Reaction of 1-substituted 3,5-diamino-1,2,4-triazoles with β-keto esters: synthesis and new rearrangement of mesoionic 3-amino-2H-[1,2,4]triazolo-[4,3-a]pyrimidin-5-ones

Reaction of 3,5-diamino-1-R-1,2,4-triazoles (R=Ph, Bn) with β-keto esters results in the reversible formation of N-(5-amino-1-R-1,2,4-triazol-3-yl)-substituted enaminoesters (8). Subsequent transformations depended on the reaction conditions. Compounds 8 undergo intermolecular reactions of condensation and amidation in the absence of solvent. However, in the presence of acetic acid they form 3-amino-5-oxo-2-R-2,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidin-4-ium-8-ides (10) followed by rearrangement to 3-amino-1-R-[1,2,4]triazolo[4,3-a]pyrimidin-5-ones (11). The transformation of 10 into 11 represents a new type of rearrangement in the azolopyrimidine series. Heating of enaminoesters 8 in ethanol with sodium ethoxide present, proved to be a suitable method for the preparation of the mesoionic compounds 10.     

The preparation of optically active α-amino 4H-[1,2,4]oxadiazol-5-ones from optically active α-amino acids

Optically active α-amino 4H-[1,2,4]oxadiazol-5-ones (oxadiazolones) were prepared from optically active α-amino acids in five synthetic steps. The oxadiazolone moiety serves as a bioisosteric replacement for the carboxylic acid. Incorporation of an α-amino oxadiazolone into a representative dipeptide mimic is described.     

Diversity-oriented synthesis of 1,2,3,5-tetrahydrobenzo[e][1,2,4]oxadiazepines and 2,3-dihydro-1H-benzo[e][1,2,4]triazepines by base-induced [4 + 3] annulation reactions

The base-induced formal [4 + 3] annulation reactions of N-(ortho-chloromethyl)aryl amides with nitrones or hydrazonoyl chlorides have been reported. When nitrones are used as the 1,3-dipole, the corresponding reaction afforded a series of 1,2,3,5-tetrahydrobenzo[e][1,2,4]oxadiazepine derivatives. Highly functionalized 2,3-dihydro-1H-benzo[e][1,2,4]triazepine derivatives were also synthesized via an unprecedented tandem aza-Michael addition/rearrangement aromatization between N-(ortho-chloromethyl)aryl amides and hydrazonoyl chlorides.     

Synthesis of new pyrido[2′,3′:3,4]pyrazolo[5,1-c]-[1,2,4]triazin-4(6H)-one derivatives

Russian Chemical Bulletin - New pyrido[2′,3′:3,4]pyrazolo[5,1-c][1,2,4]triazin-4(6H)-one derivatives were synthesized from accessible 1,2,4-triazine and pyrazolo[5,1-c][1,2,4]triazine...     

Synthesis of 4-substituted 3-oxabicyclo[3.1.0]hexan-2-one

Cyclopropanedicarboxylic acid anhydride can be converted to 4-substituted 3-oxabicyclo-[3.1.0]hexan-2-one by reaction with Grignard reagents in ether or tetrahydrofuran solution.     

Synthesis of 4-aryl-5,5-dimethyl-5H-1,2,3-triazoles and 4-aryl-3-cyano-5,5-dimethyl Δ-pyrazolines by cycloaddition of 2-diazopropane with iminoethers and propenenitriles

A regiospecific 1,3-dipolar cycloaddition of 2-diazopropane 3 to iminoethers 1a-c, carried out at 0 °C, afforded in two steps the corresponding 4-aryl-5,5-dimethyl-5H-1,2,3-triazoles 5a-c. Under the same conditions, 3-arylpropenenitriles 2a-d led to 3-cyano-5,5-dimethyl Δ¹-pyrazolines 6a-d. Products 4-6 were obtained in good yields (69-85%).     

Synthesis of pyrido[3′,2′:4,5]thieno[2,3-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one derivatives

Some new pyrido[3′,2′:4,5]thieno[2,3-e]-[1,2,4]triazolo[4,3-a] pyrimidin-5(4H)-ones were prepared through heterocyclization of ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate with phenyl or ethyl isothiocyanate followed by nucleophilic displacement with hydrazine, and finally cyclocondensation with orthoesters. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

A tandem hetero Diels–Alder/Mannich approach for the synthesis of a versatile hexahydro-2H-pyrano[3,2-c]pyridin-4(3H)-one core

The synthesis of a highly functionalizable hexahydro-2H-pyrano[3,2-c]pyridin-4(3H)-one core is described and sequentially involves a hetero-Diels Alder (HDA) reaction and an intramolecular Mannich reaction resulting in selective formation of the trans-fused ring geometry.     

3H-Pyrroles as a platform for the catalyst-free construction of dihydropyrrolo[2,1-b]oxazoles: [4 + 2]-cycloaddition vs [2 + 3]-annulation with 1-cyano-3-hydroxyalkynes

Non-aromatic pyrrole isomers, 3,3-dialkyl-2-aryl-3H-pyrroles, were reacted with 1-cyano-3-hydroxyalkynes under mild, catalyst-free conditions (20–60?°C) to regio- and stereoselectively afford (Z)-2-(dihydropyrrolo[2,1-b]oxazolylidene)acetonitriles in 62–82% yield, thus evidencing the preference for [2?+?3]-annulation over the [4?+?2]-Diels-Alder alternative. The reaction involves initial nucleophilic addition of the pyrrole moiety at the triple bond followed by tandem ring closure of an anionic intermediate.     

Studies on the Cyclisation of 4-[2′-Cyclohexenyl]-3-hydroxy[1]benzopyran-2-one

The bicyclic coumarin derivative-1, 3 propano-2-bromo-1,2-dihydro-3H-pyrano [2, 3-c] [1]benzo-pyran-5-one (8) was synthesised by a sequence of reaction viz. acetylation of 4-[2′-cyclohexenyl] -3-hydroxy [1] benzopyran-2-one (4), addition of bromine to cyclohexenyl double bond and treating the resulting acetyldi-bromo derivative (7) with 4% alcoholic KOH. Benzofuro [2, 3-c] [1] -benzopyran-6-one (10) was synthesised from 4 via oxymercuration with mercuric acetate in methanol followed by dehydrogenative damercuration with Pd-C in refluxing diphenyl ether.     

Synthesis and electrochemical properties of 2,6-bis（6-aryl-[1,2,4]- triazolo[3,4-b][1,3,4]-thiadiazole-3-yl）pyridines

By the condensation of 2,6-bis（4-amino-5-mercapto-[1,2,4]-triazoles-2）pyridine with aromatic acid in the presence of phosphorus oxychloride. Compounds of 2,6-bis（6-aryl-[1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazole-3-yl）pyridines were synthesized. Their structures were confirmed by IR, ^1H NMR spectroscopies and elemental analysis. Their electrochemical behavior and cyclic voltammogram also were be studied. The results showed that they have high ionization potentials and good affinity.     

Total synthesis 2-epi-α-cedren-3-one via a cobalt-catalysed Pauson-Khand reaction

Herein we target the total synthesis of 2-epi-α-cedren-3-one, a natural compound isolated from the essential oil of Juniperus thurifera. Overall, our synthetic sequence presents an optimised and robust series of chemical transformations, with prominent features including a low temperature and highly (Z)-selective Wittig olefination reaction, which is vital for the establishment of the relative stereochemistry within the final natural product, and a microwave-assisted, catalytic, intramolecular Pauson-Khand cyclisation reaction, which is used to construct the intriguing tricyclic core of the target molecule. Our optimum cyclisation protocol utilises only 20?mol% of transition metal, and delivers the complex tricyclic structure in just 10?min. Further manipulations of the annulation product culminate in the first total synthesis of the described natural target.     

Synthesis of 4′-[3-methyl-5-thioxo-1H-1,2,4-triazol-4(5H)-yl]-2′,5′-diphenyl-2′,4′-dihydro spiro[indolin-3,3′[1,2,4]triazol]-2-one derivatives

In this paper 1,3-dipolar cycloaddition reaction has been studied. An efficient synthesis of 4′-[3-methyl-5-thioxo-1H-1,2,4-triazol-4(5H)-yl]-2′,5′-diphenyl-2′,4′-dihydro spiro(indolin-3,3′[1,2,4]triazol)-2-one derivatives using triethylamine in MeCN at room temperature is reported. The structures of the obtained compounds were confirmed by means of elemental analysis, MS and spectral (IR, ¹H, and ¹³C NMR) methods.     

One Pot Synthesis of Some New Spiro[3H-Indol-3,5′(4′H)-[1,2,4] Oxadiazol]-2-Ones and Bis[Spiro[3H-Indol-3,5′(4′H)-[1,2,4] Oxadiazol]-2-Ones]

A facile preparation of the title compound by 1,3-dipolar cycloaddition reaction of benzonitrile oxides with isatin imines or isatin diimines, in excellent yield, are reported.     

Formation of 2-arylindane-1,3-diones and 3-alkylphthalides from methyl o-[α-phenylsulfonyl]toluate

2-Aryl-1,3-indanedione and phthalide derivatives have attracted considerable interest due to their anticoagulant, parasiticidal and a range of biological activities. The synthesis of 2-aryl-1,3-indanedione by the condensation of the title sulfone with aryl aldehydes through an interesting pathway and a previously unreported approach to 3-alkylphthalide from C-alkylated derivatives of 1 under microwave and conventional heating conditions are described.     

Catalyst-free glycerol-mediated green synthesis of 5′-thioxospiro[indoline-3,3′-[1,2,4]triazolidin]-2-ones/spiro[indoline-3,3′-[1,2,4]triazolidine]-2,5′-diones

The development of new catalyst-free green and efficient protocol to access 5′-thioxospiro[indoline-3,3′-[1,2,4]triazolidin]-2-ones/spiro[indoline-3,3′-[1,2,4]triazolidine]-2,5′-diones, potential privileged scaffolds for drug discovery, is disclosed. Key feature of this methodology is the dual use of glycerol—a recyclable, bioorganic compound, as a solvent cum promoter. Other highlights include use of inexpensive reagents, mild reaction conditions, operational simplicity, short reaction time, no need for chromatographic purification, and high yields.     

The synthesis of 5H-thiazolo[2,3-c][1,2,4]triazine derivatives and substituted 3-(2-acylvinylthio)-1,2,4-triazin-5-ones from 6-methyl-3-thioxo-1,2,4-triazin-5-one, 1-acyl-2-bromoacetylenes,and α-acetylenic ketones. X-ray study of 3-benzoyl-6-methyl-5H-thiazolo[2,3-c][1,2,4]triazin-5-one

3-Acyl-6-methyl-5H-thiazolo[2,3-c][1,2,4]triazines were synthesized by reaction of 1-acyl-2-bromoacetylenes with 6-methyl-3-thioxo-1,2,4-triazin-5-one in methanol in the presence of triethylamine at 20 °C. The structure of 3-benzoyl-6-methyl-5H-thiazolo[2,3-c][1,2,4]triazine was established by X-ray structural analysis. Substituted 3-(2-acetylvinylthio)1,2,4-triazin-5-ones were obtained by the reaction of -acetylenic ketones with 6-methyl-3-thioxo-1,2,4-triazin-5-one under the same conditions. The structures of the new compounds were confirmed by IR,¹H, and¹³C NMR spectroscopy.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2971–2975, December, 1996.     

A convenient synthesis of 2-aryl substituted benzo[f] [1,2,4]triazolo[1,5-a]azepine derivatives

A convenient synthetic pathway to 2-aryl-5,6-dihydro-4H-benzo[f][1,2,4]triazolo[1,5-α]azepine derivatives 7 was developed. The synthesis was based on the cycloaddition of the 1,2,3,4-tetrahydronaphthalene a-acetoxy azo compounds 3 with Ar-CN in the presence of AlCl3 and the consecutive ring enlargement.     

Sterically Controlled Regiospecific Cyclization of Aldose-5-ethyl-1,2,4-triazino[5,6- b ]indol-3-ylhydrazones to Linearly Annelated 3-Polyhydroxyalkyl-10-ethyl-1,2,4-triazolo-[4′,3′:2,3]-1,2,4-triazino[5,6- b ]indoles

 Condensation of aldoses with 5-ethyl-3-hydrazino-1,2,4-triazino[5,6-b ]indole gave the corresponding aldose-5-ethyl-1,2,4-triazino[5,6-b ]indol-3-ylhydrazones which were acetylated to their poly-O-acetyl derivatives. The latter underwent sterically controlled regiospecific oxidative cyclization with bromine in acetic acid and sodium acetate to sterically favourable linearly annelated 3-polyacetoxyalkyl-10-ethyl-1,2,4-triazole[4′,3′:2,3]-1,2,4-triazino[5,6-b ]indoles rather than to their sterically unfavourable angularly annelated regioisomers. The regiospecific outcome of this heterocyclization is discussed in terms of electronic as well as steric factors, and the assigned structures have been corroborated on the basis of chemical as well as spectroscopic evidence. De-O-acetylation of the acetoxyindoles with ammonium hydroxide in methanol gave the title compounds. Representative members of the prepared compounds were tested for antimicrobial activity.