Pyridazine 3- hydroxymethyl

Photolysis of pyridazine IV-oxide and alkylated pyridazine IV-oxides results in deoxygenation. When this is carried out in the presence of aromatic or methylated aromatic solvents or cyclohexane, the corresponding phenols, hydroxymethyl derivatives or cyclohexanol are formed in addition to pyridazines. In the presence of cyclohexene, cyclohexene oxide and cyclohexanone are generated. 

Compounds which are of interest in this context include 4-oxadiazolylpyrid-azines (35, R = cyclopropyl, Et) [117], 6-aryloxy-2-hydroxyalkyI-3(27/)-pyri-dazinones [118], 3-halo-6-hydrazinopyridazines of type (36, R = substituted amino) [119], Ar-2-isoxazolylmethyl-substituted 3-iminopyridazines (37) [ 120], carbamates derived from 3,6-bis(hydroxymethyl)-4-pyridazinones (38, R = alkyl, Ph) [121], and iminodihydropyridazine derivatives (39, R1 = acyl R2 = H,MeS R3 = aryl) [122, 123]. In Hungary, antidepressant activity has been observed with some 3,6-disubstituted pyridazines of type (40) [124]. 

A -unsubstituted 4,5-dichloropyridazin-3(277)-one (109) fails to undergo Suzuki crosscoupling reactions. In order to synthesize N-2, unsubstituted 4,5-diarylpyridazin-3(2//)-ones (112) by Suzuki reaction, the temporary protection of the lactam moiety of 109 is essential. To achieve this a simple and efficient retro-ene-assisted Suzuki methodology has been developed by Ravina and co-workers which is based on 4,5-dichloro-2-(hydroxymethyl)pyridazin-3(277)-one (110) [61]. This pyridazin-3(2//)-one is easily available from 109 via reaction with formaldehyde. Interestingly, 110 reacts smoothly with arylboronic acids to afford directly the deprotected 4,5-diarylated pyridazin-3(2//)-ones (112) in high yields. The mechanism probably involves the formation of 4,5-diarylated-2-(hydroxymethyl)pyridazin-3(277)-ones (111), which subsequently lose formaldehyde by a retro-ene reaction induced by base or heat [62]. 

The loss of formaldehyde from a structurally related 2-(hydroxymethyl)pyridazin-3(2//)-one derivative was already observed more than a decade ago Zto-Kaczian, E. Matyus P. Heterocydes 1993, 36, 519-28. 

Photoreactions of pyridazine N-oxides have been misinterpreted in part. Thus, the reported hydroxymethylation of some pyridazine N-oxides ° with concomitant loss of oxygen is probably due to secondary reaction of the parent pyridazine. Igeta et al. reported on the photochemistry of several pyridazine N-oxides that resulted mainly in deoxygenation " in the presence of benzene, toluene, or cyclohexane, the hydrocarbons were oxygenated to give phenols or cyclohexanol in moderate yield. Cyclohexene gave cyclohexene oxide and cyclohexanone in a ratio of 5 1 and polymethylbenzenes, the corresponding phenols or hydroxymethyl derivatives. ... 

Electronic spectra of samples of tetramethylcyclobutadiene prepared from different precursors differ among themselves, again indicating intermolecular interactions within the matrix [34]. Thus if pyridazine or phthalic derivatives are also present the products are coloured whereas when o-di(hydroxymethyl)benzene or 3,4-benzo-dihydrofuran are the coproducts the mixtures are colourless [34]. Cyclobutadiene and its alkyl derivatives either absorb at about 300-305 nm or have no bands above 300 nm, consistent with rectangular singlet structures [34-37]. 

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