6251 Table 1. Correlation of Nmr Sense of Nonequivalence with Absolute Configuration for Some Partially Resolved Type 1 Sulfoxideso,*
An inspection of Table I suggests that the degree of spectral nonequivalence depends upon the extent of association and upon relative population levels of varNonequivalence ious conformers.13 For example, the alkyl aryl sulf--As, Hzc--. sense % optical oxides generally show a smaller A6 for the methaneR R CH, Rd C H 3 puritye sulfinyl group than do the more basic dialkyl sulfoxides, CD3’ 1.7 Low 28 while among the substituted methyl phenyl sulfoxides CHa2CH@3 2.4. 2.5 2.5 High Low 29 s:udied, an increasing A6SOCH3is observed in the order Ha HP of increasing basicity. l 4 \ / Since the partially resolved sulfoxides in Table I were 0.8, 1.3, 1.8 1 . 9 High Low 30 prepared by the action of an excess of the appropriate CHz HY Grignard reagent upon portiors of a single batch of a CH’, 1.78 : 1.OO mixture of the diastereomeric ( R configuration / at sulfur in excess)’* (-)-menthyl methanesulfinates 2.6, 1.1, 3.0 3 . 1 High Low 37 C (3), all of the major enantiomers should have the same / \ Ha CHY3 absolute configuration ( i . e . , R),15 although they need C(CHd3 1.2 2 . 6 High Low 24 not necessarily have identical optical purities. CHzCsHi 2.5 Low 31 Further inspection of Table I reveals that in (-)-2 CsHi 1.2 Low 28 the partially resolved methyl-substituted sulfoxides all p-CHzC6Ha 1.4 Low 30 p-CH3ao-C6HP4 0.8, 2 . 9 1.8 High Low 29 exhibit low-field senses of nonequivalence for the metha-Napthyl 1.3 Low 31 anesulfinyl resonances and high-field senses of nonequivalence for the resonances of the remaining alkyl a The sulfoxides were prepared7bfrom a single batch of (-)-(R)menthyl methanesulfinate of 28 % diastereomeric purity,7b in each or aryl substituents. l 7 Contrasting senses of noncase using ca. 1 mol excess of the appropriate Grignard reagent equivalence have been previously observed and raexcept for dimethyl-l,l,l-d3sulfoxide, where a 20% excess of methyltionalized’,’* for other solutes in optically active sold3-magnesium iodide was employed. The sulfoxides have physical vents. In the present instances, the reliability of the and spectral properties consistent with their assigned structures. Nmr spectra were measured on a Varian HA-100 spectrometer a t correlation between the senses of nmr nonequivalence 28 using samples composed of 2: 1 :ca. 3 mol ratios of alcohol :sulfand sulfoxide absolute configuration suggests that the oxide :carbon tetrachloride or fluorotrichloromethane, respectively. method may be safely extended and used to assign Chemical shift differences (10.1 Hz) are for the a,p, . . . protons, absolute configurations to methyl sulfoxides of unrespectively. Proton resonances for which no A8 is reported were known stereochemistry similar to those in Table I. either obscured by other resonances or exhibited unresolvable chemical shift differences. each case where more than one The effect which added functional groups in the sulfproton in the alkyl (or aryl) group exhibits a chemical shift differoxides will have upon nonequivalence sense has not yet ence, the sense of nonequivalence is the same as that for other been ascertained. protons within the group. e Optical purities ( + l % ) calculated from the relative peak heights of the enantiomeric methanesulfinyl Acknowledgments. This work was supported by resonances. f Dimethyl-l,l, 1-d3 sulfoxide, previously unreported, Grant No. GM 14518 from the U. S. Public Health was characterized by its elemental analysis, its infrared spectrum, Service. We wish to thank Dr. R. W. Woody for and its proton and deuterium nmc spectra. Based on its observed obtaining the O R D spectrum of dimethyl-l,l,l-& optical rotation, enantiomerically pure material would have a n [CY]*~D -3.8” (neat). This sample was shown by vpc t o contain sulfoxide.
7,
less than 0.05 % menthol, menthone, or menthyl methanesulfinate, and to contain less than 0.1 % of any impurity other than water. Observed for the high-field portion of the AA‘BB’ aromatic multiplet.
arises by the formation of short-lived, hydrogen-bonded diastereomeric solvates. lo When (-)-(S)-a-methylbenzylcarbinol (4), less acidic than 2,11 is used as a solvent for methyl t-butyl sulfoxide, the magnitude of nonequivalence is reduced by a factor of ca. 1.5, consistent with weaker solvent-solute association, although other factors may also be involved. The nonequivalence of the nmr spectra of the enantiomers of type 1 sulfoxides in optically active 2 is quite general, as shown by Table I. The power of the method is strikingly demonstrated by the direct determination of the optical purity of a partially resolved sample of dimethyl- 1, l,l-d3 sulfoxide, a compound which is asymmetric only by virtue of isotopic substitution. I 2 ( I O ) A similar explanation has been recently proposed [F. A. L. Anet, L . M . Sweeting, T. A. Whitney, and D. J. Cram, Terrahedron Lett., 2617 (1968)] to account for the nmr spectral nonequivalence of enantiomeric alkylarylcarbinols in suitable optically active sulfoxides. (11) The pK, of 2 is 11.9 [R. Stewart and R . Van der Linden, Can. J . Chem., 38, 399 (1960)]. (12) Isotopic exchange of dimethyl-l,l,l-ds sulfoxide with alcohol 2 is negligible, since no change in optical purity (by nmr) was observed for the partially resolved sulfoxide in (-)-2 over a period of several weeks.
(13) The magnitudes of the enantiomeric chemical shift differences may be enhanced by lowering the temperature or by increasing the alcohol concentration. (14) I
