Barbier-Wieland procedure

BARBIER - WIELAND Degradation A multi-step procedure tor chain degradation ot esters... 

This procedure, coupled with the procedure described on p. 41, illustrates the Barbier-Wieland method for systematically degrading carboxylic acids. foxwor-Desoxycholic acid may be prepared from wor-desoxycholic acid by repetition of this procedure. If the chromic acid oxidation product is not sufficiently solid to filter after dilution with water, the mixture must be extracted with ether and washed with dilute hydrochloric acid before the alkaline extraction. Wxwor-Desoxycholic acid may be crystallized from ethyl alcohol. It melts at 239-241°. 

A further advance of major importance in the practical utilization of the bile acids for cortisone syntheses was the replacement of the laborious Barbier-Wieland degradation (cf. Fig. 2) by the Meystre-Miescher degradation. As applied by Wettstein and Meystre (1947) to methyl 3a-acetoxy-ll-ketocholanate (VI, R = Ac R = CH3), this procedure involves reaction with phenylmagnesium bromide and acetylation to produce the diphenyl olefin (IX), which upon bromination with N-bromo-suooinimide and dehydrobromination smoothly yields the diene (X). 

A two-step alternative to the Barbier-Wieland method for chain shortening an acid by one carbon involves a-hydroxylation (LDA-O2) followed by oxidative cleavage (NaI04 CrOa HOAc H20). Overall yields (>50%) compare well with those of the established procedure. 

In the Barbier-Wieland degradation, the alpha-methylene group in an aliphatic carboxylic acid is removed in a sequence of reaction steps, effectively a chainshortening. The inverse procedure is the Amdt-Eistert synthesis, where an acid is converted into acyl halide and reacts with diazomethane to give the highest homolog. 

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