Chloral–ketone condensations in acetic anhydride. Reaction of chloral with butanone, 3-pentanone, cyclohexanone, and 4-methyl-2-pentanone

Abstract

In the presence of sodium acetate as catalyst, chloral hydrate undergoes a mixed aldol condensation with aliphatic and alicyclic ketones in acetic anhydride as solvent. Contrary to previous literature reports, reaction occurs at both the methyl and the methylene group in α-position to the carbonyl group of butanone, to give a mixture of 1,1,1-trichloro-2-hydroxy-4-hexanone (1) and 1,1,1-trichloro-2-hydroxy-3-methyl-4-pentanone (2a and 2b, diastereomers). 3-Pentanone, cyclohexanone, and 4-methyl-2-pentanoneyield 1,1,1-trichloro-2-hydroxy-3-methyl-4-hexanone (3a and 3b, diastereomers), 2-(1-hydroxy-2,2,2-trichloroethyl-) cyclohexanone (4a and 4b, diastereomers), and 1,1,1-trichloro-2-hydroxy-6-methyl-4- heptanone (5), respectively. Compound 5 is the exclusive product formed from chloral hydrate and 4-methyl-2-pentanone since attack at the methylene group is sterically hindered. The low-melting diastereomers 2a, 3a, and 4a which have not been characterized before, exhibit strong intramolecular hydrogen bonding and have been assigned the threo configuration on the basis of nuclear magnetic resonance and molecular model studies.