Pyridazine 1.4- dihydro

Pyrido]3,4-d]pyridazin 1,4-Dihydro-xy-7,8-dimethyl-5-isopropyl- E9c, 55 [2,3-(COOR)2 — subst,-py 4-... 

Pyrido[3,4-d]pyridazine, 1,4-dimorpholino-biological activity, 3, 261 Pyrido[4,3-c]pyridazine, dihydro-NMR, 3, 234 UV spectra, 3, 236... 

The role of carbonyl compounds is dominant in the chemistry of dihydro derivatives of pyridazines. Dihydro-3 (2/ -pyridazinone derivatives are more stable than the corresponding simple dihydropyridazine derivatives and constitute the majority of dihydro compounds reported. The analogous derivatives are of course not possible in the phthalazine and cinnoline series, though 1,4-dihydro-3 (2/ -cinnolinones are known. 

In some instances a carbon-carbon bond can be formed with C-nucleophiles. For example, 3-carboxamido-6-methylpyridazine is produced from 3-iodo-6-methylpyridazine by treatment with potassium cyanide in aqueous ethanol and l,3-dimethyl-6-oxo-l,6-dihydro-pyridazine-4-carboxylic acid from 4-chloro-l,3-dimethylpyridazin-6-(lH)-one by reaction with a mixture of cuprous chloride and potassium cyanide. Chloro-substituted pyridazines react with Grignard reagents. For example, 3,4,6-trichloropyridazine reacts with f-butyl-magnesium chloride to give 4-t-butyl-3,5,6-trichloro-l,4-dihydropyridazine (120) and 4,5-di-t-butyl-3,6-dichloro-l,4-dihydropyridazine (121) and both are converted into 4-t-butyl-3,6-dichloropyridazine (122 Scheme 38). 

Some 4,5-disubstituted pyridazines exhibit ring-chain isomerism involving heterospiro compounds. For example, 5-(o-aminophenylcarbamoyl)pyridazine-4-carboxylic acid exists in a zwitterionic form in the solid state, but in a solution of DMSO it is almost exclusively 3, 4 -dihydro-3 -oxospiro[pyridazine-5(2//),2 (l //)-quinoxaline]-4-carboxylic acid (134). The equilibrium is strongly influenced by the nature of the solvent, the substituents on the pyridazine ring and the nucleophilicity of the group attached to the phenyl ring (Scheme 48) <80JCS(P2)1339). 

The NMR spectra of the parent compounds of the pyrido-[2,3-d]- and -[3,4- f]-pyridazine systems have been studied, together with those of some closely related derivatives parent compound, 282). In the pyrido[4,3-c]pyridazine series, only the spectrum of the dihydro compound (302) has been recorded <79X2027). 

The 6- and 7-quaternary salts of pyrido[2,3-d]pyridazine are reduced by borohydride with subsequent air oxidation to 5,6- and 7,8-dihydro oxo derivatives respectively (77BSF919), whilst the [3,4-d] analogues give the corresponding 1,2- and 3,4-dihydro oxo compounds 72CR(C)(275)1383). ... 

Benzofurobenzopyrans, 4, 995-1000 6H-Benzofuro[3,2-c][l]benzopyrans, 6a,l la-dihydro-— see Pterocarpans Benzofurofurans mass spectrometry, 4, 585 Benzofuro[2,3-d]pyridazines synthesis, 4, 985... 

H-Furo[3,4-e]pyrazole, 1,4-dihydro-4-oxo-l-substituted synthesis, 6, 989 Furo[2,3-d]pyrazoles synthesis, 6, 998 Furo[3,4-d]pyrazoles synthesis, 6, 998 Furo[2,3-d]pyridazine H NMR, 4, 984 synthesis, 4, 984... 

Oxospiro[pyridazine-5(2H),2 (l H)-quinoxaline]-4-carboxylic acid, 3,4-dihydro-, 3, 33 Oxotremorine toxicity, 1, 120 Oxyberberine... 

Pyrazino[2,3-d]pyridazine, 3,4-dihydro-dehydrogenation, 3, 348 Pyrazino[2,3-d]pyridazine, 5,8-dimorpholino-reactions... 

Pyridazine, 3-alkylidene-2,3-dihydro-synthesis, 3, 28 Pyridazine, alkylthio-synthesis, 3, 27 Pyridazine, 3-alkynyl-synthesis, 3, 28 Pyridazine, amino-acylation, 3, 35 diazotization, 3, 35 reaction... 

Pyridazine-3-carboxamide, 1,6-dihydro-6-oxo-analysis, 3, 2 tautomerism, 3, 4 Pyridazinecarboxamides synthesis, 3, 33... 

Pyridazine-3,6-dione, 3,6-dihydro-[4- 2] cycloaddition, 3, 38 ring contraction, 4, 148 synthesis, 3, 38... 

Pyridazin-3(2H)-one, 4-amino-5,6-diphenyl-methylation, 3, 16 Pyridazin-3(2f/)-one, 2-aryl-Mannich reaction, 3, 20 Pyridazin-3(2H)-one, 6-aryl-4,5-dihydro-reaction... 

The cycloisomerization of hydrazide 80, catalyzed by CuCl, gives diazine 81, 5-Ai-aminolactam 82, and, unexpectedly, 6,7-dihydro-4-vinyl-1-methylpyrazolo [3,4-if]pyridazine-7 83 (85MI2) (Scheme 135). 

In this work the possibility of the existence of 1,2-dihydro isomer with the core structure 42 was not considered. Recently, however, it was shown that 1,2-dihydropyridazines could be prepared by careful electroreduction of the corresponding pyridazines, and that their stability depends significantly on the ring substitutions. Thus, dimethyl l,2-dihydropyridazine-3,6-dicarboxylate 43a (R = H) is reasonably stable and rearranges into the 1,4-dihydro tautomer 43b only at a more negative potential, while the tautomerization in its tetrasubstituted analog 43a (R = COOMe) occurs more readily (Scheme 14) [00TL647]. 

Die Reduzierbarkeit cyclischer Hydrazone mit Hydriden ist stark strukturabhangig. 7,8-Dihydro-( 1,3,4-triazolo-[4,3-b]-pyridazin) (I) und auch l,3,4-Triazolo-[4,3-b ]-pyridazin (II) werden durch 10 Mol-Aquiva-lente Natriumboranat in siedendem Athanol mit guten Ausbeuten unter Sattigung des Pyridazin-Rings zu 5,6,7,8-Tetrahydro- (1,3,4-triazolo-[4,3-b]-pyridazin) reduziert2 ... 

Another interesting scavenger is polymer-supported anthracene, developed by Porco for the scavenging of dienophiles [109]. An example of its application to the synthesis of a complex 5,8-dihydro-(l,2,4)triazolo[l,2-a]pyridazine-l,3-diones via hetero-Diels-Alder reaction followed by removal of the excess of triazole-3,5-dione under microwave irradiation is depicted in Scheme 24. For this particular example, moving from thermal heating (toluene, 100 °C) to a microwave-assisted protocol (DCE, 150 °C) reduced scavenging time from 3 h to just 15 min. 

Methyl-2,4,6-triazatricyclo[5.2.2.02 6]undeca-8-ene-3,5-dione (5,8-Dihydro-2-methyl-5,8-ethano-17/-[l,2,4]triazolo[l,2a] pyridazine-l,3(2//)dione)... 

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