January 19, 1917] 



SCIENCE 



55 



salt. Upon heating this salt carbon dioxide 

 was split off, rendering the central carbon 

 atom asymmetric. The resulting salt was 

 treated with an acid, liberating the free 

 methylethylaeetic acid : 



HOOG . CCHs,&H, . COOH 



HOOG . CCHsCHj . COOBrue. 



H . CCHsCH, . COOBrue 



H . fiCHaO^Hs ■ COOH 



This product was found to be slightly 

 levo-rotatory. The results showed that while 

 both the dextro and levo forms of the acid 

 had been produced, there was an excess of 

 about 16 per cent, of the levo form. 



5. Following Marckwald, MacKenzie and 

 his co-workers carried on a series of inves- 

 tigations in 1904, 1905, 1906, 1907, and in 

 1909, in which they were able to effect a 

 number of partial asymmetric syntheses. 

 The principal method employed by Mac- 

 Kenzie was very similar to that used by 

 Kipping. An acid of the general formula 

 K-CO-COOH was selected and changed 

 into an optically active ester by combina- 

 tion with an active alcohol, such as amyl 

 alcohol, borneol or menthol. The carbon 

 atom of the carbonyl group was then ren- 

 dered asymmetric by the action of Grig- 

 nard's reagent as well as by reduction. 



The resulting products, freed from the 

 active alcohol groups, proved to be slightly 

 active, showing that a partial asymmetric 

 synthesis had been accomplished. A com- 

 parison of the results obtained by the use of 

 amyl alcohol, borneol and menthol led to 

 the conclusion that the greater the optical 

 activity of the influencing group present, 

 the greater is the extent of the asymmetric 

 synthesis. 



MacKenzie was also able to synthesize 

 both dextro and levo tartaric acids in an 

 ingenious way (1907). Fumaric acid was 

 changed into the active bornyl or menthyl 

 ester and this ester was then oxidized by 



potassium permanganate. The two central 

 carbon atoms were thereby rendered asym- 

 metric : 



HOOC CH:CH.COOH 



i 

 BylOOC . CH : CH . COOByl 



BylOOC . 6hOH . &HOH • COOByl 



HOOC . CHOH . CHOH • COOH 



On saponification the resulting product 

 yielded an optically active mixture of tar- 

 taric acids, indicating an excess of either 

 the dextro or levo form. When menthol 

 was used as the active agent the levo acid 

 was in excess; when borneol was used, an 

 excess of the dextro acid was obtained. 



6. Mention should be made of the at- 

 tempts to effect the synthesis of compounds 

 containing asymmetric groups other than 

 those of carbon. Smiles, in 1905, effected 

 the synthesis of compounds containing 

 asymmetric sulfur groups while E. and 0. 

 Wedekind, in 1908, built up asymmetric 

 nitrogen groups. In neither ease, how- 

 ever, were partial asymmetric syntheses ef- 

 fected. The method employed by E. and 0. 

 Wedekind was similar to that employed by 

 Kipping in that the reactions were carried 

 out in an optically active solvent such as l- 

 menthol and cZ-limonene. 



7. A distinct advance in our knowledge 

 of asymmetric syntheses was made by Ros- 

 enthaler in 1908. Recalling the discovery 

 of Pasteur that certain enzymes have a dif- 

 ferent action upon the dextro and levo 

 forms of some of the sugars, Rosenthaler at- 

 tempted an asymmetric synthesis by the 

 addition of hydrocyanic acid to benzalde- 

 hyde in the presence of emulsin. By hy- 

 drolyzing the resulting compound pure 

 levo-mandelic acid was obtained. Rosen- 

 thaler's results are especially signiiicant; 

 for while all the other attempts to effect 

 partial asymmetric syntheses yielded both 

 active forms, but with the one in slight ex- 

 cess of the other, Rosenthaler obtained 



