38 



VITAMINS A AND CAROTENES 



tive of the variations in the method of preparation. ^^^ The chemical evidence 

 accumulated in the author's laboratory during the past several years is 

 still strongly in favor of structure LXV, which will be used throughout the 

 present report. An improved method for the preparation of Cu-aldehyde 

 has been patented by Lindlar.^^*^ The various intermediates involved in 

 this preparation are best expressed by the following equations which are 

 based on the most recent extended study of this reaction. ^^^ 



/3-Ionone 



CH3 



I 

 -C=0 



HjC^ ,CH 



CH3 



CICH2COOC2HS 



NaOCjHj 



CH=CH-C = C-COOC2H5 

 CH, 



OH 



LXII 



HjC^.CH 



CH3 



CH2-CH=C-CH0 

 CHj 



LXVa 



H3C CH3 ?^V''?/0- 



l^'>-CH=CH-C=C-CC' 

 l^jLcH, i OC,H, 



0- 



LXIII 



H,0 



HjC^ ^CH 



CH=CH- 

 CH3 



CHj 

 -CH-CHO 



HsC^ ^CH 



CH3 



PY"*^'H=cn-c=CH + CO3 + C2H5OH 

 ^!L-cH3 



OH 



LXV Cu-Aldehycle 



LXIV 



Referring to Fig. 7, the first practical method^^^ for the synthesis of 

 vitamin A involves the condensation via the Grignard reaction of Cu- 

 aldehyde with the acetylenic carbinol LXIX to form the glycol LXX. This is 

 selectively hydrogenated in a 50-50 ethyl acetate-pyridine mixture using 

 palladium deposited on charcoal to give the glycol LXXI which undergoes 

 dehydration accompanied by allylic rearrangement and acetylation in gla- 

 cial acetic acid and in the presence of pyridine hydrobromide.^'*^-'^^ The 

 yields of vitamin A acetate are equally as high as those obtained by the 

 sequence of reactions using the Grignard of the acetylenic carbinol LXVI.^^ ■ 

 133b , 144-146 jj^ ^j^^g gg^gg ^Yie important step is that which makes use of the 

 poisoned palladium catalyst. ^^^ Partial hydrogenation of the acetylene bond 



"» H. Lindlar, U. S. Pat. 2,451,740 (Oct. 19, 1948); see also ref. 133b. 



1" N. A. Milas, U. S. Pat. 2,577,538 (Dec. 4, 1951). 



"2 N. A. Milas, British Pat. 664,815 (Jan. 16, 1952). 



'" N. A. Milas, Swiss Pat. 288,645 (March 11, 1953). 



i« O. Isler, U. S. Pat. 2,451,739 (Oct. 19, 1948). 



1^^ N. A. Milas, U. S. Pat. 2,567,572 (Sept. 11, 1951). 



1^6 O. Isler, Che7n. Eng. News 29, 3962 (1951). 



1" H. Lindlar, Helv. Chim. Acta 35, 446 (1952). 



