24.14: Summary

24 • Summary 24 • Summary

We’ve now seen all the common functional groups that occur in organic and biological chemistry. Of those groups, amines are among the most abundant and have among the richest chemistry. In addition to proteins and nucleic acids, the majority of pharmaceutical agents contain amine functional groups and many of the common coenzymes necessary for biological reactions are amines.

Amines are organic derivatives of ammonia. They are named in the IUPAC system either by adding the suffix -amine to the name of the alkyl substituent or by considering the amino group as a substituent on a more complex parent molecule.

The chemistry of amines is dominated by the lone-pair electrons on nitrogen, which makes amines both basic and nucleophilic. The basicity of arylamines is generally lower than that of alkylamines because the nitrogen lone-pair electrons are delocalized by interaction with the aromatic π system. Electron-withdrawing substituents on the aromatic ring further weaken the basicity of a substituted aniline, while electron-donating substituents increase basicity. Alkylamines are sufficiently basic that they exist almost entirely in their protonated form at the physiological pH of 7.3.

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic π system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules.

Arylamines are prepared by nitration of an aromatic ring followed by reduction. Alkylamines are prepared by S_N2 reaction of ammonia or an amine with an alkyl halide or by the Gabriel amine synthesis. Amines can also be prepared by a number of reductive methods, including LiAlH₄ reduction of amides, nitriles, and azides. Also important is the reductive amination reaction in which a ketone or an aldehyde is treated with an amine in the presence of a reducing agent such as NaBH₄. In addition, amines result from Hofmann and Curtius rearrangements of carboxylic acid derivatives. Both methods involve migration of the –R group bonded to the carbonyl carbon and yield a product that has one less carbon atom than the starting material.

Many of the reactions of amines are familiar from past chapters. Thus, amines react with alkyl halides in S_N2 reactions and with acid chlorides in nucleophilic acyl substitution reactions. Amines also undergo E2 elimination to yield alkenes if they are first quaternized by treatment with iodomethane and then heated with silver oxide, a process called the Hofmann elimination.

Arylamines are converted by diazotization with nitrous acid into arenediazonium salts, ArN₂⁺ X^–. The diazonio group can then be replaced by many other substituents by the Sandmeyer reaction to give a wide variety of substituted aromatic compounds. Aryl chlorides, bromides, iodides, and nitriles can be prepared from arenediazonium salts, as can arenes and phenols. In addition to their reactivity toward substitution reactions, diazonium salts undergo coupling with phenols and arylamines to give brightly colored azo compounds.