4.1.2. General procedure for the Synthesis of novel 1-aryl-1H, 3H-thiazolo[3,4-a]-6-nitro-benzimidazole derivatives (2a-e)
To a one pot reaction, (4 mmol) of 4-nitro-o-phenylenediamine was dissolved in MeCN (12 mL) and equivalent amount of 2-mercaptoacetic acid (4 mmol) together with (4 mmol) of aromatic aldehydes were added and allowed to stir in presence of (800 mg) of the previously prepared catalyst; NaHSO4-SiO2 at 75°C for 1 h. The reaction mixture was then cooled at room temperature and washed several times with adequate amount of methylene chloride [27]. The catalyst was recovered and concentrated under reduced then purified using column chromatography over silica gel with eluent (hexane: dichloromethane (7:3) and finally recrystallized using ethanol.
1-(Phenyl)-1H, 3H-thiazolo[3,4-a]-6-nitro-benzimidazole (2a)
1H-NMR (DMSO-d6): 6.55–6.57 (d, 2H, J = 8Hz, CH2-S), 7.45 (s, 1H, N-CH-S), 7.47–7.48 (d, 1H, Ar-H), 7.59–7.60 (t, 1H, Ar-H), 7.62 (s, 1H, Ar-H), 7.641–7.648 (t, 1H, Ar-H), 7.79–7.81 (d, 1H, Ar-H), 8.14–8.17 (dd, 1H, Ar-H), 8.23–8.25 (t, 1H, Ar-H), 8.514–8.519 (d, 1H, Ar-H) ppm; IR (KBr): 3090, 2988 cm− 1; MS:(M+1): 279.06; yield 89%.
1-(4-Hydroxyphenyl)-1H,3H-thiazolo[3,4-a]-6-nitrobenzimidazole (2b)
1H-NMR (DMSO-d6): 5.61 (s, 1H, OH (exchangeable peak)), 6.53–6.55 (d, 2H, J = 8Hz, CH2-S), 6.66–6.69 (d, 1H, Ar-H), 6.92 (s, 1H, N-CH-S), 7.41–7.45 (d, 1H, Ar-H), 7.70–7.73 (d, 1H, Ar-H), 8.05–8.09 (d, 1H, Ar-H), 8.10 (s, 1H, Ar-H), 8.11–8.15 (dd, 1H, Ar-H), 8.41–8.45 (d, 1H, Ar-H) ppm; IR (KBr): 3280 − 2850, 3030, 2920 cm− 1; MS:(M+1): 313.05; yield 92%.
1-(4-Chlorophenyl)-1H, 3H-thiazolo[3,4-a]-6-nitro-benzimidazole (2c)
1H-NMR (DMSO-d6): 6.52–6.54 (d, 2H, J = 8Hz, CH2-S), 7.40–7.41 (d, 1H, Ar-H), 7.419 (s, 1H, N-CH-S), 7.442–7.447 (d, 1H, Ar-H), 7.67–7.69 (d, 1H, Ar-H), 7.77–7.80 (d, 1H, Ar-H), 8.13–8.15 (dd, 1H, Ar-H), 8.22–8.24 (d, 1H, Ar-H), 8.49 (s, 1H, Ar-H) ppm; IR (KBr): 3060, 2962 cm− 1; MS: (M+2): 333.02, (M+1): 331.02; yield 93%.
1-(4-Chlorophenyl)-1H, 3H-thiazolo[3,4-a]-6-nitro-benzimidazole (2d)
1H-NMR (DMSO-d6): 3.79 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 3.91 (s, 3H, OCH3), 6.98 (s, 1H, CH2-S), 7.11 (s, 1H, CH2-S), 7.23 (s, 1H, N-CH-S), 7.54–7.56 (d, 1H, Ar-H), 7.58–7.59 (d, 1H, Ar-H), 8.13 (s, 1H, Ar-H), 8.15 (s, 1H, Ar-H), 8.18 (s, 1H, Ar-H), 8.57 (s, 1H, Ar-H) ppm; IR (KBr): 3075, 2925 cm− 1; MS: (M+1): 387.09; yield 95%.
1-(2-Furo)-1H, 3H-thiazolo[3,4-a]-6-nitro-benzimidazole (2e)
1H-NMR (DMSO-d6): 6.51–6.54 (dd, 2H, J = 8Hz, CH2-S), 7.38 (s, 1H, Ar-H), 7.39 (s, 1H, N-CH-S), 7.40–7.41 (d, 1H, Ar-H), 7.418 (s, 1H, Ar-H), 7.425–7.427 (d, 1H, Ar-H), 7.43 (s, 1H, Ar-H), 7.44 (s, 1H, Ar-H) ppm; IR (KBr): 3110, 3090, 2985 cm− 1; MS: (M+1): 287.04; yield 89%.
4.1.4. General procedure for the synthesis of 1-aryl-1H, 3H-thiazolo[3,4-a]-6-benzamide-benzimidazole derivatives (4a-e)
The final targets were obtained via acylation reaction, where (3 mmol) of the previously prepared intermediates (3a-e) was allowed to stir in a rounded flask surrounded by ice with 15 mL methylene chloride. An equivalent amount of TEA (3 mmol) was slowly added to the stirring solution followed by dropwise addition of benzoyl chloride (5 mmol). The mixture was refluxed for further 1.5 h and the resultant was purified and washed with methylene chloride and ether then dried under vacuum. [28]
1-(Phenyl)-1H 3H-thiazolo[3,4-a]-6-benzamide-benzimidazole (4a)
1H-NMR (DMSO-d6): 7.32–7.34 (d, 2H, J = 8Hz, CH2-S), 7.45 (s, 1H, N-CH-S), 7.47–7.48 (d, 1H, Ar-H), 7.51–7.53 (t, 1H, Ar-H), 7.59–7.60 (t, 1H, Ar-H), 7.62 (s, 1H, Ar-H), 7.641–7.648 (t, 1H, Ar-H), 7.79–7.81 (d, 1H, Ar-H), 7.82–7.84 (t, 1H, Ar-H), (7.95–8.03 (d, 2H, Ar-H), 8.14–8.17 (dd, 1H, Ar-H), 8.23–8.25 (t, 1H, Ar-H), 8.34–8.36 ( t, 1H, Ar-H), 8.514–8.519 (d, 1H, Ar-H), 10.45 (s, 1H, NH(exchangeable peak)) ppm; 13C-NMR (DMSO-d6): 39.3, 57.8, 128.9, 129.1, 129.6, 130.1, 130.2, 131.2, 133.4, 134.1, 167.7 ppm; IR (KBr): 3220, 3090, 2988 cm− 1; MS:(M+1): 371.11; yield 72%.
1-(4-Hydroxyphenyl)-1H, 3H-thiazolo[3,4-a]-6-benzamide-benzimidazole (4b)
1H-NMR (DMSO-d6): 5.61 (s, 1H, OH (exchangeable peak)), 6.53–6.55 (d, 2H, J = 8hz, CH2-S), 6.66–6.69 (t, 1H, Ar-H), 6.84–6.87 (d, 1H, Ar-H), 6.92 (s, 1H, N-CH-), 6.94–6.97 (t, 1H, Ar-H), 7.41–7.42 (d, 1H, Ar-H), 7.45 (s, 1H, Ar-H), 7.64–7.73 (dd, 2H, J = 8Hz, Ar-H), 7.83–7.85 (d, 1H, Ar-H), 8.05–8.10 (t, 1H, Ar-H), 8.11–8.12 (d, 1H, Ar-H), 8.13–8.15 (d, 1H, Ar-H), 8.41–8.45 (d, 1H, Ar-H) ppm; 10.23 (s, 1H, NH(exchangeable peak)) ppm; 13C-NMR (DMSO-d6): 39.2, 57.9, 128.9, 129.1, 129.6, 130.1, 130.2, 131.2, 133.4, 132.1, 134.1, 139.7, 156.2, 167.7 ppm; IR (KBr): 3288, 3280 − 2850, 3030, 2920 cm− 1; MS:(M+1): 387.1; yield 67%.
1-(4-Chlorophenyl)-1H, 3H-thiazolo[3,4-a]-6-benzamide-benzimidazole (4c)
1H-NMR (DMSO-d6): 7.49–7.53 (t, 1H, Ar-H), 7.56–7.59 (t, 1H, Ar-H), 7.62–7.66 (t, 1H, Ar-H), 7.80–7.81 (d, 2H, J = 6Hz, CH2-S), 7.83 (s, 1H, N-CH-S), 7.94–7.97 (dd, J = 8Hz, 4H, Ar-H), 8.01–8.03 (dd, 2H, Ar-H), 8.27–8.29 (d, 2H, Ar-H), 10.60 (s, 1H, NH(exchangeable peak)) ppm; 13C-NMR (DMSO-d6): 39.33, 57.69, 128.22, 128.95, 129.06, 129.74, 130.14, 131.19, 133.37, 167.80 ppm; IR (KBr): 3255, 3060, 2962 cm− 1; MS: (M+2): 407.07, (M+1): 405.07; yield 75%.
1-(4-Chlorophenyl)-1H, 3H-thiazolo[3,4-a]-6-benzamide-benzimidazole (4d)
1H-NMR (DMSO-d6): 3.02–3.03 (m, 3H, OCH3), 3.05–3.06 (m, 3H, OCH3), 3..07-3.08 (m, 3H, OCH3), 7.49 (s, 1H, CH2-S), 7.50 (s, 1H, CH2-S), 7.51 (s, 2H, Ar-H), 7.53 (s, 1H, N-CH-S), 7.61–7.62 (t, 1H, Ar-H), 7.62–7.65 (t, 1H, Ar-H), 7.65–7.66 (t, 1H, Ar-H), 7.946–7.949 (d, 4H, Ar-H), 7.96 (s, 1H, Ar-H), 10.62 (s, 1H, NH (exchangeable peak)) ppm; 13C-NMR (DMSO-d6): 8.853, 39.33, 45.67, 129.06, 129.73, 131.20, 133.36, 167.77 ppm;IR (KBr): 3290, 3075, 2925 cm− 1; MS: (M+1): 461.14; yield 84%
1-(2-Furo)-1H, 3H-thiazolo[3,4-a]-6-benzamide-benzimidazole (4e)
1H-NMR (DMSO-d6): 5.17 (s, 1H, CH2-S), 5.32 (s, 1H, CH2-S), 7.04 (s, 1H, Ar-H), 7.16 (s, 1H, Ar-H), 7.29 (s, 1H, Ar-H), 7.59 (s, 1H, N-CH-S), 7.61 (t, 1H, Ar-H), 7.62 (d, 2H, Ar-H), 7.70 (t, 1H, Ar-H), 7.71 (t, 1H, Ar-H), 8.07 (s, 1H, Ar-H), 8.09 (d, 2H, Ar-H), 8.95 (s, 1H, NH (exchangeable peak)) ppm; 13C-NMR (DMSO-d6): 39.7, 59.8, 128.9, 129.1, 129.6, 130.1,, 131.2, 133.4, 132.1, 139.7, 156.2, 167.7 ppm; IR (KBr): 3280, 3110, 3090, 2985 cm− 1; MS: (M+1): 361.09; yield 80%.