Regiospecific synthesis of new non-condensed heteropolycyclic systems from beta-heteroaryl-beta-methoxyvinyl trihalomethyl ketones

Abstract

isonicotinoil-hidrazinas (heteroarilhidrazidas), realizadas sob condições brandas e em meio alcoólico, forneceram em passo reacional único e regioespecificamente, uma série inédita composta por doze heteroaroil-2-pirazolinas trialometil heteroaril substituídas em rendimentos de 50-78%; um novo sistema heteropolicíclico não condensado.A novel series of twelve heteroaroyl-2-pyrazolines trihalomethyl and substituted heteroaryl, as non-condensed heteropolycyclic systems, have been synthesized in one-step in 50-78% yield from the regiospecific cyclocondensation reaction of 1,1,1-trifluoro(chloro)-4-methoxy-4-(2-furyl)-and 4-(2-thienyl)-3-buten-2-ones (β-alkoxyvinyl trihalometil ketones) with furoic hydrazide, 2-thiophenecarboxylic hydrazide and isonicotinic acid hydrazide (heteroaroylhydrazines) under mild conditions in methanol as solvent.Keywords: 2-pyrazolines, pyrazoles, 4-alkoxy-1,1,1-trihalo-alk-3-en-2-ones, hydrazides, heteroaroylhydrazines, hydrazines IntroductionAlthough many methods have been published for the synthesis of 1H-pyrazoles and their derivatives, attempts to perform the synthesis of a simple 4,5-dihydro-1H-pyrazoles (2-pyrazolines), has not yet been sucessfully achieved.1-3 By conventional procedure, pyrazoles have been obtained by directly reacting β-diketones with hydrazine.1 However, in most cases, 5-hydroxy-4,5-dihydro-1H-pyrazoles have been obtained when the N-1 atom is substituted with a strong electron-withdrawing group which stabilizes the -OH group and possibly hinders the elimination of the water molecule and the subsequent aromatization of the pyrazoline ring. 1Regarding pharmacological applications, 2-pyrazolines (4,5-dihydro-1H-pyrazoles) have been found to possess antitumor, 4 antibacterial, antifungal, antiviral, antiparasitic, antitubercular and insecticidal and others properties. [5][6][7][8][9][10][11][12][13][14][15][16] Some of these compounds also presented anti-inflammatory, anti-diabetic, anesthetic and analgesic properties. [13][14][15] For example, in a recent work Mamolo et al. 16 have synthesized a series of 5-aryl-1-isonicotinoyl-3-(pyridin-2-yl)-4,5-dihydro-1H-pyrazoles in a three-step in low yields, which involved an aldol condensation, cyclocondensation with hydrazine and N-acylation with isonicotinoyl chloride. These 2-pyrazolines showed an interesting antimycobacterial activity in vitro.In 2002, our research group reported 17 a new approach for the synthesis of a series of four ketones as 1,1,1-trifluoro(chloro)-4-methoxy-4-(2-furyl)-and 4-(2-thienyl)-3-buten-2-ones and their 4,4,4-trihalo-1-(2-heteroaryl)-1,3-butanediones derivatives. The autors also showed that mixtures of β-alkoxyvinyl trifluoromethyl ketones and the respective 1,3-butanediones derived from 2-acetylthiophene and 2-acetylfuran react with hydroxylamine hydrochloride, dry hydrazine and thiosemicarbazide hydrochloride leading to 3-(2-thienyl)-and 3-(2-furyl)azoles 869 Regiospecific Synthesis of New Non-Condensed Heteropolycyclic Systems Vol. 16, No. 4, 2005 derivatives. In this case, only one ...

Pyrazoline as a medicinal scaffold

“…Derivatives of the pyrazolopyrimidine ring system are known to possess potent biological properties 23 Out of these many natural and synthetic products having heterocyclic rings as Derivatives of the pyrazolopyrimidine ring system are known to possess potent biological properties 24 .Also condensed pyrazoles are biologically active and their chemistry has received considerable attention as pyrano [2,3-c]pyrazoles are reported to have useful biological effects, such as analgesic and anti-inflammatory activities 25 .In recent years significant progress has been made relating to oxidation in biological cells resulted from reactive oxygen species (ROS) and initiates lipid peroxidation in healthy cells leading to Alzheimer's disease, atherosclerosis, diabetes, Parkinson's disease, etc. Among plant kingdom and animal kingdom coumarins, Xanthones pyrazoles and acrylonitriles showed widespread use in medicine 26 .Synthetically, several methods have been published for the synthesis of 2-pyrazolines for the treatment of tumor, fungal and viral infection, Tuberculosis and depression, etc 27 .…”

Synthesis and in vitro antimycobacterial activity of 3-substituted 5-hydroxy-5-trifluoro[chloro]methyl-4,5-dihydro-1H-1-(isonicotinoyl) pyrazoles

“…The 1-isonicotinoyl-3-alkyl(aryl/heteroaryl)-5-trihalomethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles (2a-i) were prepared from the reaction of 4-alkyl(aryl/heteroaryl)-1,1,1-trihalo-4-alkoxy-3-alken-2-ones with isonicotinic acid hydrazide, according to our previous publications [35][36][37] (Scheme 1). Compounds 2a-d were prepared according to reference [35], compounds 2e, 2f, 2h and 2i were prepared according to reference [36] and compound 2g was prepared according to reference [37,38].…”

“…Compounds 2a-d were prepared according to reference [35], compounds 2e, 2f, 2h and 2i were prepared according to reference [36] and compound 2g was prepared according to reference [37,38]. Compounds 2a-i were fully characterised by spectroscopic methods and gave satisfactory analytical and spectral data.…”

“…The 1-isonicotinoyl-3-alkyl(aryl/heteroaryl)-5-trihalomethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles 2a-d [35], 2e, 2f, 2h and 2i [36] and 2g [37] were prepared from the reaction of 4-alkyl(aryl/heteroaryl)-1,1,1-trihalo-4-alkoxy-3-alken-2-ones with isonicotinic acid hydrazide, according to our previous publications (Fig. 1).…”

Synthesis and Characterization of 1,3,5-Trisubstituted Pyrazoline Derivatives by Ultrasonic Irradiation Method and Evaluation of its Antibacterial Activity

“…A large number of organic reactions can be carried out in a higher yield shorter reaction time and milder conditions under ultrasound 9 . Pyrazoles and their derivatives are widely used as pharmaceutical [10][11][12] and agrochemical agents 13 and consequently a large number of synthetic routes to pyrazoles has been reported [14][15][16][17][18] In view of these observations and in continuation of our research programme on the synthesis of five-membered heterocyclic compounds, we report herein the synthesis of some pyrazoline derivatives from substituted chalcone using ultrasonic irradiation , which have been found to possess an interesting profile of antimicrobial activity. …”