Carboxylic acids, amides prepared solubility

The acyl chloride (the crude material prepared by the thionyl chloride method is quite satisfactory) is added dropwise to well-stirred concentrated aqueous ammonia cooled in a freezing mixture. The amides of the higher carboxylic acids crystallise out on standing and need only to be filtered and recrystallised. Water-soluble amides are isolated by extraction with hot ethyl acetate following removal of water on a rotary evaporator. 

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 ... 

Among the ethers of prolinol, (5)-2-methoxymethylpyrrolidinc [SMP, (S)-10] has found most applications. It is readily prepared from prolinol by the normal sodium hydride/iodo-methane technique9,13 (sec also Section 2.3. for O-alkylations of other amino alcohols) and is also commercially available. An improved synthesis from proline avoids the isolation of intermediates and gives the product (which is highly soluble in water) by continuous extraction14. SMP has been used as the lithium salt in deprotonation and elimination reactions (Section C.) and as an auxiliary for the formation of chiral amides with carboxylic acids, which in turn can undergo carbanionic reactions (Sections D.l.3.1.4., D.l. 1.1.2.. D.l. 1.1.3.1., in the latter experimental procedures for the formation of amides can be found). Other important derivatives are the enamines of SMP which are frequently used for further alkylation reactions via enolates (Sections D.l.1.2.2.. where experimental procedures for the formation of enamines are... 

Benzonitrile acts in a similar way to form benzoic acid but requires sulfuric acid in the reacting mixture. Nicotinic acid amide (nicotinamide) has been prepared by the mild hydrolysis of 3-cyanopyridine, and acrylamide by the partial hydrolysis of acrylonitrile. Acrylonitrile may also be hydrolyzed to acrylic acid with mineral acids or with alkalies. Polyacrylonitrile is partially converted to the amide by nitric acid, and the nitrile oups of a number of polymers and copolymers have been hydrolyzed to amide and carboxylic acid groups to produce water-soluble polyelectrolytes. Isooyanides are stable toward alkalies but hydrolyze in the presence of acids to form an acid and an amine ... 

Three satisfactory solid derivatives of carboxylic acids are amides (Eq. 25.46), anilides (Eq. 25.47), and p-toluidides (Eq. 25.48). These derivatives are prepared by treating the corresponding acid chlorides with ammonia, aniline, or p-tolui-dine. The amides are generally less satisfactory derivatives than the other two because they tend to be more soluble in water and thus are harder to isolate. The acid chlorides are most conveniently prepared from the acid, or its salt, and thionyl chloride (Eq. 25.49). 

These catalysts are useful in the reactions of both primary and secondary amines with various carboxylic acids (Equation 10). Catalytic amidation of optically active aliphatic a-hydroxycarboxylic acids with benzylamine proceeds with no measurable loss (<2%) of enantiomeric purity under reflux conditions in toluene. Most amino acids are barely soluble in non-aqueous solvents. Nevertheless, their lactams can be prepared by the present technique under heterogeneous conditions. For example, when 6-aminocaproic acid and 1 mol% of the boron catalyst 3.4,5-FjC5H2B OH)2 are suspended in refluxing xylene, the solid slowly dissolves and caprolactam is formed in 93% yield. 

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