Synthesis of polycyclic pyridazinediones as chemiluminescent compounds

摘要

Reactions of 1,3-disubstituted 5-aminopyrazole-4-carbonitrile derivatives 3a-o with dimethyl acetylenedicarboxylate in the presence of potassium carbonate in dimethyl sulfoxide gave the corresponding dimethyl 1,3-disubstituted pyrazolo[3,4-b]pyridine-5,6-dicarboxylates 4a-o which were allowed to react with excess hydrazine hydrate under ethanol refluxing conditions followed by heating at 250-300 degrees to give 1,3-disubstituted 4-amino-1H-pyrazolo[4',3':5,6]pyrido[2,3-d] pyridazine-5,8 (6H,7H)-diones 7a-s in good yields. Similarly, 1,3-disubstituted 4-hydroxy-1H-pyrazolo[4',3':5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-diones 10a-c were obtained from alkyl 1,3-disubstituted 5-aminopyrazole-4-carboxylates 8a-c. These tricyclic pyridazine derivatives were alternatively synthesized from 4-hydroxypyrrolo[3,4-e]pyrazolo[3,4-b]pyridine-5,7-diones 13a-c prepared by reactions of 5-aminopyrazoles (8e-g) with methyl. 1-methyl-4-methylthio-2,5-dioxo-1H-pyrrole-3-carboxylate (11a) followed by the Gould/Jacobs reaction. 1 -Methyl-4-methylthio-2,5-dioxo- 1 H-pyrrole-3-carbonitrile smoothly reacted with Zaminobenzimidazoles to give the corresponding 5-amino-3-methyl-1H-pyrrolo[3',4':4,5]pyrimido[1,2-a]benzimidazole-1,3(2H) -diones 16a-e, which were readily converted to the desired 12-aminopyridazino[4',5': 4,5]pyrimido-[1,2-a]benzimidazole-1,4(2H,3H)-diones 17a-e in good yields. Other pyridazinopyrimidine derivatives were also obtained by the reaction of the corresponding 2-aminoheterocycles with the maleimide in good yields. Substituted anilines reacted 11b in refluxing methanol to give the corresponding methyl 4-phenylamino-1-methyl-2,5-dioxo-1H-pyrrole-3-carboxylates 25a-e which were converted in good yields to 2-methylpyrrolo[3,4-b]quinoline derivatives 26a-e by heating in diphenyl ether. Reaction of 26a-e with hydrazine hydrate gave 10-hydroxypyridazino[4,5-b]quinoline-1,4(2H,3H)-diones 27a-e in good yields. The desired 10-aminopyridazino[4,5-b]pyridazine- 1,4(2H,3H)-diones 30a-e were obtained in good yields by the chlorination of 4a-e with phosphorus oxychloride followed by aminolysis with 28% ammonium hydroxide. Some pyridazino[4,5-a][2.2.3]cyclazine-1,4(2H,3H)-diones 37a,b as luminescent compounds were synthesized via several steps from indolizine derivatives. The key intermediates, dimethyl 6-dimethyl -amino[2.2.3]cyclazine-1,2-dicarboxylates 34, 36, were synthesized by the [8 + 2] cycloaddition reaction of the corresponding 7-dimethylaminoindolizines 33, 35 with dimethyl acetylenedicarboxylate in the presence of Pd-C in refluxing toluene. Some were found to be more efficient than luminol in light production. 4-Amino-3 -methylsufonyl-1phenyl- 1H-pyrazolo[4',3':5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-dione (7r), 10-hydroxypyridazino[4,5-b]quinoline-l,4(2H,3H)-diones 27a-e, and l0-aminopyridazino[4,5-b]quinoline-l,4(2H,3H)-diones 30a-e showed the greatest chemiluminescence intensity in the presence of hydrogen peroxide peroxidase in a solution of phosphate buffer at pH 8.0. [References: 35]