Esters with ammonia and amines

The reactions of enolized keto carboxylic esters with ammonia and amines are described on page 507, and those of a-amino alcohols, cyanohydrins, and a-hydroxy sulfonic acids on pages 516-520. 

Table 1.2. Reaction of P-keto esters with ammonia and amines.

Reaction with ammonia and amines (Sec tion 20 12) Esters react with ammonia and amines to form amides Methyl and ethyl esters are the most reactive... 

In the second major method of peptide synthesis the carboxyl group is activated by converting it to an active ester, usually a p-nitrophenyl ester. Recall from Section 20.12 that esters react with ammonia and amines to give fflnides. p-Nitrophenyl esters are much more reactive than methyl and ethyl esters in these reactions because p-nitrophenoxide is a better (less basic) leaving group than methoxide and ethoxide. Simply allowing the active ester and a C-protected amino acid to stand in a suitable solvent is sufficient to bring about peptide bond formation by nucleophilic acyl substitution. 

Conversion of Acid Halides into Amides Aminolysis Acid chlorides react rapidly with ammonia and amines to give amides. As with the acid chloride plus alcohol method for preparing esters, this reaction of acid chlorides with amines is the most commonly used laboratory method for preparing amides. Both monosubstituted and disubstituted amines can be used, but not trisubstituted amines (R3N). 

Conversion of Esters into Amides Aminolysis Esters react with ammonia and amines to yield amides. The reaction is not often used, however, because it s usually easier to start with an acid chloride (Section 21.4). 

The esters of carbamic acid, the urethanes, which are formed by combination of alcohols with compounds of the cyanic acid series, are stable substances. The reaction by which they are formed is, likewise, capable of undergoing many variations. It may be recalled that a second method of synthesising them consists in acting on the esters of chloroformic acid with ammonia and amines. 

Reactions of 5f/-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-one 71, prepared by reaction of 1,2-diaminobenz-imidazole 72 with acetoacetic ester 73, with different reagents was described, in the search of new heterocycles with biological activity <2002CHE598>. When lactam 71 was treated with aromatic aldehydes in boiling 1-BuOH with addition of piperidine 74, 577-3-arylidene-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-ones 75a-c were obtained (Scheme 7). Coupling lactam 71 with phenyldiazonium chloride 76 in dioxane afforded the 3-phenylazo-substituted tricycle 77. When 71 was treated with phosphorus pentasulfide 78 in boiling dioxane or pyridine, its thio analog 79 was obtained. The reaction proceeded most efficiently when lactam 71 was refluxed with twofold excess of 78 in dry dioxane. These thiones 79 react with ammonia and amines by nucleophilic substitution. When 79 was refluxed with ammonia, benzylamine, piperidine, or morpholine, the 4-amino-substituted tricycles 80a-d were obtained. All the described compounds were identified by NMR, mass spectrometry, and IR spectroscopy. 

Dioiganotin dihalides are moderately strong Lewis acids and form stable complexes with ammonia and amines. The commercially important diorganotin compounds are most frequently the oxides, carboxylates, and mercaptocarboxylic acid esters. The oxides are amorphous or polycrystalline, highly polymeric, infusible, and insoluble solids. They are moderately strong bases and react readily with a wide variety of strongly and weakly acidic compounds. Their insolubility in all nonreactive solvents makes the choice of proper reaction conditions for such a neutralization reaction an important consideration for optimum yields. 

The hydride-donating potential of 1,4-dihydropyridines has already been discussed in a mechanistic context in Section 1.3.2.3. Commonly available 1,4-dihydropyridines are the Hantzsch esters (7 X = OR), obtained from condensation of a -keto ester with ammonia and an aldehyde. By far the simplest syntheses of Hantzsch esters involve condensation of ammonia (substituted amines react in general poorly) and an aldehyde if a hydride equivalent at the 4-position is desired. The Hantzsch synthesis has been used in many guises, also to produce nonsymmetrical systems. The interest in these compounds as calcium antagonists has doubtless stimulated the extensive synthetic effort. ... 

The usual acid derivatives of 5-oxo-2-pyrazolin-3- and 4-carboxylic acids are known. Amides are prepared by reaction of esters and ammonia,1339 by the reaction of urea with 2-pyrazolin-5-ones, and by the reaction of azides with ammonia and amines. Hydrolysis of nitriles... 

It solidifies in a freezing mixture to crystals which melt at 14.5°. The compound possesses the chemical properties which are characteristic of acyl chlorides. It is decomposed slowly by hot water, reacts with alcohols to form esters, and with ammonia and amines to form amides. 

Section 19.8 Esters give amides on reaction with ammonia and amines and are cleaved to a carboxylic acid and an alcohol on hydrolysis (Table 19.4). Esters react with Grignard reagents and are reduced by lithium aluminum hydride (Table 19.5). 

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