Pyridazines formation

Hydrazone formation of pyridazine-3-hydrazines with aldoses, dialdofuranoses, and dialdopyranoses was studied by Stanovnik and co-workers. The respective hydrazones could be cyclized with Bt2 in MeOH or Pb(OAc)4 to j-triazolo[4,3-3]pyridazin-3-yl substituted polyols <1997JHC1115, 1998JHC513>. Similarly, 4-[(dimethylamino)-methylene]-l,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one was reacted with pyridazine-3-hydrazines and the resulting mixtures were subsequently treated with Pb(OAc)4. Besides j-triazolo[4,3-3]pyridazine formation also diazenes were obtained. This can be rationalized by the enehydrazine-hydrazone mixtures observed in the first reaction. For phthalazin-l-hydrazines only diazenes were obtained after oxidation <2005TA2927>. Also cyclizations of... 

A mixture of 20.0 g of 3-hydrazino-4-methyl-6-piperidinopyridazine in 100 ml of aqueous 99% formic acid was heated at the boiling temperature under reflux for 3 h and then evaporated to dryness. The residue, containing 8-methyl-6-piperidino-s-triazolo[4,3-b]pyridazine formate was taken up in excess aqueous sodium carbonate and extracted with chloroform. After evaporation of the chloroform solvent the 8-methyl-6-piperidino-s-triazolo[4,3-b]pyridazine was crystallized from ethyl acetate. Yield 4.4 g, melting point 118-120°C. 

Several pyridazines were prepared unintentionally by the attempted Wolff-Kishner reduction of ketoacids. It has been claimed that the ease of pyridazine formation during the Wolff-Kishner-Huang-Minlon reduction of aromatic 1,4-ketoacids depends on the nature of... 

The steric effect has an important influence on pyridazine formation. This is particularly the case when the double bond of the anhydride is incorporated in a cyclic system, or with cyclic 1,2 diesters. At least four types of products can be produced and they were identified as a monohydrazide as 24, a dihydrazide as 27, an iV-aminomaleimide derivative as 25, or a pyridazinone as 21. The dihydrazides are relatively easily converted into pyridazinones when heated with excess hydrazine or in dilute hydrochloric acid, and treatment with nitrous acid has the same effect. - ... 

Upon heating a mixture of benzaldehyde and hydrazine salt in the presence of styrene (2 1 6 molar mixture), in addition to 1,5-diazabicyclo [3.3.0] octane, 3,5,6-triphenyl-l,4,5,6-tetrahydropyridazine was obtained as byproduct. The latter was the only product when a 2 1 2 ratio was used. The pyridazine formation is explained on the basis of cycloaddition of benzaldehyde azine to styrene, followed by tautomerization (87JOC2277). Similarly, other diazadienes add ethyl vinyl ether to give also 1,4,5,6-tetrahydropyridazines [83JCS(PI)1803j. 

There are several examples of pyridazine formation from seven-membered precursors, in particular diazepines. 2-Tosyldiazepin-4-one rearranges in the presence of sodium alkoxide or cyanide ion in methanol to a pyridazine. The... 

There are examples of pyridazine formation from bicyclic heterocycles. 

There are examples of pyridazine formation from bicyclic heterocycles. 1-Substituted carboxyalkylpyridazines (83) are obtained by alkaline hydrolysis of the corresponding pyrazolo[l,2-a]pyridazines (82), obtainable from maleic hydrazide and chlorides of a,/(-unsaturated acids.198 1-Phenacy-... 

While the condensation conditions required for pyridazine formation are often relatively mild, hydrolytic side reactions may be observed. For example, reaction of 2-(alkylamino)-3-(trifluoro-acetyl)butenedioates with hydrazines failed to give the expected 1,6-dihydro-5-alkylamino-6-oxo-3-trifluoromethyl-4-pyridazinecarboxylates (116), but gave the alkylamino salts of the corresponding... 

In the above pyridazine formation, both nitrogen atoms in the ring originate from hydrazine. The actual existence of intermediate structures like 445 and 446, which are finally converted into methylpyridazinone 447, is also supported by the fact that 2-a-aminoethylbenzoic acid 450 heated with hydrazine turns into 4-methyl-1-phthalazone 453 in almost quantitative yield through hydrazide 451 and dihydrophthalazone 452 (91ZOR1120). 

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