2-Bromo-3-ethylthiazolium Tetrafluoroborate (BET)

Recent progress in peptide synthesis resulted in the elaboration of novel coupling agents. One successful approach involves the application of thiazolium salts, e.g. 2-bromo-3-ethyl-4-methylthiazolium tetrafluoroborate (BEMT) [1,2,3]. This compound can be prepared from 2-bromo-3-ethyl-4-methylthiazole [1,2]. We have found that a simpler analogue, 2-bromo-3-ethylthiazolium tetrafluoroborate (BET), can be prepared in convenient steps from the commercially available 2-aminothiazole using the procedure by Dondoni et al. [4] to obtain 2-bromothiazole which, in turn, was readily transformed into the title compound. In our experience BET is a highly efficient coupling reagent in the synthesis of peptide nucleic acid (PNA) oligomers in solution phase.

To a stirred solution of 2-bromothiazole [4] (1.78 mL, 20.0 mmol) in 1,2-dichloroethane (DCE, 20 mL) the solution of triethyloxonium tetrafluoroborate (11.4 g, 60.0 mmol) in DCE(60 mL) was added over 45 min. at 80 °C. When the reaction was complete (16 h) according to TLC (n-buthanol : acetic acid : water = 4:1:1) the solution was concentrated in vacuo. After the residue was precipitated from diethyl ether it was recrystallized from abs. acetonitrile/ethyl acetate to afford white plates. Yield: 4.48 g (80 %).

Mp: 137.9-139.2 °C.

¹H NMR (DMSO-d₆, 500 MHz, d, ppm): 1.47 (t, J = 7.0 Hz, 3H, CH₂CH₃); 4.52 (q, J = 7.0 Hz, 2H, CH₂CH₃); 8.35 (d, J = 4.1 Hz, 1H, aryl); 8.56 (d, J = 4.1 Hz, 1H, aryl).

¹³C NMR (DMSO-d₆, 125 MHz, d, ppm): 14.19 (CH₂CH₃); 50.61 (CH₂CH₃); 127.45 (C-5); 137.73 (C-4); 146.50 (C-2).

ESI-MS (m/z, %): 191.8 (100, [C₅H₇⁷⁹BrNS]⁺); 193.8 (97, [C₅H₇⁸¹BrNS]⁺).

Anal. cald. for C₅H₇BBrF₄NS (279.891): C, 21.45; H, 2.52; Br, 28.55; F, 27.15; N, 5.00; S, 11.46; found C, 21.47; H, 2.51; Br, 28.52; F, 27.20; N, 5.01; S, 11.44.