54 



8GIENCE 



[N. S. Vol. XLV. No. 1151 



evident, then, that the production of the 

 two forms in equal amounts with their sub- 

 sequent separation from each other — a task 

 often easily accomplished — does not con- 

 stitute a complete asymmetric synthesis. 



A brief discussion of the more impor- 

 tant attempts to effect partial asymmetric 

 syntheses follows: 



1. The first serious attempt to effect a 

 partial asymmetric synthesis was made by 

 Cohen and Whitely in 1901. An optically 

 active ester was prepared by heating an un- 

 saturated acid (mesaconic acid was used) 

 or its derivatives with levo-menthol. The 

 resulting ester was then reduced, whereby 

 one of the carbon atoms present was ren- 

 dered asymmetric. The ester was then 

 saponified so that the active menthyl group 

 was eliminated, leaving methyl succinic acid 

 containing the newly formed asymmetric 

 group. The course of the reactions is 

 shown in the following equations in which 

 the abbreviation Myl represents the menthyl 

 group, while the newly formed asymmetric 

 carbon atom is designated by a star : 



HOOC CHrCCHs- COOH 



i 

 MylOOC . CH . CCH, . COOMyl 



MylOOC . CH,: (ShCHj ■ COOMyl 



HOOC . CH,: CHCH3 • COOH 



The resulting product, however, was in- 

 active, showing that the dextro and levo 

 forms had been produced in equal amounts. 

 Pyruvic acid yielded similar results. The 

 method selected was ingenious but did not 

 lead to the desired end. 



2. In the same year (1901) Kipping at- 

 tempted to solve the problem by a method 

 similar to that used by Cohen and Whitely. 

 Benzoyl-formic acid was changed into an 

 active ester by heating with borneol. The 

 resulting ester was then reduced, whereby 

 the carbon atom of the carbonyl group was 

 rendered asymmetric. By hydrolysis the 

 active bornyl radical (Byl) was removed. 



leaving an acid which contained the newly 

 synthesized asymmetric group : 



CoHjCOCOOH -^ CoHsCOCOOByl -» C.H.dHOH 

 COOByl -^ C0H5CHOHCOOH. 



The results however were negative, the 

 mandelic acid formed being inactive. 



Kipping also attempted to effect a partial 

 asymmetric synthesis through the influence 

 of an optically active solvent. For this 

 purpose he prepared benzoin through the 

 action of potassium cyanide upon benzalde- 

 hyde in an alcoholic solution of camphor: 



2 CsHjCHO -^ CeH^CHOHCOCoHs. 



He likewise synthesized mandelic acid 

 nitrile by the action of hydrocyanic acid 

 upon benzaldehyde in an alcoholic solu- 

 tion of camphor; pyruvic acid and methyl- 

 ethylketone were reduced in a concentrated 

 solution of grape sugar. While all of these 

 reactions led to the synthesis of compounds 

 containing an asymmetric group, the prod- 

 ucts in each case were inactive, showing 

 that the two forms had been synthesized in 

 equal quantities. 



3. Two years later (1902-03) Fischer 

 and Slimmer made another unsuccessful 

 attempt to effect a partial asymmetric syn- 

 thesis, using the optically active aldehyde, 

 helicin, which is readily obtained from nat- 

 ural sources, as the active constituent for 

 influencing the synthesis. The aldehyde 

 group was rendered asymmetric by the ad- 

 dition of hydrocyanic acid as weU as by the 

 action of zinc ethyl. The resulting com- 

 pounds were decomposed so that one of the 

 products formed contained the newly syn- 

 thesized asymmetric group. The products, 

 however, proved to be inactive. 



4. The first successful attempt to effect 

 a partial asymmetric synthesis was made 

 by Marckwald in 1904. In this investiga- 

 tion, brucine was used as the active agent. 

 Marckwald started with methylethylmalonic 

 acid. This was converted into the brucine 



