3-pyridazinone 6- hydroxy

Since pyridazinones are acidic compounds, they undergo IV-hydroxy- and N-amino-methylation. They react also with aromatic aldehydes in the presence of acetic anhydride in the ratio of 2 1 to give the condensation product (73 Scheme 23). 

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). 

A somewhat similar method for the preparation of l,3-oxazolo[4,5-d]pyridazi-nones has been described by Ivachtchenko and coworkers (Scheme 6.214) [385]. Here, the key intermediate 5-amino-4-hydroxy-3(2H)-pyridazinone was treated with... 

C9H12N206 4-Hydroxy-l-/3-D-ribofuranosyl-6-pyridazinone (3-deaza-6-azauridine)210... 

Reaction of the 2-acetoxy-3(2//)-furanones (526) with monosubstituted hydrazines gives good yields of the pyridazinium-5-olates (527) together with varying amounts of isomeric products. Alkyl derivatives (527 R = alkyl) have also been prepared by base-catalyzed alkylation (Mel, Me2SO4, PhCH2Cl) of 3-methyl-6-phenyl-5-ethoxycarbonyl-4( 1 //)-pyridazinone. Reduction of the diphenyl compound 527 (R = Ar = Ph) by zinc and hydrochloric acid gives 3-ethoxycarbonyl-5-hydroxy-5-methyl-l,2-diphenyl-2-pyrrolin-4-one (528 R = Ar = Ph) (Scheme 21... 

Reactive chlorine atoms at the 4-position may also be replaced by nitro groups using sodium nitrite in dimethylformamide. Thus, 4,5-dichloro-3(2H)-pyridazinones have been converted into 4-hydroxy-5-nitro-3(2H)-pyridazinones, the replacement of the second chlorine by a hydroxyl taking place simultaneously. ... 

Pyridazines with hydroxyl groups (generally in the oxo form) at different positions in the ring can be prepared by several methods as outlined in Section III. Syntheses from open-chain compounds are particularly suitable for obtaining 3(2/I)-pyridazinones and their 6-hydroxy analogs. If more complex pyridazinones are available, such as halogenated pyridazinones, catalytic dehalogenation is one of the preferred methods. In this manner 3(2 I)-pyridazinone ... 

Maleic hydrazide has also been investigated in detail and its structure determined as the monohydroxymonooxo form, i.e., 6-hydroxy-3(2I )-pyridazinone, from spectroscopic data (for summary see Volume 1 of this Series, Chapter VII, p. 366). Similar conclusions were reached for substituted maleic hydrazides, although for 4- or 5-substituted maleic hydrazides it is not known which of the amide groups relative to the substituent is in the lactam and which in the enolized form. 

Hydrolysis of 3-chloropyridazine 1-oxide with dilute sodium hydroxide solution gives 3-hydroxypyridazine 1-oxide (identical with that synthesized by another method ) and likewise 6-chloro-3-methoxypyridazine 1-oxide (126) with acetic acid and sodium acetate yields 3-methoxy-6-hydroxypyridazine 1-oxide or its tautomeric form, i.e., l-hydroxy-3-methoxy-6(ljH )-pyridazinone (127). ... 

Compound 127 exists in the l-hydroxy-3-methoxy-6(lH)-pyrid-azinone form, on the basis of UV and IR data. By contrast, 6-chloro-3-methoxypyridazine 1-oxide when heated with 5% sodium hydroxide afforded 6-ehloro-3(2H)-pyridazinone 1-oxide. ... 

Removal of alkoxy groups from 3-(4-, 5-, or 6-)alkoxypyridazine 1-oxides in alkaline medium produces the corresponding hydroxy-pyridazine l-oxides. - - On the basis of UV spectra and pK values for 3-hydroxypyridazine 1-oxides it is postulated that there is a larger contribution of the phenolic structure (128) than of the tautomeric pyridazinone N-oxide structure (129). ... 

Dimethoxypyridazine 1-oxide and its 4-chloro and 4-methoxy analogs are hydrolyzed with sodium methoxide or hydrazine hydrate to l-hydroxy-3-methoxy-6(lH)-pyridazinone and its 4-chloro and 4-methoxy analogs. ... 

Acylation or alkylation of 1-hydroxypyridazinones, as exemplified by benzoylation of l-hydroxy-3-methoxy-6(l.ff)-pyridazinone and its 4- or 5-substituted derivatives or methylation of 1-hydroxy-3,4-disubstituted-6(l.f )-pyridazinones, affords the corresponding 1-benzyloxy and 1-methoxy derivatives, respectively. 

Methylation with methyl iodide proceeds normally with 3,6-dimethyl-5-hydroxypyridazine 1-oxide to give the corresponding 5-methoxy derivative, although in low yield, whereas from 4-hydroxy-pyridazine 1-oxide and its 3,6-dimethyl analog the corresponding l-methoxy-4(l/f)-pyridazinones were obtained. - ... 

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