Pyridine carboxylic acids, decarboxylation esterification

In most of their reactions, the pyridine- and azinecarboxylic acids and their derivatives behave as any other acid (cf. Scheme 86). However, some acid chlorides can be obtained only as hydrochlorides, and we must also consider decarboxylation. Esterification of pyridine carboxylic acids can be usefully achieved via in situ generation of the acid fluoride. For example, treatment of picolinic acid with a stoichiometric amount of N,N,N,A-tetramethylfluoroformami-dinium hexafluorophosphate (TFFH) in dichloromethane and triethylamine leads to generation of the acid fluoride, which reacts with (3-methyloxetan-3-yl)methanol to give the corresponding ester in 95% yield <2004S2485>. 

All four isomeric selenolopyridines which can be derived from benzoselenophene (423— 426 Scheme 123) have been described. Ethyl 3-hydroxyselenolo[2,3-fe]pyridine-2-carboxy-late (429) has been prepared as shown in Scheme 124 (73BSF704). Treatment of ethyl 2-chloropyridine-3-carboxylate with methaneselenol yields (427). Nucleophilic displacement of bromine in bromoacetic acid with subsequent loss of methyl bromide yields (428), which after esterification is cyclized under Dieckmann conditions to give (429). The parent compound (423 colorless oil with b.p. 92 °C/1 mmHg) is prepared either by cyclization of compound (430) and subsequent decarboxylation of the intermediate acid (equation 57) or by reduction of 2-nitroselenophene and subsequent condensation of the amino compound with malonaldehyde bis(diethyl acetal) in the presence of zinc chloride (equation 58) (76BSF883). Selenolo[3,2-6]pyridine (426 b.p. 127-129°C/10 mmHg m.p. 35.5-37.0°C) has been obtained in an analogous manner. 

A further synthesis of quinuclidine was devised by Clemo and Metcalfe (197), who decarboxylated 2,4-lutidinic acid (CLVIII), obtuned by oxidation of 2,4-lutidine, and reduced the resulting pyridine-4-carT boxylic acid (CLIX) with sodium and alcohol. Esterification of the product afforded ethyl piperidine-4-carboxylate (CLX), which was condensed with ethyl chloroacetate to give ethyl piperidine-l-acetate-4-carboxylate (CLXII). Dieekmann cyclization followed by decarboxylation yielded 3-ketoquinuclidine, which on reduction by the Wolff-Kishner or Clemmensen methods gave quinuclidine. 

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See also in sourсe #XX -- [ ]

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