A Selective and Convenient Method for the Synthesis of 2-Phenylaminothiazolines

Abstract

A series of 2-phenylaminothiazolines have been prepared from the corresponding N-(2-hydroxyethyl)-N'-phenylthioureas under mild reaction conditions using either thio-CDI (1,1'-thiocarbonyldiimidazole) or CDI (1,1'-carbonyldiimidazole) to promote the cyclization. This protocol provides the desired cyclization products in good yield with excellent selectivity. The scope and selectivity of this methodology are also described.

Synthesis and Antiplatelet Activity of Antithrombotic Thiourea Compounds: Biological and Structure-Activity Relationship Studies

“…N-(2-Hydroxyethyl)-N'-phenylthiourea ( 3c ) [ 70 ]. White solid; mp 139–141 °C; IR (KBr): 3361, 3184, 3001, 2949, 1544, 1253, 1056, 929, 690 cm −1 ; 1 H-NMR (DMSO- d 6 ) δ 9.60 (br s, 1H), 7.70 (br s, 1H), 7.47–7.42 (m, 2H), 7.35–7.27 (m, 2H), 7.14–7.05 (m, 1H), 4.82 (br s, 1H), 3.56–3.54 (m, 4H); 13 C-NMR (50 MHz, DMSO- d 6 ) δ 180.5, 139.3, 128.5, 124.0, 123.0, 59.3, 46.4; HRMS-ESI: m/z [M+Na] + calculated for C 9 H 12 N 2 OS: 219.0562; found: 219.0563.…”

Utility of Bifunctional N-Heterocyclic Phosphine (NHP)-Thioureas for Metal-Free Carbon–Phosphorus Bond Construction toward Regio- and Stereoselective Formation of Vinylphosphonates

“…To a solution of 2-chloro-1,3-diphenyl-1,3,2-diazaphospholidine (1.00 g, 3.62 mmol) in DCM (25 mL) were added 1-(2-hydroxyethyl)-3-phenyl­thiourea (0.711 g, 3.62 mmol) and triethylamine (0.438 g, 4.34 mmol) at 0 °C. The reaction mixture was warmed up to room temperature and stirred for 2 h. After stirring for 2 h at room temperature, the reaction mixture was concentrated under reduced pressure.…”

Synthesis of a 6-CF3-Substituted 2-Amino-dihydro-1,3-thiazine β-Secretase Inhibitor by N,N-Diethylaminosulfur Trifluoride-Mediated Chemoselective Cyclization

“…This undesired oxazine formation is known to be a competitive side reaction in 1,3-thiazine synthesis using N -hydroxypropyl thioureas. Scientists at Eli Lilly addressed this issue in their synthesis of LY2886721 and discovered that use of CDI under heated conditions gave 1,3-thiazine 5d with high yield and chemoselectivity over the 1,3-oxazine formation (Table ; condition D) . Unfortunately, this protocol also failed as shown in entry 4, probably due to the bulky and high electron-withdrawing nature of the CF 3 group.…”