Primary carboxylic amide

Conversion of primary carboxylic amides to primary amines with one fewer carbon atom upon treatment with hypohalites or hydroxide via the intermediate isocyanate ... 

The melting points of a few selected primary aromatic amides (together with those of the xanthylamides, where known) are collected in Table IV,191. A more detailed list will be found in the column headed Amides in Table IV,175 (Armnalic Carboxylic Acids). 

Carboxylic acids, alcohols, and primary/ secondary amides... 

Primary aliphatic amides are formed on heating the ammonium salts of the corresponding carboxylic acids, or by heating an acid or its ammonium salt with urea. 

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. 

Amides differ from carboxylic acids and other acid derivatives in their reaction with Li A1H4 Instead of forming primary alcohols, amides are reduced to amines (Fig.P). The mechanism (Fig.Q) involves addition of the hydride ion to form an intermediate that is converted to an organoaluminium intermediate. The difference in this mechanism is the intervention of the nitrogen s lone pair of electrons. These are fed into the electrophilic centre to eliminate the oxygen that is then followed by the second hydride addition. 

Primary, secondary, and tertiary carboxylic amides, carboxylic esters, and carboxylic acids are protonated by mineral acids or sulfonic acids at the carboxyl oxygen to a small extent (Figure 6.9). This corresponds to the activation discussed in Section 6.2.3. This activation is used in acid hydrolyses of amides and esters, in esterifications of carboxylic acids and in Friedel-Crafts acylations of aromatic compounds with carboxylic acids. 

Fig. 7.4. Triftuoromethane-sulfonic acid an hydride/pyridine-mediated dehydration of primary carboxylic acid amides (A) to give the corresponding nitriles (B) with the reagents converting into pyridinium trifluormethanesulfonate pyrH F3C-S03 .

Fig. 7.8. Partial hydrolysis of a nitrile to a primary carboxylic acid amide under acidic conditions initiating the two-step total hydrolysis of acetone cyanohydrin (B). Grey background overall reaction above the grey area competing reactions with inappropriate choice of pH below the grey area mechanistic details.

Fig. 7.9. Partial hydrolysis of phenylacetonitrile (A) under basic conditions to give the primary carboxylic acid amide B, and the possibility of hydrolyzing the latter to yield phenylacetic acid (C).

Carboxylic acids and esters (and other acid derivatives) are generally inert to Sm. However, in strongly basic or acidic conditions, reduction occurs Carboxylic acids and amides are reduced to primary alcohols (amides afford some amine as secondary... 

Another route to carboxylic acids from aldehyde products (once again, generally produced via hydroformylation catalysis) was discovered by Wakamatsu and coworkers. They reported the carbonylation of aldehydes and primary organic amides to produce A-acylamino acids (equation 16). The reaction is efficiently catalyzed by HCo(CO)4 at 100 °C and 140 bar of 3 2 H2/CO (hydrogen is needed to help stabilize HCo(CO)4). Yields of over 90% of the appropriate... 

A study similar to that of the carboxylic esters was done for carboxylic amides by Chakrabarti and Dunitz [28]. A general conclusion for the amides from primary, secondary and tertiary C(a) amines is that the C(a)-CGff) bond of an alkyl substituent avoids the synperiplanar arrangement to the C(0)-N bond. For the (er(-alkyl substituents one of the C - C bonds is therefore always in an antiperiplanar position... 

Several important hormones such as oxytocin, secretin, and LHRH are known to be peptidyl amides (1-3). In addition to these, other peptidyl amides such as indolicidin and the protegrins have been shown to exhibit potent antimicrobial activity (4, 5). The in vivo production of such compounds is via endogenous enzymatic cleavage of propeptides (6), making their synthesis by genetic engineering notoriously difficult. Furthermore, to facilitate the survival of synthetic peptidyl amides in vivo, an obvious defence against the action of carboxypeptidases is the N-alkylation of the carboxylic amide terminus. Such secondary amides would be expected to exhibit vastly different solubility and transport properties to primary amides, thus their chemical synthesis is of immense importance. 

A number of important chemical and biochemical synthetic sequences are initiated by the addition of a nitrogen nucleophile to a carbonyl carbon atom to yield carboxylic amides. Amides are classified as primary (1°), secondary (2 ) or tertiary (3 ) based on the number of carbon afoms affached to the nitrogen. 

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