II. CHEMISTRY AND INDUSTRIAL PREPARATION 39 



seems to be entirely selective, and the desired glycol is obtained in high 

 yields. Although in the original process selective acetylation of the primary 

 hydroxyl group is essential prior to the final step, it can be omitted if the 

 reaction is carried out in glacial acetic acid using pyridine hydrobromide as 

 the dehydrating agent. 



Vitamin A acetate was also prepared by a slightly different route. ^^"'' '^^ 

 The acetylenic carbinol LXXII was condensed via the Clrignard reaction 

 with 4-acetoxybutanone-2 to yield the 5-dehydroglycol acetate LXXIII 

 which was selecti\'ely hydrogenated to the glycol LXXIV. Upon dehydra- 

 tion of this glycol in glacial acetic acid, using pyridine hydrobromide, vita- 

 min A acetate was obtained in good yields. These reactions have been 

 repeated recently,"' and the over-all yield of vitamin A acetate obtained 

 was somewhat lower than that obtained in the other two methods shown 

 in Fig. 7. 



Synthetic purified \itamin A acetate and \ntamin A obtained from it by 

 hydrolysis were found to be identical in every respect with the natural 

 vitamin A and its acetate. 



Vitamin A ethers have also been synthesized in good yields by meth- 

 Q(^si33a, 150, 151 aualogous to those outlined in Fig. 7. Other methods,'^-- ^^' 

 which are subject to the limitations mentioned on p. 34, produced very 

 little or no biologically active ethers. 



(3) Synthesis via 2 ,6 ,6-Trimeihylcyclohexanone. The synthesis of vitamin 

 A via this route is outlined in Fig. 8.^^^ 2,6,6-Trimethyl-l-ethynylcyclo- 

 hexanol-1, LXXVT, was prepared**^' ^^^ in good yields by the addition of 

 sodium acetylide in liquid ammonia to trimethylcyclohexanone, LXXV. 

 This was condensed via the Grignard reaction with the ketone LXXVIP" 

 to yield the glycol LXXVIII, which was allowed in a homogeneous acidic 

 medium to undergo an anionic rearrangement to give the glycol LXXIX. 

 It was found impossible to reduce this glycol or the glycol LXXXIII selec- 

 tively by any ordinary means of reduction except b}^ the use of lithium 

 aluminum hydride previously applied to this type of compounds by Sobotka 



1" N. A. Milas, U. S. Pat. 2,369,168 (Feb. 13, 1945). 



"9 N. A. Milas, P. Davis, and M. T. Burgess, Unpublished results. 



»« N. A. Milas, U. S. Pat. 2,-369, 157 (Feb. 13, 1945). 



1" N. A. Milas, E. Sakal, J. T. Plati, J. T. Rivers, J. K. Gladding, F. X. Grossi, Z. 



Weiss, M. A. Campbell, and H. F. Wright, /. Am. Chem. Soc. 70, 1597 (1948). 

 '" F. B. Kipping and F. Wild, Chemistry & Industry 1939, 802. 

 »" W. Oroshnik, G. Karmas, and A. D. Mebane, J. Am. Chem. Soc. 74, 295 (1952). 

 "^ J. Attenburrovv, A. F. B. Cameron, J. H. Chapman, R. M. Evans, B. A. Hems, 



A. B. A. Jansen, and T. Walker, J. Chem. Soc. 1952, 1094. 

 1" N. A. Milas, N. S. MacDonald, and D. B. Black, J. .4m. Chem. Soc. 70, 1829 (1948). 

 1" H. Sobotka and J. D. Chanley, J. Am. Chem. Soc. 71, 4136 (1949). 

 ^" G. W. H. Cheeseman, I. Heilbron, E. R. H. Jones, F. Sondheimer, and B. C. L., 



Weedon, J. Chem. Soc. 1949, 2031. 



