James 0. Traynham
Louisiano State University Baton Rouge
The Rotation of Optically Pure
Values of some physical constants which presumably should be simple to measure prove elusive in actual experimental practice. One example is the optical rotation of 2-hronlooctane. Because of the relative ease of resolution of 2-octanol, its subsequent conversion into 2-bromooctane, and various replacements of the bromine by other substituents, this alkyl halide has been widely used in experiments concerned with organic reaction mechanisms. The precise magnitude of its maximum optical rotation, however, has been a matter of considerable disagreement and investigation. In their early studies, Hughes, Ingold, and Masterman (1) bracketed the value, on the basis of empirical correlations, between 33.8' and 38.1°,' strongly favoring the smaller value. Although these limits have in effect been challenged by publications citing other values, these numbers continue to appear in current literature, and the numerical conclusions about extents of racernization continue to be cited without comment. The highest value reported for the maximum rotation of 2-bromooctane is 42.1' (8), and this has been criticized as being "somewhat too high" (3). The intent of this paper is to review the various values reported in the literature, evaluate them and indicate that the most probable value for this important physical constant lies in the range 39.3-40.8'. In 1937, Hughes, Ingold and Masterman (cited hereafter as H-I-M) reported their studies of the solvolysis of 2-bromooctane under what were considered to be reaction conditions favorable for SN2and SN1reactions, separately (1). In ethanol solution, with either KOH or NaOEt added, 2-bromooctane (RBr) was converted into alcohol (ROH) or ether (ROEt), respectively, with appreciable optical activity. In 60% aqueous alcohol, without any added base (HBr accumulates), RBr was converted into alcohol and ether which exhibited much less optical activity. Since the Sw2 description requires complete inversion of configuration, assessment of the extents of racemization in these transformations was vital a t this early stage in the development of theory. The calculation is seriously complicated by the fact that racemization attends the preparation of RBr from ROH, to different extents with different procedures, and probably most transformations of RBr as well. The maximum rotation of 2-octauol was taken to be 9.9°.2 Since the maximum experimental ratio of rotations RBr/ROH, obtained in the hydrolysis reaction, was 3.85, if no racemization a t all occurred in this reaction, the rotation of optically
pure 2-bromooctane would be 38.1'. On the hasis of a kinetic analysis of the data, however, in which separate SN2and SN1contributions to the overall reaction were estimated, H-I-M calculated another, lower maximum rotation for RBr: 35.1°. The data for the conversion of RBr to ROEt led to a still lower value. Presumably optically pure ROEt, synthesized from ROH by the Williamson synthesis (no attack on the asymmetric carbon), exhibited rotation of 17.1°; the maximum experimental ratio of rotations RBr/ROEt was 1.975; if no racemization is assumed, the maximum rotation for RBr must be 33.8'. In this fashion, the bracketing figures 33.8-38.1° were obtained and used, first by H-I-M and subsequently by numerous investigators. Because any racemization occurring in these reactions would necessitate lowering, rather than raising, the calculated maximum rotation of RBr, the lowest figure for this rotation is clearly favored. The figure 33.8' leads to a calculated value of 89% net inversion for RBr -+ ROH and 100% net inversion for RBr + ROEt; correction for SN1contribution to the overall hydrolysis raised the estimate for the S N ~ part of the conversion RBr + ROH to 937& net inversion. In 1945 Gerrard (4) and in 1946 Brauns (2) reported multiple preparations of RBr from ROH in an effort to delineate the conditions most suitable for the preparation of RBr with high optical purity. In his paper, Brauns gently reminded the reader of work by Hsueh and Marvel (5),published in 1928 and apparently overlooked by H-I-M, in which RBr with actual rotation of 34.2', higher than the value most favored by the English authors, was prepared. Several preparations reported by Gerrard and Brauns resulted in RBr with rotations still higher, the highest values reported by each being 40.V and 42.1°,3 respectively. Both of these are higher than even the upper limit set by the English authors and clearly demand a new assessment. In 1955, Kornblum, Fishbein and Snliley included a brief review and evaluation in a paper describing reactions of RBr with nitrites (3). They stated that the highest value reported, that by Brauns, "probably errs by being a little on the high side." Although no explicit indication of the reason for this criticism is given, examination of the experimental details in Brauns' paper does indeed raise questions. A forerun in the preparation, immediately preceding the 2-bromooctane, was considerably more optically active than the bromide itself. Whatever this lower boiling material was, slight contamination of the RBr by it would a The experimental data. have been corrected to correspond to the maximum rotation of ROH. The maximum value calculated from data of H-I-M, with corresponding correction for rotation of ROH, is 39.7".
Volume 41, Number 1 I, November 1964
/
617
account for too high a rotation. No more exact estimate of the actual rotation of 2-bromooctane was given (5). Now, even though several values higher than those used by H-I-M had been reported and reviewed in the literature, some review publications appearing as late as 1962 still cited the 33.V figure for RBr rotation and the unchanged extents of racemization given by those authors. What is the rotation of optically pure 2-bromooctane? If preparations of RBr from ROH are subject to uncertainty, perhaps the value can be fixed by some reaction of RBr which proceeds with no loss of optical purity. An examination of the literature reveals several recent data which appear promising. One of the most promising a t first inspection involves the transformation of RBr, by reaction with potassium thiocyanate in acetone solution (good SN2 conditions), into RSCN (the ratio of rotations RBr/RSCN was 0.63) (6). Although no forthright statement is made in the paper, the treatment of the data tacitly assumes that this reaction proceeds with loo'% inversion. If we knew then the rotation of optically pure RSCN, we could calculate back to that of optically pure RBr. The minimum rotation of optically pure RSCN, as indicated by data obtained for the transformation of ROH through ROTS to RSCN, is 70.4' (7). This leads to 0.63 X 70.4O or 44.4" for the rotation of RBr-a value higher still than Brauns' value which has already been criticized. Some racemization must have occurred in the transformation RBr to RSCN, and these data cannot be used to establish the rotation of optically pure RBr. More fruitful data come from a malonic ester synthesis.' RBr reacts with sodiomalonic ester to give an alkylmalonio ester which was hydrolyzed to 3-methylnonauoic acid and the acid reduced to 3-methylnonane (8). The ratio of rotations RBr/REt was 4.23. The maximum rotation of 3-methylnonane has been established, by a synthesis not affecting the asymmetric center, to be 9.30' (9). This allows a calculation of a maximum rotation for optically pure RBr of 9.30' X 4.23 or 39.3'. If any racemization occurred in the malonic ester synthesis, this calculated value will be too high. This value lies close to the highest one reported by Gerrard (4) (40.8') for RBr prepared from ROH; any racemization occurring in this synthesis would require that the actual rotation be higher than 40.8". These numbers-39.3' and 40.8°-establish a narrow range within which the rotation of optically pure 2-bromooctane most probably lies. Any racemization attributed to either of the critieal reactions (ROH to RBr or RBr to RCH(COOEt)n)will require that the range he widened; in effect, the two approaches yield overlapping data. The upper limit (39.7" after correction for ROH rotation to 10.3") assigned originally by H-I-M lies within this narrow range. It is often instructive to reconsider old data in the light of new physical constants. Using the limits 39.M0.8" for the rotation of optically pure 2-bromooctane, one may calculate that the conversion RBr to ROH under SN2conditions originally reported by H-I-M A large number of papers reporting transformations of optically active RBr were examined. Since m y racemization attending the transformation of RBr into RZ will lead to the calculation of a rotation for optically pure RBr which is too high, we will favor dat,a which lead to the lowest maximum rotation of RBr.
618
/
Journal of Chemical Education
proceeded with 99-103% net inversion. This more nearly approaches the results predicted by the theoretical description which the investigation was designed to test than did the original estimate (89% corrected to 93% net inversion); it also raises questions about the validity of the corrections made (1) on the basis of a kinetic analysis for SN1 contributions to the overall hydrolysis. A recalculation of the stereochemical consequences of the conversion RBr to ROEt (ratio of rotations ROEt/RBr, 0.507, maximum rotation of ROEt, 17.1') leads to the unacceptable conclusion that the reaction occurred with a t least 116% net inversion. This calculation rests not only on the rotation of optically pure RBr but also on that of optically pure ROEt. The latter figure was established (1) by a synthesis which presumably did not affect the asymmetric center. Most likely it has been fixed a t too low a value. Some unexpected racemization prob* bly did occur in the Williamson synthesis, and partially racemized ROEt was obtained. A few other instances of racemization of alcohol by strong base have been reported (lo), though not often considered. Considerable interest and significance are attached to the stereochemistry of reactions involving organometallic compounds. Wurtz coupling reactions with optically active alkyl halides usually give low yields of hydrocarbon products formed with extensive or complete racemization ( l l ) , but the reaction of 2-bromooctane with allylsodium (heterogeneous) or allylmagnesium bromide (homogeneous) has been reported to proceed with high stereospecificity (9). A recalculation, employing the new limits for the rotation of RBr, of the stereochemical consequences of these reactions indicates that they proceed with 90-93.5% net inversion, whereas the older limits led to estimates as high as 21% racemisation. AUTHOR'S N o ~ e A f t e galley r proof for this paper was checked, a publication describing a new preparation of gas chromttto-
W., A N D graphicdy-pure Zbromooctane appeared (GERRARD, HUDSON, H. R., J. C h a . Soc., 2310 (1964)). ZOohnol ( a ~ ' ~ 4 . 0 7 " ) gave Zbromooctane (mm-44.0").Although densities were not reported in that paper, reasonable values (da160.823 for ROE and d P 1.10 for RBr) lead to a value of [olo'O 42.0" for RBr from optically pure ROH. The data presented by Gerrard and Hudson make this value appear unquestionable, but it does lead to the same internal inconsistency which mused Braun's report to be challenged (3). It will of course revise upward the cdoulstions of stereospecificity in the last two paragraphs. Literature Cited
(1) HUGHES,E. D., INGOLD, C. K., AND MASTERMAN, S., J . C h m . Sac., 1937,1196. (2) BRAUNS, H., Rec. trav. ehim., 65,805 (1946). N., FISHBEIN, L., AND SMILEY, R. A,, J . Am. (3) KORNBLUM, C h m . Soc., 77,6261 (1955). W., J. C h a . Sac., 848 (1945). (4) GERRARD, C. S., J. Am. C h m . Sac.,. 50.855 (5) . . HSUEH.C.. AND MARVEL. . (1928). G. E., AND BLOOMFIELD, J. J., J. Am. (6) FUCHS,R., MCCRARY, C h m . Soc., 83,4281 (1961). J., PHILIPS, H., AND PITTMAN, J. P.,J. Chem. Soe., (7) KENYON, 1072 (1935). S. E., AND DENNEY,D. B., J. Am. (8) LEGOFF,E., ULRICH, Chem. Soe., 80,622 (1958). (9) LETSINGER, R. L., AND TRAYNHAM, J. G., J. Am. Chem. Sac., 72, 849 (1950). J. G., AND BAT~ISTE, M. A,, (10) For example, TRAYNHAM, J. 078. Chem., 22, 1551 (1957). R. L., Angew. (11) Far s review with references, see LETSINGER, Chem., 70, 151 (1958).
