Three novel benzothiazine‐fused triazoles as potential centrally acting muscle relaxants

The structures of the novel triazolobenzothiazines 2,4‐dihydro‐1H‐benzo[b][1,2,4]triazolo[4,3‐d][1,4]thiazin‐1‐one (IDPH‐791), C₉H₇N₃OS, (I), a potential muscle relaxant, its benzoyl derivative, 2‐(2‐oxo‐2‐phenylethyl)‐2,4‐dihydro‐1H‐benzo[b][1,2,4]triazolo[4,3‐d][1,4]thiazin‐1‐one, C₂₀H₁₇N₃O₄S, (II), and the β‐keto ester derivative, ethyl 3‐oxo‐2‐(1‐oxo‐2,4‐dihydro‐1H‐benzo[b][1,2,4]triazolo[4,3‐d][1,4]thiazin‐2‐yl)‐3‐phenylpropanoate, C₁₇H₁₃N₃O₂S, (III), are the first examples of benzothiazine‐fused triazoles in the crystallographic literature. The heterocyclic thiazine rings in all three structures adopt a distorted half‐chair conformation. Compound (III) exists in the trans‐β‐diketo form. Other than N—H...O hydrogen bonds in (I) forming dimers, no formal intermolecular hydrogen bonds are involved in the crystal packing of any of the three structures, which is dominated by C—H...O/N and π–π stacking interactions.     

Synthesis of Novel Benzotriazoloazepine Derivatives

Eight new benzotriazoloazepine derivatives have been synthesized starting from 7‐methoxy‐2,3,4,5‐tetrahydro‐1H‐2‐benzo[c]azepin‐1‐one. The compounds 2a–c have been synthesized by the reaction of 7‐methoxy‐2,3,4,5‐tetrahydro‐1H‐2‐benzo[c]azepin‐1‐thione with various hydrazides. Reaction of 5 with hydrazine hydrate, followed by treatment of the resultant hydrazone with formic acid, gave corresponding 9‐alkoxy‐6,7‐dihydro‐5H‐benzo[c][1,2,4]triazolo[4,3‐a]azepine(6 a , b ). Cyclization of 5 with methyl carbazate gave 9‐alkoxy‐6,7‐dihydro‐2H‐benzo[c][1,2,4]triazolo[4,3‐a]azepin‐3(5H)‐one (7 a–c ). The structures of the compounds were confirmed by their elemental analysis and spectral data. Their anticonvulsant activities have been initially screened.     

Utilization of cleavage of the [1]benzofuro[2,3‐e][1,2,4]triazine ring for the synthesis of oxygen,nitrogen and sulfur derivatives of [1,2,4]triazine

A series of 6‐azacytosines 4a‐4k and 5a‐5c were prepared by nucleophilic cleavage of furan ring of [1]benzofuro[2,3‐e][1,2,4]triazine derivative 1 . Some of them were used for the preparation of derivatives of [1,2,4]triazolo[4,3‐d][1,2,4]triazine ( 6a‐6d ) and tetrazolo[1,5‐d][1,2,4]triazine (7). The reaction of 1 with hydrogen sulfide afforded the corresponding 6‐(2‐hydroxyphenyl)‐2‐phenyl‐5‐thioxo‐4,5‐dihydro‐1,2,4‐tri‐azin‐3(2H)‐one ( 8 ), while with hydrogen selenide 6‐(2‐hydroxyphenyl)‐2‐phenyl‐4,5‐dihydro‐1,2,4‐triazin‐3(2H)‐one ( 9 ) was formed. The prepared compounds were tested for biological activity.     

The different modes of chiral [1,2,3]triazolo[5,1‐b][1,3,4]thiadiazines: crystal packing,conformation investigation and cellular activity

The crystal structures of four new chiral [1,2,3]triazolo[5,1‐b][1,3,4]thiadiazines are described, namely, ethyl 5′‐benzoyl‐5′H,7′H‐spiro[cyclohexane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate, C₁₉H₂₂N₄O₃S, ethyl 5′‐(4‐methoxybenzoyl)‐5′H,7′H‐spiro[cyclohexane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate, C₂₀H₂₄N₄O₄S, ethyl 6,6‐dimethyl‐5‐(4‐methylbenzoyl)‐6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine‐3‐carboxylate, C₁₇H₂₀N₄O₃S, and ethyl 5‐benzoyl‐6‐(4‐methoxyphenyl)‐6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine‐3‐carboxylate, C₂₁H₂₀N₄O₄S. The crystallographic data and cell activities of these four compounds and of the structures of three previously reported similar compounds, namely, ethyl 5′‐(4‐methylbenzoyl)‐5′H,7′H‐spiro[cyclopentane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate, C₁₉H₂₂N₄O₃S, ethyl 5′‐(4‐methoxybenzoyl)‐5′H,7′H‐spiro[cyclopentane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate, C₁₉H₂₂N₄O₄S, and ethyl 6‐methyl‐5‐(4‐methylbenzoyl)‐6‐phenyl‐6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine‐3‐carboxylate, C₂₂H₂₂N₄O₃S, are contrasted and compared. For both crystallization and an MTT assay, racemic mixtures of the corresponding [1,2,3]triazolo[5,1‐b][1,3,4]thiadiazines were used. The main manner of molecular packing in these compounds is the organization of either enantiomeric pairs or dimers. In both cases, the formation of two three‐centre hydrogen bonds can be detected resulting from intramolecular N—H…O and intermolecular N—H…O or N—H…N interactions. Molecules of different enantiomeric forms can also form chains through N—H…O hydrogen bonds or form layers between which only weak hydrophobic contacts exist. Unlike other [1,2,3]triazolo[5,1‐b][1,3,4]thiadiazines, ethyl 5′‐benzoyl‐5′H,7′H‐spiro[cyclohexane‐1,6′‐[1,2,3]triazolo[5,1‐b][1,3,4]thiadiazine]‐3′‐carboxylate contains molecules of only the (R)‐enantiomer; moreover, the N—H group does not participate in any significant intermolecular interactions. Molecular mechanics methods (force field OPLS3e) and the DFT B3LYP/6‐31G+(d,p) method show that the compound forming enantiomeric pairs via weak N—H…N hydrogen bonds is subject to greater distortion of the geometry under the influence of the intermolecular interactions in the crystal. For intramolecular N—H…O and S…O interactions, an analysis of the noncovalent interactions (NCIs) was carried out. The cellular activities of the compounds were tested by evaluating their antiproliferative effect against two normal human cell lines and two cancer cell lines in terms of half‐maximum inhibitory concentration (IC₅₀). Some derivatives have been found to be very effective in inhibiting the growth of Hela cells at nanomolar and submicromolar concentrations with minimal cytotoxicity in relation to normal cells.     

Two regioisomers of condensed thioheterocyclic triazine synthesized from 6‐phenyl‐3‐thioxo‐2,3,4,5‐tetrahydro‐1,2,4‐triazin‐5‐one

In the crystal structure of 6‐phenyl‐3‐thioxo‐2,3,4,5‐tetrahydro‐1,2,4‐triazin‐5‐one, C₉H₇N₃OS, (I), the 1,2,4‐triazine moieties are connected by face‐to‐face contacts through two kinds of double hydrogen bonds (N—H...O and N—H...S), which form planar ribbons along the a axis. The ribbons are crosslinked through C—H...π interactions between the phenyl rings. The molecular structures of two regioisomeric compounds, namely 6‐phenyl‐2,3‐dihydro‐7H‐1,3‐thiazolo[3,2‐b][1,2,4]triazin‐7‐one, C₁₁H₉N₃OS, (II), and 3‐phenyl‐6,7‐dihydro‐4H‐1,3‐thiazolo[2,3‐c][1,2,4]triazin‐4‐one, C₁₁H₉N₃OS, (III), which were prepared by the condensation reaction of (I) with 1,2‐dibromoethane, have been characterized by X‐ray crystallography and spectroscopic studies. The crystal structures of (II) and (III) both show two crystallographically independent molecules. While the two compounds are isomers, the unit‐cell parameters and crystal packing are quite different and (II) has a chiral crystal structure.     

Synthesis of new hetero[1,2,4]thiadiazin‐3‐one S,S‐dioxides and oxazolo[3,2‐b]hetero[1,2,4]thiadiazine S,S‐dioxides as potential psychotropic drugs

A series of 2‐substituted 2H‐thieno[3,4‐e][1,2,4]thiadiazin‐3(4H)‐one 1,1‐dioxides ( 2 ), 2‐substituted 2H‐thieno[2,3‐e][1,2,4]thiadiazin‐3(4H)‐one 1,1‐dioxides ( 3 ), 2‐substituted 4,6‐dihydropyrazolo[4,3‐e]‐[1,2,4]thiadiazin‐3(2H)‐one 1,1‐dioxides ( 4 ), 2‐substituted 2,3‐dihydrooxazolo[3,2‐b]thieno[3,4‐e]‐[1,2,4]thiadiazine 5,5‐dioxides, ( 5 ), 6‐substituted 6,7‐dihydro‐2H‐oxazolo[3,2‐b]pyrazolo[4,3‐e][1,2,4]thia‐diazine 9,9‐dioxides ( 6 ) and 7‐substituted 6,7‐dihydro‐2H‐oxazolo[3,2‐b]pyrazolo[4,3‐e][1,2,4]thiadiazine 9,9‐dioxides ( 7 ) were synthesized as potential psychotropic agents.     

Synthesis and antiviral evaluation of some novel [1,2,4]triazolo[4,3-β][1,2,4]triazole nucleoside analogs

Ribosylation of 3-amino-5H-[1,2,4]triazolo[4,3-b][1,2,4]triazole ( 1 ) with l-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose and stannic chloride resulted in the following protected nucleoside analogs: 3-amino-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 4 ), 3-amino-1-(2,3,5-tri-O-benzoyl-α-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 5 ), 3-amino-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 5 ), and 3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl) amino-5H-[1,2,4]triazolo[4,3-b]-[1,2,4]triazole ( 7 ). Compounds 4–6 were deprotected to 3-amino-1-β-D-ribofuranosyl[1,2,4]triazolo[4,3-b][1,2,4]-triazole ( 3 ), 3-amino-1-α-D-ribofuranosyl[1,2,4]triazolo[4,5-b][1,2,4]triazole ( 8 ), and 3-imino-2H-2-β-D-ribo-furanosyl[1,2,4]triazolo[4,3-b][1,2,4]triazole ( 9 ), while 7 could not be deprotected without decomposition. Compounds 1, 4, 6, 7 , and 9 were screened and found to have no antiviral activity.     

An Expedient Method for the Synthesis of 1,2,4‐Triazolo‐fused 1,5‐Benzodiazepine, 1,5‐Benzoxazepine,and 1,5‐Benzothiazepine Scaffolds: A Novel Seven‐membered Ring System of Biological Interest

New heterocyclic compounds 1‐(3‐methyl‐9H‐dibenzo[b,f][1,2,4]triazolo[4,3‐d][1,4]diazepin‐6‐yl)ethanone 8a , 1‐(3‐methyldibenzo[b,f][1,2,4]triazolo[4,3‐d][1,4]oxazepin‐6‐yl)ethanone 8b , and 1‐(3‐methyldibenzo[b,f][1,2,4]triazolo[4,3‐d][1,4]thiazepin‐6‐yl)ethanone 8c are synthesized from benzodiazepinone, benzoxazepinone, and benzothiazepinone derivatives. These heterocyclic scaffolds have wide medicinal importance. Best results were obtained in antibacterial screening against Escherichia coli, Enterobacter cloacae, and Staphylococcus aureus and antifungal screening against Candida albicans and Fusarium oxysporum. 1,1‐Diphenyl‐2‐picrylhydrazyl radical scavenging activities of compounds 6c , 7c , and 8c were tested in doses 10, 20, 30, 40, and 50 μg/mL and were expressed as IC₅₀ values and percent of inhibition with means ± standard deviation of three different concentrations of synthesized compounds. The assignment of the structures of synthesized compounds was made by thin‐layer chromatography, elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and liquid chromatography–mass spectrometry.     

Hydrazonoyl Halides Precursors to Synthesis of New Thiazole,Thiadiazole, and Benzothiazepine Derivatives

New series of substituted thiazole and thiadiazoles were prepared starting from N ′‐(3,4‐dihydronaphthalen‐1(2H )‐ylidene)hydrazinecarbothiohydrazide by reacting with different types of hydrazonoyl chlorides. In addition, 7‐(4‐chlorophenyl)‐5,6,6a,7‐tetrahydrobenzo [b ]naphtha‐[1,2‐e ][1,4]thiazepine reacted with hydrazonoyl halides to afford a new derivatives of 7‐(4‐chlorophenyl)‐14‐phenyl‐5,6,6a,7‐tetrahydro‐16H‐benzo[b]naphtho[1,2‐e][1,2,4]triazolo[4,3‐d ][1,4]thiazepine. Structures of the newly synthesized compounds were elucidated on the basis of elemental analyses and spectral data.     

Synthesis and anticonvulsant activities of 5-(2-Chlorophenyl)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepines

A group of 5-(2-chlorophenyl)-10-(substituted)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepines 7a-c were synthesized by the acid catalyzed reaction of 5-(2-chlorophenyl)-2-hydrazino-3H-pyrido[3,4-e]-[1,4]diazepine ( 6 ) with either trimethyl orthoformate, triethyl orthoacetate or triethyl orthobenzoate, respectively. 5-(2-Chlorophenyl)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepine ( 7a ) and 5-(2-chlo-rophenyl)-10-methyl-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepine ( 7b ) exhibited good anticonvulsant activity in the subcutaneous metrazol anticonvulsant screen which serves as a model for absence (petit mal) epilepsy.     

A new approach for the synthesis of some pyrazolo[5,1‐c]triazines and pyrazolo[1,5‐a]pyrimidines containing naphtofuran moiety

Naphtho[2,1‐b]furan‐2‐yl)(8‐phenylpyrazolo[5,1‐c][1,2,4]triazin‐3‐yl)methanone, ([1,2,4]triazolo[3,4‐c][1,2,4]triazin‐6‐yl)(naphtho[2,1‐b]furan‐2‐yl)methanone, benzo[4,5]imidazo[2,1‐c][1,2,4]triazin‐3‐yl‐naphtho[2,1‐b]furan‐2‐yl‐methanone, 5‐(naphtho[2,1‐b]furan‐2‐yl)pyrazolo[1,5‐a]pyrimidine, 7‐(naphtho[2,1‐b]furan‐2‐yl)‐[1,2,4]triazolo[4,3‐a]pyrimidine, 2‐naphtho[2,1‐b]furan‐2‐yl‐benzo[4,5]imidazo[1,2‐a]pyrimidine, pyridine, and pyrazole derivatives are synthesized from sodium salt of 5‐hydroxy‐1‐naphtho[2,1‐b]furan‐2‐ylpropenone and various reagents. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation, and alternative synthetic route whenever possible. J. Heterocyclic Chem., (2012).     

Synthesis and Anticancer Evaluation of Some Novel 5‐Amino[1,2,4]Triazole Derivatives

Novel [1,2,4]triazole derivatives were synthesized via various synthetic pathways. Among which were different substituted [1,2,4]triazole analogues that were synthesized, in addition to various fused [1,2,4]triazolo[1,5‐a]pyrimidine derivatives, [1,2,4]triazolo[1,5‐a][1,3,5]triazines, and [1,2,4]triazolo[5,1‐c][1,2,4]triazines. Besides, benzo[h][1,2,4]triazolo[5,1‐b]quinazolines, [1,2,4]triazolo‐[5,1‐b]quinazoline, [1,2,4]triazolo[1,5‐a]quinazoline and [1,2,4]triazolo[5,1‐d][1,2,3,5]tetrazine derivatives were also synthesized. The newly synthesized compounds were evaluated for their in vitro anticancer activity against liver cancer HepG2 and breast cancer MCF7 cell lines compared with the reference drug doxorubicin. Compounds 4 , 7 , 15 , 17 , 28 , 34 , and 47 were found to exert promising anticancer activity against HepG2 cell line showing IC₅₀ values ranging from 17.69 to 25.4 μM/L, while compounds 7 , 14a , 17 , 28 , and 34 showed significant activity against MCF7 cell line with IC₅₀ values ranging from 17.69 to 27.09 μM/L.     

Eight 7‐benzyl‐3‐tert‐butyl‐1‐phenylpyrazolo[3,4‐d]oxazines,encompassing structures containing no intermolecular hydrogen bonds,and hydrogen‐bonded structures in one,two or three dimensions

7‐Benzyl‐3‐tert‐butyl‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₂H₂₅N₃O, (I), and 3‐tert‐butyl‐7‐(4‐methylbenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₇N₃O, (II), are isomorphous in the space group P2₁, and molecules are linked into chains by C—H...O hydrogen bonds. In each of 3‐tert‐butyl‐7‐(4‐methoxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₇N₃O₂, (III), which has cell dimensions rather similar to those of (I) and (II), also in P2₁, and 3‐tert‐butyl‐1‐phenyl‐7‐[4‐(trifluoromethyl)benzyl]‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₄F₃N₃O, (IV), there are no direction‐specific interactions between the molecules. In 3‐tert‐butyl‐7‐(4‐nitrobenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₂H₂₄N₄O₃, (V), a combination of C—H...O and C—H...N hydrogen bonds links the molecules into complex sheets. There are no direction‐specific interactions between the molecules of 3‐tert‐butyl‐7‐(2,3‐dimethoxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₄H₂₉N₃O₃, (VI), but a three‐dimensional framework is formed in 3‐tert‐butyl‐7‐(3,4‐methylenedioxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₅N₃O₃, (VII), by a combination of C—H...O, C—H...N and C—H...π(arene) hydrogen bonds, while a combination of C—H...O and C—H...π(arene) hydrogen bonds links the molecules of 3‐tert‐butyl‐1‐phenyl‐7‐(3,4,5‐trimethoxybenzyl)‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₅H₃₁N₃O₄, (VIII), into complex sheets. In each compound, the oxazine ring adopts a half‐chair conformation, while the orientations of the pendent phenyl and tert‐butyl substituents relative to the pyrazolo[3,4‐d]oxazine unit are all very similar.     

Azinoiminophosphorane mediated 4H,8H‐1,2,4‐triazolo[1,5‐C]‐[1,3]oxazepin‐4‐ones and 5,6‐dihydro‐7H, 12H‐naphtho[2,1‐f]‐[1,2,4]triazolo[1,5‐c][1,3]oxazepin‐7‐ones synthesis

The aza‐Wittig reactions of benzaldehyde‐, acetophenone‐ and benzophenone 1‐[(triphenylphosphor‐anylidene)amino]ethylidenehydrazones ( 1 ) with 2,3‐furandiones 6 provide a new route to 4H,8H‐1,2,4‐triazolo[1,5‐c][1,3]oxazepin‐4‐ones 14 or 5,6‐dihydro‐7H,12H‐naphtho[2,1‐f|[1,2,4]triazolo[1,5‐c]‐[1,3]oxazepin‐7‐ones 17 via the thermal reaction of the expected azinoimine vinylogous lactones.     

Synthesis of 1,3,3a,5‐tetraaryl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a] [1,5]benzodiazepines

A series of 3a,5‐diaryl‐1,3‐diphenyl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a][1,5]benzo‐diazepines was synthesized by the cycloaddition reactions of 2,4‐diaryl‐2,3‐dihydro‐1H‐1,5‐benzo‐diazepines and N‐phenylbenzonitrileimine generated from N‐phenylbenzenecarbohydrazonic chloride in the presence of triethylamine in anhydrous tetrahydrofuran. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:557–559, 2001     

Regioselectivity of cyclization of 1-(6-methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)-4-arylthiosemicarbazides by treating with methyl iodide and dicyclohexylcarbodiimide

1-(6-Methyl-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl)-4-arylthiosemicarbazides treated with methyl iodide in the presence of sodium acetate in ethanol convert into 6-methyl-3-arylamino[1,2,4]-triazolo[4,3-b][1,2,4]triazin-7(1H)-ones. In reaction with dicyclohexylcarbodiimide 6-methyl-3-arylamino[1,2,4]triazolo[3,4-c][1,2,4]triazin-5(1H)-ones were obtained which at heating in alcohol solution in the presence of sodium acetate or at 262–272°C underwent the Dimroth rearrangement to give 3-methyl-7-arylamino[1,2,4]triazolo[5,1-c][1,2,4]-triazin-4(8H)-ones.     

Formylation of 4,7‐Dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines Using Vilsmeier–Haack Conditions

Formylation of 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine 1a using Vilsmeier–Haack conditions yields 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidin‐6‐ylcarbaldehyde 3a . 5,7‐Diaryl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines 1b , 1c in this reaction apart from formylation undergo recyclization into 5‐aryl‐1,2,4‐triazolo[1,5‐a]pyrimidin‐6‐ylmethane derivatives 4b , 4c , 5b , 5c , and 6 . The structure of the synthesized compounds was determined on the basis of NMR, IR, and MS spectroscopic data and confirmed by the X‐ray analysis of the 6‐(ethoxy‐phenyl‐methyl)‐5‐phenyl‐[1,2,4]triazolo[1,5‐a]pyrimidine 6 , 5‐phenyl‐6‐(1‐phenyl‐vinyl)‐[1,2,4]triazolo[1,5‐a]pyrimidine 11 , and 7‐phenyl‐6‐(1‐phenyl‐vinyl)‐[1,2,4]triazolo[4,3‐a]pyrimidine 12 .     

Conversion of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones to 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones: synthesis,spectroscopic characterization and the structures of four products and one ring‐opened derivative

An efficient synthesis of 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones, involving the diazotization of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones in weakly acidic solution, has been developed and the spectroscopic characterization and crystal structures of four examples are reported. The molecules of 1‐phenylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₉N₃O₂, (I), are linked into sheets by a combination of C—H…N and C—H…O hydrogen bonds, while the structures of 1‐(2‐methylphenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₆H₁₁N₃O₂, (II), and 1‐(3‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₈ClN₃O₂, (III), each contain just one hydrogen bond which links the molecules into simple chains, which are further linked into sheets by π‐stacking interactions in (II) but not in (III). In the structure of 1‐(4‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, (IV), isomeric with (III), a combination of C—H…O and C—H…π(arene) hydrogen bonds links the molecules into sheets. When compound (II) was exposed to a strong acid in methanol, quantitative conversion occurred to give the ring‐opened transesterification product methyl 2‐[4‐hydroxy‐1‐(2‐methylphenyl)‐1H‐1,2,3‐triazol‐5‐yl]benzoate, C₁₇H₁₅N₃O₃, (V), where the molecules are linked by paired O—H…O hydrogen bonds to form centrosymmetric dimers.     

Synthesis of 4‐(1‐phenyl‐1H‐pyrazol‐3‐yl)‐[1,2,4]triazolo[4,3‐a]quinoxalines and their 4‐halogenopyrazolyl analogs

Synthesis of {3‐[1‐(ethoxycarbonyl)‐[1,2,4]triazolo[4,3‐a]quinoxalin‐4‐yl]‐1‐phenyl‐1H‐pyrazol‐5‐yl}methyl ethyl oxalate ( 2 ), ethyl 4‐[5‐(acetoxymethyl)‐1‐phenyl‐1H‐pyrazol‐3‐yl]‐[1,2,4]triazolo[4,3‐a]quioxaline‐1‐carboxylate ( 4 ), [4‐halo‐1‐phenyl‐3‐(1‐phenyl‐[1,2,4]triazolo[4,3‐a]quioxalin‐4‐yl)‐1H‐pyrazol‐5‐yl]methyl acetate ( 11 ), {4‐halo‐3‐[1‐methyl‐[1,2,4]triazolo[4,3‐a]quinoxalin‐4‐yl]‐1‐phenyl‐1H‐pyraz‐ol‐5‐yl}methyl acetate ( 13 ), and [3‐([1,2,4]triazolo‐[4,3‐a]quinoxalin‐4‐yl)‐4‐halo‐1‐phenyl‐1H‐pyrazol‐5‐yl] methyl formate ( 15 ) was accomplished. The structural investigation of the new compounds is based on chemical and spectroscopic evidences. J. Heterocyclic Chem., (2011)     

Synthesis of Thienotriazolopyrimidine Derivatives Containing Triazolothiadiazole Moiety

A series of diheterocyclic compounds 15 and 16 was synthesized by the introduction of 6‐aryl or 6‐benzyl‐1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazole moiety to thieno[1,2,4]triazolo[4,3‐c]pyrimidine ring through a sulfur linkage.