Pyridine-2,3-dicarboxylates, synthesis from

Reaction of -picoline over degassed Raney nickel was found to give 5,5 -dimethyl-2,2 -bipyridine (5), the structure of which was established by its synthesis from 2-bromo-5-methylpyridine. Oxidation of this dimethyl-2,2 -bipyridine, and similar oxidation of the diethyl-2,2 -bipyridine derived from 3-ethylpyridinc, gave the corresponding dicarboxylic acid and the same acid was produced by the action of degassed Raney nickel on sodium nicotinate (in water) or on ethyl nicotinate. These transformations established the 5,5 -substitution pattern for three 2,2 -bipyridines derived from 3-substituted pyridines but such evidence is not available for the biaryls... 

A new metabolite, 4-aminopyridine-2,3-dicarboxylic acid, was recently isolated from C. acromelalga in a yield of 0.000056% based on the weight of frozen fruiting bodies (41)5). A lethal effect of this compound on mice has not been observed however, bioactivity is still expected because of the similarity of its structure to the physiologicaUy active pyridine-2,3-dicarboxylic acid. The structure of this compound was deduced from H-NMR, C-NMR, and mass spectra, and the position of the substituents was assumed from comparison with clitidine, which contains a 4-aminopyridine-3-carboxylic acid moiety. The structural proposal was confirmed by synthesis from 2,3-dimethyl-4-nitropyridine 1-oxide (Scheme 91) when this compound was subjected to successive reduction and oxidation it yielded a product identical to the one occurring naturally. 

A second important quinoline synthesis, from o-aminobenzaldehyde and acetaldehyde, was discovered by P. Friedlaender. Isoquinoline was discovered in coal tar, and its constitution established, by S. Hoogewerff and W. A. van Dorp, by oxidation to phthalic acid and cinchomeronic acid (pyridine-3 4-dicarboxylic acid). It was synthesised by Gabriel (see p. 839). 

In order to modify the state-of-the-art PBI stmcture and consequently its properties, significant effort has been focused on the synthesis of pyridine-based polybenzimidazoles. A systematic synthesis with different stractures was initiated to study the effect of the polymer molecular stmcture on the final film properties. The substitution of pyridine dicarboxylic acids (PDA) for the iso-/terephthalic acids is particularly interesting, because it increases the number of basic groups in the polymer backbones. The general stmcture of the series of pyridine-based polybenzimidazole (PPBI) homopolymers from 3,3 -4,4 -tetraaminobiphenyl (TAB) and 2,4-, 2,6-, 2,5- or 3,5-pyridine dicarboxylic acids using the PPA synthetic process is shown in Fig. 6. Monomer purity and accurate stoichiometry are cmcial to obtain high molecular weight polymers. 

The polyamide obtained by polycondensation of 2,6-diaminopyridine and 2,6-pyridine dicarboxylic acid was the first polymer to assemble itself into a double helix (DNA-type) in solution. The synthesis and physicochemical characterization of some polymer-supported rhodium catalysts based on polyamides containing 2,6- and 2,5-pyridine units were reported by Michalska and Strzelec (2000) these catalysts were used for the hydrosilylation of vinyl compounds such as phenylacetylene. Chevallier et al. (2002) prepared polyamide-esters from 2,6-pyridine dicarboxylic acid and thanolamine derivatives and investigated their polymer sorption behavior towards heavy metal ions. Finally, Scorlanu et al. (2006) also prepared a polymer with improved performance based on polyureas containing 2,6-pyridine moiety and polyparabanic acids, and polymethane-ureas containing 2,6-pyridine rings. 

While there are a number of related reactions that can assemble the pyridine nucleus, the oldest of these classical reactions is due to Arthur Hantzsch. In 1882 he reported the first synthesis of l,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates from a refluxing... 

Reaction of pyridines with dialkyl acetylenedicarboxylates in the presence of isocyanates in dry CH2C12 at room temperature produced 1-substituted 2-oxo-l,9a-dihydro-2/7-pyrido[l,2-tf]pyrimidine-3,4-dicarboxylates <2004TL1803>. One-pot, three-component synthesis of 1-substituted 2-oxo-l,llb-dihydro-2//-pyrimido[2,l- ]iso-quinoline-3,4-dicarboxylates and 4-(3-chloro-4-methylphenyl)-3-oxo-4,4a-dihydro-3/7-pyrimido[l,2-tf]quinoline-l,2-dicarboxylate was realized by the reaction of isoquinoline and quinoline with isocyanates and dialkyl acetylenedicarboxylates <2004S861>. Diastereomeric mixtures of l-tosyl-2-aryl-l,llb-dihydro-2/7-pyrimido[2,Ttf]isoquinoline-3,4-dicarboxylates were obtained from isoquinoline, iV-tosyl-benzaldehyde imines, and DMAD <2002OL3575>. 

Synthesis of the Thiono Isostere of Imazethapyr. The thiono isostere of imazethapyr was prepared in the same fashion from 5-ethyl-pyridine-2,3-dicarboxylic anhydride 13. The resulting mixture of regioisomers 14 and 15 was treated with aqueous sodium hydroxide to afford acid 16 after acidification and fractional crystallization. 

Another example of a carbonylation of chloropyridines is the synthesis of alkyl 3-chloropicolinates and dialkyl pyridine-2,3-dicarboxylates by Bessard and Roduit at Lonza Starting from 2,3-dichloro-5-(methoxymethyl)pyridine, both the mono- and the dicarbonylated pyridine derivatives can be obtained at low CO pressure (15 atm) with high selectivities and yields (Scheme 15). Utilizing PdCl2(PPh3)2 and dppb at 145 °C, 94% of methyl 3-chloropicolinate has been isolated, whereas palladium(II) acetate and dppf at 160 C leads to a double alkoxycarbonylation reaction. 

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