Figure 3.13). The dioctyl derivatives have the added benefit of not forming a third phase at 3 M HNO3 as is seen with each of the dihexyl derivatives.

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104 org: 50 mM UDGA in 5% v/v 1-octanol/n-dodecane 152,154 aq: Eu(III) spike in 0.0097-3.0 M HNO3 103 (org. pre-contacted with metal-free aq. for 30 min.) (spiked org./aq. phases contacted for 30 min.)

2 0.7 10  0.1

0.2

101 slope = 1.9 slope = 5.9 DEu slope = 2.7 100 0.2

slope = 0.8 0.1 10-1 slope = 0.5

-2 DOpyrDGA(4)* 10 DOpipDGA(5) DOmorDGA(6) *quantitative metal extraction at 1.9 and 3.0 M HNO3 10-3 1E-3 0.01 0.1 1 10

[HNO3] (M)

Figure 3.18. The extraction of 152,154Eu(III) by the dioctyl derivatives (4-6) from varying concentrations of nitric acid.

Ligands 4-6 achieve distribution ratios greater than 1000 at 3.0 M HNO3 and less than 1 at

0.0097 M HNO3. This demonstrates the ability of the ligands to extract Ln(III) at high acidity and to allow stripping of the metal at low acidity. DOpyrDGA(4) exhibits a slightly steeper, but consistently linear nitric acid dependence (slope = 1.9 ± 0.1) compared to DHpyrDGA(1)

(slope = 1.5 ± 0.2). Each of these slopes are well below the theoretical slope of three for the requisite extracted nitrates, which is due to a combination of nitrate complexation in the aqueous phase and nitric acid extraction in the organic phase, both of which decrease the metal partitioning.

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The relatively constant slope over a large range of acidity (0.0097-0.99 M HNO3) is also unusual for diglycolamides and interestingly is only seen with the pyrrolidinyl ligands.

DOpipDGA(5) and DOmorDGA(6) derivatives both have regions of shallow nitric acid dependence at low acidity and steeper slopes at higher acidity. DOmorDGA(6) achieves the first observed hyperstoichiometric nitric acid dependence (slope = 5.9 ± 0.7) from 0.49 to 1.9 M HNO3.

This stoichiometry would require a reorganization of the HNO3-DOmorDGA complex into a supramolecular aggregate with the ability to contain 6 molecules of nitric acid. This interesting result was tempered by previous data with DOmorDGA(6) (see Table 3.4) where a third phase was detected at lower concentrations of ligand (e.g., 10 or 20 mM). DOpipDGA(5) and DOmorDGA(6) both demonstrated a decrease in DEu between 1.9 and 3.0 M HNO3, which may suggest a saturation of the organic phase with nitric acid, although no third phase formation was detected. The distribution ratios are also over 2000, which is close to the upper limit for reliable DEu values. The most promising candidate for the extraction of Ln(III) and An(III) from used nuclear fuel of these first two sets of ligands is DOpipDGA(5) because it has two distinct regions of nitric acid dependence at low and high acidity (metal stripping region: slope1 = 0.8 ± 0.2; metal extraction region: slope2 = 2.7 ± 0.2) and does not form a third phase at high nitric acid concentrations.

The third triad of ligands examined was the di-2-ethylhexyl (DEH) derivatives (7-9).

The DEH derivatives are the weakest of all the ligands due to the ethyl branch off the 2-position, which appears to sterically hinder metal complexation at the binding pocket (see Figure 3.13).

Nevertheless, the symmetrical 2-ethylhexyl diglycolamide (TEHDGA)33 is the second most studied diglycolamide after TODGA. TEHDGA is a branched isomer of TODGA that exhibits suppressed metal extraction compared to the straight-chain n-octyl derivative.26 It was hoped that the branched alkyl groups would also decrease the extraction of unwanted fission products

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(e.g., Sr(II)).33 TEHDGA did show suppressed Sr(II) metal extraction at lower acidity (<1 M

HNO3) but extracted Sr(II) similarly to TODGA at higher acidity (>1 M HNO3). TEHDGA was found to extract Am(III) from 1 M HNO3 as the 3:1 complex instead of the apparent 4:1 complex seen with TODGA.26 Interestingly, TODGA was shown to have higher Am(III) distribution ratios and to continue to efficiently extract metal at up to 6 M HNO3, whereas TEHDGA exhibited lower

34 DAm values and formed a third phase at a [HNO3] above 3 M. The nitric acid dependence data for the DEH derivatives (DEHpyrDGA, DEHpipDGA, DEHmorDGA) in this study are shown in

Figure 3.19.

104 org: 50 mM UDGA in 5.0% v/v 1-octanol/n-dodecane 152,154 aq: Eu(III) spike in 0.0097-3.0 M HNO3 103 (org. pre-contacted with metal-free aq. for 30 min.) (spiked org./aq. phases contacted for 30 min.)

102 DEHpyrDGA(7)* DEHpipDGA(8) DEHmorDGA(9)* 0.1 101 D slope = 2.1 Eu 0.4 0 10 0.3

slope = 2.8

-1 10 0.4 slope = 3.0 slope = 0.7 0.1 10-2 slope = 1.4

*quantitative metal extraction at 1.9 and/or 3.0 M HNO3 10-3 1E-3 0.01 0.1 1 10

[HNO3] (M)

Figure 3.19. The extraction of 152,154Eu(III) by the di-2-ethylhexyl derivatives (7-9) from varying concentrations of nitric acid.

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As expected, the DEH derivatives (7-9) have suppressed DEu values compared to the straight-chain dihexyl and dioctyl ligands. The metal extraction is particularly low at 0.0097 M

HNO3, where all three ligands have a DEu ≤ 0.04. Nevertheless, the nitric acid dependence slopes for DEHpyrDGA(7) (slope = 2.1 ± 0.1) and DEHpipDGA(8) (slope1 = 0.7 ± 0.4; slope2 = 2.8 ± 0.4) match up almost perfectly with their respective dioctyl analogues,

DOpyrDGA(4) (slope = 1.9 ± 0.1) and DOpipDGA(5) (slope1 = 0.8 ± 0.2; slope2 = 2.7 ± 0.2). This suggests that similar complexes are being extracted for both the dioctyl and DEH derivatives, even if the metal extraction is much weaker for the DEH ligands. The morpholino ligand

DEHmorDGA(9) differs from its dioctyl analogue in both slope values for the nitric acid dependence and in the location of the inflection point. The nitric acid dependence increases sharply to ca. 6 after 0.49 HNO3 for DOmorDGA(6) while the slope increases to ca. 3 after 0.097 M HNO3 for DEHmorDGA(9). This difference may suggest that the UDGA complexes contain different amounts of HNO3 for DOmorDGA(6) and DEHmorDGA(9). The morpholino ligands also have lower metal distribution ratios than the piperidinyl and pyrrolidinyl ligands, which may suggest that the morpholino ligands are extracting more HNO3 and decreasing the [UDGA]free. The most promising candidate for possible reprocessing applications (Ln(III) extraction) from the DEH derivatives is DEHmorDGA(9). DEHmorDGA has the lowest metal extraction at 0.0097 M HNO3

(DEu = 0.004 ± 0.002) for metal stripping purposes and still has nearly quantitative metal extraction at 1.9 M HNO3 (DEu = 1080 ± 316) for the selective partitioning of Ln(III) metals into the organic phase.

The last triad of ligands studied was the bis(3,7-dimethyloctyl) (DMO) group of derivatives

(10-12). This doubly branched C10 alkyl group has never before been incorporated into any

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diglycolamide or diamide ligand. The advantage of this new C10 alkyl group is that it includes two extra carbons (compared to the unbranched n-octyl group) for increased ligand solubility in aliphatic diluents while not greatly increasing the steric hindrance around the binding pocket of the ligand (see Figure 3.13). The DMO derivatives (10-12) were expected to demonstrate slightly lower metal extraction than the dioctyl derivatives (4-6) but would likely be stronger extractants than the more structurally-hindered di-2-ethylhexyl derivatives (7-9). The nitric acid dependence extraction data for ligands 10-12 (DMOpyrDGA, DMOpipDGA, DMOmorDGA) are shown in

Figure 3.20.

0.1 102 

slope = 2.1 101 0.3 DEu slope = 2.5 100 0.1 0.1 slope = 0.3

slope = 2.6 10-1

DMOpyrDGA(10)* 10-2 slope = 0.5 DMOpipDGA(11)*

*quantitative metal extraction at 1.9 and 3.0 M HNO DMOmorDGA(12) 10-3 3 1E-3 0.01 0.1 1 10

[HNO3] (M)

Figure 3.20. The extraction of 152,154Eu(III) by the bis(3,7-dimethyloctyl) derivatives (10-12) from varying concentrations of nitric acid.

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As predicted, the DMO derivatives (10-12) fell directly in between the di-2-ethylhexyl and dioctyl derivatives in terms of overall extraction strength (i.e., DEu). Nevertheless, the shape and slope of the nitric acid dependence curves for DMOpyrDGA(10) and DMOpipDGA(11) mirrored their analogues in the di-2-ethylhexyl (7 and 8) and dioctyl (4 and 5) groups, with similar slope values and inflection points at 0.01 M HNO3 for three of the piperidinyl ligands: DOpipDGA(5),

DEHpipDGA(8), and DMOpipDGA(11). Interestingly, DMOpyrDGA(10) demonstrates no clear evidence for extractant reorganization with increasing [HNO3] (evidenced by the single, linear dependence of 2.1 ± 0.2) and has a lower DEu at 0.01 M HNO3 (more useful for Ln(III) stripping) than DMOpipDGA(11), which is not seen with the other “pyr/pip” ligand pairs. The morpholino derivative, DMOmorDGA(12), again displayed a singular behavior by changing nitric acid dependence slopes (from 0.5 to 2.6) at the lowest acidity yet (0.025 M HNO3). DMOmorDGA(12) is the most promising DMO extractant for possible fuel reprocessing application because it has a

3 DEu < 0.01 at 0.0097 and 0.024 M HNO3 (Ln(III) stripping region) and a DEu > 10 at 1.9 and

3.0 M HNO3 (quantitative Ln(III) extraction region). The variability of the morpholino derivatives provided for an intriguing problem and further nitrate dependence studies were completed with

DMOmorDGA(12).

3.11. Nitrate Dependence Extraction with DMOmorDGA

The diglycolamides are solvating extractants and, as such, are required to extract negative counterions into the organic phase along with the metal cations. An experiment that varies the

- concentration of counterion (e.g., NO3 ) while maintaining the same aqueous phase acidity and organic phase conditions should result in a constant nitrate dependence slope that corresponds to

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the charge on the metal cation (e.g., ideal slope = 3 for Eu3+ extraction). A nitrate dependence experiment at pH = 3 was run with 20.0 mM DMOmorDGA in 5.0% v/v 1-octanol/n-dodecane to probe this behavior. Unfortunately, a visible third phase (white gel) formed with the higher nitrate concentrations (0.998, 2.00, and 3.00 M NaNO3) after the samples were spiked with radiotracer

152,154Eu and mixed for 30 minutes. No visible third phase was observed for the lower nitrate concentrations (0.0102, 0.0516, 0.101, and 0.500 M NaNO3) and there was no loss of cpm seen in the gamma counting results (compared to activity in cpm of 5.00 μL 152,154Eu spike). The pH of the aqueous phase was measured before (pH = 3.0) and after (pH = 4.1-3.9) metal extraction; the

[HNO3]org calculates to ca. 1 mM for this change in pH, which would not be expected to cause a third phase with the 20 mM DMOmorDGA. The organic phase (20 mM DMOmorDGA in 5% v/v

1-octanol/n-dodecane) was pre-equilibrated with metal-free sodium nitrate solutions and no third phase formation was observed. Thus, the metal cation (ca. 10-5 M Eu3+) must be involved in the formation of the dense organic phase. The white gel third phase must be made up of mostly NaNO3, however, since it is the only component present at the molar concentrations necessary to form a visible gel (ca. 10% of the total sample volume). No new conclusions were taken from this sodium nitrate dependence experiment, other than the possible existence of NaNO3 enriched dense organic phases.

3.12. Lanthanide Series Extractions

The radiotracer 152,154Eu(III) is a useful and convenient representative of lanthanide metal behavior, but it is always interesting to examine the pattern of extraction of all of the lanthanide metals (La-Lu, excluding Pm) under the same conditions; it has been noted that the effect of changing cationic radius on extraction efficiency does not always follow a simple pattern. Grenthe

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and Tobiasson determined stability constants by potentiometry for the Ln(III) tris-diglycolate

35 complexes in 1 M NaClO4. The trend in log β103 values is shown in Figure 3.21.

titrand = Ln(III) tris-diglycolate in 1.00 M NaClO4 titrant = NaOH 14 T = 20.0C

103 

11 log log

Stability constants taken from Grenthe and Tobiasson, Acta Chem. Scand. 1963, 17, 2101-2112. *ionic radii were taken from Shannon, R. D. Acta Cryst. 1976, 32, 751-767. (CN=9 for Ln(III)) 8 0.80 0.82 0.84 0.86 0.88 0.90 0.92 0.94 0.96 0.98 1.00 1/r (Å-1)

Figure 3.21. The log β103 values for the tris-diglycolate complexes with La(III)-Lu(III) (μ = 1.00 35 M NaClO4, T = 20.0°C) from work by Grenthe and Tobiasson. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon.36

The largest increase in the 1:3 Ln(III)-diglycolate stability constant values occurs between the lightest lanthanides La (log β103 = 10.2) and Ce (log β103 = 11.2). The log β103 values continue to increase by regular increments until Gd, where a decrease in complex stability (compared to the previous Ln(III), Eu) is seen. The trend in log β103 flattens out after Gd with a slight decrease in complex stability for the heaviest lanthanides (Yb and Lu) compared to Tm.

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For the purposes of Ln(III) separations from spent nuclear fuel, only La-Tb are present in significant quantities to warrant evaluation of their extractability. The heavier lanthanides (Dy-Lu) are still useful to study because the decreasing ionic radii (Dy3+ = 1.027 Å (CN = 8); Lu3+ = 0.977 Å

(CN = 8)) can be compared to other fission products of interest in spent nuclear fuel (e.g. Cd(II) =

0.95 Å (CN = 6)).36 Lanthanide series extractions were performed for the unsymmetrical diglycolamides (1-12) and the symmetrical diglycolamide N,N,N',N'-tetraoctyldiglycolamide

(TODGA). The extraction of the Ln(III) metals by TODGA will be used as a baseline for comparison. The results of the experiment are shown in Figure 3.22.

104 org: 10.2 mM TODGA in 5.0% v/v 1-octanol/n-dodecane

aq: 0.120 mM Ln(III)* in 1.8 M HNO3 (org. pre-contacted with metal-free aq. for 30 min.) 3 10 (spiked org./aq. phases contacted for 30 min.)

102

101 DM 100

10-1

10-2

*ionic radii were taken from Shannon, R. D. Acta Cryst. 1976, 32, 751-767. (CN=9 for Ln(III)) 10-3 0.80 0.82 0.84 0.86 0.88 0.90 0.92 0.94 0.96 0.98 1.00 1/r (Å-1)

Figure 3.22. The extraction of La(III)-Lu(III) by N,N,N',N'-tetraoctyldiglycolamide (TODGA) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon.36

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As expected, the heavy lanthanides are more strongly extracted than the light lanthanides with the highest distribution ratio coming at lutetium and the lowest distribution ratio coming at lanthanum. The ionic radii steadily decrease across the lanthanide series while the charge remains constant at +3. This causes the electrostatic field (E) to increase around the trivalent cations.

Coulomb’s Law37 explains this increase in Equation 3.26,

1 z E  2 4 0 r E  electrostatic field (N C-1 ) (3.26) 2 -1 -2 zr charge (C),  ionic radius (m), 0  permittivity of free space (C  N  m )

A decrease in ionic radius (r) at a constant charge (z) increases the electrostatic field around the cation and should increase the complexation strength of the partially negative carbonyl and etheric oxygens on the ligand. In simple terms, the charge is becoming more concentrated, which should strengthen the attraction between the positive (hard-sphere) cation and the negative end of the triple dipole of the diglycolamide (two amide O atoms and one ether O atom). This coulombic attraction controls the extraction strength to a point, but TODGA is also size selective, which is evidenced by the flat extraction trend between Tm, Yb, and Lu.

The cation size selectivity and electrostatic attraction between the partial negative charges on the oxygen donor atoms and the +3 positive charge on the Ln3+ cations are only two of many factors determining the metal-ligand complex stability. The extracted species is actually

Ln(DGA)x(NO3)3(HNO3)y(H2O)z so the trans-lanthanide pattern of thermodynamic

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stability-instability is actually governed by several competing equilibria, including the extraction of nitric acid and water.

The UDGA results have been separated based on the four different long-chain alkyl groups

(n-hexyl, n-octyl, 2-ethylhexyl, and 3,7-dimethyloctyl). The extraction results for ligands 1-3

(DHpyrDGA, DHpipDGA, DHmorDGA) are shown in Figure 3.23.

104 org: 10 mM UDGA in 5.0% v/v 1-octanol/n-dodecane

aq: 0.120 mM Ln(III)* in 1.8 M HNO3 (org. pre-contacted with metal-free aq. for 30 min.) 3 10 (spiked org./aq. phases contacted for 30 min.)

102

101 DM 100

10-1 DHpyrDGA(1)

-2 DHpipDGA(2) 10 DHmorDGA(3)

*ionic radii were taken from Shannon, R. D. Acta Cryst. 1976, 32, 751-767. (CN=9 for Ln(III)) 10-3 0.80 0.82 0.84 0.86 0.88 0.90 0.92 0.94 0.96 0.98 1.00 1/r (Å-1)

Figure 3.23. The extraction of La(III)-Lu(III) by the dihexyl derivatives (1-3) from 1.8 M 36 HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon.

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The metal extraction curves for ligands 1-3 (DHpyrDGA, DHpipDGA, DHmorDGA) follow the same general trend as TODGA, except at elevated distribution ratios. There is, however, a decrease in metal extraction after Yb3+ (r = 1.042 Å (CN = 9)), which means that the binding pocket for ligands 1-3 is optimized for cations with a slightly larger ionic radius than seen with

TODGA and Lu3+ (r = 1.032 Å (CN = 9)).36

The metal extraction strength of each ligand follows the general trend seen with Eu(III) studies except at the lightest lanthanides (La-Nd) where DHmorDGA(3) is slightly stronger than

DHpipDGA(2). DHpyrDGA(1) has a steeper initial curve with the light lanthanides and achieves separation factors of 2.4 ± 0.1 (Ce/La), 2.3 ± 0.1 (Pr/Ce), and 2.5 ± 0.1 (Nd/Pr) for the first three metal pairs. The separation factor between metal 1 and metal 2 (SFM1/M2) is defined as the distribution ration of metal 1 divided by the distribution ratio of metal 2, as seen in Equation 3.27.38

D SF  M1 (3.27) M12 /M D M2

The separation factor is a measure of metal ion selectivity and provides a quantitative method for comparing the ability of a ligand to separate two metals from one another. As the separation factor increases the number of biphasic contacts necessary for metal decontamination decreases, which is favorable for industrial solvent extraction processes.

The second group of ligands are the dioctyl derivatives (4-6, DOpyrDGA, DOpipDGA,

DOmorDGA). This group of ligands was slightly weaker than the dihexyl derivatives (1-3) in the

Eu(III) extraction experiments and the DOmorDGA(6) ligand showed the anomalous hyperstoichiometric nitric acid dependence (slope = 6, see Figure 3.17) between 0.5 and 2 M

HNO3. The lanthanide series extraction data for ligands 4-6 are shown in Figure 3.24.

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104 org: 10 mM UDGA in 5.0% v/v 1-octanol/n-dodecane

aq: 0.120 mM Ln(III)* in 1.8 M HNO3 (org. pre-contacted with metal-free aq. for 30 min.) 3 10 (spiked org./aq. phases contacted for 30 min.)

102

101 DM 100

10-1 DOpyrDGA(4)

-2 DOpipDGA(5) 10 DOmorDGA(6)

*ionic radii were taken from Shannon, R. D. Acta Cryst. 1976, 32, 751-767. (CN=9 for Ln(III)) 10-3 0.80 0.82 0.84 0.86 0.88 0.90 0.92 0.94 0.96 0.98 1.00 1/r (Å-1)

Figure 3.24. The extraction of La(III)-Lu(III) by the dioctyl derivatives (4-6) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon.36

The dioctyl pyrrolidinyl ligand, DOpyrDGA, behaves nearly identically to the dihexyl pyrrolidinyl analogue, DHpyrDGA, with similar distribution ratios throughout. The separation factors for DOpyrDGA with the first three lanthanide metal pairs (2.3 ± 0.1 (Ce/La), 2.2 ± 0.1

(Pr/Ce), and 2.5 ± 0.1 (Nd/Ce)) also match the DHpyrDGA values. The DOmorDGA ligand does exhibit interesting behavior across the lanthanide series, with slightly higher distribution ratios than DOpipDGA from lanthanum to dysprosium. This is in contrast to the dihexyl derivatives where DHpipDGA had considerably higher metal extraction with the heavy lanthanides (from Tb

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to Lu). DOpipDGA and DOmorDGA also share at a maximum at ytterbium (1/Å = 0.96 Å-1) although there is little difference between the extraction of heaviest lanthanides: Tm, Yb, and Lu.

DOpyrDGA has a maximum metal distribution ratio at erbium (1/Å = 0.94 Å-1) but the error for this data point is unusually high (ca. 40%) so it is possible that the true maximum still comes at ytterbium like the rest of the group.

The third group of ligands examined were the di-2-ethylhexyl derivatives (7-9,

DEHpyrDGA, DEHpipDGA, DEHmorDGA). These ligands were shown to be the weakest extractants for Eu(III) in previous radiotracer solvent extraction studies. The Ln(III) series metal extraction experiments are particularly interesting with these derivatives because the change in ionic radius across the series can help to determine whether the ethyl group in the 2-position is shrinking the size of the binding pocket or merely hindering the metal cation from reaching the binding pocket. The Ln(III) series extraction results for ligands 7-9 are shown in Figure 3.25.

As predicted, the overall metal extraction by the di-2-ethylhexyl derivatives (7-9) is much weaker than for the dihexyl (1-3) and dioctyl (4-6) derivatives. The extraction curve for

DEHpyrDGA is also less steep for the light lanthanides with separation factors of 2.1 ± 0.1

(Ce/La), 1.9 ± 0.1 (Pr/Ce), and 2.1 ± 0.1 (Nd/Pr). DEHpyrDGA has its maximum metal extraction at Yb, which is a commonality among the first seven ligands. DEHpipDGA and DEHmorDGA do not share this maximum, however, and see a slight selectivity for Lu (1/Å = 0.97 Å-1) over Yb

(1/Å = 0.96 Å-1). This result fits with the hypothesis that the ethyl group in the 2-position of the

2-ethylhexyl group is directly interfering with metal complexation at the binding pocket. The smaller Lu(III) cation may not be as sterically-hindered as the slightly larger Yb(III) cation.

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104 org: 10 mM UDGA in 5.0% v/v 1-octanol/n-dodecane

aq: 0.120 mM Ln(III)* in 1.8 M HNO3 (org. pre-contacted with metal-free aq. for 30 min.) 3 10 (spiked org./aq. phases contacted for 30 min.)

102

101 DM 100

10-1 DEHpyrDGA(7) 10-2 DEHpipDGA(8) DEHmorDGA(9)

*ionic radii were taken from Shannon, R. D. Acta Cryst. 1976, 32, 751-767. (CN=9 for Ln(III)) 10-3 0.80 0.82 0.84 0.86 0.88 0.90 0.92 0.94 0.96 0.98 1.00 1/r (Å-1)

Figure 3.25. The extraction of La(III)-Lu(III) by the di-2-ethylhexyl derivatives (7-9) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon.36

The final group of ligands tested were the bis(3,7-dimethyloctyl) derivatives (10-12,

DMOpyrDGA, DMOpipDGA, DMOmorDGA). These extractants were shown to be stronger than the bis(2-ethylhexyl) derivatives for the partitioning of Eu(III) from a nitric acid aqueous phase. It was also postulated that the methyl groups branching off the octyl backbone at the 3- and

7-positions do not directly interfere with metal complexation at the binding pocket. The results of the Ln(III) series metal extraction for ligands 10-12 are shown in Figure 3.26.

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104 org: 10 mM UDGA in 5.0% v/v 1-octanol/n-dodecane

aq: 0.120 mM Ln(III)* in 1.8 M HNO3 (org. pre-contacted with metal-free aq. for 30 min.) 3 10 (spiked org./aq. phases contacted for 30 min.)

102

101 DM 100

10-1 DMOpyrDGA(10) 10-2 DMOpipDGA(11) DMOmorDGA(12)

*ionic radii were taken from Shannon, R. D. Acta Cryst. 1976, 32, 751-767. (CN=9 for Ln(III)) 10-3 0.80 0.82 0.84 0.86 0.88 0.90 0.92 0.94 0.96 0.98 1.00 1/r (Å-1)

Figure 3.26. The extraction of La(III)-Lu(III) by the bis(3,7-dimethyloctyl) derivatives (10-12) from 1.8 M HNO3. Ionic radii for Ln(III) cations (CN = 9) were taken from a study by R. D. Shannon.36

As anticipated, the overall extraction of the Ln(III) metals is higher for the bis(3,7-dimethyloctyl) derivatives than for the di-2-ethylhexyl derivatives. DMOpyrDGA(10) also produces a steeper extraction trend slope at the lightest lanthanides with separation factors of

2.6 ± 0.1 (Ce/La), 2.3 ± 0.1 (Pr/Ce), and 2.4 ± 0.1 (Nd/Pr), which most closely matches the trend seen with DHpyrDGA(1). DMOpyrDGA also has a clear maximum at Yb and quickly decreases in metal extraction at Lu (SFYb/Lu = 2.0 ± 0.1). DMOpipDGA(11) and DMOmorDGA(12) unexpectedly repeat the extraction trend seen with their di-2-ethylhexyl analogues and have a

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slight selectivity for Lu over Yb. This could mean that there is some similarity in the steric hindrance produced by both of the branched ligands. These two sets of ligands also display a large difference in overall extraction strength between the piperidinyl and morpholino derivatives, whereas there was little difference seen in the first two sets of ligands (2 vs. 3 and 5 vs. 6). This means that the branched alkyl groups are actively affecting the metal extraction whereas the straight-chain derivatives depend more on the type of cyclic amide group (i.e., pyrrolidinyl, piperidinyl, or morpholino).

3.13. Conclusions

The metal extraction behavior of the unsymmetrical diglycolamides (1-12) has been studied using radiometric and ICP-MS techniques. The dihexyl derivatives (1-3) have exhibited the highest distribution ratios for the Ln(III) metals, but were observed to demonstrate phase incompatibility (forming a third phase) at high nitric acid concentration (e.g., 2 M). The dioctyl derivatives (4-6) were similar to the dihexyl ligands (1-3) except for the absence of third phase formation at 2-3 M HNO3 for DOpyrDGA(4) and DOpipDGA(5). The di-2-ethylhexyl derivatives

(7-9) were by far the weakest UDGA extractants, but were relatively similar to the industry standard TODGA in both extraction strength and cation size selectivity. The bis(3,7-dimethyloctyl) derivatives (10-12) were found to be stronger extractants than the smaller alkyl chain di-2-ethylhexyl derivatives, which goes against the usual trend of lower metal extraction with increasing alkyl chain size. This behavior is likely due to the smaller, less sterically-hindering methyl groups attached to the octyl chain. The unsymmetrical diglycolamides were compared to TODGA and found to have comparable or higher metal extraction strength but were also found to form a third phase in the diluent n-dodecane (or n-octane) without the addition

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of a phase modifier (i.e., 1-octanol). The best ligand candidates out of the twelve new unsymmetrical diglycolamides for Ln(III) extraction at high acidity (e.g., 3.0 M HNO3), Ln(III) stripping at low acidity (e.g., 0.0097 M HNO3), and phase compatibility were the dioctyl piperidinyl diglycolamide (DOpipDGA), the di-2-ethylhexyl morpholino diglycolamide

(DEHmorDGA), and the bis(3,7-dimethyloctyl) morpholino diglycolamide (DMOmorDGA).

3.14. Further Work

Further solvent extraction studies would be useful to determine maximum metal loading at high acidity (e.g., 3-4 M HNO3) and to better understand the nitric acid and water extraction (both quantitatively and qualitatively) by these solvating extractants. Nitrate dependence experiments could be expanded to all twelve ligands with optimized levels of acidity and buffers to prevent third phase formation. Elevated temperature experiments (e.g., 40°C) could possibly disrupt third phase formation at conditions of high acidity and/or high metal loading and would more accurately represent reprocessing conditions. The use of other phase modifiers (e.g., 1-decanol, tributyl phosphate, or N,N-dihexyloctanamide) with the UDGA ligands would also be of interest for probing third phase formation more thoroughly. It is also possible that an alternative base diluent

(e.g., hydrogenated tetrapropylene, toluene, or 1-octanol) could be used with the UDGAs without the need of a phase modifier. The biggest challenge for these ligands moving forward is their tendency toward third phase formation and finding the right solvent conditions for a particular ligand. Overcoming this phase incompatibility obstacle may end up being more difficult than synthesizing longer alkyl chain ligands with better inherent solubility in aliphatic diluents.

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Chapter 4

PROBING THE EUROPIUM-UNSYMMETRICAL DIGLYCOLAMIDE COMPLEX USING

LUMINESCENCE SPECTROSCOPY

4.1. Introduction

The symmetrical diglycolamide (DGA) extractant N,N,N',N'-tetraoctyldiglycolamide

(TODGA, Figure 4.1) has been studied extensively for the co-extraction of trivalent actinides

(e.g., Am(III)) and trivalent lanthanides (e.g., Eu(III)) in the context of several nuclear fuel reprocessing schemes. Under some conditions, TODGA displays a unique preferential extraction for the trivalent oxidation state over the tetravalent oxidation state (e.g., Pu(IV)), which cannot be explained by the usual electrostatic bonding model of metal-ligand complexation that usually correlates such data.1

Figure 4.1. Structure of N,N,N',N'-tetraoctyldiglycolamide (TODGA).

Improving understanding of the stoichiometry and stability of the metal-ligand complexes in the organic phase of a liquid-liquid solvent extraction system could help to explain this anomalous extraction behavior. Unfortunately, the experimental techniques used to obtain stability constants (e.g., potentiometry or optical spectroscopy) are generally performed in aqueous media,

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which are not representative of the extracted metal-ligand complex. Tian et al. studied the aqueous-soluble TODGA analogue N,N,N',N'-tetramethyldiglycolamide (TMDGA) and diglycolic acid (ODA) using potentiometry, spectrophotometry, x-ray diffractometry, and calorimetry and were able to determine stability constants, a crystal structure, and enthalpic and entropic

2 complexation data for the 1:1, 1:2, and 1:3 Nd(III)-(TMDGA)n and Nd(III)-(ODA)n species. The crystal structure of the Nd(III)-(TMDGA)3 complex confirmed the assumption that nine-coordinate Ln(III) metals prefer a tri-capped trigonal prismatic geometry (Figure 4.2).3

Figure 4.2. Nine-coordinate tri-capped trigonal prismatic structure of Nd(III)-(TMDGA)3.

The stability constants (log β) and thermodynamic data (ΔG, ΔH, and ΔS) for the 1:1, 1:2, and 1:3 complexes are shown in Table 4.1. The data were obtained using both spectrophotometric and potentiometric titrations; the values represent an average of both techniques. The Gibbs free energy was calculated from the reported enthalpy (ΔH) and entropy (ΔS) values using the definition of the Gibbs free energy in an isolated system in Equation 4.1.

GHTS     (4.1)

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Table 4.1. The stability constants (log β) and thermodynamic data (ΔG, ΔH, and ΔS) for the 1:1, 1:2, and 1:3 complexes of Nd(III) and N,N,N',N'-tetramethyldiglycolamide (TMDGA) and diglycolic acid (ODA). Data were taken from work by Tian et al.2 Ligand/Complex log β ΔG (kJ·mol-1) ΔH (kJ·mol-1) ΔS (J·mol-1·K-1) TMDGA Nd3+ + L = NdL3+ 3.53 ± 0.10 -19 ± 1 -10.9 ± 0.9 26 ± 1 3+ 3+ Nd + 2L = NdL2 5.84 ± 0.19 -27 ± 2 -15.6 ± 1.5 39 ± 2 3+ 3+ Nd + 3L = NdL3 6.80 ± 0.19 -37 ± 3 -19.3 ± 2.2 59 ± 7 Diglycolic acid Nd3+ + L2- = NdL+ 5.31 ± 0.14 -30.2 ± 0.5 -3.94 ± 0.24 88 ± 2 3+ 2- - Nd + 2L = NdL2 9.28 ± 0.18 -53.1 ± 0.8 -9.90 ± 0.30 145 ± 2 3+ 2- 3- Nd + 3L = NdL3 12.07 ± 0.21 -69 ± 1 -14.0 ± 0.6 184 ± 2

While the aqueous phase metal complexation behavior of the diglycolamides is vital to the fundamental understanding of their chemistry, further studies of the DGAs in organic media are more directly relevant to elucidating features of the complexation phenomena that describe thermodynamics in these DGA systems. Jensen et al. performed small-angle neutron scattering

(SANS) experiments with TODGA in aliphatic diluents (e.g., n-octane) and determined the extracted Nd(III)-TODGA complex to be primarily “tetrameric” (i.e., quaternary complex) at

4 greater than 0.7 M HNO3. This 1:4 Ln(III)-TODGA complex in aliphatic diluents was also

1 reported using basic slope analysis solvent extraction experiments at 1 M HNO3. Pathak et al. examined Eu(III)-TODGA complexes in 60% v/v ethanol/water using luminescence spectroscopy and calculated stability constants for three metal-ligand species (log β101 = 6.1 ± 0.4,

5 log β102 = 10.8 ± 0.7, log β103 = 14.3 ± 0.6). The ethanol-water solvent was used in the luminescence spectroscopy experiments to allow for concurrent solvation of the Eu3+ cation and the TODGA ligand. However, the 40% water solvent did not promote the formation of the TODGA

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quaternary species, which have been shown to be reverse micelles in work by Jensen et al.6 and not fully coordinated to the metal center.

The unsymmetrical diglycolamides (UDGAs, 1-12, Figure 4.3) share a binding pocket with three oxygen atoms with the other DGAs, but should exhibit a fundamentally different degree of amphiphilic behavior between the two dialkylamide ends of the molecule. TODGA has four nonpolar n-octyl groups and TMDGA has four polar methyl groups, while DOpyrDGA has two nonpolar n-octyl groups and one polar pyrrolidinyl group – it might be reasonable to expect some intermediate behavior in the UDGA systems.

Figure 4.3. Structures of unsymmetrical diglycolamides (1-12) with acronyms provided (DH = di-n-hexyl, DO = di-n-octyl, DEH = di-2-ethylhexyl, DMO = bis(3,7-dimethyloctyl), pyr = pyrrolidinyl, pip = piperidinyl, mor = morpholino, DGA = diglycolamide).

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Learning more about the stability constants and stoichiometry of the Eu(III)-UDGA complexes could be important for improving the overall understanding of unsymmetrical diglycolamide Ln(III) metal extraction. Luminescence spectroscopy experiments were completed in this work to better understand the nature of the extracted Eu(III)-UDGA complex. These experiments were also done in acetonitrile (MeCN), rather than in 60% v/v ethanol/water, to better imitate organic phase speciation. Physical and thermodynamic data for the three different solvents are listed in Table 4.2.

Table 4.2. Physical and thermodynamic data for water, ethanol, and acetonitrile. Data taken from the CRC Handbook of Chemistry and Physics (2004).7 Enthalpy of Dielectric Dipole Boiling Molecular MW Vaporization Solvent Constant Moment Point Formula (g/mol) (Δ H(t ), (ε ) (μ, debye) (t , °C) vap b r b kJ/mol)

water H2O 18.01 80.100 1.855 100.0 40.65

ethanol CH3CH2OH 46.07 25.3 1.69 78.29 38.56

acetonitrile CH3CN 41.05 36.64 3.925 81.65 29.75

The solvent structuring of water (H2O) and ethanol (EtOH) is directed by the hydrogen bonding interactions between the lone pairs of electrons on their oxygen atoms and the H-donor atom on an adjacent molecule. This hydrogen bonding increases the solvent ordering and therefore more energy (kilojoules) is required to overcome the intermolecular forces and vaporize a certain number of solvent molecules (moles) compared to acetonitrile. However, acetonitrile does have a large dipole moment due to the carbon-nitrogen triple bond and has a slightly higher boiling point than ethanol notwithstanding its lower molecular weight (MeCN: bp 81.7°C; EtOH: bp 78.3°C).

Acetonitrile has a fairly large dielectric constant (εr), which allows for the solvation of charged

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Eu3+ cations. Acetonitrile is also an organic solvent so the UDGA ligands are also soluble in the single polar organic phase.

4.2. Materials

The europium nitrate stock solution was prepared by the addition of concentrated nitric acid (EMD Millipore OmniTrace®, 67-70%) to Eu2O3 (Arris International Corp., 99.999%). The solution of europium and concentrated HNO3 was then evaporated to near dryness. The solid was redissolved in concentrated HNO3 and evaporated again. This process was repeated until no solid

(Eu2O3) remained in solution. The final dilution was performed with ca. 0.1 M HNO3. The solution

3+ - was standardized for [Eu ] and [NO3 ] using ion-exchange chromatography (Dowex 50x beads,

H+ form) and [H+] using a potentiometric titration. The standardized concentrations were:

3+ - [Eu ] = 0.1468 ± 0.0013 M, [NO3 ] = 0.5240 ± 0.0007 M, [H+] = 0.0837 ± 0.0047 M. An aliquot of this standardized solution was added to acetonitrile (MeCN, Fisher Scientific, HPLC grade) to create a more dilute europium nitrate solution appropriate for luminescence spectroscopy

(0.482 mM Eu(NO3)3 in 0.252 mM HNO3/179 mM H2O/99.7% MeCN).

Synthesized unsymmetrical diglycolamide ligands were purified by Kugelrohr distillation or flash chromatography and the purity and identification were confirmed using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and high resolution mass spectrometry (HRMS). The symmetrical diglycolamide N,N,N',N'-tetraoctyldiglycolamide

(TODGA, >98% purity) was generously donated by Dr. Yuji Sasaki from the Japan Atomic Energy

Research Institute in Tokai, Ibaraki, Japan. For the luminescence experiments, ligands were dissolved in acetonitrile and a small aliquot of nitric acid was added to maintain the acidity at

0.3 mM HNO3 and water concentration at 0.2 M H2O.

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4.3. Methods

All luminescence spectroscopy titrations were performed at room temperature (22 ± 1°C).

Both the titrand and titrant were dissolved in the solvent acetonitrile (dielectric constant = 36.64) to allow for mutual solubility of both the free metal and the UDGA ligand in a single phase.

The titrand for these experiments was a solution of 0.482 mM Eu(NO3)3 in 0.252 mM HNO3/179 mM H2O/99.7% MeCN. The same titrand solution was used for each of the thirteen titrations

(ligands 1-12 and TODGA). The titrant solution was created fresh for each experiment entirely by mass for each component (purified UDGA or TODGA ligand, MeCN (d = 0.781 g⋅cm-3), 0.096 M

-3 HNO3 (d = 1.004 g cm )). The ligand concentrations varied from about 5 to 8 mM UDGA in

0.3 mM HNO3/0.2 M H2O/99.7% MeCN. The titrand (1000 ± 0.4 μL of 0.482 mM Eu(NO3)3 in

0.252 mM HNO3/179 mM H2O/99.7% MeCN) was pipetted (200-1000 μL Finnpipette®) into an open top, 1.4 mL Spectrocell Semi-Micro Fluorimeter FUV cell (quartz) with a PTFE lid and five polished windows (path length = 4 × 10 mm, spectral range = 170-2200 nm). The titrant was added in 10.00 ± 0.06 μL aliquots using a 5-50 μL Finnpipette®. The solution was allowed to equilibrate for 1 minute before the emission spectrum was acquired. A lifetime measurement was taken of the original titrand and after the final 10.00 μL aliquot addition. The number of 10.00 μL aliquots needed to reach the end of the titration (defined as a 5:1 ligand-to-metal ratio) was determined by the concentration of the titrant solution.

Luminescence spectroscopy emission experiments were performed using a HORIBA Jobin

Yvon FluoroMax®-4 spectrofluorometer. The excitation source for the emission experiments was an ozone-free, continuous output 150 W xenon lamp with an excitation wavelength range of

220-600 nm. An excitation wavelength of 393 nm (excitation slit width = 3 nm) was used to excite

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the 4f electrons in the Eu3+ cation. The excitation source was coupled to a Czerny-Turner monochromator8 with 1200 grooves/mm gratings. A second monochromator was set up at a 90° angle from the excitation source to avoid reflected light and collimate the emission. The emission slit width was set to 1 nm. Emission spectra were obtained using the FluorEssence™ software

(HORIBA Scientific, version 3.5 for Windows®). The emission spectra were recorded in the range of 550-650 nm at increments of 0.25 nm and an integration time of 1 second.

Luminescence lifetimes (τ) of Eu3+ were determined using a pulsed diode light source

(SpectraLED-390, peak wavelength = 394 nm, wavelength FWHM = 25 nm) to excite the 4f

5 5 7 electrons to the L6 energy level. The emission intensity of the D0 → F1 transition at 590 nm was then measured to obtain the Eu3+ lifetime.9 Lifetime measurements were made using a time-correlated single photon counting (TCSPC) accessory (FluoroHub®, HORIBA Scientific) run with the software DataStation™ (HORIBA Scientific, version 2.6). The analysis and fitting of the data was performed using the Decay Analysis Software or DAS (HORIBA Scientific, version 6.6). Chi-squared values for the decay curves were minimized to a range of 0.99 to 1.09.

4.4. Luminescence Lifetimes for Eu(III)-UDGA Complexes

Luminescence lifetimes (τ) were acquired for the original titrand and after the final aliquot

5 7 for each titration. The lifetime of the D0 → F1 transition varies as a function of the number of -OH oscillators (or water molecules in this case) directly coordinated to the Eu3+ cation. The -OH bond vibronic motions provide a nonradiative de-excitation pathway, or quenching, of the Eu3+ cation and shorten the luminescence lifetime. The luminescence quenching pathway for Eu3+ is shown in

Figure 4.4. The disappearance of -OH oscillators (or dehydration of the Eu3+ metal center)

5 7 predictably increases the luminescence lifetime of the D0 → F1 transition. This correlation

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between the primary hydration number (NH2O) and the luminescence lifetime (τ) has been studied by Kimura and Kato10 and the following Equation 4.2 has been derived for Eu(III):

1 N..1 05 ms   0 44 (4.2) HO2 

where τ is given in milliseconds and the error associated with NH2O is ± 0.5 water molecules.

The preferred coordination number of Eu(III) varies between 8 and 9 depending on the surrounding ligands.12 The theoretical hydration number of Eu(III) in a dilute aqueous solution of nitric acid would then be expected to fall between 8 and 9. A preliminary luminescence

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spectroscopy experiment was performed with 1.00 mM Eu(NO3)3 in 0.0981, 0.961, and 3.01 M

HNO3. The emission spectra are shown in Figure 4.5. The transitions from the lowest excited state

3+ 5 7 7 7 3+ of the Eu 4f electrons ( D0) to the F2, F1, and F0 states are the most important peaks for Eu

5 7 5 7 luminescence and are seen at: 578 nm ( D0 → F0, electric dipole transition), 592 nm ( D0 → F1,

5 7 magnetic dipole transition), and 615 nm ( D0 → F2, electric dipole transition).

1.5x105 1.00 mM Eu(III) in 0.0981 M HNO3

1.00 mM Eu(III) in 0.961 M HNO3

1.00 mM Eu(III) in 3.01 M HNO3 5 7 5D 7F D0 F1 0 2

1.0x105 Intensity (cps) Intensity 5.0x104

5 7 D0 F0

0.0 570 580 590 600 610 620 630 640 Wavelength (nm)

Figure 4.5. Emission spectra of 1.00 mM Eu(NO3)3 in 0.0981, 0.961, and 3.01 M HNO3.

5 7 The D0 → F0 transition occurs between two unsplit states so the presence of a single, weak peak implies the existence of a single Eu3+ metal center in the complex. This electric dipole transition would also not be seen if the symmetry of the complex were high (i.e., inversion center).

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5 7 The D0 → F1 transition is magnetic dipole allowed and insensitive to the changes in symmetry

5 7 around the metal center. The D0 → F2 transition is electric dipole allowed and is hypersensitive to changes in symmetry around the Eu3+ cation. The spectra seen in Figure 4.5 display the

5 7 characteristics of each transition. The D0 → F0 transition at 578 nm is weak overall but greatly

5 7 increases in intensity with increasing [HNO3]. The D0 → F1 transition at 592 nm is initially the

5 7 most intense peak but does not change greatly with the increase in [HNO3]. The D0 → F2 transition at 613/617 nm is less intense than the 592 nm peak at first but greatly increases in intensity and splits more clearly into two peaks as the titration progresses, suggesting a less symmetric environment around the Eu3+ metal center.

Luminescence lifetimes were also acquired for the 1.00 mM Eu3+ in media of three

5 7 different nitric acid concentrations. The emission of the D0 → F1 transition at 592 nm was measured to obtain a luminescence decay curve. The decay curve was fit using a single exponential

-1 to obtain the luminescence decay rate, kobs (ms ), which in turn gave the luminescence lifetime

(τobs = 1/kobs). The experimental lifetimes (τobs) and calculated inner-sphere hydration numbers

(NH2O) are compared to literature lifetime values (τlit) in Table 4.3.

Table 4.3. Luminescence lifetimes (τobs) and inner-sphere hydration numbers (NH2O) for 3+ 1.00 mM Eu in 0.0981, 0.961, and 3.01 M HNO3. 3+ [HNO3] (M) [Eu ] (mM) τ (obs.) (μs) τ (lit.) (μs) N(H2O) (obs.) N(H2O) (lit.) 0.0981 1.00 122.3 ± 0.7 120 ± 3† 8.1 ± 0.5 8.3 ± 0.5† 0.961 1.00 125.3 ± 0.7 124 ± 2‡ 7.9 ± 0.5 8.0 ± 0.5‡ 3.01 1.00 128.5 ± 0.7 130 ± 3† 7.7 ± 0.5 7.6 ± 0.5†

†Pathak et al. Spectrochim. Acta A, 2009, 73, 348-352.5 ‡Arisaka et al. Solvent Extr. Ion Exch. 2011, 29, 72-85.13

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The luminescence lifetimes (τ) become longer with increasing [HNO3], which is interpreted to indicate a smaller inner-sphere hydration number (NH2O). This trend fits with the

- 3+ explanation that one H2O molecules is being displaced by one NO3 anion on the Eu metal center

2+ as more nitrate becomes available. The data support a predominance of the Eu(H2O)8(NO3) inner-sphere complex, which means the nitrato anion is binding in a monodentate fashion.

However, the luminescence experiments with the UDGA ligands (1-12) and TODGA were performed in the polar organic solvent acetonitrile to accommodate the solubility requirements of both the free Eu3+ and diglycolamide ligands in a single phase. Only 0.3% of the phase was aqueous

3+ (179 mM H2O) so the inner-sphere hydration numbers for Eu were expected to be much lower due to the solvation by the abundant MeCN molecules. The luminescence lifetime (τobs) for the

0.482 mM Eu(NO3)3 in 0.252 mM HNO3/179 mM H2O/99.7% MeCN titrand was found to be

299.7 ± 0.6 μs (which corresponds to NH2O = 3.1 ± 0.5, based on the Kimura relationship in

Equation 4.2). As expected, the Eu3+ metal center is mostly dehydrated in the MeCN solvent. There

3+ are three molecules of water bound to each Eu , which means that only 1.5 mM H2O is

Eu-associated while the remaining 177 mM H2O is either free or associated with the UDGA or nitrate. Lifetimes were also determined for each solution after the final aliquot of titrant was added.

Predictably, the stronger complexation of the UDGA and TODGA ligands displaced the remaining water molecules from the Eu3+ metal center and all these samples were found to have an inner-sphere hydration number of zero within the uncertainty of the measurement. The luminescence lifetimes (τobs) and calculated inner-sphere hydration numbers (NH2O) for ligands

1-12 and TODGA are reported in Table 4.4. There was some variation in the lifetime values overall, with the morpholino ligands (3, 6, 9, and 12) having slightly shorter lifetimes and 0.1 ± 0.5

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water molecules in the primary hydration sphere (as opposed to 0.0 ± 0.5). Even though all the hydration values are statistically identical, the idea of the morpholino ligands allowing some residual water to remain in the Eu3+ inner coordination sphere is consistent with the weaker complexation strength of these derivatives that was reported in the solvent extraction experiments.

Table 4.4. Luminescence lifetimes (τobs) and inner-sphere hydration numbers (NH2O) for the terminal Eu(III)-L complex (L = UDGA ligands 1-12 and TODGA). [L] (mM) [Eu3+] (mM) Final # DGA Ligand τ (ms) N(H O) "titrant" "titrand" [L]:[Eu3+] 2 1 DHpyrDGA 7.0 0.482 5.8 2.258(1) 0.0 ± 0.5 2 DHpipDGA 6.0 0.482 5.3 2.392(1) 0.0 ± 0.5 3 DHmorDGA 7.8 0.482 5.3 2.042(1) 0.1 ± 0.5 4 DOpyrDGA 4.9 0.482 4.8 1.922(4) 0.1 ± 0.5 5 DOpipDGA 5.9 0.482 6.4 2.231(1) 0.0 ± 0.5 6 DOmorDGA 5.9 0.482 5.1 2.009(1) 0.1 ± 0.5 7 DEHpyrDGA 6.3 0.482 5.5 2.307(1) 0.0 ± 0.5 8 DEHpipDGA 5.7 0.482 5.3 2.235(1) 0.0 ± 0.5 9 DEHmorDGA 5.6 0.482 5.3 1.921(1) 0.1 ± 0.5 10 DMOpyrDGA 4.6 0.482 5.2 2.294(1) 0.0 ± 0.5 11 DMOpipDGA 4.8 0.482 4.3 2.131(1) 0.1 ± 0.5 12 DMOmorDGA 4.9 0.482 4.3 1.932(1) 0.1 ± 0.5 - TODGA 8.4 0.482 5.4 2.475(1) 0.0 ± 0.5

The luminescence lifetime for the terminal complex was also taken as a measure of the completeness of the complexation, since total dehydration would normally accompany a saturated metal-ligand complex. The lifetimes do not, however, supply information about the stoichiometry of the final complex or the relative strengths of each Eu-(UDGA)n complex. A broader titration experiment was necessary to obtain a sufficient number of emission spectra for the analysis of metal-ligand stoichiometry and complex stability.

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4.5. Luminescence Emission Spectroscopy for Eu(III)-UDGA Complexes

A solution of Eu3+ in the polar organic solvent MeCN was titrated with the unsymmetrical diglycolamides (also dissolved in MeCN) and spectral changes were monitored using luminescence spectroscopy. Changes in the hypersensitive peak around 615 nm and the magnetic dipole peak at 592 nm represented changes in the metal-ligand complex speciation. In each ligand system, the titrations were run until the ligand-to-metal ratio was greater than five or to the point at which there were no additional spectral changes. The spectra from a representative titration are shown in Figure 4.6.

2.8x105 titrand = 0.482 mM Eu(NO3)3 in 0.252 mM HNO3/0.179 M H2O/99.7% MeCN

titrant = 4.8 mM DMOpipDGA in 0.3 mM HNO3/0.2 M H2O/99.7% MeCN (Final DMOpipDGA:Eu = 4.3:1) 2.4x105

2.0x105

5 5 7 1.6x10 D0 F2

1.2x105

608 610 612 614 616 618 620 622 624 Intensity (cps)* Intensity

4 8.0x10 5 7 D0 F1

4.0x104 5 7 D0 F0 0.0 570 580 590 600 610 620 630 640 *intensities are dilution corrected Wavelength (nm)

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In every ligand system, the vast majority of the spectral changes occur at the hypersensitive peak (ca. 615 nm), which eventually splits into two peaks at ca. 613 and 617 nm (see inset in

Figure 4.6). The magnetic dipole transition peak at 592 nm remains at the same wavelength throughout the titration but does steadily increase in magnitude until levelling off at the end of the titration. The relatively weak electric dipole transition at 578 nm does experience a small redshift to 578.5 nm during the titration but the peak intensity was too small for data fitting purposes. Most of the UDGA ligands generated spectra nearly identical to those seen in Figure 4.6. There were two of the ligands (DEHmorDGA and DMOmorDGA), however, that exhibited simpler spectra with a limited amount of splitting in the hypersensitive peak at ca. 615 nm. The spectra from the titration of Eu(III) with DMOmorDGA are shown in Figure 4.7.

The theoretical speciation in the DMOmorDGA titration should be nearly identical to the speciation in the DMOpipDGA titration since the final ligand-to-metal ratios were 4.4:1 and 4.3:1 for the respective ligands. The spectra of the hypersensitive peak at 617 nm continue to rise in intensity until the very end of the titration with DMOmorDGA, while this same peak decreases substantially in intensity toward the end of the titration with DMOpipDGA. The lack of hypersensitive peak splitting in the Eu-DMOmorDGA titration could indicate that there is a smaller change in coordination modes for DEHmorDGA and DMOmorDGA than with the ligands where major hypersensitive peak splitting is observed. It is intriguing to speculate for these two ligands on the potential impact of the branched, greasy tail amides and a terminal extra oxygen donor atom at the opposite end of the DGA binding pocket of these ligands.

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2.8x105 titrand = 0.482 mM Eu(NO3)3 in 0.252 mM HNO3/0.179 M H2O/99.7% MeCN

titrant = 4.9 mM DMOmorDGA in 0.3 mM HNO3/0.2 M H2O/99.7% MeCN (Final DMOmorDGA:Eu = 4.4:1) 2.4x105

5 5 7 2.0x10 D0 F2

1.6x105

1.2x105

608 610 612 614 616 618 620 622 624 Intensity (cps)* Intensity

8.0x104 5 7 D0 F1

4.0x104 5 7 D0 F0 0.0 570 580 590 600 610 620 630 640 *intensities are dilution corrected Wavelength (nm)

The raw intensity data were adjusted to approximately one using an appropriate correction factor before fitting. The Windows® application HypSpec was designed to work with numerical values ≤ 1, which is typical for absorbance values. The intensity of the emission spectra is directly related to the concentration of the sample, so that data can be treated mathematically in the same manner as absorbance values. The intensity of the excitation source (I0) varies between different spectrofluorometers, however, so the magnitude of the fluorescence intensity (F) will also change

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between different instruments. The fluorescent intensity (F) is directly related to the fluorescent solute concentration (c) in Equation 4.3.14

F23 .  I0    b  c FIfluorescence intensity; intensity of the excitation source; 0 (4.3) fluorescence quantum yield;  extinction coefficient (M-1  cm -1 ); bcpath length (cm); fluorescence solute concentration (M)

The corrected data (from 550-650 nm) for every spectrum in the titration were converted

5 7 into a composite text file and then loaded into the HypSpec program. The D0 → F1 transition

5 7 peak centered around 592 nm and the D0 → F2 transition peak centered around 615 nm were selected for fitting of metal-ligand complex equilibrium constants. The spectral data analysis program HypSpec is part of the HYPERQUAD suite of programs, which solves non-linear simultaneous mass balance equations using the Newton-Raphson method.15 A simplified mass balance equation for the formation of the 1:1 complex is shown in Equation 4.4 (UDGA =

DMOpipDGA).

Eu(III) + UDGA Eu-UDGA (4.4)

- The H2O, NO3 , and MeCN molecules have been neglected in this equation, as they are considered not to be important in the equilibrium constant fitting. The fluorescence intensity values

(F) for each of these species can be represented by a summation version of Equation 4.3 in

Equation 4.5.

ii F = 2 . 3 I0   bεi  c i = k ε i  c i  nn11 (4.5)

k = 2 . 3 I0   b (constant)

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The concentrations of the three possible species from Equation 4.4 can be represented separately in Equation 4.6.

cEu = [Eu]; c UDGA = [UDGA]; c Eu-UDGA = β 101 [Eu][UDGA] (4.6)

Substituting these concentrations into Equation 4.5 yields an expression (Equation 4.7) containing both the extinction coefficient (ε) and the 1:1 metal-ligand complex stability constant

(β101).

F = kεEu [Eu] + k  ε UDGA [UDGA] + k  ε Eu-UDGA  β 101 [Eu][UDGA] (4.7)

Equation 4.7 only includes the formation of a 1:1 metal-ligand species but higher order complexes are likely to be present in acetonitrile as the excess of ligand to metal increases throughout the titration. The basic model was adjusted by adding different potential complexes with the objective of converging on a complete model that was consistent with the array of spectroscopic data acquired. The data fitting process ultimately resulted in a model based on the formation of four distinctive metal-ligand species (1:1, 1:2, 1:3, and 1:4). Corrected fluorescence intensity spectra were determined by the HypSpec program for the four metal-ligand species and

Eu(III). The spectra for the 1:1 through 1:4 Eu(III) complexes with DMOpipDGA are shown in

Figure 4.8. Similar spectra were resolved for each system that converged on an internally consistent model.

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5000 Eu(III) 4500 Eu-(DMOpipDGA)1 Eu-(DMOpipDGA) 4000 2

Eu-(DMOpipDGA)3 3500 Eu-(DMOpipDGA)4 5D 7F 3000 0 2

2500

2000 5D 7F 1500 0 1

1000 Corrected Fluorescence Intensity Fluorescence Corrected

500 5 7 D0 F0 0 570 580 590 600 610 620 630 640

Wavelength (nm) Figure 4.8. Corrected fluorescence intensity spectra for Eu(III)-DMOpipDGA complexes in 0.3 mM HNO3/0.2 M H2O/99.7% MeCN.

The corrected fluorescence intensity spectra show the changes in both peak intensity and wavelength. The magnetic dipole peak at 592 nm exhibits a subtle blue-shift to 591 nm from

Eu(III) to Eu-DMOpipDGA and a red-shift back to 592 nm between Eu-(DMOpipDGA)3 and

Eu-(DMOpipDGA)4. The intensity of the 592 nm peak also increases exponentially from the beginning to the end of the titration. The largest spectral changes occur at the hypersensitive peak around 615 nm where the development of a second blue-shifted peak adds a shoulder to the 1:1,

1:2, and 1:3 complexes. The blue-shifted peak (613 nm) is almost baseline resolved from the red-shifted peak (617 nm) in the 1:4 complex spectrum and the relative intensity of the 613 nm

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peak becomes greater than the 617 nm peak with the formation of the terminal complex,

Eu-(DMOpipDGA)4. The corrected fluorescence intensity spectra were also obtained for the 1:1 through 1:4 Eu(III) complexes with DMOmorDGA to further explore the differences seen in the hypersensitive peak (i.e., lack of splitting) in the metal-ligand titration spectra. The corrected fluorescence intensity spectra for Eu-DMOmorDGA complexes are shown in Figure 4.9.

5000 Eu(III)

4500 Eu-(DMOmorDGA)1

Eu-(DMOmorDGA)2 4000 Eu-(DMOmorDGA)3 Eu-(DMOmorDGA) 3500 4 5 7 D0 F2 5 7 3000 D0 F1

2500

2000

1500

1000 Corrected Fluorescence Intensity Fluorescence Corrected

500 5 7 D0 F0 0 570 580 590 600 610 620 630 640

Wavelength (nm) Figure 4.9. Corrected fluorescence intensity spectra for Eu(III)-DMOmorDGA complexes in 0.3 mM HNO3/0.2 M H2O/99.7% MeCN.

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The shape and intensity of the corrected fluorescence spectra are nearly identical for the

1:1, 1:2, and 1:3 metal-ligand complexes for both DMOmorDGA and DMOpipDGA. A noticeable difference does come with the large increase in the magnitude of the intensity (particularly at

592 nm) for the 1:4 species of Eu-(DMOmorDGA)4. Nevertheless, the similarity in spectral shape for the 1:4 complex with both DMOmorDGA and DMOpipDGA does support the existence of structurally-similar coordination complexes, even if the previously shown luminescence spectra appear different.

The HypSpec program was used to obtain conditional stability constants (log β) for the four metal-ligand species using non-linear least-squares regression analysis.14 The first step was to import the full titration data (intensity corrected for a maximum value of 1) into HypSpec. A known Eu spectrum (the titrand) was also imported into HypSpec separately to aide in the fitting.

The wavelengths around the magnetic dipole peak (ca. 588-596 nm) and the hypersensitive peak

(ca. 610-620 nm) were selected in the experimental data and estimates for the log β values were entered into the model data. The model was tested starting with the 1:1 metal-ligand complex

(log β101) and new fits were attempted after the addition of each new species (e.g., log β102, log β103, log β104, log β105, etc.). Different sets of stability constants were obtained for the two, three, and four species systems but the four species system was accepted as the most accurate due to the final experimental metal-ligand ratios. Factor analysis was also employed to determine the number of species present relatively smooth curves were observed for the 1:1, 1:2, and 1:3 species. The 1:4

Eu-UDGA species was slightly more irregular than the previous three species but was included in the model nonetheless.

Most of the full data sets did not successfully converge on stability constant values immediately. Series of data points were graphed at important wavelengths (e.g., 592, 613, and 617

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nm) and observed for discontinuities or aberrations in the curve. The data sets were then truncated

(usually near the 1:4 metal-ligand ratio) and the model was tested as before. This process was repeated until stability constants converged with reasonable values and low error (≤ 0.2). The magnitude of the fit was tested by entering much lower initial values (e.g., log β101 = 4) and confirming the convergence to the same higher value (e.g., log β101 (DOpyrDGA) = 7.9). The titrations and data fitting routines were repeated for all twelve unsymmetrical diglycolamide ligands and TODGA. The conditional stability constants are reported in Table 4.5. The uncertainties in the conditional stability constants (log β) were calculated in HypSpec and reported at ±2σ. Aqueous phase stability constant values of the 1:1 through 1:3 europium-diglycolic acid system from Grenthe and Tobiasson are also included as a reference point.16

Spectral data describing europium complexes with the first two UDGA ligands (1 and 2) failed to converge on stability constant values due to a persistent tendency towards a meaningless negative β value. The luminescence spectra for DHpyrDGA(1) and DHpipDGA(2) were nearly identical to the other ligands (except DMOmorDGA and DEHmorDGA) so the inability to converge on log β values is probably a failure in the Newton-Raphson fitting method and not an indication of different coordination complexes.

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Table 4.5. Conditional stability constants (log β) for Eu(III)-UDGA and Eu(III)-TODGA complexes in 0.3 mM HNO3/0.2 M H2O/99.7% MeCN (log β101 = Eu-DGA, log β102 = Eu-(DGA)2, log β103 = Eu-(DGA)3, log β104 = Eu-(DGA)4). # Ligand log β101 log β102 log β103 log β104 3 DHmorDGA 7.83 ± 0.08 14.4 ± 0.1 19.6 ± 0.1 22.7 ± 0.1 4 DOpyrDGA 7.9 ± 0.2 15.1 ± 0.3 20.9 ± 0.4 23.5 ± 0.4 5 DOpipDGA 7.3 ± 0.2 14.5 ± 0.3 20.0 ± 0.4 22.8 ± 0.8 6 DOmorDGA 6.8 ± 0.2 12.6 ± 0.3 18.1 ± 0.3 22.4 ± 0.4 7 DEHpyrDGA 8.9 ± 0.2 15.9 ± 0.3 21.9 ± 0.4 24.5 ± 0.4 8 DEHpipDGA 7.89 ± 0.08 14.7 ± 0.1 19.8 ± 0.1 23.2 ± 0.2 9 DEHmorDGA 7.5 ± 0.1 14.0 ± 0.1 19.3 ± 0.1 21.8 ± 0.2 10 DMOpyrDGA 7.9 ± 0.1 14.8 ± 0.2 20.5 ± 0.3 24.8 ± 0.3 11 DMOpipDGA 7.66 ± 0.04 13.7 ± 0.1 18.7 ± 0.1 22.5 ± 0.1 12 DMOmorDGA 7.49 ± 0.06 13.7 ± 0.1 18.6 ± 0.1 21.1 ± 0.2 - TODGA 6.28 ± 0.02 11.69 ± 0.02 17.03 ± 0.02 21.55 ± 0.02

Literature values for stability constants (log β) of aqueous Eu(III)-diglycolic acid complexes 16 (μ = 1.00 M NaClO4) - Diglycolic acid 5.53 ± 0.02 10.04 ± 0.02 13.20 ± 0.02 -

The aqueous phase Eu(III)-diglycolic acid stability constants are lower by more than an order of magnitude than the acetonitrile phase Eu(III)-DGA stability constants because acetonitrile solvates the lanthanide metal cations less strongly than water and is more easily displaced by the diglycolamide ligands. The 1:1 complex for Eu-TODGA (in acetonitrile) is about six times stronger than the 1:1 complex for Eu-diglycolic acid (in water). The less bulky europium- unsymmetrical diglycolamide 1:1 complexes (in acetonitrile) are 10-40 times stronger yet than the

1:1 Eu-TODGA complex. These data support the idea that a decrease in steric crowding around the binding site can increase metal-ligand complex stability.

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The trend in the stepwise stability constants (log K) for the UDGA ligands (average),

TODGA, and diglycolic acid is also illuminating and shown in Figure 4.10.

8 UDGA (average) TODGA Diglycolic acid* 7

log log 5

4 (stepwise stability constant) stability (stepwise

3 *1:4 Eu(III)-diglycolic acid complex not observed

1 2 3 4 Eu(III)-(DGA) Complex n

Figure 4.10. Stepwise stability constants (log K) calculated from Table 4.5 for the UDGA ligands (average of data from ligands 3-12), TODGA, and diglycolic acid.

The pattern in stepwise stability constants (log K) is similar for diglycolic acid (blue triangles) and the unsymmetrical diglycolamides (black squares), which may suggest similarities in coordination modes (as far as the 1:3 complexes). TODGA follows the same trend as diglycolic acid and the UDGA ligands for the 1:1 and 1:2 species, but increases in magnitude relative to the

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other ligands for the 1:3 and 1:4 species. This could suggest that the weaker Eu-TODGA complexes for the 1:1 and 1:2 species are a result of steric crowding around the metal center, while the relative increase in stepwise stability constants for the 1:3 and 1:4 species arises from favorable van der Waals interactions between the longer, symmetrical octyl chains. Even so, all of the 1:1 through 1:4 Eu-UDGA complexes (except for Eu(DMOmorDGA)4) have higher conditional stability constant (log β) values than the symmetrical diglycolamide, TODGA. This points towards the steric crowding in TODGA as the main contributing factor to complex instability, as opposed to the decrease in van der Waals interaction between the unsymmetrical diglycolamide alkyl groups.

The same trend in complex stability was seen in earlier experiments using liquid-liquid solvent extraction (log K'ex values) wherein all the UDGAs (except DMOmorDGA) were found to be consistently stronger Eu(III) extractants than TODGA. A direct comparison of the Eu(III)

152,154 luminescence spectroscopy data (log β103) with the radiotracer Eu(III) solvent extraction data

(log K'ex) is illustrated graphically in Figure 4.11. The solvent extraction data determined the extracted Eu-UDGA complex to be 1:3 on average, so the corresponding 1:3 complex stability constant (log β103) was used as a comparison.

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32 32

log K'ex (Eu solvent extraction)

28 log 103 (Eu luminescence spectroscopy) 28

24 24

20 20

103 

K' 16 16

log log log log 12 12

8 8

4 4

0 0 1 2 3 4 5 6 7 8 9 10 11 12 T Diglycolamide Ligand

152,154 Figure 4.11. Comparison of log K'ex values (obtained from previous radiotracer Eu(III) solvent extraction ligand dependence data in Table 3.4) and log β103 values (obtained from Eu(III) luminescence spectroscopy titrations in Table 4.5) for the unsymmetrical diglycolamides (1-12) and TODGA (T).

The general trend for the log K'ex and log β103 values is nearly identical: pyrrolidinyl ligands

(1, 4, 7, and 10) form the strongest Eu(III) complexes, piperidinyl ligands (2, 5, 8, and 11) form the second strongest Eu(III) complexes, and morpholino ligands (3, 6, 9, and 12) form the weakest

Eu(III) complexes. The difference in complexation strength between these three amide ring types is less pronounced for the dihexyl (1-3) and dioctyl (4-6) groups and more prominent within the branched di-2-ethylhexyl (DEH, 7-9) and bis(3,7-dimethyloctyl) (DMO, 10-12) groups. For example, the 1:3 complexes for Eu-DOpyrDGA are only ten times stronger than 1:3

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Eu-DOpipDGA complexes, whereas the same complexes are over one hundred times stronger for

DMOpyrDGA as opposed to DMOpipDGA.

One major difference between the log K'ex and log β103 values is the relative complexation strength of the di-2-ethylhexyl (7-9) derivatives compared to the other dialkyl groups. The DEH derivatives form slightly weaker complexes than the other dialkyl groups in the solvent extraction log K'ex trend whereas ligands 7-9 have similar log β103 values compared to the dioctyl (4-6) derivatives and slightly higher log β103 values than the bis(3,7-dimethyloctyl) (10-12) group.

Stability constant values for the 1:3 Eu-DHpyrDGA and 1:3 Eu-DHpipDGA complexes were also estimated by calculating the Δ(ΔG) between the two sets of data for ligand 3-12

(ΔG = -RTlnKex and ΔG = -RTlnβ103). The average Δ(ΔG) was determined to be 74 ± 5 kJ/mol.

This number was used to calculate theoretical stability constant values for DHpyrDGA (log β103

(calc.) = 20.9) and DHpipDGA (log β103 (calc.) = 19.9). These theoretical values are consistent with the trends discussed previously.

The comparison of the log K'ex and log β103 values is mostly qualitative, however, since the solvent conditions between the experiments vary greatly (5.0% v/v 1-octanol/n-dodecane in contact with 0.985 M HNO3 vs. 0.3 mM HNO3/0.2 M H2O/99.7% MeCN). The radiotracer

152,154Eu(III) solvent extraction experiments determined the metal-ligand stoichiometry in

5.0% v/v 1-octanol/n-dodecane to be approximately 1:3 for all UDGA ligands and TODGA. The extraction mechanism is represented in Equation 4.8.

3+ - Eu(aq) + 3NO 3 + x HNO 3 + 3UDGA Eu(UDGA) 3 (NO 3 ) 3 (HNO 3 )x (4.8)

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The extraction equilibrium constant (K'ex) is thus written as seen in Equation 4.9.

Eu(UDGA)3 (NO 3 ) 3 (HNO 3 )x K'   ex 3 x 3 (4.9) Eu3+   NO -   HNO   UDGA  (free) 33    

The biphasic solvent extraction experiment includes the extraction of nitric acid into the organic phase, which further complicates the system. The organic phase also contains the phase modifier, 1-octanol, which likely aides in the solvation of the metal-ligand complex in the aliphatic diluent, n-dodecane.

The Eu(III) luminescence spectroscopy titrations found the metal-ligand stoichiometry in

0.3 mM HNO3/0.2 M H2O/99.7% MeCN to be 1:4 for UDGA ligands 3-12 and TODGA. These titrations were monophasic with fewer equivalents of nitric acid available ([Eu3+] = 0.482 mM,

[HNO3] = 0.3 mM) compared to the extracted nitric acid determined in the solvent extraction

3+ -5 experiments ([Eu ] = 10 M, [HNO3] = 10-70 mM). The formation reaction for the 1:4

Eu(III)-UDGA complex is shown in Equation 4.10.

3+ - Eu(solv) + 3NO 3 + 4UDGA Eu(UDGA) 4 (NO 3 ) 3 (4.10)

The solvation of the Eu3+ cation changes greatly between the acidic aqueous environment in Equation 4.8 and the predominantly acetonitrile (99.7% volume) environment in Equation 4.10.

The weaker MeCN ligands (compared to H2O) are more easily displaced by the UDGA ligands, which leads to much larger values for the 1:4 conditional stability constants (β104, Equation 4.11).

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Eu(UDGA)4 (NO 3 ) 3    104 3 4 (4.11) Eu3+   NO -   UDGA  (solv) 3  

The evident predominance of the terminal 1:4 metal-UDGA complex, assuming a tridentate ligand, would suggest a Eu3+ metal center with a coordination number of 12. Although possible, 12-coordinate complexes with Eu3+ are rare and involve small multidentate ligands that take up very little space in the coordination sphere (e.g., nitrate).12

Alternatively, it is also possible that all or some of the tridentate UDGA ligands are functioning as bidentate ligands, which would give a more common Ln(III) coordination number of eight. There are at least two possible bidentate configurations for the UDGA ligands. The first bidentate UDGA configuration was inspired by recent work by Antonio et al.17 It was suggested that in order to accommodate four DGA ligands in the primary coordination sphere of the Ln(III) metal center, it was necessary for a conformational change where one end of the DGA molecule rotated away from the metal center, leaving the two remaining ether and amidic oxygens to coordinate to the metal. This conformer maintains the favorable 5-membered chelate rings and could theoretically direct a portion of a bulky DGA away from the binding pocket of the ligand.

This configuration is even more appealing for the UDGAs (relative to TODGA), where the bulkier long-chain alkyl group could be further removed from the metal coordination site. This structure has only been proposed, however, and the loss of coordination from the second carbonyl oxygen greatly decreases the conformational freedom of the complex, which adopts a rectangular version of the preferred 8-coordinate square antiprismatic geometry (Figure 4.12).

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Figure 4.12. Possible square antiprismatic structure (#1, 5-membered chelate rings) for the 8-coordinate Eu(III)-pyrDGA metal-ligand complex (R = hexyl, octyl, 2-ethylhexyl, 3,7-dimethyloctyl).

The second possible bidentate UDGA ligand configuration coordinates with all eight amidic oxygens, which have been shown to be about 80 pm closer to the Ln(III) metal than the etheric oxygens in x-ray crystal structures.18 This structure would easily adopt a square antiprismatic molecular geometry with each UDGA ligand coordinating at the top and bottom of the antiprism. The 8-coordinate structure of a pyrrolidinyl UDGA ligand is shown in Figure 4.13 from above. Each of the ligands is tilted in three-dimensional space to minimize steric hindrance between the long-chain alkyl groups (–R) and the pyrrolidinyl group.

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Figure 4.13. Possible square antiprismatic structure (#2, 8-membered chelate rings) for the 8-coordinate Eu(III)-pyrDGA metal-ligand complex (R = hexyl, octyl, 2-ethylhexyl, 3,7-dimethyloctyl).

The loss of the etheric oxygen coordination could slightly decrease the metal-ligand complex stability but it is also possible that the amidic oxygens offer a more favorable geometry with the Eu3+ cation. The tridentate binding mode requires the metal cation to be in close proximity to all three donor oxygen atoms, which may introduce stress into the UDGA ligand backbone.

Binding through only the amidic oxygens could relieve the ligand strain and lead to enhanced metal-ligand complex stability; the resulting 8-membered ring would likely not be thermodynamically favorable in a strongly hydrogen-bonding solvent like water, but might be more energetically favorable in less polar media. Unfortunately, there are no crystal structures in the literature to further illuminate the 1:4 Ln(III)-DGA complex because this stoichiometry is only observed in the organic phase (1:3 Ln(III)-DGA crystal structures have been solved).18

Nevertheless, the existence of diglycolamide (e.g., TODGA) quaternary complexes in the organic

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phase (e.g., n-dodecane) has been deduced using small-angle neutron scattering (SANS)4,6 and small-angle x-ray scattering (SAXS)19.

4.6. Conclusions

The unsymmetrical diglycolamides have been shown to form 10-1000 times stronger 1:4 complexes with the Eu(III) than the symmetrical diglycolamide, TODGA (log βUDGA4 > log βTODGA4) in acetonitrile. The 1:3 Eu(III)-UDGA conditional extraction equilibrium constants

(log K'ex) from previous solvent extraction experiments (in 5.0% v/v 1-octanol/n-dodecane in contact with 0.985 M HNO3) were compared to the 1:3 Eu(III)-UDGA conditional stability constants (log β103) from the current work and found to have a similar pattern, separated by a

Δ(ΔG) of 74 ± 5. These two separate sets of experiments with different techniques confirm the accuracy of the values in both cases. Additional spectroscopic techniques (e.g., Tb(III) luminescence spectroscopy, Nd(III) absorbance spectroscopy, Sm(III) NMR spectroscopy) could also be employed to further probe the Ln(III)-UDGA complexes.

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4.7. References

(1) Zhu, Z. X.; Sasaki, Y.; Suzuki, H.; Suzuki, S.; Kimura, T. Cumulative Study on Solvent Extraction of Elements by N,N,N',N'-tetraoctyl-3-oxapentanediamide (TODGA) from Nitric Acid into n-Dodecane. Anal. Chim. Acta 2004, 527(2), 163–168.

(2) Tian, G.; Teat, S. J.; Rao, L. Structural and Thermodynamic Study of the Complexes of Nd(III) with N,N,N′,N′‑tetramethyl-3-oxa-glutaramide and the Acid Analogues. Inorg. Chem. 2014, 53, 9477–9485.

(3) Atkins, P.; Overton, T.; Rourke, J.; Weller, M.; Armstrong, F. The f-Block Elements. In Shriver & Atkins’ Inorganic Chemistry; Oxford University Press: Oxford, 2010; pp 579– 598.

(4) Jensen, M. P.; Yaita, T.; Chiarizia, R. Extractant Aggregation as a Mechanism of Metal Ion Selectivity. In International Solvent Extraction Conference; 2008.

(5) Pathak, P. N.; Ansari, S. A.; Godbole, S. V; Dhobale, A. R.; Manchanda, V. K. Interaction of Eu3+ with N,N,N',N'-tetraoctyldiglycolamide: A Time Resolved Luminescence Spectroscopy Study. Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 2009, 73(2), 348–352.

(6) Jensen, M. P.; Yaita, T.; Chiarizia, R. Reverse-Micelle Formation in the Partitioning of Trivalent f-Element Cations by Biphasic Systems Containing a Tetraalkyldiglycolamide. Langmuir 2007, 23(9), 4765–4774.

(7) Lide, D. R. Fluid Properties. In CRC Handbook of Chemistry and Physics; Lide, D. R., Ed.; CRC Press, Inc.: Boca Raton, Florida, 2004; pp 6-1–6-223.

(8) Czerny, M.; Turner, A. F. Uber Den Astigmatismus Bei Spiegelspektrometern. Zeitschrift fur Phys. 1930, 61(11), 792–797.

(9) Dutra, J. D. L.; Gimenez, I. F.; Junior, N. B. D. C.; Freire, R. O. Theoretical Design of Highly Luminescent Europium(III) Complexes: A Factorial Study. J. Photochem. Photobiol. A Chem. 2011, 217(2-3), 389–394.

(10) Kimura, T.; Kato, Y. Luminescence Study on Hydration States of Lanthanide(III)- Polyaminopolycarboxylate Complexes in Aqueous Solution. J. Alloys Compd. 1998, 275- 277, 806–810.

(11) Cotton, S. Electronic and Magnetic Properties of the Lanthanides. In Lanthanide and Actinide Chemistry; Wiley: Chichester, England, 2006; pp 61–87.

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(12) Cotton, S. Coordination Chemistry of the Lanthanides. In Lanthanide and Actinide Chemistry; Wiley: Chichester, England, 2006; pp 35–59.

(13) Arisaka, M.; Kimura, T. Thermodynamic and Spectroscopic Studies on Am(III) and Eu(III) in the Extraction System of N,N,N',N'-diamide in n-Dodecane/Nitric Acid. Solvent Extr. Ion Exch. 2011, 29, 72–85.

(14) Connors, K. Optical Methods. In Binding Constants. The Measurement of Molecular Complex Stability; Wiley-Interscience: New York, 1987; pp 339–346.

(15) Gans, P.; Sabatini, A.; Vacca, A. Investigation of Equilibria in Solution. Determination of Equilibrium Constants with the HYPERQUAD Suite of Programs. Talanta 1996, 43(10), 1739–1753.

(16) Grenthe, I.; Tobiasson, I. Thermodynamic Properties of Rare Earth Complexes. I. Stability Constants for the Rare Earth Diglycolate Complexes. Acta Chem. Scand. 1963, pp 2101–2112.

(17) Kannan, S.; Moody, M. A.; Barnes, C. L.; Duval, P. B. Lanthanum(III) and Uranyl(VI) Diglycolamide Complexes: Synthetic Precursors and Structural Studies Involving Nitrate Complexation. Inorg. Chem. 2008, 47(11), 4691–4695.

(18) Antonio, M. R.; McAlister, D. R.; Horwitz, E. P. An Europium(III) Diglycolamide Complex: Insights into the Coordination Chemistry of Lanthanides in Solvent Extraction. Dalt. Trans. 2015, 44(2), 515–521.

(19) Nave, S.; Modolo, G.; Madic, C.; Testard, F. Aggregation Properties of N,N,N',N'- tetraoctyl-3-oxapentane (TODGA) in n-Dodecane. Solvent Extr. Ion Exch. 2004, 22(4), 527–551.

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Chapter 5

CONCLUSIONS

5.1. Projects Goals

The main goal of this work was to gain a better understanding of the influence of increasing the asymmetry between two opposite amide ends of the diglycolamide backbone on extraction performance, in essence, to determine whether the increasing “amphiphilicity” of diglycolamides might alter the extraction properties of this ligand class. Twelve different unsymmetrical diglycolamide (UDGA) extractants, or ligands, were designed with more polar/more compact alkyl groups on one amide (pyrrolidinyl, piperidinyl, morpholino) and more aliphatic alkyl groups on the other amide (hexyl, octyl, 2-ethylhexyl, 3,7-dimethyloctyl). This unsymmetrical, amphiphilic character of the UDGA extractants could in principle lead to improved phase-transfer kinetics due to increased interfacial activity and stronger metal-ligands complexes due to less structurally-hindered metal binding pockets. The asymmetry of the ligands could also limit the aggregation of the ligand molecules in the organic phase because of a decrease in the intermolecular forces between the previously identical alkyl chains on neighboring ligand molecules.

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5.2. Organic Synthesis

Twelve different unsymmetrical diglycolamide (UDGA) ligands were synthesized using a two-step synthetic route. All of the necessary reagents (except for the separately synthesized bis(3,7-dimethyloctyl)amine) were commercially available and relatively inexpensive. The majority of the compounds (all except 3, 6, 9, and 12) were purified by evaporative distillation to yield clear, colorless oils with good overall percent yields (average = 70.6%). The remaining compounds (3, 6, 9, and 12) were purified using flash chromatography to yield clear, colorless oils with lower overall percent yields (average = 42.8%). The two-step synthetic route was designed for the eventual scaling-up to ligand quantities required for industrial solvent extraction processes.

The main byproducts of the synthesis include methanol, sulfate, and diisopropylethylamine salts, which have fairly low toxicity and do not require special handling.

5.3. Solvent Extraction Studies

The trivalent lanthanide metal extraction behavior of the unsymmetrical diglycolamides

(1-12) was studied using radiometric and ICP-MS techniques. DHpyrDGA(1) and

DMOpyrDGA(10) in 5.0% v/v 1-octanol/n-octane were contacted via Vortex mixing with

Eu(NO3)3 in 0.985 M HNO3 for varying amounts of time and were found to reach equilibrium in less than 30 minutes. The conditional metal extraction equilibrium constants (K'ex) were determined using a ligand dependence slope analysis experiment and the UDGA ligands were found to be comparable or stronger extractants than the symmetrical diglycolamide, TODGA. The same slope analysis experiment also determined the metal-ligand complex stoichiometry

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(in 5.0% v/v 1-octanol/n-dodecane) to be approximately 1:3 for the UDGA ligands and TODGA.

DMOmorDGA(12) was found to extract approximately one molecule of HNO3 per ligand when in contact with 3.01 M HNO3 but a nitric acid extraction constant (KH) for the

(HNO3)(DMOmorDGA) species was not able to be determined with the inconsistent experimental data.

The change in Eu(III) extraction with varying concentrations of HNO3 was determined radiometrically and compared across the ligand series. The dihexyl derivatives (1-3) dissolved in

5.0% v/v 1-octanol/n-dodecane were the strongest extractants for Eu(III), but formed a dense third phase when contacted with 1.94 or 3.01 M HNO3, which is undesirable for a biphasic liquid-liquid solvent extraction process. The dioctyl derivatives (4-6) had the second highest distribution ratios

(DEu) for Eu(III) and did not form a third phase at 1.94 and 3.01 M HNO3. The di-2-ethylhexyl derivatives (7-9) were the weakest extractants for Eu(III); nonetheless, DEHmorDGA(9) exhibited

3 a DEu > 10 (at 1.94 M HNO3) and DEu < 0.01 (at 0.00967 M HNO3), which is desirable for metal stripping at low acidity and metal extraction at high acidity. The bis(3,7-dimethyloctyl) derivatives

(10-12) had slightly higher DEu than the smaller di-2-ethylhexyl derivatives (7-9), which goes against the usual trend of decreasing metal extraction with increasing alkyl group size. It was speculated that the metal extraction of the 2-ethylhexyl derivatives was suppressed because the ethyl group in the 2-position hinders metal cation access to the binding pocket. The entire lanthanide series extraction trend was determined using ICP-MS and most of the ligands (except

8, 9, 11, 12) preferentially extracted Yb3+ over all other Ln3+. The branched derivatives

(2-ethylhexyl and 3,7-dimethyloctyl) with six-membered rings (piperidinyl and morpholino) (8, 9,

11, 12) exhibited maximum metal extraction with the smallest lanthanide, Lu3+, suggesting possible steric hindrance at the binding pocket for both types of branched ligands.

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5.4. Luminescence Spectroscopy

Solutions of 0.482 mM Eu(NO3)3 in MeCN were titrated with 5-8 mM solutions of each

UDGA ligand (1-12) and TODGA in MeCN and emission spectra were collected after each titrant addition. The luminescence lifetime of Eu was determined for the final titration solutions for each ligand and the inner-sphere hydration number (NH2O) was calculated. There was no residual hydration of the metal ion for all twelve ligands and TODGA. The titration spectra were imported into the program HypSpec and the spectroscopic data were used to calculate conditional stability constants (log β) for the 1:1, 1:2, 1:3, and 1:4 complexes. The HypSpec program converged on reasonable values for conditional stability constants for ten of the twelve UDGA ligands (no fit for

1 and 2) and TODGA. The 1:3 conditional stability constants (log β103) were compared directly to the 1:3 conditional extraction equilibrium constants (log K'ex) from previous solvent extraction studies and the overall trends were the same (with a Δ(ΔG) of 74 ± 5 kJ/mol across the ligand series).

5.5. Future Work

The extraction of nitric acid and water by solvating extractants (like the UDGA ligands) decreases the amount of free ligand in the organic phase and can lead to the formation of a dense organic phase (third phase). A preliminary study on the extraction of HNO3 by DMOmorDGA(12) was conducted in this work but a more thorough investigation would be able to determine extraction equilibrium constants (KH) for all the UDGA ligands. The extraction of nitric acid by the phase modifier 1-octanol adds a further complication to the system, which could be eliminated

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if the extractions were completed solely in n-dodecane. A trend in nitric acid extraction could also help to select for desirable structural features for future ligand design. The organic phase concentration of water can be determined using Karl Fischer titrations1, which would also be useful for a more detailed description of the organic phase Ln(UDGA)x(NO3)3(HNO3)y(H2O)z complexes.

The conditional stability constants (log β) of the 1:1, 1:2, 1:3, and 1:4 Eu-UDGA complexes in MeCN were determined using luminescence spectroscopy. Similar experimental

3+ conditions could be used with Nd in spectrophotometric titrations to obtain conditional stability constants (log β) for the 1:1, 1:2, 1:3, and 1:4 Nd-UDGA. The two sets of data could be directly compared to validate the method and the accuracy of the log β values. Molecular modelling would be particularly useful for illuminating the denticity and conformation of the UDGA ligands in the

1:4 metal-ligand complex in MeCN, which would require a 12-coordinate Ln(III) cation to maintain the tridentate UDGA ligand binding mode.

A synthetic pathway to these unsymmetrical diglycolamides has been created and iterated for improved product purity and minimal byproduct waste. The long-chain alkyl groups from the current study (hexyl, octyl, 2-ethylhexyl, and 3,7-dimethyloctyl) do not lend enough lipophilic character to the UDGA ligands; all the UDGA ligands required the addition of 5% 1-octanol to the preferred diluent, n-dodecane, to maintain one homogeneous organic phase when contacted with

-5 dilute Eu(III) metal (10 M) in highly acidic media (e.g., 3 M HNO3). In the closing stages of this research, a triply-branched secondary amine bis(3,7,11-trimethyldodecyl)amine (C30) was synthesized from the sesquiterpene, farnesol. This secondary amine was used to synthesize another unsymmetrical diglycolamide (TMDpipDGA, Figure 5.1), which could in principle improve miscibility with the preferred normal paraffinic hydrocarbon diluent.

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Figure 5.1. Structure of N,N-bis(3,7,11-trimethyldodecyl)-N′-piperidinyldiglycolamide (TMDpipDGA).

It is reasonable to postulate that TMDpipDGA could potentially be used to extract Ln(III) from highly acidic media without the use of a phase modifier. Commercially available amines like didecylamine (C20) and didodecylamine (C24) could also be used as a comparison to bis(3,7-dimethyloctyl)amine (C20) and bis(3,7,11-trimethyldodecyl)amine (C30). The longer chain alkyl groups would be expected to decrease metal extraction (compared to the UDGA ligands in this work) because of the increase in steric hindrance around the binding pocket. A decrease in metal extraction would not be a problem for the UDGA ligands (1-12), each of which exhibited

3 quantitative Eu(III) extraction (DEu > 10 ) at 3 M HNO3. The balance of solubility (longer alkyl chain) and metal extraction strength (smaller alkyl chain) could be investigated further by synthesizing more UDGA ligands with greater amphiphilic behavior.

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