Halogen-substituted ammonia

Reaction of hypochlorous acid with ammonia leads to rapid formation of chloroamine, step (1) . Reaction of the product with ammonia forms hydrazine (2) and this last may then form nitrogen (3), viz. 

2NH3 + H2NCI = N2H4+NH4CI N2H4 + 2 H2NCI = N2 + 2 NH + 2 Cr 

Reaction (1) has been shown to involve either the uncharged molecules (as written, fc = 6.2x10 l.mole sec at 25 °C, E — 1.5 kcal.mole ) or NH4 +OC1 . By examination of the rates of nitrogen evolution and by titration of hypochlorite, reaction (2) was shown to obey the rate law (4) under conditions where reaction (3) was so much faster than (2) that very little hydrazine was present, viz. 

The same workers demonstrated that catalysis by copper salts affected the rate of (3), but not of (2). Perhaps because the reaction in nearly neutral solution was reported to pursue a remarkable course , no other kinetic work was done on the system for thirty years. A number of determinations of reaction yields were made, however, and these were subsequently rationalized in mechanistic terms. A kinetic study in liquid ammonia demonstrated first-order decomposition of chloramine and confirmed the earlier complex rate behaviour and indicated that it was due to the rapid reaction (3) of hydrazine and chloramine. In this system, the rates of the reaction were apparently independent of acidity (10 -10 M NH4.CI). Liquid ammonia had the advantage of diminishing stray catalytic paths for reaction (3). Yagil and Anbar examined the rates of reaction (2) in aqueous solution in the range pH 10.15 to that of 9.0 M KOH. Between pH 10.15 and 14, the rate expression was 

Intermediate formation of hydroxylamine was confirmed by an isotope dilution method. Only low concentrations were present at any time, due to the speed of its reaction with chloroamine. A side product in presence of oxygen is peroxynitrite which probably forms from hydroxylamine. The rates of hydrolysis below 1 M OH obey the expression 

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Under this heading it is convenient to discuss not only reactions of the amide ion, NHJ, but also some reactions of ammonia and halogen-substituted ammonia with hypochlorous acid, hydroxide ion and with other nucleophiles. 

Despite the increasing information on the photochemistry of 2,4-dienones and other unsaturated ketones, as well as on the ring-chain valence isomerism of halogen-substituted pyran and dihydi opyran systems,the data are still very scarce. The intermediate formation of pyrans valence-isomeric with unsaturated carbonyl compounds in the pyridine syntheses based on reactions of ammonia with aldehydes or ketones, advocated by various authors (cf. Section II,B,2,f), is still rather speculative. (See also Section II,B,2,e for the valence isomerism of 5-chloro-2,4-dienones with pyrylium chlorides.)... 

SALT. A compound formed by replacement of part or all of the hydrogen of an acid by one (or more) element(s) or radrcal(s) that are essentially inorganic. Alkaloids, amines, pyridines, and other basic organic substances may be regarded as substituted ammonias in this connection. The characteristic properties of salts are the ionic lattice in the solid state and the ability to dissociate completely in solution. The halogen derivatives of hydrocarbon radicals and esters are not regarded as salts in the strict definition of the term,... 

Another synthetic method which has been very fruitful is based on the use of the chlorides of halogen-substituted acids. Chloroacetyl chloride and a-amino-propionic acid, for example, yield an acid, which is converted by ammonia into a dipeptid. The equation for the first reaction is as follows —... 

E. Fischer and E. Otto first described this method of synthesising polypeptides in 1903. Just as an ordinary acyl radical can be combined with an amino acid, e.g., in the preparation of benzoylalanine, so also can a halogen substituted acyl radical be combined with an amino acid. The subsequent action of ammonia upon this compound replaces the halogen atom by the amino group and a dipeptide results, thus —... 

Nucleophilic substitution by ammonia on a halo acids (Section 19 16) The a halo acids obtained by halogenation of car boxylic acids under conditions of the Hell-Volhard-Zelinsky reaction are reac tive substrates in nucleophilic substitu tion processes A standard method for the preparation of a ammo acids is dis placement of halide from a halo acids by nucleophilic substitution using excess aqueous ammonia... 

An extensive study of the amination of halopyridines has been carried out by den Hertog and co-workers.A comparison of their results with studies in inert solvents using primary and tertiary amines should permit some evaluation of the postulated factors. 2,4-Dichloropyridine in concentrated aqueous ammonia (180°, 5 hr) resulted in the formation of 4-amino- (60% yield) and 2-amino-chloropyridines (20% yield). Under similar conditions, only 4-substitution of 3,4,6-trichloro- and of 2,3,4,5-tetrabromo- and -tetrachloro-pyridines was observed. However, in these and the other polyhalo pyridines, the appreciable and unequal mutual activation by the halogen substituents needs to be emphasized. 

Chloroquinoline (401) reacts well with potassium fluoride in dimethylsulfone while its monocyclic analog 2-chloropyridine does not. Greater reactivity of derivatives of the bicyclic azine is evident also from the kinetic data (Table X, p. 336). 2-Chloroquinoline is alkoxylated by brief heating with methanolic methoxide or ethano-lic potassium hydroxide and is converted in very high yield into the thioether by trituration with thiocresol (20°, few hrs). It also reacts with active methylene carbanions (45-100% yield). The less reactive 3-halogen can be replaced under vigorous conditions (160°, aqueous ammonia-copper sulfate), as used for 3-bromoquino-line or its iV-oxide. 4-Chloroquinoline (406) is substituted by alcoholic hydrazine hydrate (80°, < 8 hr, 20% yield) and by methanolic methoxide (140°, < 3 hr, > 90% yield). This apparent reversal of the relative reactivity does not appear to be reliable in the face of the kinetic data (Tables X and XI, pp. 336 and 338) and the other qualitative comparisons presented here. 

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