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Solutions For An Introduction to Medicinal Chemistry Chapter 11 Problem 1Q

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Solution 1

Benzene is an aromatic organic compound that consists of a cyclic six-carbon structure that has a resonance structure. Toluene on the other hand is a derivative of benzene that has a methyl group attached to one of the carbon atoms. Benzene is a potential carcinogen, and hence is not used as an organic solvent. Toluene is being used in its place, as a safer alternative.

Benzene is carcinogenic as a result of its metabolism by the cytochrome P450 family of enzymes, producing a highly reactive electrophilic metabolite known as an epoxide. This epoxide causes damage to proteins and DNA, which can trigger cancerous malignancy.

Toluene, by contrast, is not as toxic and carcinogenic. In humans, toluene gets metabolized to benzyl alcohol and ortho, meta and para-cresols. Benzyl alcohol gets converted to benzoic acid, which later gets converted and excreted as hippuric acid. The cresols, on the other hand, are excreted directly.

The metabolism of toluene differs from that of benzene due to the presence of a methyl group bound to one of the carbon atoms of the cyclic core structure. This methylated carbon can be chemically altered without disrupting the core ring structure of the benzene ring, thus minimizing the likelihood of epoxide formation.

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