Benzene Derivatives with a Nitrogen Containing Side-Chain

1 Benzene Derivatives with a Nitrogen Containing Side-Chain 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be expected to stop at any specifle stage. Secondary amides, however, can be monoalkylated and lydrolyzed or be reduced to secondary amines (p. 11 If.). In the elegant synthesis of phenyl- phrine an intermediate -hydroxy isocyanate (from a hydrazide and nitrous acid) cyclizes to pve an oxazolidinone which is monomethylated. Treatment with strong acid cleaves the cyclic irethan. 

Urea derivadves are of general interest in medicinal chemistry. They may be obtained cither from urea itself (barbiturates, sec p. 306) or from amines and isocyanates. The latter are usually prepared from amines and phosgene under evolution of hydrogen chloride. Alkyl isocyanates are highly reactive in nucleophilic addidon reactions. Even amides, e.g. sulfonamides, are nucleophilic enough to produce urea derivatives. 

Other aromatic best-sellers in the pharmacy are given below. Syntheses of these compounds are simple and may be outlined by the interested reader himself. The only common open-chain synthetic drug is meprobamate. Its conventional synthesis is given. 

The 2-alken-4-ynylamine analogues (A. Stiitz, 1987) are best synthesized by Grignard-type additions of lithium acetylides to propenal and either 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be ex- 

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