The Synthesis and Reactions of N-Hydroxy-3-Arylsydnone-4-Carboxamide Oximes

N-Hydroxy-3-arylsydnone-4-carboxamide oximes (7) were prepared from the corresponding 3-arylsydnone-4-carbohydroximic acid chlorides (6) and hydroxylamine in high yield. The chemical reactivity of compound (2) is somewhat different from 3-arylsydnone-4-carboxamide oximes (2) in that the former compounds reacted with both aromatic and aliphatic aldehydes in the presence of acid catalyst to give 3-aryl-4-(5-aryl-1,2,4-oxadiazol-3-yl)sydnones (5) and 3-aryl-4-(5-alkyl-1,2,4-oxadiazol-3-yl)sydnones (3).     

Preparation of 3-Aryl-4-(5-ARYL-Δ2-1,2,4-Oxadiazolin-3-YL)Sydnones and their Conversion into 3-ARYL-4-(5-ARYL-1,2,4-Oxadiazol-3-YL)Sydnones

3-Aryl-4-(5-aryl-Δ²-1,2,4-oxadiazolin-3-yl)sydnones (5) were synthesized in high yields by the reaction of 3-arylsydnone-4-carboxamide oximes (prepared from the corresponding 3-arylsydnone-4-carbonitriles) with aromatic aldehydes in the presence of acid catalysts. No reaction occurred when aliphatic aldehydes were used. The oxadiazolin-3-ylsydnones (5) were easily converted into the corresponding 3-aryl-4-(5-aryl-1,2,4-oxadiazol-3-yl)sydnones by N-bromosuccinimide oxidation. The 3-arylsydnone-4-carbonitrile oxides were synthesized in good yields by N-bromosuccinimide oxidation of the corresponding 3-arylsydnone-4-carboxaldehyde oximes.     

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 .     

Synthesis of 1,2,4- and 1,3,4-oxadiazoles from 1-aryl-5-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-4-carbonyl chlorides

5-Substituted 2-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazoles were synthesized by reaction of 1-aryl-5-methyl-1H-1,2,3-triazole-4-carbonyl chlorides with the corresponding 5-substituted 1H-tetrazoles. 5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl chloride reacted with N′-hydroxybenzimidamides to give 3-aryl-5-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazoles. Reactions of 4-(5-methyl-1H-1,2,3-triazol-1-yl)benzoic acid with N′-hydroxybenzimidamides resulted in the formation of 3-aryl-5-[4-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl]-1,2,4-oxadiazoles.     

Synthesis of [5-(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)-1,3,4-oxadiazol-2-yl]pyridines

2-, 3-, and 4-[5-(1-Aryl-5-R-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazol-2-yl]pyridines were synthesized from the corresponding 1-aryl-5-R-1H-1,2,3-triazole-4-carbonyl chlorides and 2-, 3-, and 4-(1H-tetrazol-5-yl)-pyridines.     

Construction of Coplanar Bicyclic Backbones for 1,2,4-Triazole-1,2,4-Oxadiazole-Derived Energetic Materials

Combining different nitrogen-rich heterocycles into a molecule can fine-tune its energetic performance and physical properties as well as its safety for use in energetic materials. Here, 1,2,4-oxadiazole was incorporated into 1,2,4-triazole to construct new energetic backbones. 3-(5-Amino-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazol-5-amine ( 5 ) was designed and synthesized. Nitramino-functionalized N-(5-(5-amino-1,2,4-oxadiazol-3-yl)-3H-1,2,4-triazol-3-yl)nitramide ( 6 ) and N-(5-(5-(nitramino)-1,2,4-oxadiazol-3-yl)-3H-1,2,4-triazol-3-yl)nitramide ( 7 ) were also obtained, and two series of corresponding nitrogen-rich salts were prepared, leading to the creation of new energetic compounds. All derivatives were fully characterized, and five of them were further confirmed by X-ray diffraction. The theoretical calculations, energetic performance, safety, and the main decomposition gaseous products of 1,2,4-triazole-1,2,4-oxadiazole-derived energetic materials were studied. Compound 7 and its dihydroxylammonium salt ( 7 c ) exhibited prominent detonation performance comparable to that of RDX while possessing satisfying thermal stabilities and mechanical sensitivities.     

Microwave-induced one-pot synthesis of 4-[3-(aryl)-1,2,4-oxadiazol-5-yl]-butan-2-ones under solvent free conditions

The synthesis of 4-[3-(aryl)-1,2,4-oxadiazol-5-yl]-butan-2-ones (5a-l) from methyl levulinate (4) and arylamidoximes (1a-l) is described. The reaction was carried out in a microwave oven without any solvent in much shorter time and in yields comparable with conventional heating.     

Design,Synthesis, and Cytotoxicity of Semisynthetic Betulinic Acid-1,2,4-Oxadiazole Amide Derivatives

Biological activity of betulinic acid derivatives containing a 1,2,4-oxadiazole ring prompted us to synthesize betulinic acid-1,2,4-oxadiazole amide derivatives 14–25 starting with the amide coupling reaction of betulinic acid 1 and (3-aryl-1,2,4-oxadiazol-5-yl)methanamines 2–13. The products were tested for cytotoxicity on three human cancer cell lines in vitro. All tested compounds demonstrated high activity. The structures of the synthesized compounds were elucidated from IR, NMR and mass spectra.     

Syntheses based on nitrile oxides. 1. Reaction of aromatic nitrile oxides with N-cyanimides

The reaction of trialkylaminocyanimides with aromatic nitrile oxides leads to trialkylamino-(3-aryl-1,2,4-oxadiazol-5-yl)imides, while the corresponding reactions with sulfylcyanimines and phosphincyanimides do not take place. Using x-ray structural analysis the principal structural features of the 1,2,4-oxadiazole products have been elucidated.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2084–2089, September, 1990.     

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.     

Reactivity of 3,5-bis-(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4-triazole

Alkylation of 3,5-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4-triazole with haloalkanes afforded N-CH₂R derivatives, and nitration furnished the corresponding bis-N-nitramine isolated as a trisodium salt. Treatment of the latter with CH₃I resulted in denitration. Diazotization and oxidation of 3,5-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4- triazole, its N-methyl and N-carboxy derivatives gave rise to the corresponding azido and nitro derivatives. Salts of 3,5-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4-triazol-5-acetic acid with nitrogen-containing bases were synthesized. It was established that the character of reaction products of 3,5-bis(4-amino-1,2,5-oxadiazol-3-yl)-1,2,4-triazole with formaldehyde depended on the acid-base properties of the medium.__________Translated from Zhurnal Organicheskoi Khirmii, Vol. 41, No. 2, 2005, pp. 270–276.Original Russian Text Copyright © 2005 by Sergievskii, Romanova, Mel’nikova, Tselinskii.     

Design,Synthesis, and Anticancer Evaluation of 2-{3-{4-[(5-Aryl-1,2,4-oxadiazol-3-yl)methoxy]phenyl}isoxazol-5-yl}-N-(3,4,5-trimethylphenyl)thiazol-4-amine Derivatives

Russian Journal of General Chemistry - A series of new 2-{3-{4-[(5-aryl-1,2,4-oxadiazol-3-yl)methoxy]phenyl}isoxazol-5-yl}-N-(3,4,5-tri-methylphenyl)thiazol-4-amine derivatives is synthesized, and...     

Synthesis of 1-(1-aryl-1H-1,2,3-triazol-4-yl)-β-carboline derivatives

Reaction of 5-methyl-1-aryl-1H-1,2,3-triazole-4-carbocylic acid chlorides with tryptamine derivatives afforded substituted 1-aryl-N-[2-(1H-indol-3-yl)ethyl]-5-methyl-1H-1,2,3-triazole-4-carboxamides. At heating these compounds in toluene in the presence of POCl₃ and P₂O₅ Bischler-Napieralski cyclization occurs giving 1-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-4,9-dihydro-3H-β-carbolines that can be transformed into β-carboline and tetrahydro-β-carboline derivatives.     

Facile TICl<Subscript>4</Subscript>-catalyzed synthesis of novel 1,2,4-triazoles appended to thiazoles

The reaction of sydnone-derived 3-aryl-5-methyl-1,3,4-oxadiazol-2(3H)-ones with thiourea and α-bromoacetophenone derivatives in the presence of a catalytic amount of TiCl₄ produces 2-aryl-4-(4-aryl-1,3-thiazol-2-yl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-ones. The title compounds were screened for their antibacterial and antifungal activity. The toxicity of the compounds was evaluated in terms of mutagenicity, tumorigenicity, and reproductive effects. The drug-relevant properties (ClogP, drug-likeness, and drug score) were calculated, and the structure–activity relationship was discussed.     

4-functionally substituted 3-hetarylpyrazoles: XX. Synthesis of derivatives of 5-(pyrasol-4-yl)-1,2,4-triazole and 3-(pyrazol-4-yl)-1,2,4-triazolo[3,4-c][1,4]oxazine

N-Methylimines of 3-aryl-1-phenylpyrazole-4-carbaldehyde react with ethyl 2-aryl-hydrazino-2-chloroacetate with the formation of ethyl 1-aryl-5-(pyrazole-4-yl)-4,5-dihydro-1H-1,2,4-triazolecarboxylates. Analogous reactions of pyrazol-4-carbaldehyde N-(2-hydroxy)ethylimines results in derivatives of 3-(pyrazol-4-yl)-1,2,4-triazolo[3,4-c][1,4]-oxazines.     

The 1,3-Dipolar Cycloadditions of 3-Arylsydnone-4-Carbonitrile Oxides with Nitriles

3-Arylsydnone-4-carbonitrile oxides (2), which are generated in situ by thermal dehydrochlorination of the corresponding hydroximic acid chlorides (1), undergo 1,3-dipolar cycloadditions with sydnone-4-carbonitriles (6) to give 3-aryl-4-[5-(3-arylsydnonyl)-1,2, 4-oxadiazol-3-yl] sydnones (9). These nitrile oxides (2) also react with alkyl- and arylnitriles to give 1,3-dipolar cycloaddition products.     

Synthesis of heterocycles. Part VI. Synthesis and antimicrobial activity of some 4-amino-5-aryl-1,2,4-triazole-3-thiones and their derivatives

4-Amino-5-aryi-1,2,4-triazole-3-thiones I react with acid chlorides to yield 4-acylamino-5-aryl-1,2,4-triazole-3-thiones II. Compounds I also react with methylene iodide, chloroacetonitrile and methyl bromoacetate to give bis-(4-amino-5-aryl-1,2,4-triazol-3-ylthio)methanes III, 4-amino-5-aryl-3-cyanomethylthio-1,2,4-triazoles IV and 4-amino-5-aryl-3-carbomethoxymethylthio-1,2,4-triazoles V, respectively. Compounds V react with hydrazine hydrate to give the corresponding acid hydrazides VI which in turn condenses with acid chlorides and aldehydes to afford respectively 1-[(4-amino-5-aryl-1,2,4-triazol-3-ylthio)acetyl]-2-aroylhydrazines VII and aryl methylene (4-amino-5-aryl-1,2,4-triazol-3-ylthio)acethydrazones VIII. The antimicrobial activities of the above compounds were screened against different strains of bacteria and fungi.     

Synthesis and reactions of 3-(3-ethoxycarbonyl-1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)propenic acid

The reaction of ethyl 4-formyl-1-phenyl-1H-pyrazole-3-carboxylate with the malonic acid led to the formation (2E)-3-(3-ethoxycarbonyl-1-phenyl-1H-pyrazol-4-yl)propenic acid. In reactions of this acid chloride with 4-amino-5-aryl(hetaryl)-4H-1,2,4-triazole-3-thiols were obtained ethyl 4-[(E)-2-{3-aryl(hetaryl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl}ethenyl]-1-phenyl-1H-pyrazoe-3-carboxylates, with 5-aryltetrazoles, ethyl 4-[(E)-2-(5-aryl-1,3,4-oxadiazol-2-yl)-ethenyl]-1-phenyl-1H-pyrazole-3-carboxylates, with 1-(2-hydroxy-3,5-dimethylphenyl) followed by the Baker-Venkataraman rearrangement and the cyclization, ethyl 4-[(E)-2-(6,8-dimethyl-4-oxo-4Hchromen-2-yl)ethenyl]-1-phenyl-1H-pyrazole-3-carboxylate.     

Synthesis of heterocycles based on arylation products of unsaturated compounds: XVII. Arylation of 2-acetylfuran and synthesis of 3-R-6-(5-aryl-2-furyl)-7<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazines

Reaction of 2-acetylfuran with arenediazonium chlorides under Meerwein reaction conditions led to the formation of 5-aryl-2-acetylfurans. The bromination of these compounds gave 2-bromo-1-(5-aryl-2-furyl)-ethanones that reacted with 4-amino-4H-5-R-1,2,4-triazole-3-thiols to form 3-R-6-(5-aryl-2-furyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines.     

Synthesis of 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one. Derivatives and their ring transformation into 5-benzamido-1,2,4-triazolidine-3,5-dione derivatives

Some 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one derivatives 6 and 9 have been synthesized in two ways. The expected thermal ring transformation into 2,5-disubstituted 1,3,4-oxadiazoles did not occur but, by acid hydrolysis of 5-aryl-3-[3-benzylidene-2-methyl(or phenyl)carbazoyl]-1,3,4-oxadiazol-2(3H)-ones 6 , a new ring transformation took place and the corresponding 4-benzamido-1-methyl(or phenyl)-1,2,4-triazolidine-3,5-dione derivatives 11 were formed. The 4-amino-1-phenyl-1,2,4-triazolidine-3,5-dione ( 19 ) has been prepared and its structure was confirmed by some reactions.