An Efficient and Facile Synthesis of 5‐(Thiophene‐2‐carbonyl)‐6‐(trifluoromethyl)‐tetrahydro‐pyrimidin‐2(1H)‐one and 6‐(Thiophen‐2‐yl)‐4,5‐dihydropyrimidin‐2(1H)‐one from Same Substrates Under Different Conditions

Abstract

A series of 5‐(thiophene‐2‐carbonyl)‐6‐(trifluoromethyl)‐tetrahydropyrimidin‐2(1H)‐one and 6‐(thiophen‐2‐yl)‐4,5‐dihydropyrimidin‐2(1H)‐one derivatives have been synthesized from the reactions of aromatic aldehydes, 4,4,4‐trifluoro‐1‐(thien‐2‐yl)butane‐1,3‐dione and urea under the different conditions with high yields. In this research, it was found that the p‐toluenesulfonic acid was an efficient catalyst for obtaining 5‐(thiophene‐2‐carbonyl)‐6‐(trifluoromethyl)‐tetrahydropyrimidin‐2(1H)‐one derivative. At the same time, solvent‐free and NaOH were the preferred conditions for the synthesis of 6‐(thiophen‐2‐yl)‐4,5‐dihydropyrimidin‐2(1H)‐one derivative. Moreover, because of short reaction time, excellent yields, simple setup, this research offered an efficient process for preparing these kind compounds.

Trifluoromethyl‐β‐dicarbonyls as Versatile Synthons in Synthesis of Heterocycles

“…Liang-Ce et al put forward an efficient synthesis of a series of 5-(thiophene-2-carbonyl)-6-(trifluoromethyl)-tetrahydropyrimidin-2(1H)-ones 413 and 6-(thiophen-2-yl)-4,5-dihydropyrimidin-2(1H)-ones 414 in high yields by reacting 1,1,1-trifluoro-4-(thiophen-2-yl)butane-2,4-dione 1 with urea 313 and aryl aldehydes 138 under different reaction conditions (Scheme 142). [240] Xu et al disclosed an environmentally benign, efficient synthesis of 5',6'-dihydro-6'-hydroxy-6'-(trifluoromethyl)-1'Hspiro[indoline-3,4'-pyrimidine]-2,2'(3'H)diones 416 via threecomponent Biginelli reaction of isatins 415, trifluoromethyl-βdiketones 1 and urea 313 using p-TsOH as catalyst under solvent-free conditions (Scheme 143). [241] This solvent-free approach has advantages over the solvent mediated synthesis in terms of low cost, short reaction time, mild reaction conditions and high yields.…”

“…put forward an efficient synthesis of a series of 5‐(thiophene‐2‐carbonyl)‐6‐(trifluoromethyl)‐tetrahydropyrimidin‐2(1 H )‐ones 413 and 6‐(thiophen‐2‐yl)‐4,5‐dihydropyrimidin‐2(1 H )‐ones 414 in high yields by reacting 1,1,1‐trifluoro‐4‐(thiophen‐2‐yl)butane‐2,4‐dione 1 with urea 313 and aryl aldehydes 138 under different reaction conditions (Scheme 142). [240] …”