492. Ring–chain tautomerism in the acid esters of pyridine-2 : 3-dicarboxylic acid

Abstract

Ring-Chain Tautomerim in the Acid Esters of Pyrdine-2 : 3-dimrboxylic Acid. By J. KENYON and KUMAR THAKER.Pyridine-2 : 3-dicarboxylic anhydride and methanol combine exothermally in equimolecdar proportions a t room temperature, to form a viscous compound which is probably a hemi-acetal. Within an hour a t room temperature this changes spontaneously and completely into crystalline methyl 2-carboxypyridine-3-carboxylate which in turn changes to the isomeric methyl 3-carboxypyridine-2-carboxylate when its solutions are heated ; conversely methyl 3-carboxypyridine-2-carboxylate is smoothly re-converted into methyl 2-carboxypyridine-3-carboxylate at 150'. The viscous compound is hygroscopic and forms a stable crystalline hydrate. Both the viscous compound and its crystalline hydrate with diazomethane readily give dimethyl pyridine-2 : 3-dicarboxylate.(+ )-sec.-Butyl 2-carboxypyridine-3-carboxylate, when heated in ethyl acetate, is converted into ( + ) -sec.-butyl 3-carboxypyridine-2-carboxylate without significant loss of molecular cllssymmetry. (-)-sec.-Butyl 3-carboxypyridine-2-carboxyIate is smoothly decarboxylated a t 160' to optically pure (-)-sec.-butyl nicotinate.BY heating a mixture of pyridine-2 : 3-carboxylic anhydride and methanol for several hours, Kirpal obtained a methyl carboxypyridinecarboxylate which, since it gave methyl nicotinate on decarboxylation, he believed to be methyl 2-carboxypyridine-3-carboxylate (V). Later he showed that by the successive action of ammonia, hypobromite, and heat this compound gave 2-aminopyridine; accordingly he concluded that the compound was

Efficient Access to Novel Mono- and Disubstituted Pyrido[3,2-d]pyrimidines

“…9,10 The first step consisted in a methanolysis, carried out in refluxing MeOH to afford, after recrystallization in a small amount of EtOAc, the pure regioisomer 2 in a 72% yield. 11 A further multistep sequence led to the isocyanate 3 from compound 2. Only degradation products were obtained when the nonisolated intermediate 3 was reacted with ammonia.…”

“…9,10 The first step consisted in a methanolysis, carried out in refluxing MeOH to afford, after recrystallization in a small amount of EtOAc, the pure regioisomer 2 in a 72% yield. 11 A further multistep sequence led to the isocyanate 3 from compound 2. Scheme 1 Reagents and conditions: a) dry MeOH, reflux, 48 h; b) i) ClCO 2 Et (1.5 equiv), Et 3 N (1.3 equiv), -10°C, 1.5 h; ii) NaN 3 (1.7 equiv) in H 2 O, -10°C to 0°C, 1.5 h; iii) r.t. and aqueous treatment then toluene, reflux, 2 h; c) PMBNH 2 (1 equiv), pyridine-toluene 1:1, reflux, 24 h; d) AlCl 3 (10 equiv), anisole, r.t., 2 h; e) PCl 5 (4 equiv), POCl 3 , reflux, 4 h.…”

1,6- and 1,7-naphthyridines. IV. Synthesis of hydroxycarboxamide derivatives

“…A suspension of 2,3-pyridinedicarboxylic acid 2-methyl ester 5 (0.85 g, 5 mmoles), prepared following Kenyon and Thaker´s procedure [30], in dry benzene (5 mL) and oxalyl chloride (0.75 g, 6 mmoles) was stirred at 40º for 3 hours. The solvent and excess of oxalyl chloride were removed in vacuo.…”

Total Synthesis of Phomazarin

“…Hydrogenolysis deprotection of both 15a , b provided the same carboxylic acid 17 , and deprotection of both 16a , b provided the isomeric acid 18 . Although equilibration isomerism between pyridine-2,3-dicarboxylic acid monoesters and monoacid chlorides has been observed, no isomerism between 17 and 18 was observed at 25 °C (48 h, CH 3 OH). However at reflux, a 62:38 mixture of 18 : 17 was observed after 48 h (CH 3 OH) starting with 18 .…”