Pyridazines ring contractions

There are several examples of the formation of pyridazines from other heterocycles, such as azirines, furans, pyrroles, isoxazoles, pyrazoles or pyrans and by ring contraction of 1,2-diazepines. Their formation is mentioned in Section 2.12.6.3.2. 

Pyridazine, 4-amino-3,6-dihalo-ring contraction, 3, 29 Pyridazine, 4-amino-3,6-dimethoxy-nitration, 3, 20... 

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

Pyridazine-3(2H)-thione, 4,5,6-triphenyl-ring contraction, 3, 29 Pyridazineth lones acylation, 3, 37 glycosides... 

A kinetic study of thermolysis reactions of TV-crotyl substituted 1,2,4-triazoles was performed at temperatures in the range of 260-350 CC <00JHC1135>. Thermolysis of tetrazolo[l, 5- >]pyridazines, tetrazolo[l,5-a]pyrimidines and tetrazolo[l,5-a]pyridines allowed easy ring contraction to a facile preparation of cyanopyrazole heterocycles . 

The reaction of oxime 323 with concentrated aqueous HCl proceeded with a ring contraction and afforded pyridazine 324 as a single product (equation 140) . On the contrary, the rearrangement of pyrrol-3-one oxime in the presence of hydrazine proceeded with ring enlargement and led to l//-pyridazin-4-one oxime . ... 

Ring contractions may occur during reductions or oxidations. In Part I1 the ring contractions that were described included reductions of pyridazines... 

Certain pyridazine iV-oxides are isomerized into the corresponding diazoketones, e.g. (994) — (995) ring contraction to the corresponding furan (996) can then occur. 

Several important examples of ring transformation are referred to elsewhere in this chapter. These include the extrusion of nitrogen from tetraazaphenanthridines and S02 from dipyridothiophene dioxides to yield diazabiphenylenes (Section 7.23.8.1.1), the benzylic-type ring contraction of phen-anthridine diones to give diazafluorenones (Section 7.23.8.2.1), and the extrusion of nitrogen from the Diels-Alder adducts formed from enamines and pyridazo[4,5-d]pyridazines (Section 7.23.8.3.2). 

The synthesis of pyrano[3,4-Z>]pyrroles was achieved utilizing a zinc-mediated ring contraction of pyridazines 07EJ03296 07SL403>. The pyridazines were formed by the cycloaddition of alkynes with tetrazines. 

Reaction of 4 (R = H, Ar = C6H5) with i T-bromosuccinimide or, more cleanly, with. Y-chlorosuccinimide gave 4-methyl-3,6-diphenyl-pyridazine (24, R = CH3).26 Two possible mechanisms for the formation of 24 imply that carbon 5 is extruded in the ring contraction. 

Some interesting ring contractions from pyridazine derivatives to pyrazolone, pyrrole, or indole derivatives are known. 

Rearrangement of a pyridazine into a pyrrole has been found when 3-anilinopyridazine is heated in the presence of Raney nickel 2-anilino-2-pyrroline is formed in this reductive ring contraction. Similarly, 2,3,4-triphenylpyrrole is obtained from 4,5,6-triphenyl-3(2H)-pyridazinethione by reductive desulfurization with Raney nickel. A mechanism suggested for similar ring contractions of cinno-lines into indoles may be operating also in this case. Another... 

Ring contraction of a pyridazine with concurrent cyclization to indole derivatives proceeds with l-aryl-6-oxo-l,4,5,6-tetrahydro-pyridazines having at position 3 a carboxyl or methyl group (161). 137,186,707 reaction is usually performed in ethanolic solution containing hydrogen chloride or sulfuric acid, and also potassium hydroxide. Indoles of the general formula 162 (R2 = COOEt, COOH, or Me) are obtained. 

The acetylene 24 was allowed to react with 1,2,4,5-tetrazine 25 to give the desired pyridazine 26 in excellent yield. Zinc reductive ring contraction followed by A-alkylation of... 

Many 1,2-diazines undergo N-N-bond cleavage upon electroreduction, eventually resulting either in reductive ring opening or in ring contraction, e.g. of the type pyridazine —> pyrrole [111] or phthalazine —> isoindole [112],... 

Similar ring contractions in which the nitrogen-nitrogen bond is cleaved are found in the reductive ring contractions of pyridazines to pyrroles [148, 149], phthalazines to isoindoles [150], 5,6-diphenyl-1,2,4-triazinones to imidazolones [151], benzo-l,2,4-triazines to benzimidazoles [71], benzo-l,2,3-triazinone to indazolone [la, 152], benzo-l,2,3-triazin-3-oxide to indazole [la], benzo-2,3-diazepines to isoquinolines [153], benzo-l-pyrano-[4,3-e ]-as-triazin-3-one to benzopyranoimidazolone [154], and 2-methyl-4,5-dihydropyridazin-3-ones to pyrrolin-2-ones [155]. 

New examples of base- or acid-induced ring contraction of pyridazines include the formation of azoles. An investigation of the known cyclization of the phenylhydrazone of ethyl levulinate to pyridazinone revealed that in the presence of BF3-etherate the corresponding indole derivative (262) is obtained. The latter is formed also from the pyridazinone and ethanolic hydrogen chloride. 5-Phenylpyridazinone-4-oxime, when treated with zinc in acetic acid, is rearranged to the pyrrole 263. ... 

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