Pyridinecarboxylic acids, reduction

Hydrogenation of 3-pyridinecarboxylic acids is apt to be accompanied by extensive decarboxylation (2S), but this unwanted reaction can be prevented by carrying out the reaction in the presence of one equivalent of base (33,79). Ruthenium (33), rhodium (29), platinum oxide (2S,59), and palladium (30) have all proved effective catalysts for reduction of pyridinecarboxylic acids to the saturated acid. 

The oxidative cleavage of carbon-carbon double bonds has been reviewed by StewartIn general, carboxylic acids are produced under acidic conditions. However, since many alkenes lack sufficient solubility in water, cosolvents such as pyridine, acetone or acetic acid have often been used to bring the oxidant and reductant into contact For example, a good yield of 2,6-diphenyl-4-pyridinecarboxylic acid was obtained from the reaction depicted in equation (29). Table 9 contains additional examples. 

The 4-pyridinecarboxylic acids [440, 441], 2-carboxythiazoles [445] and 2-carboxyi-midazoles [436, 446], and their esters amides, and thiamides [392, 447-450] are reduced in this way. The corresponding hydrazides [451] and hydroxamic acids [51] are reduced to the amides in the first step and then further reduced. When the activating group in pyridine is in the 3-position the reduction may take place in the nucleus, depending on pH. 

Oxidation of coniine with chromic acid produces butyric acid (115, 124), while dehydrogenation of the alkaloid with silver acetate converts it to abase, conyrine (125), which is also obtained from coniine hydrochloride by distillation with zinc dust (126). Conyrine, CgHnN, is a colorless, fluorescent oil, b.p. 166-168°, which forms a chloroplatinate and an aurichloride it can be converted back to coniine by reduction with hydriodic acid, it behaves on methylation like a pyridine base, and further, it gives rise on oxidation to a-pyridinecarboxylic acid. Therefore, conyrine is a 2-propylpyridine (XCIV) while coniine is a 2-propylpiperidine (XCV) (126), in which the side chain is normal since conyrine is not identical with 2-isopropylpyridine (127). 

Reduction of ArCOOH and derivatives Aryl carboxylic acids can be reduced to ArCH20H by Sml2 (excess) in the presence of an acid, particularly phosphoric acid (85%). In contrast pyridinecarboxylic acids are reduced to the corresponding methylpyridine in 43—48% yield. Benzoic anhydride and benzoyl chloride are also reduced to benzyl alcohol, but in lower yield. Benzonitrile is reduced under the same conditions to benzylamine in 99% yield. This behavior is characteristic for aryl nitriles. 

The use of lithium aluminum hydride for the reduction of pyridinecarboxylic acid amides (IX-227) to side-chain aminopyridines (IX-228) has been reported thus, AyV-dibenzylnicotinamide (IX-227, Ri = R2 = C6HSCH2) is reduced to... 

Reduction of pyridinecarboxylic acid methyl esters with a large excess of sodium borohydride in methanol is reported to give the corresponding alcohol. Thus, using a twentyfold excess of hydride, nicotinic acid gave high yields of 3-hydroxymethylpyridine. Similar reductions of unsaturated pyridinecarboxylic acid esters such as X-124 gave predominantly the saturated alcohols pC-125). 

Rhodium (5%) on carbon is a better catalyst for the reduction of the isomeric pyridinecarboxylic acids, their esters, and amides to the corresponding piperidine analogues than is rhodium on alumina. Reductions are generally slow, but yields are very satisfactory. Catalytic reductions of pyridylalkane... 

Catalytic reductions of substituted pyridinecarboxylic acids continue to play an important role in some syntheses of pyridoxol. Thus 4-carbethoxy-6-chloro-5-cyano-2-methyl-3-nitropyridine (X-132) is reduced over Raney Nickel in water to 3-amino-5-aminomethyl-4-carboxy-2-methylpyridine-4,5-lactam (X-133). - ... 

Wynberg described the photolysis of some pyridinecarboxylic acid derivatives. 3,5-Dicarbethoxy-2,4,6-trimethylpyridine (X-198) gave 3,5-di-carbethoxy-2,4,6-trimethyl-l, 4-dihydropyridine (X-199) and 3-carbethoxy-2,4,5-trimethylpyrrole (X-200) upon irradiation in ethanol. Irradiation of the 4-desmethyl derivative of X-198 in methanol afforded only reduction products or those of addition of solvent at the 2- or 4-positions. 

A new method for the conversion of an oxazoline into its parent carboxylic acid has been reported which involves treatment with NaOCl followed by hydrolysis with mild base yields between 60 and 93% are obtained for eight examples. 3-Acyl-pyridines (59) undergo a Minisci reaction to give 6-substituted products (60) in 20—82% yield Wolff-Kishner reduction then generates the pyridinecarboxylic acids (61) (Scheme 29). ... 

---