Aromatic acid amides primary

Nearly every substitution of the aromatic ring has been tolerated for the cyclization step using thermal conditions, while acid-promoted conditions limited the functionality utilized. Substituents included halogens, esters, nitriles, nitro, thio-ethers, tertiary amines, alkyl, ethers, acetates, ketals, and amides. Primary and secondary amines are not well tolerated and poor yield resulted in the cyclization containing a free phenol. The Gould-Jacobs reaction has been applied to heterocycles attached and fused to the aniline. 

The melting points of aliphatic and aromatic primary carboxylic acid amides and those of the corresponding xanthylamides are collected in Tables 10.27 and 10.28. 

Reactions between a representative range of alkyl- and aryl-amines and of aliphatic and aromatic acids showed that the direct formation of amides from primary amines and carboxylic acids without catalyst occurs under relatively low-temperature conditions (Scheme 1). The best result obtained was a 60% yield of N-bcnzyl-4-phenylbutan-amide from benzylamine and 4-phenylbutanoic acid. For all these reactions, an anhydride intermediate was proposed. Boric and boronic acid-based catalysts improved the reaction, especially for the less reactive aromatic acids, and initial results indicated that bifunctional catalysts showed even greater potential. Again, anhydride intermediates were proposed, in these cases mixed anhydrides of carboxylic acids and arylboronic acids, e.g. (I).1... 

Enzymes are made from just 20 a-amino acid building blocks (structures and abbreviations are shown in Table 5.1). Each amino acid has a unique side chain, or residue, which can be polar, aliphatic, aromatic, acidic, or basic. The amide bonds (peptide bonds) make up the enzyme s backbone, and the residues determine the ultimate structure and catalytic activity of the enzyme. When the sequence of amino acids (the primary structure) for an enzyme is assembled in vivo, it folds... 

In the synthesis of specially substituted methylene diphosphines, made from secondary phosphines and carbonyl derivatives (7), a carbenium ion adjacent to trivalent phosphorus as the transition state has been discussed. The transfer of this reaction principle to primary phosphines and suitable carbonyl compound revealed a further pathway to derivatives of dicoordinated phosphorus (8). Aromatic phosphines react with carboxylic acid amide acetals under elimination of alcohol giving dialkylamino-alkylidene phosphines (Scheme 5). A modification of the synthesis... 

Alane (AIH3) and its derivatives have also been utilized in the reduction of carboxylic acids to primary alcohols. It rapidly reduces aldehydes, ketones, acid chlorides, lactones, esters, carboxylic acids and salts, tertiary amides, nitriles and epoxides. In contrast, nitro compounds and alkenes are slow to react. AIH3 is particularly useful for the chemoselective reduction of carboxylic acids containing halogen or nitro substituents, to produce the corresponding primary alcohols. DIBAL-H reduces aliphatic or aromatic carboxylic acids to produce either aldehydes (-75 °C) or primary alcohols (25 C) Aminoalu-minum hydrides are less reactive reagents and are superior for aldehyde synthesis. ... 

Hofmann established a route to higher homologues of aromatic amines by intramolecular rearrangement of /V-alkylated anilines, a reaction that was of great theoretical and technical importance. In 1870, he reported the conversion of an acid amide into an amine, with loss of one carbon. In 1881, he discovered that when the degradation was carried out with sodium hypochlorite or hypobromite, the yields of primary amines were excellent. This is the Hofmann degradation, or reaction, that takes place via formation of isocyanate60. 

Kamochi and Kudo have reported the use of the Sml2/THF-H20 system to reduce aromatic carboxylic acids to alcohols (Scheme 50). Furthermore, aromatic esters amides and nitriles were similarly reduced by this system in good yield [104]. As indicated above, reduction of carboxylic acids to primary alcohols is also effective with Sml2 in a THF-H20-NaOH mixture [105]. In contrast, without water these substrates remain unchanged. With the Sml2/THF-H20 system, pyridine was rapidly reduced to piperidine in similar reactions with pyridine derivatives bearing chloro, amino and cyano substituents, these functionalities were partly eliminated to afford pyridine or piperidine [107]. 

OF PRIMARY AROMATIC AMIDES Primary aromatic amides are crystalline solids with definite melting points. Upon boiling with 10-20 per cent, sodium or potassium hydroxide solution, they are hydrolysed with the evolution of ammonia (vapour turns red litmus paper blue and mercurous nitrate paper black) and the formation df the alkali metal salt of the acid ... 

These pol)uners are not resistant to highly alkaline solutions of sodium hydroxide, concentrated sulfuric acid, alkaline solutions with pFI greater than 10, aliphatic, primary and aromatic amines, amides, and other alkaline organics, phenols, and acid halides. Table 3.11 provides the compatibility of halogenated polyesters with selected corrodents. Reference [1] provides a more comprehensive listing. 

In the presence of LiHMDS in 1,4-dioxane, aromatic and aliphatic hydroxyl compounds, benzoic acids and benzoic acid amides can be converted with primary amines in high yields even at high temperature using the biarylphosphine (28c)-derived precatalyst. 

A solution of 0.1 g of substance in 4 ml of 2 n HCl is cooled to 5 and mixed with a 10% NaN02 solution, until a drop of the mixture gives a blue color with Kl-starch paper. Nitrogen is set free by amides, aliphatic primary amines, and amino acids (amides are converted to acids, and amines to alcohols yields are often small, but the products can be isolated). A yellow oil or a solid substance (nitrosamine) is formed in the case of secondary aliphatic and aromatic amines. Nitrosamines can be extracted with ether. 

It will also reduce acid chlorides, acid anhydrides and aldehydes to primary alcohols, ketones to secondary alcohols, and amides to the corresponding amines R-CONHi -> R CHiNH. Nitro-hydrocarbons if aromatic are... 

To 5 ml. of water add 1-2 drops of the amine if the amine does not dissolve, add a drop or two of concentrated hydrochloric acid. Add 0-5-1 ml. of this amine solution to 2-3 ml. of the reagent an almost immediate precipitate indicates the presence of a primary amine. A slight turbidity indicates the presence of a primary amine as an impurity. (Primary aromatic amines generally require 2-3 minutes for the test. Urea and other amides, as well as amino acids, do not react.)... 

The characterisation of a primary aromatic amide is based upon its own m.p. and the identification of the acid (see Section IV,175) produced on hydrolysis. A crystalline derivative may be prepared directly with xanthhydrol (for experimental details, see Section 111,110, 1). 

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