HYDROCARBONS 343 



(c) Higher Homologues of Benzene. When the aliphatic side-chain is 

 lengthened, the metabolic changes become largely dependent upon the 

 nature of the substituent. Williams ^^^ outlined the several types of reac- 

 tion which may be expected, as related to structure, as follows: 



(1) When the side-chain is a normal alkyl group such as methyl, ethyl, 

 ri-propyl, n-butyl, and n-amyl, the oxidation proceeds on the side-chain 

 which is oxidized to the carboxyl ( — COOH) or to the acetate ( — CH2- 

 COOH) group. No change takes place in the benzene ring. The aromatic 

 acids are excreted as conjugates with glycine (hippuric or phenaceturic 

 acid), or possibly with glucuronic acid as benzoyl glucuronide, or as the 

 phenylaceturic glucuronide. 



{2) When there is no aliphatic side-chain {i.e., in benzene) or if the side- 

 chain is branched, as in isopropyl, no oxidation occurs in the side-chain, 

 and the benzene nucleus is oxidized to phenol; the latter product is ex- 

 creted in combination with sulfuric acid, as evidenced by the increased 

 ethereal sulfate excretion. 



(5) When both a methyl group and a branched side-chain are combined 

 with the benzene nucleus, the methyl group is oxidized to carboxyl, while 

 no reaction takes place in the ring or in the branched side-chain. 



a' . Ethylbenzene : It was first demonstrated by Nencki and Giacosa, '^* 

 in 1880, that, in the case of the dog, ethylbenzene is oxidized to benzoic 

 acid, which is excreted as hippuric acid. Methylphenylcarbinol was 

 found by Neubauer^^^ to be an intermediate in the rabbit, and mandelic 

 acid was later identified as another metabolite-'^ in this animal. Pre- 

 sumably no oxidation occurs in the benzene nucleus, as the urine was 

 found to contain the normal amount of ethereal sulfate after the ad- 

 ministration of ethylbenzene.'^^ Methylphenylcarbinol is excreted in 

 combination with glucuronic acid,''^ and the conjugate corresponds to 

 that found when the closely-related acetophenone, CeHs-CO-CHs, is 

 metabolized.'^" 



C6H5CH2CH3 * C6H5CHOHCH3 > CeHsCOOH 



Ethylbenzene Phenylmethyl- Benzoic acid 



carbinol 



I * CsH^CHOHCOOH 



Mandelic acid 

 The Oxidation of Ethylbenzene in the Case of the Dog and the Rabbit 



^'* O. Neubauer, Naunyn-Schmiedeberg' s Arch, exptl. Pathol. Pharmakol., 46, 133-154 

 (1901). 



"6 H. Thierfelder and K. Daiber, Z. physiol. Chem., ISO, 380-396 (1923). 



