Carboxylic acids reaction with pyridine

The use of much-neglected bismuth derivatives for the oxidation of organic compounds has been reviewed.74 Bismuth(III) carboxylates, obtained by reaction of Bi2C>3 with pyridine mono- and di-carboxylic acids and with phthalic acid, act as catalysts for the oxidation of styrene oxide to benzoic acid in DM SO in the presence of 02.75 It is proposed that the bismuth may activate both epoxide and oxidant in a solvate, from which dimethyl sulfide evolution and elimination leads to a ketoalkoxide-bismuth complex (and hence to the initial product, 2-hydroxyacetophenone). Further oxidation to tlie ketoaldehyde and acid requires molecular oxygen, but is also found to be catalysed by bismuth. 

Lactone 529 is also observed in the reaction of the carboxylic acid 528 with DCC in pyridine. ... 

Decarboxylative condensation of N-unsubstituted tx-amino acids with benzaldehyde as an aromatic aldehyde requires somewhat harsher conditions. Benzaldehyde and oc-amino acids are heated under reflux in DMF together with N-phenylmaleimide. The azomethine ylides 108 generated can be captured as mixtures of several stereoisomeric cycloadducts (84CC180). 1-Aminocyclopentane-l-carboxylic acid undergoes a similar reaction with pyridine-3-carbaldehyde in the presence of N-phenylmaleimide to afford a spirocyclic cycloadduct, the maleimide cycloadduct of azomethine ylide 109 (84CC182). 

Kamochi and Kudo have reported the use of the Sml2/THF-H20 system to reduce aromatic carboxylic acids to alcohols (Scheme 50). Furthermore, aromatic esters amides and nitriles were similarly reduced by this system in good yield [104]. As indicated above, reduction of carboxylic acids to primary alcohols is also effective with Sml2 in a THF-H20-NaOH mixture [105]. In contrast, without water these substrates remain unchanged. With the Sml2/THF-H20 system, pyridine was rapidly reduced to piperidine in similar reactions with pyridine derivatives bearing chloro, amino and cyano substituents, these functionalities were partly eliminated to afford pyridine or piperidine [107]. 

For acylation in pyridine by Einhorn s method it is not always necessary to start with preformed acyl chloride. Its preparation and reaction can be effected in one operation by dissolving the amine and carboxylic acid together in pyridine, adding the calculated amount of thionyl chloride with cooling, and after some time pouring the mixture into water the amide is precipitated and is washed successively with dilute acid, dilute alkali hydroxide, and water. 

Krohnke138 has described a different, very smooth degradation of methyl ketones to the carboxylic acid containing one fewer carbon atoms. The principle of his method is to convert the methyl ketone by bromine into its mono-bromo derivative and to bring this into reaction with pyridine this forms the pyridinium bromide which usually crystallizes nicely and, when treated with sodium hydroxide in aqueous-alcoholic solution is hydrolysed to the carboxylic acid and methylpyridinium bromide ... 

An acid anhydride reacts with an alcohol to form an ester and a carboxylic acid, with water to form two equivalents of a carboxylic acid, and with an amine to form an amide and a carboxylate ion. In each case, the incoming nucleophile—after it loses a proton—is a stronger base than the departing carboxylate ion. In the reaction of an amine with an anhydride, two equivalents of the amine or one equivalent of the amine plus one equivalent of a tertiary amine such as pyridine must be used so that sufficient amine is present to react with the proton produced in the reaction. 

Pyridinecarboxylates (99) give photosubstitution products on irradiation with alcohols the products have alkyl or alkoxy substituents, and the product ratios depend on the absence or presence of added mineral acid. A mechanistic rationalization is presented, based on the involvement of a triplet excited state located largely on C==0 or a triplet located largely on the ring (for alkylation), and a singlet excited state (for alkoxylation). The reaction of pyridinecarboxylic acids in the presence of transition-metal ions is reported pyridine-2-carboxylic acid gives pyridine and 2,2 -bipyridyl with iron(iii), but 2-pyridone with copper(ii) pyridine-3-carboxylic acid (100) with Fe gives a dehydrodimer without decarboxylation. 

Aminocyclopentane-l-carboxylic acid undergoes a similar reaction with pyridine-3-carbaldehyde in the presence of N-phenylmaleimide to afford a spirocyclic cycloadduct, the maleimide cycloadduct of azomethine ylide 109 (84CC182). 

Pummerer rearrangements leading to thiolesters are discussed in the later sections on sulphoxides. A superficially related Arbuzov-type reaction, with a 1,2-shift of sulphur, through the intermediate (5), has a similar outcome. 2-Thiopyridyl chloroformate has been advocated as a reagent for the conversion of carboxylic acids into their pyridine-2-thiolesters under mild conditions. 

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