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

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Abstract
IsoPropylbenzene (cumene) when fed to rabbits is oxidized to 2-phenylpropan-2-ol, 2-phenylpropan-l-ol (hydratropyl alcohol) and alpha-phenylpropionic acid (hydratropic acid), which are excreted as conjugated glucuronic acids. The conjugated glucuronic acids of cumene urine were isolated and characterized as triacetyl methyl esters. The feeding of ([plus or minus])-hydratropic aldehyde to rabbits results in the excretion of hydratropoyl-glucosiduronic acid, but only the (+)-diastereoisomer could be isolated in crystalline form. This was identical with the reducing glucuronide isolated after feeding (+)-hydratropic acid or cumene. Hydratropyl alcohol gives rise in rabbits to hydratropyl and hydratropoylglucuronides. The former, characterized as its triacetyl methyl ester, was identical with the non-reducing relatively stable glucuronide found in cumene urine. Only the (+)-diastereoisomer of hydratropoyl glucuronide was isolated. 2-Phenylpropan-2-ol gives rise in rabbits to 2-phenylisopropyl glucuronide, which was isolated and characterized as the triacetyl methyl ester and the potassium salt. This glucuronide is readily decomposed by dilute acid to yield alpha-methyl-styrene and is identical with acid-labile glucuronide of cumene urine. These results are discussed, and it appears that the alpha-carbon atom of cumene is more readily oxidized in vivo than the beta-carbons, since the yield of 2-phenylpropan-2-ol is about 40% of the dose, whereas the yields of hydratropyl alcohol and hydratropic acid are 25% each, the total w -oxidation being about 50%.