720 



VII. VITAMINS A 



(XXI). The methyl ketone (XVII) was prepared by treating the acid 

 chloride (XXIII) prepared from the dehydrated acid (XXII) with methyl 

 zinc iodide. The remaining reactions were similar to those of Arens and 

 van Dorp. 



CH3 



P KOH I 



R- ch:ch-c:ch-ch: cH-c-ocHj r- ch:ch- c:ch -chich -c-oh 



XXII 



1CTCX 



CH, 



R- ch:ch-c: ch-ch:ch-c-ci 



XXIII 



CHjMgl 



•XVTT 



— VITAMIN A 



Synthesis of Vitamin A b}' the Method of Karrer et al. 

 (7) Synthesis of Vitamin A from Dimethylaminovitamin A 



Vitamin A has also been synthesized by Milas/^'^^^ using exhaustive 

 methylation of dimethylaminovitamin A. This reaction would be ex- 

 pected to proceed satisfactorily, since it is known that, when heat is ap- 

 plied to trimethylalkyl quaternary salts or bases in which the alkyl group 

 contains no loosely bound hydrogen atoms on the carbon combined with 

 the quaternary nitrogen, decomposition results, trimethylamine and 

 alcohol being the chief end products. In this procedure acetylenic car- 

 binol (VI) is condensed with 4-dimetliylaminobutan-2-one (XXIV) by 

 means of the Grignard reaction, to give the dimethylaminoacetylenic gly- 

 col (XXV) in 30% yields. On selective hydrogenation of XXV, the glycol 

 XXVI is formed which, in turn, is converted to the hydrobromide by pyri- 

 dine hydrobromide. The dimethylaminovitamin A is prepared from this 

 by treatment of the hydrobromide with phosphorus tribromide followed by 

 debromination of the dibromide with alcoholic potash. The dimethyl- 

 aminovitamin A (XXVII) can be converted into vitamin A by forming its 

 methiodide, converting the latter into the hydroxide with alcoholic potash 

 and heating the hydroxide to 60-70°C. These reactions are given in 

 detail below: 



CH, CH3 



R- CH:CH-CH-CH-C; CH + 0-C • CH^- CHj,- N (CHj) j " 



21 OH XXIV 



CH3 



CH, 



R-CH:CH-CH-CH-C: C-C- CH/ CH/ NiCHj) 



I 



"yyy oh 



OH 



1% Pd 

 C0CO3 



CH, CM, 



I ' 



=-*■ R- CH:CH- CH- CH-CH:CH- C- CH,- CH,- N :CH,1, 



x-xvr OH OH 



(1) PxMdine -t- HBr 



(2) PBfj + Pyridine 



(3) KOH +C2H50H 



(60- 80- C I 



CH, 



CH, 



VITAMIN A 



(2) KOH + C2H5OH 



r-ch:CH-c:Ch-ch:ch-c:ch-ch/N>ch,)2 



Synthesis of Vitamin A from Dimeth5daminovitamin A 

 211 N. A. Milas, U. S. Patent No. 2,415,834, Feb. 18, 1947. 



