Pyridazine IV-oxides

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. 

When nitration of pyridazine iV-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 iV-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. 

Mono- and dilithio derivatives of p-tosylmethyl isocyanide 297a were shown to display interesting reactions. Reaction of the monoanion with unsaturated esters was shown to give pyrrole derivatives . Dianion 297b was found to add to the carbon-nitrogen double bonds of isoquinoline, quinoline and quinoxaline affording compounds 298, 299 and 300, respectively. In the reactions with pyridine iV-oxide and pyridazine iV-oxide, unstable open-chain products 301 and 302 were obtained . 

Photochemical hydroxyalkylation has been carried out with pyri-dines, quinolines, isoquinolines,acridine, pyridazines, pyrimidines, ethoxyquinolinium salts,and imidazoles. It also occurs with iV-oxides the mechanism of Scheme 13 has been suggested for pyridazine iV -oxide. ... 

Certain pyridazine iV-oxides are isomerized into the corresponding diazoketones, e.g. (994) — (995) ring contraction to the corresponding furan (996) can then occur. 

The 11 NMR spectra of pyrido[2,3-d]pyridazine iV-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). 

When there is an N-oxide function present in an azine, another site becomes available for proton attack. Although pyridazine iV-oxides often react at the free nitrogen, pyrimidine oxides frequently form the hydroxy salts (83CHE1012). 

Introduction of chlorine into the pyridazine nucleus is possible also via pyridazine iV-oxides (Section IV, G). Hypohalous acids react with pyridazinones with unsubstituted NH groups to yield the relatively stable iV-halopyridazinones, and it is also possible to replace the hydrazino group of a hydrazinopyridazine with bromine atom with a mixture of hypobromous and hydrobromic acids. ... 

Two brief surveys concerning pyridazine iV -oxides have been published recently. -... 

Dipole moment examinations proved useful in connection with structure determinations in a number of methyl-substituted or methylchloro-disubstituted pyridazine iV-oxides. The calculated values for various mono- or disubstituted pyridazine iV -oxides are in good agreement with the observed. Structures of several compounds, predicted on the basis of dipole moments, have later been confirmed by chemical transformations. 

Pyridazine iV -oxide is formed in 89% yield when pyridazine is treated with hydrogen peroxide in glacial acetic acid. 3-Methyl-pyridazine similarly gives a mono-i -oxide for which the 2-oxide structure (109) has been ascribed. Ogata and Kano ° repeated this V-oxidation and were able to isolate the 2-oxide (109) and 1-oxide (110) in a ratio of 3 1. Likewise, 4-methylpyridazine yielded the corresponding 2-oxide and 1-oxide in a ratio of about 4 1. The... 

There are individual cases of replacement of other groups in substituted pyridazine iV-oxides, such as the substitution of methoxy or ethoxy groups with amino or hydrazino groups, and replacement of an azido group with a methoxy, ethoxy, or benzyloxy group... 

With pyridazine iV-oxides with an unsubstituted ortho position, the reaction with phosphorus oxychloride seems to give primarily the ortho chloro-substituted pyridazine. 3-Methoxypyridazine 1-oxide thus gives 3-chloro-6-methoxypyridazine. ... 

There are only two examples of attempted side chain bromination of pyridazine iV-oxides. 3-Methoxy-5-methylpyridazine 1-oxide did not react with iV-bromosuccinimide, but 3-methoxy-6-methyl-pyridazine 1-oxide yielded 6-bromomethyl-3-methoxypyridazine 1-oxide. 

There are several other reactions pertinent to functional groups present in pyridazine iV -oxides. The cyano group of 6-cyano-3-methylpyridazine 1-oxide is normally hydrolyzed to the carboxyl in concentrated sulfuric acid, whereas heating 5-chloro-6-cyano-3-methylpyridazine 1-oxide with 2 equivalents of sodium methoxide in a sealed tube gave 6-carbamoyl-5-hydroxy-3-methylpyridazine... 

The wideline NMR, IR, and Raman spectra of maleic hydrazide were determined and discussed in connection with its tautomeric forms. NMR techniques have been used to predict the structure of cyclization products from 3-carboxyacryloylhydrazines. The NMR spectra of JV-methyl-pyridazinium iodides and pyridazine iV-oxide were investigated, and the... 

Addition of an A -acetamidopyridazinium ylide to benzyne in the presence of butyl nitrite gives a pyridazinoindazole in good yield and under mild conditions, but pyridazine iV-oxide reacts with benzyne differently, a 1-benzoxepine and a pyridazine being formed. 

The reactivity of pyridazine and pyridazine iV-oxide methyl substituents is reviewed in CHEC-I <84CHEC-l(3B)l>. In particular, susceptibility to oxidation to the aldehydes or acids, condensation with aldehydes, and reactions of lithiated intermediates are discussed for instance, treatment of 3-methylpyridazine-1 -oxide with acetic anhydride gives, after hydrolysis, 3-hydroxymethylpy ridazine. 

V-Oxides, just as in the pyridine series, show a remarkable duality of effect -they encourage both electrophilic substitutions and nucleophilic displacements. The sequence below shows pyridazine iV-oxide undergoing first, electrophilic... 

Hydrogen peroxide can also be used to oxidize pyridazine in the presence of acetic acid, although the resulting pyridazine iV-oxide was obtained in only 8% yield. ... 

Under rhodium catalysis, pyridazine iV-oxide is able to undergo hydrometalation reactions (eq 5). In this case, CsOAc was determined to be essential for reactivity and has been postulated to facilitate the insertion of Rh into the heteroaryl C-H bond. 

Pyridazine IV-oxide, 557 C4H4O Furan, 334 C4H5N Pyrrole, 572 C4H6Cl2N2Pd... 

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