Synthesis of arylamino-substituted pyrazolo[3,4-d][1,2,4]triazolo[4,3-a]pyrimidinones,pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidinones,and their thermal isomerization

The reaction of 1-(4-oxo-1-R-5H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-arylthiosemicarbazides with methyl iodide gave rise to 1,2,4-triazolo-pyrazolopyrimidinones of linear structure, and with dicyclohexylcarbodiimide the products had angular and linear structure. The heating of compounds obtained higher than their melting point resulted in their isomerization into 7-aryl-amino-1-R-1,8-dihydro-4H-pyrazolo[3,4-d]-[1,2,4]triazolo[1,5-a]pyrimidin-4-ones.     

Structural Elucidation and Antimicrobial Evaluation of Novel [1,2,4]Triazolo[4,3‐a]pyrimidines and Pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinones

1,3‐Di(thiophen‐2‐yl)prop‐2‐en‐1‐one ( 1 ) was utilized in the synthesis of 4,6‐di(thiophen‐2‐yl)‐3,4‐dihydropyrimidine‐2(1H)‐thione ( 2 ) and 5,7‐di(thiophen‐2‐yl)‐2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐one ( 4 ). The latter thiones were used in the synthesis of two new series of [1,2,4]triazolo[4,3‐a]pyrimidines 10a – i and pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinones 5a – i via reaction with the appropriate hydrazonoyl halides using triethylamine as a basic catalyst in dioxane. The mechanism of formation of the synthesized compounds was discussed, and the assigned structure was established via microanalysis, spectral data (infrared, ¹H NMR, and Mass), and density functional calculations. Moreover, the newly synthesized products were evaluated for their antimicrobial activities, and the results show that some derivatives have been well with mild activities. Finally, quantum chemistry calculations confirmed the mechanism and structure of the products.     

Synthesis of new 1‐phenylthieno[1,2,4]triazolo[4,3‐a]pyrimidin‐5(4H)‐one derivatives

A series of novel 1‐phenylthieno[1,2,4]triazolo[4,3‐a]pyrimidin‐5(4H)‐one derivatives 5 and 6 were synthesized by oxidative cyclization of thienopyrimidinonyl hydrazones using iodobenzene diacetate. J. Heterocyclic Chem., (2011).     

New 1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidine derivatives II

The 7‐chloro‐3‐(2‐chlorobenzyl)‐ and 7‐chloro‐3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐d]pyrimidines ( 1 and 4 ), by nucleophilic replacement with some hydrazides, gave the corresponding 7‐hydrazidoderivatives ( 2a‐e and 5a‐e ). These, by heating in Dowtherm, underwent an intramolecular cyclization to form the new tricyclic 7‐substituted‐3‐(2‐chlorobenzyl)‐ and 3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidines ( 3a‐d and 6a‐d ). The 7‐hydrazino‐3‐(2‐chlorobenzyl)‐ and 7‐hydrazino‐3‐(2‐fluorobenzyl)‐triazolo‐pyrimidines ( 9a and 9b ) were also prepared via the corresponding mercapto ( 7a and 7b ) and thiomethyl ( 8a and 8b ) derivatives.     

Regioselective synthesis and characterization of new 3‐aryl‐7‐trifluoromethyl‐[1,2,4]triazolo[4,3–a]pyrimidines

The regioselective synthesis and characterization of a new series of 3‐aryl‐7‐trifluoromethyl[1,2,4]triazolo[4,3–a]pyrimidines from the oxidative heterocyclization of 2‐(N′‐benzylidenehydrazino)‐4‐trifluoromethylpyrimidines with copper dichloride is described. J. Heterocyclic Chem., (2011).     

Studies on uracils: A facile one‐pot synthesis of pyrazolo[3,4‐d]pyrimidines

The reaction of 6‐hydrazino uracils 1 and nitrones 2 result in an efficient one‐pot synthesis of pyrazolo[3,4‐d]pyrimidines 3 in excellent yields. The isolation of the by‐product aniline from the reaction mixture supported the plausible mechanism for the formation of pyrazolo[3,4‐d]pyrimidines.     

Synthesis and antifungal activity of novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b][1,2,4]triazepines

5‐Aryl‐3,4‐diamino‐1,2,4‐triazoles 5 on treatment with β‐chlorocinnamaldehydes 7 in the presence of catalytic amount of p‐TsOH and N,N‐dimethylformamide as an energy transfer medium under microwave irradiation and as solvent with oil‐bath heating at 80 °C affords novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b]‐1,2,4]triazepines 8 . The structures of the synthesized compounds were established on the basis of ¹H NMR, IR, mass spectral data and elemental analysis.     

Synthesis and antimicrobial activity of new functionalized derivatives of [1,2,4]triazolo[4,3‐a]pyrimidin‐5(1H)‐one

New functionalized 1,7‐diaryl‐6‐cyano‐1,2,4‐triazolo[4,3‐a]pyrimidin‐5(1H)‐one derivatives ( 5a–j ) were synthesized via reaction of 5‐cyano‐6‐phenyl‐2‐thiouracil 1 with the respective hydrazonoyl halides 2a–j and their biological activity was evaluated. The mechanism and the regioselectivity of the studied reactions are discussed. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:393–398, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20311     

Facile one‐pot synthesis of [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines and 3,7‐dimethyl‐4H‐[1,2,4]triazino[3,4‐b][1,3,4]thiadiazin‐6‐one using heteropolyacid catalysts

[1,2,4]Triazolo[3,4‐b][1,3,4]thiadiazines 2a , 2b , 2c , 2d , 2e , 2f and 3,7‐dimethyl‐4H‐[1,2,4]triazino[3,4‐b][1,3,4]thiadiazin‐6‐one 4 were synthesized by one‐pot cyclocondensation reaction with α‐chloroacetonitrile and α‐haloketones in the presence of catalytic amounts of heteropolyacids in very high yields and rates. J. Heterocyclic Chem., (2011).     

Differentiation between [1,2,4]triazolo[1,5‐a] pyrimidine and [1,2,4]triazolo[4,3‐a]‐ pyrimidine regioisomers by 1H?15N HMBC experiments

The condensation of malonoaldehyde derivatives with either a 3‐amino‐[1,2,4]‐triazole or a 3,5‐diamino‐[1,2,4]‐triazole precursor was studied. In agreement with previous reports, two different bicycles, namely, bearing the regioisomeric [1,2,4]triazolo[1,5‐a]pyrimidine ( 1 ) or[1,2,4] triazolo [4,3‐a]pyrimidine ( 2 ) structural surrogates, could be obtained. We found that, depending on the triazole precursor, only one regioisomer resulted, either of the 1 or 2 series. We also observed that these two structural surrogates could be unambiguously differentiated by indirectly measuring their ¹⁵N chemical shifts by ¹H? ¹⁵N HMBC experiments. The occasional conversion of [1,2,4]triazolo[4,3‐a]pyrimidines to the [1,2,4]triazolo[1,5‐a]pyrimidine counterparts could be unequivocally determined by ¹⁵N NMR data. Copyright © 2010 John Wiley & Sons, Ltd.     

Catalyst‐free one‐pot regioselective synthesis of benzo[d]imidazo[2,1‐b]thiazoles by heating or grinding

Eco‐friendly, efficient, and simple one‐pot catalyst‐free new procedures have been reported for the synthesis of benzo[d]imidazo[2,1‐b]thiazoles by condensation of phenylglyoxal, cyclic enolizable carbonyl compounds, and 2‐aminobenzothiazole at 80°C or by grinding the components at room temperature in glycerol. Cyclic enolizable carbonyl compounds employed in the protocol include dimedone, cyclohexa‐1,3‐dione, cyclopenta‐1,3‐dione, 5‐methylcyclohexa‐1,3‐dione, and 4‐hydroxy‐6‐methyl‐2‐pyrone. All the reactions were complete in ~30 min. The structures of all the products were confirmed by spectral data. The structures of compounds IVl and IVe have also been confirmed by X‐ray crystallographic studies. This protocol offers advantages such as short reaction time, easy workup, high yields and an environmentally benign methodology.     

A facile one‐pot synthesis of novel substituted 1,2,3,4‐tetrahydropyrimidines

A facile one‐pot synthesis of 5‐benzoyl‐6‐methylthio‐1,2,3,4‐tetrahydropyrimidines in good yields is reported.     

Stereoselective synthesis of pyrano[3,2‐c]‐ and furano[3,2‐c]quinolines: Gadolinium chloride catalyzed one‐pot aza–Diels–Alder reactions

A simple and efficient method for the cis‐selective synthesis of pyrano‐ and furano[3,2‐c]quinolines via gadolinium chloride catalyzed one‐pot aza–Diels–Alder reaction is described. Solvent conditions played a major role in affecting the diastereoselectivity of the products. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:351–354, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20612     

Synthesis of New Pyrimido[4,5‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine Derivatives via S/N Smiles Rearrangement

Several new pyrimido[4,5‐e ][1,2,4]triazolo[3,4‐b ][1,3,4]thiadiazine derivatives ( 5a , 5b , 5c , 5d , 5e , 5f , 5g ) were synthesized through the condensation reaction of 5‐bromo‐4,6‐dichloropyrimidine ( 1 ) and 4‐amino‐5‐methyl‐4H‐1,2,4‐triazole‐3‐thiol ( 2 ). The single crystal X‐ray data of one of the derivatives confirmed the occurrence of the S/N type Smiles rearrangement during the course of the reaction.     

Organoiodine(III)‐mediated efficient synthesis of new 3,9‐diaryl‐bis‐1,2,4‐triazolo[4,3‐a][4,3‐c]pyrimidines

Oxidation of bis‐2,4‐pyrimidinylhydrazones of various araldehydes with two equivalents of iodobenzene diacetate in dichloromethane provides an efficient and easy method for the synthesis of eight new 3,9‐diaryl‐bis‐1,2,4‐triazolo[4,3‐a][4,3‐c]pyrimidines. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:653–655, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20250     

Synthesis and reactivity of cyanomethyl 2‐amino‐4‐methylthiazolyl ketone. A facile synthesis of novel pyrazolo[5,1‐c]1,2,4‐triazine, 1,2,4‐triazolo[5,1‐c]1,2,4‐triazine, 1,2,4‐triazino[4,3‐a]benzimidazole,pyridazine‐6‐imine and 6‐oxopyridazinone derivatives

The novel and versatile cyanomethyl 2‐amino‐4‐methylthiazolyl ketone (5) was prepared by treatment of bromomethyl 2‐amino‐4‐methyl thiazolyl ketone (4) with potassium cyanide. Reaction of 5 with heterocyclic diazonium salts 6a,b and 10 afforded the corresponding hydrazones 7a,b and 11, respectively. Refluxing of the hydrazones in pyridine afforded the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine, 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine, and 1,2,4‐triazolo[4,3‐a]benzimidazole derivatives 8a,b and 12, respectively, via intramolecular cyclization. Compound 5 coupled also with benzenediazonium chloride to afford the corresponding hydrazone 14, which is an excellent precursor for the synthesis of pyridazine‐6‐imine 17a and pyridazinone 17b. The pyridazine derivatives 17a,b were also prepared by an independent route, that is, the condensation with malononitriles and coupling with benzenediazonium chloride, followed by intramolecular cyclization. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 385–390, 1999     

Novel synthesis of 2‐amino[1,4,5]benzoxadiazepine derivatives via a mild one‐pot reaction

The diazonium salt of 2‐aminophenol 2 was coupled in situ with malononitrile derivatives 3a‐d , 2‐cyanomethylthiazolin‐4‐one 9 , 2‐cyanomethylbenzimidazole 11a , and 2‐cyanomethylbenzothiazole 11b to give 2‐amino[1,4,5]benzoxadiazepine derivatives 6a‐d, 10 and 12a,b via a one‐pot reaction.     

Synthesis of 1,2,4‐triazolo[1,5‐d]‐1,2,4‐triazine‐5‐thiones

In an attempt to discover bicyclic compounds containing the 1,2,4‐triazine moiety, 1,2,4‐triazolo[1,5‐d]‐1,2,4‐triazine‐5‐thiones from one pot reaction of arylnitriles with 4‐amino‐1,2,4‐triazine‐3‐thione‐5‐one in the presence of potassium tert‐butoxide were synthesized.