Pyridazine 1-oxide, 3-hydroxy

Pyridazine 5-Hydroxy-6-(methyl-amino-methyl)- -1-oxid E9a, 620 (H- CH2-NHR)... 

H5C2 —CHO or Aceton) Pyrido[2,3-d pyridazin 5-Hydroxy-8-methyl- -1-oxid E9c, 17 (2-CO —... 

IV-Oxidation of 3,6-dialkoxypyridazines (OMe, OEt, OPr", OBu") gives monoxides, while 3,6-di-r-butoxy- and 3,6-dibenzyloxy-pyridazine cannot be IV-oxidized, but give 6-hydroxy-pyridazin-3(2/f)-one and 6-benzyloxypyridazin-3(2//)-one as hydrolysis products. Methyl-thiopyridazines give both 5-oxidation and IV-oxidation products with various oxidizing agents in some instances. 

Amino groups in pyridazine A-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 A-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 A-oxides can readily be replaced with sodium alkoxides. 

In pyridazin-3(2//)-one only the hydrogen at position 6 is replaced at 180 °C, while in 3-hydroxypyridazine 1-oxide the deuterium exchange takes place first at position 6 and then at position 4 at 140 °C. 5-Hydroxy- and 5-methoxy-pyridazine 1-oxide exchange only the hydrogen at position 6 at 150 °C. 

Pyridazine N-ethoxycarbonylimide photolysis, 3, 13 Pyridazine, 4-gJycosyloxy-rearrangement, 3, 15 Pyridazine, halo-applications, 3, 56 Pyridazine, hexahydro-, 3, 40 photoelectron spectra, 2, 20-21 Pyridazine, hydrazino-reductive cleavage, 3, 34 synthesis, 3, 35 Pyridazine, hydroxy-acidity, 3, 4 Pyridazine, 3-hydroxyl-oxide... 

Cyclooctatetraene reacts as a dienophile with 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine to form, upon loss of N2, a cycloocta[4]pyridazine and a tetracyclic bis-Diels-Alder cycloadduct [95LA661]. In a nonpolar solvent, the former produced a dihydrobarrelenofrflpyridazine that could be oxidized (with 4-phenyltriazolinedione) to the barreleno[d]pyridazine, but in a polar solvent it gave a dihydrocycloocta[d]pyridazine in a multistep process. X-ray crystal structures of some of these compounds have been obtained. The attempted dehydrogenation of 4,4a-dihydro-5//[ 1 ]benzopyrano[4,3-c]pyridazin-3(2//)-ones with m-CgH NC SOjNa unexpectedly led to new 5-hydroxy[ 1 ]benzopyrano[4,3-c]pyridazin-3(2//)-ones [95JHC79]. 

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). 

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). 

Six-membered heterocyclic substrates showing regioselective aminomethylation include a substantial number of hydroxy-pyridine, -pyrimidine, and -pyridazine derivatives as well as their N-oxide derivatives (89-91, Fig. 35). 

In addition to the foregoing 1,4-difunctional compounds used for cyclizations, the following have been used to give pyridazines or theirreduced analogs , 4-hydroxy ketones, l,4-haloketones, l,4-dibromobutane, 2,5-dibromohexane, 1,4-halo-esters, or butadiene dioxide. Hexahydropyridazine results as one of the oxidation products of 1,4-diaminobutane and its 1-butyl analog is formed in the reduction of iV-nitroso-4-chloro-dibutylamine. ... 

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). ... 

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. - ... 

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... 

---