Secondary carboxylic amide

Secondary carboxylic amides of the type PhC(0)NR(H) were rapidly deprotonated with dimethylzinc to furnish mainly tetrameric and hexameric mono(methylzinc) derivatives.147... 

An aryl alkyl ketone 1 can be converted into an tn-arylalkane carboxylic amide 2 by employing the Willgerodt reaction The number of carbon centers is retained. The reaction is carried out by treating the ketone with an aqueous solution of ammonium polysulfide. A variant that has been developed by Kindler, and which is called the Willgerodt-Kindler reaction, uses a mixture of sulfur and a secondary amine instead of the ammonium polysulfide. 

In addition to carbonyl substrates, imines have been used extensively with phosphorus-halogen reagents for the preparation of a variety of phosphonates and phosphinates. Combined in a reaction medium, secondary amines react with formaldehyde and phosphorus trichloride134 135 or alkyldichlorophosphines136 to produce N,N-disubstituted aminomethylphosphonates or -phosphinates. These reactions occur under mild conditions with good yield. Similarly, aliphatic carboxylic amides react with aldehydes to generate imines, which can be used in situ with diphenylchlorophosphine to produce... 

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. 

Heating of secondary carboxylic acid amides with HMPA gives rise to formation of A(-substituted V JV -dimethylamidines (310 Scheme 48). - In this procedure the secondary amide can be replaced by a ketoxime in which at least one substituent has to be an aromatic one. Similar methods were de-... 

High-sudsing detergent with //-alkoxy polyhydroxy fatty acid amide and secondary carboxylate... 

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. 

Strong pyridine anhydrides sulfoxides tertiary amines aliphatic or aromatic hydroxyl carboxylic acid urea urethane sulfonic acids primary and secondary amines amide phosphonic acids... 

Starting from amides on solid supports one could cleave to get fimctional-ities hke carboxylic adds 145, esters 144, primary, secondary, tertiary amides (147,148) and other targets 146 obtainable via nucleophilic substitution. Car-boxyhc acids can be obtained by treatment of the resin with strong bases like aq. NaOH or alternatively by addition of enzymes imder mild, neutral and aqueous conditions (Scheme 23) [177]. 

The melting points of some typical substituted aromatic amides are collected in Table IV,192. Other examples will be found in the appropriate columns of Tables IV,100A and B Primary and Secondary Aromatic Amines) and of Table IV,175 (Aromatic Carboxylic Acids). 

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