1780
Vol. 86
EDGARW. GARBISCH, JR.
[CONlRIBUTION FROM THE
DEPARTMENTS OF CHEMISTRY OF THE UNIVERSITY OF CHICAGO, MISNESOTA, MINNEAPOLIS 11, AMINN.]
Conformations. V.
CHICAGO
37,
I L L . , A S D THE UNIVERSITY O F
Conformational Analysis of 2-Bromocyclohexanone by Nuclear Magnetic Resonance Spectroscopy BY EDGAR W. GARBISCH, JR.' RECEIVED OCTOBER 2, 1963
Conformational analysis of 2-brornocyclohesanone using both proton spin coupling and chemical shift paraineters shows that the Conformational isomer with the axial bromine (11) is preferred to the extent of 38-91 f 1tiA over the concentration range of 100-0 mole 56, respectively, of ketone in carbon tetrachloride.
Mobile systems under conformational equilibria often are amenable to quantitative or semiquantitative conformational analysis by n.m.r. s p e c t r o ~ c o p ;y ~ ~ ~ however, the success of this approach (as well as others) often relies on the availability of conformationally H homogeneous model substrates from which the nuclear I I1 spin coupling and/or chemical shift parameters for the various possible conformational isomers are derived. Cz-protons in I and I1 must be known. LVith regard to the proton couplings, these three spin systems in I In the absence of model substrates, the problem of conand I1 are of the ABX type5 where X is the Cz-proton formational analysis is reduced to the qualitative, or a t whose resonance is isolated downfield from the other best, semiquantitative level, for the necessary paring proton resonances. Neglecting the weak comrameters then must be estimated for the hypothetical bination transitions which are not often observed, the conformationally homogeneous isomers from theoretiseparation between the terminal peaks of the X resocal or empirical relationships (structural deformations J ( H 2 , H3e).5 If this and magnetic effects arising from the substituent being nance is equal to J(H2, H3a) coupling constant sum is designated J I and JIIfor I presumed negligible) or be obtained from "frozen out" conformational isomers a t reduced temperatures (temand 11, respectively, J" = J I W I JrINrr where J" is the observed separation between the terminal lines perature independence of chemical shifts being asof the Cz-proton resonance for 2-bromocyclohexanone. sumed). Ideally, conformational analysis of a subIt follows t h a t stance may be successful employing either the timeaveraged coupling constants or the chemical shift NI = J o - JII/Jr - JII (1) parameters of appropriate nuclei. In practice, however, coupling patterns are often complex or obscured Equation 2 gives the mole fraction of I utilizing the by long range virtual coupling, and model chemical chemical shifts of Hza (SI) and HPe (Sir) of I and 11, shift parameters may be rendered unreliable because respectively, and the observed chemical shift of Hz of the magnetic effects of the additional group or (SO) of 2-bromocyclohexanone. groups positioned so as to ensure model conformational homogeneity. Using the technique of nuclear spin NI = S o - 6 1 1 ! 6 I - 611 (2) decoupling, coupling patterns conceivably may be In order to estimate values of Jr and J I I ,representasimplified often to the extent where they could be used tive couplings were determined for a number of consuccessfully. formationally homogeneous model compounds. The As an example illustrating both the nuclear spin results are summarized in Table I . The Hzaresonance coupling and the shielding parameter approach to of no. 1 is slightly perturbed from the expected X-part conformational analysis, 2-bromocyclohexanone has of an ABX absorption, probably because of virtual been chosen, since this material has been investigated coupling to H4a.6 In no. 2 and 3 where the chemical extensively by other methods and data are available shift of the Cd axial proton is s p f t e d to lower field as for comparison. compared to t h a t of no. 1, the H,,,resonance is seen Results to be normal. The Hze absorption of no. 4 and 5 For rapidly equilibrating systems, observed couplings appear as triplets with each component of the triplet (and chemical shifts) are time averages of the couplings being split into doublets by about 1.5 C.P.S. This (and chemical shifts) in the various components under splitting has been found to arise from a stereospecific equilibrium. In order to estimate the equilibrium long range coupling to H6e.7 From the couplings in between the two conformational isomers of 2-bromoTable I , average values of 1S.2 and 5.7 C.P.S. are esticyclohexanone, I and 11, the proton spin couplings mated for J1 and J I I ,respectively. between Hs and Hsa, Ha, and the chemical shifts of the Values of J o as a function of the mole percentage of 2-bromocyclohexanone in carbon tetrachloride were (1) Address correspondence t o University of Chicagc,. ( 2 ) (a) E. I,. Bliel and M . H. Gianni, 7'eivnhriirorr f . e l l e r s , 97 ( 1 0 6 2 ) ; detertnined and are shown in Fig. 1. There was no I)ailey. J ( ' h e m . P h y s , 38, 445 (1963),
+
+
(c) ( h ) W. C . Neikam and R . P A . H . Lewin and S Winstein, J A m . C h r m . .So( , 8 4 , 2464 ( 1 9 6 2 ) . (3) A. A. B o t h n e r ~ B yand C . Naar-Colin. ibiii.. 84, 743 (1062), F. A . A n e t , ibid , 84, 717 ( 1 9 6 2 ) ; and H S . G u t o w s k y , G. G Belfurd, a n d P. M c M a h o n , J . ( ' h e m P h y s . , 36, :3353 (1962). (4) (a) J . Allinger a n d S 1. hllinjier. T e t r a h e d r o n , 2 , 64 (1958); (b) S . 1,. Allinger, J Allinger, and S . A . 1.e Bel. J A m . ( ' h e m .Sot.. 82, 2026 (1960); (c) B Waegell a n d G. Ourisson, R d i . soc. c h i n . F r a n c e , 496 (1968).
(.;) J . A . Pople, W G Schnedier, and H . J . Bernstein, "High-Resolution Nuclear hfagnetic Resunancp." hIcGraw-Hill Book Co..Tnc., S e w Yiirk, t i Y . , 1959. p . 134; and R T Abraham and H J. Bernstein. r o l l . J . r h e i n . . 39, 216 (1961). ( 6 ) J . I . hIusher a n d E. J. Corey, T p l r a h e d r o n , 18, 701 (1062). ( 7 ) E . W. Garbisch, J r . , Abstracts, 11.5th S a t i o n a l hIeeting r i f t h e American Chemical Society, Kew Y o r k , N . Y . , September 9-13, 1963. p . 36Q.
May 5 , 1964
1781
C O N F O R M A T I O N OF 2 - B R O M O C Y C L O H E X A N O N E
TABLE I COUPLINGPARAMETERS FOR MODEL SUBSTRATES
12.0
4
J(Hu,Hga)
+
Model
NO.
11.0
J(Ha,Hge), C.P.S.
Proton resonance
10.0
d
:9.0 5
8 0
7 0 6.8 6.0
I
0
1
I
1
20
1
40
.
1
60
1
1
,
100
80
%. Fig. 1.-Values of J o as a function of the mole percentage of 2-bromocyclohexanone in carbon tetrachloride. Mole
5.8
5.4
r' 5.5
5.6
5.7 5.72 5.74
concentration dependence of the couplings representative of J I and JIJin no. 1 and 5 of Table I. I n Fig. 2 are shown 61,611,and 6' as a function of concentration.8 Using the data in Fig. 1 and 2, J I and J I ~and , eq. 1 and 2, the percentage of I a t conformational equilibrium as a function of concentration in carbon tetrachloride may be estimated from either chemical shift or proton spin coupling measurements. The percentages of I a t several selected concentrations are shown in Table I1 along with reported results from other approaches for comparison.
5.8
: 0
10
20
40
30
50
60
70
To. Fig. 2.--Values of 61, 611, and 6' as a function of the mole percentage of ketone in carbon tetrachloride. Mole
determine whether or not eq. 1 leads to a comparable result. Rapid chair-chair interconversion of 111should
Br
TABLE I1 CONFORMATIONAL ANALYSIS O F 2-BROMOCYCLOHEXANONE"
Mole % 2-
..
hromocyclohexanone
Mole % I using eq. 1*
Mole % I using eq. 2 b
100 50 33 15 8
48
, . .
43 37 27 20 9
... 31 (35)d 26 (31)d 22 (29)d 8
Mole
% '
I , lit.
Ca. 50
Br
111
lead to a time-averaged coupling of the 2,6-protons representative of ( J I J I I ) /or ~ 11.9 C.P.S. The ... observed separation between the terminal lines of the ... a-proton resonance of I11 is 11.1 C.P.S. which leads to ... Nr = 0.43 in only fair agreement with expectation. 0 15 (heptane, dipole Possibly, a slight structural deformation of I11 could moment)< 17 ( C C I 4 , u l t r a v i ~ l e t ) ~ ~account for this discrepancy; however, the normal aproton resonances of no. 3 in Table I suggest that this a 25 f 2' in C C l 4 . ' =t4Yo7,. Ref. 4b and W. D. Kumler and may not be an adequate explanation. A . C . Huitric, J . Am. Chem. SOC.,78, 3369 (1956). Empirically ..
+
corrected (see text).
As trans-2,6-dibromocyclohexanone(111) represents a model for the case of N I = 0.5, it is of interest to (8) T h e a-axial protons ( a t o both t h e carbonyl and halogen) in a-haloketones are known t o resonate a t lower magnetic field t h a n t h e a-equatorial protons: A. N i r k o n , M. A. Castle, R . H a r a d a , C. E. Berkoff, a n d R. 0. Williams, J . A m . Chem. Soc., 86, 2185 (1963);a n d K.M .Wellman a n d F. G. Bordwell, Telrahedron Lellers, 1703 (1963). This is in contrast t o what is normally observed for cyclohexane systems.'
Discussion Mole percentages of I derived from eq. 1 and 2 appear to be in good agreement over the concentration range of 2-bromocyclohexanone in carbon tetrachloride shown in Table 11. The dependence of N I on fhe concentration of 2-bromocyclohexanone is expected, as it has been shown from previous work4 that NI (I
RUDOLFM.
1782
SALINGER AND
having a larger dipole moment than 11) increases as the dielectric constant of the solvent increases. At infinite dilution, N I = 0.09 f 0.04 as determined by n.m.r. spectroscopy employing both proton spin coupling (eq. 1) and chemical shift (eq. 2 ) parameters is in fair agreement with NI = 0.15 (in heptane) as determined by dipole moment measurement .4b Although there appears to be good agreement between the results employing eq. 1 and 2 (Table 11), there exists a possibility that model compounds used to obtain values of 61 and 6rI (no. 1 and 5 in Table I) are not totally satisfactory because of long range shielding effects arising from the t-butyl group.2b,C Eliel and co-workers10 have tabulated empirical corrections for the shielding effects of alkyl groups on the a-carbinol protons of alkylated cyclohexanols. From their results, a correction of +0.03 p.p.m. for the 611 values and no correction for the 61 values (Fig. 2 ) can be estimated. Using the "corrected" 611 values, new values of N I were derived from eq. 2 and these are shown as parenthetical entries in Table 11. It is difficult to justify (9) J. I. Musher, J . Chem. P h y s . , 36, 1159 ( 1 9 6 1 ) , 37, 192 (1962). (IO) E. I,, Eliel, M . H. Gianni, T h . H . Williams, and J . B . Stuthers, Telrahedron L e l l e r s , 741 (1962).
[CONTRIBUTIONFROM
THE
HARRYs. MOSHER
Vol. 86
the need for these corrections in this instance, since agreement between the uncorrected values of -Vl (Table 11) obtained from eq. 1 and 2 appears satisfactory. Experimental cis- and tr~ns-2-bromo-4-t-butylcyclohexanones,'~ 2-bromocy~lohexanone,~"and truns-2,6-dibromocyclohexanone1*were prepared according to reported procedures. Freshly distilled or crystallized materials were used for all n.m.r. spectra which were determined using Varian DP-56.4 and DP-40 spectrometers. Chemical shifts and coupling constants represent averages of a t least four sweeps (both directions) and are reproducible to 0.01 p.p.m. and0.1-0.2c.p.s.,respectively.
Acknowledgments.-The author wishes to thank Dr. F. G. Bordwell and K . M. Wellman for samples of no. 2-4 in Table I. The author is grateful for a postdoctoral fellowship from the National Science Foundation (1961-1962) during which time some preliminary work on this problem was completed, and for support from the Petroleum Research Fund (Grant No. 1536) of the American Chemical Society. (11) pi. L. hllinger and J. Allinger, J . A m . Chem. Soc., 8 0 , 5476 (1958) (12) E. J Corey, i b i d . , 75, 3297 (1953). T h e procedure used f o r t h e s y n thesis of both cis- and frans~2.6-dibromocyclohexanoneswas t h a t described by R . Metze and P Schreiber, Chem. Ber., 89, 2470 (1956).
DEPARTMENT O F CHEMISTRY, STANFORD UNIVERSITY, STANFORD, CALIF.]
Infrared Spectral Studies of Grignard Solutions BY RUDOLFM. SALINGER AND HARRY S. MOSHER RECEIVEDNOVEMBER 4, 1963 The infrared spectra of the Grignard and dialkyl- or diphenylmagnesium reagents prepared from methyl, ethyl, and phenyl halides in ethyl ether and in tetrahydrofuran have been investigated. The K-Mg absorption shows as a rather wide band between 500 and 535 c n r l for R = M e or E t and between 365 and 383 em.-' for R = Ph. The spectra of the Grignard solutions prepared in T H F from methyl chloride, methyl bromide, ethyl chloride, ethyl bromide, and phenyl bromide and the corresponding dialkylmagnesium solutions in T H F MgX2 a 2RMgX, where are noticeably different and can be interpreted in terms of the equilibrium, R2Mg the species may be in part ionized. The infrared spectra of ether solutions of the same reagents, in contrast to those of the T H F solutions, are not definitive and do not warrant such a conclusion. I n every case the infrared spectrum of a n equimolecular mixture of dialkylmagnesium (or diphenylmagnesium) and magnesium halide was identical with that of the corresponding solution of Grignard reagent. Reactions of alkyl iodides with magnesium in T H F gave heterogeneous mixtures, the solutions from which were rich in dialkylmagnesium and contained but little iodide. I t is evident from these data that conclusions drawn concerning the nature of any one Grignard reagent cannot be safely extrapolated to other such reagents because of the varying effects of R , X, and solvent on the Grignard system
+
Introduction The problem of the precise nature of the Grignard reagent has attracted renewed interest since the definitive experiments of Dessy, et al.' demonstrated that there was essentially no magnesium exchange between diethylmagnesium in ether solvent and radioactive magnesium bromide. Recently Ashby and Becker2 showed that in tetrahydrofuran ( T H F ) , monomeric species predominate in some simple Grignard reagents, in contrast to the dimeric species existing in ethyl ether. Vreugdenhil and Blomberg3 reported that dilute solutions (cu. 0.01 M ) of ethylmagnesium bromide in ethyl ether or in T H F contain only monomeric species. Stucky and R ~ n d l eby , ~ X-ray studies, found that phenylmagnesium bromide etherate crystals con(1) R. E. Ilessy, J. H. Wotie. and C . A. Hollingsworth,
J . A m . Chem.
SOL.,79, 3476 (1957). (2) E. C Ashby a n d W. E . Becker. ibid , 85, 118 (1963). . 81, 453, 461 (3) A. I). Vreugdenhil and C. Blomberg, Rec. I r a ~ chim., (1963). (4) G . D. Stucky and R . E . Rundle,
J . A m . Chem. Soc., 85, 1002 (1983).
tain PhMgBr.2Etz0 units. Nuclear magnetic resonance studies5have been veryrevealing but not definitive concerning the species RMgX V S . RzMg.MgX2. The demonstration by WalborskyB of the stereochemical stability of the Grignard reagent from I-bromo-lmethyl-2,2-diphenylcyclopropane establishes the integrity of the carbon-magnesium bond in this specific case. This body of diverse and partially conflicting data suggests t h a t the nature of the Grignard reagent may be very dependent upon the variables of solvent, R group, and halide, and that a comparative study of several reagents by some suitable physical method should be made. It should be emphasized that physical methods may reveal the composition of the Grignard solution but may reveal little or nothing concerning the reactive species of the Grignard reagent. Infrared spectroscopy should serve as a useful tool, ( 5 ) G. M. Whitesides, F. K a p l a n , and J. D . Roberts, i b i d . , 85, 2167 (1963), and papers cited therein. ( 6 ) H. M . Walborsky and A E . Young, Record Chem. Progr , 3 3 , 75 (1982).
