Studies on pyridazine compounds,XIX. Mesylation of 5-aminopyrazoles and related compounds

Summary Acylation of 5-amino-1-substituted pyrazoles gave — depending on the substituents in position 3 and agents used — mono-, di- and triacylated products, respectively.Poster presented at the 10^th International Congress on Heterocyclic Chemistry, Waterloo/Canada, August 11–16, 1985.     

Studies on the synthesis of heterocyclic compounds. Part IV. Further investigation of the pschorr reaction with some pyrazole derivatives

Thermal decomposition of the diazonium sulfate derived from N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-aminobenzamide afforded products formulated as 1-phenyl-3-methyl[2]benzopyrano[4,3-c]pyrazol-5-one (yield 10%), 1,4-dimethyl-3-phenylpyrazolo[3,4-c]isoquinolin-5-one (yield 10%), N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-hydroxybenzamide (yield 8%) and 4′-hydroxy-2,3′-dimethyl-1′-phenylspiro[isoindoline-1,5′-[2]-pyrazolin]-3-one (yield 20%). Decomposition of the diazonium sulfate derived from N-methyl-(1,3-diphenylpyrazol-5-yl)-2-aminobenzamide gave products formulated as 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]-diazocin-10-(9H)one (yield 8%), 4-methyl-1,3-diphenylpyrazolo[3,4-c]isoquinolin-5-one (yield 7%) and 4′-hydroxy-2-methyl-1′,3′-diphenylspiro[isoindoline-1,5′-[2]pyrazolin]3-one (yield 10%). The spiro compounds 6a,b underwent thermal and acid-catalysed conversion into the hitherto unknown 2-benzopyrano[4,3-c]pyrazole ring system 7a,b in good yield. Analytical and spectral data are presented which supported the structures proposed.     

Pyridazines. LXXXIV. Studies on borohydride reduction of pyridazine compounds

Imidazo[1,2-b]pyridazine, s-triazolo[4,3-b]pyridazine and tetrazolo[1,5-b]pyridazine and some derivatives thereof were reduced with sodium borohydride to give the corresponding 5,6,7,8-tetrahydro derivatives. A mechanism for these reductions is proposed and reduction at the C₇-C₈ bond occurs before the reduction of the C₆? N₅ bond. Substituents at position 7 and/or 8 cause a significant decrease in the extent of reduction or lead to a 5,6-dihydro derivative by competitive attack at the 6 position.     

Synthesis of pyridazine derivatives XXII. s-triazolo[4, 3-b]pyridazine 5-oxides

The synthesis of s-triazolo[4,3-b] pyridazine 5-oxides is reported. To our knowledge, they are the first example of N-oxides of heteroaromatic azoloazines with a bridgehead nitrogen. They are easily rearranged, in particular when irradiated with ultraviolet light, into 6-hydroxy-s-triazolo[4,3-b]pyridazines.     

Studies on pyridazine azide cyclisation reactions

Reaction of sodium azide with 4-methyl-3,5,6-tribromopyridazine results in the formation of 3,5,6-triazide intermediate which could cyclise to give two possible bicyclic products while ab initio calculations show that the formation of a tricyclic compound is extremely energetically unfavourable. However, experimentally, only one major product is isolated. The structure of this unstable product has been conclusively established by X-ray crystallography as 3,5-diazido-4-methyl[1,5-b]tetrazolopyridazine confirming theoretical predictions.     

Synthesis of 3,6-disubstituted pyridazine derivatives

The synthesis of pyridazine functionalized with dioximes side chains are described. Several 3,6-disubsti-tuted pyridazine derivatives were prepared and their structures determined by spectroscopic methods (nmr, ir and ms).     

Cyclization of diketones to pyridazine and furan derivatives

Condensation of (±)-2,3-bis(3,4-dimethoxybenzoyl)butane-1,4-dione 1 with different hydrazine bases afforded the corresponding pyridazines 2 and 3 . Refluxing the diketone 1 with methanolic hydrogen chloride yielded the corresponding 3,4-dimethylfuran derivative 5 . Reaction of acetonylacetone 6 with p-sulfamylphenylhydrazine afforded the corresponding 3,6-dimethyl-1H-pyridazine derivative 7 . Reaction of 7 with the appropriate isocyanate and isothiocyanate yielded the corresponding benzenesulfonylurea 8 and thiourea 9 derivatives respectively. The structures of the compounds synthesized were affirmed by microanalyses and spectral studies.     

Synthesis of pyridazine derivatives. XXI. Tetrazolo-azido transformations in some fused azolopyridazines

6-Azidotetrazolo[1,5-b]pyridazine (III) has been prepared by two different routes and is easily transformed into the 6-amino derivative (IV). The attempted cyclization of 6-hydrazinotetrazolo[1,5-b] pyridazine (II) into the postulated tricycle has been shown to result in the formation of 6-azido-s-triazolo [4,3-b]pyridazine (VI), obtained also in a separate experiment from VII. The azido structure of VI has been confirmed from spectroscopic data and from its conversion into 6-amino-s-triazolo [4,3-b]pyridazine (VIII), obtained in another experiment from VII. Similarly, cyclization of II with cyanogen bromide resulted in the simultaneous formation of the s-triazolo ring and ring opening of the fused tetrazolo ring, giving IX. For 6-azido-2-phenylimidazo[1,2-b]pyridazine (XII) the expected azide structure proved to be correct.     

Studies on the photocyclization reaction of 8-styryl-substituted coralyne derivatives

The photoreactivity of four 8-styryl-substituted coralyne derivatives was examined by UV/VIS- and ¹H-NMR-spectroscopy. Except for the dimethylamino-substituted derivative, these cationic azoniaheterocyclic dyes undergo photocyclization that most likely proceeds through an initial E-Z-isomerization of the double bond. Subsequent oxidation of the intermediates under aerobic conditions gave the pyrrolo-annelated quinolizinium derivatives as final products, thus providing a useful synthetic route to polycyclic azoniahetarene derivatives. The 6-(4-chlorophenyl)-substituted pyrroloquinolizinium derivative was isolated on a preparative scale, and the investigation of its photophysical properties revealed significantly red-shifted absorption (λ_abs = 465–480 nm) and emission bands (λ_fl = 550–562 nm) in comparison to the parent coralyne and the styryl-substituted derivatives.     

1,3-Dipolar cycloadditions of diazoalkanes to pyridazine derivatives. Thermal 1,5-sigmatropic rearrangement of methyl groups in 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazine derivatives

Thermal 1,5-sigmatropic rearrangements of one of the methyl group attached at position 3 of 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazin-4(5H)-ones 1–3 taking place either in a clock-wise or anti-clockwise direction gave N₂-methylated products 4–6 and C_3a-methylated products 7– 9 . The -7(6)-one derivative 10 and -4,7(5H,6H)-dione derivative 12 gave only N₂-methylated products 11 and 13 respectively, and 1,2-dihydro derivative 14 produced after elimination of methane, 15 .