This dissertation has been 64—9547 microfilmed exactly as received
ADAMS, David George, 1936— NUCLEAR MAGNETIC RESONANCE STUDIES OF SOME GRIGNARD REAGENTS AND ORGANO- LITHIUM COMPOUNDS.
The Ohio State University, Ph.D., 1964 Chemistry, physical
University Microfilms, Inc., Ann Arbor, Michigan
NUCLEAR MAGNETIC RESONANCE STUDIES OF
SOME GRIGNARD REAGENTS AND ORGANOLITHIUM COMPOUNDS
DISSERTATION
Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University
By
David George Adams, S. M.
* * * *
The Ohio State University 1964
Approved by
Adviser Department of Chemistry DEDICATION
This dissertation is dedicated to my wife, Barbara, who has aided me immeasurably in many ways in its preparation, and whose complete understanding and belief in me has promoted the task from drudgery to a pursuit of workman ship. ACKNOWLEDGMENTS
I wish to thank the McGraw-Hill Book Company, New York,
New York, for permission to include portions of the book "High- resolution Nuclear Magnetic Resonance" by J. A. Pople, W. G.
Schneider and H. J. Bernstein, copyright 1959.
I wish also to thank all of my fellow graduate students, who aided me in my efforts, and especially Englebert Pechhold, as much for his quiet understanding as for his careful synthesis of a necessary compound.
My most sincere gratitude to Dr. Gideon Fraenkel, for whose knowledge and dedication I have the deepest respect, and for whose open-mindedness and lack of pedantry in accepting my disputatious nature I have profound admiration.
This investigation was supported in part by the Petroleum
Research Fund administered by The American Chemical Society, and in part by Public Health Service Fellowship 5 FI GM-17,
815-02 from the Division of General Medical Sciences, Public
Health Service. CONTENTS
Page
DEDICATION 11
ACKNOWLEDGMENTS iii
TABLES vi
ILLUSTRATIONS vii
C hapter ; L INTRODUCTION 1
Historical Background Previous Research Discussion of Problem and Methods Aromatic Grignard Reagents
IL EXPERIMENTAL 25
Chemical Reagents Purification and Treatment of Reagents A pparatus P ro ced u res
Preparation of organometallic compounds Calibration of spectra
n T. RESULTS AND DISCUSSION 47
General Considerations: Aliphatic Grignard Reagents Lithium and Magnesium Organometallic Compounds Mixed Grignard Reagents Asymmetric Grignard Reagents Aromatic Organolithium Compounds and Grignard Reagents iv Chapter Page
IV. SUMMARY AND CONCLUSIONS...... 84
BIBLIOGRAPHY...... 87
AUTOBIOGRAPHY...... 92
v TABLES
Table Page
1. Chemical Reagents ...... 26
2. Reaction Conditions for the Grignard R eaction ...... 36
3. Chemical Shift of Methyl Groups in Solvents ...... 46
4. Proton Chemical Shifts, RMgBr and RgMg ...... 48
5. Proton Chemical Shifts, RMgBr and RH ...... 50
6. Proton Chemical Shifts, RMgBr and R L i ...... 54
7. Bond Hybridization in MeMgl and M eLi ...... 55
8. NMR Parameters, 2-bromo- 1-phenylpropane and 2-bromomagnesio- 1-phenylpropane ...... 62
9. NMR Parameters, l-bromo-2-phenylpropane and l-bromomagnesio-2-phenylpropane ...... 66
10. Chemical Shift, 2-bromo-1, 1-dimethylcyclo- pentane and 2-bromomagnesio-1, 1- dimethylcyclopentane ...... 67
11. NMR Parameters, Aromatic Organometallic C om pounds ...... 69
vi ILLUSTRATIONS
Figure Page
1. Magnetic Field Induced by Ring Current ...... 22
2. Apparatus for Grignard Reaction ...... 33
3. Apparatus for Organolithium Preparation ...... 38
4. Apparatus for Dialkylmagnesium Purification ...... 42
5. NMR Spectrum of 2-bromo-1-phenylpropane ...... 59
6. NMR Spectrum of 2-bromomagnesio-1-phenyl propane ...... 61
7. NMR Spectrum of l-bromo-2-phenylpropane ...... 63
8. NMR Spectrum of l-bromomagnesio-2-phenyl- p r o p a n e ...... 65
9. NMR Spectra of ]D-phenyl-di magnesium bromide and ]3-phenyl-di-lithium ...... 70
10. Paramagnetic Transitions in Aromatic Organo metallic Compounds ...... 74
11. Paramagnetic Effect in Aromatic Organometallic C om pounds ...... 80 J CHAPTER I
INTRODUCTION
Historical Background
The direct precursor of the Grignard reagent was the
Wagner-Saytzeff reaction. In 1875, Wagner and Saytzeff ^ reported a new synthesis for alcohols. They had mixed zinc, an alkyl iodide, and a carbonyl compound to obtain a complex which gave a low yield of an alcohol on hydrolysis. They characterized the reaction as proceeding through the formation of dialkylzinc, with subsequent addition to the carbonyl compound.
Barbier^ substituted magnesium for zinc and obtained higher yields of alcohol in many cases. Victor Grignard (1871-1935), as a student of Barbier, was assigned the problem of studying the mechanism of this type of reaction. His research in this direction finally reached an impasse, and he decided that this reaction might well proceed in two steps. Accordingly, Grignard set out to
^G. Wagner and A. Saytzeff, Ann. 175, 351 (1875).
2p. Barbier, Compt. Rend. 128, 110 (1899).
1 investigate these steps separately. He postulated the first step to be a reaction of magnesium with the organic halide, much the same as Wagner and Saytzeff had suggested.
Grignard1 s attempts to react magnesium with an organic halide in ether met with immediate success. A product was formed which would complex with carbonyl compounds to give alcohols on hydrolysis. The scope of these reactions was quickly expanded to include a large variety of halides and solvents in the first step—the formation of the reagent which bears Grignard's name. New reac tions with the Grignard reagent to produce useful products are still being discovered today.
In the publication of his work, Grignard^ suggested that the structure of his reagent was RMgX. Grignard and others^? 5 found that a solid precipitated on evaporation, and that one molecule of ether per molecule of alkylmagnesium halide was bound very tenaciously in the solid. This observation was used to support a hypothesis of Baeyer and Villiger, ® who suggested that the Grignard
^V. Grignard, Gompt. Rend. 130, 1322 (1900).
^V. Grignard, Ann. Chim. (Paris) 24, 433 (1901).
^E. -E. Blaise, Compt. Rend. 132, 839 (1901).
®A. Baeyer and V. Villiger, Ber. 35, 1201 (1902). reagent was an oxonium compound; for example, methylmagnesium iodide in diethyl ether would have the structure
E t f MeMg — O — I f Et
Grignard 7 ’ ft accepted the idea of a tetrahedrally coordinated oxygen atom, but preferred the structure
E t f Me — O — Mgl I E t
The oxonium theory received much attention, but was disproven unequivocally by Thorp and Kamm, ^ who showed that the magnesium compound prepared from diethyl ether and bromobenzene was different from that prepared from ethoxybenzene and bromoethane.
During the period in which the oxonium theory enjoyed its greatest popularity, Abegg^ proposed an ionic structure for the
Grignard reagent. This theory was largely ignored at that time, but was later revived. He suggested that the Grignard reagent was a
^V. Grignard, Compt. Rend. 136, 1260 (1903).
®V. Grignard, Bull. Soc. Chim. France 29, 944 (1903).
^L. Thorp and O. Kamm, J. Am. Chem. Soc. 36, 1022 (1914).
lOR. Abegg, Ber. 38, 4112 (1905). 4 polar compound best represented as an alkylmagnesium halide and that the equilibrium
2 R M gX ^ MgX2 + R-2M^ might exist in solution.
Jolibois, H as well as others, prepared dialkylmagnesium by the reaction RgHg + Mg—>R2Mg + Hg. He showed that this compound was more soluble in an ethereal solution of magnesium iodide than in pure ether. From these results, Jolibois suggested the structure
MgR2 • Mgl2 to be the best representation for the Grignard reagent.
More evidence for this coordination arose from the early work of
Menschutkin, 12 who determined the solubility of magnesium bromide dietherate in ether. The solubility of Grignard reagents far exceeds that of magnesium bromide, indicating that the magnesium bromide in Grignard reagents must be coordinated to the rest of the compound to account for its high solubility.
Molecular weight determination by Terentjew^ and Grignard^ indicated the molecular weight to be twice that predicted by the single alkylmagnesium halide formula, RMgX; Grignard ascribed this effect
Up. Jolibois, Compt. Rend. 155, 353 (1912).
12b . N. Menschutkin, Z. Anorg. Chem. 49, 34 (1906).
13a . P. Terentjew, Z. Anorg. Chem. 156, 73 (1926).
14v. Grignard, Bull. Soc. Chim. France 39, 1285 (1926). to molecular aggregation in solution. Later work showed that the association varied with concentration, from just over one to about four. 15
Thus, the research during the first quarter-century after
Grignard's discovery had elucidated the composition of the Grignard reagent in ether solution. However, differentiation between the association of two alkylmagnesium halide molecules and the associa tion of dialkylmagnesium with magnesium bromide was not made.
This distinction is still being studied today, and is one of the problems with which this work is concerned.
Previous Research on the Structure of the Grignard Reagent
Schlenk and S c h l e n k 16 were the first to obtain lasting evidence for the structure of the Grignard reagent. They discovered that the addition of 1, 4-dioxane to an ether solution of a Grignard reagent would precipitate almost all of the halogen in the solution, along with some, but not all, of the alkylated magnesium compounds.
The compound left in solution was found to have the empirical form ula R 2 Mg, and reacted with other substances in much the same
15 j. Meisenheimer and W. Schlichenmaier, Ber. 611, 720 (1928). 16w. Schlenk and W. Schlenk, J r., Ber. 62, 920 (1929). way as the original Grignard reagent. The amount of dialkyl - magnesium left in solution was found to vary with the alkyl group.
These data were coupled with the finding that evaporation of an ether solution of the Grignard reagent from bromobenzene gave crystals which had the correct empirical formula for the dietherate of phenylmagnesium bromide. Schlenk and Schlenk postulated the equilibrium 2 RMgX^^RgMg + MgXg to account for their results, and calculated equilibrium constants on the assumption that RMgX and MgX 2 were coprecipitated by 1, 4-dioxane.
Some doubt was cast on these conclusions when it was found that the constitution of the precipitate changed with time and with the manner of precipitation. Evans and Pearsonl? suggested that a variety of association reactions rendered Schlenks’ conclusions invalid.
Strong evidence against the presence of the Schlenk equilibrium
(above) was provided by Dessy etal. Investigations of the reac tion^18> I 9 RC = CH + R'MgX—»RC= CMgX + R'H using hexyne-1 and ethylmagnesium bromide showed that, kinetically, a mixture
l^W. V. Evans and R. Pearson, J. Am. Chem. Soc. 64, 2865 (1942), and references therein.
J. h . Wotiz, C. A. Hollingsworth, and R. E. Dessy, J. Qrq. Chem. 21, 1063 (1956).
19r . e . Dessy, !. H. Wotiz, and C. A. Hollingsworth, j[. Am. Chem. Soc. 79, 358 (1957). of diethylmagnesium and magnesium bromide gave the same results as ethylmagnesium bromide. In other works, 20, 21 Dessy etal. prepared and isolated radioactive Mg28 (tQ ^ = 21. 25 h r.). The metal was reacted with bromine in ether to produce radioactive magnesium bromide, which was equilibriated with ordinary diethyl magnesium in ether. Addition of 1, 4-dioxane then precipitated magnesium bromide, whose radioactivity was measured. The radioactive magnesium was found to have exchanged only from 6 to
10% with the non-radioactive dialkylated magnesium, after contact times between the two reagents of 10 minutes and 36 hours. Dessy et al. therefore postulated RgMg • MgX 2 to be the correct represen tation of the Grignard reagent in solution and in the solid state, to account for the empirical formula RMgX. The molecule RMgX was concluded to be non-existent.
These results may be questioned on two bases: first, no exchange at all should occur if RMgX does not exist. Secondly, in the same studies, Mg^^Brg was found to exchange completely with
RgMg in ether solution. Dessy and Handler attributed the exchange to impurities in the magnesium.
2Qr. E. Dessy etal. J. Am. Chem. Soc. 79, 3476 (1957).
21r . e. Dessy and G. S. Handler, J. Am. Chem. Soc. 80, 5824 (1958). Stucky and Rundle^ have recently obtained x-ray diffraction data on crystals obtained by evaporation of an ether solution of phenylmagnesium bromide. A three-dimensional Patterson map of the positions of the atoms showed that the actual structure in the solid state is RMgX, with two ether molecules also coordinated to the magnesium atom. Stucky and Rundle do not generalize this result to the solution state, but point out that a mixture of diphenyl - magnesium and magnesium bromide may not be identical at first to phenylmagnesium bromide,, if phenyl-bromine exchange were slow. f o Also from x-ray diffraction analysis, a value of 2. 06 A for the magnesium-oxygen distance in phenylmagnesium bromide dietherate was obtained. The great strength of this bond was inferred by com- o parison with the Mg-O bond length in magnesium oxide (2.10 A) and o in magnesium hydroxide (2. 09 A).
Their comparison is misleading; if the ether is coordinated to magnesium by ion-dipole attraction, the low value for the magnesium- oxygen distance is a result of a small radius of the magnesium atom in the direction of the ether molecules, indicating little overlap of the orbitals of the two atoms. Use of the bond length as a criterion of strength is unjustified when the bonds compared are of different types.
22g . D. Stucky and R. E. Rundle, _J. Am. Chem. Soc. 85, 1003 (1963). The extensive work of Hamelin et al. ^3, 24, 25, 26 on solvation of Grignard reagents in solution has indicated that R^Mg and M gBr 2 are the only species in solution. In ether, an infrared band at 932 cm“l is assigned to a vibration of the C-O-C system in ether. In ether solutions of diethylmagnesium, a band at 926 cm '^ appears, which is attributed to bound ether molecules. In MgCl 2 and M gB r 2 , bands at 902 cm" 1. and 900 cm“l, respectively, appear.
Infrared spectra of "EtMgCl" and "EtMgBr" show bands at 920 and
902 cm- -*-, and at 920 and 900 cm"-*-, respectively.
The critical work of Kirrmann et al. 27 Qn ethylmagnesium bromide in different solvents has shown that the composition of solid material precipitated from solution varies with the solvent; non-integral solvation and a deficiency of alkyl groups is commonly
observed. Finally, thermogravimetric evaporation curves of
23a . Kirrmann and R. Hamelin, Compt. Rend. 251, 2990 (1960).
24r . Hamelin, Bull Soc. Chim. France 684 (1961).
25r . Hamelin and S. Hayes, Bull. Soc. Chim. France 692 (1961).
26r . Hamelin and S. Hayes, Compt. Rend. 252, 1616 (1961).
27 a . Kirrmann, R. Hamelin, and S. Hayes, Bull. Soc. Chim. France 1395 (1963). Grignard reagents showed inflection points rather than a horizontal section, indicating the Grignard reagent is neither a definite com pound nor a simple mixture. From these studies, the conclusion was drawn that an easily shifted equilibrium of copolymers exists in solution, which is composed of chains of MgY 4 tetrahedra sharing edges, where Y = solvent, alkyl, or halide.
Prevost and Gross28 obtained the infrared spectrum of allylmagnesium compounds in various solvents. The vibrational band at 1588 crn"^ in allylmagnesium bromide and iodide (1580 cm ^ in the chloride) was observed to be independent of concentration in all solvents. The bond appeared at the same frequency in diethyl etherdibutyl ether, and trimethylamine solution. Addition of tetrahydrofuran (THF) to the diethyl ether solution caused the bond to appear at 1570 cm“l in the bromide, and 1560 in the iodide. In
1, 4-dioxane solution, the band appeared at 1577 cm '^. From these . data, Prevost and Gross concluded that solvents more weakly basic than THF coordinate with the magnesium of magnesium halide; dioxane and THF coordinate on RgMg by displacement of the MgX 2 «
28c. Prevost and B. Gross, Compt. Rend. 252, 1023 (1961). 11
The kinetic data of B e c k e r 2 9 parallel these findings. In the
reaction of ethylmagnesium bromide with benzonitrile, the rate
constants (k^XlO^) in various solvents were as follows:
Solvent k£
4-methyl-1, 3-dioxane 19.3
methylal 18.7
diethyl ether 17. 8
tetrahydrofuran 3.65
diglyme 0.483
The oxygen atoms in the first three solvents all presumably
coordinate in a similar manner to Grignard reagents. It is reason
able to assume that trimethylamine also coordinates in the same
way. Further evidence that these compounds coordinate on the
magnesium halide arises from the observation^ that the conductance
of a Grignard reagent in diethyl ether decreases in inverse propor
tionality to added trialkylamine, whereas the kinetics of the
.Grignard-hexyne-1 reaction remain unchanged with trialkylamine
addition. 31
29e . I. Becker, Trans. N.Y. Acad. Sci. 25, 513 (1963).
E. Dessy and R. M. Jones, J. Org. Chem. 24, 1685 (1959). 31j. H. Wotiz etal., J. Org. Chem. 23, 228 (1958). 12
Recently, Roos and Zeil32 have studied the ethylmagnesium bromide system in diethyl ether by the methods of NMR spectro scopy, and conclude that the ether is coordinated as
OEt2
R
R
O Et2
The superior coordinating power of diglyme appears to'be due to the ability of the molecules to chelate. Evidently, the distance between the two outermost oxygen atoms is sufficient for both to coordinate with the Grignard reagent; the part of the molecule between these oxygen atoms then tends to block the approach of other reacting molecules. Two oxygen atoms separated by only 2 carbon atoms are apparently less effective in coordination, since aliphatic Grignard reagents were found by the investigator to be only slightly soluble in 1, 2-dimethoxyethane.
The solvation of Grignard reagents in THF presents a more complex situation; the five membered ring structure prevents formation of the 90° C-O-C bond angle predicted by bonding.
32h . Roos and W. Zeil, Ber. Bunsenges. Phvsik. Chem. 67, 28 (1963). 13
The exact hybridization of the bond is unknown. If the suggestion that THF coordinates to the alkylmagnesium to replace magnesium
QO halide ° is accepted, the fact that magnesium halide does not precipitate must be explained, since the solution would be super saturated with respect to MgX 2 * On this basis, Ashby and Becker3^ suggest that ethylmagnesium halide in THF has the structure RMgX, since a study of boiling point elevation indicated that ethylmagnesium halide is monomeric in THF, while dimeric in ether.
If the monomers were R£Mg and MgX 2 , presumably MgX 2 would precipitate. Guild et al. 3^ determined the composition of the vapor phase over Grignard reagents in mixtures of THF and ether by the methods of gas chromatography. Their results indicate one THF molecule per alkyl group of the Grignard reagent is bonded; consequently, the structure
THF
R - Mg - R r THF was preferred over a singly solvated RMgX molecule.
33Prevost and Gross, loc. cit.
3^E. C. Ashby and W. E. Becker, J. Am. Chem. Soc. 85, 118 (1963).
33L.. V. Guild etal., Inorcr. Chem. 1, 921 (1962). 14
Discussion of Problem and Methods of Research
The nature of the bond between the alkyl groups and the magnesium is of great interest. The ionic character of the carbon- magnesium bond, calculated from Pauling's^6 electronegativities, is 34%. Hannay and Smyth^? have proposed a different method of calculation which gives a value of 26. 8% for the ionic character.
The alkyl group of a Grignard reagent may be expected to exhibit some of the properties of a carbanion; however, it does not attack ether, whereas sodium alkyls (in which carbanions are present) attack ethers rapidly.
The methods of NMR spectroscopy may be used with effect to study several aspects of the Grignard reagent problem:
1. To the extent that the alkyl groups possess carbanionic character, the alkyl groups may be compared with amines isoelec- tronic with carbanions. Ammonia and amines are known to have a yr. pyramidal configuration rather than a planar one
36l . Pauling, J. Am. Chem. Soc. 54, 3570 (1932).
3?N. B. Hannay and C. P. Smyth, J. Am. Chem. Soc. 68, 171 (1946).
^Methylmaghesium iodide in ether was unchanged after twenty years. H. Gilman and D. L. Esmay, _J. Org. Chem. 22, 1011 (1957). 15
a. by virtue of possessing dipole moments, 39, 40
b. by electron-diffraction studies of trimethylamine, showing the C-N-C angle to be 108?4, 41
c. by spectroscopic studies on ammonia, which showed
the H-N-H angles to be about 107°. 42 Nevertheless, no optically
active amines have been isolated, 43 although a pyramidal structure
would permit optical isomers of an amine with the formula NABC,
in which A, B, C represent different groups. The difference in
stability of the pyramidal and planar forms is apparently small
enough so that an appreciable fraction of the molecules have enough
energy at any time to invert through the planar intermediate form.
Dennison^ calculated the planar configuration to be less stable than
the pyramidal one by 6 kcal per mole.
^H . Watson, Proc. Roy. Soc. (London) A117, 43 (1927).
4°G. C. Hampson and R. J. B. Marsden, Trans. Faraday Soc. 30, Appendix (1934).
41L. O. Brockway and H. O. Jenkins, J. Am. Chem. Soc. 58, 2036 (1936).
^3d . M. Dennison, Revs. Mod. Phvs. 12, 175 (1940).
43,,Troger,s base” has been resolved; however, the nitrogen atoms are rigidly held. V. Prelog and P. Wieland, Helv. Chim. Acta. 27, 1127 (1944).
44p>ennis0n, loc. cit. 16
By analogy to amines, carbanions may be expected to invert rapidly. If Grignard reagents possess sufficient carbanionic character to invert easily, suitable compounds can be synthesized in which inversion can be detected by the methods of NMR spectro scopy.
2. The alkyl groups of Grignard reagents may exchange between magnesium atoms. Different NMR spectra may result from different rates of exchange.
3. The actual structure of the organomagnesium compound in solution may be RMgX or R 2 Mg. If alkyl exchange is slow enough, two different NMR spectra of an alkyl group may result, depending on the nature of the other group attached to magnesium..
The Grignard reagent from 2-bromo-l, 1-dimethylcyclo- pentane, for example, will exhibit two methyl resonances (because no plane of symmetry exists in the molecule) as long as the ring does not invert rapidly. The rate of inversion at which collapse to one line will occur may be estimated from the uncertainty prin ciple in the form t A E ssh. where t is the life time of the methyl group in one position and A E is the energy separation of the two methyl resonances. Division by h gives
^ 2TTA0
X 17
If A J, the separation of the two possible methyl resonances, were about 10 cps, two peaks would be observed if the configuration remained stable for about .016 seconds. If the ring were to invert many times during this interval, one sharp line would appear in the
NMR spectrum at a position halfway between the two possible posi tions. At intermediate rates of inversion a partially collapsed doublet would be observed.
If more than one species exists in solution, several types of spectra are possible for the methyl protons:
a. If alkyl exchange and inversion were slow, the enantiomorphic forms RMgX would each give identical doublets.
Both dextro- and levo-Rs>Md forms would give identical doublets, different from RMgX. The diastereomeric meso-RgMq form would give yet another doublet. The relative areas under the doublets would give the relative concentrations of the species, assuming all
the doublets could be separately resolved.
b. If alkyl exchange were fast, but inversion of the alkyl
group slow, one doublet would appear; d- andj.- forms of the alkyl
group would be indistinguishable.
c. If alkyl exchange and inversion were both fast, one
methyl resonance peak would be observed. The other possible combination, slow exchange and fast inversion, probably does not occur. Fast inversion has not been observed in compounds in which the carbon atoms remain tetra- hedrally coordinated.
The rate of exchange of alkyl groups is probably determined by the ionic character of the carbon-magnesium bond, and cannot be adjusted for purposes of observation. The rate of inversion, on the other hand, can be affected by changing the rigidity of the carbon skeleton of the alkyl group. Acyclic compounds containing an asymmetric carbon atom oc or p to magnesium would show inversion rates much higher than similar cyclic* compounds. The rate of inversion could be determined most easily in compounds with the formulas RiCH2(R2)(r 3)c M9x or RlR 2 R 3 CCH2 MgX. ^ bottl cases> the methylene hydrogens will be magnetically non-equivalent in the parent halide, since the hydrogen atoms in the three rotational isomers are in different magnetic environments, independent of the rate of rotation. 45 jn the Grignard reagents, if rapid inversion of the carbanionic forms occurs, the two methylene hydrogens will
45p. M. Nair and J. D. Roberts, J. Am. Chem. Soc. 79, 4565 (1957). 19 become magnetically equivalent. This phenomenon has been observed in sim ilar compounds. 46
If alkyl groups exchange slowly, the equilibrium mixture of two different Grignard reagents will contain RgMg, RR’Mg and
R 2 'Mg, if dialkylmagnesium is the prevalent species in solution.
New peaks may appear in the NMR spectrum, due to the RR'Mg species. If alkyl exchange is fast, the spectra of the two alkyl groups will be essentially independent of one another, given by
= 5 1 Ni S f 1, where Nj is the mole fraction of the ith species, and tTf1 is the chemical shift of each equivalent group (m) of protons in the ith species.
Insight into the nature of the carbon-magnesium bond can be gained by a determination of the bond hybridization. Juan and
Gutowsky^ have explained theoretically the observed4®* 49 linear dependency of the C-^-H coupling constant ( Jq 13_jj) on bond hybridization in substituted methanes. The equation
13-H = JotfSH
4§g . M. Whitesides, F. Kaplan, and J. D. Roberts, _J. Am. Ghem. Soc. 85, 2167 (1963).
4?C. Juan and H. S. Gutowsky, J. Chem. Phys. 37, 2198 (1962). 4®N. Muller and D. E. Pritchard, J. Chem. Phys. 31, 768 (1959). 49Ibid., p. 1471. 20
gives the proportionality, where oC-§- is the s.-character of the bond i l and JQ is 500 cps. ^
Aromatic Grignard Reagents
Several factors contributing to the chemical shift of protons
are peculiar to aromatic compounds. These factors are (1) ring
current, (2) charge on the ring carbon atoms, and (3) paramagnetic
effects.
Ring- current^ 51-*•
Aromatic compounds are known to possess tt electrons which
are relatively free to circulate about a conjugated ring. When a
magnetic field is applied perpendicular to the plane of the ring, the
m obile it electrons behave much like charged particles free to move
on a circular wire. ^2 This circulation is diamagnetic; that is, in
such a direction as to generate a moment opposed to the primary
is determined from the observed value Jc 13-H = 125 cps in methane, where oc|| = 0. 25, corresponding to sp2 hybridization. Juan and Gutowsky, loc. cit.
51-J. A. Pople, W. G. Schneider and H. J. Bernstein, "High- resolution Nuclear Magnetic Resonance, " McGraw-Hill, New York, N. Y ., 1959, p. 180. (In future references, this book will be abbreviated as HRNMR.)
52L. Pauling, J. Chem. Phys. 4, 673 (1936). field. The secondary magnetic field, while opposing the primary field at the center of the ring, reinforces the primary field outside the ring (see Fig. 1). Since the aromatic protons are outside the ring, they experience a small additional field parallel to the primary field; consequently, they undergo NMR absorption at a lower field strength than do similarly bonded protons in the absence of a ring c u rre n t. 53> 54
Charge on the carbon atoms
The presence of.negative charge in the sp% orbital of an aromatic carbon atom will increase electron density in the hydrogen
Is orbital at the expense of the electron density in the C-H bond; the nuclear shielding at the proton will be thereby increased. 55 The presence of one full electronic charge on the carbon atom will result in an increase of 10 ppm. in the chemical shift of the proton.
The dependence of the chemical shift ( <£g) on charge is linear, so
53 j. s. Waugh and R. W. Fessenden, J_. Am. Chem. Soc. 79, 846 (1957).
54l . H. Meyer, A. Saika, and H. S. Gutowsky, .J. Am. Chem. Soc. 75, 4567 (1953).
55g . Fraenkel et al., J. Am. Chem. Soc. 82, 5846 (1960). / \ Magnetic lines I ' ofX force£ From "High-resolution Nuclear Magnetic Resonance" by Pople, Schneider and Bernstein, copyright 1959, McGraw-Hill Book Company. Used by permission.
Fig. 1. —Magnetic Field Induced by Ring Current that the electronic charge (Z) may be calculated from the equation
10 where cf(J)H is the chemical shift of the benzene protons. 56
Since the carbon-magnesium bond in phenylmagnesium halide is partially ionic, some electronic charge is expected to appear on the carbon atoms.
Paramagnetic effects
Paramagnetic effects arise from the presence of low-lying excited states in the aromatic molecule. This will be discussed in detail in Chapter HI.
Phenylmagnesium halide, like other mono-substituted benzenes, will constitute an A 2 B 2 C system (formalism of Pople et al.). Each proton will couple with all others, making direct analysis difficult.
Simplification may be effected by deuteration of various positions, particularly (2, 6-) (3, 5-),’ and (4-). TJse of the double irradiation technique is necessary to remove interactions with deuterium (1=1).
The double irradiation technique was first applied by Bloch, 5V and the theory developed by Bloom and Schoolery. 58 The method
5 ® Ib id .
57 f . Bloch, Phvs. Rev. 93, 944 (1954).
58 a . l . Bloom and J. N. Schoolery, Phvs. Rev. 97, 1261 (1955). 24 utilizes a strong radio frequency (rf) magnetic field in addition to the usual weak rf field.
The stronger field is adjusted to cause saturation of the deuterium resonance. Frequent transitions between the nuclear spin states of deuterium occur and the deuterium nuclei thus are effectively decoupled from the rest of the system. With the deuterium decoupled, the NMR spectra of the protons in phenyl magnesium bromide substituted (2, 6-), (3, 5-), and (4-) with deuterium become A^>, A^X, and AgX 2 , respectively. The chemical shifts of these protons should be practically unaffected by deuterium substitution. 59
59 j. B igeleisen and M. G. M ayer, _J. Chem. Phys. 15, 261 (1947). CHAPTER H
EXPERIMENTAL
Chemical Reagents
Most of the chemical reagents used in this study were obtained from commercial sources. Table 1 lists these compounds, grade, and source.
Synthesis of 2-bromo-l, 1-dimethylcyclopentane: ^
Synthesis of l-bromo-2-phenylpropane: Allyl bromide (121 g;
1 mole) was mixed with benzene (390 g; 5 moles) in a 2-liter flask and concentrated sulfuric acid (196 g; 2 moles) added in 10-20 cc portions at 2-minute intervals with shaking and cooling to keep the temperature below 60° C. When addition was complete, the mix ture (which had turned black) was cooled to room temperature, transferred to a 5-liter bottle, and shaken for 24 hours. The mixture was then poured onto 2000 grams of ice, steam distilled, and the distillate extracted with 300 cc. ether. The ether solution was dried over anhydrous potassium carbonate and the ether
^Courtesy of E. Pechhold (unpublished synthesis). 25 26
TABLE 1
CHEMICAL REAGENTS
Gradea or percentage Halides purity Manufacturer3-
Bromomethane WL EK
Iodomethane WLEK
Iodomethane (50% Cl3) ------MSD
Bromoethene K& L
Bromoethane WL EK
1, 2-dibromoethane ARMCB
3-bromopropene-1 ARMCB
2-bromobutane ARMCB
Bromocyclopentane P ra c t EK
Bromobenzene AR MCB
1, 4-dibromobenzene WL EK
1, 4-bromochlorobenzene WL EK
oC - br omotoluene P ra c t MCB
oc-bromo-jg-xylene WL EK
-iodoethylbenzene WL EK
/3-bromopropylbenzene Tech A ldrich 27
TABLE 1—Continued
Gradea or percentage Solvents pu rity Manufacturer3-
Diethyl ether [ CP OSU
Tetr ahydr ofur an ------DuPont
1, 4-dioxane AR MCB
Bis (2-methoxyethyl) ether Pract MCB
Anisole AR MCB
Miscellaneous
M agnesium Sublim ed Dow
Lithium wire ------Lithium C orp.
Lithium sand Dispersion in Lithium wax C orp.
Methylmagnesium bromide Tech Arapahoe
Te tr ame thyls ilane ------A nderson
H elium 99. 9% M atheson
Deuterium oxide 99.9% C olumbia n - butyllithium ------Foote
aWhite Label (WL) is Eastman Kodak’s (EK) highest grade. Analytical Reagent (AR) is Matheson Coleman & Bell's (MCB) highest grade. Merck, Sharp & Dohme (MSD), Kaufmann and Latimer (K & L), and others do not specify grade. 28 removed, by distillation. The remaining liquid was distilled under reduced pressure, b. p. 71?0 - 71?5, 3 mm, 51% yield.
Synthesis of 4-deuterobromobenzene: Magnesium turnings
(2. 9 g; 0. 12 mole) were placed in a 3-neck 500 cc flask fitted with addition funnel, mechanical stirrer, and reflux condensor with dry ing tube. Diethyl ether (100 cc) was distilled into the flask from a solution of methylmagnesium bromide in ether. _P-dibromobenzene
(23. 6 g; 0. 1 mole) was dissolved in an additional 100 cc of anhydrous ethyl ether and transferred to the addition funnel under helium.
Ethylene dibromide (0. 5 g; 0. 003 mole) was added to the magnesium - ether mixture to initiate reaction. Stirring was begun and the dihalide-ether mixture admitted at a rate sufficient to cause con tinuous reflux of ether. After addition was complete, the mixture was refluxed 30 minutes to insure reaction of any bromobenzene formed by hydrolysis of jD-bromophenylmagnesium bromide.
Deuterium oxide (10 g; 0. 5 mole) was added dropwise. followed by
100 cc 10% ammonium chloride solution added rapidly. The ether layer was separated, dried over anhydrous magnesium sulfate, and the ether removed by distillation. The product, 4-deuterobromo benzene, was distilled under reduced pressure b. p. 74?0 - 74?5,
40 mm, 75% yield. 29
Synthesis of 3, 5-dideuterobromobenzene: Sym-tribromo- benzene^ (31. 5 g; 0. 1 mole) was reacted with magnesium (3. 6 g;
0. 15 mole) in the same manner as the previous preparation and hydrolyzed with deuterium oxide (12 g; 0. 6 mole). The product,
3, 5-dibromodeuterobenzene, was separated from bromobenzene in an Aerograph Autoprep Gas Chromatograph in 45% yield. The entire yield of 3, 5-dibromodeuterobenzene (10. 6 g; . 045 mole) was reacted with magnesium (1. 2 g; .05 mole) in the same manner as above and hydrolyzed with deuterium oxide (3. 6 g; 0. 18 mole). The product,
3, 5-dideuterobromobenzene, was separated in the Autoprep in
80% yield, 36% overall.
Purification and Treatment of Reagents
M etals 1. Sublimed magnesium was milled by a machinist to fine
shavings, care being taken to avoid contamination by iron. The
metal shavings were washed with benzene, then with 3 portions of
diethyl ether (C. P .}. The ether was removed in a stream of dry
helium and the magnesium stored over anhydrous magnesium
sulfate.
^Courtesy of the undergraduate Organic Chemistry students. 30
2. Lithium metal dispersion in wax was cleaned in the reaction vessel by distilling in ethyl ether and filtering or decanting until the ether showed no residual paraffin on evaporation.
3. Lithium wire was dipped into anhydrous ethanol, scraped under petroleum ether, and cut into 1 mm lengths immediately before use.
Solvents
1. The stock solution of diethyl ether was prepared by addi tion of methylmagnesium bromide in ether to five times its volume of diethyl ether. A small amount of magnesium turnings was added and the mixture refluxed under helium to remove small amounts of residual methyl bromide. The stock solution was stored under helium .
2. Stock solutions of anisole, tetrahydrofuran (THF), dioxane, and bis (2-methoxyethyl) ether (diglyme) were prepared by addition of methylmagnesium bromide in diethyl ether to the solvent. When a precipitate formed which was so voluminous as to be troublesome, the suspension was centrifuged and the solution decanted. The ether was removed by distillation and the remaining stock solution stored under helium. H alides
Liquid halides were stored under refrigeration and distilled
before use. Solid halides were sublimed or evaporated under
reduced pressure before use.
A pparatus
NMR sample tubes
The NMR sample tubes were made from ordinary soft glass
or Pyrex tubing. A tubing gauge was made from a 1/2" brass plate
by drilling cylindrical openings of the correct diameter for spectrom
eter usage. Tubing which was nominally 5 mm OD was selected
which fitted within close tolerance. The tubing was cut into 5"-7"
lengths and cleaned first with trisodium phosphate solution for one-
half hour on a steam bath. The tubes were rinsed three times with
water and warmed for one-half hour in aqua regia. The tubes were
then rinsed with water, dilute aqueous ammonia, and distilled
water, then covered loosely in aluminum foil and oven-dried at
90° C.
For use, the tubes were sealed off in a small hot oxygas
flame and rounded by pulling off the excess glass and rotating the
tube until the desired hemispherical shape was obtained. The tubes
were then stored over anhydrous magnesium sulfate (Drierite). Syringes
The syringes used for addition of the bromides were ordinary hypodermic syringes (Multifit) with a locking needle; the syringe used for extractions of samples of Grignard reagents was a 1 cc gastight syringe (Hamilton). All syringes were oven-dried at 90° C and stored over phosphorus pentoxide. Just before use, the syringes were flushed with dry helium.
Instrumentation
Two NMR spectrometers were employed in this study; a
Varian HR-60 High Resolution NMR spectrometer equipped with a
Hewlett-Packard wide range audio-oscillator, Hewlett-Packard
Model 522D digital counter, and an NMR Specialties heteronuclear decoupler; and a Varian A-60 High Resolution NMR spectrometer.
The A-60 was used for the majority of spectra not requiring decoupling nor precise calibration by audio side band modulation.
P ro ced u res
Preparation of organometallic compounds
1. Grignard reagents. —Grignard reactions were carried out in the apparatus shown in Figure 2. Dimensions are not shown since none are critical, and several reaction vessels, of approxi mate capacity 3 ml, 10 ml, 30 ml, and 50 ml were used. The flask 33 Drying tube A 2. ——App3.r3.tus for Grignard R eaction
Drying tube
^Support rod
.Teflon stopcock
Stock flask 34 containing stock solvent had from three to five times the capacity of the reaction vessel. When expensive or rare halides were used, a tube equipped with a glass break seal containing the halide was sealed onto the reaction vessel.
The Grignard apparatus (excluding the solvent flask) was dried by passing a stream of high purity helium through it while flaming the glass parts. After cooling, a small Teflon-covered magnet and magnesium turnings in 100% excess were added. The helium flow was then stopped and the flask containing stock solvent connected to the apparatus. During distillation, drying tube B was open to permit equalization of pressure, while drying tube A was closed with a serum cap. After the desired amount of solvent had been distilled into the reaction vessel, drying tube B was capped. Drying tube A was uncapped to permit reflux in the condensor and helium bled through a hypodermic needle into the top of tube A to inhibit air diffusion. Stirring was then begun and approximately 0. 1 cc of the halide injected into the solvent by means of an ordinary hypodermic syringe. Reaction usually set in within a few minutes, accompanied by ebullition, cloudiness, and/or color formation. In some instances, addition of 0. 1 cc 1, 2-dibromoethane was necessary to initiate reaction. The remaining halide was added at the rate of about 1 millimole/minute, and the mixture then heated for 30 minutes 35 to complete reaction. The given reaction conditions hold for primary aliphatic bromides and iodides. Important deviations from the general procedure are given in Table 2.
The NMR tube was dried with a flow of dry helium through a
10" 18 gauge hypodermic needle inserted in the tube, with simul taneous warming in a Bunsen flame. After removal of the flame, the flow of helium was continued until the tube cooled to room
temperature, when the needle was withdrawn and the tube closed
with a serum cap. Before use, the 1 cc gastight syringe for sample
withdrawal was flushed several times with helium. The syringe
was fitted with the 10" needle used for drying the NMR tube and was inserted through the serum cap and stopcock on the reaction
vessel. After filling the syringe, the needle was withdrawn from
the reaction vessel and quickly inserted through the serum cap on
the NMR tube. The tube was filled to a depth of 1-1/2", cooled in
dry ice, and the upper end quickly drawn off in a flame just below
the level of the serum cap.
A 1. 00 cc aliquot was withdrawn from the reaction vessel,
expelled into 10 cc of water in a small Erlenmeyer flask, and one
drop of methyl red indicator added. The solution was titrated with 36
TABLE 2
REACTION CONDITIONS. FOR THE GRIGNARD REACTION
Initiation R ate of (1 m m ole Induction addition Heating Temp. ethylene tim e (mmole tim e Halide Solvent (° C) dibrom ide) (min. X /m in .) (m in .)
Prim ary- Ether Reflux No 1 1 "30
Diglyme 30 No 1 1 30
Anisole 30 No 1 1 30
Secondary Ether Reflux Yes 2-5 0. 5 60
Diglyme 25 Yes 5 0 .5 60
Benzyllic Ether Reflux No 15 1 60
Cyclic Ether Reflux Yes 5 0 .5 120
Diglyme 80 No 2 0 .2 60
Aromatic Ether Reflux Yes 15 0 .2 60
D ibrom o- benzene THF 60 Yes 15 0 .3 120 37
0. 1 N HC1 solution. 3 since the NMR spectra of Grignard reagents were found to change slowly with concentration, this simple pro cedure was deemed to be adequate.
After titration, the mixture was extracted with 1 cc carbon tetrachloride. The organic phase was separated, dried over anhydrous potassium carbonate, and transferred to an NMR tube.
Spectral lines were compared with the organometallic spectrum for positive identification of impurities.
2. Organolithium compounds. —The apparatus shown in
Figure 3 was dried by the procedure described in subsection 1
(Grignard reagents). The majority of organolithium compounds were prepared using 2. 2 equivalents of lithium sand dispersed in wax (exceptions are noted below). Five to ten cc of ether were distilled into the reaction flask and the mixture stirred. The reaction flask was then tilted and the solution of wax and ether drained through stopcock A. Washing of the lithium sand was repeated until the decantate showed no paraffin on evaporation.
The rest of the procedure is similar to that used in Grignard preparation (subsection 1).
3No corrections to the values obtained were made, although the method described here gives results which are probably 3-4% too high. H. Gilman, E. A. Zoellner, J. B. Dickey, J. Am. Chem. Soc. 51, 1576 (1929). Drying tube A
Fig. 3. —Apparatus for Organolithium Preparation
Drying tube
Support rod
Serum cop ^‘•-v'-Teflon stopcock
Stock flask 39 Phenvllithium and methvllithium. --These preparations required the use cf lithium wire. Lithium wire (2. 3 equivalents) was dipped into anhydrous ethanol and the coating scraped off under petroleum ether. The wire was cut into 1 mm lengths and dropped into the reaction vessel in a stream of helium. Ether was distilled in and decanted through stopcock A to remove traces of impurities.
Ether (10-15 cc) was again distilled in and the mixture cooled to
-25° G in an acetone-crushed ice bath. A small amount (1 mmole) of the halide (bromobenzene or iodomethane) was added and reaction began within 15 minutes, evidenced by the lithium wire turning black, then white, with formation of a white precipitate. The remainder of the halide (9 mmole) was added over a period of
30 minutes, during which time the reaction mixture was permitted to warm to 10° C.
The mixture was then stirred 1 hour at room temperature to complete reaction. Sampling was done as in subsection 1.
P -chlorophenvllithium. —This compound was prepared by exchange between jo-bromochlorobenzene and n-butyllithium. A
250 cc flask, fitted with a straight 1 mm stopcock, was dried with a flow of helium while warming the flask in a Bunsen flame. Helium flow was continued until the flask cooled to room temperature. The flask was attached to a vacuum line (but not evacuated) and 40 n-butyllithium (.011 mole) in 50 cc ether transferred by means of a syringe. P-bromochlorobenzene (.01 mole) was placed in a dry flask and 100 cc dry ether added. Both solutions were cooled to
0° C and the dihalide added dropwise to the n-butyllithium solution from a syringe. The mixture was stirred thirty minutes and evacuation begun. Ether was removed until the volume was reduced to approximately 20 cc. Helium was admitted to bring the vessel to atmospheric pressure and sampling was done as in subsection 1.
3. Dialkylmacrnesium compounds. -A 3-neck 500 cc flask was fitted with a reflux condensor bearing a drying tube, a sealed mechanical stirrer, and a 250 cc addition funnel fitted with a pressure equalization tube. This apparatus was dried with an internal flow of dry helium with simultaneous warming of the glass parts in a Bunsen flame. After cooling, the distillation apparatus and ether stock flask used in Grignard preparation (see Fig. 2) were attached at the top of the addition funnel. Magnesium turnings (5 g; 0. 2 mole) were placed in the reaction flask and 100 cc ether distilled into the addi tion funnel. One-half of the ether was admitted to the reaction flask.
The organic halide (0. 1 mole) was injected into the addition funnel through a serum cap on the side arm of the distillation head.
Ethylene dibromide (0. 2 g; .01 mole) was added to the flask through
^W. Strohmeier, Chem. Ber. 88, 1218 (1955). 41 the condensor outlet to initiate reaction. After onset of reaction, the ether-halide mixture was added at a rate sufficient to give gentle reflux. The mixture was refluxed for 30 minutes to complete reactio n .
The dioxane stock flask was substituted for the ether stock flask. The water condensor was drained so that the distillate would be quite warm. A stream of dry helium was bled in through the sidearm so that dioxane vapor would be carried across the surface of the Grignard reagent. Slow precipitation of magnesium bromide was found to be necessary to prevent coprecipitation of alkyl magnesium compounds with magnesium bromide. When precipi tation was complete, the attachments were removed and stoppers placed in the necks of the reaction flask.
A centrifuge flask (Fig. 4) was made by attaching an 18/9 ball joint and a 50 cc round bottom flask to either end of a vacuum stopcock. The flask was evacuated (so that the Grignard suspension in dioxane and ether could be drawn in) and attached tightly to the reaction vessel by means of an adapter. The apparatus was tilted
to fill the adaptor tube and the stopcock on the centrifuge bulb
opened. After filling, the stopcock was closed and the bulb centrifuged at low speed for 15 minutes. I Top view i stopcock
^ A _ Stopcock
Stopcock Stopcock
Centrifuge flask
Fig. 4. --Apparatus for Dialkylmagnesium Purification
CO 43
The apparatus used for isolation and purification of dialkyl- magnesium compounds was modeled after the Schenkelfrittengefass of Strohmeier^ (Fig. 4).
The Schenkelfrittengefass (Sfg) was evacuated through J and gently heated with a Bunsen flame to remove moisture. The centrifuge bulb was attached to H and the intervening space between the stopcocks evacuated by turning the stopcock A one- quarter turn. Another one-quarter turn connected the Sfg and the centrifuge bulb. The stopcock on the bulb was then opened and the clear liquid discharged into D. The Sfg was tilted to pour the liquid into E for removal of the solvent with a minimum of loss by bumping.
The solution was stirred magnetically while the solvent was pumped off slowly and crystallization occurred. Stopcock A was then closed, and the Sfg detached from the vacuum system to facilitate further operations. The solvent was drained off through the sintered glass filter, then bulb E containing crystals cooled in ice to distill solvent back for recrystallizing and washing the dialkylmagnesium. After two recrystallizations, the Sfg was reattached to the vacuum system at H and all the solvent removed by pumping and gentle warming of the dialkylmagnesium.
5Ibid. 44
The ether stock flask was then attached to H, cooled in dry ice, and evacuated. Ether was distilled onto the dialkylmagnesium by cooling bulb E and permitting the ether to warm to room tempera ture. Helium was admitted through stopcock B to bring the apparatus to atmospheric pressure. The suspension was stirred and warmed to bring the solid into solution. A sample was withdrawn through stopcock C for NMR analysis and titration.
Calibration of spectra
The chemical shift(
X10 = ~ ^ T “ X10 where H and are the magnetic field and the frequency, respec tively, at which resonance absorption occurs for the nucleus in question; Href and i) ref refer to the same quantities for the protons of the reference compound. On the *T scale, ® the chemical shift of the protons in tetramethylsilane (TMS) is defined to be 1 0 . 0 0 0 ppm, and the chemical shift of all other protons is referred to this value. The Y scale will be used through out this paper. The close approximation t^ref = Uo = 60 x-10® cps
®G. V. D. Tiers, Minnesota Mining and Manufacturing, Minneapolis, Minn. 45 may be substituted in the denominator, with an error of less than
1 0 0 0 cps.
The NMR spectra were calibrated by the method of audio side band modulation;^ when the primary magnetic field is modulated with a low amplitude audio-frequency signal, bands appear on either side of all resonance signals. The separation between each side band and the resonance signal is equal to the modulation of frequency.
By changing the audio-frequency, it is possible to superimpose a sideband of a known resonance signal onto the resonance signal whose chemical shift is to be determined. The audio-frequency was counted for 10 seconds on a Hewlett-Packard digital counter with an accuracy of + 0 . 2% or better.
The chemical shift of easily recognizable solvent peaks was determined with respect to TMS in separate experiments and the
solvent peaks used as secondary internal standards for most^
T. Arnold and M. E. Packard, _J. Chem. Phvs. 19, 1608 (1951).
^Solutions of dialkylmagnesium compounds in ether were often too dilute for accurate measurement by audio side bands; the value of Jq 13 _h for the methyl group of ether was determined to be 130. 2 cps, and chemical shifts determined by linear extrapolation.
Solvent bands in tetrahydrofuran (THF) are complex multi- plets and unsuitable for calibration purposes. Arylmetallic compounds in THF were calibrated by use of a benzene resonance peak, present in solution from hydrolysis. 46 solutions of organometallic compounds. Direct addition of TMS to solutions of organometallic compounds for use as an internal standard was found to introduce sufficient moisture to hydrolyze much of the sample. The chemical shift of the methyl groups of solvents, determined in 0. 5 M. solutions of methylmagnesium iodide, is shown in Table 3.
TABLE 3
CHEMICAL SHIFT OF METHYL GROUPS IN SOLVENTS
Solvent
Diethyl ether 8. 88
Anisole 6. 53
Diglyme 6.72
Chem ical shift in ppm; cTt MS = PPm CHAPTER HE
RESULTS AND DISCUSSION
General Considerations: Aliphatic Grignard Reagents
The range of concentration of the organometallic compounds studied was limited by the broadening of the spectral lines due to increased viscosity at higher concentrations. Most solutions of organometallic compounds were prepared in the range 0. 5 M to
1. 0 M for nuclear magnetic resonance (NMR) analysis.
The first problem investigated was that of the dependence of the NMR spectrum of Grignard reagents on the concentration of magnesium bromide.
Magnesium bromide was precipitated from an ether solution of the Grignard reagent by the addition of 1, 4-dioxane. ^ The resultant suspension was centrifuged and evaporated to dryness.
The dialkylmagnesium was redissolved in anhydrous diethyl ether.
Representative results for samples with the most similar concen trations are given in Table 4.
Isee Chapter n for details.
47 48
TABLE 4
PROTON CHEMICAL SHIFTS OF GRIGNARD REAGENTS DIALKYLMAGNESIUM COMPOUNDS
Compound Solvent C one.a g ^ p p m ) ^ ( p p m )
MeMgBr E t20 0. 51 11.31
MeMgl E t2G 0 . 60 1 1 . 2 2
M e2Mg Dioxane 0. 15 11. 55
M e2Mg E t20 0. 1 11.4
EtM gBr E t20 0.65 10.62 8.9
E t 2Mg Dioxane 0. 40 1 0 . 8 8 .9
E t 2Mg E t 2 0 0 . 60 10.7 8 .9
0 CH2MgBr EtgO 0.75 8.62
(0CH 2)2Mg Dioxane 0 . 62 8.7
(0CH2)2Mg EtgO 0.51 8.7
Sec-BuM gBr E t20 0. 55 1 0 . 2
(Sec-Bu)2Mg Dioxane 0.49 10.3
Concentrations in acid equivalents/liter.
^Chemical shifts on Y scale, based on *fsi(CH 3 ) 4 = 10.00 ppm.
Subscript oc refers to protons on carbon bonded to magnesium. 49
The results given indicate the small differences (~0. 1 ppm) between the spectra of the alkylmagnesium halide and the dialkyl magnesium compounds in ether. 2 Accordingly, small additional amounts of magnesium bromide in Grignard reagents (from coupling reactions or from ethylene dibromide initiation) will be assumed to have negligible effect on the NMR spectra.
The most noticeable effect of magnesium substitution in aliphatic compounds occurs in the chemical shift of the oc protons
(those bonded to the carbon atom bearing magnesium). The chemical shift of these protons is well above the chemical shift of the corresponding protons in the saturated hydrocarbons t (Table 5). Substitution of magnesium increases the chemical shift by a constant amount, about 1 . 4 ppm. ^ This upfield shift may be partially ascribed to the ionic character of the carbon-magnesium bond. Negative charge on the carbon atom will repel the electrons forming the carbon-hydrogen bonds, increasing the electron density in the hydrogen Is orbitals at the expense of the orbitals^
2cf. H. Roos and W. Zeil, Ber. Bunsenges. Phvsik. Chem. 67, 28 (1963).
^The chemical shifts cannot be directly compared, due to the large differences in concentration and environment.
^The hybridization of the carbon orbitals is not sp^ (see below). 50
TABLE 5
PROTON CHEMICAL SHIFT OF ALIPHATIC GRIGNARD REAGENTS AND HYDROCARBONS
Grignard reagent Hydrocarbon df H a JHf b (ppm) (ppm)
Methylmagnesium bromide 11.31 M ethane 4 .8
Ethylmagnesium bromide 1 0 . 6 Ethane 4. 1
Sec - butylmagnes ium brom ide 1 0 . 2 Butane 3.7
Chemical shift, onTscale, of protons nearest magnesium; Si(CH3 ) 4 = 10, 00 ppm.
^Chemical shift of protons in ppm referred to water. Pople, Scheider and Bernstein, HRNMR, p. 236. For approximate conver sion to the Tscale, 5,1 ppm may be added to these values. (This value was estimated from'cyclopentane in which = 3. 3 ppm [HRNMR] and = 8. 40 ppm in 0. 5 M cyclopentylmagnesium bromide [investigator's value]).
7 51 of carbon. As a result, the nuclear shielding of the protons will be increased. 5
Positive contributions to the chemical shift of the protons will also occur due to the neighbor-anisotropy effect. ® The magnetic susceptibility of the carbon atom in methane is isotropic by sym metry. The substitution of a metallic atom for a hydrogen atom introduces anisotropy into the electronic structure of carbon; the carbon atom of methylmagnesium halide will have an axis of sym metry instead of spherical symmetry.
The effect of neighbor anisotropy on the chemical shift of the protons has been estimated in some compounds by substitution of a point magnetic dipole at the center of the anisotropic atom; 7 this
appears to be a poor approximation in the caseof methylmagnesium
halides and sim ilar compounds. A case in point is the pyramidal
ammonia molecule; assuming the nitrogen atom to have an effective axis of symmetry, the neighbor-anisotropy contribution to the
chemical shift of the protons is given^ by
-lR"3.A X . (l-3cos2y)in the magnetic dipole 2 atom ic q
^G. Fraenkel et al., J. Am. Chem. Soc. 82, 5846 (1960).
^Pople, Schneider and Bernstein, HRNMR, p. 176.
7J. A. Pople, Proc. Rov. Soc. (London) A239, 550 (1957).
^Pople, Schneider and Bernstein, HRNMR, p. 178. approximation. The internuclear distance R is certainly positive;
A X atomic, the anisotropy of the susceptibility tensor, is defined
such that it is negative. The term (1 - 3 cos^) is negative between
0° and 57°, and between 123° and 180°. The bonds of hydrogen in
molecules with approximately sp® hybridization (such as ammonia
or methylcarbanion) would form an angle y of about 108° with the
symmetry axis, giving a positive ( 1 - 3cos®y) term and a negative
contribution (A G *) to the chemical shift. A quantitative calculation for the ammonia molecule has shown the contribution to the chemical
shift to be 0 . 25 x 1 0 “® ppm, in the positive direction. ^
Pople's value was obtained by estimating the paramagnetic
electron circulation about the nitrogen atom. This circulation
arises from a mixing of the ground state and the electronic excited states of the molecule and may be calculated if the electronic wave functions are known. These wave functions for the methylcarbanion are unknown, but since it is isoelectronic with ammonia, the value
+0. 25 ppm should be of the correct order of magnitude for the neighbor-anisotropy effect in the partially ionic methylmagnesium halide compounds. 53 Lithium and Magnesium Organometallic Compounds
Organolithium compounds were prepared from lithium metal and alkyl halides in ether (Ch. U) and their NMR spectra obtained.
A comparison between representative samples of alkyllithium compounds is shown in Table 6.
The NMR spectra, the NMR parameters, and consequently the electronic structure of the Grignard reagents and the corre sponding lithium reagents are remarkably similar. The small differences between the two may be partially explained on the basis of different hybridization of the carbon-metal bond. The bond hybridization of methylmagnesium iodide and methyllithium 3 in ether solution was calculated from the observed carbon-hydrogen „ coupling constant (Jq13_jj in cps) by the equation
JC 13-H = 5 0 0 where is the s_-character of the C-H bond. ^
Table 7 illustrates the results.
^Prepared from iodomethane containing C ^-3 as 50% of total carbon. ^Details in Ch. I; C. Juan and H. S. Gutowsky, loc. cit. 54
TABLE 6
PROTON CHEMICAL SHIFTS AND COUPLING CONSTANTS OF GRIGNARD REAGENTS AND ALKYLLITHIUM COMPOUNDS
Compound^ Solvent Cone, f a (eq. / I.) "H(D c£h(2) <$H(3) J l , 2 J l,3 J2,3 (ppm) (cps)
MeMgBr E t20 0.51 11.31
MeLi EtgO 0. 50 11.4
EtM gBr EtgO 0.65 1 0 . 62 8.9 8. 96
EtLi EtgO 0. 50 10.99 8.9 8. 90
(2)H H(l) 1 1 C = C THF 0.51 0 . 0 0 0. 50 0 . 82 17. 2 2 2. 1 7 .4 il i (3)H MgBr
(2)H H (l) 1 1 C = C THF 0. 5 0 . 0 0 0.51 1. 19 19.3 23.9 7.3 1 1 (3)H - Li n Chemical shift of methyl and ethyl compounds referred to dSi(CH 3 ) 4 = 10. 00 ppm. Chemical shift of vinyl compounds referred to ^Hi = 0.00.
^Vinyllithium data of C. S. Johnson et al., J. Am. Chem. Soc. 83, 1306 (1961). 55 TABLE 7
BOND HYBRIDIZATION IN METHYLMETALLIC COMPOUNDS
Compound JC 13_H.(cps) or2 C-H C -M etal
Methylmagnes ium iodide 100.4 . 2 0 1 s- 6 0R2- 4 0 s- 4 0jp- 6 0
M ethyllithium 8 8. 5 . 177 s . 53^2. 47 s* ^
During formation of the organometallic compounds, rehybridi zation of the carbon orbitals occurs. The orbital of carbon bonded to metal gains s_-character at the expense of the other orbitals. The hybridization of the orbital comprising the carbon-metal bond becomes very close to the sjg bonding found in acetylenes, particu larly in methyllithium. The ability of acetylene itself to form stable ionic salts with active metals is well known. The sp. hybridization and the formation of ionic bonds with active metals; the ionic nature of the alkyl group and the increased chemical shift of adjacent protons; the sim ilarities between the chemical shift of protons adjacent to lithium and those near magnesium—all these are self-consistent properties of the carbon-metal bond. 56
Mixed Grignard Reagents
Methylmagnesium iodide and methyllithium were mixed
together in ether to determine the rate of exchange of the two metals.
In every mixture one sharp line was observed which obeyed the
formula XCH3MgI «/*CH3MgI + x CH3Li ^CH 3 Li =
where X is the mole fraction and J* the chemical shift. The
chemical shift is thus the average of the two possible positions of
the methyl group, indicating that fast exchange occurs. Since no
broadening of the line occurs, the lifetime of the bound state may
* be estimated from the formula TT l 4 - )?b
The chemical shift 0&( - q 0-) between pure methylmetallic
groups is of the order of 6 cps, putting an upper limit of 0. 07
seconds on the lifetime of both C-Mg and C-Li bonds. This value
is much higher than the upper limiting value of . 008 seconds found
by Dessy etal. in studies of mixture of Me 2Mg and CdMe 2 « H
Undoubtedly, the mean lifetime of a methyl group on lithium is of
the order of that for magnesium, but a low temperature would be
necessary to observe slow exchange.
l^H. S. Gutowsky and C. H. Holm, J. Chem. Phys. 25, 1228 (1956).
H r . E. Dessy etal., J[. Am. Soc. 85, 1191 (1963). 57
Even with fast exchange, differences might occur between the spectrum of R" in R2Mg and in R'RMg. In order to investigate this, solutions of mixed Grignards were prepared in one or more of three ways:
1. Separate preparation of the Grignard reagents with sub sequent mixing in an NMR sample tube in various proportions.
2. Reaction of a mixture of the two halides.
3. Reaction of the halides in the same vessel in sequence.
Methylmagnesium iodide-phenylmagnesium bromide mixtures were prepared in all three ways; other alkylmagnesium bromide pairs were prepared by method ( 2 ) as follows:
Benzyl; sec-butyl
Methyl; sec-butyl
Methyl; 2, 2 -dimethylcyclopentyl
In each case, the resulting spectrum was a superimposition of the
spectra of the two components.
The conclusions that were drawn from these results were
largely negative; the molecules RMgX and R 2M g may or may not
exist in solution. If the fast exchange of alkyl groups observed in
methylmagnesium bromide-methyllithium also occurs for other
Grignard reagents, only the average environment of the alkyl groups
can be observed by NMR spectroscopy. 58
Asymmetric Grignard Reagents
The problems of alkyl inversion and exchange were investi gated further by means of asymmetric bromides and Grignard reagents.
The Grignard reagent of 2 -bromobutane was prepared in ether and the NMR spectrum studied with particular attention paid to the methylene group. This group was largely obscured by ether peaks, hence a 1, 4-dioxane solution was prepared. In dioxane, the methylene group is an equally spaced quintet in the Grignard reagent and a complex multiplet in the starting material, which would be expected if the methylene protons were magnetically non-equivalent in the bromide and equivalent in the Grignard reagents. The complexity of the spectrum, though, made it unsuitable for exact analysis.
The Grignard reagent of 2 -bromo-l-phenylpropane was prepared, 12 the NMR spectra of the bromide and the Grignard reagent analyzed as follows:
1. The protons in the aliphatic moiety of 2-bromo-1-phenyl - propane constituted an ABRY 3 system (Fig. 5); the NMR spectrum
l^The lithium derivative of 2 -bromo-l-phenylpropane was not prepared since coupling products prevailed; coupling also occurred to some extent in the Grignard reagent. NMR 60Me 33°
0C H 2CHCH3Br in CCI4
8.49 7.98
H Fig. 5. —NMR Spectrum of 2-bromo-l-phenylpropane 60 showed the expected magnetic non-equivalence of the methylene protons CAB), due to the adjacent asymmetric carbon atom.
2. The aliphatic protons of the Grignard reagent were analyzed as an A 2RY3 system (Fig. 6), with magnetically equivalent protons in the methylene group. The chemical shifts and coupling constants for these compounds are shown in Table 8.
The magnetic equivalence of the methylene protons in the
Grignard reagent indicates that the adjacent carbon atom does not remain asymmetric, barring the possibility of inversion about the methylene group itself. This loss of asymmetry is presumably due to the ease with which a carbanionic form may invert (Chap. I).
Rapid inversion precludes any possibility of detecting optical isomers in this reagent; d,- and N- enantiomorphs do not exist long enough at room temperature to be caught by NMR spectroscopy.
To furnish a reactive primary bromide with an asymmetric carbon atom, l-bromo-2-phenylpropane was synthesized from allyl bromide and benzene, with the aid of sulfuric acid (Chap. n). The
NMR spectrum of the aliphatic protons was found to comprise an
ABCX3 system (Fig. 7), with the magnetically non-equivalent methylene protons (AB) fortuitously close to the benzyllic proton
(C). NMR 60 Me 33* a CH2CHCH3MgBr in Ether
7.33 9.81 CHt CH
6. —NMR Spectrum of 2-bromomagnesio-l-phenylpropane CT5 62
TABLE 8
CHEMICAL SHIFTS AND COUPLING CONSTANTS OF 2-BROMO- 1-PHENYLPROPANE AND THE GRIGNARD DERIVATIVE
Compound fa d A 4 4 4
R B r 6.95 7. 07 5. 87 8.49
RMgBr 7.33 7.33 9.81 8.75
jb Compound AB JAR JBR JRY
R B r 14.0 7 .0 7 .0 6 .9
RMgBr * 0 . 0 7 .4 7 .4 7 .4
Chem ical shifts given in ppm on T scale ~ ^0 ppm. t f c h2(a b ) CH2(A2)
Br -C-H(R) RMgCH(R) I I CH3 (Y3) c h3 cy3)
^Coupling constants (J) in cps. NMR 60 Me 33° 63
H I I I 8 . 4 9 5.87 6.65 Tau Scale
CH 3 C H . C H 2
7. —NMR Spectrum of l-brom o- 2 -phenylpropane
« 3 3 . 6 c p s 64
The Grignard reagent was prepared easily, and the NMR spectrum of the aliphatic protons analyzed as A 2RX3 (Fig. 8).
Table 9 shows the chemical shifts and coupling constants of the
bromide and the Grignard reagent.
To investigate possible variations of exchange rates in other solvents, the Grignard reagent of l-bromo- 2 -phenylpropane was prepared in a solvent less basic than ether--anisole—and in a more basic solvent--diglyme. In all solvents, the spectra were nearly identical, with the aliphatic protons constituting an A 2RX3 system .
The Grignard reagent from l-bromo- 2 -phenylpropane is dissimilar to those from 2 -bromobutane and 2 -b ro m o - 1 -phenyl - propane in that the asymmetric carbon atom itself is not involved in the Grignard reaction and presumably maintains its configuration throughout. The methylene group itself inverts and would probably have the smallest energy barrier to inversion of the three.
To investigate the behavior of an alkyl group with a high energy barrier to inversion, the Grignard reagent of 2 -b ro m o - 1 ,
1-dimethylcyclopentane was prepared. This bromide reacted incompletely in ether, even after 24 hours reflux; some purification of the ether solution proved to be possible, since the Grignard reagent separated into two metastable 12 liquid phases at 17° C.
l^Cooling in dry ice resulted in slow formation of a stable solid phase which would not redissolve completely on heating. NMR 6 0 Me 33°
" ^(CHCHjCHjMgBr" in Ether
Fig. 8. --NMR Spectrum of l-bromomagnesio-2-phenylpropane a CJI 66
TABLE 9
CHEMICAL SHIFTS OF l-BROMO-2-PHENYLPROPANE AND THE GRIGNARD DERIVATIVE
C ompound h 4
R B r 6. 63 6.74 6. 94 8.72
RMgX 1 0 . 0 0 1 0 . 0 0 7.06 8.77
Compound jb AB JAC JBC JCX
R B r 11.7 6 . 6 6. 6 6 .4
RMgX 0 . 0 0 6 . 6 6 . 6 6.5
Chemical shifts in ppm referred to
Me(X3) Me(X3) I I 0-C-H(C) 0-C-H(C) I I CHgBrCAB) CH 2 MgBr(A2)
^Coupling constants in cps. On cooling, the lower phase increased slowly in concentration of the Grignard reagent, and the upper phase increased in concentra tion of impurities, particularly starting material . 14
The methyl peaks in the ether solution of the reagent were clearly observable only at high concentration, when the ether triplet had shifted considerably downfield; consequently, samples were pre pared in diglyme solution. Comparison of the chemical shift of the
-< * methyl groups is shown in Table 10.
TABLE 10
CHEMICAL SHIFT OF METHYL GROUPS OF 2-BROMO-l, 1-DIMETHYLCYC LOPENTANE AND THE GRIGNARD DERIVATIVE
C ompound Solvent Concentration Bromide Diglyme 0. 50 8. 89 8. 89 G rignard reag en t E th er 1 . 62 8.75 8.91 G rignard reagent Diglyme 1. 73 8. 79 8. 99 G rignard reag en t Diglyme 0.61 8.78 8. 98 l^The Grignard reagent from 2 -b ro m o -l, 1 -dimethylcyclo- hexane exhibited similar behavior; two phases separated below 37° C in a sealed tube. The NMR samples were so contaminated with side products that the analyses were uncertain. 68 The magnetic equivalence of the methyl groups in the bromide is apparently accidental; molecular models indicate steric interac tions may occur between one methyl group and the bromine atom. Both methyl resonance peaks are somewhat broadened in the Grig nard solutions, the upfield one more than the other; this could be due to unequal long-range coupling with other protons in the mole cule. The presence of two methyl peaks indicates that fast exchange of alkyl groups occurs, but carbanion inversion is slow. Aromatic Orqanolithium and Grignard Compounds Aromatic Grignard reagents were prepared with the aid of initiators as described in Chapter II; the presence of small amounts of excess magnesium bromide or methylmagnesium iodide did not noticeably affect the NMR spectra. Table 11 lists the NMR parameters obtained. The spectra of the deuterium-substituted compounds were simplified by double-irradiation methods; p- substituted compounds in ether were analyzed as AgB 2 systems (Fig. 9), and the m- disubstituted compound as A 2 X. 15 15pople, Schneider and Bernstein, HRNMR, chap. vi. TABLE 11 CHEMICAL SHIFTS AND COUPLING CONSTANTS OF AROMATIC ORGANOMETALLIC COMPOUNDS Compound Concentration Solvent rb J2,4 J2 ,5 J2,6 J3,5 (moles/liter) So ^P 2,3 P-0-d;[-MgBr 0.53 Ether 2.290 2. 909 7. 26 .8 0 .80 1.39 3, 5-0-d2-MgBr 0. 40 Ether 2.29 2.95 1.6 P-0-di-Li 0.50 Ether 1.896 2. 900 6.81 .8 1 .8 2 1. 26 P-C10MgBr 0.75 Ether 2.41 2.93 6.3 P-Br0MgBr 0.83 Ether 2.40 2. 93 6.3 P-BrMg0MgBr 0.72 THF 2.40 Chemical shift (cf) in ppm on T scale, Coupling constants(J) in cps. G i CO 70 NMR 60 Me 33' ,VD0MgBr" in Ether "/?[)0U " in Ether 68 cps Fig. 9. —NMR Spectra of p-phenyl-d^ magnesium bromide and jo-phenyl-d^-lithium 71 The analyses of p-phenyl-d^-metallic compounds were accomplished with the aid of an IBM 7090 computer. ^ The ultraviolet spectrum of an ether solution . 0026 M. in phenylmagnesium bromide and . 002 M. in ethylmagnesium bromide o was obtained; a maximum occurs at 2650 A , with a long tail toward higher wavelength. The sample was hydrolyzed and the UV spectrum of the hydrolyzate obtained and subtracted from the spectrum of the Grignard reagent; the resultant spectrum shows a distinct maximum at 2900 A, with € = 815. In the range 2300 - 3000 A, . 005 M. ethylmagnesium bromide and . 005 M. magnesium bromide both had negligible absorption. The low field shift of protons ^o- to magnesium is remarkable in view of the fact that the opposite effect occurs in aliphatic Grignard reagents. The three effects most responsible for the chemical shift of the aromatic protons--ring current, charge on the carbon atom, and paramagnetic effects--may be examined by comparison with benzene to account for the anomalous ortho proton shift in phenylmetallic compounds. ^ ^Computer programs (NMREN and NMRIT) courtesy of J. Swalen, IBM Corp., San Jose, Calif.; the assistance of K. Bucher, Sohio Research, Parma, Ohio, is gratefully acknowledged. -^See Chap. I for a more general discussion of these effects; solvent effects are probably small and will not be considered here. Pople, Schneider and Bernstein, HRNMR, ch. xvi. 72 1. The ring current is presumably unaffected by the substitu tion of a metal for. bromine, since the TT electrons are not involved in the bonding between carbon and the metal. 2. The effect of charge would cause a chemical shift to higher field; the upfield shift of the protons meta and para to the metal, with respect to the chemical shift of benzene, is presumably due to a small negative charge on the respective carbon atoms. That the protons in the p-di(bromomagnesio)benzene appears to the low field side of benzene provides striking proof that the effect of charge, tending to cause chemical shift to higher fields, is not the most important factor. 3. The paramagnetic effects would appear to be responsible, barring additional unknown effects. Insight Into the behavior of an aromatic carbanion may be r attained by a study of the isoelectronic nitrogen heterocyclic com pound; insofar as Grignard reagents may be considered to be associated salts of carbanions, the same conclusions will apply to compounds. Phenylmagnesium bromide and pyridine, the simplest isoelectronic pair, will be considered as a case in point. l^Steric effects have been postulated in some cases, but would ‘be difficult to invoke in this case, since the factor causing low field shift of the ortho protons is operative to a greater extent when the smaller lithium atom is present. Pyridine and other nitrogen heterocycles have low-lying excited states. Transitions between the ground states and their excited states (Fig. 10) can be detected in the ultraviolet absorp tion spectrum of the molecule. Two transitions are of particular in te re st: 1. The n-frTr transition, in which one of the paired elec trons on the nitrogen atom is promoted to the low-lying IT * antibonding orbital. This is the weaker transition of the two, but is of lower energy. 2. The rr-»TT* transition, in which one of the tt electro n s is promoted out of the i t bonding orbital into the t t antibonding orbital. This transition gives rise to a strong absorption band in the ultraviolet. The n —kTT* absorption band of nitrogen heterocyclic com pounds in different solvents does not always appear at the same wavelength. ^ Hydrogen bonding solvents increase the energy of this transition by an amount corresponding to the strength of the hydrogen bond; when complete protonation occurs, this energy change increases to a maximum. 2 0 -^G. J. Brealey and M. Kasha, J. Am. Chem. Soc. 77, 4462 (1955). 20q . Fraenkel and J. Kim, private communication. charge transfer D hv Strong n-+Tr* Excitation hv Weak Variation of n -> u * energy Antibonding MO TT* ------^— ^ 4 - Nonbonding MO n f H- Bonded Protonated AE n^TT* increases with H-bonding Fig. 10. —Paramagnetic Transitions in Aromatic Organometallic Compounds 75 An effect analogous to hydrogen bonding should appear in phenyl carbanion since a metal is more or less strongly bonded to the ring. An ionic bond should give a lower energy n-^Tp* gfe transition than a more covalent bond. The TT—* TT transition on the other hand, is relatively insensitive to solvent effects and pro vides a convenient reference absorption, as well as some assurance that nothing drastic is occurring in the molecule. A third type of transition—charge transfer—is available to phenylmagnesium bromide but unavailable to pyridine. This type of transition in aromatic compounds has been observed in benzene- iodine ^ 4 and in pyridine-iodine2^ complexes; in non-aromatic complexes, many different types of compound pairs have been observed to undergo charge transfer, particularly amine complexes with metal halides. 23 Recently, an additional absorption peak has been observed to appear in pyridine when complexed with magnesium bromide. Charge transfer absorption arises when an electron 21r . S. Mulliken, _J. Am. Chem. Soc. 74, 811 (1952). 2 2 E. m. Kosower and P. E. KLinedinst, Jr., J. Am. Chem. Soc. 78, 3493 (1956). 23r . s . Mulliken, J. Phvs. Chem. 56, 801 (1952). 2 4 G. Fraenkel and S. Dayagi, private communication. 76 is promoted from the electron-donor compound to an excited state of the electron acceptor. The energy required for the transition (AE) will depend on the ground state and the excited states of the molecule. The AE of the n—>77* excited state in pyridine cannot be determined because this transition is covered up in the ultra violet spectrum of the molecule. Measurement of the chemical shifts of pyridine in hydrogen bonding solvents shows qualitatively that the ortho protons are moved to higher magnetic fields in more strongly hydrogen-bonding solvents. 25, 26 Verification of the paramagnetic effect as the principal cause of low field shifts has been found in the ultraviolet spectrum of azines. The energy of 7j —> 77* absorption in azines has been found to increase in more strongly hydrogen-bonding solvents. 27 a comparison of NMR and ultraviolet spectra of pyrimidine shows that then —>77* excitation energy in different solvents is inversely proportional to the chemical shift between the protons in the three and four position to nitrogen. 28 2 5I. C. Smith and W. G. Schneider, Can. J. Chem. 39, 1158 (1961). 26j. a . Elvidge and L. M. Jackman, J. Chem. Soc. 859 (1961). 27 f . Halverson and R. C. Hirt, J. Chem. Phys. 17, 1165 (1949). 28j, Kim, unpublished results. 77 o The absorption band at 2900 A in the UV spectrum of phenyl- magnesium bromide may be due to either charge transfer or n —»7T* absorption, since only one band is observable. Both transitions are likely to occur, but the n—> TT* is probably the weaker absorption and may be hidden; both will contribute to the chemical shift in phenylmagnesium bromide. Quantitatively, the determination of the nuclear screening of an atom in a large molecule is extremely difficult to calculate. The general expression for an isolated molecule was first obtained by Ramsey, ^ but is unsuitable in that both the diamagnetic term and the paramagnetic term in the equation become large and tend to cancel each other for all but the smallest molecules. Qualitatively, the diamagnetic term measures the strength of the secondary field (opposed to the prim ary field) which is generated by the induced motion of the electrons about the nucleus under consideration. Physically, it corresponds to the rotation of the electronic structure of the entire molecule about the nucleus under consideration. The paramagnetic term effectively corrects for hindrance to this free rotation, and vanishes if the system is axially symmetric about the direction of the primary field. F. Ramsey, Phvs. Rev. 78, 699 (1950). 78 Of) Saika and Slichterow divided this screening into separate atomic contributions: 1. Diamagnetic term for the atom itself. 2. Paramagnetic term for the atom itself. 3. Contributions from other atoms in the molecule. Since the protons ortho to a metal are concerned here, the first two contributions are not likely to change a great deal in going from benzene to an aromatic organometallic compound. The contribu tions from other atoms will be altered most by the egregious change in the anisotropy of the carbon atom undergoing substitution by a metal. The anisotropy effect has been calculated for an atom bonded to the proton in question, whereas the anisotropic carbon atom is further from the ortho protons and is not bonded. The benzene ring is quite rigid; therefore, the atoms remain in the same posi tions relative to one another. Using the magnetic dipole approximation, the mean contribu tion to the proton screening constant (ACT) is given by ACT= -^3- Atomic u - 3 cosV i = 1, 2, 3, where R is the internuclear separation, X^- the three principle 30a . Saika and C. P. Slichter, J. Chem. Phvs. 22, 26 (1954). 79 susceptibilities of the carbon-magnesium bond, and the angle between the inter nuclear line and each direction i (Fig. 11 [a ] ) . 3 1 The distance R between two protons ortho to one another in benzene o o is about 2. 5 A, the sum of the carbon-carbon bond length (1. 4 A) and o the carbon-hydrogen bond length (1.1 A) in benzene. The distance R is difficult to estimate exactly in arylmetallic compounds, since the electrons responsible for the anisotropy are presumably closer o to carbon than to the metal. The carbon atom itself is 2. 17 A from the ortho protons, so that the effective distance R from the protons o to the magnetic dipole may be about 2. 2 A. The same difficulties beset estimation of the angle £; a line connecting two ortho protons makes a 60° angle with a symmetry axis through either of the C-H bonds, but the line from the anisotropic carbon atom to an ortho proton makes an angle of 94° with the symmetry axis of the carbon atom. If the magnetic dipole approximation is made, a point dipole is substituted at the center of the anisotropic carbon atom. The ortho protons will be within 4° of the perpendicular to it, and o 2. 17 A away. Unfortunately, no data are available for the principal magnetic susceptibilities (X^tomic) of phenyl carbanion. 3-4?ople, Schneider and Bernstein, HRNMR, section 7-5. 80 M 2.17 H I I Fig. 11. —Paramagnetic Effect in Aromatic Organometallic Compounds On a qualitative basis, it may be seen from Fig. 11 (b) that a shift to low field may be expected; to quote from Pople, Schneider and Bernstein, "If the neighboring atom [2Q has a greater dia magnetic susceptibility along the XH bond than perpendicular to it, the proton will experience increased shielding. "32 Other estimates of the neighbor-anisotropy effect have been made on the theory that the anisotropy arises from a mixing of the ground state with electronic excited states when the applied field is perpendicular to the molecular axis. 33 p Gr exact calculation, a knowledge of the wave functions for the excited states is necessary; however, these wave functions are generally unavailable. The "closure approximation, " in which the orbital operator giving the sum over the excited states is replaced by a single constant 1 - —r , is often used. The constant A e has the meaning of an AE average excitation energy of the molecule, and is correct if the contribution of one particular excited state far exceeds that of the others, for instance if this state is close to the ground state. An 3 2 i b i d . 3 3Ibid. 82 order of magnitude calculation of the paramagnetic shift in phenyl - carbanionic compounds may be made using the e q u a t i o n ^ fj- -4 /3 2 -e 2 t l 2 p 3 /iE R 3 3m 2c 2 AER 8 The distance R between the anisotropic carbon atom and the ortho o protons is 2. 17 A. The mean excitation energy AE will be taken to be equal to that of the transition observed in the ultraviolet o absorption spectrum; the absorption maximum at 2900 A corre sponds to a AE of about 4. 5 ev. Substitution of these values gives a chemical shift of -1.6 X 10"® due to the paramagnetic transitions in phenylmagnesium bromide. This value is only a rough estimate because of the approximations used, but is large enough to cause the anomalous downfield shift of the protons ortho to a metal. Comparison of theory with experiment cannot be exactly done, since the amount of charge on the o.- carbon atom is unknown. The chemical shift of theo- proton has been ascribed to inductive and resonance effects; that of the m- protons to the inductive effect alone; and that of the jg- protons to resonance effects alone. 35 Since no conventional resonance forms can be written for phenyl 3^A. Abragam, "Principles of Nuclear Magnetism, " Oxford University Press, London, 1961, pp. 173-83. 35p 0 ple, Schneider and Bernstein, HRNMR, sec. 11-5. 83 carbanion, to a first approximation the chemical shift of the jd- proton will be affected by paramagnetic effects only. If the charged carbon atom is axially symmetric, the formula 0 " = ^ 3 ^ ^atomic (1-3 co s 2^ ) may be used to calculate -AXatomic from the observed chemical shift for the jd- proton. Substitution of the values for AXatomic, for the m- protons, Rm = 3.32 A, y m = 41?5, and o n O' m = + • 121; fo r the o- protons, R 0 = 2. 17 A, = 94 , and (fo = - .62. Comparison with the observed values CTm = + .18 and CJ"o = - • 44 shows that contributions of + 0.06 ppm and +• 0.18 ppm occur in the m- and _p- positions, respectively, which could reasonably be attributed to charge induced in these positions. The value of - 1 . 6 for O'0 from excited states is therefore high by about a factor of 2. 5 to 3. The presence of charge transfer as well as n —» TT* excited states in organometallic compounds makes exact correlation between the chemical shift and the excitation energy difficult, but the paramagnetic shift clearly occurs in these compounds. The lower shift of phenyllithium is explained by the more ionic carbon metal bond which permits a lower electronic excitation energy. CHAPTER IV SUMMARY AND CONCLUSIONS In this paper, several problems concerning the structure of Grignard reagent and organolithium compounds have been studied with the aid of nuclear magnetic resonance (NMR) spectroscopy; they are the electron hybridization, the carbanionic character, the rate of inversion, and the rate of exchange of the alkyl groups. The NMR spectra of the compounds have been analyzed, and the NMR parameters tabulated. The behavior of organometallic compounds in solution may be consistently explained by the hypothesis that the carbon-metal bond is partially ionic. As carbanions, the organic groups exchange rapidly with each other and readily invert their configuration about the negatively charged carbon atom; however, they also possess sufficient covalent character so that some macroscopic properties of carbanions, e. g. abstraction of a proton from a solvent molecule, are not observed. The effect of the partial negative charge on the NMR parameters of the protons in the alkyl groups has been explained. 85 The inductive effect of charge predominates in protons bonded directly to the charged carbon atom; the neighbor-anisotropy effect makes smaller positive contributions to the chemical shift of protons. These effects are attenuated quite rapidly, increasing the chemical shift of the other protons in the molecule by about 0 . 1 ppm if they are one carbon atom away, and practically not at all if they are further removed. The effect of a partial negative charge on the protons bonded to an aromatic ring is quite different, compared to the effect on aliphatic protons. The inductive effect of this charge is counter acted at the ortho positions by the effect of a secondary magnetic field induced by the motion of the electrons in the carbon-metal bond. The correction to the chemical shift caused by this magnetic field was termed the "paramagnetic shift, " and the magnitude of this shift was estimated to be -1.6 ppm at the o- positions; the esti mate was made from considerations of the geometry of the molecule and from the energy required for paramagnetic transitions. The paramagnetic shift was calculated to be positive at the meta and para positions, reinforcing the inductive effect of charge. The source of paramagnetic transitions was explained on the basis of low-lying excited states in aromatic molecules. The ultra violet absorption spectrum of phenylmagnesium bromide was .86 o obtained and the observed band at 2900 A was tentatively assigned to charge transfer absorption, by comparison with the pyridine- magnesium bromide complex. Further research on the exchange rate of bromide ion in solutions of Grignard reagents would be necessary to clearly formulate the structure; if bromide ion exchanges slowly, the Grignard reagent may have a different structure depending on the way in which it is made. If, however, bromide exchanges rapidly with itself and with alkyl groups, the molecules RMgX and R 2Mg are formed during precipitation and exist in solution only as pedagogical devices. BIBLIOGRAPHY Books Abragam, A. "Principles of Nuclear Magnetism. " Oxford Uni versity Press, London, England, 1961. Pople, J. A., Schneider, W. G., and Bernstein, H. J. "High- resolution Nuclear Magnetic Resonance. " McGraw-Hill Book Company, Inc., New York, N. Y ., 1959. Articles and Periodicals Abegg, R. Ber. 38, 4112 (1905). Arnold, J. T ., and Packard, M. E. J. Chem. Phvs. 19, 1608 (1951). Ashby, E. C ., and Becker, W. E. L Am. Chem. Soc. 85, 118 (1963). Baeyer, A., and Villiger, V. Ber. 35, 1201 (1902). Barbier, P. Compt. Rend. 128, 110 (1899). Becker, E. L Trans. N. Y. Acad. Sci. 25, 513 (1963). Bigeleisen, J., and Mayer, M. G. _J. Chem. Phys. 15, 261 (1947). Blaise, E. -E. Compt. Rend. 132, 839 (1901). Bloch, F. Phvs. Rev. 93, 944 (1954). Bloom, A. L ., and Schoolery, J. N. Phvs. Rev. 97, 1261 (1955). Brealey, G. J., and Kasha, M. J. Am. Chem. Soc. 77, 4462 (1955). 87 88 Brockway, L. O., and Jenkins, H. O. _J. Am. Chem. Soc. 58, 2036 (1936). Dennison, D. M ., R evs. Mod. Phvs. 12, 175 (1940). Dessy, R. E ., and Handler, G. S. J. Am. Chem. Soc. 80, 5824 (1958). Dessy, R. E ., and Jones, R. M. J. Org. Chem. 24, 1685 (1959). Dessy, R. E ., Wotiz, J. H., and Hollingsworth, C. A. _J. Am. Chem. Soc. 79, 358 (1957). Dessy, R. E ., Handler, G. S., Wotiz, J. H., and Hollingsworth, C. A. jJ. Am. Chem. Soc. 79, 3476 (1957). Dessy, R. E ., Kaplan, F ., Coe, G. R ., and Salinger, R. M. _J. Am. Chem. Soc. 85, 1191 (1963). Elvridge, J. A., and Jackman, L. M. J. Chem. Soc. 859 (1961). Evans, W. V., and Pearson, R. J. Am. Chem. Soc. 64, 2865 (1942). Fraenkel, G., Carter, R. E ., McLachlan, A., and Richards, J. H. J. Am. Chem. Soc. 82, 5846 (1960). Gilman, H ., and Esmay, D. L. _J. Org. Chem. 22, 1011 (1957). Gilman, H., Zoellmer, E. A., and Dickey, J. B. J. Am. Chem. Soc. 51, 1576 (1929). Grignard, V. Ann. Chim. (Paris) 24, 433 (1901). ______. Bull. Soc. Chim. France 29, 944 (1903). ______. Bull. Soc. Chim. France 39, 1285 (1926). ______. Compt. Rend. 130, 1322 (1900). ______. Compt. Rend. 136, 1260 (1903). Guild, L. V., Hollingsworth, C. A., McDaniel, D. H ., and Podder, S. K. Inorg. Chem. 1, 921 (1962). 89 Gutowsky, H. S., and Holm, C. H. J. Chem. Phvs. 25, 1228 (1956). Halverson, F ., and Hirt, R. C. J. Chem. Phvs. 17, 1165 (1949). Hamelin, R. Bull. Soc. Chim. France 684 (1961). Hamelin, R ., and Hayes S. Bull. Soc. Chim. France 692 (1961). ______. Compt. Rend. 252, 1616 (1961). Hampson, G. C ., and Mars den, R. J. B. Trans. Faraday Soc. 30, Appendix (1934). Hannay, N. B ., and Smyth, C. P. _J. Am. Chem. Soc. 68, 171 (1946). Johnson, C. S., Weiner, M. A., Waugh, J. S., and Seyferth, D. _J. Am. Chem. Soc. 83, 1306 (1961). Jolibois, P. Compt. Rend. 155, 353 (1912). Juan, C., and Gutowsky, H. S. j[. Chem. Phvs. 37, 2198 (1962). Kirrmann, A., and Hamelin, R. Compt. Rend. 251, 2990 (1960). Kirrmann, A., Hamelin, R ., and Hayes, S. Bull. Soc. Chim. France 1395 (1963). Kosower, E. M ., and KLinedinst, P. E ., Jr. J. Am. Chem. Soc. 78, 3493 (1956). Meisenheimer, J., and Schlichenmaier, W. Ber. 611, 720 (1928). Menschutkin, B. N. _Z. Anorg. Chem. 49, 34 (1906). Meyer, L. H ., Saika, A., and Gutowsky, H. S. _J. Am. Chem. Soc. 75, 4567 (1953). Muller, N ., and Pritchard, D. E. _J. Chem. Phvs. 31, 768 (1959). ______. J. Chem. Phvs. 31, 1471 (1959). Mulliken, R. S. _J. Am. Chem. Soc. 74, 811 (1952). Mulliken, R. S. J, Phvs. Chem. 56, 801 (1952). Nair, P. M ., and Roberts, J. D. J. Am. Chem. Soc. 79, 4565 (1957). Pauling, L. J. Am. Chem. Soc. 54, 3570 (1932). ______. J. Chem. Phys. 4, 673 (1936). Pople, J. A. Proc. Roy. Soc. (London) A239, 550 (1957). Prelog, V., and WIeland, P. Helv. Chim. Acta 27, 1127 (1944). Prevost, C., and Gross, B. Cornpt. Rend. 252, 1023 (1961). Ramsey, N. F. Phvs. Rev. 78, 699 (1950). Roos, H ., and Zeil, W. Ber. Bunsenges. Phvsik. Chem. 67, 28 (1963). Saika, A., and Slichter, C. P. J. Chem. Phvs. 22, 26 (1954). Schlenk, W., and Schlenk, W., Jr. Ber. 62, 920 (1929). Smith, I. C., and Schneider, W. G. Can. J. Chem. 39, 1158 (1961). Strohmeier, W. Chem. Ber. 88, 1218 (1955). Stucky, G. D ., and Rundle, R. E. J. Am. Chem. Soc. 85, 1003 (1963). Terentjew, A. P. Z. Anorg. Chem. 156, 73 (1926). Thorp, L ., and Kamm, O. L Am. Chem. Soc. 36, 1022 (1914). Wagner, G ., and Saytzeff, A. Ann. 175, 351 (1875). Watson, H. Proc. Rov. Soc. (London) A117, 43 (1927). Waugh, J. S., and Fessenden, R. W. _J. Am. Chem. Soc. 79, 846 (1957). 91 Whitesides, G. M ., Kaplan, F ., and Roberts, J. D. _J. Am. Chem. Soc. 85, 2167 (1963). Wotiz, J. H., Hollingsworth, C. A., and Dessy, R. E. J. Orq. Chem. 21, 1063 (1956). Wotiz, J. H., Hollingsworth, C. A., Dessy, R. E ., and Lin, L. C. J. Org. Chem. 23, 228 (1958). Unpublished Materials Tiers, G. V. D. "Characteristic Nuclear Magnetic Resonance (NMR) 'Shielding Values' (Spectral Positions) for Hydrogen in Organic Structures, " Minnesota Mining and Manufacturing Company, St. Paul, Minnesota, 1958. Other Sources Fraenkel, G., and Kim, J. Ultraviolet and Nuclear Magnetic Resonance Spectra of Pyridine in Hydrogen-bonding Solvents. March, 1963. Fraenkel, G., and Dayagi, S. Ultraviolet Spectra of Pyridine- magnesium Bromide Complex. January, 1964. Kim, J. Ultraviolet and Nuclear Magnetic Resonance Spectra of Pyrimidine in Hydrogen-bonding Solvents. September, 1963. A UTOBIO GRAPHY I, David George Adams, was born in Mansfield, Ohio, June 17, 1936. I received my grade and high school education at St. Peter’s, Mansfield, Ohio, and my first two years of under graduate training at the Ohio State University. I received the remainder of my undergraduate training at the University of Chicago, which granted me the Master of Science degree in 1959. While in residence there, I was assistant to Dr. Peter Eberhardt and Professor Harold C. Urey. In October, 1959, I was appointed a Teaching Assistant at the Ohio State University, where I specialized in the Department of Chemistry. I taught general chemistry for one and one-half years; then was appointed a Petroleum Research Foundation Fellow in 1961. I held this position for one year; then was appointed a National Institute of Health Fellow for two years while completing the requirements for the Doctor of Philosophy degree. I am currently being inter viewed by industrial research laboratories, and have not yet accepted a position. 92