5.2 The Reaction of Amines
Ammonia and its derivatives are nucleophiles. One type of substitution process that is synthetically practical is the cyclization of a haloalkyl amine，which occurs with displacement of the halide ion by the nitrogen atom. The intramolecular reaction of a β-haloethylamines is particularly important cyclization process，leading to the formation of an aziridine. The starting compounds belong to a class of molecules called mustards，which are potent alkylating agents. An aziridine undergoes ring opening under either acidic or basic conditions，like an epoxide.
An amine reacts in addition processes such as the Michael reaction. With an aldehyde or ketone，an amine undergoes addition-elimination to generate an imine or enamine; with carboxylic acid derivatives，it reacts to form an amide，a cyclic amide is called a lactam，and these compounds are classified like lactones. The β-lactam is a four-membered ring，and it is an integral feature of penicillin and related antibiotics. Penicillin disrupts the crosslinking of bacterial cell walls by reacting via its β-lactam ring with a serine alcohol group at the active site of the enzyme used to make the cell membrane.
Another important type of amide comprises the polyamides. Nylon is the best known polyamide，and it is prepared in much the same way as polyester is. A diamine is treated with a diacid under conditions that lead to expulsion of water. A step-growth process occurs，producing the polyamide. Another way to prepare a polyamide is to start with an amino acid.
Aryl diazonium compounds are more stable than their aliphatic analogs，and they can be used to prepare benzene derivatives，providing an alternative to electrophilic aromatic substitution reactions. The diazonium group is readily displaced by a variety of nucleophiles，although many of the reactions actually occur via radical intermediates. Reaction of an aryl diazonium salt with water produces a phenol; with iodide ion，an aryl iodide; and with copper（I），bromide，chloride，and cyanide，the corresponding aryl halide or nitrile. The BF-4-salt of the diazonium compound undergoes thermal decomposition to yield an aryl fluoride. The diazonium ion can react as an electrophile with another arene. This coupling reaction produces brightly colored molecules that are used as dyes. Sulfite ion reduces the nitrogen-nitrogen bond to produce the corresponding hydrazine. Hypophosphorus acid reduces the carbon-nitrogen bond，replacing the diazonium group with a hydrogen atom.
A nitro compound contains the most oxidized type of nitrogen atom. Whereas an amine has a nucleophilic nitrogen atom，a nitro compound has an electrophilic one. Oxidation and reduction therefore provides a way to change the reactivity profile of a nitrogen-containing functional group. If there are no C—H bonds adjacent to an amine group，then oxidation occurs at the nitrogen atom. A particularly useful reagent for the oxidation of amines is dimethyldioxirane，which converts all types of primary amines，including aryl amines，to nitro compounds. Under certain conditions，the hydroxylamine can be isolated. A secondary amine is oxidized cleanly by this reagent to the corresponding hydroxylamine.
If a nitro group is in the position ortho or parato a halogen atom attached to a benzene ring，then the carbon atom that bears the halogen atom is electrophilic and susceptible to reaction with a nucleophile，leading to substitution. The reaction of para -chloronitrobenzene with a nucleophile proceeds via an anionic intermediate with a tetrahedral carbon atom，so this reaction is actually an addition-elimination process.
Several nitrogen-containing compounds undergo rearrangement via a nitrene intermediate，which contains a neutral and electrophilic nitrogen atom. A nitrene is formally the same as a carbene with regard to distribution of the electrons. In the Hofmann rearrangement，a primary amide is treated with hydroxide ion and bromine，producing carbon dioxide and a primary amine that has one less carbon atom. Under the reactions conditions，the R group migrates from the carbon to the nitrogen atom with concomitant movement of an electron pair from nitrogen，generating an isocyanate. An isocyanate has an electrophilic carbon atom，so it reacts readily with a nucleophile. Addition of hydroxide ion to the carbonyl group of an isocyanate leads to production of a carbamic acid，after protonation. A carbamic acid is generally unstable and decarboxylates to form an amine and carbon dioxide. The scope of the Hofmann reaction is quite broad，encompassing alkyl，aryl，and heterocyclic amides as substrates. If the R group attached to the amide carbonyl group is chiral，it migrates with retention of configuration.
In the Beckmann rearrangement，an oxime，which is prepared from an aldehyde or ketone，re-arranges under acidic conditions，yielding an amide. This is a concerted rearrangement because the R group that is anti to the —OH group in the oxime is the one that migrates.