Simplified Approach to the Regiospecific Synthesis of Trichloromethylpyrazolines Using Microwave Irradiation

Abstract

Twelve novel 3-alkyl[aryl]-1-carboxamides-5-trichloromethyl-5-hydroxy-4,5-dihydro-lH-pyrazole have been synthesized in good yields (72–90%) using environmentally benign microwave-induced techniques. The compounds were synthesized from the cyclocondensation of 4-alkoxy-1,1,1-trichloro-3-alkyl[aryl]-2-ones [Cl₃CC(O)C(R²) = C(R¹)OR, where R = Me, Et; R¹ = H, Me, Et, Pr, i-Pr, i-Bu, t-Bu, Ph, Ph-4-NO₂, Ph-4-F, Ph-4-Cl, Ph-4-Br; and R² = H, Me] with semicarbazide hydrochloride in the presence of pyridine and using methanol/water (3:1 v/v) as the solvent. The advantages of using microwave irradiation, rather than a conventional method, were demonstrated.

Keywords:

• Biological activity
• enones
• microwave irradiation
• pyrazoles
• trichloromethyl compounds

ACKNOWLEDGMENTS

The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Contract Nos. 46.0804/00–6 and 480067/01-5), Fundação de Amparo à pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for financial support and fellowships. Also, the authors thank E. M. D. Flores (Departamento de Química, Universidade Federal de Santa Maria) for the providing the microwave equipment ETHOS 1 (Milestone Inc.) for the compound synthesis.

Notes

^a Yields of isolated products.

^b Reaction conditions: methanol/water (3:1 v/v), pyridine, 70 °C, MW, 100 W, 2.2 bar.

^c Reaction conditions: methanol/water (3:1 v/v), 30–85 °C (2a–b, 2h–i, 2l; see Ref. 22).