Strategies for the Efficient Synthesis of Biheterocyclic 5-[2-(Trifluoromethylheteroaryl)-ethyl]-1,3,4-oxadiazoles from Levulinic Acid

Abstract

The synthesis of 5-[2-(trifluoromethylheteroaryl)-ethyl]-1,3,4-oxadiazoles derived from levulinic acid is reported. Cyclocondensations [4 + 1] between four different 5- [2-(trifluoromethylheteroaryl) propionylhydrazides derived from methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate obtained from levulinic acid, and electrophilic orthoesters RC(OR 1 ) 3 (where R = H, Me, Ph) and CS 2 were carried out in a mild medium. Good yields (69-96%) of isolated products were obtained. The structures of the new ethylene-spaced biheterocycles were characterized using 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization coupled to tandem mass spectrometric (ESI MS/MS) data.

Heterocyclizations of β-alkoxy, β-diaminoalkyl, and related β-functionalized enones (enals) with NCN-binucleophiles

“…The known examples included the reaction of 22a with guanidine [67,68], urea [67,69], thiourea [67], isothiourea [70], formamidine [69] acetamidine, and benzamidine [71]. The variability of substituents and heterocyclization conditions of trifluoro-4-alkoxybut-3-en-2-ones 22 for the synthesis of 4-CF3-substituted pyrimidines is summarized in Table 1 [29,[66][67][68][69][72][73][74][75][76][77][78][79].…”

(Het)aryl Difluoromethyl‐Substituted β‐Alkoxyenones: Synthesis and Heterocyclizations

“…In this work, we considered another approach to difluorodi(het)arylmethanes, which also relied on the use of (het)aryl difluoro methyl‐substituted building blocks, namely, β‐alkoxyenones of the type 1 [X = (het)aryl, Scheme ]. It should be noted that heterocyclizations of various fluorinated β‐alkoxyenones 1 (X = H, F, Cl, CF 3 , CHF 2 ) were reported in recent publications descri‐bing synthesis of fluoroalkyl‐substituted pyrazoles, isoxazoles, and pyrimidines,, , as well as other heterocycles , . However, no examples of (het)aryl difluoromethyl ‐substituted enones of the type 1 were reported to date.…”