Synthesis and Antimicrobial activity of Bulky molecules comprising Benzothiazole and Sulphonamide moieties

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Synthesis of Substituted 2-amino benzothiazole
To Substituted aniline (0.2742 mol), conc. hydrochloric acid (25 mL) was added and the solution was warmed. A saturated solution of ammonium thiocyanate in water (30g in 60 mL) was added slowly in above solution. The mixture was boiled until the solution got turbid. The turbid solution was poured in cold water. The separated precipitate as phenylthiourea was filtered and recrystallized from aqueous ethanol (80%) so as to obtain pure compound.1
Phenylthiourea (0.144 mol) was dissolved in sulphuric acid (45.39 mL, 85%) during half of an hour at 20 to 25 °C. In the period of 3 hours, 8.64 g of 40% NH4Br solution was then continuously metered in the resulting solution at 25 to 30 °C with stirring. The solution was then added to water, clarified by filtration and adjusted to pH 8 with sodium hydroxide solution. The mixture was stirred for half an hour at 40 °C and filtered using suction. The residue was washed free of sulfate with water, dried and recrystallized from aqueous ethanol.5

2-amino benzothiazole (SK1a)
Yield (%): 68.3; M.P. (OC): 128-134; Rf: 0.40 (Hexane : Ethyl acetate, 9:1).

6-chlorobenzothiazol-2-amine (SK1b)
Yield (%): 63.4; M.P. (OC): 194-196; Rf: 0.42 (Hexane : Ethyl acetate, 9:1).

6-methylbenzothiazol-2-amine (SK1c)
Yield (%): 61.8; M.P. (OC): 136-140; Rf: 0.41 (Hexane : Ethyl acetate, 9:1)

7-chloro-6-fluorobenzothiazol-2-amine (SK1d)
Yield (%): 72.5; M.P. (OC): 182-188; Rf: 0.36 (Hexane : Ethyl acetate, 9:1).

6-nitrobenzothiazol-2-amine (SK1e)
Yield (%): 73.6; M.P. (OC): 200-206; Rf: 0.39 (Hexane : Ethyl acetate, 9:1).

6-methoxybenzothiazol-2-amine (SK1f)
Yield (%): 65.6; M.P. (OC): 166-170; Rf: 0.41 (Hexane : Ethyl acetate, 9:1).

4,7-dimethoxybenzothiazol-2-amine (SK1g)
Yield (%): 59.2; M.P. (OC): 196-200; Rf: 0.47 (Hexane : Ethyl acetate, 9:1).

4,7-dichlorobenzothiazol-2-amine (SK1h)
Yield (%): 64.9; M.P. (OC): 164-168; Rf: 0.44 (Hexane : Ethyl acetate, 9:1).

7-chloro-4-methylbenzothiazol-2-amine (SK1i)
Yield (%): 62.6; M.P. (OC): 206-212; Rf: 0.46 (Hexane : Ethyl acetate, 9:1).

4-fluoro-7-nitrobenzothiazol-2-amine (SK1j)
Yield (%): 74.5; M.P. (OC): 214-218; Rf: 0.40 (Hexane : Ethyl acetate, 9:1).

Synthesis of 4-acetamidophenyl sulphonyl chloride (SK2)
To acetanilide (2.84 g, 0.021 mol) and good grade chlorosulphonic acid (7.3 mL) was added in small portions with constant stirring. The reaction mixture was heated on water bath for 1 hour then cooled and the oily mixture was poured in a thin stream with constant stirring into crushed ice (300 g). The lumps of the solid material were broken and the mixture was stirred for several minutes. The residue was filtered and washed with cold water.1

Yield (%): 67.8; M.P. (OC): 288-294; Rf: 0.50 (Hexane : Ethyl acetate, 9:1).

Synthesis of 4-acetamido-N-(substituted 1, 3-benzothiazol-2-yl) benzenesulphonamide
Substituted 2-amino benzothiazole (0.01 mol) was dissolved in stirring solution of pyridine (4 mL) and acetic anhydride (20 mL). To this mixture, 4-acetamidophenyl sulphonyl chloride (0.01 mol) was added. The mixture was heated on water bath for 2 hours. The reaction mixture was cooled and poured in cold water (20 mL). The solid obtained was filtered and crystallized from aqueous ethanol (80%) so as to obtain pure compound.1

4- acetamido-N- (benzothiazol-2-yl) benzenesulphonamide (SK3a)
Yield (%): 65.7; M.P. (OC): 188-190; Rf: 0.61 (Hexane : Ethyl acetate, 8:2).

4- acetamido-N-(6-chloro benzothiazol-2-yl) benzenesulphonamide (SK3b)
Yield (%): 63.2; M.P. (OC): 238-242; Rf: 0.60 (Hexane : Ethyl acetate, 8:2).

4- acetamido-N-(6-methyl benzothiazol-2-yl) benzenesulphonamide (SK3c)
Yield (%): 56.5; M.P. (OC): 194-198; Rf: 0.64 (Hexane : Ethyl acetate, 8:2).

4- acetamido-N-(7-chloro, 6-fluoro benzothiazol-2-yl) benzenesulphonamide (SK3d)
Yield (%): 68.6; M.P. (OC): 230-236; Rf: 0.65 (Hexane : Ethyl acetate, 8:2).

4- acetamido-N-(6-nitro benzothiazol-2-yl) benzenesulphonamide (SK3e)
Yield (%): 61; M.P. (OC): 242-248; Rf: 0.64 (Hexane : Ethyl acetate, 8:2).                                 

4- acetamido-N-(6-methoxy benzothiazol-2-yl) benzenesulphonamide (SK3f)
Yield (%): 63.5; M.P. (OC): 206-210; Rf: 0.62 (Hexane : Ethyl acetate, 8:2).

4- acetamido-N-(4, 7-dimethoxy benzothiazol-2-yl) benzenesulphonamide (SK3g)
Yield (%): 63.5; M.P. (OC): 222-224; Rf: 0.66 (Hexane : Ethyl acetate, 8:2); IR (KBr, cm-1): 3326 (-NH-); 1722 (C=O), 1668 (C=N), 1349, 1125 (SO2), 1051 (C-O), 678 (C-S); 1H- NMR (DMSO, ppm): 12.35 (s, 1H, NHSO2), 11.24 (s, 1H, NHCO), 6.80- 7.90 (m, 6H, Ar-H), 2.57 (s, 3H, COCH3), 1.95 (s, 6H, OCH3); Mass spectra (m/z): 408.2 (M+1)+.

4- acetamido-N-(4, 7-dichloro benzothiazol-2-yl) benzenesulphonamide (SK3h)
Yield (%): 61.8; M.P. (OC): 212-216; Rf: 0.62 (Hexane : Ethyl acetate, 8:2); IR (KBr, cm-1): 3301 (NH); 1695 (C=O), 1646 (C=N), 1373, 1113 (SO2), 1279 (C-N), 711 (C-Cl), 668 (C-S).

4- acetamido-N-(4-methyl, 7-chloro benzothiazol-2-yl) benzenesulphonamide
Yield (%): 55.4; M.P. (OC): 234-238; Rf: 0.64 (Hexane : Ethyl acetate, 8:2); IR (KBr, cm-1): 3200 (NH), 1750 (C=O), 1640 (C=N), 1325, 1120 (SO2), 1300 (C-N), 750 (C-Cl), 680 (C-S).

4- acetamido-N-(4-fluoro, 7-nitro benzothiazol-2-yl) benzenesulphonamide
Yield (%): 70.6; M.P. (OC): 250-254; Rf: 0.67 (Hexane : Ethyl acetate, 8:2); IR (KBr, cm-1): 3357, 3259 (NH), 1699 (C=O), 1549 (C=N), 1506 (NO2), 1314, 1117 (SO2), 1076 (C-F); 642 (C-S); 1H- NMR (DMSO, ppm): 12.60 (s, 1H, NHSO2), 11.35 (s, 1H, NHCO), 7.07-8.57 (m, 6H, Ar-H), 2.52 (s, 3H, COCH3); Mass spectra (m/z): 412.3 (M+2)+.

Synthesis of 4-amino-N-(substituted1, 3-benzothiazol-2-yl) benzenesulphonamide
The compound 4-acetamido-N-(substituted1, 3-benzothiazol-2-yl) benzenesulphonamide(0.01 mol) was dissolved in acetic acid (80%, 50 mL). The solution was refluxed for 6 hours and cooled. The solution was poured in cold water (100 mL). The residue was filtered and washed with excess water and dried. The dried residue was recrystallized from aqueous ethanol (80%).1

4-amino-N-(benzothiazol-2-yl)benzenesulphonamide (SK4a)

Yield(%): 61.5; M.P. (°C): 166-170; Rf: 0.48 (Hexane : Ethyl acetate, 8:2).

4-amino-N-(6-chlorobenzothiazol-2-yl)benzenesulphonamide (SK4b)

Yield(%): 60.4; M.P. (°C): 212-218; Rf: 0.53 (Hexane : Ethyl acetate, 8:2).

4-amino-N-(6-methylbenzothiazol-2-yl)benzenesulphonamide (SK4c)

Yield(%): 55.3; M.P. (°C): 162-164; Rf: 0.52 (Hexane : Ethyl acetate, 8:2).

4-amino-N-(7-chloro-6-fluorobenzothiazol-2-yl)benzenesulphonamide (SK4d)

Yield(%): 62.7; M.P. (°C): 204-210; Rf: 0.54 (Hexane : Ethyl acetate, 8:2).

4-amino-N-(6-nitrobenzothiazol-2-yl)benzenesulphonamide (SK4e)

Yield(%): 61.8; M.P. (°C): 220-224; Rf: 0.57 (Hexane : Ethyl acetate, 8:2).

4-amino-N-(6-methoxybenzothiazol-2-yl)benzenesulphonamide (SK4f)

Yield(%): 62.6; M.P. (°C): 180-184; Rf: 0.55 (Hexane : Ethyl acetate, 8:2).

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