Ammonium carboxylates dehydration

In practice, one proceeds as follows. The value of bh >s determined for the reaction with a series of acids of similar structure, that is, for carboxylic acids or ammonium ions, etc. Limiting the data to a single catalyst type improves the fit. since the inclusion of data for a second ype of acid catalyst might define a close but not identical line. This means that Ga may be somewhat different for each catalyst type. A plot of log(kBH/p) versus log(A BH(7//i) is then constructed. This procedure most often results in a straight line, within the usual —10-15 percent precision found for LFERs. One straightforward example is provided by the acid-catalyzed dehydration of acetaldehyde hydrate,... 

Nucleophilic attack only occurs upon heating the ammonium salt, resulting in overall dehydration of the salt. Consequently, it is usual to prepare amides by using a more favourable substrate than the carboxylic acid, one that is more reactive towards nucleophiles by virtue of possessing a better leaving group, and where salt formation does not hinder the reaction. 

Heating at high temperature (>100 °C) dehydrates the resulting ammonium salt of the carboxylate anion to form an amide, though the yield can be low. 

In fact, amides can be made from carboxylic acids plus amines, but only if the ammonium salt is heated strongly to dehydrate it. This is not usually a good way of making amides ... 

Introduction. The general methods for the preparation of amides are (1) ammonolysis of esters, acyl halides, and anhydrides (2) the dehydration of the ammonium salts of carboxylic acids ... 

Removal of water by distillation shifts the equilibrium point to favor formation of the amide. For preparation of the amide by this method the ammonium salt of the carboxylic acid is prepared and dehydrated, melted, allowed to cool, and then pulverized. The powdered material is placed in a distilling flask and heated. Another method is to add solid ammonium carbonate to the carboxylic acid, and distill directly. 

The reaction occurs only because ammonium butyrate, being the salt of a weak acid and a weak base, is in equilibrium with a significant amount of ammonia and butyric acid. The actual dehydration step is probably the result of nucleophilic additon of ammonia to the carboxyl group of butyric acid itself. 

Amides can be prepared by the reaction of an acid chloride, acid anhydride, or an ester with ammonia or an amine. Acids and amines can be coupled in the presence of a dehydrating agent such as DCC. Amines react with carboxylic acids to give ammonium salts. Heating these salts to around 200°C will usually give the amide. Lactams are cyclic amides. 

General procedure. 4-Cyanoimidazoles 1444 [1098] A mixture of ethyl 4-imidazole-carboxylate (33 g) and ammonium hydroxide (250 mL) was heated to 100 °C in a sealed glass vessel for 1-7 days. The mixture was then cooled and the solid 4-imi-dazolecarboxamide 1443 was recovered by filtration in near quantitative yield and air dried. Dehydration was carried out by heating a solution of 4-imidazolecarbox-amide 1443 (5 g) in PhPOCli (25 mL) at 80 °C for 12 h. The cooled reaction mixture was then poured over ice (200 mL) and adjusted to pH 11 with 50% aqueous sodium hydroxide. The 4-cyanoimidazole 1444 was isolated by extraction with ethyl acetate and concentration of the extracts in vacuo. 

The reaction of carboxylic acids with ammonia normally produces its ammonium salt. The dehydration of ammonium salts may be used to prepare amides. 

Amides can, in principle, be prepared by thermal dehydration of ammonium salts of carboxylic acids, such as [NH4] [RCOO] or [RNH3]+[RCOO], but this route is rarely used in practice, because of the reversibility of the process. Most strategies depend on the reaction of amines with carbonyl derivatives where there is a better leaving group than OH attached to the carbonyl. 

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