Copper- and Palladium-Catalyzed Cross-Coupling Reactions for the Synthesis of N-Fused Benzo[4,5]imidazo[2,1-b]thiazole Derivatives via Substituted trans-1,2-Diiodoalkenes, 1H-Benzo[d]imidazole-2-thiols, and Halobenzenes

Abstract

Two transition metal (Cu and Pd)-catalyzed C-S, C-N, and C-C bond cross-coupling reactions for the preparation of N-fused benzo[4,5]imidazo[2,1-b]thiazole derivatives were developed. A variety of 3-substituted and 2,3-disubstituted benzo[4,5]imidazo[2,1-b]thiazoles were efficiently and conveniently synthesized from the coupling reaction via trans-1,2-diiodoalkenes, 1H-benzo[d]imidazole-2-thiols, and halobenzenes in moderate to excellent yields.

Synthesis of Benzo[4,5]imidazo[2,1‐b]thiazole by Copper(II)‐Catalyzed Thioamination of Nitroalkene with 1H‐Benzo[d]imidazole‐2‐thiol

“…We commenced our study by reacting 1 H ‐benzo[ d ]imidazole‐2‐thiol ( 1 a ) with ( E )‐1‐methyl‐4‐(2‐nitrovinyl)benzene ( 2 a ) in presence of 10 mol% Cu(OAc) 2 ⋅ H 2 O in DMSO at 80 °C (Table , entry 1). Interestingly, the desired product 3 aa was isolated in 35% yield after 8 h. The structure was confirmed on the basis of 1 H NMR spectra in which the characteristic peak for thiazole ( sp 2 ‐H) is observed as singlet at 6.55 ppm and also by comparing with literature ,,. In order to determine the optimal conditions, the reaction was screened with several solvents like MeCN, DMF, DMA, toluene, nitrobenzene, NMP, DCB and AcOH (Table , entries 2 to 9).…”

“…3‐( p ‐Tolyl)benzo[4,5]imidazo[2,1‐ b ]thiazole (3 aa) :,, Yellow solid (69 mg, 87%), mp 118–120 °C (lit. mp 118–121 °C); 1 H NMR (CDCl 3 , 400 MHz): δ 7.78 (d, J =8.4 Hz, 1H), 7.54 (d, J =8.0 Hz, 2H), 7.37 (d, J =7.6 Hz, 2H), 7.32 (t, J =8.4 Hz, 1H), 7.08–7.06 (m, 1H), 6.99–6.96 (m, 1H), 6.55 (s, 1H), 2.49 (s, 3H); 13 C{ 1 H} NMR (CDCl 3 , 100 MHz): δ 157.3, 148.6, 140.4, 134.4, 130.2, 129.7, 128.8, 126.5, 123.4, 120.4, 119.2, 111.8, 106.8, 21.6.…”

“…3‐(4‐Fluorophenyl)benzo[4,5]imidazo[2,1‐ b ]thiazole (3 af) :, Yellow solid (72 mg, 89%), mp 173–174 °C (lit. mp 174–177 °C); 1 H NMR (CDCl 3 , 400 MHz): δ 7.82 (d, J =8.0 Hz, 1H), 7.66–7.62 (m, 2H), 7.36–7.26 (m, 3H), 7.15 (d, J =8.4 Hz, 1H), 7.09 (t, J =7.2 Hz, 1H), 6.62 (s, 1H); 13 C{ 1 H} NMR (CDCl 3 , 100 MHz): δ 163.8 (d, J =232 Hz), 157.2, 148.3, 132.8, 131.0 (d, J =8 Hz), 125.5 (d, J =3 Hz), 123.7, 120.8, 119.3, 116.4 (d, J =22 Hz), 115.8, 111.6, 107.9.…”

“…2,3‐Diphenylbenzo[4,5]imidazo[2,1‐ b ]thiazole (5 h ): White solid (64 mg, 65%), mp 195–197 °C (lit. mp 196–197 °C); 1 H NMR (CDCl 3 , 400 MHz): δ 7.81 (d, J =8.4 Hz, 1H), 7.59–7.55 (m, 5H), 7.32–7.27 (m, 6H), 6.99 (t, J =8.0 Hz, 1H), 6.74 (d, J =8.4 Hz, 1H); 13 C{ 1 H} NMR (CDCl 3 , 100 MHz): δ 154.7, 147.6, 131.4, 130.6, 130.4, 130.3, 129.5, 129.1, 128.87, 128.83, 128.47, 128.44, 123.6, 123.4, 120.8, 119.0, 111.5.…”

“…6‐Methyl‐3‐( p ‐tolyl)benzo[4,5]imidazo[2,1‐ b ]thiazole compound with 7‐methyl‐3‐( p ‐tolyl)benzo[4,5]imidazo[2,1‐ b ]thiazole (1:1) (3ba+3b′a) : Yellow solid (72 mg, 86%); 1 H NMR (CDCl 3 , 400 MHz): δ 7.66 (d, J =8.4 Hz, 1H), 7.57 (s, 1H), 7.54–7.52 (m, 4H), 7.38–7.35 (m, 4H), 7.14 (d, J =8.4 Hz, 2H), 7.05 (s, 1H), 6.88 (d, J =8.8 Hz, 1H), 6.52–6.51 (m, 2H), 2.50 (s, 3H), 2.49 (s, 3H), 2.47 (s, 3H), 2.37 (s, 3H); 13 C{ 1 H} NMR (CDCl 3 , 100 MHz): δ 157.2, 156.8, 149.1, 148.4, 140.4, 133.2, 129.75, 129.72, 128.83, 128.80, 126.7, 124.9, 121.8, 119.1, 118.7, 117.1, 111.8, 111.3, 106.6, 106.4, 21.9, 21.7, 21.67, 21.64; Anal. Calcd for C 17 H 14 N 2 S: C, 73.35; H, 5.07; N, 10.06; Found C, 73.21; H, 5.16; N, 10.01%.…”