تفاعل #420661

معادلة التفاعل

isobutyraldehyde

phenylmagnesium bromide

3-iodo-4-nitrobenzonitrile

dry ice isopropanol

→

racemic (RS)-1-(5-cyano-2-nitrophenyl)-2-methyl-1-propanol

المردود 23.0%

المذيبات

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرى40° C
2. 2
   workup.ADDITIONUpon completion of the addition the mixture
3. 3
   أخرىquenched with saturated NH4Cl (2 mL)
4. 4
   workup.ADDITIONpoured into water (50 mL)/dichloromethane (50 mL)
5. 5
   أخرىThe organic layer was separated
6. 6
   استخلاصaqueous layer was extracted three times with dichloromethane (25 mL each)
7. 7
   استخلاصCombined organic extract
8. 8
   تجفيفwas dried over anhydrous Na2SO4
9. 9
   تركيزconcentrated under reduced pressure
10. 10
    أخرىpurified by silica gel column chromatography

الإجراء التجريبي

To a solution of 3-iodo-4-nitrobenzonitrile (314 mg, 1.14 mmol) in anhydrous tetrahydrofuran (5.5 mL) cooled at minus 45° C. (dry ice-isopropanol bath) under nitrogen atmosphere, phenylmagnesium bromide (2 M in THF, 3.16 mL, 6.32 mmol) was added at a rate to keep the temperature at or below minus 40° C. Upon completion of the addition the mixture was stirred for five minutes, then isobutyraldehyde (0.957 mL, 10.54 mmol) was added. The mixture was allowed to gradually warm up to room temperature, then quenched with saturated NH4Cl (2 mL) and poured into water (50 mL)/dichloromethane (50 mL). The organic layer was separated; aqueous layer was extracted three times with dichloromethane (25 mL each). Combined organic extract was dried over anhydrous Na2SO4, concentrated under reduced pressure, and purified by silica gel column chromatography to yield racemic (RS)-1-(5-cyano-2-nitrophenyl)-2-methyl-1-propanol (57 mg, 23%) as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.93 (d, 1H, J=8.1 Hz, Ph-H), 7.74 (s, 1H, Ph-H), 7.21 (d, 1H, J=8.1 Hz, Ph-H), 4.72 (d, 1H, J=3.6 Hz, Ph-CH), 2.33 (br. s, 1H, OH), 2.03 (m, 1H, CHCH(CH3)2), 1.04 (d, 3H, J=6.8 Hz, CH3), 0.89 (d, 3H, J=6.6 Hz, CH3); 13C NMR (100 MHz, CDCl3): δ 147.78 (C), 140.25 (CH), 131.40 (CH), 131.24 (CH), 118.36 (C), 112.27 (CN), 103.82 (C), 80.80 (CH), 33.56 (CH), 19.70 (CH3), 15.62 (CH3).

المصدر