Pyridazines, 2,3-dihydro-4-hydroxy

R2N - CH = C(OR) - CHO] Pyridazine 6-Hydroxy-3-methyl-4,5-dihydro- E9a, 569 (4-Oxo-penta-noic Acid + N2H4 or Ethyl 4-Oxo-pentanoat semicarbazone/A)... 

Pyridazine 6-Hydroxy-3-(5-nitro-2-furyl)-4,5-dihydro- E9a, 570 (4-Oxo-4-het-butanoic Acid + N2H4)... 

Malonsaure (2-Phenyl-hydrazinome-thylen)- -formylamid-nitril E15/1,775 (OR - NH — NH — R) Pyridazine 6-Hydroxy-3-(2-oxo-2.3-dihydro-benzimidazol-5-yl)-4.5-dihydro- E9a, 570 (4-Oxo—4-Ar—butanoic Acid 4- N2H4)... 

Dieckmann condensation of piperidine-2-carboxylate 138 in toluene in the presence of NaOEt furnished pyrido[l,2-h]pyridazine-3-carboxylate (139) (71CPB159). Ethyl 2-methyl-4-hydroxy-5,6-dihydro-4a//-pyridaz-ino[l,6-a]quinoline-3-carboxylate (7,8-benzolog of 139) was prepared similarly (66YZ613). 

A novel ring-closure starting from 2-aryl-l-(12/-l,2,4-triazol-l-yl)alk-3-yn-2-ols has been reported <2006T8966>. Treatment of these alkynols with Bt2 at room temperature yielded 5-alkyl-7-aryl-6-bromo-7-hydroxy-7,8-dihydro-[l,2,4]triazolo[l,2- ]pyridazin-4-ium bromides which upon hydrolysis give 3-alkyl-5-arylpyridazines. 

Cyclooctatetraene reacts as a dienophile with 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine to form, upon loss of N2, a cycloocta[4]pyridazine and a tetracyclic bis-Diels-Alder cycloadduct [95LA661]. In a nonpolar solvent, the former produced a dihydrobarrelenofrflpyridazine that could be oxidized (with 4-phenyltriazolinedione) to the barreleno[d]pyridazine, but in a polar solvent it gave a dihydrocycloocta[d]pyridazine in a multistep process. X-ray crystal structures of some of these compounds have been obtained. The attempted dehydrogenation of 4,4a-dihydro-5//[ 1 ]benzopyrano[4,3-c]pyridazin-3(2//)-ones with m-CgH NC SOjNa unexpectedly led to new 5-hydroxy[ 1 ]benzopyrano[4,3-c]pyridazin-3(2//)-ones [95JHC79]. 

Benzofurazan 4,5-Diamino- E8c, 704 (Imidazol-Ringspalt.) Furo 2,3-d pyridazin 4-Hydrazino-E16a, 718 (C1->NC1-NH2) Pteridin 2-Hydroxy-3,4-dihydro-IV/lc, 331... 

Pyridazine 6-[2,4-(or 3,4)-Dichloro-phenyl)-3-hydroxy-4,5-dihydro-E9a, 570 (4-Oxo —4-Ar —butan-oid-Acid + N2H2)... 

Dimethyl-5-ethoxycarbonyl-E16c, 122 (En-azid/Ringschl.) Pyrido[3,4-d pyridazin 1,4-Diethoxy-E9c, 68 (Cl - OR) Pyrido[2,3-d(pyrimidin 1 -Butyl-4-hydroxy-2-oxo-l,2-dihydro- E9c, 97 (2-NH R — 3-COOH—py + Urea)... 

Pyrazin 2-(bzw. 4)-(4-Methyl-anilinocarbonyl)- E5, 1017 (N3 -v CO-NH-Ar) Pyridazine 4-Cyan-6-hydroxy-5-methyl-3-phenyl-4,5-dihydro-E9a, 570 (4-Oxo -4-Ar-3-CN-2-CH3 —butanoic Acid + N2H4) Pyridin 2-Methoxy-5-phenylazo-E16d, 57 (R-NH2 + R-NO) Pyrrol 2-Amino-3-cyan-1 -(4-methyl-phenyl)- 5-oxo-4,5-dihydro-E15/2, 1946 (Cl-CH2-CO-NR2 + NC-CH2-CN) Quinolin... 

Pyridazin 4-Ethoxy-6-oxo-l-phenyl- 1,6-dihydro- VII/4, 369 Pyrimidin-l-oxid 4,6-Dimethyl-5-hydroxy-2-phenyl- E9b/2, 193 (N-Oxidat.)... 

Amino-3-halogen-pyridazine reagieren mit einem 6fachen molaren UberschuB Kaliumamid in flussigem Ammoniak unter Ringkontraktion zu 4-Cyan-1 H-pyrazol (50-67% Schmp. 89 90°)1655, 4-Chlor-3-oxo-, 4-Hydroxy-3-oxo- und 4-Alkoxy-3-oxo-2,3-dihydro-pyridazine mit Basen zu S-Carboxy-lH-pyrazolen1227- 1233 1656,1724-1918 ... 

Reaction of 3-methylpyridazine with TMSCN/benzoyl chloride gives the normal Reissert adduct. Elowever, reaction of pyridazine and 3-methylpyridazine with potassium cyanide/benzoyl chloride in water/dichloromethane is complicated by tautomerizm of the initial product under the reaction conditions the initial 2,3-dihydro adduct is completely tautomerized to the 2,5-dihydro adduct on silica gel. The 2,5-dihydro tautomer formed in situ undergoes further benzoylation (Scheme 19) and finally hydrolysis gives 5-benzoylpyridazine-3-carboxylic acid via the corresponding 5-(hydroxy-benzyl) derivative, which is oxidized under the reaction conditions <85JHC1543). 

The synthesis of pyridazine derivatives from hydrazones includes the thermal cyclization of 2-arylhydrazono-3-oxo-5-phenyl-4-pentenenitriles (readily obtained from ethyl cinnamate by condensation with acetonitrile followed by Japp-Klingemann type reactions) to l-aryl-3-cyano-6-phenyl-5,6-dihydro-4(l//)-pyridazinones (Scheme 85) <86JHC93>, and base-induced cyclization of a hydrazone of a 4-chloro-l-arylbutan-l-one to prepare a 2,3,4,5-tetrahydropyridazine (Scheme 85) <88JHC1543>. An earlier route to 6-carboxy-5-hydroxy-2-phenyl-3(2//)-pyridazinone via condensation of benzenediazonium chloride and dimethyl acetonedicarboxylate has been adapted to give a series of aryl derivatives either as esters (by thermal cyclization) or as acids (by cyclization with hydroxide). Both cyclizations proceed in high overall yield (Scheme 86) and decarboxylation of the acids also proceeds in high yield <89JHC169>. 

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