Pyridazinones rearrangement

Pyridazinones may undergo ring contraction to pyrroles, pyrazoles and indoles, the process being induced either by an acid or base. The structure of the final product is strongly dependent on the reaction conditions. For example, 4,5-dichloro-l-phenylpyridazin-6(lFT)-one rearranges thermally to 4-chloro-l-phenylpyrazole-5-carboxylic acid (12S), while in aqueous base the corresponding 4-hydroxy acid (126) is formed (Scheme 40). 

Pyridazines are formed from pyrones or their thioxo analogs or from appropriate pyridones. Pyrones or pyridones react with diazonium salts to give the corresponding hydrazones (187) and (188) which are rearranged under the influence of acid or base into pyridazinones as shown in Scheme 107. On the other hand, kojic acid is transformed with hydrazine into a 1,4-dihydropyridazine and a pyrazole derivative. 4H-Pyran-4-thiones... 

Xanthone is unreactive towards hydrazine and phenylhydrazine. The oxime is obtained by reaction of xanthione (xanthene-9-thione) with hydroxylamine, or from xanthone and hydroxylamine in pyridine. When the oxime is heated in water with phenylhydrazine, the phenylhydrazone is formed. In acid solution, xanthone reacts normally with 2,4-dinitro-phenylhydrazine but xanthone-1 -carboxylic acid (435) gives the pyridazinone (436), possibly via the hydrazone (57JCS1922). When the oxime is heated with phosphorus pentachloride it undergoes a Beckmann rearrangement to give the amide (437) (70MI22300). 

When 3,6-dialkoxypyridazines (4) are heated with a variety of catalysts (e.g., mineral acids, p-toluene sulfonic acid, Lewis acids), rearrangement occurs to give the 3-alkoxy-l-alkylpyridazin-6(l//)-ones (5). Thus N-methylated pyridazinones can be prepared by treatment of 3,6-dialkoxypyridazines with methyl iodide or dimethyl sulfate (84MI2), the reaction mechanism presumably involving an intermediate quaternary pyridazinium salt. 

A-Glycosyl rearrangements of pyridazine glycosides are also known. 0-)3-D-glucosides or ribosides of pyridazinones and maleic... 

A few instances of A-acylation are also known. 6-Chloro-3(2.H)-pyridazinone reacts preferentially on the nitrogen with chloro-carbonates and the structure of the products has been assigned on the basis of IR data. A-Acylations of maleic hydrazide are claimed to proceed with unsaturated acid chlorides in nitrobenzene at 160° or with chloromethylsulfonyl chloride. The acetylated 4-methyl analog of maleic hydrazide has been also assigned as the A-acyl derivative on the basis of spectroscopic evidence. Finally, N-acylated maleic hydrazides result from the rearrangement of the corresponding acylated A-aminomaleimides. ... 

Reaction of amino-3(2If)-pyridazinones and 4-amino-3,6-dimeth-oxypyridazine with tosyl chloride has been investigated recently. Thus, 4-amino-3(2.ff)-pyridazinone (or its 6-methoxy analog) (99) when treated with tosyl chloride in pyridine at room temperature for several days yielded a mixture of 100 (R = OMe, 30%) and 101 (R = OMe, 24% R = H, 1-2%). That 100 is formed by rearrangement... 

Rearrangement of 2-phenyl-4,6-dichloro-3(2. f)-pyridazinone into l-phenyl-3-pyrazolone-5-carboxylic acid, described previously, is recorded in connection with the synthesis of some pyrazolone derivatives. ... 

Diethoxy-3(2//)-pyridazinones are rearranged under the influence of sodium ethoxide into 4,5-diethoxypyrazoles (78YZ413), and these are also formed from aryl(4-pyridazinyl) methanols after treatment with p-toluenesulfonic acid at elevated temperatures (84JHC1727). Diazopy-ridazine 109 is converted in the solid state under strictly anhydrous conditions into lactone 110, which is extremely reactive and, with water or ethanol, gives pyrazole 111 [79H( 12)457]. 

Some lactones serve as starting material. y-Phenylazo-y-valerolactone is thermally rearranged to a mixture of pyridazinones 20 and 21 in a ratio of 1.75 1. A complex mechanism is proposed. Pyridazines also result from hydrazines and substituted y-lactones - or -acyl-y-lactones, which react as 1,4-dicarbonyl compounds. y-Chloroketones react with substituted hydrazines to gives pyridazines or Af-aminopyrrolines, depending upon the hydrazine used. ° y-Chlorobutanal gives the corresponding 1,4,5,6-tetrahydropyridazine. ... 

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. ... 

Padwa and Gehrlein reported139 that excited-state behavior of 1,6-dihydropyridazines differs from that of other diazacyclohexadienes. Thus photooxidation of 2,5,6-triphenyl-1,6-dihydropyridazine (36a) in 95% ethanol gave pyridazinone (83). However, when irradiation of dihydropyridazines (36) was carried out in cyclohexene in the presence of fumaronitrile, a [2 + 2] cycloadduct (84) was obtained. Furthermore, the authors noted that the dihydropyridazine system underwent a deep-seated skeletal rearrangement when treated with aqueous acid. Thus reaction of 36a with aqueous hydrochloric acid results in the formation of 1,3,4-triphenylpyrazole (85) [Eq. (24)]. 

Direct chlorination of 2-phenyl-6-hydroxy-3(2//)-pyridazinone (50) in polar solvents (DMF, acetic acid) resulted in chlorination of the phenyl ring and rearrangement of the pyridazinone to give the trichlorophenylaminopyrrole-2,5-dione (51) as the major product the dichlorophenyl-aminopyrrole-2,5-dione (52, Scheme 7) was isolated as an intermediate. It is proposed that the pyridazinone is less stable after dichlorination of the phenyl ring and rearranges to the A -amino-maleimide (52), but the reasons for this are unclear <89JHC1649>. 

A detailed reinvestigation of the 1,3-dipolar cycloaddition of 2-diazopropane to 2-methyl-6-phenyl-3(2//)-pyridazinone has shown that the initial adduct (isolated in 68% yield) is the thermally labile pyrazolopyridazine (79), which undergoes subsequent tautomerization, oxidation, or rearrangement with loss of nitrogen, depending on the conditions (Scheme 36). The iso-propylpyridazine (80) is the major product formed in polar solvents (DMSO) while the diazepine... 

The ease of dehydration of pyridazine carboxamides, their hydrolysis, and Hofmann degradation to amines was outlined in CHEC-I <84CHEC-I(3B)1>. More recently, in the early 1990s, the Curtius rearrangement (Equation (19)) of the 4-carboxylic hydrazide of 6-(4-pyridyl)-3(2//)-pyridazinone to give an aza analogue of amrinone has been reported <90H(3i)2l63>. 

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