Carboxylic acid amid synthesis with addition

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

Potassium amide Carboxylic acids from hydrocarbons Synthesis with addition of 1 C-Atom s. 4, 614 KNHS H -> COOH... 

Synthesis of amides and peptides. The simplest compound of this type, dimethylaminopropynal (CH3)aNC=CCHO, is known, but it polymerizes within minutes at room temperature. The thermal stability is improved by introduction of bulky constituents. A whole series of these acetylenes have been prepared of these 1 and a few related compounds have been found useful for synthesis of CO—NH bonds by a push-pull mechanism shown in equation (I). The reaction of 1 with a carboxylic acid proceeds by Michael addition to give a, which rearranges by a cyclic intermediate (b) to the enol ester (2). Reaction of 2 with an amine yields an amide (3) and the water adduct (4) of 1. Yields of amides are in the range 85-95y . This sequence cannot be used for esterification of carboxylic acids. 

Nickel carbonyl-sodium alcohol Carboxylic acid esters and amides from halides Synthesis with addition of 1 C-atom... 

Formation of anhydride succeeds with Ni catalysts even at lower temperatures (230 to 250 °C) than the synthesis of propionic acid from ethylene. Thiolcarboxylic acid esters are obtained analogously by addition of thiols instead of carboxylic acids (2). Olefins, carbon monoxide and amines react to give saturated carboxylic acid amides (3) and acid chlorides are formed from hydrogen chloride and carbon monoxide in the presence of noble metal catalysts of the 8th group of the periodic table of the elements (4). 

Use of the relatively small cyclopropane ring drastically reduces the potential for deleterious steric bulk effects and adds only a relatively small lipophilic increment to the partition coefficient of the drug. One of the clever elements of the rolicyprine synthesis itself is the reaction of d,l tranylcypromine (67) with L-5-pyrrolidone-2-carboxylic acid (derived from glutamic acid) to form a highly crystalline diastereomeric salt, thereby effecting resolution. Addition of dicyclohexylcarbodiimide activates the carboxyl group to nucleophilic attack by the primary amine thus forming the amide rolicyprine (68). 

Isoniazide, the hydrazide of pyridine-4-carboxylic acid, is still, well over half a century after its discovery, one of the mainstays for the treatment of tuberculosis. Widespread use led to the serendipitous discovery of its antidepressant activity. This latter activity is retained when pyridine is replaced by isoxazole. The requisite ester (45-4) is obtained in a single step by condensation of the diketo ester (45-1), obtained by aldol condensation of acetone with diethyl oxalate, with hydroxylamine. One explanation of the outcome of the reaction assumes the hrst step to consist of conjugate addition-elimination of hydroxylamine to the enolized diketone to afford (45-2) an intermediate probably in equilibrium with the enol form (45-3). An ester-amide interchange of the product with hydrazine then affords the corresponding hydrazide (45-5) reductive alkylation with benzaldehyde completes the synthesis of isocarboxazid (45-6) [47]. 

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