Question

Describe how mescaline can be synthesized from benzene. The structure of mescaline is given on page 869.

Short answer

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Step-by-step solution

Reactivity of benzene

Benzene is a six-carbon aromatic ring with alternating single and double bonds. The pi-electron cloud is delocalized above and below the benzene ring making the compound nucleophilic.

The resonance in benzene gives the molecule stability, and therefore, reactions that retain the aromatic structure are favored. These include electrophilic substitution reactions. Friedel crafts alkylation and acylation reactions are used to replace hydrogen atoms of benzene with alkyl or acyl groups at room temperature.

Mescaline

Mescaline is a hallucinogen drug belonging to the substituted phenethylamine class. It is naturally found in small, spineless cacti and can be produced synthetically from benzene.

The IUPAC name of the compound is 3,4,5-trimethoxypenethylamine. It contains a trimethoxy phenyl group attached to the second position of ethylamine. The biosynthesis of mescaline is from tyrosine obtained from phenylalanine. It can also be prepared chemically from benzene.

Synthesis of mescaline

The synthesis is initiated by the bromination of benzene using bromine in ferric bromide. The bromobenzene thus obtained is nitrated using the nitrating mixture. The bromide group is replaced using methoxide ion, which is a strong base.

The para methoxy nitrobenzene thus formed is reduced by catalytic hydrogenation in the presence of palladium catalyst to form para-methoxy aniline. Diazotization of the amine using sodium nitrile followed by bromination gives para-bromo methoxy benzene.

Nitration of the product introduces the nitro group at the two ortho positions of the methoxy group to form amines. Diazotization, followed by a reaction with methanol, converts the amine group into methoxy groups. The product is bromobenzene with methoxy substituents at 3,4, and 5 positions.

The bromo group is converted to an ethylamine group in a series of steps to obtain mescaline. The reaction can be given as: