Silver-Catalyzed Synthesis of CF₃-Substituted 2-Imidazolines

Abstract

The silver salt catalyzed [3＋2] cycloaddition reaction of trifluoromethylated N-acylhydrazones and ethyl isocyanoacetate was investigated. The reaction proceeds quickly to produce a series of trifluoromethylated 2-imidazoline compounds in high yields with excellent stereoselectivity, which provides a novel and efficient method for the synthesis of trifluoromethylated 2-imidazoline compounds.

Tandem Addition/Cyclization/Halogenation Reaction of Difluoromethylated N-Acylhydrazones with Allyltrimethylsilanes

“…Purified by column chromatography (EA/petroleum ether, 1:7, R f = 0.5); colorless oily liquid (81 mg, 85%); 3, 128.8, 122.0, 117.4, 114.7, 110.3 (t, J C−F = 233. 3 Hz),57.8,55.3,33.8,33.8;19 F NMR (376 MHz, CDCl 3 ): δ −118.89 (dd, J = 327.5, 53.8 Hz), −120.37 (dd, J = 327.9, 53.8 Hz); HRMS (ESI): m/z calcd for C 13 H 13 BrF 2 N 2 NaO 2 [M + Na] + 369.0021, found 369.0020.…”

“…NMR experiments were carried out in deuterated chloroform, acetone, or dimethyl sulfoxide (CDCl 3 , CO(CD 3 ) 2 , or DMSO-d 6 ). 1 H NMR, 13 C{ 1 H} NMR, and 19 F NMR spectra were recorded in 400 or 600…”

“…Purified by column chromatography (EA/petroleum ether, 1:8, R f = 0.6); white solid (74 mg, 67%), mp 91−93 °C; 1 H NMR (400 MHz, CDCl 3 ): δ 8.37 (s, 1H), 7.94 (d,J = 8.0 Hz,1H),7.87 (s,3H),2H),6.36 (t,J = 53.6 Hz,1H),1H),4.06 (dd,J = 10.4,5.2 Hz,1H),3.75 (d,J = 10.4 Hz,1H),3.31 (dd,J = 18.4,12.0 Hz,1H),3.12 (dd,J = 18.4,5.6 Hz,1H); 13 C{ 1 H} NMR (150 MHz, CDCl 3 ): δ 168.1, 150.4 (t, J C−F = 31.8 Hz),134.7,132.2,130.7,130.5,129.1,127.9,127.7,127.5,126.6,125.9,110.5 (d,J C−F = 233.1 Hz), 57.9, 34.0, 33.9; 19 F NMR (376 MHz, CDCl 3 ): δ −118.75 (dd, J = 327.9, 54.1 Hz), −120.29 (dd, J = 327.5, 53. 8 Hz); HRMS (ESI): m/z calcd for C 16 H 13 BrF 2 N 2 NaO [M + Na] + 389.0072, found 389.0070.…”

“…Purified by column chromatography (EA/petroleum ether, 1:8, R f = 0.6); yellowish solid (58 mg, 60%), mp 81−84 °C; 1 H NMR (400 MHz, CDCl 3 ): δ 8.09 (dd, J = 3.6, 1.2 Hz, 1H), 7.61 (dd, J = 5.2, 1.2 Hz, 1H), 7.12 (dd, J = 5.2, 4.0 Hz, 1H), 6.47 (t, J = 54.0 Hz, 1H), 5.10−5.03 (m, 1H), 3.92 (dd, J = 10.5, 6.0 Hz, 1H), 3.73 (dd, J = 10.4, 2.4 Hz, 1H), 3.35−3.26 (m, 1H), 3.12− 3.05 (m, 1H); 13 C{ 1 H} NMR (150 MHz, CDCl 3 ): δ 160.2, 150.2 (t, J C−F = 31.5 Hz),135.1,134.2,133.6,127.1,110.3 (d,58.3,34.0,33.6;19 F NMR (376 MHz, CDCl 3 ): δ −123.54 (dd, J = 327.1, 53. 8 Hz),J = 327.1,53.8 Hz); HRMS (ESI): m/z calcd for C 10 H 10 BrF 2 N 2 OS [M + H] + 322.9660, found 322.9661.…”

“…In our group, we are endeavoring on the development of efficient methods to construct fluorine-containing heterocycles and find that fluoroalkylated N -acylhydrazones and nitrile imines are versatile building blocks for the synthesis of various fluorine-containing heterocycles such as pyrazoles, pyrazolines, pyrazolidines, imidazolines, imidazolidines, dihydropyridazines, oxadiazoles, triazoles, and triazolines . However, difluoromethylated N -acylhydrazones have never been synthesized and used for the construction of difluoromethylated heterocycles.…”