Synthesis of 4,5-dichloro-1-(4,5-dichloropyridazin-3-yl)pyridazin-6-one

This paper presents the synthesis of 4,5-dichloro-1-(4,5-dichloropyridazin-3-yl)pyridazin-6-one from 4,5-dichloropyridazin-6-one.     

Reaction of 1-chloromethyl-4,5-dichloropyridazin-6-one

Reaction of 1-chloromethyl-4,5-dichloropyridazin-6-one with some nucleophiles such as sodium methoxide, sodium azide, 2-mercaptopyrimidine and phenol gave 2, 3, 4, 7, 8 and 10 . 5-Chloro-4-phenoxypyridazin-6-one ( 10 ) was also synthesized from 8 through 9.     

Retro-ene reaction. II. Reaction of 4,5-dichloro-1-hydroxy-methylpyridazin-6-one with alkyl halides and carboxylic acid chlorides

1-Alkyl-4,5-dichloropyridazin-6-oncs and (4,5-dichloro-6-oxopyridazin-1-yl)methylcarboxylates were synthesized from 4,5-dichloro-1-hydroxymethylpyridazin-6-one and the corresponding alkyl halides or carboxylic acid chlorides. Also the reaction mechanisms via a fragmentation of retro-ene type are discussed.     

Alkylation of 4,5-dichloropyridazin-6-one with α,ω-dibromoalkanes or 4,5-dichloro-1-(ω-bromoalkyl)pyridazin-6-ones

Alkylations of 4,5-dichloropyridazin-6-one (1) with dibromoalkanes 2 or 3 in the presence of potassium carbonate or tetrabutylammonium bromide/potassium hydroxide were investigated under restricted condition. Reactions of 1 with 2 or 3, except for 2b and 3b , in the presence of potassium carbonate or tetrabutylammonium bromide/potassium hydroxide gave only the N-alkylation products 3 and/or 4. Alkylation of 1 with 2b or 3b in the presence of potassium carbonate yielded the N-alkylation products 3b and/or 4b and the O-alkylation product 5 as the main product, whereas treatment of 1 with 2b or 3b in the presence of tetrabutylammonium bromide/potassium hydroxide afforded selectively the N-alkylation products 3b and/or 4b.     

An efficient synthesis of [1,4]pyridazinooxazine[3,4-a]tetrahydro isoquinolines

A series of fused isoquinoline-pyridazinooxazine chimera were prepared in good overall yield from phenethylamide 1 and 4,5-dichloropyridazin-3-one 2 via Smiles rearrangement and Pictet-Spengler cyclization.     

Synthesis of analogues of the 2,3,6,-triazaphenothiazine ring system

Treatment of 2,3-dichloroquinoxalines with 2-amino-6-picoline-3-thiol gave a mixture of 2,3-bis(2-amino-6-picolinyl-3-thio)quinoxalines ( 16 , R = H, CI) and 2,3-bis (N,N-dimethylamino)quinoxalines ( 15 , R = H, CI) separated by fractional crystallization. A similar reaction of 3-amino-6-methoxypyridine-2(1H)-thione ( 9 ) with 4,5-dichloropyridazin-3(2H)-one ( 21 ) gave 4-chloro-5-(3-amino-6-methoxypyridyl-2-thio)pyridazin-3(2H)-one ( 22 ). Concentrated hydrochloric acid-catalysed cyclization of 22 gave the non-rearranged 7-methoxy-2,3,6-triazaphenothiazin-1(2H)-one. The action of compound 22 in refluxing glacial acetic acid gave, on the other hand, 7-methoxy-2,3,6-triazaphenothiazin-4(3H)-one via a Smiles rearrangement. These cyclized compounds are the first known derivatives of the new 2,3,6-triazaphenothiazine ring system.     

The condensation products of 6-methoxy-2,3-dihydro-4H-benzopyran-4-one and 6-nitroveratraldehyde. Part I

The condensation of 2,3-dihydro-6-methoxy-4H-benzopyran-4-one ( 1 ) and 6-nitroveratr-aldehyde ( 2 ) gave the expected 2,3-dihydro-6-methoxy-3-(6-nitroveratrylidene)-4H-benzopyran-4-one ( 3 ) plus an unexpected product identified as 2,3-dihydro-3-(α-ethoxy-4,5-dimethoxy-2-nitrobenzyl)-6-methoxy-4H-benzopyran-4-one ( 4 ).     

Stoffwechselprodukte von Mikroorganismen. 187. Mitteilung. Synthese des 3-Isobutyl-4,5-dimethylisoindolin-1-ons,eines Abbauproduktes von Aspochalasin D

Metabolites of Microorganisms. Synthesis of 3-Isobutyl-4,5-dimethylisoindolin-1-one, a Degradation Product of Aspochalasin D 3-Isobutyl-4,5-dimethylisoindolin-1-one ( 1 ) and 3-isobutyl-6, 7-dimethyl-isoindolin-1-one ( 6 ) were synthesized in a non-regioselective way. The structures could be assigned unequivocally by spectroscopic means. Compound 1 was identical with a degradation product of Aspochalasin D.     

Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .     

Synthesis of novel pyridazine acyclonucleosides

Some pyridazine acyclonucleosides containing hydroxymethyl and 4-hydroxybutyl groups as an alkanol side chain were prepared. Nucleophilic displacement of N₁-alkyl-4,5-dichloropyridazin-6-ones is discussed.     

Thermal and photochemical reaction of isoxazolone with indole-2,3-dione derivatives

The reaction of indole-2,3-dione derivatives with five membered heterocycle, viz isoxazolone under ther mal as well as photochemical conditions is described. While under refluxing ethanol these conditions afforded 2,3-dihydro-3-(5′-oxo-3′-phenylisoxazolidyl)indol-2-one 3 and a spiro product 2′,3′-dihydro-3,7-diphenylspiro[diisoxazolo[4,5-e:4,5-b]pyran-8,3′-indol]-2′-one 4 , the uv light induced irradiation mainly produced 4,5-dioxo-3-phenylisoxazolo[5,4-b][1]benzazepine 5 and 3-phenylisoxazolo[5,4-b]quinoline-4-carboxylic acid 6 . The products have been characterised on the basis of spectral data and elemental analyses.     

Synthesis of novel acyclonucleosides. Reactions of 1-(1-bromo or 3-bromo-2-oxopropyl)pyridazin-6-ones

Reaction of 1-(3-bromo-2-oxopropyl)pyridazin-6-ones 1 and 2 with sodium azide at room temperature gave the corresponding 1-(3-azido-2-oxopropyl)pyridazin-6-ones 3 and 4 , whereas reaction of 1-(1-bromo-2-oxo-propyl)pyridazin-6-ones 5 and 6 with excess sodium azide afforded 4-azido-5-chloropyridazin-6-one 7 and 4,5-diazido-3-nitropyridazin-6-one 8 by dealkylation. Some 1-(2-hydroxypropyl)pyridazin-6-ones 9, 10, 11 were synthesized from the corresponding 1-(2-oxopropyl) derivatives 1, 2, 3 . 4,5-Dichloro-1-(2,3-dihydroxypropyl)-pyridazin-6-one 13 was also prepared from compound 9 via the corresponding 2,3-epoxypropyl derivative 12 . Treatment of compound 5 with thiourea gave 4,5-dichloro-1-(2-amino-4-methylthiazol-5-yl)pyridazin-6-one 14 . Reaction of compounds 1 and 2 with thiourea at 20° afforded the corresponding 3-formamidinylthio-2-oxo-propyl derivatives 15 and 16 , whereas treatment of compound 1 with thiourea at 45° gave 4,5-dichloro-1-[(2-aminothiazol-5-yl)methyl]pyridazin-6-one 17 . Compound 17 was also prepared from compound 15 by refluxing in ethanol.     

Tri-component reaction of 2-alkyl-4,5-dichloropyridazin-3(2H)-ones: synthesis of 5-cyano-5-(pyrimidin-2-yl)-2,7-dialkyl-5H-dipyridazino-[4,5-b:4,5-e]-4H-thiopyran-1,6-dione and 2-(4-cyanophenoxy) pyrimidine

Reaction of 2-alkyl-4,5-dichloropyridazin-3(2H)-ones with p-cyanophenol and 2-mercaptopyrimidine in the presence of base gave 2,4,5-trisubstituted-pyridazin-3(2H)-ones 4-9, 2-(4-cyanophenoxy)pyrimidine (10) and 5-cyano-5-(pyrimidin-2-yl)-2,7-dialkyl-5H-dipyridazino[4,5-b:4,5-e]-4H-thiopyran-1,6-diones 11 as a novel heterocycle.     

Reaction of 4,5-diaminopyrimidine and ethyl acetoacetate: Synthesis and chemistry of isomeric dihydropyrimido[4,5-b][1,4] diazepinones

Depending upon reaction conditions, 4,5-diaminopyrimidine and acetoacetic ester gave a variety of condensation products, including the two isomeric dihydropyrimido[4,5-b][1,4]-diazepinones. Under conditions leading to bicyclic products, the formation of 1,5-dihydro-4-methyl-2H-pyrimido[4,5-b][1,4]diazepin-2-one ( 2 ) was strongly favored. The isomeric 3,5-dihydro-2-methyl-4H-4-one compound ( 4 ) was best obtained by cyclization of ethyl 3-(4-amino-5-pyrimidylamino)crotonate ( 3 ) under base catalysis. Thermal rearrangement of 2 and 4 proceeded, in each instance, with loss of the isopropenyl moiety and gave 8-purinone. Compound 4 underwent ring contraction under the influence of alkoxide to yield a product which was shown to be the 7-isopropenyl-8-purinone ( 6 ).     

Synthesis of 8-methyl-2-azainosine and related nucleosides

The synthesis of 6-methyl-7-(β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-4-one (8-methyl-2-azainosine ( 2) ) and 6-methyl-7-(β-D-glucopyranosyl)imidazo[4,5-d]-v-triazin-4-one ( 5 ) by diazotization of 5-amino-1-(β-D-ribofuranosyl)-2-methylimidazole-4-carboxamide ( 1 ) and diazotization of 5-amino-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2-methylimidazole-4-carboxamide ( 3 ), followed by deacetylation of the resulting compound 4 , is described. The preparation of 6-methyl-5-(β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-4-one ( 10 ) and 6-methyl-5-(β-D-glucopyranosyl)imidazo[4,5-d]-v-triazin-4-one ( 11 ) by glycosylation of 6-methylimidazo[4,5-d]-v-triazin-4-one (8-methyl-2-azahypoxanthine, ( 7) ) is also described. Structural assignments were made on basis of analytical and ¹H-nmr and uv spectral data.     

Analysis of microbiocidal isothiazolones

Summary Methyl resp. octyl isothiazolone formulations (Kathon CG resp. Kathon 893) were fractionated by flash chromatography to receive their microbiocidal major components which were investigated by ultraviolet spectrophotometry. UV-spectra and absorption spectral data of 2-methyl-isothiazole-3-one, 5-chloro-2-methyl-isothiazole-3-one, 4,5-dichloro-2-methyl-isothiazole-3-one and 2-noctyl-isothiazole-3-one are given. The isothiazolones considered have their main absorption maxima between 275 and 281 nm. The logarithmic molar extinction coefficients differ from 3.82 to 3.92 for a defined wavelength of 280 nm.Selected compounds, as 6-methoxy-2-methylbenzothiazole and 2-acetyl-5-chlorothiophene were also analysed by ultraviolet spectrophotometry to be used as an internal standard for quantitative high-performance liquid-chromatographic analysis with UV-detection (280 nm). 2-Acetyl-5-chlorothiophene (3.79) is more suitable than 6-methyl-2-methylbenzothiazole (3.99), because of a more favourable logarithmic molar extinction coefficient at 280 nm.

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Teil IV: Fresenius Z Anal Chem (1986) 325:293     

Reaction of 4,5-dichloro-3-nitropyridazin-6-one with dimethylchloromethyleneammonium chloride

3,4,5-Trichloropyridazin-6-one, 3,4,5,6-tetrachloropyridzine and 4,5-dichloro-3-(N,N-dimethylamino)-pyridazin-6-one were synthesized from 4,5-dichloro-3-nitropyridazin-6-one and dimethylchloromethylene-ammonium chloride selectively.     

Benzofused tricycles based on 2-quinoxalinol

This paper describes our recent efforts to synthesize novel compound scaffolds integrating 2-quinoxalinol with privileged structures of 1,3-dihydro-benzoimidazol-2-one, 1,3-dihydro-benzoimidazole-2-thione, 3-hydroxy-1H-quinoxalin-2-one, 2H-benzo[1,4]oxazin-3-ol, 2H-benzo[1,4]thiazin-3-ol, and 1,3,4,5-tetrahydro-benzo[1,4]diazepin-2-one, respectively. Eight novel benzofused tricycles and their substituent diversity points were developed. These include pyrazino[2,3-g]quinoxaline-2,8-diol (I), 3-hydroxy-6,8,9,10-tetrahydro-1,4,6,10-tetraaza-cyclohepta[b]naphthalen-7-one (II), 6-hydroxy-4H-1-oxa-4,5,8-triaza-anthracen-3-one (III), 6-hydroxy-4H-1-thia-4,5,8-triaza-anthracen-3-one (IV), 6-hydroxy-1,1-dioxo-1,4-dihydro-2H-1lambda(6)-thia-4,5,8-triaza-anthracen-3-one (V), 6-hydroxy-1,3-dihydro-imidazo[4,5-g]quinoxalin-2-one (VI), 6-hydroxy-1,3-dihydro-imidazo[4,5-g]quinoxaline-2-thione (VII), and 7-hydroxy-1,4-dihydro-pyrazino[2,3-g]quinoxaline-2,3-dione (VIII). This strategy of integrating two benzofused privileged structures into one molecule may provide a greater chance for the discovery of novel lead compounds.     

Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita

Abstract

A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0?mg L^?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0?mg L^?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.     

A consecutive double-Criegee rearrangement using TFPAA: stepwise conversion of homoadamantane to oxahomoadamantanes

Rearrangement of 4-methylhomoadamantan-4-ol (1) with trifluoroperacetic acid (TFPAA) in trifluoroacetic acid (TFAA) proceeds with the formation of 4-oxahomoadamantane 6 and its derivatives (4 and 5). 2-exo-Hydroxy-4-oxahomoadamantane (5) and 6 were identified as a result of consecutive O-insertion Criegee rearrangement processes. The absence of methyl trifluoroacetate and methyl trifluoroperacetate among the reaction products, as well as the presence of acetyltrifluoroacetyl peroxide, is consistent with a double rather that a triple oxygen insertion during the course of the Criegee reaction. A mechanism involving initial Criegee rearrangement followed by a Baeyer-Villiger reaction is also excluded by kinetic considerations. The parallel formation of 4-ethyl-3-oxahomoadamantan-2-one (4) was determined to be the result of 4-methylhomoadmantan-4-ol (3) dehydration, with subsequent epoxidation of 4-methylhomoadamant-4-ene (32) to 4,5-epoxy-4-methylhomoadamantane (33), acid-catalyzed isomerization of 33 to 3-methylhomoadamantan-2-one (34), and Baeyer-Villiger oxidation to 3-methyl-5-oxabishomoadamantan-6-one (35). This sequence of reactions was followed by the acid-catalyzed isomerization to the final product 4. The proposed mechanisms for these transformations are discussed on the basis of model experiments and supporting density functional theory (DFT) calculations.