Ring contractions of pyridazines

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. 

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. ... 

Selective reduction and ring contraction of pyridazin-3-ones provide access to 3-pyrroUn-2-ones. Brown and coworkers explored the reduction of pyridazin-3-ones with zinc dust and acetic acid to give reduced products which underwent ring contractions, thus offering 3-pyrrolin-2-ones and... 

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. 

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). 

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 ring contraction of pyridazinones to pyrazoles has been further in-vestigated. l-Phenyl-4,5-disubstituted pyridazin-6-ones are transformed with hot alkali into pyrazoles (264), accompanied sometimes by other substituted pyridazines. Unexpectedly, l-phenyl-4-methylthio-5-chloro-pyridazin-6-one gave in addition to 264 also another pyridazine [Eq. (31)], which originates by the attack of the liberated methylthio anion on the starting compound. 

A novel ring contraction of 4,6-dihydro-3,7-diphenyl-5-(4-methylphenylsulfonyl)-l,2,5-triazepine (135, X = NTs) occurs under specific, monochlorination conditions <85H(23)1675>. An excess of chlorine or sulfuryl chloride in dichloromethane leads to the dichlorotriazepine derivative (136), but with one equivalent of sulfuryl chloride in dichloromethane, or one equivalent of NBS in carbon tetrachloride, formation of the dichlorotriazepine is minimized and up to 86% of4-tosylamino-3,6-diphenylpyridazine (137) is produced (Scheme 106). In polar solvents other, 5-membered ring, products are produced. Thermal decomposition of a series of 3,6-diaryl-2,7-dihydro-l,4,5-thia-diazepines (135, X = S) gave 3,6-disubstituted pyridazines in high yield <89BCJ2608>. 

Photochemical ring contraction of etheral solutions of diazo compound (216) in the presence of nucleophiles (e.g., ethanol or water) provides low yields of the products (265). Higher yields of products of splitting (266) and (267) can be detected (Scheme 47). The pyridazine (267), formed in the reaction, is itself sufficiently nucleophilic to intercept the ketene intermediate when the reaction is performed without any nucleophile. Compound (268) is then obtained in 11 % yield. No product of the ring contraction is formed when 5-5 bicycUc diazo derivative compound (214) is similarly treated <87JCS(Pl)885>. 

Symmetrically 3,6-disubstituted pyridazines, with a variety of alkyl and aryl substituents, can be constructed via ring contraction of a 7-membered sulfide. 

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... 

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. 

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],... 

Ring contraction occurs also on irradiation of pyridazine-3(2ff)-ones to give a mixture of pyrrolines 278 and 279 (minor product). Similarly,... 

When the hydrazine adduct of 2-phenylpyrimido[4,5-d]pyridazine-5,8-diol (7) was treated with hydrochloric acid, the expected 2-phenylpyrimido[4.5-d]pyridazine-5,8-diol (8) was not formed. Instead the pyridazine ring underwent ring contraction leading to 9.54... 

Ring contraction occurs also on irradiation of pyridazine-3(2//)-ones to give a mixture of pyrrolines 278 and 279 (minor product).576 Similarly, 3-methyl-l-phenyl-hexahydropyridazine-6-one gives 280.577 However, photolysis of 5-amino-4-chloro-2-phenylpyridazine-3(2H)-one, a selective herbicide, in sunlight gives a mixture of 281 and 282, the last compound originating from 281.578 The first photoisomerization of 3-hydroxypyrid-azinium betaines into pyrimidinones converts 283 into 284 the mechanism proposed involves valence isomerization.579... 

Photochemical reactions of pyridazines, phthalazines and cinnolines were extensively reviewed in CHEC-I <84CHEC-l(3B)l>, with many reactions proceeding via ring contraction. Since 1985, the photolysis of 4-azidopyridazines to give significant yields of ring expansion products, unsaturated... 

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