Halogeno-amines

Almost insoluble in cold water. Higher alcohols (including benzyl alcohol), higher phenols (e.g., naphthols), metaformaldehyde, paraldehyde, aromatic aldehydes, higher ketones (including acetophenone), aromatic acids, most esters, ethers, oxamide and domatic amides, sulphonamides, aromatic imides, aromatic nitriles, aromatic acid anhydrides, aromatic acid chlorides, sulphonyl chlorides, starch, aromatic amines, anilides, tyrosine, cystine, nitrocompounds, uric acid, halogeno-hydrocarbons, hydrocarbons. 

A.mina.tlon. Amination describes the introduction of amino groups into aromatic molecules by reaction of ammonia or an amine with suitably substituted halogeno, hydroxy, or sulfonated derivatives by nucleophilic displacement. Although reaction and operational conditions vary, the process always involves the heating of the appropriate precursor with excess aqueous ammonia or amine under pressure. 

Halogeno-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halogeno analogs do not. 5-Chloro-l,4-diphenyl-l,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative (63JCS2032). 1-Substituted 3-chloro- and 5-chloro-l,2,4-triazoles both react with amines. 

The independence of the composition of the reaction products from the nature and position of the halogeno substituent clearly demonstrates that the amination of the isomeric 3- (27, X = Cl, Br, I) and 4-halogenopyridines (32, X = Cl, Br, I) proceeds exclusively via 3,4-pyridine (31). It is surprising that the 4-halogenopyridines did not... 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

Note Aminolysis of halogeno esters may be accompanied by amide formation, depending on the amine and conditions employed. 

This technique is used to diazotise anilines carrying two or more electron-withdrawing substituents, such as 2,4-dinitro- and 2-cyano-4-nitro-aniline, as well as aminoanthra-quinones and heteroaromatic amines [4]. Some diazonium salts prepared by this technique, such as those from 6-halogeno-2,4-dinitroanilines, are unstable in water and have to be added directly to the coupling component solution. 

D. la Intramolecular attack by the dialkylamino-group on a neighbouring ester group 254, D.lb Intramolecular nucleophilic attack by imidazole and pyridine 255, D.2 Intramolecular attack by the NHR group 256, D.3 The cyclization of halogeno-amines, etc. 256, D.4 Intramolecular nucleophilic attack on phosphorus 259... 

In some of Forlani s works, such as the reactions of l-halogeno-2,4,6-trinitrobenzene with 2-hydroxypyridine123,125, a substrate-catalyst molecular complex was assumed, but the kinetic law showed the regular second order in amine. Rather interestingly in this scheme, the authors assume that the molecular complex can lead to the formation of products following a second order in nucleophile kinetics, while in the reactions with amines it was presumed that the complex was not on the reaction coordinate, and that an additional molecule of amine was required (the authors needed to include this additional molecule to account for the third order in amine rate law). 

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