Pyrido pyridazine, oxidative

The NMR spectra of pyrido[2,3-d]pyridazine Af-oxides reduced derivatives and quaternary salts have also been studied and alkaline deuterium exchange reactions investigated <77BSF919). 

True electrophilic substitution is very difficult in pyridopyridazines. For example, the [3,4-d] parent (286) is inert to hot 65% oleum (68AJC1291), and although formation of a 3-bromo derivative (308) was reported in the [2,3-d] series, it seems to have arisen by an addition-elimination reaction via the dibromide (309) (69AJC1745). Attempted chlorination led to ring opening. A similar effect was observed in the [3,4-d] system, where an 8-bromo derivative was obtained (77BSF665), and in iV-oxides of the pyrido[2,3-c]pyridazine and fused pyridazino[3,4-c]isoquinoline series (72JHC351). The formation of (311) from (310)... 

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). ... 

Acetyl (79GEP2808070,71FES1074) and Other groups on the pyridine ring have been oxidized to the corresponding carboxylic acids in the pyrido-[2,3-c]- and -[3,4-d]-pyridazine fields. Acid groups in pyridopyridazines behave normally on esterification (66CPB1010). 

Finally, the activated 3-aminopyridazine AT-oxide (381), mimicking 6-aminouracil, cyclizes with /3-ketoesters to give the pyrido[2,3-c]pyridazin-7-one AC-oxide (382). A reduced fused... 

Pyrido[3,4-i]pyridazine, 2,3-dimethyl-bromination, 3, 252 Pyrido[3,4-c]pyridazine, 4-methyI-reactions, 3, 240 Pyrido[3,4-(i]pyridazine, acetyl-oxidation, 3, 240... 

Pyridopyridazines, hydroxyalkyl-nucleophilic attack, 3, 241 Pyridopyridazines, methyl-electrophilic reactions, 3, 240 Pyrido[2,3-6]pyridazines nucleophilic substitution, 3, 253-254 Pyrido[2,3-c]pyridazines, 3, 232-233 benzo fused, 3, 233 N-oxide... 

The thermal cyclization of 3-pyridazinylaminomethylenemalonate N-oxide (1052) by heating in diphenyl ether at 250°C for 15 min gave pyrido[2,3-c]pyridazine-6-carboxylate jV-oxide (1053) in 70% yield (72JHC351). 

When pyridinium A -imine salts 157 were reacted with methylphenyl-cyclopropenone (158, R = Ph, R = Me) in the presence of a base, dihydro-pyrido[l,2-h]pyridazin-3-ones (159) were formed, which subsequently underwent oxidation to produce 3//-pyrido[l,2-h]pyridazin-3-ones (160) under the reaction conditions [76JCS(CC)275 78JOC2892], In some cases the dihydro intermediates (159) could be isolated. 3-Substituted derivatives (157, R = 3-Me, 3-CN R = H) gave mixtures of isomers of 160 (R = 5-... 

Lithium ester enolate-imine condensation has been used for the preparation of / -lactam rings via addition at the imine moiety <1996H(43)1057>. But treatment of imino derivatives of the pyridazine 293 with the lithium enolate of ethyl a,a-dimethylacetate 294 in THE led to the formation of the pyrido[3,4-r/ pyridazine 295 and its oxidized form 296. Compound 295 was obtained by nucleophilic attack of the carbanion species at C-5 of the pyridazine ring followed by cyclization (Equation 24) <1996JHC1731>. 

Oxidation of pyrido[2,3-<7]pyridazine-5,8-dione with peracetic acid gave the N( )-oxide <84AJC87>, which could also be obtained by reaction of pyridine-2,3-dicarboxylate 1-oxide with hydrazine hydrate. Similarly, the pyrido[3,4-r/]pyridazine-1,4-dione was oxidized to the 6-oxide. 

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