718 VIT. VITAMINS A 



CH, ^0 . ^"' . CH, CH, 



R- CH.-CH-CH-C-H hc = c-c:ch-cH;OR ^ R- CH : CH- CH • CH- C : C- C: CH • CH^OR' - 



2: OH X 



R-CH:CH-C:CH-C :C-C:CH-CH;OR " R-CH:CH-C: CH-CH:CH-C:CH-CH:OR 



vrn IX 



Synthesis of Vitamin A (Milas "B" Method and Procedure of Isler et al.) 



(4) Oroshnik Synthesis 



The method of Oroshnik*^' ^"^ is quite similar to the Milas method and the 

 procedure of Isler et al., except that it differs in the starting material. The 

 acetylenecarbinol (XI) is treated with ethyl magnesium bromide (Grignard 

 reagent); the resulting Grignard acetylenecarbinol is reacted with 2- 

 methyl-4-hydroxy-l-chloro-2-butene (XII) to form methoxyacetylene- 

 carbinol (XIII), which is then catalytically reduced to the methoxycarbinol 

 (XIV). The latter compound can then be dehydrated in glacial acetic acid 

 with p-toluenesulfonic acid to form vitamin A methyl ether. 



CH3 CH3 CH3 CHi 



I I CjH^MgBr | | 



R-CH:CH-C-C;CH + CI- CHp- C = CH- CHjOCH, " R • CH: CH • C • C : C • CHa' C:CH-CH20CH3 



XI OH XH OH 



CH, CH, CHj 



R- CH:CH-C:CH -CH : CH- C : CH -CH^OCH, - ^'""'"J^""" R-CH:CH-C- CH rCH-CHj- C: CH-CH^OCHj 

 IX OH XTY 



Oroshnik Synthesis of ^^itamin A Methyl Ether 



Milas*^ is of the opinion that vitamin A methyl ether prepared by the 

 Oroshnik procedure is quite impure. 



(<5 ) Synthesis of A rens and van Dorp 



a. Synthesis 1. Two different syntheses of vitamin A have been dis- 

 covered by Arens and van Dorp. The first of these procedures involves 

 the synthesis of vitamin A acid/^^'^™ which seems to be about as potent as 

 vitamin A itself. ^^^ In this synthesis, |3-ionone and 7-bromocrotonate are 

 condensed by the Ref ormatsky reaction to produce an hydroxy ester (XV) . 

 After dehydration and saponification of the ester, the resulting acid (XVI) 

 is treated with methyl lithium to yield a methyl ketone (XVII). After 

 another Reformatsky reaction using bromoacetic ester, an hydroxy ester 



(XVIII) is formed which, on dehydration with oxalic acid and saponification, 

 gives rise to an orange oil from which the acid corresponding to vitamin A 



(XIX) can be crystallized. 



209 W. Oroshnik, /. Am. Chem. Soc, 67, 1627-1628 (1945). 



210 D. A. van Dorp and J. F. Arens, Nature, 158, 60 (1946). 



CH, 



