Synthesis of polycyclic pyridazinediones as chemiluminescent compounds

Yoshinori Tominaga, Kenji Sasaki, Raymond N. Castle

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17 Citations (Scopus)


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° 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]pyridazine5, 8(6H, 7W)-diones 10a-c were obtained from alkyl 1, 3-disubstituted 5-aminopyrazole-4-carboxyIates 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-1H-pyrrole-3-carbonitrile smoothly reacted with 2-aminobenzimidazoles to give the corresponding 5-amino-3-methyl-lH-pyrrolo[3′, 4′:4, 5]pyrimido[l, 2-a]benzimidazolel, 3(2H)-diones 16a-e, which were readily converted to the desired 12-aminopyridazino[4′, 5′:4, 5]pyrimido[l, 2-a]benzimidazole-l, 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 lib in refluxing methanol to give the corresponding methyl 4-phenylamino-l-methyl-2, 5-dioxo-l H-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-c with hydrazine hydrate gave 10-hydroxypyridazino[4, 5-b]quinoline-l, 4(2H, 3H)-diones 27a-e in good yields. The desired 10-aminopyridazino[4, 5-b]pyridazine-l, 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-l, 4(2H, 3H)-diones 37a, b as luminescent compounds were synthesized via several steps from indolizine derivatives. The key intermediates, dimethyl 6-dimethylamino[2.2.3]cyclazine-l, 2-dicarboxylates 34, 36, were synthesized by the [8 + 2] cycloaddition reaction of the corresponding 7-dimethyIaminoindolizines 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-l-phenyl-lH-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 10-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.

Original languageEnglish
Pages (from-to)1219-1234
Number of pages16
JournalJournal of Heterocyclic Chemistry
Issue number5
Publication statusPublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry


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