Pyridazine N-oxide

The reactivity of halogens in pyridazine N- oxides towards nucleophilic substitution is in the order 5 > 3 > 6 > 4. This is supported by kinetic studies of the reaction between the corresponding chloropyridazine 1-oxides and piperidine. In general, the chlorine atoms in pyridazine A-oxides undergo replacement with alkoxy, aryloxy, piperidino, hydrazino, azido, hydroxylamino, mercapto, alkylmercapto, methylsulfonyl and other groups. 

There are several examples of replacement of methoxy and ethoxy groups in substituted pyridazine N- oxides, with ammonia or hydrazine producing the corresponding amino and hydrazino compounds. 

Methylpyridazine can be oxidized with selenium dioxide to give 3-formylpyridazine, and methyl groups attached to any position in pyridazine N-oxides are transformed with pentyl nitrite in the presence of sodium amide in liquid ammonia into the corresponding... 

Pyridazines form complexes with iodine, iodine monochloride, bromine, nickel(II) ethyl xanthate, iron carbonyls, iron carbonyl and triphenylphosphine, boron trihalides, silver salts, mercury(I) salts, iridium and ruthenium salts, chromium carbonyl and transition metals, and pentammine complexes of osmium(II) and osmium(III) (79ACS(A)125). Pyridazine N- oxide and its methyl and phenyl substituted derivatives form copper complexes (78TL1979). 

Table 8 Spectral Data for Pyridazine N- Oxides (CDCI3)...

Photolysis of pyridazine N-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. 

When nitration of pyridazine N-oxides is carried out with acyl nitrates (prepared in situ from acyl chlorides and silver nitrate) the reaction takes place at the /3-position relative to the N-oxide group. Under these circumstances only mononitro derivatives are formed. For example, nitration of pyridazine 1-oxide with acetyl nitrate yields 3-nitropyridazine 1-oxide (17%) and 5-nitropyridazine 1-oxide (0.8%), whereas with benzoyl nitrate a better yield of 5-nitropyridazine 1-oxide is obtained. 

Amino groups in pyridazine N- oxides can be diazotized and the diazonium group further replaced by halogens, hydroxy group or hydrogen. So, 3-, 4-, 5- and 6-bromopyridazine 1-oxides can be prepared from the corresponding amino N- oxides. 

When 6-amino-3-chloropyridazine 1-oxide is diazotized in 50% sulfuric acid, 6-hydroxy-3-pyridazinediazonium anhydro salt is formed. An azido group at either position in pyridazine N- oxides can readily be replaced with sodium alkoxides. 

Pyridazine N- oxides react with benzyne to give a mixture of 1-benzoxepin (129) and arylpyridazine (130), while N- acetylpyridaziniumimide forms a cycloadduct (131) which is further transformed into (132) and (133) (Scheme 44). 

Tsuchiya, T., Arai, H. and Igeta, H. (1973) Photochemistry - IX. Formation of cyclopropenyl ketones and furans from pyridazine N-oxides by irradiation. Tetrahedron, 29 (18), 2747-2751. 

A few examples of Mannich reactions exist in the series. Pyridazine N-oxides, substituted at the 3- or 5-position by hydroxy, are alkylated at either of the vacant ring positions, although activated methyl groups may react preferentially (68CPB939 73CPB1510 75CPB923). 

The second most important nucleophilic substitution in pyridazine N- oxides is the replacement of a nitro group. Nitro groups at the 3-, 4-, 5- and 6-position are easily substituted thermally with a chlorine or bromine atom, using acetyl chloride or hydrobromic acid respectively. Phosphorus oxychloride and benzoyl chloride are used less frequently for this purpose. Nitro groups in nitropyridazine N- oxides are easily replaced by alkoxide. The... 

The n NMR spectra of pyrido[2,3-d]pyridazine N-oxides (e.g. 69AJC1745), 1-ones (69BSF3678) and 1,4-diones (69MI21501) have been recorded and discussed. Some reduced derivatives and quaternary salts have also been studied and alkaline deuterium exchange reactions investigated (77BSF919). 

Bis-Jthieno][3,4-a 3, 4 -c]cyclobntadien E17f., 755 (Pyridazin-N-oxid - Cyclobutan)... 

When 3-cyclopropenyl ketones (230), formed by irradiation of pyridazine N-oxides (229), were heated with n-butylamine under reflux for 1 h or stirred at room temperature for 3-4 h a mixture of pyrroles was formed in 80% yield (equation 151). ... 

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