Pyridine-3,5-dicarboxylic acid hydrogenation

SCHEME 8 A STEPWISE ROUTE TO UNSYMMETRICAL MACROCYCLES. WITH 2,6-PYRIDINE DICARBOXYLIC ACID DICHLORIDE BUILDING BLOCK 17 IS FORMED WHICH IS PREORGANIZED FOR MACROCYCLIZATION AND THUS GIVES HIGHER YIELDS OF MACROCYCLE 18 AS COMPARED TO 13. THE INSET SHOWS THE HYDROGEN BONDING PATTERN IN THE PYRIDINE BUILDING BLOCKS AND THE EFFECTS IT HAS ON CONFORMATIONAL EQUILIBRIA AND... 

Fig. 8.3 Hydrogen bonded nanotube from aromatic oligoamides. a The structure of an aromatic oligoamide derived from 2,6-diaminopyridine and 2,6-pyridine dicarboxylic acids and the hydrogen bonding pattern in the formation of the helical structure, b Hydrogen bonding patterns that cause the oligoamide backbone to switch between the folded and unfolded cotrformations...

Unexpectedly strong intermolecular hydrogen bonding has been reported by IR spectroscopic studies for tetrahydro-4,7-phenanthroline-l,10-dione-3,8-dicarboxylic acids, which exist in the oxo-hydroxy form 165 in both solid state and in solution [78JCS(CC)369].Tlie conclusion was based on comparison of B-, C-, and D-type bands for 165 and their dimethyl esters (detection of hydrogen bonding) and on analysis of IR spectra in the 6 /xm region (pyridine- and pyridone-like bands). 

Oxidation of methylpyridines in 60-80 % sulphuric acid at a lead dioxide anode leads to the pyridinecarboxylic acid [213]. The sulphuric acid concentration is critical and little of the product is formed in dilute sulphuric acid [214]. In these reactions, electron loss from the n-system is driven by concerted cleavage of a carbon-hydrogen bond in the methyl substituent. This leaves a pyridylmethyl radical, which is then further oxidised to the acid, fhe procedure is run on a technical scale in a divided cell to give the pyridinecarboxylic acid in 80 % yields [215]. Oxida-tionof quinoline under the same conditions leads to pyridine-2,3-dicarboxylic acid [214, 216]. 3-HaIoquino ines afford the 5-halopyridine-2,3-dicarboxylic acid [217]. Quinoxaline is converted to pyrazine-2,3-dicarboxylic acid by oxidation at a copper anode in aqueous sodium hydroxide containing potassium permanganate [218]. 

Reaction of 1,2 -dicarboxylic acids has been used for the formation of a number of strained alkenes and also applied to the Diels-Alder addition products from maleic anhydride (Table 9.5). Both cis- and tr s-diacids take part in the process. Aqueous pyridine containing, triethylamine as a strong base, is considered the best solvent and higher yields are obtained at temperatures of around 80 "C [130]. Use of a divided cell avoids a possibility of electrocatalytic hydrogenation of the product at the cathode. The addition of /a/-butylhydroquinone as a radical scavenger prevents polymerization of the product [127], An alternative chemical decarboxylation process is available which uses lead tetraacetate [131] but problems can arise because of reaction between the alkene and lead tetraacetate. 

A, and the O H -0 length 2.53 A. The 2,6-dicarboxylic acid monohydrate exists in the neutral form, while the 3,5-isomer, dinicotinic acid, exists in the intermediate form, but here each molecule is joined by two kinds of hydrogen bond (O—H- O, 2.59 A O H- -N, 2.52 A) to four surrounding molecules. Pyridine-2,3-dicarboxylic acid exists in the zwitterionic form (38), as does cinchomeronic acid, the 3,4-dicarboxylic isomer (39), the N—H bond distances being 0.89 A and 1.09 A respectively. 

The catenane shown bears one furane dicarboxylic acid building BLOCK instead OF THE ISOPHTHALIC ACID ANALOGUE. SIMILAR TO PYRIDINE, THE FURANE FORMS INTRAMOLECULAR HYDROGEN BONDS WITH THE ADJACENT AMIDE NH PROTONS. 

A mixture of the oxazole (I) with two moles of diethyl maleate (Ila) is heated and the adduct cleaved with ethanolic hydrogen chloride to form the diethyl ester of 2-methyl-3-hydroxy-pyridine-4,5-dicarboxylic acid hydrochloride (Ilia) (85%). This diester is reduced with lithium aluminum hydride to pyridoxine (41-42) isolated as its hydrochloride. 

Gutman,50 in his process route, which did not report any yields, hydrogenated the pyridine ring first to access the piperidine moiety and constructed the indanone ring system via an intramolecular Friedel-Crafts acylation (Scheme 5). Hydrogenation of diester 31, obtained from condensation of 4-pyridine carboxaldehyde and dimethyl malonate, followed by benzylation of the piperidine intermediate afforded A-benzylated piperidine 32. Alkylation of 32 with 3,4-dimethoxybenzyl chloride (33) and subsequent hydrolysis gave dicarboxylic acid 34. Subjection of 34 to strong acid resulted in intramolecular Friedel-Crafts acylation and in situ decarboxylation to provide 3. 

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