تفاعل #816428

معادلة التفاعل

DMF

oxalyl chloride

oxalyl chloride

2-ethyl-4-hydroxy-5-phenylisothiazol-3(2H)-one 1,1-dioxide

DMF

2-Ethyl-4-hydroxy-5-phenylisothiazol-3(2H)-one 1,1-dioxide

→

title compound

4-Chloro-2-ethyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide

المذيبات

DCM

DCM

ظروف التفاعل

المعالجة

1. 1
   أخرىThe ice-bath was removed
2. 2
   درجة الحرارةthe mixture was refluxed at 50° C. under N2 for 4 h
3. 3
   أخرىThe reaction mixture was evaporated
4. 4
   workup.ADDITIONthe residue was diluted with EtOAc
5. 5
   غسيلwashed with water (3×25 mL) and brine
6. 6
   تجفيفdried over Na2SO4
7. 7
   أخرىevaporated
8. 8
   درجة الحرارةcooled to 0° C. under N2
9. 9
   أخرىThe ice-bath was removed
10. 10
    درجة الحرارةthe mixture was refluxed at 50° C. under N2 for 4 h
11. 11
    أخرىThe reaction mixture was evaporated
12. 12
    workup.ADDITIONthe residue was diluted with EtOAc
13. 13
    غسيلwashed with water (3×50 mL) and brine
14. 14
    تجفيفdried over Na2SO4
15. 15
    أخرىevaporated where by red solid
16. 16
    أخرىwas obtained
17. 17
    أخرىpurified by column chromatography on silica gel using 2.5-3% EtOAc in petroleum ether as eluant
18. 18
    أخرىrecrystallised from MeOH

الإجراء التجريبي

2-Ethyl-4-hydroxy-5-phenylisothiazol-3(2H)-one 1,1-dioxide (5 g, 19.76 mmol) was dissolved in dry DCM (250 mL) and cooled to 0° C. under N2. Dry DMF (15 mL) was added, followed by oxalyl chloride (3 mL, 34.4 mmol). The ice-bath was removed and the mixture was refluxed at 50° C. under N2 for 4 h. The reaction mixture was evaporated and the residue was diluted with EtOAc and washed with water (3×25 mL) and brine, dried over Na2SO4 and evaporated. Another (16 g, 63.24 mmol) of 2-ethyl-4-hydroxy-5-phenylisothiazol-3(2H)-one 1,1-dioxide was dissolved in dry DCM (500 mL) and cooled to 0° C. under N2. Dry DMF (20 mL) was added followed by oxalyl chloride (9 mL, 103.2 mmol). The ice-bath was removed and the mixture was refluxed at 50° C. under N2 for 4 h. The reaction mixture was evaporated and the residue was diluted with EtOAc and washed with water (3×50 mL) and brine, dried over Na2SO4 and evaporated where by red solid was obtained. The crude material from both batches were combined and purified by column chromatography on silica gel using 2.5-3% EtOAc in petroleum ether as eluant, and recrystallised from MeOH to give the title compound (15.7 g, 70%) as a white solid; 1H NMR (400 MHz, CD3OD) δ 1.42 (t, 3H, J=7.3 Hz), 3.84 (q, 2H, J=7.3 Hz), 7.6-7.7 (m, 3H), 7.9-8.0 (m, 2H); Mass Spectrum: M+H+ 272.

المصدر