تفاعل #9011

معادلة التفاعل

AlCl3

CH3SCN

BCl3

m-cresol

→

2-Hydroxy-4-methylbenzonitrile

المردود 91.1%

المذيبات

1,2-dichloroethane

ظروف التفاعل

المعالجة

1. 1
   أخرى2-Hydroxy-4-methylbenzonitrile was prepared
2. 2
   أخرىThe cooling bath was removed
3. 3
   درجة الحرارةthen cooled to room temperature
4. 4
   workup.ADDITIONThe mixture was poured into 4 N NaOH (35 mL)
5. 5
   درجة الحرارةthe mixture was heated at 80° C. for 45 minutes
6. 6
   درجة الحرارةthen cooled to room temperature
7. 7
   أخرىThe phases were separated
8. 8
   استخلاصthe aqueous phase was extracted with CH2Cl2 (3×50 mL)
9. 9
   استخلاصextracted with diethyl ether (3×50 mL)
10. 10
    تجفيفThe combined ether extracts were dried (MgSO4)
11. 11
    تركيزconcentrated
12. 12
    أخرىPurification of the crude material by column chromatography on silica gel (20:1 CH2Cl2—EtOAc)

الإجراء التجريبي

2-Hydroxy-4-methylbenzonitrile was prepared following a modification of the procedure reported by Makoto Adachi and Tsutomu Sugasawa (Synthetic Communications 1990, 20, 71–84.). To a cold (0° C.) solution of BCl3 (1.0 M in heptane, 12.0 mL, 12.0 mmol) in 1,2-dichloroethane was added neat m-cresol (1.00 mL, 9.56 mmol) followed by CH3SCN (0.83 mL, 12.1 mmol) and AlCl3 (1.38 g, 10.4 mmol). The cooling bath was removed and the resultant mixture was heated to 80° C. for 3 hours then cooled to room temperature. The mixture was poured into 4 N NaOH (35 mL) and the mixture was heated at 80° C. for 45 minutes then cooled to room temperature. The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×50 mL). The aqueous phase was acidified with 6 N HCl (30 mL) and extracted with diethyl ether (3×50 mL). The combined ether extracts were dried (MgSO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1 CH2Cl2—EtOAc) provided 1.16 g (91%) of 2-Hydroxy-4-methylbenzonitrile as a white solid. 1H NMR (CDCl3) δ 2.36 (s, 3H), 6.20 (br s, 1H), 6.79–6.81 (m, 2H), 7.38 (d, 1H, J=9 Hz).

المصدر