Reaction #9662

Reaction equation

HCl

isoamyl nitrite

2-amino-4-methylbenzothiazole

→

2-chloro-4-methyl-1,3-benzothiazole

Yield 71.0%

Solvents

acetonitrile

—

tri(ethylene glycol) dimethyl ether

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction mixture was stirred at rt for 10 minutes
2. 2
   Temperatureheated at 50° C. for 2.5 h
3. 3
   TemperatureThe reaction mixture was cooled to rt
4. 4
   ExtractionThe solution was extracted with EtOAc
5. 5
   WashThe organic layer was washed with HCl (1.0 M), water, brine
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   OtherThe residue was purified by flash chromatography (Biotage Flash 40M)

Procedure

To a solution containing copper chloride (II) (1.96 g, 14.61 mmol) and tri(ethylene glycol) dimethyl ether (6 mL) in acetonitrile (100 mL) was added isoamyl nitrite (2.14 g, 18.27 mmol), and the reaction mixture was stirred at rt for 30 minutes. To this suspension was added dropwise a solution of 2-amino-4-methylbenzothiazole (2.0 g, 12.18 mmol) in tri(ethylene glycol) dimethyl ether (10 mL). The reaction mixture was stirred at rt for 10 minutes, and then heated at 50° C. for 2.5 h. The reaction mixture was cooled to rt, and then poured cautiously into cold aqueous 6 M HCl (400 mL). The solution was extracted with EtOAc. The organic layer was washed with HCl (1.0 M), water, brine, filtered and concentrated in vacuo. The residue was purified by flash chromatography (Biotage Flash 40M) using 5% ethyl acetate in hexane to afford 2-chloro-4-methyl-1,3-benzothiazole (1.6 g, 71%). 1H NMR (400 MHz, CD2Cl2) δ 2.70 (s, 3H), 7.32 (m, 2H), 7.64 (m, 1H).

Source