Microwave-assisted synthesis of novel 5-trichloromethyl-4,5-dihydro-1H-1-pyrazole methyl esters under solvent free conditions

Abstract

A preparação, com bons rendimentos (70-98%), de doze novos ésteres etílicos de 5-triclorometil-4,5-diidro-1H-1-pirazóis, usando-se ambientalmente boas técnicas induzidas por microondas, é descrita. Estes compostos foram sintetizados a partir da reação de ciclocondensação de 1,1,1-tricloro-4-alcoxi-3-alquen-2-onas [CCl 3 C(O)C(R 2 )=C(R 1 )OR, onde R, R 2 = H, alquila; R 1 = H, alquila e arila] com metil carboxilato hidrazina. As vantagens obtidas pelo uso de irradiações de microondas na ausência de solventes, em relação ao método convencional foram demonstradas.Twelve novel 5-trichloromethyl-4,5-dihydro-1H-1-pyrazole ethyl esters have been synthesized in good yields (70-98%) by using environmentally benign microwave induced techniques. The compounds were synthesized from the cyclocondensation of 1,1,1-trichloro-4-alkoxy-3-alken-2-ones [CCl 3 C(O)C(R 2 )=C(R 1 )OR, where R, R 2 = H, alkyl; R 1 = H, alkyl and aryl] with hydrazine methyl carboxylate. The advantages obtained by the using of microwave irradiation under solvent-free conditions, rather than a conventional method, were demonstrated. Keywords: pyrazoles, enones, microwave irradiations, green chemistry IntroductionTrihalomethyl substituted pyrazoles belong to an important class of compounds, which possess a wide variety of pharmaceutical and agrochemical properties. 1,2 The main synthetic method used to prepare trihalomethylpyrazoles involves a [3+2] cyclization such as the classical 1,3-diketone with hydrazines. 3 In recent years, we have developed a general synthesis of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones, 4,5 important halogen-containing building blocks and their use in heterocyclic preparations (e.g. isoxazoles, pyrazoles, pyrazolium chlorides, pyrrolidines, pyrimidines, thiazines, diazepines, thiazoles, selenazoles, and quinolines) has been extensively described. 5 In particular, trichloromethyl substituted azoles are important as synthons and reagents in organic synthesis. These compounds have also been used as precursors for the synthesis of carbonyl-azole derivatives 6 in a one-pot procedure. Moreover, the pharmaceutical properties of trichloromethyl substituted pyrazolines have been reported by our research group. 7 Recently, we reported the application of microwave irradiation for the synthesis of halomethylsubstituted azoles. 8 The beneficial effects of microwave irradiation are playing an increasing role in process chemistry, especially in cases where classical methods require forcing conditions or prolonged reaction times. When processes involve sensitive reagents, or there is the possibility of compound decomposition under prolonged reactions conditions, microwaves have also shown an advantage. The use of focused microwave irradiation to decrease reaction times and improve yields has been demonstrated. 9 Microwave irradiation (MW), using commercial domestic ovens, has been recently used to accelerate organic reactions, due to its high heating efficiency, giving remarkable rate enhancement and dramatic reduction in reaction times. In recent...

Microwave-assisted synthesis of nitrogen-containing heterocycles

“…Manna et al [59] Martins et al [60] reported the synthesis of novel 4,5-dihydro-1H-pyrazole 107 (12 examples) from cyclocondensation reaction of enones 105 with hydrazine methyl carboxylate 106 under solvent-free conditions (Scheme 30) at 50-55˚C in 6 min with 70-98% yield. Conventional heating gave only moderate yields (70-79%) in 24 h.…”

Irradiação de micro-ondas aplicada à síntese orgânica: uma história de sucesso no Brasil

“…[37][38][39][40][41][42][43] Em seus trabalhos, os pesquisadores também relatam atividade anti-inflamatória e analgésica para os produtos sintetizados. 38,39 Em seus artigos, Martins e colaboradores realizam estudos comparativos entre reações sob aquecimento convencional e sob irradiação de micro-ondas (aparelho doméstico) mostrando que é possível reduzir os tempos de reação sem que haja perda de rendimento, como pode ser observado na Tabela 5.…”

Synergic Effects of Ionic Liquid and Microwave Irradiation in Promoting Trifluoromethylpyrazole Synthesis

“…Recently, we have published a number of works related to the minimization of environmental impacts through the use of ionic liquids [9][10][11] or solvent-free reactions [12,13] Electronic supplementary material The online version of this article (doi:10.1007/s10562-011-0571-9) contains supplementary material, which is available to authorized users. and by using ultrasound [14,15] or MW [12,13] to promote the reactions. Our current review about heterocyclic synthesis in ionic liquid [16] has demonstrated that there is a lack of reports dealing with pyrazole synthesis in this media.…”