Stereoselective synthesis of dihydrothiadiazinoazines and dihydrothiadiazinoazoles and their pyrolytic desulfurization ring contraction

Intramolecular base catalyzed C-C bond formation led to exclusive stereoselective syntheses of trans-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, trans-7,8-dihydro-6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-ones, and trans-3,4-dihydro-2H-[1,3,4]thiadiazino[2,3-b]quinazolin-10-one. trans-6,7-Dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines isomerize slowly in CDCl₃ and more rapidly in DMSO-d₆ into the corresponding cis-stereoisomers. The other trans-6,7-dihydro-[1,3,4]thiadiazines isomerize also in DMSO-d₆ into the corresponding cis-stereoisomers. Pyrolytic conversion of these heterocyclic condensed dihydrothiadiazines into their corresponding pyrazolo[5,1-b][1,2,4]triazoles, pyrazolo[5,1-c][1,2,4]triazin-4-ones and pyrazolo[4,3-b]quinazolin-9-ones via desulfurization ring contraction is described.     

Synthesis of 4-Amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones and 8H-3-R-7-Aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones

A study was carried out on the reaction of 4-amino-6-R-2,3,4,5-tetrahydro-3-thioxo-1,2,4-triazin-5-ones with halo ketones in alkaline media to yield 4-amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones, which then convert to 8H-3-R-7-aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones.     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1-b]quinazolin-9-one Derivatives

Summary.  A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives. Received March 22, 2001. Accepted (revised) May 11, 2001     

Partially hydrogenated 2-amino[1,2,4]triazolo[1,5-a]pyrimidines as synthons for the preparation of polycondensed heterocycles: reaction with chlorocarboxylic acid chlorides

Partially hydrogenated 2-amino[1,2,4]triazolo[1,5-a]pyrimidines and 2-amino[1,2,4]triazolo[5,1-b]quinazolines react with the chlorides of chloroacetic, 3-chloropropanoic, and 4-chlorobutanoic acids at 0–5 °C to give amides through acylation of the 2-amino group. Heating the corresponding 3-chloropropanoyl derivatives at 80–90 °C in DMF leads to selective intramolecular alkylation at N-3 to form the chlorides of partially hydrogenated [1,2,4]triazolo[1,5-a:4,3-a′]dipyrimidin-5-ones and pyrimido[2′,1′:3,4][1,2,4]triazolo[5,1-b]quinazolin-12-ones. It may be more convenient to prepare such compounds through one-pot processes. Some reactions of the synthesized chlorides of polycondensed heterocycles have been studied. Conditions have been found to effect the selective synthesis of free bases, oxidative aromatization or hydrolysis of the dihydropyrimidine cycle, and the selective hydrolytic cleavage or elimination of the pyrimidone ring. Some of the resulting compounds represent new mesoionic heterocycles.     

Reaction of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazin-7-ones with Aryl Bromomethyl Ketones and Benzyl Bromide

The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles and 3-phenyl-2-propenoic acid, depending on the structure of R. The reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with benzyl bromide yields 5-aryl-3-benzylthio-4H-1,2,4-triazoles and 3-aryl-2-propenoyl bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 905–909, June, 2005.     

Cascade cyclization reactions of 3,4,5-triamino-1,2,4-triazole with aromatic aldehydes and cycloalkanones

A three-component condensation of 3,4,5-triamino-1,2,4-triazole (1) with aromatic aldehydes 2a–f and dimedone (3) or cyclohexanone (8) afforded partially hydrogenated 9-aryl-[1,2,4]triazolo[5,1-b]quinazolin-8-ones. The structure of 2-amino-6,6-dimethyl-3-(4-nitrobenzylidene)amino-9-(4-nitrophenyl)-5,6,7,9-tetrahydro[1,2,4]triazolo[5,1-b]quinazolin-8-one (4e) was confirmed by X-ray diffraction data. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1178–1182, July, 2006.     

Regioselective alkylation of 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole

Alkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole using different alkylating agents leads regioselectively to 1-N-alkylated products. The hydrolysis-decarboxylation of 1,6-dimethyl-7-ethoxycarbonyl-pyrazolo[5,1-c][1,2,4]triazole yields a compound identical with that obtained by the direct methylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole. The 1-N-alkylation is confirmed by NMR spectroscopy and mass spectrometry.     

Interaction of 7-Chloro-9-methylthio-3-phenylpyrimido[5,4-f][1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine with Some Nucleophiles

The reactions of 7-chloro-9-methylthio-3-phenylpyrimido[5,4-f][1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine (1) with some nucleophiles have been studied. Substitution of the chlorine atom with hydrogen occurs with ammonia in DMSO to give 9-methylthio-3-phenylpyrimido[5,4-f][1,2,4]triazolo[3,4-b][1,3,4]thiadiazepin-7(8H)-one. With a methanolic solution of ammonia the 7-methoxy derivative is formed. Reaction of compound 1 with an excess of sodium methoxide in methanol gave 6,7-dimethoxy-9-methylthio-3-phenyl-5,6-dihydropyrimido[5,4-f][1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine. The corresponding 7-substituted derivatives were obtained when compound 1 was heated with morpholine or 2-(dimethylamino)ethylamine. The azomethine bond of the thiadiazepine ring is reduced by sodium borohydride to give the corresponding 5,6-dihydro derivatives.     

Synthesis of novel dipyrazolo[3,4-b:3,4-d]pyridines and study of their fluorescence behavior

A convenient route was successfully developed for the synthesis of novel heterocycles such as pyrazolo[3,4-h][1,6]naphthyridine and dipyrazolo[3,4-b:3,4-d]pyridine (DPP) from pyrazolo[3,4-b]pyridine in good yield. The DPP derivatives synthesized were further studied for their fluorescence properties.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

Synthesis of trifluoromethyl-promoted functional pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-d][1,2,3,5]tetrazine-4(3H)-ones

Ethyl 5-amino-3-trifluoromethyl-1H-pyrazole-4-carboxylate (1) was efficiently synthesized via the condensation of ethyl cyanoacetate and trifluoroacetic anhydride, followed by chloridization and the condensation with aqueous hydrazine. Its unique reactivity was exploited for the synthesis of trifluoromethylated pyrazolo[1,5-a]pyrimidine (5) and pyrazolo[5,1-d][1,2,3,5]tetrazine-4(3H)-ones (8a-j). Among them, 5 was firstly found to be a novel fluorescent molecule that might be exploited as an attractive fluorophore for possessing many binding sites, and its fluorescence intensity was obviously stronger than its methyl analogue. 8 were found to be a new chemical class of potential monocotyledonous Echinochloa crus-galli L. Beauv inhibitors, and were more active than their methyl analogues.     

Synthesis of pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]pyrimidines

Starting from 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones, a synthesis pathway to the tricyclic pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines is described. Reaction of 1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-ones with phosphoryl chloride afforded the corresponding 4-chloro-1H-pyrazolo[3,4-d]pyrimidines. Treatment of these compounds with hydrazine hydrate at reflux temperature gave the hydrazino derivatives, which were subsequently cyclized to the titled compounds on heating with orthoesters in ethanol. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

Microwave-assisted three component synthesis of novel bis-fused quinazolin-8(4H)-ones linked to aliphatic or aromatic spacer via amide linkages

Abstract

A novel series of bis(tetrahydro[1,2,4]triazolo[5,1-b]quinazolin-8-ones) and bis(tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolinones) containing amide linkages were regionselectively prepared via a three-component reaction of bis(aldehydes) with dimedone and 3-amino-1,2,4-triazole (or 2-aminobenzimidazole) under conventional heating as well as under microwave irradiation.     

Synthesis of 3,5-difunctionalized 1-methyl-1H-pyrazolo[3,4-b]pyridines involving palladium-mediated coupling reactions

Indirect iodination of 2-chloro-nicotinonitrile gave 2-chloro-5-iodonicotinonitrile, which was cyclized with methylhydrazine to lead to 3-amino-5-iodopyrazolo[3,4-b]pyridine. Position 3 was then protected by pivaloyl group and the resulting 5-iodo-3-pivaloylaminopyrazolo[3,4-b]pyridine was engaged in palladium-promoted coupling reactions with various reagents to give 3-pivaloylamino-5-substituted compounds. Deprotection and iododediazoniation followed by cross-coupling reactions in position 3 afforded novel unsymmetrical 3,5-disubstituted pyrazolo[3,4-b]pyridine species.     

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.     

The reaction of 2-(1-hydropolyfluoro-1-alkenyl)-4H-3,1-benzoxin-4-ones with dinucleophilic reagents: a convenient route to fluoroalkylated nitrogen-containing tricyclic compounds

The reactions of 2-(1-hydropolyfluoro-1-alkenyl)-4H-3,1-benzoxin-4-ones (2) with hydrazine hydrate and phenyl hydrazine were investigated. The reaction of 2 with hydrazine hydrate in ethanol under reflux condition readily gave 2-fluoroalkyl-4H-pyrazolo[5,1-b]quinazolin-9-ones (3) in high yields. The reaction of 2 with phenyl hydrazine, however, resulted in the formation of 2-(2-phenyl-5-fluoroalkyl-2H-pyrazol-3-yl) benzoic acids (7). Further treatment of 7 with PPA gave 1-phenyl-4,9-dihydro-3-fluoroalkyl-1H-pyrozolo[3,4-b]quinolin-4-ones (4) in 65-80% overall yields.     

微波促进下3-(2-苯并呋喃基)-4-氨基-5-巯基-1,2,4-三唑

微波辐射条件下, 首先由2-苯并呋喃甲酰肼依次与二硫化碳和水合肼反应合成3-(2-苯并呋喃基)-4-氨基-5-巯基- 1,2,4-三唑, 进一步在微波辐射条件下由4-氨基-5-巯基-1,2,4-三唑分别与芳甲酸/芳氧基乙酸、α-溴代苯乙酮及芳醛反应以较高产率制得了相应的1,2,4-三唑并[3,4-b]-1,3,4-噻二唑、1,2,4-三唑并[3,4-b]-1,3,4-噻二嗪及4-芳亚甲基亚胺基-5-巯基-1,2,4-三唑. 产物结构经IR, ¹H NMR, MS及元素分析进行了表征.     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1- b ]quinazolin-9-one Derivatives

 A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives.     

Convenient synthesis of pyrazolo[3,4-b]pyridin-3-ones and pyrazolo[3,4-b]pyridine-5-carbaldehyde using vinamidinium salts

An expedient method for the synthesis of 2-phenyl-5-aryl-2,3-dihydropyrazolo[3,4-b]pyridin-3-ones and 2-phenyl-3-oxo-2,3-dihydropyrazolo[3,4-b]pyridine-5-carbaldehyde in a single-step via condensation of vinamidinium salts with 3-amino-1-phenyl-2-pyrazolin-5-one is described.     

Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: routes towards condensed thieno[2,3-b]pyridines

Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:3′,2′-e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have been achieved by application of intramolecular 4+2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered with alkene or alkyne terminals.