Direct functionalization of 4,5-dichloropyridazin-6-one

Direct functionalization of 4,5-dichloropyridazin-6-one with some nucleophiles in seven solvents gave regioselectively 5-halo-4-substituted-pyridazin-6-ones as main product. Reaction of 4,5-dichloropyridazin-6-one with 2-mercaptopyrimidine (2 equivalents) also afforded 4,5-di(pyrimidin-2-ylsulfanyl)pyridazin-6-one as the main product.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

The synthesis of pyrimido[4,5-d] pyridazines

The synthesis of pyrimido[4,5-d]pyridazin-2-one-4-thione (II), pyrimido[4,5-d]pyridazine-2,4-dithione (VI), 4-aminopyrimido[4,5-d]pyridazine-2-thione (III), 2-aminopyrimido[4,5-d]-pyridazin-4-one (X), 2-methylpyrimido[4,5-d]pyridazin-4-one (XII), and pyrimido[4,5-d]-pyridazin-4-one (XIII) are reported together with several new pyridazine intermediates.     

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.     

Synthesis of Substituted 2-Aryl- and 2-Hetarylimidazo[4,5-d]pyridazines

Substituted 2-aryl- and 2-hetarylimidazo[4,5-d]pyridazines were synthesized by oxidative cyclization in the presence of sulfur of 4,5-diamino-6-methylpyridazin-3-one with substituted arene(hetarene)carbaldehydes or heterocyclic compounds having an activated methyl group.     

A new efficient route to imidazo[4,5-c]pyrazol-5-ones

The synthesis of imidazo[4,5-c]pyrazol-5-ones ( 6 ) is reported. 5-Amino-4-ethoxycarbonylaminopyra-zoles 3a-g when heated at 200° for 2 hours afford 6a-g. In a similar manner imidazo[4,5-c]pyrazol-5-one ( 6a ) is readily obtained from 4-amino-5-ethoxycarbonylaminopyrazole ( 5a ).     

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 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.     

Reaction of 4,5-diamino-1,6-dihydropyrimidin-6-ones with two equivalents of chalcones

The reaction of 4,5-diamino-1,6-dihydropyrimidin-6-ones 1 with two equivalents of the chalcones 2 leads in an acidic medium to the formation of the 2,3,6,7-tetrahydro-1H-pyrimido[4,5-b][1,4]diazepin-6-one derivatives 3a-d . The structure elucidation of the products is based on nmr measurements and an X-ray diffraction.     

Retro-ene reactions. III. Alkylation of 4,5-dichloro-1-hydroxymethylpyridazin-6-ones: Synthesis of 4,5-dichloro-1-(ω-phthalimido and saccharin-2′-ylalkyl)pyridazin-6-ones

4,5-Dichloro-1-(ω-phthalimido and saccharinyl-2′-ylalkyl)pyridazin-6-ones were synthesized from 4,5-dichloro-1-hydroxymethylpyridazin-6-one and the corresponding N-(ω-haloalkyl)phthalimides and saccharins via a fragmentation of retro-ene type.     

Fused imidazoacridines: Synthesis of 1,3-dihydroimidazo[4,5-b]-acridin-2-one and 1,3-dihydroimidazo[4,5-a]acridin-2-one

The synthesis of new 1,3-dihydroimidazo[4,5-a]acridin-2-one and 1,3-dihydroimidazo[4,5-b]acridin-2-one derivatives is reported. The yield and the structure of each isomer were determined by nmr spectroscopy.     

The synthesis of pyridazino[4,5-d] pyridazines,pyrazino [2,3-d] pyridazines and a pyrimido [4,5-d] pyridazine

The synthetic chemistry of the relatively unknown pyridazino [4,5-d]pyridazine ring system has been extended. 1,4-Diaminopyridazino [4,5-d]pyridazine (VIII) has been prepared by two routes, the most interesting of these being the one-step conversion of 4,5-dicyanopyridazine into VIII with hydrazine. Upon nitration VIII gave only the mononitramine (X). Attempts to prepare 1,4-dichloropyridazino [4,5-d]pyridazine gave only 4-chloro-2H-pyridazino [4,5-d]pyridazin-1-one (XII). Pyrimido [4,5-d]pyridazine-1,3-dione (XIV) was prepared from pyridazine-4,5-dicarboxamide (IV). The hydrolysis of 5,8-dichloropyrazino [2,3-d]pyridazine (XV) gave 5-chloropyrazino [2,3-d]pyridazin-8-one (XVII) and likewise the ammonolysis of XV gave 5-amino-8-chloropyrazino [2,3-d]pyridazine (XX). As expected the hydrolysis of 5,8-dibromo-pyrazino [2,3-d]pyridazine (XXI) gave 5-bromopyrazino [2,3-d]pyridazin-8-one (XXII). Attempted catalytic dechlorination of 5-chloropyrazino [2,3-d]pyridazin-8-one (XVII) gave 1,2,3,4-tetrahydropyrazino [2,3-d]pyridazin-5-one (XIX).     

Isothiazoles VI: 4,5-dihaloisothiazolidin-3-one 1-Oxides

A useful and facile procedure for preparing 4,5-dihaloisothiazolidin-3-one 1-oxides is reported. Chlorination or bromination of various 4-isothiazolin-3-one 1-oxides yielded the title compounds.