Pyridine-3-carboxylic acid hydrazide

Pyridine-4-carboxylic acid hydrazide (isonicotinic hydrazide) (C H70N3)... 

For the sake of completeness, we conclude by mentioning a carbonic acid hydra-zide, namely pyridine-4-carboxylic acid hydrazide (isonicotinic acid hydrazide, Isoniazide), an amide compound with a major potential for antimicrobial efficacy but also general toxicity, which is an obstacle to its practical application as a microbicide for the protection of materials. 

The first inhibitors of flavin-dependent MAO that were developed for clinical use were hydrazines and hydrazides. The chance discovery that the antitubercular drug, 4-pyridine carboxylic acid hydrazide (isoniazid, 40), was also a potent MAO inhibitor led to the development of the related drug, iproniazid (41), used for the treatment of depressive illness. Although this compound demonstrated remarkable antidepressant action, its clinical value was seriously compromised by side effects [19]. 

The reduction of acyl hydrazines has been investigated very little. Polarography of 4-pyridine carboxylic acid hydrazide in acid and neutral solution shows that it is reduced in two, two-electrons steps [141]. The result of controlled potential electrolysis is cleavage of the N-N bond to form 4-pyridine-carboxamide, which then undergoes reduction to the aldehyde in the second step. Other hydrazides of heterocyclic carboxylic acids behave analogously. 

C H. ON Pyridine-2-carboxylic acid hydrazide (pico 1 inoyIhydrazine)... 

The amides and hydrazides of pyridine-carboxylic acids arc of some importance, though their chemistry is not marked by unusual properties. Nicotinamide is, of course, an important compound, and isonicotinic acid hydrazide (isoniazid) is an antitubercular drug. Substituted derivatives are used as antidepressants. In general, however, these compounds show normal chemical behaviour. The amides undergo hydrolysis, dehydration and Hofmann bromination without difficulty. Their reduction has been much studied as a route to pyridine aldehydes. The Sonn-Muller reduction is not very satisfactory in this series, but the McFadyen-Stevens reaction is useful . Nicotinic acid diethylamide gives only poor yields of the aldehyde upon reduction with lithium aluminium hydride, but yields from the methyl-phenylamide are high. Most satisfactory is the reduction of nicotinic acid dimethylamide with lithium diethoxyaluminium hydride . 

Methyl-3,3 -bipyridine has been oxidized by permanganate to 3,3 -bi-pyridine-4-carboxylic acid. " 3,3 -Bipyridine carboxylic acids are easily decarboxylated and have been esterified and converted to amides, hydrazides, and acylazides. The Hofmann degradation, of the diamide of 3,3 -bipyridine-2,2 -dicarboxylic acid affords the expected 2,2 -diamino-3,3 -bipyridine, but some of the tricyclic system 108 is formed as well. A 2,2 -bis(acylazide) is converted to a similar tricyclic system with ethanol via the intermediate isocyanate, and several related reactions have been described. The simultaneous dehydration... 

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]. 

In the pyrazolo [ 1,5-a]pyridine series, the reaction of hydrazine with the 2,3-dimethoxycarbonyl derivative afforded the corresponding 2-hydrazide, whereas saponification and decarboxylation gave the 3-carboxylic acid.169 Further, several 2-substituted 3-carboxamides, -hydrazides, and -carboxylic acids were obtained,169,239 using standard methods. Decarboxylation was also reported.169 A number of transformations of py razolo [3,4-h]pyridine... 

Nicotinic acid pyridine 3-carboxylic acid, 123.11, m.p. 234-237°C, first obtained in 1867 from the oxidation of nicotine. It is biologically important as a member of the vitamin Bj complex (see Vitamins). Isonicotinic hydrazide (INH), iff, 137.14, m.p. 163 °C, is an antitubeteulosis agent, which shows antivitamin properties against both nicotinic acid and vitamin B. ... 

Hydrazides of 4-arylethynyl-5-carboxylic acid undergo a regioselective base-catalysed 6-endo-dig cyclization with the formation of pyrazolo[3,4-c]pyridine-7-ones (Scheme 32)45... 

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