Studies in detoxication. 60. The metabolism of alkylbenzenes: isopropylbenzene (cumene) and derivatives of hydratropic acid.

isoPropylbenzene (cumene) is used as a solvent for cellulose lacquer, although not extensively. It has narcotic properties but no toxic effects in man have been reported (see Browning, 1953). When fed to rabbits it causes the excretion of considerable amounts of conjugated glucuronic acid and the urine reduces Benedict's reagent (Smith, Smithies & Williams, 1954a), but nothing definite is known concerning the nature of the metabolites of cumene. The earlier work of Nencki & Giacosa (1880) and of Thierfelder & Klenk (1924) showed that it did not give rise to hippuric acid or any other aromatic acid. However, the former authors found that the ratio of inorganic sulphate to ethereal sulphate in the urine of the dog was reduced after administering cumene, and on these grounds suggested that a phenol was formed (cf. Donahue & Harris, 1945), but Smith et al. (1954a) found that in the rabbit ethereal sulphate formation was very small. Our work on ethylbenzene (Smith, Smithies & Williams, 1954b) has suggested that in this compound biological oxidation occurs initially mainly at the active methylene group next to the benzene ring. We were, therefore, particularly interested in whether a similar oxidation would occur with cumene giving rise to 2-phenylpropan-2-ol (Ph.C(OH)(CH3)2). We shall show that this is, in fact, true and that cumene gives rise also to hydratropic acid (a-phenylpropionic acid) and hydratropyl alcohol (2-phenylpropan-1-ol).