Synthesis of trifluoromethyl derivatives of pyrazolidine- and 2-pyrazoline-1-carboxamides and pyrazolidine- and 1-pyrazoline-carbothioamides

Abstract

The reactions of enones containing trifluoromethyl groups with semicarbazide in basic media proceed unequivocally to give pyrazolidine-l-carboxamides. The directs'on of the reactions of these enones with thiosemicarbazide depends on their structure; the reaction products are pyrazolidine-and 2-pyrazoline-1-carbothioamides. An enone containing a CF 3 group and an ethoxy group capable of replacement reacts with semicarbazide to give 2-pyrazoline-l-carboxamide and with thiosemicarbazide to give the double addition product, 5-(1-thiosemicarbazido)-2-pyrazoline-l-carbothiamide.Fluoroheterocyclic compounds have been extensively studied [1, 2] in light of their high biological activity [3]. Trifluoromethyl derivatives of enones are convenient and promising starting compounds for the synthesis of heterocycles with a CF 3 group. Methods of synthesis for such enones have been intensively developed in the past decade [4, 5].The reaction of enones with hydrazines is the classical method for the synthesis of pyrazoles and pyrazolines, but this method has not been studied sufficiently relative to enones with a trifluoromethyl group. Only the synthesis of trifluoromethylpyrazolines from fluoroacetylated vinyl ethers (/3-alkoxyvinyltrifluoromethylketones) has been described [6, 7]. We have already studied the reactions of hydrazine, phenylhydrazine, and methylhydrazine with trifluoromethyl-containing enones lacking an alkoxy substituent, and obtained pyrazolines and pyrazolidines with a CF 3 group [8]. A feature of these reactions is formation of stable pyrazolidines containing a gem-aminoalcohol fragment stabilized by the electron-withdrawing effect of the CF 3 group. Dehydration of these pyrazolidines upon heating or maintaining at room temperature leads to the corresponding pyrazolines.Semicarbazide and its derivatives are multifunctional nucleophiles. The reaction of these compounds with enones holds both theoretical and practical interest since the reaction products often display biological activity [9, 10]. Contradictory data have been reported on the structure of the products of the reactions of unsaturated ketones with semicarbazide derivatives. Structures with a five- [11, 12], six-[13], and seven-membered ring [14] have been proposed. The greatest evidence is found for the formation of five-membered heterocycles, namely, pyrazoline-l-carboxamides and pyrazoline-l-carbothiamides based on x-ray diffraction structural analysis [15].The reactions of trifluoromethyl-containing enones with semicarbazide derivatives have not yet been examined. In continuation of a study of the synthesis of trifluoromethylheterocycles, we investigated the reaction of various enones containing a CF 3 group (I-VII) with semicarbazide and thiosemicarbazide under various conditions. We have already shown that enones lacking a trifluoromethyl group react to give heterocyclic derivatives in acid media (upon heating with semicarbazide hydrochloride or thiosemicarbazide hydrochloride in ethanol at reflux) [11, 15] or close-to-neutral media (in the ...

Single step derivatization with CF3 enone of thiophene at ambient temperature to determine propellant grade hydrazines: a study by GC and GC-MS

“…4, m/z À232 by GC-MS for both derivativesshown in Fig. S7 and S8 † respectively for which fragmentation patterns are shown in FP 06 and 07 of the ESI †) are formed [38][39][40] as a result of heterocyclization which is unexpected and not suggested by us in our previous study.…”

“…The formation of pyrazolidines/pyrazolines/pyrazoles by the room temperature (RT) reactivity of the active carbonyl group and double bond at the 3-position of the thiophene moiety {3butenone (E)-1,1,1-triuoro-4-(3-thienyl)}with hydrazines in organic medium is the characteristic one for hydrazines. [35][36][37][38][39][40][41][42] This derivatization reaction is quick and quantitative at RT. The spectrophotometric method reported previously by us 7 is based on the above principle and found to have a much higher sensitivity and supporting evidence for previous ndings.…”

Ionic Liquids: Applications in Heterocyclic Synthesis

“…The reaction was performed at 80°C during 1 h. The yields were higher and the reaction time was shorter in comparison to those found for the conventional method (MeOH, reflux, 16 h, 65-73%). (Scheme 6, i) [Sanin et al, 1998]. Later, we also employed ILs in the synthesis of 4,5-dihydropyrazoles 35 from the cyclocondensation reaction of enones 31 and cyanoacetohydrazide 34.…”

Indolylvinyl Ketones: Building Blocks for the Synthesis of Natural Products and Bioactive Compounds

“…However, a similar reaction with semicarbazide led to the formation of 3-hydroxy-5-(1H-indol-3-yl)-3-(trifluoromethyl)pyrazolidine-1-carboxamide (101) (Scheme 56). 64 3-Aryl-5-(1H-indolyl)pyrazoline-1-carboxamides 102 and 103 were synthesized by treatment of indolylvinyl ketones with an ethanolic solution of hydrazine hydrate and isocyanate (Schemes 57 and 58). 65…”