Pyridazine-thione

P3nridazines, bis-quatemary salts of, 20 quatemization of, 19, 20 Pyridazine-thione, 51 Fyridines, activation energy of, 11 -alkylation of, 227 alkyl-, reaction with carbenes, 76-78 amino-, 224, 226 aza-effects in, 318... 

Pyridazine-3(2//)-thiones exist in the thione form (14), as is evident from an X-ray structure analysis of pyridazine-3(2//)-thione. 6-Mercaptopyridazine-3(2//)-thione is predominantly in the monothiolmonothione form (15) in aqueous solution and in the solid state, 6-hydroxypyridazine-3(2//)-thiones are in the hydroxythione form (16) and 6-aminopyridazine-3(2//)-thiones exist in the aminothione form (17) for further details see (73HC(28)755). Cinnoline-4(l//)-thiones and phthalazine-l(2//)-thione have been shown on the basis of UV data and ionization constants to exist in the thione forms. 

AIkyI-substituted pyridazine-3(2//)-thiones undergo reaction with methyl iodide at the sulfur atom. Methylation of 4,5-diaminopyridazine-3(2ff)-thione with excess methyl iodide produces 4,5-diamino-l-methyIthiopyridazinium iodide (81JOC2467). 

The S ->N rearrangement of pyridazinethione glycosides proceeds smoothly under the influence of mercury(II) bromide. For example, 3-(tetraacetyl-l-/3-D-glucosylmer-capto)pyridazines rearrange to 2-(tetraacetyl-l-/3-D-glucosyl)pyridazine-3(2//)-thiones. 

Pyridazines are formed from pyrones or their thioxo analogs or from appropriate pyridones. Pyrones or pyridones react with diazonium salts to give the corresponding hydrazones (187) and (188) which are rearranged under the influence of acid or base into pyridazinones as shown in Scheme 107. On the other hand, kojic acid is transformed with hydrazine into a 1,4-dihydropyridazine and a pyrazole derivative. 4H-Pyran-4-thiones... 

Pyridazine-3(2H)-thione, 4,5,6-triphenyl-ring contraction, 3, 29 Pyridazineth lones acylation, 3, 37 glycosides... 

S-N rearrangement, 3, 36 ionization constants, 3, 4 oxidation, 3, 37 quatemization, 3, 17 Pyridazine-3 (2 H) - thiones analysis, 3, 2 tautomerism, 3, 5 Pyridazinium betaine, 3-oxido-photolysis, 3, 11 Pyridazinium betaine, 5-oxido-photolysis, 3, 11 Pyridazinium dicyanomethylide photolysis, 3, 12... 

The mesomeric effect of the C=S linkage is very pronounced and is responsible for the facile quaternization of heterocyclic N-alkylated thiones (159) this effect is operative even when such a shift does not increase the aromaticity of the ring. Thione derivatives of pyridazine, benzothiazole, quinazoline, 1,3-thiazine, triazole,and isoindole are examples of compounds which readily form quaternary salts. 

Dimethyl-l,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (41) is also an old product [7,11, 31] that has recently been found to react with GSH to give S-nitrosogluta-thione, NO and HNO [32]. It stimulates partially purified rat lung soluble guanylate cyclase, but not the heme-deficient enzyme. The activation is inhibited by ODQ. The product also displays significant vasodilator activity on rat thoracic aorta rings at nanomolar concentrations. Finally, [l,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide derivatives (42, R,Ri=CH3,H) release NO, detected as nitrite, in the presence of thiols. A mechanism for this release has been proposed [33]. 

Two methods for the preparation of [l,2,3]triazolo[4,5-, pyridazine-4-thione 29 were reported by Bussolari et al. involving nucleophilic substitution of sulfur by displacement of the 4-chloro substituent from 28 and of the oxygen atom of 4-lactam derivative 30 using sodium thiosulfate and phosphorus pentasulfide, respectively (Scheme 18) <1996BMC1725>. 

Alkylations of the 4-thione substituent of l-(2,3,5-tri-0-acetyl-/3-D-ribofuranosyl)triazolo[4,5- pyridazine-4-thione 29 were carried out using sodium hydride and various alkyl halides, and the reaction with methyl iodide to give methylthio derivative 48 is shown in Scheme 32 <1996BMC1725>. 

Dichloropyrimido[4,5- ]pyridazines react readily with amines, potassium hydrosulfide, sodium azide (72CPB1528) and alkoxides (72CPB1522) to give the corresponding disubstituted amines, thiones, azides and alkoxides, respectively. Hydrolysis of the starting compounds (88) with 1% sodium hydroxide yields a mixture of the chloro products (89) and (90) (72YZ1312). 

Methylmercaptopyridazine 6-Mercaptopyridazine-3(2ff)-thione 3,6-Bis(methylmercapto)pyridazine 6-Hydroxypyridazine-3(2//)-thione... 

---