Derivatives of hydroxyquinol. Part 4. A synthesis of di-O-methyl-citromycin; electronic effects in hydroxyquinol derivatives

Abstract

Although the dianion from 1-(2,4,5-trimethoxyphenyl)butane-1,3-dione (VII) reacted with methyl benzoate giving the 1,3,5-triketone (V), the method failed with ethyl acetate and similar reagents. Chromanone and its derivatives are converted into their 3-acetyl derivatives by acetic anhydride and boron fluoride as in preparations of compounds (XII), (XIII), and (XXXI). Structures are assigned to the isomeric acetates (XXIV) and (XXV) obtained by treating 3-acetyl-6-methylchroman-4-one (XIII) with acetic anhydride–pyridine, and either acetate is shown to be suitable for transformation by triphenylmethyl-lithium into the crude 6-methyl-3-(3-oxobutanoyl)-chroman-4-one (XXVII). Cyclisation of this in acid gives the pyranopyrone (XXIX). The methoxylated 3-acetylchromanone (XXXI) is much less reactive and gives only the one acetate (XXXIII), but this was converted into the requisite (crude) trione and thence into di-O-methylcitromycin (II).

Certain synthetic difficulties with hydroxyquinol derivatives are discussed and attributed to electron release into attached carbonyl groups. The phenomenon also serves to explain the direction and extent of enolization in the various polyketones examined by n.m.r. methods, and also the formation of an arylactic acid in addition to the benzoic acid derivative expected from the haloform reaction with 2′,4′,5′-trimethoxyacetophenone.