THE METABOLISM OF METHYLCYCLOHEXANE

Abstract

1. When [U-(14)C]methylcyclohexane is fed to rabbits (dose 2-2.5m-moles/kg. body wt.), 65% of the radioactivity is excreted in the urine as metabolites, 0.5% appears in the faeces and about 15% in the expired air, some 4-5% remaining in the body in about 60hr. after dosing. The 15% of the dose appearing in the expired air consists of unchanged methylcyclohexane (10%) and (14)CO(2) (5%). The low output of (14)CO(2) shows that reactions leading to complete oxidation of methylcyclohexane are of minor importance. 2. The main metabolite found in the urine was the glucuronide of trans-4-methylcyclohexanol which was isolated. Seven methylcyclohexanols were found in the urine as conjugated glucuronides. The amounts of these were determined by isotope dilution to be as follows: cis-2-, 0.6%; trans-2-, 1.2%; cis-3-, 11.5%; trans-3-, 10.5%; cis-4-, 2.4%; trans-4-methylcyclohexanol, 14.7%, cyclohexylmethanol, 0.3%. No 1-methylcyclohexanol was found. There was evidence also that a small amount (approx. 1%) of the hydrocarbon aromatized to benzoic acid, probably via cyclohexylmethanol and cyclohexane-carboxylic acid. 3. The pattern of hydroxylation and the various amounts of the isomers found suggest that the hydroxylation in vivo of methylcyclohexane is dependent on steric factors in the molecule, hydroxylation occurring to the greatest extent at the carbon atom furthest away from the methyl group.