Resolution by the Method of Francis T. Williams
Racemic Modification
Antioch College Yellow Springs, Ohio
I
A demonstration by analogy
The separation of a racemic mixture by the method of racemic modification, sometimes called Pasteur's second method, is usually illustrated in most textbooks of organic chemistry by a scheme such as the following: (+) Acid
-R
.
(-)Acid -L , racemic mixture
+
( - ) B a s e - l -r ~ u r eenantiamer
(+, -)Salt -
R,
1
, . - I . Salt - L. 1
(-.
d
diasteriomers
Since diasteriomers exhibit different physical properties, they are separable by physical methods whereas the enantiomers are not. Once the diasteriomers are separated, the pure enantiomeric acids may be displaced from their salts, the entire process constituting a resolution.
Many students have difficulty convincing themselves that the racemic modifications (i.e., the salts in the above scheme) are really diasteriomers. The use of models does not help in the lecture situation because they are cumbersome, especially when bond breaking and making are involved; and they are d i c u l t for the class to see clearly, especially when one tries to cover all the spatial arrangements possible to show that two models cannot possibly be mirror images. However, the following simple demonstration has met with some success. Undoubtedly many instructors have told their students that their own hands constitute models for an enantiomeric pair. The right hand is the nonsuperposable mirror image of the left and vice versa. Using these models, one recalls that when people shake hands a nice "fit" results when both participants use the same hand, both right or both left, whereas a
quite different "fit" results when the participants use different hands. The instructor's right hand is designated as the (+) acid molecule. R. and his left hand as the (-) acid molecule, L. ~ h instructor k then singles out student in the front row (preferably the most attractive girl t h e r e t o rivet attention on the proceedings, of course) and designates this student's hands as the enantiomeric base molecules; e.g., the right hand as the (+) base, r, and the left as the (-) hase, 1. Now hand shaking begins. The handclasp of the instructor's right hand with the student's right hand and then with the student's left hand demonstrates the formation of the R, r and R, 1 salts, respectively. The instructor's left hand with the student's right and left hands produces the L, r and L, 1salts, respectively. It should be apparent that the right with right and left with left handclasps are mirror images; this demonstrates that the salts R, rand L, 1are enantiomers. Similarly the salts, R, I and L, r can be shown to be enantiomers. Hence, it is evident that the reaction of the enantiomeric acid with the enantiomeric base molecules yields four different salts comprised of two pairs of enantiomers. Yow suppose we take an optically pure base obtainable from a natural source or a previous resolution, e.g., the (-) base, I, which is modeled by the student's left hand. React (shake hands) the enantiomeric acid molecules, R and L, (the instructor's right and left hands) with the hase, 1 (the student's left hand). This produces only the two salts, R, 1 and L, 1 (a rightleft and left-left handclasp). But we have seen that the enantiomer of R, 1 is L, r and the enantiomer of L, 1 is R, r. Hence, R, 1 and L, 1 are diasteriomers, a fact demonstrated by the observation that their models, the right-left and left-left handclasps, are not mirror images of one another. Separation of the diasteriomeric salts by a physical method and liberation of the enantiomeric acids from their separated salts complete the resolution.
a
Volume 39, Number
4, April 1962
/
21 1
