On the syntheses of branched saturated fatty acids

In order to investigate the relation between the structure of mono-branched saturated fatty acids and their physical properties, a three-factor central composite design was constructed. For this purpose sixteen different fatty acids were prepared. The synthetic strategy was to use if possible, a few common starting materials for the preparation of most of the acids. Thus alkylation and hydrolysis of oxazolines were used for the preparation of 2-butylhexanoic acid, 2-methyloctadecanoic acid, 2-hexadecyloctadecanoic acid and 2-pentyloctadecanoic acid. A number of acids were prepared from thiophene derivatives followed by desulfurization with Raney-Nickel alloy under alkaline conditions. Thus, starting from 3-ethylthiophene, 4-ethyl-2-thiophenecarboxylic acid and 4-ethyl-2-methyl-5-thiophenecarboxylic acid were prepared, which upon desulfurization gave the desired 4-methylhexanoic acid. From 3-bromo-2-methylthiophene, 3-ethyl-2-methyl-5-thiophenecarboxylic acid was preparedvia 3-acetyl-2-methylthiophene and 3-ethyl-2-methylthiophene. Desulfurization gave 4-ethylhexanoic acid. Another approach started with 2-acylthiophenes, which were reacted with Grignard reagent to yield the appropriate olefins. By metalation and reaction with carbon dioxide, these were transformed to the corresponding 2-thiophenecarboxylic acids. Upon desulfurization, the desired fatty acids were obtained. In this way 6-propyldecanoic acid, 6-hexyldodecanoic acid, 6-methyldodecanoic acid and 6-pentylpentadecanoic acid were prepared. The remaining four acids were prepared from some of the branched acids described above through Kolbe reactions of dioic acids. Thus 16-methyloctadecanoic acid and 10-methyl-dodecanoic acid were obtained from 4-methylhexanoic acid, 16-ethyloctadecanoic acid from 4-ethylhexanoic acid and 9-pentyloctadecanoic acid from 6-pentylpentadecanoic acid.