Access to 5-fluoroisoxazoles via the nitrosation of geminal bromo-fluoro arylcyclopropanes

A new method for the synthesis of 3-aryl-5-fluoroisoxazoles via the reaction of nitrosonium chlorosulfate with 2-aryl-1-bromo-1-fluorocyclopropanes containing acceptor substituents in the aromatic ring has been developed. The reaction proceeds highly regioselectively thus providing 3-aryl-5-fluoroisoxazoles in good yields. The structure of isoxazoles was corroborated by the DU8+ hybrid DFT/parametric computational approach.     

An efficient synthesis of highly substituted pyrroles from β-oxodithiocarboxylates

α-Oxoketene-N,S-acetals, prepared by the reaction of alkyl glycinate hydrochlorides with β-oxodithiocarboxylates followed by alkylation, underwent cyclization in presence of chloromethyleneiminium salt derived from POCl₃/DMF to afford alkyl-3-aryl-4-formyl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates in excellent yields. Alkyl-3-aryl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates were formed in moderate yields when the same N,S-acetals were treated with DBU.     

Synthesis of some 5-Aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones from benzoxepinoisoxazolone and benzocycloheptaisoxazolone derivatives

Some 5-aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones were synthesized by hydrogenolytic cleavage of the isoxazole ring of 4-aryl-3-oxo-3,3a,4,10-tetrahydro[1]-benzoxepino[3,4-c]isoxazoles or 4-aryl-3-oxo-3a,4,9,10-tetrahydro-3H-benzo[4,5]cyclohepta[1,2-c]isoxazoles which in turn were prepared from ethyl 3-oxo-4-phenoxybutanoate or ethyl 3-oxo-5-phenylpentanoate by simple methods.     

v-Triazolines. Part XIX. Thiocino[4,5-d]-1,2,3-triazole and thiocino[4,5-d]isoxazole derivatives

5-Amino-2,3,6,7-tetrahydrothiocines were reacted with arylazides yielding 1-aryl-9a-amino-1,3a,4,5,7,8,9,9a-octahydrothiocino[4,5-d]-1,2,3-triazoles which could be deaminated to 1-aryl-1,4,5,7,8,9-hexahydrothiocino-[4,5-d]-1,2,3-triazoles. Similarly, the above enamines yielded, with nitrile oxides, 3-aryl-9a-amino-3a,4,5,8,9,9a-hexahydrothiocino[4,5-d]isoxazoles which were transformed with acids into 3-aril-4,5,8,9-tetrahydrothiocino-[4,5-d]isoxazoles.     

A NOVEL SYNTHESIS OF ISOXAZOLES VIA 1,3-DIPOLAR CYCLOADDITION OF NITRILE OXIDES TO ACETYL ACETONE

ABSTRACT

Nitrile oxides (2) isolated from the oxidative dehydrogenation of aldoximes (1) by chloramines-T react with acetyl acetone (3) to afford 4-acetyl-3-aryl-5-methyl isoxazoles (5) in good yield. All new compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS studies and elemental analysis.     

An efficient synthesis of 3-aryl-2-aryl(or methyl)sulfanylbenzo[b]thiophenes via cyclization of aryl 2-aryl(or methyl)sulfanylmethylsulfanylphenyl ketones

A convenient method for the preparation of 2-aryl(or methyl)sulfanylbenzo[b]thiophenes has been developed. Thus, aryl 2-aryl(or methyl)sulfanylmethylsulfanylphenyl ketones, easily prepared from readily available aryl 2-sulfanylphenyl ketones or 2-chloro-5-nitrophenyl phenyl ketone, are treated with LDA in 1,2-dimethoxyethane (DME) to give 3-aryl-2-aryl(or methyl)sulfanylmethylsulfanyl-2,3-dihydrobenzo[b]thiophen-3-ols, which in turn were dehydrated with thionyl chloride to afford 3-aryl-2-aryl(or methyl)sulfanylbenzo[b]thiophenes in reasonable overall yields.     

Synthesis of isomeric series of aryltetrahydrobenz-isoxazoles and arylcyclopentisoxazoles

Four series of potential PAF-antagonists in which the isoxazole nucleus is condensed with a polyhydrogenated five- or six-carbon ring were prepared. The synthesis of the compounds 3-aryl-4,5,6,7-tetrahydrobenz[c]isoxazoles 1 , 3-arylcyclopent[c]isoxazoles 2 , 3-aryl-4,5,6,7-tetrahydrobenz[d]isoxazoles 3 , and 3-arylcyclopent[d]isoxazoles 4 , required an extensive optimization and comparison of the methods available in the literature.     

Synthesis and reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole

The palladium-catalyzed cross-coupling reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole with aryl iodides provided high yields of the corresponding 5-aryl-4-fluoro-1H-pyrazoles. Furthermore, these cross-coupling reactions proceeded smoothly under an atmosphere of carbon monoxide (CO) to afford the corresponding 5-acyl-4-fluoro-1H-pyrazoles as CO-insertion products.     

Synthesis of new liquid-crystalline compounds from the 3-aryl-5-alkylpyrazole series

A method was developed for the preparation of new liquid-crystalline substances, pyrazole derivatives, through the corresponding 2-isoxazolines and isoxazoles. The hydrogenolysis of the heterocycle in 3-(4-hydroxyphenyl)-5-amylisoxazole afforded 1-amino-1-(4-hydroxyphenyl)-1-octen-3-one. The acid hydrolysis of the compound followed by treating with hydrazine hydrate resulted in 5-amyl-3-(4-hydroxyphenyl)-1H-pyrazole, whose benzylation and esterification with the corresponding mesogenous benzyl chlorides and benzoyl chlorides provided liquid-crystalline 5-alkyl-3-aryl-1H-pyrazoles.     

Guanidine and amidine mediated synthesis of bridgehead triazaphenalenes, pyrimidines and pyridines through domino reactions

An efficient and concise synthesis of 8-amino-2,5-diaryl-1,9,9b-triazaphenalene-4-carbonitriles has been delineated through two successive base catalyzed heteroaromatic annulations of 6-aryl-4-(piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles by guanidine hydrochloride in moderate yield. This reaction was further explored through the ring transformation of 4 with amidines 8 and 11 to afford (2,6-diarylpyrimidin-4-yl)acetonitriles and 6-aryl-4-(piperidine-1-yl)nicotinonitriles in excellent yields.     

A multi-component synthesis of 3-aryl-1-(arylmethylideneamino)pyrrolidine-2,5-diones

A multi-component synthesis of 3-aryl-1-(arylmethylideneamino)pyrrolidine-2,5-diones is described. A mixture of N-isocyaniminotriphenylphosphorane, an aldehyde, and Meldrum's acid undergo a 1:2:1 addition reaction under mild conditions to afford the title compounds in good to excellent yields.     

Synthesis of annelated [a]aza-anthracenones and thieno[3,2-g]aza-naphthalenones through ring transformation of 2H-pyran-2-one followed by photocyclization

A concise synthesis of some new classes of heterocycles (4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a-diaza-cyclopenta[a]anthracen-6-carbonitriles and 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a-diazabenzo[a]anthracene-7-carbonitriles) has been developed by the ring transformation of suitably functionalized 2H-pyran-2-one with α-oxoketene cyclic aminals to intermediates (8-aroyl-5-aryl-2,3-dihydro-1H-imidazo[1,2-a]pyridine-7-ylidene)-acetonitriles and (9-aroyl-6-aryl-1,2,3,4-tetrahydropyrido[1,2-a]pyrimidin-8-ylidene)-acetonitriles) followed by their photocyclization either in CHCl₃ or acetonitrile. This reaction was further explored for the synthesis of methyl 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carboxylate, 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carbonitriles, 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a,10-triazabenzo[a]anthracene-7-carbonitriles, 4-aryl-10-oxo-1,2,3,10-tetrahydro-9-thia-1,3a-diazadicyclopenta[a,g]naphthalene-6-carbonitriles and 5-aryl-11-oxo-1,3,4,11-tetrahydro-2H-10-thia-1,4a-diazacyclopenta[b]phenanthrene-7-carbonitriles from the similar reactions.     

Nitrile oxide cycloaddition routes to 2-(isoxazolyl)-benzoates and 2-(1,2,4-oxadiazol-3-yl)benzoates

Cycloaddition of aromatic nitrile oxides to methyl o-vinylbenzoate produced methyl 2-(3-aryl-2-isoxazolin-5-yl)benzoates; the isoxazolines were converted to methyl 2-(3-arylisoxazol-5-yl)benzoates. Reaction of the nitrile oxide from o-methoxycarbonylbenzohydroximinoyl chloride ( 11 ) with phenylacetylene, styrenes, and aromatic nitriles resulted in methyl 2-(5-phenylisoxazol-3-yl)benzoate, methyl 2-(5-aryl-2-isoxazolin-3-yl)-benzoates ( 15 ), and methyl 2-(5-aryl-1,2,4-oxadiazol-3-yl)benzoates, respectively. The isoxazolines 15 were converted to the corresponding isoxazoles 16 .     

The reaction of (N-isocyanimino)triphenylphosphorane with benzoic acid derivatives: a novel synthesis of 2-aryl-1,3,4-oxadiazole derivatives

The reactions of benzoic acid derivatives with (N-isocyanimino)triphenylphosphorane proceed smoothly at room temperature to afford 2-aryl-1,3,4-oxadiazoles in high yields.     

Reaction of 2-Propynyl Phenylcarbamate with Benzaldehyde Oximes in the Presence of N-Chlorobenzenesulfonamide Sodium Salt

2-Propynyl phenylcarbamate reacts with substituted benzaldehyde oximes on heating in ethanol in the presence of N-chlorobenzenesulfonamide sodium salt, yielding the corresponding 3-aryl-5-(phenylcarbamoyloxymethyl)isoxazoles.     

Synthesis of new pyrazole-1,2,3-triazole dyads

An efficient two step synthetic methodology of new 5(4)-aryl-4(5)-[3(5)-(2-hydroxyphenyl)-1H-pyrazol-5(3)-yl]-1H-1,2,3-triazole dyads was established. The reaction of (E)-2-styryl-4H-chromen-4-ones, used as building blocks, with sodium azide, gave 4(5)-aryl-5(4)-(chromon-2-yl)-1H-1,2,3-triazoles bearing either electron-donating or electron-withdrawing substituents in their styryl moiety which upon reaction with hydrazine hydrate afforded the expected pyrazoles in moderate to very good yields.     

Anodic formation of 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 2(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles

3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles together with the unknown systems 2-(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles were obtained by anodic oxidation, under aprotic conditions, of aryl aldehyde N-(5-aryl-1,3,4-thiadiazol-2-yl) hydrazones. Mechanistic proposals are given.     

Synthesis of 5-alkyl-5-aryl-1-pyrroline N-oxides from 1-aryl-substituted nitroalkanes and acrolein via Michael addition and nitro reductive cyclization

A general method for accessing 5-alkyl-5-aryl-1-pyrroline N-oxides (AAPOs) has been established using readily available aryl bromides, nitroalkanes, and acrolein as the starting materials. The palladium-catalyzed arylation of nitroalkanes gave the 1-aryl-substituted nitroalkanes, which underwent the Et₃N-catalyzed Michael addition with acrolein at room temperature to afford the 4-aryl-4-nitroaldehydes. The latter were then subjected to the nitro reductive cyclization using Zn–HOAc in EtOH at 0 °C followed by warming the reaction mixture to room temperature for 24 h, furnishing the 5-alkyl-5-aryl-1-pyrroline N-oxides in good overall yields. Selected examples of 1,3-dipolar cycloaddition of the cyclic nitrones with methyl methacrylate were also described.     

Synthesis of unsymmetrical benzils using N-heterocyclic carbene catalysis

In this paper, we propose a novel and efficient method for the preparation of various unsymmetrical benzils. We first demonstrate the nucleophilic aroylation of N-phenylbenzimidoyl chlorides with aromatic aldehydes using N-heterocyclic carbene as the catalyst to afford 1-aryl-2-phenyl-2-(phenylimino)ethanones. These iminoethanones were then converted to 1,2-diaryl-1,2-diketones by acid-promoted hydrolysis.     

Synthesis of novel isoxazolines and isoxazoles of N-substituted pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives through [3+2] cycloaddition

3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 3 was prepared by an intramolecular cyclization of N-(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl) acetamide 2 in ethanol in the presence of piperidine. N-allylation and N-propargyl alkylation of N-substituted pyrazolo[3,4-d] pyrimidin-4(5H)-one 3 yielded the corresponding dipolarophiles 4 and 5 which afford by condensation with arylnitrile oxides in toluene the expected new isoxazolines 6 and isoxazoles 7, respectively. On the other hand, the aminopyrazole 1 in refluxing with ethanol in the presence of sodium hydroxide afforded the corresponding carboxamide 8, which then, was converted to its ethyl 3-methyl-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d] pyrimidine-6-carboxylate 9 with neat diethyl oxalate. The dipolarophile 10 on regiospecific 1,3-dipolar cycloaddition with arylnitrile oxides affords isoxazoles 11 and the unexpected deethoxycarbonylated isoxazoles 12. The target compounds were completely characterized by ¹H NMR, ¹³C NMR, IR and HRMS.