2-Amino-benzothiazole-6-carbonitrile

Step A: 2-Chlorobenzothiazole-6-carbonitrile; To a mixture of 4-aminobenzonitrile (23.6 g, 0.2 mol) and ammonium rhodanate (30.4 g, 0.4 mol) was added glacial acetic acid (600 ml.) and the resulting solution was cooled to 13.5 To a solution of 4-aminobenzonitrile (1.00 g, 8.47 mmol) in acetic acid (12 ml) was added potassium thiocyanate (1.00 g, 16.9 mmol) at 10°C. The reaction mixture was stirred at rt for 30 mm. A solution of bromine (0.5 ml, 10.16 mmol) in acetic acid (3 ml) was added dropwise to the reaction at rt. The reaction mixture was stirred at rt for 16 h. The resulting solid precipitates were collected byfiltration under reduced pressure, washed with acetic acid (10 ml) and dried under vacuum. The obtained precipitates were suspended in ice cold aqueous solution of NH4OH (10 ml) and stirred at rt for 30 mm. The resulting solid precipitates were collected by filtration under reduced pressure, dried under vacuum yielding 2-aminobenzo[djthiazole-6-carbonitrile (0.70 g, 4.00 mmol). This material was directly used in the next step without further purification. LCMS: Method C, 1.62 mi MS: ES+176.13.Listed below are some typical examples of said 2-aminobenzothiazole compounds: ... 2-amino-6-ethoxybenzothiazole 2-amino-6-chlorobenzothiazole 2-amino-6-bromobenzothiazole 2-amino-6-iodobenzothiazole 2-amino-6-cyanobenzothiazole 2-amino-6-thiocyanobenzothiazole 2-amino-6-methylbenzothiazole 2-amino-4, 6-dichlorobenzothiazole ...4-Aminobenzonitrile (11.8 g, 100 mmol) was dissolved in 100 ml of acetic acid and potassium thiocyanate (29.1 g, 300 mmol) was cooled to about 10 C, and liquid bromine (16 g, 100 mmol) was slowly added dropwise. After the addition, the mixture was allowed to warm to room temperature and stirred for 1 hour.The temperature was raised to 60 C and the reaction was continued for 6 hours.Concentrate under reduced pressure, distill off most of the acetic acid, add 100 mL of water, 200 ml of ethyl acetate and stir for 0.5 hour.Filtering, washing, Drying to give the intermediate A 2-amino-6-cyanobenzothiazole(12.4g, yield 71%).General procedure: A mixture of 0.1mol of appropriate 4-substituted amines and 0.1mol of Potassium thiocyanate (KCNS) in 100mL glacial acetic acid (AcOH) were cooled in an ice bath and stirred for 10-20min, and then 0.1mol bromine in glacial acetic acid was added dropwise at such a rate to keep the temperature below 10C throughout the addition. The reaction mixture was stirred at room temperature for 2-4h, the hydrobromide (HBr) salt thus separated out was filtered, washed with acetic acid, dried, dissolved in hot water and basified to pH 11.0 with ammonia solution (NH4OH) and the resulting precipitate was filtered, washed with water and dried to get the desired product 2a-k. The progress of the reaction was monitored by Thin Layer Chromatography using toluene:acetone (8:2) solvent system.General procedure: To 100 mL glacial acetic acid, 0.1 mol of appropriate para-substituted amine derivative and equimolecular amount of potassium thiocyanate was added and reaction mixture was kept in an ice bath and cooled. The mixture was allowed to cool at this temperature up to 20 min. Then, in the reaction mixture, bromine in glacial acetic acid (0.1 mol) was added very slowly to maintain the temperature of the reaction mixture below 10 C and was stirred at room temperature for 2 to 4 h to obtain the hydrobromide (HBr) salt. The salt was then filtered, washed with acetic acid, dried on vacuum oven and basified to pH 11.0 with NH3·H2O. The solid precipitate thus formed was filtered, washed with water and dried on vacuum oven to yield the intermediates 3a-k. TLC technique involving toluene : acetone (V/V, 8:2) solvent system was used to monitor the reaction progress [26].General procedure: The appropriate para-substituted amine derivative (1a-j; 0.1 mol) and an equimolecular amount of potassium thiocyanate were added to 100 mL glacial acetic acid, with cooling of the reaction mixture in an ice bath. The mixture was left at this temperature for up to 20 min then bromine (0.1 mol) in glacial acetic acid was added very slowly, to maintain the temperature of the reaction mixture below 10 C, then the mixture was stirred at room temperature for 2-4 h to furnish the hydrobromide (HBr) salt. The salt was then isolated by filtration, washed with acetic acid, dried in a vacuum oven, then dissolved in sufficient aqueous ammonia solution to ensure the pH was 11.0. The solid precipitate thus formed was filtered, washed with water, and dried in a vacuum oven to yield the intermediates 4a-j. The progress of the reaction was monitored by TLC with toluene-acetone 8:2 as mobile phase.General procedure: A mixture of 0.1 mol of 4-substituted aniline and 0.1 mol ofPotassium thiocyanate (KCNS) in 100 ml glacial acetic acid (AcOH) was cooled inan ice bath and stirred for 10 to 20 min, and then 0.1 mol bromine in glacialacetic acid was added dropwise at such a rate to keep the temperature below 10C throughout the addition. Theprogress of the reaction was monitored by Thin Layer Chromatography usingtoluene: acetone (8:2) solvent system. The reaction mixture was stirredat room temperature for 2 to 4 hrs, the hydrobromide (HBr) salt thus separatedout was filtered, washed with acetic acid, dried, dissolved in hot water and basified to pH 11.0 with ammonia solution (NH4OH)and the resulting precipitate was filtered, washed with water and dried to getthe desired product 2a-q.To a solution of 4-aminobenzonitrile (1.00 g, 8.47 mmol) in acetic acid (12 ml) was added potassium thiocyanate (1.00 g, 16.9 mmol) at 10C. The reaction mixture was stirred at rt for 30 mm. A solution of bromine (0.5 ml, 10.16 mmol) in acetic acid (3 ml) was added dropwise to the reaction at rt. The reaction mixture was stirred at rt for 16 h. The resulting solid precipitates were collected byfiltration under reduced pressure, washed with acetic acid (10 ml) and dried under vacuum. The obtained precipitates were suspended in ice cold aqueous solution of NH4OH (10 ml) and stirred at rt for 30 mm. The resulting solid precipitates were collected by filtration under reduced pressure, dried under vacuum yielding 2-aminobenzo[djthiazole-6-carbonitrile (0.70 g, 4.00 mmol). This material was directly used in the next step without further purification. LCMS: Method C, 1.62 mi MS: ES+176.13.

Molecular Weight:175.21
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:175.02041835
Monoisotopic Mass:175.02041835
Topological Polar Surface Area:90.9
Heavy Atom Count:12
Complexity:222
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes