University of Cincinnati

UNIVERSITY OF CINCINNATI

Date:October 20, 2004

I, _____Sarah Marie Mandel ______, hereby submit this work as part of the requirements for the degree of: Doctorate of Philosophy in: Chemistry It is entitled : Photolysis of Alkyl Azides Containing an Aryl Ketone Chromophore in Solution and the Solid-State

This work and its defense approved by:

Chair: _Anna Gudmundsdottir ______R. Marshall Wilson ______William Connick ______

Photolysis of Alkyl Azides Containing an Aryl Ketone Chromophore in Solution and the Solid State

A dissertation submitted to the

Division of Research and Advanced Studies of the University of Cincinnati

in partial fulfillment of the requirements for the degree of

DOCTORATE OF PHILOSOPHY (Ph.D.)

In theDepartment of Chemistry of the College of Arts of Sciences

2004

Sarah Marie Mandel

B.A. Transylvainia University, 1998 M.S University of Cincinnati, 2002

Committee Chair: Anna Dora Gudmundsdottir

Abstract:

In this research internal sensitization has been utilized to photochemically generate triplet alkyl nitrenes in solution and solid-state. Irradiating alkyl azides containing aryl ketone chromophores with light over 300 nm allows only the aryl ketone chromophore to be excited.

The triplet aryl ketone chromophore created from excitation can then transfer triplet energy to the alkyl azide moiety, forming a triplet alkyl nitrene.

Solution irradiation allowed triplet alkyl nitrenes to be trapped in bimolecular reactions.

In solution irradiations of Azides 1 the major solution photoproduct was found to be N-benzoyl benzamides derivatives formed by the trapping of a triplet alkyl nitrene with a benzoyl radical.

Photolysis of Azides 2 in solution was found to yield three products which can be attributed to bimolecular trapping of the triplet alkyl nitrene. The major photoproducts were identified as 1-phenyl-3-[5-phenylpyrazol-1-yl]-propan1-one derivatives, formed from dimerization of triplet alkyl nitrenes. The remaining photoproducts were found to be 3-(3-oxo-3- phenyl-propylamino)-1-phenyl-propenone derivatives and 3-(3-oxo-3-phenyl-propylamino)-1- phenyl-propan-1-one derivaitves formed from trapping of the triplet alkyl nitrene with propiophenone radicals.

When Azides 3 were irradiated in solution the products were found to form acetophenone derivatives and 5-(4-phenyl)-pyrrole derivatives created from 1,4 intramolecular hydrogen atom abstraction. Formation of the triplet alkyl nitrene lead to the creation of 5-(4- phenyl)-3,4- dihydro-2H-pyrrole derivatives.

Irradiations of alkyl azides within molecular crystals yielded interesting results. In solid state irradiations of Azides 1 the photoproduct was found to be N-methylene benzamide derivatives in all cases. This was interesting because the bimolecular reactivity observed in solution was changed to unimolecular reactivity within the restraints of a crystal lattice. Oxygen

trapping studies indicate that the product is formed from α-cleavage of the triplet aryl ketone, followed by rearrangement of the resultant fragments.

In solid state photolysis of Azides 2 energy transfer from the aryl ketone to the alkyl azide moiety was found to create the triplet alky nitrene which underwent dimerizaion. It was

found that the products of all solid-state irradiations can be correlated to the X-ray

crystallography of the starting azide.

Acknowledgements:

I would like to thank my family, my friends, and my co-workers for making this long process possible. I truly appreciate all the love and support you gave me before and during graduate school, and that you continue to give to this day.

Table of Contents

List of Figures and Tables 3

Introduction 10

Objective 26

Preparation of Alkyl Azido Aryl Ketones 34

Chapter One Irradiation of Azides 1 in Solution and Solid-State

Product Studies of Solution Irradiations of Azides 1 35

Product Studies of Solution Irradiation of

1-Azido Adamantane in the Prescence of Benzoyl Radicals 43

Product Studies of Solution Irradiations of Azide 1e 52

Product Studies of Solution Irradiations of 2-Azido-1-Phenyl Ethanone

In an Oxygen Environment 57

Product Studies of Solution Irradiations of Azide 1e in an

Oxygen Environment 58

Phosphorescene Emissions of Azides 1 59

Laser Flash Photolysis Experiments with 2-Azido-1-Phenyl Ethanone

And Azides 1 60

Product Studies of Solid-State Irradiations of Azides 1a-1g 64

Product Studies of Solid-State Irradiations of Azide 1e 68

Product Studies of Solid-State Irradiations of Azide 1e in an

Oxygen Environment 73

X-Ray Crystallography of Azides 1 75

Chapter Two Irradiation of Azides 2 in Solution and Solid-State

Product Studies of Solution Irradiations of Azides 2 82

Product Studies of Solution Irradiations of Azide 2a in an

Oxygen Environment 91

Phosphorescence Emissions of Azides 2 92

Laser Flash Photolysis Experiments with 3-Azido-1-Phenyl Propanone 94

Product Studies of Solid State Irradiations of Azides 2 95

Product Studies of Solid State Irradiations of Azides 2a in an

Oxygen Environment 96

X-Ray Crystallography of Azides 2a and 2b 97

Chapter Three: Irradiation of Azides 3 in Solution

Product Studies of Solution Irradiations of Azides 3 102

X-Ray Crystallography of Azide 3c 106

Phosphorescence Emission of Azide 3a 108

Laser Flash Photolysis Experiments of 4-Azido-1-Phenyl Butanone 109

Conclusions 111

Experimental Section 113

References 145

Appendix 1 149

List Of Figures

Figure 1. Resonance Structures of the Azide Group

Figure 2. Traditional Synthetic Uses of Azides

Figure 3. New Synthetic Uses of Azides

Figure 4. Reaction Pathways of Directly Excited Alkyl Azides

Figure 5. Products of Gas Phase Thermolysis of N-Butyl Azide

Figure 6. Pyrollosis Products of Azides 1

Figure 7. Reaction Pathways of Phenyl Azides

Figure 8. Spin Allowed and Spin Forbidden Intramolecular Reactions of Triplet Alkyl

Nitrenes

Figure 9. Intermolecular Sensitization of Alkyl Azides

Figure 10. Singlet Reactivity of Benzyl Azide

Figure 11. Reaction Scheme of Benzyl Azide Sensitized with Acetophenone

Figure 12. Intramolecular Sensitization of Napthalene with an Acetophenone

Chromophore

Figure 13. Cage Effect on Triplet Species

Figure 14. Reaction Scheme Benzoin Methyl Ether (16)

Figure 15. Solid-State Reactivity of Phenyl Azides

Figure 16. Reaction Mechanisms of Phenyl Azides in the Solid-State

Figure 17. Intramolecular Sensitization of an Alkyl Azide with Acetophenone to Form a

Triplet Alkyl Nitrene

Figure 18. Possible π-orbital Overalp of the Aryl Ketone Chromophore and the Alky

Azide

Figure 19. Classes of Molecules Studied in This Reseach

Figure 20. Competing Reactions of the Excited Triplet Ketone in Azides 1

Figure 21. Possible Reaction Pathway of Azides 2

Figure 22. Competing Reactions of Azides 3

Figure 23. Photoreactivity of Acetophenone in Solution

Figure 24. Displacement Reaction of Alkyl Halides to Create Alkyl Azides

Figure 25. Reaction Scheme of Azides 1 in Solution

Figure 26. Formation of Benzoyl Radicals in Irradiation of Azides 1

Figure 27. Benzoyl Trapping of Molecular Triplet Oxygen

Figure 28. Formation of Benzoyl Benzamide,(5)

Figure 29. Products Isolated From Solution Irradiation of Azide 1g

Figure 30. Observed Products of Solution Irradiation of 2-Azido 1-Phenylethanone at

Two Temperatures

Figure 31. Benzoyl Radical Attack of a Ground State Alkyl Azide to Give Benzoyl

Benzamides

Figure 32. Observed Product of Solution Irradiation of Darocur 1173, (13)

Figure 33. Direct Photolysis Products of 1-Azido Adamantane in the Presence of

Methanol

Figure 34. Possible Products of 1-Azido Adamantame and Benzoyl Radicals

Figure 35. Energy Transfer from Darocur 1173 to 1-Azido Adamantane

Figure 36. Solution Photochemistry of Benzoin Methyl Ether

Figure 37. Observed Products of Solution Irradiations of 1-Azido Adamantane and 16

Figure 38. Solution Irradiation of Azide 1e

Figure 39. The α-Cleavage Mechanism for the Formation of Deoxybenzoin, ( 9)

Figure 40. Nitrene and Non-nitrene mechanism for formation of 1.2 Acyl Shift Product in Irradiations of Azide 1e

Figure 41. Possible Intramolecular Shift Products for Azide 1e

Figure 42. Oxygen Trapping of 2-Nitreneo-1-phenyl ethanone in Solution

Figure 43. Low Temperature Phosphoresecnce Spectra of 4’Bromo Acetophenone and 2-

Azido(4- Bromphenyl)ethanone in Ethanol

Figure 44. Esimated Triplet Energy of Triplet Excited Alkyl Azides in Azides 1

Figure 45. Stern-Volmer Quenching of α-Azido Acetophenone with Isoprene

Figure 46. Transient UV Spectra of 2-Nitreno 1-Phenylethanone

Figure 47. Transient Spectra of 2-Azido-1-phenylethanone under Oxygen and Argon

Atmosphere

Figure 48. Kinetic Trace of 2-Nitreno 1-Phenylethanone

Figure 49. Possible Solid-State Mechanisms for Formation of 23

Figure 50. Reduction of 23 by Sodium Cyanoborohydride and BTPPTB

Figure 51. Synthesis of N-Methyl Benzamides

Figure 52. Observed Crystalline Photoreactivity of 2-Azido (4- methoxythiophenyl)ethanone

Figure 53. Mechanism for Acid and Ester Formation in Crystalline Irradiations of Azides

Figure 54. Solid State Photoproduct of 2,6 Diphenyl Cyclohexanone

Figure 55. Solid-State Reaction of Azide 1e at Low Conversion

Figure 56. Observed Solid-State Photoproducts of Azide 1e in an Oxygen Atmosphere

Figure 57. Unit Cell of Azide 1a

Figure 58. Unit Cell of Azide 1c

Figure 59. Unit Cell of Azide 1e

Figure 60. Crystal Lattice of Azide 1a

Figure 61. Crystal Lattice of Azide 1c

Figure 62. Crystal Lattice of Azide 1e

Figure 63. Products Isolated from Solution Irradiations of 3-Azido 1-Phenyl Propanone

Derivatives.

Figure 64. Products Isolated From Solution Irradiations of Azides 2

Figure 65. Reacitve Pathways of the Azo dimer ( 26 )

Figure 66. Formation of Product 27

Figure 67. Nitrene Mechanism for the Formation of Product 30

Figure 68. Formation of N-centered Imine Radical

Figure 69. Non-Nitrene mechanism for Formation of Product 30

Figure 70. Formation of Product 31

Figure 71. Products Resulting From α-Cleavage of Excited Chromophores of Azides 2

Figure 72. Synthesis of 1-(4-Chlorophenyl) 3-Nitro Propanone

Figure 73. New Product Observed in O 2 Solution Irradiation of Azide 2a

Figure 74. Low Temperature Phosphorescence Spectra of 1-(4-Chlorophenyl)

Propanone and 3-Azido 1-(4-Chlorophenyl) Propanone.

Figure 75. Transient UV Spectra of 3- Azido 1-Phenyl Propanone

Figure 76. Solid State Photoreactivity of 3-Azido 1-Phenyl Propanone Derivaitves

Figure 77. Trapping of Triplet Alkyl Nitrene by Oxygen in Solid State Irradiations

Figure 78. Syn and Gauche Confomers of Azides 2

Figure 79. Unit Cell of Azide 2a

Figure 80. Unit Cell of Azide 2b

Figure 81. Crystal Lattice of Azide 2a

Figure 82. Crystal Lattice of Azide 2b

Figure 83. Products Isolated From Solution Irradiation of 4-Azido-1-Phenylbutanone

Figure 84. Reactive Intermediates Formed From the Triplet Ketone

Figure 85. Products Resulting From Formation of the 1,4 Biradical of Azide 3

Figure 86. Products Resulting from Triplet Alkyl Nitrene Formation in Azides 3

Figure 87. Alternate Mechanism for the Formation of Product 40

Figure 88. Radical Ring Closure Reactions of Azides 2 and Azides 3

Figure 89. Unit Cell of Azide 3c

Figure 90. X-ray Crystal Lattice of Azide 3c

Figure 91. Phosphorescence Emission of Azide 3b

Figure 92. Transient UV Spectra of 4-Azido-1-Phenylbutanone

List of Tables

Table 1. Product Ratio of Benzyl Azide Photolysis in Toluene with Acetophenone as a

Sensitizer.

Table 2. Product Ratio of the Photolysis of Benzoin Mehtyl Ether in Various Media.

Table 3. Molecules Studied in This Research

Table 4. The Triplet Energy and Type of Excited Triplet Ketone of Selected

Acetophenone Derivatives

Table 5. Product Ratios of Various 2 Azido 1-Phenyl Ethanone Derivatives in Solution.

Table 6. Product Ratio of 2-Azido 1-Phenyl Ethanone at Various Temperatures

Table 7. Photoproduct of Darocur 1173 in Methanol/Toluene Solution.

Table 8. Photoproduct Ration of Benzoin Methyl Ether in Solution

Table 9. Product Ratios of 2-Azido 1,2 Diphenyl Ethanone in Solution Irradiation.

Table 10. Rates of Energy Trnasfer in Azides 1

Table 11. Important Distances in the Crystal Structures of Various 2-Azido 1-Phenyl

Ethanone Derivaitves.

Table 12. Product Yields of Solution Irradiation of 3-Azido -1-Phenylpropanone

Derivatives

Table 13. Important Distances in Azides 2 in Å

Table 14. Solution Irradiation Product Yields for Azides 3

Table 15. Rates of Energy Transfer in From the Triplet Ketone and the Alkyl Azide

Introduction:

The goal of this research is study the photoreactivity of alkyl azides which have an internal triplet sensitizer. It is theorized that when alkyl azides are excited they will form alkyl nitrenes. The products of triplet alkyl nitrenes are under investigation in this research.

The azide group is a thermally and photochemically reactive moiety which upon excitation expels nitrogen gas to form products. Two resonance structures for the azide can be drawn; both are zwitterionic in nature (Figure 1).

- + + - RN N N RN N N

Figure 1. Resonance Structures of the Azide Group

Alkyl azide reactivity in the ground state has been taken advantage of for decades by synthetic organic chemists to create nitrogen containing compounds. 1 These reactions traditionally include synthesis of heterocyclic ring compounds and primary amines

(Figure 2).

O O H2 NH2 N3 Pd

N RN R N N + 3

Figure 2. Traditional Synthetic Uses of Azides

More recently alkyl azides have been found to be useful in intramolecular

Schmidt reactions and intermolecular Schmidt and Mannich reactions. 2 The azide group

. can also be oxidized to a nitro moiety by the use of a HOF CH 3CN complex with high yields (Figure 3). 3

O O H+ N N3 R 91% R

O H+ NHPh N 3 O

HOF.CH3CN

8 N 8 NO2 3

Figure 3. New Synthetic Uses of Azides

The products resulting from decomposition of alkyl azides by irradiation or thermolysis has also been studied by a number of research groups since the 1950’s. 1,4

Products of direct excitation of alkyl azides were found to be due to loss of molecular nitrogen and rearrangement to imine products (Figure 4). The loss of molecular nitrogen and rearrangement can be a concerted process from the excited alkyl azide, or a nitrene intermediate.

Few of the identified products of direct excitation of alkyl azide are attributed to trapping of the alkyl nitrene intermediate in a bimolecular reaction. The lack of

bimolecular reactivity from direct alkyl azide excitation has led to the conclusion that reactivity arises through a concerted intramolecular rearrangement.

direct excitation R R N + H 3 N H N R -N H H 2 H H imine products alkyl -N azide 2 R N

H H singlet alkyl nitrene

Figure 4. Reaction Pathways of Directly Excited Alkyl Azides

The observation of mainly intramolecular reactivity of the alkyl azide is illustrated by the product ratios of butyl azide in the gas phase (Figure 5). 5 Thermolysis of butyl azide yielded butylidene amine in 82% yield and methylene propyl amine in 7% yield. Butylidene amine is created by 1,2-hydrogen atom shift, which appear to have a greater rate than 1,2-alkyl shift. Only one percent of the isolated products can be attributed to bimolecular reactivity by an alkyl nitrene intermediate, which abstracts a hydrogen atom to form the primary amine, 1-aminobutane.

hυ NH + N3 82%

N + NH2 7% 1%

Figure 5. Products of Gas Phase Thermolysis of N -Butyl Azide

Another example of decomposition of alkyl azides is the pyrrolysis studies of 2- azido 1-phenyl ethanone derivatives done by Straw and Boyer in 1952. 6 They found that primary alkyl azide reactivity was unchanged by the addition of a ketone moiety contained within the alkyl azide molecule (Figure 6). The authors claimed the thermally excited alkyl azides underwent a hydrogen atom shift to form 2-imino-1-phenylethanone derivatives. This imine then dimerized and lost water to form phenyl –(4 phenyl-1H imidizale-2-yl) methanone derivatives.

H O O N O N3 Ar Ar heat NH N Ar -N -H O Ar 2 2 Figure 6. Pyrollysis Products of Azides 1

The decomposition of alkyl azides to products is different from the decomposition products observed for phenyl azides. While the exact mechanism of alkyl azide rearrangement is unknown, the reactivity of phenyl azides is well understood. 7

Thermal and photolytic activation of aryl azides causes them to expel molecular nitrogen and form aryl nitrenes. 7, 8 Phenyl nitrenes have been studied with a variety of spectroscopic methods and product studies. Both singlet and triplet phenyl nitrenes have been detected using time-resolved IR and UV, and triplet aryl nitrenes with EPR spectroscopy.

Upon photolysis phenyl azide expels nitrogen gas to form the singlet phenyl nitrene. At room temperature singlet phenyl nitrene inserts into the benzene ring to form an azabicyclo[4.1.0]heptatrine, which collapses to form the ketene imine azaheptatetrane. 7b Ketene imines are very reactive because of the cumulative double bond, and therefore can be trapped with secondary amines.

The rate of intersystem crossing for singlet phenyl nitrene is temperature independent, while the rate of insertion by the singlet nitrene is temperature dependant. 7

At cryogenic temperatures the rate of ring insertion for the singlet nitrene is less than that of intersystem crossing, and the triplet phenyl nitrene is observed. Triplet phenyl nitrenes have been found to create bimolecular products through reaction with another azide or nitrene, to give diphenyl-1,2-diazene (Figure 7) . 7

- CN CN

gas phase

N N3 N N hυ solution

singlet nitrene

77K HNET2

N N NEt2 N N

triplet nitrene

Figure 7. Reaction Pathways of Phenyl Azides

In comparison to singlet aryl nitrenes, singlet alkyl nitrenes have never been

directly detected, and triplet alkyl nitrenes have only been directly observed in the

gas phase and in matrices. It is possible that the singlet alkyl nitrene is not an energy

minimum, and that the alkyl azide reacts in a concerted manner via a 1,2-hydrogen

atom shift or 1,2-alkyl shift to form imine products.

Negative ion photoelectron spectroscopy has found that triplet methyl nitrene is

31.2 kcal/mol lower in energy than singlet methyl nitrene. 9 This large energy gap

between the triplet alkyl nitrene and the singlet alkyl nitrene indicates that the triplet

alkyl nitrene will not likely intersystem cross to the singlet alkyl nitrene.

Since the triplet alkyl nitrene is the ground state of the alkyl nitrene it is

reasonable to theorize that it will be longer lived and more easily observed by

spectroscopic methods. This longer lifetime can be partially attributed to the fact

that triplet alkyl nitrenes are spin forbidden from directly undergoing 1,2-hydrogen

atom shift or to rearrange directly to form imine products via 1.2 alkyl shift (Figure

8). Thus it is expected that triplet alkyl nitrenes will be long lived enough to be

trapped in bimolecular reactions.

ISC N R N R R N R N 3 Spin Forbidden R HN

Figure 8. Spin Allowed and Spin Forbidden Intramolecular Reactions of Triplet Alkyl Nitrenes

Triplet alkyl nitrenes have been observed spectroscopically. Engelking and coworkers have obtained and analyzed the UV emission spectra of triplet methyl nitrene in the gas phase. 9 EPR spectra of triplet alkyl nitrenes created in frozen argon matrices by sensitized photolysis of alkyl azides have been observed as well. Platz et al. and

Ferranti have obtained UV spectra of triplet nitrenes in frozen argon matrices. 10

Directly obtaining the triplet alkyl nitrene by intersystem crossing of the singlet alkyl nitrene is theorized to be unsuccessful due to the expected low quantum yield of intersystem crossing. Instead we chose to obtain the triplet alkyl nitrene by an indirect method. Two of the possible methods of indirectly creating are triplet alkyl nitrenes intermolecular and intramolecular triplet sensitization. This will allow for bypassing the singlet manifold of the alkyl nitrene. Both methods of sensitization have the same requirements of the sensitizer. 11

These are:

1. The sensitizer chromophore and the acceptor chromophore must absorb

light at different wavelengths.

2. The sensitization quantum yield should be approaching unity.

3. The lifetime of the triplet sensitizer should be relatively long in

comparison to the singlet lifetime.

4. The sensitizer should be fairly unreactive photochemically.

5. The energy of the sensitizer and the acceptor should be similar.

Intermolecular sensitization occurs when the triplet sensitizer or energy donor, and the energy acceptor are located in separate molecules. In intermolecular sensitization only the molecule which acts as the energy donor is excited. When an excited triplet sensitizer comes in close proximity to an energy acceptor molecule energy transfer can occur (Figure 9).

The draw back of this type of system is that many collisions will not result in energy transfer, and the excited molecule will merely decay back down to the ground state.

Another drawback to intermolecular sensitization is that the amount of sensitizer used is much greater than that of the acceptor. This means that studying the reactive intermediates using laser flash photolysis and matrix IR will be complicated because the spectra of the reactive intermediate and the sensitizer will overlap.

*3 O O O R N hυ 3 Ph Ph Ph *3 -N *3 + R N3 2 R N

Figure 9. Intermolecular Sensitization of Alkyl Azides

Intermolecular sensitization of alkyl azides has been successfully employed at this time. 12 Previous to this research the singlet reactivity of benzyl azide was studied. It was found that on direct excitation benzyl azide loses nitrogen gas and undergoes either 1.2 hydrogen to form methylene-phenyl amine or a 1.2 phenyl shift to create benzylideneamine (Figure 10). 13

hυ N N3

Figure 10. Singlet Reactivity of Benzyl Azide

When acetophenone was used as a triplet sensitizer in the photolysis of benzyl azide three major photoproducts were observed. 12 The 1,2-phenyl shift imine, methylene-phenyl amine is the major product at 49%. Other products which were observed in high yields were dibenzyl amine and tribenzyl amine. When a triplet sensitizer is employed in solution, irradiations of benzyl azide products that might be attributed to a 1,2-hydrogen atom shift are not observed.

While methylene-phenyl amine is observed in both direct and sensitized excitation of phenyl azide, this does not indicate unsuccessful sensitization. As stated previously, alkyl shifts are allowed for both the singlet and the triplet alkyl nitrene

(Figure 8).

Benzyl amine, dibenzyl amine and tribenzyl amine arise through triplet alkyl nitrene abstraction of a hydrogen atom from solvent. This forms a radical which then collapses by forming a bond with a solvent radical. The fact that the major product is not a result of hydrogen abstraction is a testament to the triplet alkyl nitrene’s inefficiency at abstracting hydrogen from solvent (Figure 11) . 14

Triplet . Ph N3 . Sensitization Ph N Triplet Alkyl Nitrene

1,2 Alkyl Shift H-atom Abstraction from Toluene . N . . Ph Ph NH Biradical Radical

Ph N Ph Ph N Ph NH2

Ph Ph N Ph H Ph N Ph

Figure 11. Reaction Scheme of Benzyl Azide Sensitized with Acetophenone

Table 1. Product Ratio of Benzyl Azide Photolysis in Toluene with

Acetophenone as a Sensitizer

Product Methylene- Tribenzyl Benzyl amine Dibenzyl Benzyl-

phenyl amine amine amine benzylidene

amine

Ratio 49% 12% 1% 25% 14%

Another type of indirect excitation is intramolecular sensitization. Intramolecular sensitization occurs when the energy donor and acceptor chromophores are located in the same molecule. The energy donor chromophore is exclusively excited, and then energy can be transferred to the acceptor moiety within the molecule. 11 This method has the advantage that the energy donor and acceptor are always in close proximity. This mechanism for indirect excitation will allow for the study of triplet alkyl nitrenes in laser flash photolysis and matrices.

There are many examples of intramolecular triplet energy transfer. One interesting example of intramolecular triplet energy transfer is that of a benzoyl napthyl system. 14 When excited with light of 350 nm, the aryl ketone chromophore is exclusively excited. The aryl ketone then transfers its triplet energy to the naphtylene chromophore, which decays back to the ground state. No phosphorescence emission which could be attributed to the excited aryl ketone chromophore was observed. Nor was any fluorescence observed which could be attributed to the singlet excited naphthalene.

Phosphorescence spectra only show emission from triplet naphthalene, indicating the triplet energy transfer was successful in this system.

Ph *3 Ph Ph O O Energy O Transfer Phosphorescence hυ 350 nm 460 nm

Figure 12. Intramolecular Sensitization of Napthalene with an Acetophenone Chromophore

We were also interested in investigating whether it was possible to translate the solution photochemistry to the solid state, and study the system under the constraint of the crystal lattice. Solid-state reactions have been gaining interest in the chemistry and material science communities for their many interesting and useful characteristics.

Some of the useful characteristics of solid-state chemistry include the fact that they are environmentally friendly, with a significant reduction in the use of environmentally hazardous waste. Solid-state reactions are also important because of their unique characteristics and results in comparison to traditional solution chemistry.

In many cases new reactivity and/or selectivity is observed in these reactions.

The reason that solid-state chemistry often shows new or changed reactivity is the due to the constraints of the system.15 When reactions are carried out in crystals they occur inside a molecular reaction chamber, only large enough to contain a few tightly packed molecules. Reactions must take place through minimal motion pathways due to the strong restraints of the crystal lattice. Some products do not form due to the inability of the reactive intermediates to freely dissociate as in solution. In these cases new

reactivity or more selectivity is often observed. This is often called cage effect, and has been observed in a number of host-guest and crystalline systems.

When two radicals are formed from α-cleavage of a triplet excited species the two radicals have the same spin, and recombination is not possible before intersystem crossing (Figure 13). Product formation from radicals generated by α-cleavage in solution generally derives when a pair of geminate radicals diffuse apart. The resulting radicals can combine with other radicals or solvent and form ground state products.

When restrained within a rigid medium the radicals cannot diffuse apart. Rather products are formed by recombination of α- cleavage radicals that have previously undergone intersystem crossing and generally regenerate the starting material.

Cage effects on products of α-cleavage can be illustrated by the photochemistry

of benzoin methyl ether. 16 When benzoin methyl ether is irradiated in benzene the main

photoproducts are benzyl methylether and the pinacol ether. These products are formed

from α-cleavage of the excited ketone and recombination of the resultant radicals.

Products as a result of Norrish Type II photochemistry, deoxybenzoin and cyclobutanols

are minor. When benzoin methyl ether is photolyzed while included in the zeolite Li-X

the product ratio is significantly altered. The major photoproduct, (4-methoxymethyl-

phenyl)-phenyl methanone, is created from a benzyl radical resonance structure (Figure

14).

OMe O O O hυ Ar Ar . Ar Ar Ar Ar Ar . Ar OMe O O O O hυ

OH OH OMe Major Photoproduct . Ar Ar Ar Ar O . O

O OH Ar Ar Ar Ar

Figure 14. Reaction Scheme Benzoin Methyl Ether, (16), in Zeolite Li-X

The change in product ratios illustrates the ability of the cage medium to alter reactivity by preventing the escape of geminate radical pairs due to the rigid structure of cage medium such as zeolites or cyclodextrins. The radicals have long enough lifetimes within the rigid media to react via reorganized constituents.

Table 2. Product Ratio of the Photolysis of Benzoin Methyl Ether ( 16 ) in Various

Media.

Medium Benzil/Pinacol (4-methoxymethyl- Deoxybenzoin 2,3-Diphenyl-

Ether phenyl)-phenyl oxetan-3-ol

methanone

Benzene 26/67 1.0 1 7

Li-X 3 77 13 8

Molecular crystal lattices can act in the same manner as the rigid structure of a host. The lattice is extremely rigid, and prevents motion and diffusion of the reactive species as long as it remains intact.

The reactivity of aryl azides has already been studied in the solid-state (Figure

15). 17 The singlet aryl nitrenes formed upon direct photolysis were long-lived enough at

77 K to intersystem cross to the lower energy triplet aryl nitrenes. These reactive intermediates were also observed by EPR for several days when kept at 77 K. When allowed to reach temperatures of 340 K the triplet aryl nitrenes reacted immediately to form products. The major photoproduct observed was found to be azobenzene derivatives when the distance between adjacent azides was less than 4.2 Å. 17

N 3 hυ N N crystals X X

Figure 15. Solid-State Reactivity of Phenyl Azides

Two possible mechanisms a hypothesized for the dimerization of the aryl azide derivatives within the lattice (Figure 16). 17 Dimerization can occur when two triplet phenyl nitrenes are formed adjacent to each other inside the crystal lattice. An alternate mechanism is for a triplet aryl nitrene to attack an adjacent ground state aryl azide. Upon rearrangement and loss of molecular nitrogen diphenyl-1,2-diazobenzenes derivatives are formed.

X N . . 3 N. . N N N X X X X

. N N. 3 N N N N + + N N X X N N X X -

Figure 16. Reaction Mechanisms of Phenyl Azides in the Solid-State

Objective:

This research is focused on determining if intramolecular sensitization can be used in solution and solid state irradiations to create triplet alkyl nitrenes. Triplet alkyl nitrenes were chosen for study because:

1. The triplet is the lowest energy excited state

2. Triplet molecules are spin forbidden from rearranging into imines directly.

3. Calculations indicate that the barrier to form the imine from a singlet nitrene is

very small, from 0-2 kcal/mol. 18 This means that the lifetime of the singlet

alkyl nitrene is most likely nonexistent, or extremely short lived.

The triplet sensitizer chosen in these studies was acetophenone. Acetophenone was chosen for a variety of reasons.

1. The triplet energy of acetophenone is similar to that of the triplet excited alkyl

azide. The triplet energy of acetophenone and most of its derivatives is

approximately 310 kJ/mol or lower. 19 The triplet energy of an excited triplet

alkyl azide has been estimated at approximately 314 to 335 kcal/mol. 20 This

means that the energy transfer will be a slightly endothermic process.

2. Aryl ketones undergo intersystem crossing at a rate of 10 -11 s -1.11 This is faster

than diffusion, so all reactivity that we observe should be from triplet species.

3. Aryl ketones have a strong absorption in the UV range of 260-400 nm. 11 An

alkyl azide has a narrow, weak absorption at 285 nm. This allows for

exclusive excitation of the aryl ketone chromophore with a Pyrex filter.

4. Intermolecular sensitization of alkyl azides with acetophenone resulted in

creating products which could be attributed to trapping of the triplet alkyl

nitrene. 13

When the molecule is irradiated with light above 300 nm only the aryl ketone chromophore is excited (Figure 17). It will then rapidly intersystem cross to the triplet state. From the triplet excited ketone a variety of process are available. The triplet excited ketone can phosphoresce back to the ground state or it can transfer its energy to the alkyl azide moiety in the cases of Azides 1, Azides 2 and Azides 3 .

O *3 O O Energy *3 O N N υ 3 Transfer 3 N3 h n n -N 2 N n n >300nm X X X Excited Triplet Excited Triplet X Aryl Ketone Alkyl Azide Triplet Alkyl Nitrene Figure 17. Intramolecular Sensitization of an Alkyl Azide with Acetophenone to Form a Triplet Alkyl Nitrene

Triplet energy may be transferred through space or through the bonds of the molecule. 10 Through space energy transfer may not be the mechanism in which formation of the triplet alkyl nitrene is formed in the case of Azides 1 (Figure 18). When two conjugated chromophores are located in close proximity of each other, as in Azides 1 there can be overlap of the π-orbitals, creating in a sense one chromophore. While this is not energy transfer in the traditional sense, the term energy transfer will be used here.

N O . . N C . . N R C H 2

Figure 18. Possible πππ-Orbital Overlap of the Aryl Ketone Chromophore and the Alkyl Azide

Any of the above mentioned methods of energy transfer will create the triplet excited alkyl azide, which will expel molecular nitrogen and form the triplet alkyl nitrene. This method completely bypasses the singlet manifold of the alkyl nitrene.

In this research project three different groups of alkyl azides containing aryl ketones were synthesized (Figure 19, Table 3). These include the 2-azido-1- phenylethanone derivatives ( Azides 1 ), the 3-azido-1-phenylpropanone derivatives

(Azides 2 ) and the 4-azido-1-phenylbutanone derivatives ( Azides 3 ).

O O O N 3 N3 N3

X X X 2-Azido 1-Phenyl 3-Azido 1-Phenyl 4-Azido 1-Phenyl Ethanone Propanone Butanone Azides 1 Azides 3 Azides 2

Figure 19. Classes of Molecules Studied in This Research

Table 3. Molecules Studied In This Research

X= Azides 1 Azides 2 Azides 3

Br 1a 2b

Cl 1b 2a

Ph 1c

OMe 1d 2c 3a

Desyl 1e

O-CH 2-O 1f

CN 1g t-butyl 3b

OH 3c

O N3

O Azide 1f N3 Azide 1e O

The 2-azido-1-phenylethanone derivatives ( Azides 1 ) can undergo two competing reactions from the triplet excited ketone (Figure 20).21 Energy transfer from the excited ketone is in competition with α-cleavage. This competition of reaction allows for both benzoyl radicals and triplet alkyl nitrenes to be present in solution. Benzoyl radicals are known to be excellent traps of triplet species, such as oxygen, and therefore can be expected to trap triplet alkyl nitrenes in bimolecular reactions.22

O O α-cleavage . . CH2 N3 N3 X 3 O . X energy N. Azi des 1 transfer

X 2

Figure 20. Competing Reactions of the Excited Triplet Ketone Azides 1

In the solution irradiation of 3-azido 1-phenyl propanone derivatives ( Azides

2), α-cleavage of the excited ketone is not expected (Figure 21). The CH 2 radical formed from α-cleavage would be an extremely high energy species, and its formation is not expected. This will allow for study of the triplet alkyl nitrene without an in situ trap.

O O energy transfer N N3 X X Azi des 2 29

Figure 21. Possible Reaction Pathways of Azides 2

Solution irradiation of 4-azido-1-phenylbutanone have been known to undergo intramolecular hydrogen abstraction to form 1,4-biradicals (Figure 22).23 This reaction will be in competition with energy transfer to the azide moiety in Azides 3 . The 1,4- biradical created from intramolecular hydrogen abstraction by the excited ketone is not expected to be a trap for the triplet alkyl nitrene.

O . N.

1. Energy Transfer X 37 2.-N 2

O hυ OH

N3 N3 . .

X 1. Hydrogen Abstraction X 38 Azi des 3

Figure 22. Competing Reactions of Azides 3

It has been shown that an azide group at the γ- position is capable of intramolecular quenching of excited ketones. 24 Azides act as an energy sink because they are able to dissipate energy by losing nitrogen gas in an irreversible process.

An excited triplet ketone can be formed through two types of electron promotion. 11, 23 When an electron in the π−bond of the carbonyl is promoted to the antibonding π orbital a π−π * triplet carbonyl is created. These excited intermediates are generally not found to give products. The π−π * triplet ketone is instead found to decay back to the ground state. The phosphorescence spectra of a π−π * ketone is generally strong featureless bands because of the forbidden nature of the carbonyl coupling with the benzene ring.

Promotion of one of the non-bonding electrons of the carbonyl oxygen to the antibonding π-orbital gives an n-π* triplet ketone. The n-π* excited triplet ketone is thought to be responsible for the majority of ketone photoreactivity, including α-cleavage and hydrogen atom abstraction. The n-π* carbonyl phosphorescence spectra shows bands with splittings due to vibrational coupling with the carbonyl.

The ground state triplet of acetophenone is mainly n-π* in configuration, with an energy 310 kJ/mol in energy (Table 4). In non-polar solvents, such as toluene, the phosphorescence spectra of acetophenone has the characteristics of an n-π* triplet excited carbonyl. 19 In polar solvents, such as acetonitrile, acetophenone has a phosphorescence emission which is attributed to the π−π * triplet excited carbonyl.

This switching of lowest excited triplet states of acetophenone indicates that the

π−π * and n-π* triplet excited states are very close in energy. 11 The lowest energy triplet state can be determined by substituents located on the aryl ring and by solvent.

Substituents such as halogens and alkanes lower the energy of the n-π* triplet ketone.

Addition of a methoxy group, phenyl group, or cyano group to the ring causes the lowest energy excited triplet state to be π−π * in nature. Due to the fact that the two states are so close to each other in energy, it is very possible that reactivity in Azides 1 can arise from both the first an second lowest energy excited triplet aryl ketones, regardless of whether the n-π* or π−π * triplet excited state is lower in energy.

Table 4. The Triplet Energy and Type of Excited Triplet Ketone of Selected

Acetophenone Derivatives

Acetophenone Triplet Energy 19 Lowest Energy Excited Derivative (kj/mol) Triplet Ketone Acetophenone, (R=H) 300 n-π*

4’Chloroacetophenone ( Azide1b ) 302 n-π*

4’Bromoacetophenone (Azide1a) 297 n-π*

4’Phenylacetophenone (Azide1c) 255 π-π*

4’Methoxyacetophenone (Azide1d) 300 π-π*

3’4’(Methylenedioxy)acetophenone 283 π-π*

(Azide1f)

4’Cyanoacetophenone (Azide1g) 281 π-π*

It was important that the photochemistry of the internal sensitizer acetophenone is understood, in order to determine if the products observed were derived from nitrenes or excited acetophenone. When acetophenone and its derivatives are irradiated in hydrogen donating solvents such as alcohols and toluene, it undergoes photoreduction to 1- phenylethanol derivatives. 10

Substituents such as t-butyl or phenyl groups located on the α position can encourage α-cleavage reactions (Figure 23). These groups encourage α-cleavage by creating stable alkyl radicals and the benzoyl radical.

O O . OH OH H atom H atom R R R . abstraction . R abstraction

α-cleavage

O . . R

Figure 23. Photoreactivity of Acetophenone Derivatives in Solution

Preparation of Alkyl Azido Aryl Ketones

All of the alkyl azido aryl ketones studied here were prepared via a simple displacement reactions found in the literature. 6,25 The chloro or bromo precursors were dissolved in ethanol or DMSO and a solution of sodium azide in water was added

(Figure 24).

O O NaN X 3 N3 Ar n Ar n

Figure 24. Displacement Reaction of Alkyl Halides to Create Alkyl Azides

Chapter 1: Photolysis of Azides 1 in Solution and the Solid State

Product Studies of Solution Irradiation of Azides 1

Solution photolysis was chosen as a method of attempting to trap the triplet alkyl nitrene in bimolecular reactions. Solution irradiations are likely to yield bimolecular products because of the high degree of translational and rotational freedom; solutions allow for reactive intermediates to collide. To further encourage bimolecular reactivity of the triplet alkyl nitrene, toluene was chosen as the solvent, because it is an excellent hydrogen atom donor. After toluene loses a hydrogen atom via homolytic hydrogen- carbon bond cleavage it forms a very stable benzyl radical, which can also act as a bimolecular trap for triplet alkyl nitrenes.

O N Ar 3 1

α-Cleavage Nitrene β-cleavage . Formation - CH2N3

- N2

O O .. O O ν . h O N N N Ar Ar Ar Ar Ar . -N2 Benzoyl radical, 3 Nitrene 2 Acetophenone radical 6

O O O Ph Ar N Ar Ar H N O 7 4 5

Figure 25. Reaction Scheme of Azides 1 in Solution Photolysis of Azides 1 in solution at room temperature gave reaction mixtures containing acetophenone derivatives, 7 , benzaldehyde derivatives, 4 and the major photoproduct, N-benzoylbenzamides, 5 (Table 5). 26 The majority of reactivity was found to arise from the competing reactions of α-cleavage of the excited triplet ketone and energy transfer from the excited triplet ketone to the azide moiety (Figure 25). This created two reactive intermediates in solution, the benzoyl radical and the triplet alkyl nitrene, than can react with each other and the resulting radical abstract a hydrogen atom from the solvent to form 5.

Benzoyl radicals can be formed in solution via two mechanisms. The excited triplet n-π* ketone can undergo α-cleavage forming the benzoyl radical. This can also be

competing with rearrangement of the triplet alky nitrene and loss of CH 2=N (Figure 26).

-CH2N3

O _ O + hυ O *3 -N _ 2 . -CH N . O N N N + . 2 Ar N C N N N Ar H Ar C . 2 C H Ar 1 H 2 2 3 2

Figure 26. Formation of Benzoyl Radicals in Irradiation of Azides 1

It has been observed that triplet phenyl nitrenes abstract hydrogen atoms from solvent in competition with dimerization with other triplet phenyl nitrenes. 7 This indicates that the rate of hydrogen atom abstraction by triplet aryl nitrenes must be slow since it is competitive with dimerization.

Triplet aryl nitrenes can also be trapped in bimolecular reactions with molecular

22 oxygen. Interestingly, benzoyl radicals can also be trapped by O 2. The photochemistry of benzoyl radicals has been studied for decades. 27 Benzoyl radicals have been found to be slow to abstract hydrogen atoms from hydrogen donating solvents.

The benzoyl radical is well known to be trapped by triplet oxygen to make benzoic acids

28 (Figure 27).

O hυ O O O2 . Ar R Ar Ar OH 28 . R

Figure 27. Benzoyl Trapping of Molecular Triplet Oxygen

It is not unreasonable to believe that the benzoyl radical, a triplet species trap, can behave as in situ traps for triplet alkyl nitrenes.

Trapping of a triplet alkyl nitrene by a benzoyl radical leads to an N centered benzoyl benzamide radical. This radical can abstract a hydrogen atom from the solvent to yield benzoyl benzamide derivatives, 5. This mechanism explains the formation of the major photoproduct in all Azides 1a-g studied (Figure 28).

H O O O . O . RH N. N Ar Ar . + N Ar Ar Ar Ar 5 3 2 O O + . R

Figure 28. Formation of Benzoyl Benzamide Derivatives ( 5)

Benzaldehyde derivatives, 4, were formed by α-cleavage of the triplet aryl ketone, followed by abstraction of a hydrogen atom.

Acetophenone derivatives, 7 can be formed by two possible mechanisms. Triplet alkyl nitrene dimerization forms 6, 2-(3-oxophenylethylazo)-1-phenylethan-1-one, that upon further photolysis expels molecular nitrogen to form acetophenone radicals.

Molecule 6 was never isolated. It may be difficult to isolate 6, as it is most likely formed in solution at very low concentration, and is expected to be highly photoreactive.

Acetophenone radicals can also be formed by β-cleavage of the excited ketone

(Figure 28). While triplet excited ketones are likely to undergo α-cleavage, β-cleavage is a relatively rare process. Triplet excited ketones are normally only observed to undergo

β-cleavage when a highly electronegative atom is located in the β position of an aryl ketone. 28

Table 5. Product Ratios of Various Azides 1 in Solution at Room Temperature

Azide 1 5 7 4

X=H 90 7 3

A 90 10

B 100

C 77 16 7

D 100

F 77 16 7

G 71 12 3

It was of interest to note that when Azide 1g was irradiated in solution two additional products were observed that were generally not observed in the solution

irradiations of other Azides 1 that were studied (Figure 29). These products were

identified as 4-(2-benzylamino-acetyl)-benzonitrile and 4-[(2-benzyl)(-2-(4’-

cyano)benzaldehyde)amino-acetyl)-benzonitrile. This can be due to the electron

withdrawing ability of the cyano group increasing the lifetime of the triplet alkyl nitrene.

NC Azi de 1g hυ Solution

O O CN H H N N 11 5 O NC NC

O O O CN N H O NC 12 NC 7 NC 4

We attempted to correlate the product ratios listed in Table 4 with the electron

Configuration of the triplet excited state of the ketone in Azides 1 . α-Cleavage reactions

are generally thought to arise from the n, π* excited state, whereas triplet energy transfer

can arise from both the n, π* and the π ,π* manifolds. The triplet energy and the electronic

configuration of the lowest excited triplet ketone in Azides 1 were assumed to be

identicle to the analogus ketones without azido substituents. 19 The first excited triplet

state of Azides 1a -c can be expected to have an n, π*configuration whereas in Azides 1d -

f the π,π* excited state is expected to be lower in energy. We speculate that in Azides 1, the α-cleavage comes from the n, π* triplet excited states whereas the triplet energy transfer takes place from the π,π* excited state. Photolysis of Azides 1 yield similar amount of α-cleavage products, presumably since that the first and second triplet excited states are in equilibrium with each other 11 , and thus observed reactivity arises from both.

Even though Azides 1d -f have the first excited triplet state with an expected π,π* configuration, they do not yield a lower percentage of products attributed to α-cleavage.

Presumably, this is because the rate of triplet energy transfer from the π−π * excited triplet aryl ketone in Azides 1d-f is slower, and more endothermic than that of Azides 1a - c allowing for reaction from the n-π* excited carbonyl to compete on the time scale of energy transfer from the π−π * carbonyl.

Azides 1 can be compared to substituted valerophenones derivatives, which undergo intramolecular hydrogen atom abstraction from their n, π* triplet state, whether the electron configuration of the first excited triplet state is n, π* and π, π *. 23 It should be remembered that triplet alkyl nitrenes 2 fragment into benzoyl and imine radicals, and thus, correlating the product ratio from Azides 1 with the electron configuration of the lowest triplet excited state of the ketone is complicated.

Calculations indicate that α-cleavage is an activated process, and has a small activation energy barrier. 29 It was found that α-cleavage reactions were favored when 2- azido-1-phenylethanone were irradiated in solution at 100 oC. At this temperature almost all of the products observed were attributed to benzoyl radical formation.

When the irradiation is performed at -63 oC the ratio of products attributable to benzoyl radicals and acetophenone radicals became approximately equal (Figure 30).

The product ratios of the solution irradiation at the two different temperatures studied can be found in Table 6. The change in observed product ratios with temperature indicates that the activation energy barrier for α-cleavage is higher than that of energy transfer to the alkyl azide moiety.

O N Ph 3

hυ Toluene

O O O O H Ph Ph Ph N Ph H Ph Ph Ph 4 8 9 11 O Ph O O O O H Ph Ph Ph N N Ph Ph Ph Ph 10 5 O 12 O O 7

Figure 30. Observed Products of Solution Irradiation of 2-Azido-1-phenylethanone at Two Temperatures.

Table 6. Product Ratio of 2-Azido 1-Phenyl Ethanone at Two Temperatures

Temp. 4 8 9 11 10 5 12 7

100 oC 6% 3% 18% 1% 0% 46% 26% 0%

-63 oC 0% 0% 0% 0% 26% 60% 6% 8%

Product Studies of Solution Irradiations of 1-Azido-Adamantane in the Presence of Benzoyl Radicals

It is possible to draw a reaction mechanism for the formation of 5 where a benzoyl radical attacks a ground state azide molecule. 21 After the loss of molecular nitrogen the resulting radical would abstract hydrogen from the solvent and generate the

N-benzoyl benzamide observed as the major photoproduct of solution irradiations of

Azides 1 . This mechanism bypasses triplet alkyl nitrene formation. It was therefore necessary to determine if benzoyl radicals would react with ground state alkyl azides to form the observed solution photoproduct 5 (Figure 31).

X O O N O 3 O . . + - -N α-cleavage N N N 2 N

X -CH N 2 3 X O X X Azides 1 3 H atom abstraction

X H O N

O X 5

Figure 31. Benzoyl Radical Attack of a Ground State Alkyl Azide to Give Benzoyl Benzamides, 5

To determine if the triplet alkyl nitrene was responsible for the formation of 5 the reactivity of an alkyl azide with a benzoyl radical precursor was investigated. A model system was chosen to study the photoreactivity of a ground state azide with a benzoyl

radical, because in the systems Azides 1, 2, and 3 it is impossible to prevent intramolecular energy transfer from the excited triplet ketone to the alkyl azide.

To generate benzoyl radicals in the model study two benzoyl precursors were chosen. These were 2-benzoylpropan-2-ol, commercially available as Darocur 1173, 13 , and benzoin methyl ether, 16 . These benzoyl radical precursors were chosen because the quantum yield of benzoyl radical formation is approximately one in both cases.

The major difference between the two benzoyl radical precursor chosen is the lifetime of the excited triplet ketone. The lifetime of the triplet excited ketone of 13 is estimated at 30-50 ns, 30 while the lifetime of the excited triplet ketone in 16 which has an been estimated at 0.1 ns.31

We chose to use the alkyl azide 1-azido adamantane in this study since this alkyl azide has photochemistry which is well known and because it does not absorb light above

300 nm. 4

Exclusive excitation of the aryl ketone chromophore in this system was possible because aryl ketones have a strong broad absorption from 285 nm to 400 nm. By using a

365 nm filter we were able to ensure excitation of the benzoyl precursor exclusively.

The photochemistry of 13 has been studied previously.30 We repeated the solution irradiation of 13 and obtained the results reported previously (Figure 32). When

13 was irradiated in solution the major products were all attributed to α- cleavage of the excited triplet ketone and recombination of the benzoyl radical or hydrogen abstraction.

No products were observed which could be attributed to the 2-propanol radical. The 2- propanol radical must abstract an hydrogen atom from solvent or itself to form 2-

propanol, or to form acetone.

O O hυ . OH

OH CH3OH, + . C6H5CH3 13 3 O

O H

4 O 9 O

OMe O 8 14

. O

Figure 32. Observed Product of Solution Irradiation of Darocur 1173 (13)

The major photoproducts of the benzoyl radical were determined via GC/MS and standard authentication with GC/FID. The products were identified as 8, 4, benzoin (15), methyl benzoate (14), and deoxybenzoin ( 9). Product yields can be found in Table 7.

Table 7. Photoproducts of Darocur 1173 in Methanol/Toluene Solution

Product 8 4 15 9 14

Ratio 40% 23% 17% 10% 10%

Photolysis of 1-azidoadamantane in methanol solution, gave only the methanol traps of the 1.2 alkyl shift imine, 5-methoxy-4-aza-tricyclo[4.3.1.1 3,8 ]undecane and 4- methoxy-4-aza-tricyclo[4.3.1.1 3,8 ]undecane (Figure 33). This photochemistry of 1-azido adamantane has been previously observed by other researchers. 32

Two possible mechanisms exist for formation of the imine. The first mechanism involves forming the singlet alkyl nitrene which is followed by insertion into the adamantine ring to form the imine 4-aza-tricyclo[4.3.1.1. 3,8 ]undec-4-ene.

The second mechanism has the excited singlet alkyl azide performing a 1,2-alkyl shift while expelling nitrogen gas. Regardless of how it is formed, the imine 4-aza- tricyclo[4.3.1.1. 3,8 ]undec-4-ene is very reactive and can be trapped by methanol to give the stable products 5-methoxy-4-aza-tricyclo[4.3.1.1 3,8 ] undecane and 4-methoxy-4-aza- tricyclo[4.3.1.1 3,8 ]undecane (Figure 32).

*1 OMe hυ MeOH N N H N3 N . -N 2 .

N OMe

Figure 33. Direct Photolysis Products of 1-Azidoadamantane in the Presence of Methanol

Selective irradiation of a solution containing 13 and 1-azido adamantane resulted in a variety of products. All of the products previously observed in solution irradiations of 13 were observed again. The photolysis products of 1-azido adamantane was not observed in solution. This indicates that direct excitation of 1-azido adamantane did not occur.

Instead a new product was observed with a molecular weight of 255 g/mol by

GC/MS. The possible structures of the new products observed are 1- benzamideadamantane1 ( 16) , 4-benzoyl-4-azahomoadamantane (17 ), and 3-benzoyl-4- azahomoadamantane ( 18 ) (Figure 34). The small molecular ion peak, M would lead to the conclusion that it is 4-benzoyl-4-azahomoadamantane or 3-benzoyl-4- azahomoadamantane. The identity of this product was not firmly established however.

υ h . N. N N3

O .

O H H O O N N N H 19 18 17

Figure 34. Possible Products of 1-Azidoadamantane and Benzoyl Radicals

The new photoproducts that resulted from reaction of benzoyl radicals with 1- azidoadamantane observed in the solution irradiation of 1-azido-adamantane with 13 could arise for three possible reasons.

1. The lifetime of the excited triplet ketone of 13 was long enough to

allow for energy transfer to the 1-azido-adamantane forming the triplet

alkyl nitrene (Figure 35). The triplet alkyl nitrene can then react with

the benzoyl radical.

2. It is possible that the benzoyl radical could be reacting with a ground

state alkyl azide.

Since a new product which appeared which is due to the reaction of the

benzoyl radical and 1-azido-adamantane was observed this line of research was

halted and benzoyl radical precursor 16 was used exclusively. The products of

this reaction were not fully characterized.

*3 O O υ h *3 *3 OH OH N3 N + + O

N3 OH

Figure 35. Energy Transfer from Darocur 1173 to 1-Azido Adamantane

When we repeated the solution irradiations of 19 we obtained the same results as previously observed . 31 Solution irradiation of 19 in solution gave products that result from the benzoyl radical included 4, 14 , 9, 8, and 15 . The α-methoxy toluene radical is believed to yield both optical isomers of 1,2-dibenzyl, 1-methoxyethane, 20 and 1,2- dimethoxy, 1,2-dibenzyl ethane, 21 (Figure 36). Product ratios from solution irradiations of benzoin methyl ether can be found in Table 8.

O O O . H

OMe 19 3 4 hυ O CH OH 3 OMe

C6H5CH3 14 O O O

OH O 9 8 15

. OMe MeO OMe 21

OMe

Figure 36. Solution Photochemistry of Benzoin Methyl Ether

Table 8. Photoproduct Yields of Benzoin Methyl Ether in Solution

Product 4 14 9 8 20 21 Yield 9.4% 10% 8.6% 4% 52% 4%

When a solution of 19 and 1-azido-adamantane was photolyzed no products were observed which could be attributed to trapping of the ground state alkyl azide by a benzoyl radical. All the observed reactivity was due to the benzoyl radical and the 1- methoxy-1-phenyl methyl radical. This experiment indicated that benzoyl radicals will not react with ground state alkyl azides (Figure 37).

The different products observed depend on the benzoyl precursor used led to the belief that the longer lived triple ketone of 13 appears to not only act as a generator of benzoyl radicals, but also as a triplet sensitizer to 1-azido-adamantane. Presumably 16 is not capable of intermolecular sensitization, and therefore products were only observed arise from benzoyl radical and 1-methoxy-1-phenyl methane radical.

N3 N N3 hυ 3 + O O O . . OMe OMe O 8

OMe

Figure 37. Observed Products of Solution Irradiations of 1-Azido Adamantane and 16

Product Studies of Solution Irradiation of Azide 1e

The photochemistry of Azide 1e was also investigated to determine whether subsituents on the α− position would affect the photoreactivity in comparison to the other

Azide 1 derivatives. When Azide 1e was photolyzed in solution the products were found to be the 1,2-acyl shift product, N-benzylidenebenzamide, 22, and products 4, 8, 9 and benzonitrile, 23 (Table 9). Numerous mechanisms can explain the formation of product, including α-cleavage (Figure 38).

O β-cleavage Ph Ph

N3 energy transfer hυ α-cleavage * O O O hυ Ph . O Ph Ph Ph Ph Ph . Ph N . 3 Ph . . N N. N Ph Ph Ph N . O O O O 6 O Ph Ph Ph N Ph Ph N Ph H Ph Ph 4 8 O Ph N Ph 9 23 24 22

Figure 38. Solution Irradiation of Azide 1e

From the product studies we can conclude that a phenyl group located on the α position of a 2-azido-1-phenylethanone molecule has a significant effect on reactivity in comparison to 2-azido-1-phenylethanone itself. Irradiation of Azide 1e in solution did

not lead to a major solution photoproduct which could be attributed to bimolecular trapping of the triplet alkyl nitrene.

The major photoproduct that was observed the1,2-acyl shift product, 22, benzylidenebenzamide can be formed via two mechanisms.

1. Formation of the triplet alkyl nitrene, followed by 1.2 intramolecular acyl shift will yield product 22.

2. Alternately, α-cleavage of the triplet excited ketone will yield the the benzoyl radical and the 1-azido-1-phenyl methyl radical. The 1-azido -1-phenymethyl radical can lose molecular nitrogen to form the imine radical, which can then combine with a benzoyl radical to give 21.

Product 9 can be formed via three mechanisms.

1. Dimerization of the triplet alkyl nitrene forms the azo dimer 6. Secondary photolysis

of 6, gives the deoxybenzoin radical, which then can abstract a hydrogen atom from

solvent to give product 9.

2. A benzoyl radical created by α-cleavage of the excited ketone can be trapped by a

toluene (Figure 39).

3. β-Cleavage of the excited triplet aryl ketone will yield the deoxybenzoin radical, that

can abstract a hydrogen atom to form product 9.

Table 9. Product Ratios of Azide 1e in Solution Irradiation

Product 4 8 23 24 22 9

Ratio 10% 7% 23% 3% 42% 15%

. O Ph υ O Ph h O Ph . Ph α-cleavage Ph Ph N 3 9 Azide1e

Figure 39. The ααα-Cleavage Mechanism of Azide 1e for the Formation of Deoxybenzoin, (9)

A number of possible reasons exist for the lack of benzoyl trapped triplet alkyl nitrene. These reasons include (Figure 40):

1. The triplet alkyl nitrene is not formed in this system, but rather formed from combination of α-cleavage radicals, the benzoyl radical and the N-centered benzyl imine radical, of Azide 1e .

2. The intramolecular 1.2- acyl shift is faster than the combination of benzoyl radical with the triplet alkyl nitrene.

O energy O O Ph transfer 1,2-shift Ph Ph Ph Ph N N3 N . Azide 1e . 22 Ph

α-cleavage

O O . Ph Ph . . Ph Ph N 3 N .

Figure 40. Nitrene and Non-Nitrene Mechanisms for Formation of 22 in Irradiations of Azide 1e

Investigations of the existence of the triplet alkyl nitrene in the solution irradiation of Azide 1e have led to interesting results. Laser flash photolysis of solutions of Azide

1e show an intermediate having a λ max of 330 that can be attributed to the triplet alkyl nitrene of Azide 1e .33 The existence of the triplet alkyl nitrene of Azide 1e has not been confirmed with oxygen quenching.

Oxygen quenching can used in this system to determine if the UV absorbtion observed is due to the benzoyl radical or the triplet alkyl nitrene. This is possible because the rate of oxygen quenching of the benzoy radical is faster than the rate of oxygen quenching of the triplet alkyl nitrene. By waiting 100-200 ns after excitation by the laser to collect the UV spectra of reactive intemdiates, detection of the benzoyl radical is inhibited.27 The rate of trapping by oxygen of the triplet alkyl nitrene is theorized to be much slower than trapping of the benzoyl radical. The product of benzoyl trapping with

O2 is UV inactive in the region the triplet alkyl nitrene is observed. This allows the triplet alkyl nitrene to be detected without benzoyl radical absobtion.

It is most probable that product 22 is formed by a nitrene and a non-nitrene mechanism (Figure 40).

Presumably bimolecular trapping of the triplet alkyl nitrene is not observed in solution irradiations of Azide 1e because intramolecular reactions can have faster rates than intermolecular reactions. Diffusion through solution limits the rate of intermolecular reactions to a maximum rate of 10 -10 s. It is possible that an intramolecular 1.2 acyl shift could have a faster rate constant. It must also be recognized that the effect of a solvent cage on radical recombination could make it complicated to determine the actual mechanism.

O O 1.2 acyl shift Ph N . Ph N O O υ . Ph h Ph Ph Ph Ph Ph . N3 N X . 1.2 phenyl O shift O Ph . Ph N . Ph N 22 Ph

Figure 41. Possible Intramolecular Shift Products for Azide 1e

If formed the triplet alkyl nitrene intermediate of Azide 1e can undergo two different intramolecular shifts. The product which are formed include the 1.2 phenyl shift product, 1-phenyl-2-phenylimino ethanone, and the 1.2 acyl shift product, 22 are allowed in the triplet alkyl nitrene, yet in solution irradiation only 22 is observed (Figure

41).

Selective formation of product 22 can be explained by recognizing that formation of products is not due to a nitrene mechanism. If product formation is only a result of α- cleavage of the excited ketone it would be impossible to form the 1-phenyl-2- phenylimino ethanone biradical intermediate.

The α- phenyl substituent has significantly increased the rate of α-cleavage in comparison to the other Azide 1 studied in this research. The increase in observed α- cleavage products is most likely due to the increased stability of the alkyl radical formed.

Solution irradiation of Azide 1e at room temperature gave a ratio of approximately 1:1 for products resulting from α-cleavage in comparison to products attributed to the triplet alkyl nitrene. Addition of the phenyl ring on the α position increases the ratio to 100 %

of all of the products formed in Azide 1e from approximately 2:1 in the other Azide 1 derivatives.

Product Studies of Solution Irradiation of 2-Azido-1- phenylethanone in an Oxygen Environment

In order to determine that the triplet nitrene was formed in solution photolysis of

Azides 1, 2-azido-1-phenylethanone was irradiated in a solution purged with oxygen. 34

Molecular oxygen was chosen as a bimolecular trap of the triplet alkyl nitrene for a variety of reasons.

1. We have shown that benzoyl radicals are able to trap triplet alkyl

nitrenes. It seemed possible that molecular oxygen, a ground state

triplet, should able to do this also.

2. Triplet phenyl nitrenes have been successfully trapped by molecular

oxygen. 22

3. We had no concerns that molecular oxygen would react with the

ground state 2-azido-1-phenylethanone.

When 2-azido-1-phenylethanone was irradiated at -63 oC the major solution product was 2-nitro-phenylethanone ( 25). By observing the nitro compound 25, we have showed that the triplet nitrene is in fact being formed upon excitation (Figure 42).

O O O . N NO2 3 . hυ, toluene N O -63 oC 2 64% -N2 2 25

Figure 42. Oxygen Trapping of 2-Nitreno 1-phenylethanone in Solution

Product Studies of Solution Irradiation of Azide 1e in an Oxygen

Atmosphere

In a further attempt to better understand the reaction mechanism of Azide 1e solution irradiation was performed under an oxygen atmosphere to trap the reactive intermediates. The products of this reaction were identified as benzaldehyde, benzoic acid and benzonitrile. No products were identified by GC/FID or GC/MS that could be attributed to trapping of the triplet alkyl nitrene by molecular oxygen.

The lack of oxygen trapped nitrene of Azide 1e could be due to two reasons.

These reasons are:

1. The triplet alkyl nitrene is not formed in this system

2. The triplet alkyl nitrene is formed, but undergoes α-cleavage or 1.2 alkyl shift

before it can be trapped by molecular oxygen.

The triplet alkyl nitrene has been trapped by molecular oxygen in other systems.

This fact would indicate that the triplet alkyl nitrene is not formed in the solution irradiations of Azide 1e . However, the phenyl ring on the α position may increase the rate of α-cleavage or 1. akyl shift of the triplet alkyl nitrene to a rate greater than that of oxygen trapping.

Phosphorescence Emission of Azides 1

To study the intramolecular energy transfer from the excited triplet ketone to the azide moiety in Azides 1 was efficient phosphorescence spectroscopy was undertaken to observe any possible quenching of the triplet ketone. At 77K in an ethanol glass acetophenone derivatives have a strong phosphorescence emission. The phosphorescence emission of acetophenne has n-π∗ character.

When the azide group is added to the α position, phosphorescence is quenched, indicating efficient energy transfer from the excited ketone to the azide moiety (Figure

43).

. O

3 200x10

Br 150 O 4'Br acetophenone 4'Br α azido acetophenone N3

100 Intensity(cps)

400 450 500 550 600 nm Figure 43. Low Temperature Phosphorescence Emission of 4’Bromo Acetophenone and Azide 1b in Ethanol.

Laser Flash Photolysis Experiments with 2-Azido 1-Phenyl

Ethanone and Azides 1

The triplet energy of the azide group in Azides 1 was estimated by measuring the rate of triplet energy transfer in Azides 1 and comparing it to their triplet ketone energies. 21

For Azides 1a and 1b Stern Volmer quenching with isoprene was used to estimate the lifetime of the triplet ketone (Figure 44). Stern Volmer quenching is a method of determining reactive intermediate lifetime when the resolution of an instrument cannot resolve the decay of the reactive intermediate.

Stern Volmer plots variations of quantum yields of a photochemical process.

Plots of Ao/A vs [quencher] yield a line with the equation 1+K[Q]. In this equation K equals the quenching constant multiplied by the excited state lifetime. By estimating the rate of quenching it is possible to obtain the lifetime of the excited state (Table 10).

3.0

2.5

2.0 /A 0

A 1.5

1.0

0.5 y=1.0344 + 0.90628*[Isoprene M]

0.0

0.0 0.5 1.0 1.5 2.0 2.5 [Isoprene] M

Figure 44. Stern Volmer Quenching of ααα-Azido Acetophenone with Isoprene

The rate of energy transfer in Azides 1d and 1e was measured directly. As these compounds do not show any phosphorescence emission due to the efficient

intramolecular quenching of the triplet ketone, we estimate that the triplet energies of the ketones are the same as the analogous ketones without azide substitutients (Table 10).

Table 10. Rate of Energy Transfer from the Ketone Moiety to the Azido Group in Azides 1 -1 Azide Estimated Slope (k qτ) from τ (ns) kobserved (s ) Triplet Energy Stern Volmer Plots (kJ/mol) 1a 311 0.9 0.9-0.09 a 2 x 10 9 1b 305 1.4 1.4-0.14 a 1.3 x 10 9 1c 299 2.82 2.8-0.28 a 6 x 10 8 1d 291 50 b 2 x 10 7 1e 275 330 b 3.0 x 10 6 1f 254 700 b 1.4 x 10 6 9 a) Assuming k q or diffusion is between 1-10 x 10 b) Measured directly with Laser Flash Photolysis

The triplet energy of the acetophenone derivatives used in this research can be found in Table 4. 19 Energy transfer was observed in all the system studied. In the case of Azide

1c the difference in energy from the triplet aryl ketone and the triplet excited alkyl azide is approximately 55 kcal/mol. The energy transfer is extremely endothermic, yet because only the reactions of energy transfer and α-cleavage are available to the triplet aryl ketone, the same reactivity is observed as in other Azides 1 .

The rates of triplet energy transfer versus the triplet energy of the ketone can be found in Figure 45. From this graph we can approximate that the triplet energy of the alkyl azide group must be approximately 310 kJ/mol. This is in an agreement with Lewis et al ., who estimated the triplet energy of simple alkyl azides to be between 314 and 335 kJ/mol. 20

Figure 45. Estimated Triplet Energy of Triplet Excited Alkyl Azides in Azides 1

Laser flash photolysis was also utilized to determine if the triplet alkyl nitrene was formed upon photolysis. 21 A solution of 2-azido-1-phenyl ethanone excited with a

308 nm laser pulse gave a transient UV with an absorption maximum at 280 nm, which has been assigned to the triplet alkyl nitrene (Figure 46). The absorption of the benzoyl radical was also observed from 370 nm to 600 nm. The spectra were deconvoluted by oxygen purging which reacts with the benzoyl radical signal in the time resolution of the detection equipment utilized.

0.10

0.05 Absorbance

0.00

300 400 500 600 Wavelength (nm)

Figure 46. Transient UV Spectra of 2-Nitreno 1-Phenylethanone in Argon Atmosphere

The absorption at 320 nm was unaffected when the solution was purged with O 2.

This indicates that the rate of oxygen trapping of the triplet alkyl nitrene is slower that 10 -

4 s -1 (Figure 47). 22

0.20 Under Oxygen' Under Argon

0.15

0.10 Absrobance

0.05

300 320 340 360 380 400 420 440

Wavelength (nm)

Figure 47. Transient Spectra of 2-Azido 1-phenylethanone Under Oxygen and Argon Atmosphere

Formation of the triplet alkyl nitrene was found to be faster than the time resolution of the laser, indicating that triplet energy transfer must occur in fewer than 20

ns (Figure 48). 22 The lifetime of the triplet aryl ketone has been measured to be between 0.9 and 0.09 ns by Stern Volmer quenching studies.

0.05 Absorbance

0 500 1000 Time [ns] Figure 48. Kinetic Trace of 2-Nitreno-1-phenylethanone.

Product Studies of Solid-State Irradiations of Azides 1a-1g:

When Azides 1 were irradiated in molecular crystals with UV light above 300 nm

N-methylene benzamide derivatives, 26 were observed by GC/MS (Figure 49). Imines similar to the ones observed in this research have been reported in the literature and are known to be very reactive. 34

This was an interesting development because the bimolecular reactivity of the solution irradiations has been translated to unimolecular reactivity by the reduction of freedom of motion. It was also of interest to us because it was significantly different than the solid-state photoreactivity of aryl azides, which generally undergo bimolecular reaction through dimerization when irradiated in molecular crystals. 17

This reaction was also unique in comparison to many solid-state photoreactions in that it could be taken to extremely high yields. 35 The reaction was not topiotatic, meaning that the crystal lattice remained intact though out the reaction.36 Instead, the crystals became powders quickly, due to escaping nitrogen gas, or the inability of 26 to fit within the unit cell of the starting Azide 1 .

The destruction of the crystal lattice during photolysis can also be due to a phenomenom known as phase separation. 37 During irradiation as product is formed within the lattice two distinct “phases” form, the starting material phase and the photoproduct phase.

Schmidt has described the concept of phase separation using solid state irradiations of cinnamic acid derivatives. 37 He theorized that the photoproduct is dissolved in a solid solution of starting material until such point that the product reaches its solubility limit. When the solubility limit is reached the product and the starting material will separate into two phases, destroying the crystal lattice.

O O α - . cleavage N3 . N CH2 X X Azide 1 Radical 3 Recombination α- cleavage Energy Transfer O

O .. 1.2 Acyl Shift N N. . X 26 X 2 Figure 49. Possible Solid-State Mechanisms for Formation of 23

Reaction can occur in the crystals via three possible mechanisms (Figure 49).

1. Formation of the excited triplet ketone can be followed by α-cleavage, creating

. . benzoyl and methylene azide ( CH 2N3) radicals. Loss of nitrogen gas from the CH 2N3

. radical leads to the N-centered methylene imine radical, CH 2=N. The two resultant

. radicals, the benzoyl radical and the N-centered methylene imine radical, CH 2=N radical inside the lattice allow for product formation.

Radical recombination in crystal lattices zeolites and matrices are well known as

15 . cage effect. The small space constraints of the crystal lattice prevent the CH 2N3 radical from polymerizing as observed in solution. The cage effect allows for the two radicals to be held in close proximity due to the lattice, encouraging formation of product 26.

2. Energy transfer from the excited triplet ketone can create the triplet alkyl nitrene. The triplet alkyl nitrene can then undergo a 1.2 intramolecular benzoyl shift to create 26.

3. Energy transfer to the alkyl azide from the triplet excited ketone will create the triplet alkyl nitrene. This intermediate will the undergo α-cleavage to form the benzoyl radical and the N-centered methyl imine radical. These radicals will then combine in the lattice to form 26.

The N-methylene benzamide derivatives, 26 are extremely water sensitive and it was only possible to observe them directly by GC/MS. In order to confirm that the product 26 was in fact formed, and it was decided to reduce the imine bond in order to characterize the more stable N-methyl benzamide product, 27 (Figure 50).

Two types of reductions were employed. 38 Solution reduction with sodium cyanoborohydride reduction yielded 27 as the major solid-state product.

Sodium cyanoborohydride is a pH dependent, selective reducing agent.38a The reducing agent and the irradiated crystals of Azide 1 are dissolved in a small amount of methanol, and the pH is closely monitored. When the pH of the reduction reaction is kept at 7 the imine bond is selectively reduced over the ketone double bond.

BTPPTB, solid state

O O O

N3 υ 1.h crystal N 2. NaBH 3CN, N MeOH X X pH>7 X

Figure 50. Reduction of 26 by Sodium Cyanoborohydride and BTPPTB

Another method that was used in order to obtain the reduced solid state product was reduction by using butyltriphenylphosphonium tetraborate (BTPPTB, Figure 50). 38b

The reducing agent BTPPTB is known to selectively reduce imines, enamines and oximes. This method has the advantage that it is not pH dependant and requires no solvent. The two solids are ground together and give 27 in high yield.

Product 27 was compared to an authentic standard synthesized via a literature method (Figure 51).39 Substituted aryl cyanides can be N-methylated to give N- monomethyl amides when they are reacted with methyl fluorosulfonate. This reaction in the presence of water yields the desired product in good yields.

N H CN O

MeOSO2F

H2O

X X

Figure 51. Synthesis of N-Methyl Benzamides

In order to further determine that α-cleavage was the mechanism responsible for product 26, 2-azido(4-methylthiolphenyl)ethanone was irradiated as molecular crystals. 36

The 2-azido-1-(4-methylthiolphenyl)ethanone derivative was chosen for two reasons.

The reasons included:

1. Phosphorescence spectra of the 4’methylthiol acetophenone show only π−π *

character, with no mixing of the n-π* higher energy excited triplet state. 19,23a

2. The energy gap between the n-π* and π−π * state is extremely large in

comparison to other acetophenone derivatives. 23a

Therefore, all observed reactivity should be from the π−π * carbonyl, which may undergo efficient energy transfer to the azide acceptor, but will not undergo α-cleavage.

For the product 26 to be formed in solid-state irradiations only two mechanisms are possible. The possible mechanisms include:

1. Energy transfer from the excited triplet ketone to the alkyl azide will

lead to formation of the triplet alkyl nitrene. The triplet alkyl nitrene

can then perform an intra-molecular 1.2 acyl shift to form 26.

2. Energy transfer from the excited triplet ketone can form the triplet alkyl

nitrene. To form 26 the triplet alkyl nitrene must then undergo α-

. cleavage to form the methylene azide radical, CH 2N3, and the benzoyl

. radical. The CH 2N3 radical will then lose molecular nitrogen and

. rearrange to form the radical CH 2=N . The benzoyl radical and the

. CH 2=N radical can then combine to form 26.

Formation of product 26 in the 2-azido-1-(4-methylthiolphenyl) ethanone would indicate that energy transfer was occurring via the π−π * excited carbonyl in the system inside molecular crystals. When irradiated in the solid-state 2-azido (4- methylthiolphenyl) ethanone showed no reactivity (Figure 52).40 The lack of reactivity in this case indicates that α-cleavage is the mechanism by which the product is formed in the solid state.

*3 O O hυ N3 N3 crystals No Reactivity

MeS MeS

Figure 52. Observed Crystalline Photoreactivity of 2-Azido-1-(4-methoxythiophenyl)ethanone

It was interesting to note that it was possible to form benzoic acid, 28 or ester derivatives, 27 , from solid-state reactions of Azides 1 (Figure 53). When irradiated solids of Azides 1 were dissolved in non-anyhdrous solvent, such as ethyl acetate and acetone, 28 was observed by GC/FID with standard authentication. Use of an anhydrous alcohol as the solvent allowed for the isolation of the esters derivatives of 27 only by standard authentication on a GC/FID or GC/MS.

We believed that products 27 and 28 were formed via addition of ROH at the carbonyl center of the 1,2 acyl shift product N-methylene benzamide (Figure 53). The identification of 28 from solid-state irradiations of Azides 1 is to be expected. Padwa et al. have reported the hydrolysis of imines to amines. It is theorized that the strained planar system of an acylimine, 26 is not resonance stabilized, and therefore more susceptible to hydrolysis.38a,b

O O O N 3 υ CH ROH h 2 OR N crystal -NCH 2 X X X Azides 1 26 28

Figure 53. Mechanism for Acid and Ester Formation in Crystalline Irradiations of Azides 1

The solid-state irradiations of Azides 1 are a rare example of α-cleavage in the solid state leading to new photoproducts. The α-cleavage reactions of triplet ketones are unusual because when α-cleavage occurs in the solid-state the cage effect of the lattice generally prevents radicals redistribution to form new products. 15 The crystal lattice is destroyed during irradiation, but this does not affect the ability of Azide 1 to form product 26.

This can be due to phase separation of the solid reaction mixture. 41 The solid matrix of the molecular crystals prohibits a variety of process from occurring. These processes include:

1. Polymerization of the methyl azide radical

2. Separation of the benzoyl radical and the methylene imine radical

Most of the previous examples of α-cleavage leading to products have often resulted from loss of carbon monoxide and combination of the resultant radicals. These solid-state α-cleavage reactions have a higher success rate for yielding new products than other systems because carbon monoxide escapes from within the crystal lattice. An example of α-cleavage leading to photoproducts is the solid state is illustrated by the crystalline irradiation of 2,6-diphenylcyclohexanone (Figure 54). 42

When irradiated in molecular crystals the triplet excited alkyl ketone undergoes

α-cleavage to give a biradical intermediate. Further α-cleavage of the ketone creates carbon monoxide, which escapes the crystal lattice, and a 1,5-biradical. This biradical then recombines to give 1,2-diphenylcyclopentane.

O O Ph O Ph hυ, crystal Ph . . Ph Ph -CO . . Ph Ph Ph

Figure 54. Solid State Photolysis of 2,6- Diphenylcyclohexanone

Product Studies of Solid State Irradiations of Azide 1e

In solid state irradiations of Azide 1e taken to low conversion only photoproduct

22 was observed (Figure 55). Product 22 was already known to be the major solution

photoproduct at 42% yield.

O O hυ N crystals

N3 22 Azide 1e

Figure 55. Solid-State Reaction of Azide 1e at Low Conversion

Photolysis in the molecular crystals of Azide 1e was found to be much more selective than solution photolysis. At low conversion, approximately five percent conversion as determined by GC/FID, crystalline samples were found to yield 21 in one hundred percent yield.

Higher conversion caused the crystal to melt, and selectivity was lost as the crystal lattice was destroyed. At higher conversion, some α-cleavage products were observed. These products were identified as 4 and 23 by standard authentication.

Product 8 was not observed, because the melted crystals were not fluid enough to allow for such combination of the benzoyl radicals.

Product Studies of Solid State Irradiations of Azide 1e in an

Oxygen Environment

In order to determine whether α-cleavage of the triplet aryl ketone or energy transfer to the alkyl azide to form triplet alkyl nitrene was responsible for product

formation in the solid state, Azide 1e was irradiated in molecular crystals under an oxygen atmosphere. 41 This experiment was expected to give an indication of which reactive intermediate was responsible for imine formation because triplet alkyl nitrenes and benzoyl radicals can be trapped by molecular oxygen. 7

When crystalline irradiations were performed with Azide 1e under an oxygen environment, the photoproducts were identified as 23 and 28. Product 28 is a result of trapping of the benzoyl radical by triplet ground state oxygen. Observation of benzoic acid from the solid state irradiation indicates that reactivity arises from α-cleavage of the excited ketone (Figure 56). Product 23 is an oxidation product the N-centered benzyl imine radical.

O O . N H . 1. h υ, solid-state

Azide1e O2 O2

O N OH

28 23

Figure 56. Observed Solid-State Photoproducts of Azide 1e in an Oxygen Atmosphere

The benzoyl radical and the N-centered benzyl imine radical can be created by two

separate α-cleavage processes. α-Cleavage can arise directly from the triplet excited

aryl ketone to yield the benzoyl radical and the benzylic radical of benzonitrile. The

benzylic radical of 1-azido-1-phenylmethane can then lose molecular nitrogen and

rearrange to form the N-centered benzyl imine radical.

Another possible mechanism for forming the N-centered benzyl imine radical and

the benzoyl radical can be due to the energy transfer from the excited triplet ketone to

the alkyl azide. The triplet excited alkyl azide will the lose N 2 to form the triplet alkyl

nitrene. The triplet alkyl nitrene of Azide 1e can then undergo α-cleavage to form the

benzoyl radical and the N-centered benzyl imine radical.

X-ray Crystallography of Azides 1

X-ray crystallography of Azides 1 was employed in order to correlate solid-state products with crystal packing and to gain insight into the reaction mechanism.

Similarities were observed in all of the structures (Table 11). Overall crystal lattice packing was determined by π-stacking interactions of the phenyl rings, as well as non- traditional hydrogen bonds of type C-H..O from the carbonyl oxygen to one of the methylene hydrogens and type C-H..N from a methylene hydrogen to one of the azide nitrogens.

Table 11. Important Distances in the Crystal Structures of Various 2-Azido1- phenylethanone Derivatives

N1-N1(Å) N1-N3(Å) N1-C8(Å) Torsion Angle(degrees) Azide (a) (b) (c) (C8-N1) 1a 3.378 3.328 2.48 76 1b1 3.707 3.366 2.48 67 1b2 3.975 3.761 2.48 67 1c 3.999 3.328 2.48 68.2 1e 5.39 3.23 2.48 76 a. Closest intermolecular N1-N1 distance, b. Closest intermolecular N1-N3 distance c. Intramolecular distance from C8-N1, d.Torsion angle around C8-N1 in molecule

All molecules were found to be held in the syn conformation. This indicates that there is a strong electrostatic interaction between the oxygen carbonyl and the positively charged azide nitrogen. This syn conformation holds the distance between the carbonyl carbon and the N1 nitrogen of the azide group at 2.48Å in all the molecules investigated. This syn conformation can be observed in the unit cell of all the Azide 1 derivatives studied

(Figures 57-60). The azide and the carbonyl are held in the same plane and the molecule is almost completely planar since the torsion angle between C4-C7-C8-N1 is less than

10 o.

Figure 57. Unit Cell Azide 1a The unit cell of Azide 1b shows two unique molecules (Figure 58). These molecules are different in the torsion angle related to the carbonyl and phenyl rings. The dihedral between the carbonyl carbon and N1 is approximately 67 o in both molecules, and the torsion angle around ketone carbon and methylene carbon in molecule 1 is –14.1 o and the torsion angle around the carbonyl carbon and methylene carbon in molecule 2 is

11.4 o . Both of the independent molecules are almost completely planar.

Figure 58. Unit cell of Azide 1b

In comparison to the unit cell of other Azides 1a, 1b, where the molecules are almost completely flat, Azide 1c is not planar (Figure 59). The dihedral angle between the phenyl rings is 37.5 o. This angle is often observed in the crystal structures of other biphenyl derivatives, as a method of preventing overlap of the π orbitals of the phenyl rings. The azide moeity is still held in a syn conformation in relation to the carbonyl.

Figure 59. Unit Cell of Azide 1c

Addition of a phenyl group at the α-position did not change the relationship in space between the carbonyl and the azide moiety (Figure 59). The molecule is no longer planar however, and the molecule shows a torsion angle of 76 o around C4 C7 C8. This is to presumably allow for greater t-stacking and π-stacking interactions of the phenyl rings.

Figure 60. Unit cell of Azide 1e

Crystal lattice packing in all of the Azides 1 studied showed many similarities

(Figures 61- 64). The distance between azide moieties was less than 4.5 Å either as a distance from N1 to N1 of another molecule or from N1 to N3 of another molecule. The short distances between adjacent azide moieties in Azides 1 theoretically allows for dimerization of azides to form molecule 6.17 In Azide 1 derivatives the azide groups crossed at either N1 or N2.

Interesting features identified in Azide 1a were the non-traditional hydrogen atom bonds, which seem to help hold the molecules together in zig-zagging sheets (Figure 60).

The phenyl rings overlap to encourage π-stacking interactions. The azide moieties cross at N2, allowing for the observed short distances between azide moeties.

Figure 61. Crystal Lattice of Azide 1a

The crystal lattice of Azide 1c shows zig-zagging layers of molecules with extensive π-stacking interactions of the phenyl rings and stacking of azide moieties

(Figure 62). T-stacking interactions are observed between the phenyl rings, but there are no hydrogen bonds in this Azide 1 derivative.

Figure 62. Crystal Lattice Packing of Azide 1c

The crystal lattice of Azide 1e shows alignment of the azide groups, presumably allowing for overlap of the azide lone pair orbitals (Figure 63). The phenyl rings have arranged themselves for the maximum π-stacking interactions with three phenyl rings being perfectly aligned within the lattice. This arrangement also allows for a t-stacking interaction between H1 and the phenyl ring.

Figure 63. Crystal Lattice of Azide 1e.

Chapter 2: Irradiation of Azides 2 in Solution and Solid

State

Product Studies of Solution Irradiations of Azides 2

Azides 2 were synthesized in order to study the reactivity of triplet alkyl nitrenes without a benzoyl radical present as an in situ trap. We believed that this would give a greater understanding of the rate of triplet alkyl nitrene dimerization versus intermolecular hydrogen abstraction by the triplet alkyl nitrene.

The three derivatives were chosen to investigate the photoreactivity of Azides 2 .

These derivatives were 3-azido-1-(4-chlorophenyl)propanone, Azide 2a , 3-azido-1-(4- bromophenyl)propanone, Azide 2b, and 3-azido-1-(4-methoxyphenyl)propanone, Azide

2c. These derivatives were chosen because they all are solids at room temperature and that they exhibit both n −π * and π−π∗ lowest energy configurations of their excited triplet aryl ketone. Azides 2a and 2b have an n-π* lowest energy configuration, while Azide 2c has a π−π * lowest energy configuration of the excited triplet aryl ketone.

Solution irradiations of all Azides 2 yielded a variety of products (Figure 64,

Table 12). These products were identified as 1-phenyl-3-(3-phenyl-pyrazol-1-yl)- propane-1-one derivatives 33, propiophenone derivatives 35, 3-(3-oxo-3-phenyl- propylamino)-1-phenyl-propenone derivatives 32, and 3-(3-oxo-3-phenyl-propylamino)-

1-phenyl propan-1-one derivatives 31. Product ratios for Azides 2 can be found in Table

9. We did not observe any products which we attributed to hydrogen atom abstraction by the triplet alkyl nitrene.

Products 31, 32, 33, and 35 were attributed to the excitation of the aryl ketone chromophore followed by energy transfer to create the triplet alkyl nitrene. In the solution irradiations of Azides 2 no benzoyl radicals were present for bimolecular reaction with the triplet alkyl nitrene. Instead the triplet alkyl nitrenes formed from the photolysis of Azides 2 underwent bimolecular reaction with another triplet alkyl nitrene or a ground state alkyl azide, or trapped by 35.

O O * O O hυ . N Ar 3 Ar N . -N Ar 2 29 NN Ar Azide 2 30

O O

Ar N Ar N O 32 H O O Ar N cis and trans Ar Ar N Ar O Ar 35 H 33 31

Figure 64. Products Isolated from Solution Irradiations of Azides 2

We were never able to isolate 3-(3-oxo-3-pheny-propylazo)-1-phenyl propan-1- one, molecule 30, and we theorize that it is extremely unstable. The proposed azo dimer,

30 conjectured in solution photolysis of Azides 2 was theorized to undergo two types of reactions to form more stable intermediates.

Presumably azo dimer 30 underwent tautomerization to form the more stable 3-

[3-oxo-3-phenyl-propyl)-hydrazonono]-1-phenyl-propan-1-one, (Figure 65). This tautomer of 30 was also not isolated because it undergoes further reaction.

1.2 H shift O O O O

Ar NN Ar Ar NN Ar 29 H

-N2

O O . . Ar Ar 34 34

Figure 65. Reacitve Pathways of the Azo dimer 26.

Tautomerization of 30 gives a secondary amine moiety which then can perform a nucleophilic attack on a carbonyl center. Attack of a carbonyl the secondary amine gives a five membered ring. Dehydration then yields product 33 (Figure 66).

O O Ar O Ar N N Ar Ar N N N O Ar N 29 H O HO Ar

-H2O

N Ar N

Ar 33

Figure 66. Formation of Product 33

Azo dimer 29 can also undergo secondary photolysis to lose molecular nitrogen and form the propiophenone radical, 35 (Figure 64). The radical 34 was found to abstract

a hydrogen atom from solvent or another solvent molecule to form 35 , or to combine with triplet alkyl nitrenes in solution to form the products 31 and 32.

The formation of propiophenone derivatives, 35, in irradiations of Azides 2 has to be due to secondary photolysis of the azo-dimer 29.

This also has implications for the solution irradiation of Azides 1 . The formation of propiophenone derivatives of Azides 2 by dimerization to 29 further supports the hypothesis that the acetophenone derivatives formed in Azides 1 are most likely due to secondary photolysis of dimer 6.

Two possible mechanisms have to be considered for the formation of product 32.

The first mechanism for creation of 32 includes formation of the triplet alkyl nitrene intermediate. Formation of the triplet alkyl nitrene is followed by trapping with 34 to give an N-centered radical. This radical then rearranges to form an imine radical.

Homolytic cleavage of a C-H bond at the carbonyl α-carbon yields product 32 (Figure

67).

O O O O hυ O H O . Ar N 3 Ar N. Ar N Ar Ar N Ar . O Azides 2 H 29 . Ar 34

O O

Ar N Ar H 32

Figure 67. Nitrene Mechanism for the Formation of Product 32

Photoproduct 32 can also be formed by a non-nitrene mechanism. A solvent radical or another reactive radical can abstracts the hydrogen located α to the azide moiety to give

an unstable α-azido radical intermediate. This radical can rearrange to form an imine radical after the loss of nitrogen gas. The rearrangement of a α-azido radical has never been reported in literature (Figure 68).

Another possible mechanism that can be considered for formation of the N- centered imine radical involves 1,4-intramolecular hydrogen atom abstraction by the excited triplet ketone. While 1,4-intramolecular hydrogen abstraction is not as favorable as 1,5- hydrogen atom transfer, it is observed in many systems where 1,5 hydrogen transfer are not possible. 23a The 1,4 hydrogen transfer will create a 1,3-biradical.

Homolytic cleavage of the β-hydrogen will create the enol imine –centered radical, which should undergo rapid tautomerization to form the N-centered imine radical (Figure 68).

O H . . R O -N O . 2 + Ar N Ar NN N Ar N. Azides 2 3 - + 1,4 Intramolecular hυ Hydrogen Abstraction RH

OH OH -N OH . 2 . Ar . N Ar N 3 Ar . N .

H + RH . R

Figure 68. Formation of N-centered Imine Radical

This imine radical can then combine with a propiophenone radical to form a tautomer of product 32 (Figure 69). Literature indicates that this is not the most stable

form of this molecule, and it will undergo hydrogen shift to form the more stable tautomer.43

* . O R . O -N2 O .

Ar N3 Ar N Ar N . 3 Azides 2 O . Ar O H O

Ar N Ar

H shift

O O

Ar N Ar H

32 cis and trans

Figure 69. Non-Nitrene Mechanism for Formation of Product 32

Formation of 3-(3-oxo-3-phenyl-propylamino)-1-phenylpropan-1-one derivatives,

32, is presumably due to trapping of the triplet nitrene with a propiophenone radical.

This creates a radical intermediate which then abstracts a hydrogen atom from the solvent to give the amine product 32 (Figure 70).

υ O O h O O . O . Ar Ar N. N3 solution Ar N Ar Azides 2 28 Ar . 33 hydrogen abstraction

O O

Ar N Ar H 31

Figure 70. Formation of Product 31

It should be pointed out that four types of possible products were not observed in this system. These four types of photoproducts include:

1. Products as a result of hydrogen abstraction by the triplet alkyl nitrene.

No products were observed which could be directly attributed to hydrogen

abstraction by the triplet alkyl nitrene, further indicating that triplet alkyl nitrenes

are very sluggish at abstracting hydrogen from appropriate solvents. 1,2-

diphenylethane is observed in the reaction mixture, but must be attributed to

hydrogen abstraction by other reactive species.

2. Products that result from Norrish type I photochemistry of the triplet excited

ketone.

Products not observed from Norrish type I photochemistry can include

photoreduction products such as 1-phenylpropan-1-ol derivatives and

benzaldehyde derivaitves formed from α-cleavage of the triplet excited ketone of

the ketone chromophore are not observed (Figure 71).

The observed products in the case of solution irradiations of Azides 2

indicates that energy transfer from the excited ketone to the azide moiety is more

favorable than other possible reactions of the triplet excited ketone despite the

increased distance between the chromophores in comparison to Azides 1 . This

. may be due to the fact that formation of ethyl azide radical, CH 2CH 2N3, should

have a much higher energy of activation barrier than α-cleavage of the triplet aryl

ketone of Azides 1 . This higher energy of activation barrier is most likely due to

the fact that rearrangement of the ethyl azide radical is not possible.

3. Products which arise from α- cleavage of the triplet alkyl nitrene intermediate

itself.

No acetophenone derivatives were observed in the product mixtures of solution irradiations of Azides 2 (Figure 71) which indcates that the triplet alkyl nitrene does not undergo α-cleavage in solution irradiation of Azides 2 . This can be due to the higher energy of the products of triplet alkyl nitrene α-cleavage in Azides 2 .

4. Products as a result of Norrish Type II photochemistry of the aryl ketone.

There were no products which could be attributed to hydrogen atom abstraction by the excited ketone.

*3 energy O υ O transfer O h O -N Ar N *3 2 3 Ar N3 Ar N 3 Ar N. Azides 2 28 . α-cleavage α-cleavage

O O . . Ar . N Ar . N 3 3

O O N Ar 3 H NH Ar 7

Figure 71. Products Resulting From ααα-Cleavage of Excited Chromophores of Azides 2

Table 12. Product Yields of Solution Irradiation of Azides 2

Azide 32 35 33 31

2a 37% Trace 63% 0%

2b 14.5% Trace 6.3% 79%

2c 0% 0% 0% 100%

A trend in reactivity was observed in Azides 2. Both Azide 2b and Azide 2c have been found to give the diamine product 31 as the major solution photoproduct. No product 31 was observed in the solution irradiations of Azide 2a . This difference in product ratios can be attributed to the absorbtion efficiency of Azide 2c . The higher conjugation of Azide 2c would make it and its photoproducts more reactive, and give higher yields of secondary photoproducts, which is observed in Azide 2c . This might

also be due to the fact that 30c is not as susceptible to nucleophilic attack due to the methoxy group, and hence less likely to cyclize.

Product Studies of Solution Irradiations of Azide 2a in an Oxygen

Environment

When Azide 2a was irradiated in solution under an oxygen atmosphere a new product was observed by HPLC along with products 32 and 35. This product was believed to be the oxygen trap of the triplet alkyl nitrene. In order to confirm this hypothesis 3-nitro (4 chlorophenyl) propanone was synthesized by standard S N2 substitution using sodium nitrate and 3-chloro (4-chlorophenyl) propanone in DMSO,

(Figure 72).

O O

NaNO2 Cl NO2 Cl Cl

Figure 72. Synthesis of 1-(4-Chlorophenyl) 3-Nitro Propanone.

A peak with a retention time which corresponded to the retention time of pure 3- nitro 1-(4-chlorophenyl) propanone was observed. This indicates that the triplet alkyl nitrene is formed in solution, and can be trapped by molecular oxygen (Figure 73).

O O O hυ . + O2 N N. N O 3 - O Cl Cl Cl

Figure 73. New Product Observed in O 2 Solution Irradiation of Azide 2a

Phosphorescence Emission of Azide 2a

In order to better understand the energy transfer from the triplet aryl ketone to the alkyl azide of Azides 2, phosphorescence spectra were obtained. All spectra were obtained at liquid nitrogen temperatures in both ethanol and 2-methyltetrahydrofuran glasses. No significant differences were observed depending on solvent.

The spectra of Azide 2a has a mixture of n-π* and π-π*character in ethanol glasses and methyltetrahydrofuran glasses.

The 0- 0 band of Azide 2a was located at 390 nm. When an azide moiety is added to the 3 position the intensity of the phosphorescence is quenched significantly.

The spectra also changes to completely n-π* in character. A shift is observed for the 0-0 and from 390 nm to 405 nm (Figure 74).

The significant reduction of intensity of phosphorescence upon addition of the azido group indicates that energy transfer is occurring readily. The ability of the azide group to quench the triplet ketone via energy transfer appears to be diminished from

Azides 1 . This decrease in energy transfer is most likely due to the extra distance

between the ketone and azide chromophores added by the additional methylene group in comparison to Azides 1 .

Calculations indicate that two conformers are energy minimum (Figure

78). One of the conformers is in an extended conformation, with the azide oriented away from the carbonyl. The second conformation has the azide moiety and the chromophore in the same plane, as a syn conformation. The extended conformation will not be as effcient at energy transfer as the syn conformation. This could explain the spectra observed. O

3 25x10 Cl

20 O

4'Chloro propiophenone in ethanol 4'C hloro 3-azido propiophenone in ethanol N3 15 cps Cl

400 450 500 550 600 nm

Figure 74. Low Temperature Phosphorescence Spectra of 1-(4-Chlorophenyl)propanone (red) and 3-Azido 1-(4-Chlorophenyl)propanone

Laser Flash Photolysis Experiments of 3-Azido 1-Phenyl

Propanone

Laser flash photolysis experiments with 3-azido-1-phenyl propanone show that an intermediate with UV absorption appears at approximately 375 nm (Figure 75).44 This absorption is very similar to the UV absorption observed in the laser flash photolysis experiments with 2-azido-1-phenylethanone (Figures 46 and 47). The difference is that the emission spectra of 3-azido-1-phenylethanone has a much sharper peak than the UV emission spectra of 2-azido-1-phenylethanone because there is no benzoyl radical absorption broadening the spectra.

The lifetime of the triplet excited ketone was estimated to be in the range of 1.5 to

0.15 ns by Stern Volmer quenching studies using isoprene.44

Oxygen quenching studies of Azides 2 in solution have not been done at this time.

0.05

Absorbance 0.00

400 600

Wavelength (nm) Figure 75. Transient UV Spectra of 3- Azido 1-Phenyl Propanone

Product Studies of Solid State Irradiations of Azides 2

In solid state irradiations of Azides 2 the photoproduct was found arise from the dimer 26 exclusively which immediately rearranges to 27 as soon as dissolving in solvent. The dimerization of the alkyl azide moieties indicated that energy transfer was found to be successful, in contrast to Azides 1 , where reactivity was found to arise from

α-cleavage of the triplet excited aryl ketone.

The selectivity observed in solid-state irradiations of Azides 2 is rare in transforming solution reactions to the solid state. Dimerization is observed in solid-state irradiations because the azide moieties are held in an orientation such that the azides are within 4.5 Å of each other (Figure 76). 17

O O O O hυ Ar Ar N3 Ar NN Ar -N N Azides 2 2 28 29 Figure 76. Solid State Photoreactivity of Azides 2

The reaction could not be taken to high conversion because the crystals melted upon extended irradiation. When melting occurs in irradiations of molecular crystals reaction selectivity is lost because the crystal lattice is destroyed. No propiophenone was observed, indicating the crystal lattice has a stabilizing effect on 26 that is not observed in solution irradiations of Azides 2 .

As found in solution irradiations of Azides 2 molecule 26 could not be isolated, because it very quickly tautomerizes to yield 27 as the only photoproduct.

The tautomerization may be occurring within the lattice of the crystal, but cyclization and dehydration are not likely to be occurring inside the crystal lattice because of the high degree of rotational freedom necessary. Product 27 is easily identified in the solid-state reaction mixture as the only product of solid-state photolysis.

Solid State Irradiation of Azide 2a in an Oxygen Environment

When azide 2a was photolyzed in an oxygen environment a new product was observed by HPLC along with the product 27 observed in argon purged solution irradiations. The new product had the same retention time as 3-nitro-1-(4- chlorophenyl)propanone which had been synthesized previously, leading to the belief that it is the oxygen trapping of the triplet alkyl nitrene intermediate. This experiment indicates that triplet alkyl nitrenes are created inside the crystal lattice, and can be trapped by oxygen, (Figure 77).

O hυ O O O2 crystal Ar N . Ar N3 Ar NO2 .

Figure 77. Trapping of Triplet Alkyl Nitrene by Oxygen in Solid State Irradiations

X-ray Crystallography of Azides 2a and 2b

X-ray crystallography was employed in order to correlate the solid-state photoreactivity of Azides 2 . While an X-ray crystal structures were obtained only for

Azide 2a and Azide 2b, it is possible to assume that all of the derivatives studied in these experiments pack in very similar conformations because the reactivity of all Azides 2 were identical (Figures 79,80, Table 13).

Table 13. Important Distances in Azides 2 in Å Azide 2 N1-N1 N1-N3

A 3.7 3.9

B 3.7 5.7

The unit cell showed that the molecule is completely linear, with the azide moeity stretched away from the rest of the molecule. This is very different from the Azides 1 which were all found to crystallize in the syn conformation (Figure 78). Azides 2a and

2b are held in an extended conformation unlike previous alkyl azides studied.

Figure 78. Syn and Gauche Conformers of Azides 2

This extended conformation prevents intramolecular reactivity. The azide has the normally observed 7 o bend to allow the lone pairs maximum space between them. The benzene ring is completely planar (Figures 79, 80). Changes in the size and electronegativity of the substituent on the phenyl ring did not appear to impact the unit cell. The change in size of substituent did affect the crystal lattice slightly.

The overall packing has remained the same, in that the crystal lattice is held together via overlap of the phenyl rings which allows for π-stacking interactions. The difference seems to be in the shortest distance between N1-N3.

Figure 79. Unit Cell of Azide 2a

Figure 80. Unit Cell of Azide 2b

In the repeating crystal lattice the molecules are in sheets held together by π- stacking interactions. The azide moieties align perfectly with the smallest distance

Figure 81. X-ray Crystal Lattice Packing of Azide 2a

between the azide groups being 4.2 Å. As shown in the reactivity of phenyl nitrenes this distance allows for dimerization of nitrenes (Figure 81). 17

100

Figure 82. X-ray Crystal Lattice Packing of Azide 2b

101

Chapter 3: Irradiation of Azides 3 in Solution and Solid

State

Product Studies of Solution Irradiations of Azides 3

The solution reactivity of 4-azido-1-phenylbutanone was studied by Wagner et al in 1979.24 This research determined the azide moiety was capable of quenching intramolecular triplet excited ketones. The rate of energy transfer from the ketone to the azide was found to be 3.7x10 8s.

Three photoproducts were observed in solution irradiations in hydrogen donating solvents and included acetophenone, 2-phenyl-∆-pyrrolidene and 2-phenyl dihydropyrrole (Figure 83). The research of Wagner and coworkers was repeated by our research group, and the results were found to be similar.37

*3 O O hυ N3 N N3 solution 41

OH . Azide 3 N . 3 N H 38 40

Figure 83. Product Isolated From Solution Irradiation of 4-Azido-1-Phenylbutanone

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When substituents were added to the acetophenone chromophore different product ratios were obtained. The molecules studied here included: 4-azido -1-(4- methoxyphenyl) butanone ( Azide 3a ), 4-azido -1-(4-t-butyl phenyl) butanone ( Azide 3b ), and 4-azido-1-(4-hydroxyphenyl) butanone ( Azide 3c ). Solution irradiation of Azides 3 derivatives lead to a variety of products determined by which aryl ketone derivative is used as the energy donor chromophore (Table 13).

All the products were a result of formation of the excited triplet ketone which led to two different reactive intermediates the triplet excited alkyl azide created by energy transfer to the alkyl azide and the 1,4-biradical formed by intramolecular hydrogen abstraction (Figure 84).

O N Energy Ar O O *3 Transfer hυ 37 N3 N3 Ar Ar OH Intramolecular H-Atom Azide 3 N3 Abstraction Ar . . 35

Figure 84. Reactive Intermediates Formed From the Triplet Ketone

Intramolecular hydrogen abstraction creates a 1.4 biradical 35 (Figure 85). This reactive intermediate can then rearrange and expel molecular nitrogen to form the N- centered radical 39. The radical 39 undergoes intramolecular radical ring closure followed by dehydration to form product 40 . Alternatively, the 1,4-biradical can also undergo cleavage to form an acetophenone enol, which will tautomerize to the ketone 7.

103

OH O OH OH -H2O N Solution N3 3 Ar . . N. Ar Ar . Ar Azides 3 hυ N Ar N 1,4 Biradical 39 H 38 40

OH O

Ar Ar 7

Figure 85. Products Resulting from Formation of the 1,4 Biradical of Azides 3

When Azide 2a was irradiated in solution the only photoproduct isolated was identified as the 5-(4-phenyl)-3,4-dihydro-2H-pyrrole derivative (Figure 86). This product was formed by energy transfer from the triplet aryl ketone chromophore to the alkyl azide chromophore. This created the triplet excited azide which can then expel nitrogen gas and form the triplet alkyl nitrene intermediate.

Two possible mechanisms exist for formation of product 40 . The first mechanism has been put forward by Wagner et al .24

1. Energy transfer from the triplet aryl ketone to the alkyl azide forms the triplet alkyl nitrene intermediate after the loss of molecular nitrogen (Figure 86). This intermediate can then abstract two hydrogen atoms from the solvent to form 4-amino-1-

(4-methoxyphenyl)-1-butanone. This intermediate was not isolated, as the primary amine

39 attacks the carbonyl. Dehydration then yields product 41. In solution irradiations of

Azide 3a the only product isolated was 41. Isolation of this single product in the case of

Azide 3a is most likely due to the completely π−π * configuration of the triplet ketone.

104

O O O hυ . . -H 2O N3 N NH Ar Ar 2 Solution Ar Ar Triplet Alkyl Nitrene N Azides 3 H 41 38 39

Figure 86. Products Resultant of Triplet Alkyl Nitrene Formation in Azides 3

This type of excited ketone is not prone to hydrogen atom abstraction, and is only capable of decaying to the ground state, or energy transfer to the alkyl azide.

2. Energy transfer from the triplet aryl ketone to the alkyl azide forming the triplet alkyl nitrene intermediate. This intermediate then can attack to aryl ketone moiety.

The resultant biradical can then abstract two hydrogen atoms from solvent to form the intermediate molecule 39 which was not isolated. Dehydration then can yield product 41

(Figure 86).

. O O O . HO H hυ . N . N N -H 0 Ar N3 N Ar Ar 2 Ar Ar Azides 3 38 41

Figure 86. Alternate Mechanism for the Formation of Product 40

While this mechanism is not necessarily attractive it should beconsidered because the triplet alkyl nitrene intermediates studied in Azides 1 and Azides 2 were not found to be prone to hydrogen atom abstraction from appropriate solvents. The alternate mechanism offered in Figure 86 bypasses hydrogen abstraction by the triplet alkyl nitrene intermediate.

Cyclization of the triplet alkyl nitrene intermediate was not observed in the solution irradiations of Azides 2 (Figure 87). Presumably this is because the steric strain

105

of ring closure to form a four membered ring is prohibitive.

. O hυ Ar Ar N. Ar N3 . N O . O Azides 3 38

O O . O hυ . X Ar Ar N Ar N . 3 N Azides 2 25 .

Figure 87. Ring Closure Reactions of Azides 2 and Azides 3

Table 13. Solution Irradiation Product Yields for Azides 3

Azide 3 42 41 40 7

R=H 19 0 67 14

A 0 90 0 Trace

B 100 0 0 0

C37 88.3 0 11.7 0

X-ray Crystallography of Azide 3c

X-ray crystallography of Azide 3c was undertaken in order to understand the crystal packing and assist in the prediction of solid –state photoreactivity. The

106

derivative Azide 3c was chosen because it had the highest melting point and was the most crystalline of all the Azides 3 synthesized.

The unit cell of Azide 3c shows that the azide moeity and the carbonyl are found in the syn conformation within molecular crystals as observed in the unit cell of all

Azides 1 (Figure 88). The phenyl ring is planar, and the azide shows the 7o bend that eases electronic strain created from the lone pairs.

Figure 88. Unit Cell of Azide 3c

In the repeating crystal lattice we have observed many interesting traits (Figure

89). The distances between nitrogen atoms in the azide groups is quite large. The N1-N1 distance is 8.33 A. The N1-N3 distance was found to be 8.15 A. These long distances would seem to prevent dimerization of the triplet alkyl nitrenes.

Another interesting point is that the hydroxyl groups are not aligned to allow for hydrogen bonding. In most phenols and alcohols this hydrogen bonding is a very prominent feature in the crystal lattice. Instead here we observe a hydrogen bonding interaction between the phenolic OH group as the hydrogen donor and the carbonyl

107

oxygen as the hydrogen acceptor. There are no obvious pi-stacking interactions in the phenyl rings, which have been observed in all the other Azides 1 and Azides 2 studied with X-ray crystallography.

Figure 89. X-ray Crystal Lattice of Azide 3c

Phosphorescence Emission of Azide 3a

Phosphorescence emission spectra obtained of 4’methoxy acetophenone at -63 oC, are almost completely π−π * in configuration (Figure 90). The phosphorescence of Azide

3b is almost as intense as that of 4’methoxy acetophenone in ethanol glasses. This indicates that energy transfer is not as efficient in these molecules as in Azides 1 and 2.

The n-0 band is shows a red shift of 2 to 3 nm. The overall shape of the transmission is the same π−π * shape, showing very little n-π* character. The 1,4 biradical is formed

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exclusively from the n-π* excited ketone, which explains that the only product observed is from the triplet nitrene.

Figure 90. Phosphorescence Emission of Azide 3b

3 15x10 p-Meothxy Acetophenone in ethanol 4'Methoxy-4 azido -1, phenyl butanone in ethanol Cl O

N3 10 cps Cl

340 360 380 400 420 440 460 480 500 520 540 560 580 600

As the azide moiety has been moved further away from the ketone chromophore the phosphorescence has increased in intensity. This indicates that distance is an important factor in intramolecular energy transfer.

Laser Flash Photolysis Experiments of 4-Azido-1-Phenyl

Butanone

The transient UV spectra of 4-azido 1-phenyl butanone show two distinct features

(Figure 91).47 The larger absorption with a maximum of 325 nm is very similar to the absorption observed in the other alkyl azides researched. There is another feature in the

109

transient spectra with a maximum at 390 nm. This has not been observed in the transient

UV spectra of other triplet alkyl nitrenes. This feature can be due to the 1,4 biradical formed from hydrogen abstraction. Oxygen quenching studies have not been performed in the case of Azides 3.

0.10

0.08

0.06

0.04

0.02

300 350 400 450

Figure 91. Transient UV Spectra of 4-Azido-1-Phenyl Butanone

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Conclusions:

This research has shown that intramolecular sensitization, using acetophenone as the triplet sensitizer, is successful in creating triplet alkyl nitrenes in solution and in the solid state. We have learned that the rate of energy transfer seems to decrease at approximately ten fold for each new CH 2 group located between the two chromophores

(Table 14). The decrease in rate may not only be due the distance between the chromophores, but also can be attributed to the ability of the azide group and the ketone chromophore to obtain a favorable conformation for energy transfer. The conformation required for energy transfer in Azides 2 and Azides 3 may have considerable steric strain which can be preventing or slowing energy transfer in comparison to Azides 1 .

Table 14. Rate of Energy Transfer from the Triplet Aryl Ketone and the Alkyl

Azide

Azide Rate of Energy Transfer (s -1 x 10 -9), 21,44,24

1 0.09-0.9

2 1.7

3 37.0

In solution we have proven that triplet alkyl nitrenes can be trapped by benzoyl radicals, as shown in the solution irradiations of Azides 1 or other triplet alkyl nitrenes, as observed in solution photolysis of Azides 2 , but are not generally suitable for abstracting hydrogen from appropriate solvents. Only in the case of Azides 3 wasit considered possible that the triplet alkyl nitrene could abstract hydrogen atoms from

111

solvent, followed by intramolecular reactivity. This research is the first time that triplet

alkyl nitrenes have been trapped in bimolecular reactions in solution.

It was found in the solution irradiations of Azides 1 and Azides 2 that reactivity is not significantly altered by the nature of the triplet excited aryl ketone. In the solution photolysis of Azides 3 it was found that the configuration of the triplet excited ketone did

play a significant role in the solution reactivity observed. When the triplet ketone had a

π−π * configuration products were only attributed to the triplet alkyl nitrene.

We have also that all of the alkyl azides studied in the solid-state showed new and interesting reactivity compared to solution irradiations. Reactions were also changed from mixtures to highly selective single products.

In solid state photolysis of Azides 1 reactivity was found to change from bimolecular reactivity to unimolecular reactivity. It was also determined that energy transfer from the excited aryl ketone chromophore to the azide chromophore ceased. In solid state irradiations of Azides 2 it was found that triplet alkyl nitrenes could be created via intramolecular sensitization. Higher reaction selectivity was illustrated in the solid state irradiations of Azides 2 which yielded a single bimolecular product in crystalline irradiations in comparison with the complex reaction mixtures observed in solution irradiations of Azides 2 .

Furthermore, it was possible to correlate this reactivity to the crystal packing of the starting azide. In the systems studied in this research it was found that not only the distance between azide moieties needed to be taken into account as illustrated in the dimerization of Azides 2 , but also intramolecular reactivity of other reactive centers was

important, as shown in the α-cleavage products Azides 1 .

112

Experimental Data:

General Procedures:

Instrumentation:

All 1H and 13 C NMR were obtained on a Bruker AC250 spectrometer at 250.13 MHz for 1H NMR spectra and 62.90MHz for 13 C NMR spectra unless otherwise noted.

Samples were dissolved in CDCl 3 and chemical shifts are referenced to TMS, 0.00 ppm,

1 13 for H, and CDCl 3, 77 ppm, for C. Infra red spectra were collected on a Perkin Elmer

Spectra One spectrometer. Samples were either neat for oils and liquids or in the form of

KBr pellets for solids unless otherwise noted. Gas chromatography with flame ionization detection was performed on a Shimadzu GC 17A with a standard 15 ft 5% diphenyl siloxane column and helium as the eluant gas. Gas chromatography with mass spectrometry detection was performed on a Hewlett Packard GC 6890 with a 5370 Mass spectrometer. Helium was used as the carrier gas, and the column was a standard 15 ft

5% diphenyl siloxane column. High pressure liquid chromatography was performed on a Shimadzu 10A series instrument with UV detection. A silica column was employed with hexanes and ethyl acetate as the eluant. Melting points were obtained on a

MEL_TEMP apparatus and are uncorrected. All X-ray structures were collected on a

Bruker SMART 1K diffractometer at low temperatures unless otherwise noted.

Phosphorescence spectra were collected on a Jobin Yovan spectrofluorimeter model

1934D at liquid nitrogen temperatures in ethanol glass. Laser flash photolysis was done at the Ohio State University. The pump was a 308nm xenon chloride excimer laser from

Lambda Physic laser. The setup has been explained in detail elsewhere. 42 All time

113

resolved UV and kinetics were collected in ethanol at room temperature and were argon

or oxygen purged.

General Procedure for Solution Irradiations :

Photolysis was accomplished using a 450 W Hanovaria lamp with a pyrex filter.

Other filters, when used are noted. Solution samples were purged with argon for five or more minutes before irradiation, unless purged with oxygen. Reaction mixtures were irradiated for 12-24 hours. Toluene was the solvent used in all cases except when noted.

Percent conversion was estimated from gas chromatography with flame ionization detection and/or 1H NMR. Solution reaction mixtures had the toluene removed en vacuo to yield orange oils. The reaction mixtures were then separated by traditional column chromatography on silica gel or alumina columns which were eluted with ethyl acetate and hexanes.

General Procedure for Solid-State Irradiations:

Solid- state samples were crushed between microscope slides and open to the

atmosphere unless otherwise noted. They were irradiated for a time period ranging from

5 minutes to 5 hours. Solid samples were not separated or further purified. Percent

conversion was determined by gas chromatography with flame ionization detection

and/or 1H NMR.

Reagents and Solvents :

All reagents were purchased from Aldrich and used without further purification.

Solvents were obtained from Fisher and used as received unless otherwise noted. The exception is the toluene used for irradiation which was distilled from sodium before use.

114

Sample Sythesis of Azides 1 6, 25:

2-Azido-1-(4-chlorophenyl)ethanone (2.0 g, 7.2 mmol) was dissolved in a solution ethanol (150 mL) and glacial acetic acid (1.5 mL). To this a solution of sodium azide

(1.7 g, 26 mmol) in water (10mL) was added. The reaction mixture was then refrigerated overnight. The reaction mixture was extracted into ethyl acetate and the organic layer was washed with saturated sodium bicarbonate (200mL x 2) and brine (200 mL). The organic layer was dried with magnesium sulfate and solvent was removed en vacuo to yield 2-Azido-1-(4-bromophenyl) ethanone .

O Azido-1-(4-bromophenyl) ethanone (1a) :

o 6 o N3 Mp (ethyl acetate/hexanes): 78-81 C, lit : 86-87 C. IR

(KBr): 2113, 1693, 816, cm -1. M/S m/z (relative Br

intensity): 200/202 (M+ -N2) (10%), 183/185 (100%),

1 155/157 (75%), 75 (75%). H NMR (250 MHz, CDCl 3): 4.53 (s, 2H), 7.73 (d, 2H, 8

13 Hz), 7.64 (d, 2H, 8 Hz) ppm. C NMR (60 MHz, CDCl 3): 54.5, 129.07, 129.14, 132.0,

132.78, 192.0 ppm. X-ray Crystallographic Data: Triclinic, P -1, a= 9.2953(3) Å, b=10.7596(3) Å, c=10.7786(2) Å, α=93.674(1) o, β=110.314(1) o , γ=111.876(1) o, Z=4,

R= 3.72%.

115

Cl 2-Azido-1-(4-chlorophenyl) ethanone (1b) : Mp

(ethyl acetate/hexanes): 69-71 o C, lit. 6: 67-70 oC. IR (KBr): 2115, 1693, 813 cm -1.

1 M/S m/z (relative intensity): 165/167 (M+-N2, 10%), 139/141 (100%), 111/113 (65%). H

13 NMR (250 MHz, CDCl 3): 4.52 (s, 2H), 7.64 (d, 2H, 8 Hz), 7.68 (d, 2H, 8 Hz) ppm. C

NMR (60 MHz, CDCl 3), 54.5, 129.1, 132.0, 132.3, 132.8 ppm. X-ray Crystallographic

o Data: Monoclinic, P2 1/c, a= 12.6761(11)Å, b=9.1007(8)Å, c=7.4679(7) Å, α=90 ,

β=93.289(2) o, γ=90 o, Z=4, R= 5.17%.

O 2-Azido-1-[1,1’-biphenyl]-4-yl-ethanone (1c): Azide 1c was N 3 synthesized following the same procedure as for Azide 1a .

Ph Mp (ethyl acetate/hexanes): 78-82 o C, lit. 6 88-88.5 o C. IR

-1 1 (KBr): 2099, 1683 cm . H NMR (250 MHz, CDCl 3): 4.59 (s, 2H), 7.45 (m, 3H), 7.64

13 (d, 2H, 5 Hz), 7.71 (d, 2H, 8 Hz), 7.98 (d, 2H, 8 Hz) ppm. C NMR (60 MHz, CDCl 3):

54.59, 126.74, 126.956, 127.6, 128.1, 128.6, 132.6, 138.9, 146.2, 192.8 ppm. X-Ray

Crystallographic Data: Orthorhombic, a= 10.5307(9)Å, b=7.9709(7)Å, c=29.396(3)Å,

α=90 o , β=90 o , γ=90 o, Z=8, R= 5.17%.

2-Azido-1-(4-methoxyphenyl) ethanone (1d): Azide O 1d was synthesized following the same procedure as N3 for Azide 1a . MeO

116

Mp (ethyl acetate/hexanes): 72-74 oC, lit 6 71-73 oC. IR (KBr): 2124, 1682, 1239cm -1.

1 M/S m/z relative intensity: 163 (1%) (M+ -N2), 135 (100%), 107 (20%), 92 (30%). H

NMR (250 MHz, CDCl 3): 3.88 (s, 3H), 4.51 (s, 2H), 6.95 (d, 2H, 8 Hz), 7.89 (d, 2H,

13 8Hz) ppm. C NMR (60 MHz, CDCl 3): 54.2, 55.2, 113.8, 127.8, 130.0, 161.2, 191.3 ppm.

O 2-Azido-1,2-Diphenyl-Ethanone (1e) . Azide 1e was

N3 synthesized by the same method as Azide 1a .

Mp (ethyl acetate/hexanes): 83-86 oC, lit. 6 125 oC. IR (KBr):

-1 2092, 1684 cm . M/S m/z relative intensity: 209 (10% (M+ -N2), 105 (100%), 77 (60%).

1 H NMR (60 MHz, CDCl 3): 5.71 (s, 2H), 7.88 (d, 2H, 7 Hz), 7.52 (t, 1H, 5 Hz), 7.36 (t,

13 7H, 7 Hz) ppm. C NMR (60 MHz, CDCl 3): 67.8, 128.2, 128.7, 128.8, 129.3, 129.5,

133.7, 133.8, 134.3, 194.3 ppm. X-ray Crystallographic Data: Orthorhombic a=

5.9414(5) Å, b=14.8154(13) Å, c=26.690(2) Å, α=90 o (1), β=90 o (1), γ=90 o (1), Z=8 , R=

4.5 %.

O 2-Azido-1-(1.3benzodioxol-5-yl) Ethanone (1f) : Azide 1f

N3 was synthesized following the same procedure as for Azide

1a . O O Mp (ethyl acetate/hexanes): 90-91 oC. IR (KBr): 2110,

-1 1 1681, 1254, 1041 cm . H NMR (250 MHz, CDCl 3) 4.47

117

(s, 2H), 6.07 (s, 2H), 6.89 (d, 1H, 8Hz), 7.46 (s, 1H), 7.48 (d, 2H, 6H) ppm. 13 C NMR

(60 MHz, CDCl 3): 54.29, 101.76, 107.37, 107.88, 124.00, 128.86, 190.87 ppm.

O 2-Azido-(4’-cyanophenyl)ethanone, 1g . Mp (ethyl

o N3 acetate/hexanes): 127-130 C. IR (KBr): 2232, 2107, 1693

-1 1 cm . H NMR (250 MHz, CDCl 3) δ 4.57 (s, 2 H), 7.82 NC (d, 8 Hz, 2H), 7.99 (d, 8 Hz, 2H) ppm. 13 C NMR (60

+ MHz, CDCl 3): 55.2, 117.5, 128.5, 132.5, 137.3, 192.2 ppm. MS (ESI): 159.1 (M -N2).

Photolysis of 1a. A solution of 1a ( 200 mg, 0.73 mmol) was irradiated in toluene

(200 mL) until 1H NMR showed 4-Bromo-N-[2-(-4-bromophenyl)-2- oxoethyl]benzamide (77 mg, 0.019 mmol, 47% yield) as the major photoproduct.

Toluene was removed en vacuo and the reaction mixture was purified on silica gel eluted

with ethyl acetate and hexanes. Two fractions of photoproducts were isolated.

The first fraction was found to contain 4’bromo acetophenone, 7a (3 mg, 0.015 mmol, 2% yield) and was identified by standard authentication on a GC/FID.

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HN O Br

The second fraction was found to be 4-Bromo-N-[2-

(-4-bromophenyl)-2-oxoethyl]benzamide, 5a (77 mg, 0.019 mmol, 47% yield). Mp.

(ethyl acetate/hexanes): 194-196 oC Lit. mp. 46 IR (KBr): 3398, 3336, 1637, 1689, 915 cm -1. M/S m/z relative intensity: 399/397/395 (M+,3%), 371/369/367 (3%), 183/185

1 (100%), 150/157 (60%). H NMR (250 MHz, CDCl 3): 4.91 (d, 2H, 3 Hz), 7.24 (s, 1H),

13 7.71 (m, 6H, 8 Hz), 7.88, (d, 2H, 8Hz) ppm. C NMR (60 MHz, CDCl 3): 47.05, 126.86,

128.25, 128.97, 129.91, 132.08, 132.93, 129.06, 129.19, 132.67, 133.37, 166.68, 193.51 ppm.

Photolysis of Azide 1b. A solution of 1b (916 mg, 1.5 mmol) in toluene (80 mL) was photolyzed over night. GC analysis of the reaction mixture showed no remaining starting material. The solvent was removed under vacuum and the resulting oil was purified on a silica column eluted with hexane in ethyl acetate.

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HN O Cl

Cl The major product isolated was 4-chloro-

N-[2-(4-chlorophenyl)-2-oxoethyl]benzamide , 5b (65 mg, 0.21 mmol, 30% yield). Mp

(Ethyl acetate/hexane): 172-174 oC. IR (KBr) 3367, 1691, 1635, 1094 cm -1. 1H NMR (250

MHz, CDCl 3) δ 4.92 (d, 6 Hz, 2H), 7.23, (s, 1H), 7.47, (m, 6 Hz, 5H), 7.80, (d, 8 Hz,

13 2H), 8.0 (d, 8 Hz, 2H) ppm. C NMR (60 MHz, CDCl 3) δ 47.0, 128.8, 129.1, 129.1,

129.2, 129.6, 129.7, 132.5, 133.0, 138.4, 141.1, 166.5, 193.3 ppm. GCMS 307/309 (M +,

2%), 168/167 (5%), 139/141 (100%).

Photolysis of Azide 1c. A solution of 1c (298 mg, 1.25 mmol) in toluene (60 mL) was photolyzed for 18 hours, when 1H NMR indicated only 40% Azide 1c remained.

The solvent was removed en vacuo and the resulting oil was purified via column chromatography on silica gel with ethyl acetate/hexanes as the eluant.

Three photoproducts were identified from the reaction mixture. The two minor photoproducts were determined to be biphenyl carboxylate, 4c, (2.4 mg, 1% yield), and

4’phenyl acetophenone, 7c (35 mg, 14% yield). These products were identified by standard authentication on GC/FID.

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HN O Ph

Ph The major photoproduct isolated was

biphenyl-4-carboxylic acid (2-biphenyl-4-yl-2-oxyethyl) amide, 5c (45 mg, 0.11 mmol, 20% yield) Mp. 212-214 oC. lit. mp: 210- 212 oC. 47 IR (KBr): 3388, 1603,

-1 1 1646cm . H NMR (250 MHz, CDCl 3): 5.02 (d, 2H, 3 Hz), 7.42 (m, 9H, 8 Hz), 7.73 (d,

3H, 8Hz), 8.11 (d, 2H, 8Hz) ppm.

Photolysis of Azide 1d: A solution of 1d (0.3956 g, 2.24 mmol) in toluene (40 mL) was irradiated for 18 hours, at which point 1H NMR showed peaks at 3.87 ppm indicating product formation. The solvent was removed en vacuo and the resulting oil was purified on a silica column with a mixture of ethyl acetate and hexanes as the eluant.

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HN O MeO

OMe Methoxy-N-[2-(-4-methoxyphenyl)-2-

oxoethyl]benzamide, 5d was isolated as a yellow oil as the major photoproduct. Lit 48

-1 1 IR (KBr): 3410 , 1640 , 1260, 1027 cm . H NMR (250 MHz, CDCl 3): 3.87 (d, 6H),

6.96 (t, 4H, 8Hz), 7.84 (d, 2H, 8Hz), 8.03 (d, 2H, 8 Hz) ppm. M/S m/z relative intensity:

299 (M+, 2%), 135 (100%), 107 (11%), 92 (17%), 77 (22%).

Photolysis of 1e: A solution of 1e (0.3728 g, 1.56 mmol) was dissolved in toluene

(10 mL). The solution was irradiated for ninety minutes and then the reaction mixture was analyzed by GC/FID. All products were determined by standard authentication with a known by GC/FID. Products were found to be Benzonitrile, 23 (23% yield),

Deoxybenzoin, 9 (15% yield), and Benzaldehyde, 4 (10% yield).

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Benzylidenebenzamide, 22 was found to be the major product at a 42% yield. It was synthesized from a known method for standard authentication.

Synthesis of Benzylidenebenzamide.

Benzylidenebenzamide was synthesisized following the method of Kupfer et al. 49

N-(Tri-methyl silyl) benzaldimine: A solution of 1,1,1,3,3,3,- hexamethyldisilazane (23.0 ml, 0.11 mol) in1.55M hexane solution of n-butyl lithium,

(64.5 ml, 0.10 mol) then the solvent was removed en vacuo until a white precipitate appeared .The resulting slurry was cooled in an ice bath and benzaldehyde (10.6 g, 100.9 mmol) was added over 10 minutes. Direct fractional distillation of the resulting solution gave the N-silyl imine (7.2g, 30.0 mmol, 30% yield ) as a pale yellow liquid. Bp: 45ºC

-1 1 (0.15mm), IR (neat): 2960, 2800, 1650, 1250 cm . HNMR (250 MHz, CDCl 3): 0.27 (s,

9H), 7.3 (m, 3H), 7.7 (m, 2H) 8.9(s, 1H) ppm. m/z relative intensity: 177 (M+, 100%)

N-methylene carboxamide : The N-silylimine (4.82 g, 20 mmol) was dissolved in

anhydrous chloroform (30ml, distilled from phosphorous(V)oxide) and the solution was

cooled to 0ºC. A solution of acyl chloride (2.78 g, 20 mmol) was added dropwise in

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anhydrous chloroform (50 mL) over 15-30 min with stirring. After the addition was

complete the mixture is refluxed for 3 hours and the solvent is evaporated en vacuo . The product was purified by fractional distillation. Bp: 116ºC (0.02 torr). IR (neat):1675,

-1 1 1620, 1595, 1570 cm . H NMR (250 MHz, CDCl 3): 7.40-7.85 (m, 6H), 8.05-8.45 (m,

4H), 8.90 (s, 1H) ppm. M/S m/z relative intensity: 209 (M+, 100%).

Photolysis of 1f . A solution of 1f (250 mg, 1.22 mmol) in toluene (50 mL) was photolyzed overnight. The solvent was removed under vacuum and the resulting oil purified on a silica column to yield four fractions. The first fraction contained (3’,4’ methylenedioxane)acetophenone, 7f (40 mg, 0.20 mmol, 16% yield), (3’,4’

methylenedioxane) benzaldehyde, 4f (15 mg, 0.091 mmol, 7% yield), (35 mg, 0.23 mmol, 19% yield) and 2-benzo[1,3]dioxol-5-yl-2oxo-ethyl)-amide benzo[1,3]dioxole-5-

carboxylic acid, 5f (60 mg, 0.18 mmol, 30% yield).

HN O O O

O The physical properties of (2-

benzo[1,3]dioxol-5-yl-2oxo-ethyl)-amide benzo[1,3]dioxole-5-carboxylic acid, 5f are

-1 1 as follows. IR (CHCl 3): 1677, 1657, 1604, 1254 cm . H NMR (250 MHz, CDCl 3) δ

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4.84 (d, 4 Hz, 2H), 6.04 (s, 2H), 6.08 (s, 2H), 6.88, (m, 2H), 7.15 (s, 1H), 7.40 (m, 4H),

13 7.63 (d, 8 Hz, 2H) ppm. C NMR (60 MHz, CDCl 3) δ 192.3, 166.5, 152.7, 150.5, 148.5,

148.0, 129.2, 128.2, 124.4, 121.8, 108.3, 108.0, 107.9, 107.6, 102.1, 101.7, 46.6 ppm..

+ HRMS calcd. for C 17 H13 NO6Na, [M+23] , 350.0641, found 350.0665.

Photolysis of Azide 1g : A solution of Azide 1g (900 mg, 5.23 mmol) in toluene

(200 mL) was irradiated 18 hours when 1H NMR showed high conversion to products.

The toluene was removed en vacuo , and the reaction mixture was purified on a silica column with ethyl acetate and hexanes as an eluant to yield three fractions.

HN NC O

CN The first fraction contained 4-Cyano-N-

[2-(4-cyanophenyl)-2-oxyethyl]benzamide, 5g and was isolate in 4.3% yield (39.2 mg,

-1 1 0.135 mmol). IR (CHCl 3): 3407, 2230, 1704, 1641, 1607, 1404 cm . H NMR (250 MHz,

CDCl 3) δ 8.14 (d, 8 Hz, 2H), 8.05 (d, 8 Hz, 2H), 7.9-7.6 (m, 4 H), 7.25 (s, 1H), 4.98 (d, 3

13 Hz, 2H) ppm. C NMR (60 MHz, DMSO-d6) δ 47.0, 118.2, 118.4, 128.2, 128.3, 132.6,

+ 132.7, 138.2, 139.7, 165.5, 195.0 ppm. HRMS (ESI): Calc. for C 17 H10 N3O2 (M -1)

288.0773. Found 288.0773.

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The second fraction was identified as 4-cyano-N-(4-cyano-benzyl)-N-[(2(4- cyanophenyl)-2-oxo-ethyl]benzamide, (0.0028 g, 0.0074 mmol) was also isolated in

1 0.0003% yeild. H NMR (250 MHz,CDCl 3): 3.2 (dd, 2H, 5Hz), 3.34 (dd, 2H, 7Hz), 5.98

(q, 2H, 5Hz), 6.95 (m, 3H, 6Hz), 7.21 (m, 2H, 4Hz), 7.81 (m, 6H, 8Hz), 8.04 (d, 2H,

13 8Hz) ppm. C NMR (60 MHz, CDCl 3): 38.7, 55.7, 115.7, 117.4, 117.6, 117.9, 127.7,

127.8, 128.8, 128.9, 129.2, 132.4, 132.5, 137.6, 137.8, 165.1, 197.1 ppm. HRMS (ESI):

Found 378.1220 Dalton

HN NC

The third fraction was found to be 4-(2-

benzylamino-acetyl)-benzonitrile,11g in 0.0014% yield (0.013g,). IR (CHCl 3): 3406,

-1 1 2233, 1667, 1607, 1521, 1422 cm . H NMR (250 MHz, CDCl 3): 4.65 (s, 2H), 4.84 (s,

13 2H) ppm. C NMR (60 MHz, CDCl 3): 38.7, 56.8, 115.6, 117.4, 127.7, 127.8, 128.7,

132.7, 132.8, 134.5, 137.7, 197.1 ppm.

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O CN N

O NC The fourth fraction was found to contain 12g. IR (KBr): 3421, 2926, 2344, 2230,1693, 1640 cm -1. 1H NMR

(250 MHz, CDCl 3): 3.20 (dd, 1H, J=5,8 Hz), 3.33 (dd, 1H, J=5,8Hz), 5.98 (q, 2H,

J=5Hz), 6.94 (m, 3H, J=3Hz), 6.97 (m, 3H, J=3Hz), 7.78 (m, 6H, J=13Hz), 8.04 (d, 2H,

13 3Hz) ppm. C NMR (60 MHz, CDCl 3): 38.7, 55.7, 115.70, 117.39, 117.57, 117.85,

127.59, 127.78, 128.75, 129.15, 129.41, 132.62, 134.69, 137.60, 137.77, 143.01, 165.10,

197.13 ppm. MS (ESI): Found 378.1220, calculated 378.1243.

Solution Irradiation of Azide 1e under Oxygen

A solution of Azide 1e (0.0116g, 0.049 mmol) in toluene, (1 mL) was purged with oxygen for five minutes. The solution was irradiated by a 450 W mercury arc lamp for thirty minutes. At this point the solution was injected on an GC/FID. Products were identified by standard authentication as Benzaldehyde, 4 (25%), Benzonitrile, 23 (25%), and Benzoic Acid, 28 (50%).

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Solution Irradiation of Darocur 1173

A solution of Darocur 1173 , 13 (0.0290 g, 0.178 mmol) and hexadecane,

(0.0065, 0.038 mmol) was combined in a 1:1 solution of methanol and toluene (2mL), and purged with argon for five minutes.

The reaction mixture found to give the following products upon irradiation with a

450 W mercury arc lamp behind a Pyrex filter: benzoin, 8 (40%), benzaldehyde, 4

(23%), benzhydrol, 15 (17%), deoxybenzoin, 9 (10%), and methyl benzoate, 14 (10%).

All products were identified using standard authentication on a GC/FID and a GC/MS.

Solution Irradiation of 1-Azido Adamantane

A solution of 1-azido adamantane , (0.0135 g, 0.0762 mmol) and hexadecane,

(0.0048 g, 0.021 mmol) was combined in a 1:1 methanol toluene solution (2 mL), and purged with argon for five minutes. The reaction mixture was irradiated using a 450 W mercury arc lamp behind a quartz filter. The reaction was found to give only one product as determined by GC/MS. This product was identified as 5-Methoxy-4-aza-

tricylo[4.3.1 3,8 ] undecane .

Irradiation of 1-Azido Adamantane with Darocur 1173, 13:

Solution photolysis of 1-azido adamantane and Darocur 1173, 13 was accomplished using a 365 nm filter of a 1:1 methanol/toluene solution (20 mL) containing Darocur 1173 , (0.0274 g, 0.17 mmol), 1-azido adamantane (0.0207 g, 0.20

128

mmol), and hexadecane, (0.0102 g, 0.06 mmol), as an internal standard and purged with

argon. Products were identified by standard authentication on a GC/FID and

identification using GC/MS. These products included the expected Darocur 1173, 13 products as observed by GC/FID and GC/MS in solution of Darocur 1173, 13 previously. A new product was observed by GC/MS with a molecular weight of 255 g/mol.

Solution Irradiation of Benzoin Methyl Ether.

A solution of benzoin methyl ether , 16 (0.0230 g, 0.103 mmol) in a 1:1 solution of toluene and methanol (2 mL) and hexadecane, (0.0048 g, 0.0212 mmol) was purged with argon for five minutes and then irradiated with a 450 Watt mercury arc lamp with a pyrex filter.

A variety of products were identified by standard authentication on a GC/FID and a GC/MS. These products were identified as benzaldehyde, 4 (9.4%), methyl benzoate,

14 (10%), deoxybenzoin, 9 (8.6%), benzil, 8 (4%), benzyhdrol , 15 (4%), 1,2-dibenzyl-

1-methoxyethane , 20 both diasteromers, (52%) and 1,2-dimethoxy, 1,2-dibenzyl

ethane, 21 (4%).

Solution Irradiation of 1-Azido Adamantane with Benzoin Methyl Ether.

A solution of 1-azido adamantane , (0.0099 g, 0.0559 mmol), benzoin methyl ether ,

(0.0100 g, 00.0446 mmol) , and hexadecane, (0.0029 g, 0.0128 mmol) was irradiated in a

1:1 solution of methanol and toluene(2mL) was purged with argon for 5 minutes.

Photolysis was accomplished using a 450 W mercury arc lamp and a 365nm filter.

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Products identified were the same as those of solution irradiations of benzoin methyl

ether alone.

X-ray Crystallography of 2-Azido-1-Phenylethanone Derivatives

Azide 1a crystallizes with two independent molecule in the unit cell, which almost related by an inversion center. Both are almost completely planar. There are two important torsion angles, that around the carbonyl carbon and N1 is approximately 67 o in both molecules, and the torsion angle around ketone carbon and methylene carbon in molecule 1 is –14.1 o and the torsion angle around the carbonyl carbon and methylene carbon in molecule 2 is 11.4 o . Molecules are arranged in stacking sheets, held in place

by four non-traditional hydrogen bonds of type C-H…N (2.69 to 2.76 Å, 127-165 o ) and three of type C-H…O (2.55 to 2.68 Å, 126-148 o ). Interactions between the π− orbitals of the phenyl rings have been maximized with there being channels between sheets. The azide groups are oriented so that they are directed towards each other, with the distance between N1 to N1 of another molecule is 3.707 Å or 3.975 Å and the distance from N1 to

N3 being 3.366 Å to 3.761 Å.

Azide 1b crystallizes in an almost completely planar configuration excepting the

torsion angles that are about the carbonyl carbon and N1 of the azide, at 76 o and the torsion angle about the ketone and methylene carbons that is 11 o . The molecules are arranged in stacking sheets, held together by non-traditional H bonds of types C-H…N,

(2.51 Å, 128 o ) and C-H…O (2.53 Å, 160.4 o) that allow for maximum π-stacking

130

interaction, with narrow channels between the sheets. In this lattice the azide moieties

cross at N2, and this allows the distances between the azides to be short, at 3.378Å for the

distance from N1 to N1, and that from N1 to N3 to be 3.328 Å.

Azide 1c has one molecule in the unit cell that exhibits three interesting torsion angles; that about the carbonyl carbon and N1 of the azide, at 68.2 o around the ketone and methylene carbons of 173.9 o and a dihedral angle of 37.5 o between the two phenyl rings. Molecules are arranged in zig-zagging sheets down the bc plane to increase π- stacking interactions, with void volumes down the ac plane. This long-range structure is held together via a network of bifurcated non-traditional H bonds of type C-H…O,

(2.53Å, 144 o and 2.55Å, 156.1 o ). The azide moieties in this crystal lattice cross at N1 with the distance from N1 to another molecule’s N1 at 3.999Å the distance from N1 to

N3 is significantly shorter at 3.328 Å.

The Azide 1e, exhibited many new crystallographic features. There is still only one molecule in the unit cell, but it is not at planar. The dihedral angle about the keto and methylene carbon is 76 o , making the molecule close like a book. The molecules are arranged in stacks to maximize π-stacking interactions. A T- stacking arrangement is

also observed between H4 and the α-phenyl ring. There are no hydrogen bonds are in this crystal structure. The azide groups are directed toward each other, and the distance from N1 to N1 one another molecule is 5.39 Å. The distance from N1 to N3 is much shorter though at 3.23 Å.

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Photolysis Conditions of Azides 1 in Molecular Crystals:

A 0.5 g sample of Azides 1 was placed in a test tube which was stoppered and purged with argon. This sample was then irradiated by a 450 W Hanovarian lamp for 3 to 4 hours. The crystals powered out within an hour. All reactions were found to go to high conversion by GC/FID. When the solid-state reaction was dissolved in any wet solvent the product was fund to be the corresponding benzoic acid by standard authentication on a GC/FID. Using a dry solvent allowed for detection of the 1.2 acyl shift imine,

X N-Methylene Benzamide, 26 product by GC/MS.

Sample Synthesis of Azides 2:

Synthesis of 3-Azido-1-(4-Chlorophenyl) Propanone

To a solution of 3-chloro-1-(4-chlorophenyl) propanone (2.0 g, 9.8 mmol) in acetone (200 mL) was added a solution of NaN 3 (2.0 g, 31.25 mmol) in water (10 mL).

The reaction was heated to 55 oC for 2 hours. It was then extracted with water (500 mL) and ethyl acetate (500 mL). The organic layer was washed with saturated sodium bicarbonate solution (300 mL) and brine (300 mL). It was then dried with MgSO 4. The solution was then filtered and the solvent removed en vacuo . The azide was purified via column chromatography with silica gel eluted with a mixture of ethyl acetate and hexanes.

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Characterization of 3-Azido-1-Phenyl Propane Derivatives

O 3-Azido-1-(4-chlorophenyl)propanone (2a):

Mp.(ethyl acetate\hexanes) 45-46.5 oC. IR(KBr): N3 2105, 1683, 1591, 1401, 836 cm -1. 1H NMR (250 Cl

MHz, CDCl 3): 3.21 (t, 2H, 6Hz), 3.73 (t, 2H, 6Hz),

13 7.44, (d, 2H, 8Hz), 7.90ppm, (d, 2H, 8Hz), C NMR (60 MHz, CDCl 3): 37.3, 45.8,

128.8, 129.1, 134.4, 139.7, 195.6 ppm. X-ray Crystallography: Triclinic, P -1, a=

3.8979(3) Å, b = 8.6911(7) Å, c = 13.8933(11) Å, α = 94.795(2)º, β = 94.495(2)º, γ =

95.972(2)º. Z=2, R= 2.87%.

O 3-Azido-1-(4-bromophenyl)propanone(2b): Azide

2b was synthesized by the same method as 2a . N3 Mp(ethyl acetate\hexanes): 52-54 oC. IR (KBr): Br 2105, 1682, 1585, 1397, 1070, cm -1. 1 H NMR (250

MHz, CDCl 3): 3.2 (t, 2H, 6Hz), 3.8 (t, 2H, 6Hz), 7.6 (d, 2H, 8Hz), 7.8 (d, 2H, 8Hz) ppm.

13 C NMR (60 MHz, CDCl 3): 37.3, 45.7, 128.5, 129.2, 131.8, 134.8, 195.8 ppm.

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O 3-Azido-1-(4-methoxyphenyl)propanone(2c):

Azide 2c was synthesized by the same method as N3 2a . MeO Mp(ethyl acetate\hexanes): 35-37 oC. IR

-1 1 (KBr):2106, 1674, 1259, 1171 cm . H NMR (250MHz, CDCl 3):3.41 (t, 2H, 6Hz), 3.9

13 (m, 7H, 8Hz), 6.9 (d, 2H, 8Hz), 7.4 (d, 2H, 8Hz) ppm. C NMR (60 MHz, CDCl 3):

36.9, 46.1, 55.2, 113.6, 129.3, 130.0, 163.5, 195.3 ppm.

General Procedure for Solution Photolysis of 3-Azido-1-Phenyl Propanone

Derivatives

Photolysis of Azide 2a: A solution of Azide 2a (0.4030g, 1.9mmol) in dry distilled toluene (200 mL) was irradiated for 48 hours until 1H NMR showed product formation. The solvent was removed en vacuo and then the resulting oil was purified on a silica column eluted with a mixture of ethyl acetate and hexanes. Three fractions were isolated. This first fraction contained 4’chloropropiophenone, 35a and

4’chloroacetophenone, 7a , as determined by standard authentication by GC/FID in trace amounts.

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N Cl N

The second fraction contained 1-(4-cholorophenyl)-3-[5-

(4-chloro-phenyl)pyrazol-1-yl]-propan1-one , 33a (9.6 mg, 0.032 mmol, 3.4% yield). It was obtained as a yellow oil. The product 1-(4-cholorophenyl)-3-[5-(4-chloro-

phenyl)pyrazol-1-yl]-propan1-one, 32a

was compared to an authentic standard by 1HNMR and HPLC with UV/Vis detection.

O O

N H Cl Cl The last product was isolated as a yellow oil and was identified as 3-(3-oxo-3-(4-chlorophenyl)-

propylamino)-1-(4-cholorphenyl)-propenone , 33a (77 mg, 0.22 mmol, 5.8% yield ).

-1 1 IR (neat): 3412, 2924, 1682, 1630, 1588, 1092 cm . HNMR (250 MHz, CDCl 3): 3.15

(t, 2H, 6Hz), 3.69 (q, 2H, 6Hz), 5.66 (d, 8H), 7.06 (dd, 2H, 5Hz, 8Hz), 7.86 (m, 3H,

8Hz), 7.60 (d, 1H, 3Hz), 7.85 (d, 2H, 7Hz), 7.88 (d, 2H, 7Hz), 10.40 (s, 1H) ppm. 13 C

NMR (60 MHz, CDCl 3): 29.36, 39.23, 91.3, 123.71, 128.15, 128.65, 129.77, 130.79,

134.38, 137.72, 148.98, 187.80 195.85 ppm. MS(ESI): Found: (M+H) 348.0520 Calc.:

348.0483

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Synthesis of 1-(4-cholorophenyl)-3-[5-(4-chloro-phenyl)pyrazol-1-yl]-propan1-one

The product 1-(4-cholorophenyl)-3-[5-(4-chloro-phenyl)pyrazol-1-yl]-propan1- one was synthesized by refluxing18 hours a solution of 3-chloro-1-(4- chlorophenyl)propanone (0.9 g, 2.02 mmol) and 3-(4-chlorophenyl)pyrazole (0.5g, 2.8 mmol) in ethanol (45mL). The solvent was then removed from the reaction mixture en

vacuo , and the resulting oil purified on a silica column with an ethyl acetate/hexane

eluant. This yielded 1-(4-cholorophenyl)-3-[5-(4-chloro-phenyl)pyrazol-1-yl]-propan1-

1 one (0.185g, 0.53mmol, 12.5%yield). HNMR (250 MHz, CDCl 3): 3.58 (t, 2H, 7Hz),

4.51 (t, 2H, 7Hz), 6.26 (s, 1H), 7.40 (m, 6H, 3Hz, 8Hz), 7.86 (d, 2H, 8Hz) ppm. 13 C NMR

(60 MHz, CDCl 3): 38.02, 44.01, 106.19, 128.64, 128.72, 129.17, 138.81, 142.44, 195.85 ppm.

Photolysis of Azide 2b : A solution of Azide 2b (0.350g, 1.38mmol) in dry distilled toluene (200 mL) was irradiated for 48 hours until 1H NMR indicated 10% conversion. The solvent was removed en vacuo and then the resulting oil was purified on a silica column eluted with a mixture of ethyl acetate and hexanes.

N Br N

Br The first fraction contained 1-(4- bromophenyl)-3-[5-(4-bromo-phenyl)pyrazol-1-yl]-propan-1-one , 33b (0.0068mg,

136

1 0.0161mmol, 2.3 % yield). H NMR (250 MHz, CDCl 3): 3.58 (t, 2H, 7Hz), 4.51, (t, 2H,

7Hz), 6.27, (s, 1H), 7.33 (d, 2H, 8Hz), 7.5-7.6 (m, 4H), 7.78 (d, 2H, 8Hz) ppm. MS (ESI

MH+): Found 434.9498, Calculated: 434.95

O O

N H Br Br The second fraction contained 3-(3-oxo-3-(4-bromophenyl)-propylamino)-1-(4-

bromophenyl)-propenone, 32b (0.0120 g, 0.0273 mmol, 1% yield). 1H NMR (250

MHz, CDCl3): 3.28 (m, 2H, 7Hz), 3.77(m, 2H, 7Hz), 5.66, (dd, 1H, 8Hz), 7.33 (d, 2H,

8Hz), 7.1-7.2 (dd, 4H, 3Hz),7.44(dd, 4H, 8Hz), 7.63 (d, 2H, 8Hz), 7.80 (d, 2H, 8Hz) ppm.

O O

N H Br Br The third fraction contained 3-(3-oxo-3-(4-bromophenyl)-propylamino)-1-(4-bromophenyl)- propan-1-one, 31b. The physical characteristics follow: Mp. (ethanol): decomposition

221 oC (0.0358 g, 0.0819 mmol, 12.6% yield). IR (KBr): 3054, 1685, 1586, 1477, 1070

-1 1 cm . H NMR (250 MHz, D 2O): 3.40 (t, 4H, 6Hz), 3.51(t, 4H, 6Hz), 7.72 (d, 4H, 8Hz),

13 7.88 (d, 4H, 8Hz) ppm. C NMR (60 MHz, CDCl 3): 39.50, 43.62, 89.91, 125.27,

128.22, 128.38, 128.51, 129.19, 131.08, 131.76, 134.72, 154.50, 191.59 196.02 ppm.

137

Photolysis of Azide 2c: A solution of Azide 2c (0.4089 g, 1.99 mmol) in dry distilled toluene (200 mL) was irradiated for 72 hours until 1H NMR showed 30% conversion to products. The solvent was removed en vacuo and the resulting oil was purified on an alumina column with a mixture of ethyl acetate/hexanes as the eluant.

O O

N H MeO OMe The product isolated was 3-(3-oxo-3-(4-methoxyphenyl)-propylamino)-1-(4-methoxyphenyl)-

propan-1-one, 32c (0.1016 g, 0.297 mmol, 29.8% yield). Mp.(ethanol): 191-193 oC. IR

(KBr): 3600, 1670, 1604, 1424, 1248, 1130 cm -1. Lit 40

Photolysis Conditions of 3-Azido-1-Phenyl Propanone Derivatives in Molecular

Crystals:

A 0.25 g sample of Azides 2 was placed between microscope slides. This sample was then irradiated by a 450 W mercury arc lamp for 3 to 4 hours. The crystals powered out within an hour. The reaction was not taken to high conversion because the crystals began to melt. All of the Azides 2 studied were found to give 1-phenyl-3-[5-

phenylpyrazol-1-yl]-propan1-one derivatives upon irradiation in molecular crystals.

138

Solution Photolysis of Azide 2a in an Oxygen Atmosphere

To dry distilled toluene was added Azide 2a, (0.0063 g, 0.0301 mmol) in dry distilled toluene (2 mL). This solution was purged with oxygen for 5 minutes. The purged solution was then irradiated with a 450 W mercury arc lamp for 1 hour. The solution was then injected on a HPLC with a normal phase silica column and UV/Vis detection. The column was washed with ethyl acetate and hexanes.

Synthesis of 3-Nitro-1-(4-chlorophenyl) Propanone

To a solution of 3-chloro (4’chloro)1-phenyl propanone, (1.01g, 5 mmol) in

DMSO (250 mL) was added a solution of NaNO 2 (0.57 g, 838 mmol) in water (10 mL).

The reaction mixture was stirred for 12 hours at room temperature. The reaction mixure was the washed with ethyl acetate (3x 200 mL) and water (200 mL). The organic layer was then washed with brine (200 mL) and the dried with magnesium sulfate. The solvent was removed en vacuo and yellow crystals were obtained. These crystals were recrystallized in ethanol to give 3-nitro 1-(4chlorophenyl) propanone, 36a (0.3155 g,

1.49 mmol, 29.8% yield). Mp 66-70 oC. IR (neat): 1688, 1591, 1557, 1216, 1093 cm -1.

1 H NMR (250 MHz, CDCl 3): 3.63 (t, 2H, 6Hz), 3.03 (4.82, 2H, 6Hz), 7.50 (d, 2H, 8Hz),

13 7.90 (d, 2H, 8Hz) ppm. C NMR (60MHz, CDCl 3): 34.4, 68.8, 128.9.5, 129.2, 133.7,

140.2, 193.5 ppm. MS (ESI): (Na+M-).236.0090 calc. 236.0090

139

Solid State Irradiation of 2a in an Oxygen Environment

A sample of Azide 2a was placed in a test tube and sealed. The tube was then purged with oxygen. The sample was then irradiated with a 450 W mercury arc lamp for approximately 4 hours. Dry distilled toluene was then added to the sample, and the sample was injected on a HPLC running on a normal phase silica column with ethyl acetate and hexanes as the eluant mixture. A peak appeared at the same retention time as

3-nitro (4’chloro)1-phenyl propanone, 36a was observed when the same method was

used.

X-ray Crystallography of Azides 2

All X-ray crystal structures were collected at liquid nitrogen temperatures. The

X—ray crystal structure of Azide 2b was collected on a SMART 1K CCD and the X-ray

crystal structure of Azide 2a was collected on the SMART 6000 CCD.

Azide 2a crystallizes with one molecule in the unit cell. The molecule is in an almost completely planar and in an extended conformation with the alkyl azide moiety at a 119 o angel from the carbonyl. The torsion angle of O1-C7-C8-C9 is only -0.4 o. The azide display a 8 o bend to release steric strain. There is no hydrogen bonding observed in the crystal lattice of this Azide 2 derivative, and the zig-zagging sheets of molecules are held together by p-stacking interactions of the phenyl rings.

Azide 2b crystallizes with one molecule in the unit cell as well. The molecule is in an almost completely planar and in an extended conformation with the alkyl azide moiety at a 119 o angel from the carbonyl. The torsion angle of O1-C7-C8-C9 is only -

140

0.4 o. The azide display a 8 o bend to release steric strain. There is no hydrogen bonding observed in the crystal lattice of this Azide 2 derivative, and the zig-zagging sheets of molecules are held together by p-stacking interactions of the phenyl rings.

Synthesis of 4-Azido-1-(4- Methoxyphenyl )Butanone

To a solution of 4-chloro-1-(4-methoxyphenyl) butanone , (2.0 g, 9.3 mmol) in

DMSO (150 mL) was added a solution of NaN 3 (1.5 g, 23.4 mmol) in water (10 mL).

The solution was heated to 55 oC for 6 hours. The reaction was then washed with ethyl acetate, (200 mL) and water (200mL). The water layer was washed then with ethyl acetate (2x 50 mL). The combined organic layers were then washed with brine (100 mL). The organic layer was then dried with magnesium sulfate. The magnesium sulfate was filtered off, and the solvent removed en vacuo . The resulting oil was then purfied by column chromatography on a silica column using a mixture of ethyl acetate and hexanes.

The product, 4-azido-1-(4-methoxyophenyl) butanone was isolated as a pale yellow solid.

Characterization of 4-Azido-1-Phenyl Butanone Derivatives:

O 4-Azido-1-(4-methoxyphenyl)butanone (3a):

o N3 Mp (ethyl acetate /hexanes): 37-40 C. IR

MeO 141

-1 1 (KBr): 2102, 1675, 1598, 1261, 1171 cm . H NMR (250 MHz, CDCl 3): 2.0 (m, 2H,

7Hz), 3.03 (t, 2H, 7Hz), 3.41 (t, 2H, 7Hz), 6.94 (d, 2H, 9Hz), 7.95(d, 2H, 9Hz) ppm. 13 C

NMR (60MHz, CDCl 3): 23.2, 34.4, 50.6, 55.1, 113.5, 129.6, 129.9, 163.3, 197.1 ppm.

MS (ESI): 242.0891(Na+M-).

O 4-Azido-1-(4-tert-butylphenyl)butanone (3b) :

N3 Azide 3b was synthesized in the same manner

as Azide 3a.

-1 1 IR (KBr): 2097, 1681cm . H NMR (250

MHz,CDCl 3): 1.33 (s, 9H), 2.02 (m, 2H, ), 3.05

(t, 2H, ), 3.39 (t, 2H, ), 7.46 (d, 2H 8Hz), 7.90, (d, 2H, 8Hz) ppm. 13 C NMR (60MHz,

CDCL 3): 23.2, 30.1, 31.9, 32.0, 32.1, 32.9, 35.0, 50.8, 126.2, 126.7, 129.2, 134.0, 156.9,

198.5 ppm.

O 4-Azido-1-(4-hydroxyphenyl)butanone (3c):

N3 Azide 3c was synthesized in the same manner as

Azide 3a. Mp: IR(KBr): 3369, 2094, 1661, HO -1 1 1207, 1176 cm . H NMR (250 MHz, CDCl 3):

2.06 (m, 2H, 7Hz), 3.04 (t, 2H, 7Hz), 3.44 (t, 2H, 7Hz), 6.02 (s, 1H), 6.90 (d, 2H, 8Hz),

13 7.91 (d, 2H, 8Hz) ppm. C NMR (60 MHz, CDCl 3): 23.8, 33.2, 35.1, 50.9, 114.4,

117.1, 132.3, 132.4, 161.4, 199.6 ppm. X- Ray Crystallographic Data: Triclinic, P -1, a =

7.3241(7) Å , b = 7.9796(7) Å, c = 9.3183(8) Å, α = 79.508(2)º , β = 86.477(3)º, γ =

67.013(2)º , Z=2, R=5.16%.

142

Photolysis of Azide 3a: A solution of Azide 3a in toluene (200mL) was irradiated for 24 hours. The solvent was removed en vacuo and the resulting oil was purified on a silica column with ethyl acetate and hexanes. The reaction mixture contained 5-(4-methoxy-phenyl)-3,4-dihydro-2H-pyrrole, 41 (0.0369 g, 0.021 mmol, ) was isolated from the reaction mixture. IR (neat): 1614, 1512, 1252, 1028cm -1. 1H

NMR, (250 MHz, CDCl 3): 2.01 (m, 2H, 8Hz), 2.88 (t, 2H, 8Hz), 4.03 (s, 3H), 4.05 (t,

13 2H, 7Hz), 6.92 (d, 2H, 8Hz), 7.82 (d, 2H, 8Hz) ppm. C NMR (60 MHz, CDCl 3): 22.4,

34.5, 60.9, 113.4, 127.1, 128.9, 161.0, 172.3 ppm.

X-ray Crystallography of Azide 3c

The unit cell of Azide 3c shows that the azide moeity and the carbonyl are found in the syn conformation within molecular crystals as observed in the unit cell of all

Azides 1 (Figure 83) . The phenyl ring is planar, and the azide shows the 7o bend that eases electronic strain created from the lone pairs. In the repeating crystal lattice we have observed many interesting traits (Figure 84). The distances between nitrogen atoms in the azide groups is quite large. The N1-N1 distance is 8.33 A. The N1-N3 distance was found to be 8.15 A. These long distances would seem to prevent dimerization of the triplet alkyl nitrenes.

143

oxygen as the hydrogen acceptor. There are no obvious pi-stacking interactions in the phenyl rings, which have been observed in all the other Azides 1 and Azides 2 studied with X-ray crystallography.

144

References

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Chapter 3.

2. Desai, P.;Schildknegt, K.; Agrios, K.A.; Mossman, C.; Milligan, G.L.; Aube, J.; J.

Am. Chem. Soc., 2000 , 122 , 7226.

3. Rozen, S.; Carmeli, M.; J. Am. Chem. Soc., 2003 , 152 , 8118.

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11. Turro, N. J. Modern Molecular Photochemistry , University Science Books,

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12. a) Moriarty, R.M.; Serridge, P. J. Am. Chem. Soc . 1971 , 93 , 1534. b)

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20. Lewis, F. D.; Saunders, W. H., Jr., J. Amer. Chem. Soc . 1968 , 90 , 7033.

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23. (a) Wagner, P. J.; Park, B.-S. Photoinduced Hydrogen Atom Abstraction by

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24. Wagner, P.J; Scheve, B.J. J. Amer. Chem. Soc . 1979 , 101, 378.

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31. Lewis, F. D. Lauterbach, R. T.; Heine, H. G.; Hartmann, W.; Rudolph, H. J. Am.

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33. Unpublished results A.D.Gudmundstdottir, laser flash photolysis of 2-Azido -1,2-

diphenyl ethanone give a spectra with a maximum absorbance of 330 nm. Laser

flash photolysis of 1,2 diphenyl ethanone give a spectra with a maximum

absorbtion of 320 nm.

34. Unpublished Results N.D. Pradeep Singh and A.D.Gudmundsdottir

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39. Unpublished results, S. R. Krishnan and A.D.Gudmundsdottir, solid state

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148

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43. Unpublished Results A.D.Gudmundsdottir, laser flash photolysis of Azides 2

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1979.

149

Azide 1a

2-Azido-1-(4-Bromophenyl)ethanone

Mp. 78-81 oC

150

151

152

153

154

Azide 1b

2-Azido-1-(4-chlorophenyl)ethanone

Mp: 69-71 oC

155

156

157

158

159

Azide 1c

2-Azido-1-biphenyl-ethanone

Mp:78-82 oC

160

161

162

163

Azide 1d

2-Azido-1-(4-methoxyphenyl) ethanone

MeO

Mp: 72-74 oC

164

165

166

167

168

Azide 1e

2-Azido-1,2- diphenyl ethanone

Mp: 83-86 oC

169

170

171

172

173

Azide 1f

2-Azido-1-(1.3benzodioxol-5-yl) Ethanone O

Mp: 90-91 oC

174

175

176

177

Azide 1g

2-Azido-1-(4-cyanophenyl) ethanone

Mp: 127-130 oC

178

179

180

181

182

Product 5a

4-Bromo-N-[2-(-4-bromophenyl)-2-oxoethyl]benzamide

HN O Br

Br Mp: 194-196 oC

183

184

185

186

187

Product 5b

4-chloro-N-[2-(4-chlorophenyl)-2-oxoethyl]benzamide

HN O Cl

Cl Mp: 172-174 oC

188

189

190

Product 5c biphenyl-4-carboxylic acid (2-biphenyl-4-yl-2-oxyethyl) amide

HN O Ph

Mp: 210-212 oC

191

192

193

Product 5d

Methoxy-N-[2-(-4-methoxyphenyl)-2-oxoethyl]benzamide O

HN O MeO

OMe

194

195

196

Product 20

N-Benzylidenebenzamide

197

198

199

Product 5f

2-benzo[1,3]dioxol-5-yl-2oxo-ethyl)-amide benzo[1,3]dioxole-5-carboxylic acid

HN O O O

O O

200

201

202

Product 5g

4-Cyano-N-[2-(4-cyanophenyl)-2-oxyethyl]benzamide

HN O NC

203

204

205

206

207

4-(2-benzylamino-acetyl)-benzonitrile

HN NC

208

209

210

211

O CN N

O NC

212

213

214

215

216

Azide 2a

3-Azido-1-(4-chlorophenyl) propanone

Mp: 45-46.5 oC

217

218

219

220

Azide 2b

3-Azido-1-(4-bromophenyl)propanone

Br Mp: 52-54 oC

221

222

223

224

Azide 2c

3-Azido-1-(4-methoxyphenyl)propanone

MeO

Mp: 35-37 oC

225

226

227

228

Product 27a

1-(4-cholorophenyl)-3-[5-(4-chloro-phenyl)pyrazol-1-yl]-propan1-one

N Cl N

229

230

231

232

Product 30a

3-(3-oxo-3-(4-chlorophenyl)-propylamino)-1-(4-cholorphenyl)-propenone ,

O O

N H Cl Cl

233

234

235

236

Product 27b

1-(4-bromophenyl)-3-[5-(4-bromo-phenyl)pyrazol-1-yl]-propan-1-one

N Br N

237

238

239

240

Product 30b

3-(3-oxo-3-(4-bromophenyl)-propylamino)-1-(4-bromophenyl)-propenone

O O

N H Br Br

241

242

243

244

245

Product 31b

3-(3-oxo-3-(4-bromophenyl)-propylamino)-1-(4-bromophenyl)-propan-1-one

O O

N H Br Br

Mp.: decomposes 212 oC

246

247

248

Product 31c

3-(3-oxo-3-(4-methoxyphenyl)-propylamino)-1-(4-methoxyphenyl)-propan-1-one

O O

N H MeO OMe

Mp.: 191-193 oC

249

250

251

252

Azide 3a

4-Azido-1-(4-methoxyphenyl)butanone

MeO

Mp-37-40 oC

253

254

255

256

Azide 3b

4-Azido-1(4-tert-butyl-phenyl) butanone

Mp.: 62-63 oC

257

258

Azide 3c

4-Azido-1-(4-hydroxy-phenyl)butanone

259

260

261

262

Product 40a

5-(4-methoxy-phenyl)-3,4-dihydro-2H-pyrrole

MeO

263

264

265

266

267