2.6- Pyridinedicarboxylic acid, reaction

Pyridinedicarboxylic acids and amino acids serve as useful starting materials for the synthesis of pyrrolo[3,4-f]-pyridines. The reactions proceed at relatively high temperatures (Equation 43) <19%EJM49>. 

The pyrido[3,2-rflpyrimidines 370 were prepared from 2,3-pyridinedicarboxylic acid anhydride 366 by the action of boiling MeOH to give the stable isomer of half-ester 367. Subsequent treatment with ethyl chloroformate in presence of EtsN and NaNs formed the azide 368 that was transformed by Curtius rearrangement into the isocyanate 369. Reaction of 369 with a series of amino acids under mild conditions gave adducts 370 (Scheme 12) <2003TL2745>. 

Iwahashi H, Kawamori H, Fukushima K. Quinolinic acid, a-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhance the Fenton reaction in phosphate buffer. Chem-Biol Interact 1999 118 201-215. 

The p-anisyloxymethyl group520 (abbreviated AOM) played an important role in the synthesis of Calicheamicinone reported by Clive and co-workers.521 Its removal from the sensitive multifunctional substrate 285 1 [Scheme 4.285] was accomplished with CAN in a mixture of pyridine, methanol and water. The excellent yield (89%) attests to the mildness of the conditions. Attempts to apply the same conditions to the deprotection of an AOM group from 286 1 [Scheme 4.286]522 failed but the deprotection was successful if it was conducted in the presence of 2,6-pyridinedicarboxylic acid N-oxide — conditions previously used to convert a phenol methyl ether to a quinone.523 AOM ethers undergo easy reductive cleavage to the corresponding methyl ethers with borane in toluene — a reaction that could have synthetic value when simple O-methylation procedures fail. 

In another protocol using a ruthenium(pyridinebisoxazoline)(pyridinedicarboxylic acid) catalyst 26 and iodosylbenzene as the terminal oxidant, Seller and co-workers <03TL7479> found that the addition of water and protic solvents resulted in a 100-fold acceleration of the epoxidation, presumably due to a ligand dissociation effect that promotes the oxidation of the ruthenium catalyst. Thus, the conversion of rrans-stilbene 27 to the corresponding 5,S-epoxide 28 required 96 h in anhydrous toluene, but only 1 h in the presence of r-butanol and water. The enantioselectivity of the reaction was not significantly affected (63% and 57% ee, respectively). 

The conversion of 2,5-pyridinedicarboxylic acid Af oxide (284) inaceto-nitrile/acetic anhydride to the corresponding 6-amino-nicotinic acid (288) seems to be a Ritter reaction of intermediate cation 285 with acetonitrile, followed by rearrangement of intermediate 286 to 287, which is then saponified by potassium hydroxide to give 49% of 6-aminonicotinic acid (2M) and 8% of 6-hydroxynicotinic acid (289) (83EUP90I73). 

Similarly, reactions with Vilsmeier reagent of the pyridinedicarboxylic acids (85), the quinolinecarboxylic acids (86), and the quinoxalinecarboxylic acids (87) gave the tricyclic products (88,89, 90), respectively (83TL4607). 

Other decarboxylations reported by Takahashi have proved irrep-roducible. The reaction between 2,2 -biphenyldicarboxylic acid anhydride in alkali and mercuric oxide in acetic acid was claimed to give 2 -mercurio-2-biphenylcarboxylate by hemidecarboxylation [Eq. (84)] (97) but yielded instead mercuric 2,2 -biphenyldicarboxylate and negligible decarboxylation [Eq. (85)] (98). Similarly, the reaction between sodium 2,3-pyridinedicarboxylate and mercuric oxide in acetic acid, reported to give... 

More reeently, there was a report on the use of dipicolinic acid in the design of layered crystalline materials using coordination chemistry and hydrogen bonds. MaeDonald et al. reported the synthesis and characterization of several first-row transition metals with dipicolinic acid as a ligand. Five bis(imidazolium 2,6-pyridinedicarboxylate)M(II) trihydrate complexes (where M = Mn, Co, Ni, Cu, or Zn ), were synthesized from the reaction between dipicolinic acid and imidazole with Mn, Co, ... 

Reactions Of anhydrides. Treatment of 2,3-pyridinedicarboxylic anhydride with methanol leads to the formation of 2-(methoxycarbonyl)nicotinic acid <2003TL2745>. 

Peroxo Complexes. One of the most characteristic reactions of aqueous TiIV solutions is the development of an intense orange color on addition of hydrogen peroxide, and this reaction can be used for the colorimetric determination of either Ti or of H202. Detailed studies of the system7 show that below pH 1, the main peroxo species is probably [Ti(02)(0H)aq]+ in less acid solutions, rather complex polymerization processes lead eventually to a precipitate of a peroxohydrate. Various crystalline salts can be isolated,7,8 e.g., of the ions [Ti(02)F5]3, [Ti(02)(S04)2]2 and [Ti20(02)2(dipic)2]2 where dipic = 2,6-pyridinedicarboxylate. The latter has a /r-oxo bridge, and all species appear to have bidentate peroxo groups. 

Copper iodide (ous) p-Cresol/dicyclopentadiene butylated reaction product 2,6-Di-t-butyl-4-ethyl phenol 3,5-Di-t-butyl-4-hydroxyhydrocinnamic acid, 1,3,5-tris (2-hydroxyethyl)-s-triazine-2,4,6-(1H,3H,5H)-trione triester 2,4-Di-t-butylphenyl 3,5-di-t-butyl-4-hydroxybenzoate Dicetyl thiodipropionate Dicyandiamide Didodecyl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate Dimethylsuccinate/tetramethyl hydroxy-1 -hydroxyethyl piperidine polymer Dimyristyl thiodipropionate... 

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