Condensations amines with carboxylic acids, pyridine

In another synthesis using a preformed pyridine derivative a cyanoacetic acid ester is condensed in a Guareschi-type reaction with an a-substituted /3-keto carboxylic acid ester and an amine to give a hydroxypyridone (18 Scheme 3). These compounds are suitable precursors for an acid catalyzed cyclization to furo[2,3-6]pyridine-6-ones (19). N-Substituted derivatives may also be prepared by this route (64AP754). The aqueous solutions of these furopyridines show an intensive blue fluorescence. 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

Metal salts, like lithium chloride, significantly enhance reactions of carboxylic acids with amines promoted by triphenyl phosphite. This allows direct polycondensation of dicarboxylic acids with diamines and self-condensation of p-aminobenzoic acid. The presence of a solvent markedly enhances the reaction with the best results being obtained in A methylpyrrolidone. High molecular weight polyamides form. Mixed solvents, like pyridine and -methylpyrrolidone, can be used to form polyisophthalamides. This combination of solvents, however, yields only low molecular weight polyterephthalamides. On the other hand, when the reaction is carried out in the presence of polymeric matrices of poly(ethylene oxide) or poly(4-vinylpyridine), high molecular weight polyterephthalamides form . ... 

Condensation of carboxylic acids with amines in pyridine in the presence of a phosphorous(III) acid/iodine complex is an effective method for the synthesis of amides (eq 5) Pyridine acts as a base and a solvent in this reaction. 

Dehydrations using chlorosulfonic acid-pyridine (pyridinium sulfamates) provide a convenient synthetic route to amides without die intermediacy of acyl halides. The carboxylic acid was condensed with the amine in pyridine solution containing chlorosulfonic acid at 0-10 °C to give the amides (Equations 9 and 10).2 ... 

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