Cinchomeronic acid

The close chemical relationship among these stmctural entities, as well as the uniqueness of (1) and (2), have been evident from the time of the earhest stmctural studies. Permanganate oxidation of (1) (2) produces 2,3-pyridinedicarboxyhc acid (quinolinic acid [89-00-9]) (3), whereas similar treatment of (2) (3) yields a mixture of 3,4-pyridinedicarboxyhc acid (cinchomeronic acid [490-11 -9]) (4) and phthaUc acid. 

Chondrodendron polyanthum, 371 Chondrodendron tomentosum, 363, 371, 373, 377, 391 alkaloids, 376 Chondrodine, 363, 364 Chondrofoline, 364, 365 Chrycentrine, 172, 313 Chiysanthemine, 773 Chrysanthemum cineraricefoHum, 773 Chuchuara, 781 Chuehuhuasha, 781 Cicuta virosa, 13 Cinchamidine, 419, 429 Cinchene, 439 Cinchenine, 438, 439, 440 apoCinchenine, 440, 441 Cincholoipon, 438 Cincholoiponic acid, 438, 443 Cinchomeronic acid, 183 Cinchona alkaloid structure, synthesis, 457 Cinchona alkaloids, bactericidal action of some derivatives, 478 centres of asymmetry, 445 constitution, 435 formulae and characters of transformation products, 449, 451 general formula, 443 hydroxydihydro-bases, 448, 452-4 melting-points and specific rotations, 446... 

Pyridine 210 is oxidized by 20% nitric acid at the acetyl group to 2-methyl-5-pyridinecarboxylic acid, while its ozonation gives cinchomeronic acid [pyridine-2,5-dicarboxylic acid (215)] (75DIS) which is decarboxylated (200°C, 2 h) to nicotinic acid 216 in 97% yield (75DIS). 

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. 

Whereas with quinoline the benzo ring is the more susceptible to oxidative ring opening, with isoquinoline the matter is more finely balanced. Use of ozone or alkaline permanganate results in attack on both the rings, the products being phthalic acid and pyridine-3,4-dicarboxylic acid (cinchomeronic acid) (38 Scheme 25). 

The partial Hofmann degradation with potassium hypobromite475 477-54h or lead(IV) acetate475 of pyridine-3,4-dicarboxamides (cinchomeronic acid diamides) gives exclusively the intermediate 3-isocyanatopyridine-4-carboxamides, which cyclize to the corresponding pyri-do[3.4-c/]pyrimidine-2,4(1 77,3//)-diones 16. 

Cinchomeronic anhydride, prepared by refluxing the acid with acetic anhydride for 30 min., taken up in benzene, dry NH3 bubbled into the refluxing and stirred soln., cooled, hot water added, the aq. phase removed, and saturated with SOa at 25 to precipitate the acid amide —> 4-cinchomeronic acid amide. Y 80%. (G. B. Bachman and R. S. Barker, J. Org. Chem. 14, 97 (1949).)... 

Cinchomeronic acid (Pyridine- 260d, w di 199- 3-mono 3-mono 4-mono Imide, 229-30,... 

Silver(n) complexes, 839-850 amino adds, 846 aqua,844,850 biguanides, 849 2,2 -bipyridyl, 843 carboxylates, 844 cinchomeronic acid, 842 dipicolinic acid, 842 dithiocarbamates, 845 isodnchomcronic add, 842 isonicotinates, 840 lutidinic acid, 842 N-heterocyclic ligands, 839 nicotinates, 840 1,10-phenanthroline, 843 phthalocyanines, 848 picolinates, 840... 

Permanganate oxidation of papaverine in neutral medium furnishes m-hemipinic acid (V), veratric acid (VI), papaverinic acid (a-veratroylcincho-meronic acid) (VII), and pyridine-2,3,4-tricarboxylic acid (VIII). The last-named product (VIII) may serve as evidence for the point of attachment of the nitrogen-free portion of the isoquinoline system. Dimethoxy-isoquinolines are oxidized to pyridine-3,4-dicarboxylic (cinchomeronic) acid, but papaverine yields VIII under analogous conditions, thus marking position 1 as the connecting point. 

A mixture of cinchomeronic acid and acetic anhydride refluxed 1 hr., then a mixture of 80%-hydrazine hydrate and glacial acetic acid added dropwise with stirring at reflux temp., and refluxing continued 3 hrs. -> 1,4-dihydroxypyrido-[3,4-d]pyridazine. Y 95%. I. Matsuura and K. Okui, Chem. Pharm. Bull. 17, 2266 (1969). 

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). 

---