Ammonolysis, acyl chlorides

Ammonolysis. Reactions involving ammonia. Ammonolysis of esters, acyl chlorides, and anhydrides give amides aniline is produced by ammonolysis of chlorobenzene. The reaction is analogous to hydrolysis, with ammonia substituted for water. 

The acylation of simple /3-keto esters with acyl chlorides to form di-acylacetic esters proceeds readily however, the subsequent cleavage for removing the smaller acyl group is complicated in that the original keto ester may be regenerated. The optimum conditions for the conversion of benzoylacetoacetic ester to benzoylacetic ester with ammonium chloride and ammonium hydroxide have been studied. The over-all synthesis of this ester has been described (57%). An improved procedure for the ammonolysis of ethyl a-acetyl-/3-oxocaproate using gaseous ammonia has been described. By a similar process, a series of alicyclic /3-keto esters has been prepared in over-all yields of 20-40%. ... 

The ammonolysis of acyl chlorides is commonly employed whenever the preparation of an amide is desired for the identification of a carboxylic acid. The acyl chloride is prepared and treated with aqueous ammonia, or, if the amide is very soluble in water, with ammonia in benzene. In the latter case the ammonium chloride is filtered off, and the amide obtained by evaporation of the benzene with powdered ammonium carbonate. The preparation of amides from carboxylic acids is based upon the formation of an equilibrium mixture when the ammonium salts of the acid are heated ... 

In considering the synthesis of this compound several alternatives are possible. Two will be considered. Aniline may be sulfo-nated to sulfanilic acid, and after acetylation the chloride may be prepared by the action of phosphorus pentachloride. The acyl chloride, on ammonolysis, will give the acetylated sulfonamide. The other possibility is to use chlorosulfonic acid and introduce the sulfo and chloro groups simultaneously. Aniline is acetylated, and the acetanilide is sulfonated with excess of chlorosulfonic acid. The sulfonic acid group is introduced first, and by further reaction the acid chloride is formed ... 

Several improvements in acylation techniques were announced. Butyllithium wwas determined to be superior to sodium amide in preparation of amide ions for ammonolysis reactions with esters. Phosgene is more reactive than ethyl chloroformate toward eneamines. The intermediate acyl chlorides may then be converted to a variety of products. a-Acetylenic aldehydes are easily prepared by the action of acetylenic Grignard reagents upon ethyl formate. ... 

Esters undergo nucleophilic addition—elimination at their acyl carbon atoms when they are treated with ammonia (called ammonolysis) or with primary and secondary amines. These reactions take place much more slowly than those of acyl chlorides and anhydrides, but they can still be synthetically useful ... 

Captopril Captopril, l-[(2S)-3-mercapto-2-methylpropionyl]-L-proline (22.7.4), is synthesized by direct acylation of L-prohne with 3-acetylthio-2-methylpropionic acid chloride (22.7.2), which is synthesized from 3-acetylthio-2-methylpropionic acid (22.7.1), which is in turn synthesized by reacting methacrylic and thioacetic acid. l-(3-Acetylthio-2-D-methylpropanoyl)-L-proline (22.7.3) is formed by reacting L-proline with 3-acetylthio-2-methylpropionic acid chloride, and it undergoes further ammonolysis with ammonia, to give the desired captopril (22.7.4). 

C The decapeptide 2 was reacted with a 3-4 fold excess of the bromo-isocaproyltriglycine chloride described above to yield the fourteen-membered a-bromo acyl compound. After a 4-5 day ammonolysis in liquid ammonia the corresponding tetradecapeptide (3) was acylated by the d-bromoisocaproyltriglycine chloride once again with difficulty and the 18-membered product converted by treatment with liquid ammonia to the famous octadecapeptide with a molecular weight of 1213. 

In the fourth approach, the carbohydrate can be reversibly converted into a glycosylamine by treatment with an ammonium salt (263,264) or an aliphatic amine (265,266). However, these derivatives are quite unstable in slightly acidic medium or neutral medium. They are further stabilized by acylation with, for example, anhydride acetic (265), p-vinylbenzoyl chloride (267), acryloyl chloride (263), or chloroacetic anhydride, followed by ammonolysis (268) (Fig. 36). The N-linked structure of these glycosynthons is distinct from the open chain structure of the carbohydrate derivatives described above. This method may be useful to introduce complex oligosaccharides. 

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