High speed synthesis of pyrazolones using microwave-assisted neat reaction technology

Abstract

Descrevemos uma síntese rápida e pratica de pirazolonas, na ausência de solvente, sob irradiação de microondas. Esta metodologia sintética envolve a reação de b-cetoésteres com hidrazinas substituídas e não-substituídas e oferece uma preparação simples e direta de diferentes pirazolonas com alta regioseletividade. Essas pirazolonas podem existir em diferentes formas tautoméricas em solução e o anel 2-aril-pirazol-3-ona permanece torcido em relação ao plano da pirazolona no estado cristalino. O mecanismo da reação é proposto levando em conta a regiosseletividade. Uma das pirazolonas obtidas nesse processo foi usada na preparação de um derivado espirociclohexanona de significativo potencial biológico.A high speed, solvent-free, and practical synthesis of pyrazolones under microwave irradiation is described. This greener synthetic methodology involves the reaction of b-keto ester with substituted or unsubstituted hydrazine and provides a simple and straightforward one-pot approach for the synthesis of a variety of pyrazolone derivatives with high regioselectivity. These pyrazolones can exist in different tautomeric forms in solution and the aryl ring of 2-aryl pyrazol-3-ones remain twisted with respect to the pyrazole plane in the crystal state. Mechanism of the reaction accounting the regioselectivity has been proposed. One of the pyrazolones obtained via this process was utilized to prepare a spirocyclohexanone derivative of potential biological significance.

Microwave-assisted synthesis of nitrogen-containing heterocycles

“…Pal et al [63] have also reported the synthesis of a series of pyrazolones 110 (12 examples) from the cyclocondensation reaction of hydrazines 109 with b-ketoesters 108 under solvent-free conditions using MW heating (Scheme 31). Compared to conventional method (in refluxing MeOH for 10 h), MW-assisted reaction completes in 2-4 min in high yield (62-89%).…”

Microwave assisted synthesis of novel pyrazolone derivatives attached to a pyrimidine moiety and evaluation of their anti-inflammatory, analgesic and antipyretic activities

“…The starting materials, 3-methyl-1-substituted-1H-pyrazol-5(4H)-ones (2a-2b), were obtained in high yields as per the method reported (Pal et al, 2008;Kimata et al, 2007) by the treatment of ethyl acetoacetate with 1-phenylhydrazine (1a) or 1-(2,4-dinitrophenyl)hydrazine (1b) using a microwave oven. The 4-acetyl-3-methyl-1-substituted-1H-pyrazol-5(4H)-ones (3a-3b) were prepared by the acylation of (2a-2b) with the corresponding acid chloride following Jensen's procedure (Jensen, 1959).…”

“…General procedure for preparation of 3-methyl-1-(substituted)-1H-pyrazol-5(4H)-one (2a-2b) The 3-methyl-1-(substituted)-1H-pyrazol-5(4H)-one derivatives were prepared as per the reported method and purified by recrystallization from ethanol (Pal et al, 2008;Kimata et al, 2007). …”

“…Edaravone (Pal et al, 2008;Chegaev et al, 2009), (3-methyl-1-phenyl-2-pyrazolin-5-one) is found as a promising drug for brain ischemia (Watanabe et al, 1994), myocardial ischemia (Kawai et al, 1997), treatment of fatal neurodegenerative diseases (Kimata et al, 2007) and cardiovascular diseases (Higashi et al, 2006).…”

Morita–Baylis–Hillman adducts as building blocks of heterocycles: a simple approach to 4-substituted pyrazolones, and mechanism investigation via ESI–MS(/MS)

“…One of the ways by which this functionalization can be achieved is using Mannich or Michael chemistry to introduce the required substituent at position 4 (Scheme 1), but this strategy adds an additional step to the synthesis. Furthermore, dialkylated products can be obtained when Michael addition is used [24][25][26].…”