F.J.S. Xavier et al. / Journal of Molecular Catalysis B: Enzymatic 108 (2014) 7–12
11
NMR 13C (50 MHz, CDCl3) ı (ppm): 73.8 (C OH), 117.2 (CN), 122.3
(CHAr), 124.5 (CHAr), 126.3 (CAr), 130.8 (CHAr), 132.1H2C , 133.5
(CHAr), 142.2 (CAr), 149.2 (CAr). GC–MS(m/z) = 204 (2%-M+), 152
(100%), 105 (28.6%), 51 (34.9%), 77 (55.5%).
67% of isolated yield. IR (KBr): 2918, 2848, 2231, 1770, 1533, 1450,
1352, 1263, 1222, 1010 cm−1; NMR 1H (200 MHz, CDCl3) ı (ppm):
8.24 (m, 2 H, 2 (CHArNO2)); 7.69 (m, 2H, 2 (CHArNO2)); 7.35 (m,
5 H, 5 (CHAr)); 6.51 (s, 1H, H
(s, 1H, H CH ); 3.41 (s, 3H, CH3). NMR 13C (50 MHz, CDCl3) ı
(ppm): 29.67 (CH3 O), 74.66 (C O and C CH2), 115.00 (CN),
C O); 6.09 (s, 1H, H CH ); 6.0
C
4.2.2. Synthesis of racemic ( )-2-cyano-1-(m-nitrophenyl)allyl
120.15 CHAr, 120.73 CHAr, 122.04 (O CH), 124.68 (CF3), 125.89 2
CHAr, 127.15 CHAr, 128.70 (CHArNO2), 130.07 (CHArNO2), 130.37
(CAr), 130.98 (C CH2), 133.0341 (CHArNO2), 133.41 (CHArNO2),
136.34 (CArNO2), 148.51 (C NO2), 165.01 (C O). GC–MS(m/z) = 189
(100%), 141 (31%), 119 (44%), 105 (69%), 77 (64%). Anal. Calcd. for
C20H15F3N2O5: C, 57.15; H, 3.60; N, 6.66. Found: C, 56.98; H, 3.65;
N, 6.72.
acetate (3)
2-[Hydroxy(m-nitrophenyl)methyl]acrylonitrile
( )-1
(2.1146 g, 10.3 mmol), triethylamine (1.5 mL), acetyl chloride
(2.0 mL) in 50 mL of dichloromethane were reacted for 3 h at
0 ◦C. After the complete reaction, the mixture was brought to
room temperature. The aqueous solution was extracted twice
with dichloromethane and dried with sodium sulfate. After
concentration, the crude material was subjected to flash col-
umn chromatography on silica gel on silica gel with 1/9 ethyl
acetate/hexane as eluent producing 82% of 3: IR (KBr) cm−1: 1751,
2229, 1531, 1354 cm−1; NMR 1H (200 MHz, CDCl3) ı (ppm): 8.24
(m, 2 H, 2 (CHAr); 7.75 (m, 1H, (CHAr)); 7.63 (m, 1H, (CHAr)); 6.40
4.2.5.2. With (S)-MTPA. The same procedure was realized.
The (S-[(R)-2-cyano-1-(3-nitrophenyl)allyl] 3,3,3-trifluoro-2-
methoxy-2phenylpropanoate (6) was obtained with 75% of
isolated yield. IR (KBr): 2920, 2850, 2231, 1759, 1535, 1454, 1352,
1271, 1236, 1020 cm−1; NMR 1H (200 MHz, CDCl3) ı (ppm): 8.24
(m, 2 H, 2 (CHArNO2)); 7.69 (m, 2H, 2 (CHArNO2)); 7.35 (m, 5 H,
(s, 1H, H
C O); 6.15 (dd, J = 1.2/0.7 Hz, 2H, ( CH2); 2.21 (s, 3H,
CH3
C
O). NMR 13C (50 MHz, CDCl3) ı: 21.5 (CH3), 73.9 (CH O),
5 (CHAr)); 6.51 (s, 1H, H
CH ); 3.41 (s, 3H, CH3). NMR 13C (50 MHz, CDCl3) ı (ppm):
29.67 (CH3 O), 56.00 (CH O), 74.91 (C O), 114.36 (C O),
115.25 (CN), 120.10 CHAr, 120.98 CHAr, 121.94 (C CH2), 124.53
(CHAr), 125.85 (CHAr), 126.91 (CF3), 128.59 (CHArNO2), 129.99
(CHArNO2), 130.21 CHAr, 131.10 (C CH2), 132.83 (CHArNO2),
134.19 (CHArNO2), 136.13 (CArNO2), 148.41 (C NO2), 165.00 (C O).
GC–MS(m/z) = 189 (100%), 119 (18%), 141 (22%), 105 (28%), 77
(20%). Anal. Calcd for C20H15F3N2O5: C, 57.15; H, 3.60; N, 6.66.
Found: C, 57.18; H, 3.57; N, 6.62.
C O); 6.09 (s, 1H, H CH ); 6.0 (s, 1H,
116.3 (CN), 122.6 (C CH2), 122.7 ( CH2), 124.9 (CHAr), 130.8
(CHAr), 133.6 (CHAr), 133.9 (CHAr), 138.4 (CAr), 149.2 (C NO2),
169.7 (C O). GC–MS(m/z) = 246 (2%-M+), 204 (26.6%), 186 (42.2%),
140 (44.4%), 43 (100%).
H
C
4.2.3. Enzymatic kinetic resolution of 2-cyano-1-(m-nitro
phenyl)allyl acetate (3) in the presence of CALB
The resolution was carried out in a 25 mL conical flask capped
with a stopper and stirred at 200 rpm. The CALB (15 mg) was sus-
pended in 10 mL of deionized H2O followed by the addition of
(
)-2-cyano-1-(m-nitrophenyl)allyl acetate (3) (50 mg) the result-
ing mixture was stirred at 30 ◦C for 48 h. The enzyme was filtered
out from the solution and washed with water (5 mL). The com-
bined organic phase was dried over anhydrous sodium sulfate
then evaporated, and the crude material was purified by flash
chromatography on silica gel with 1/9 ethyl acetate/hexane as elu-
ent producing 18.7 mg (42.9% isolated yield) of (R)-1 and 20.3 mg
(47.6% isolated yield) of (S)-3.
4.2.6. Synthesis of racemic
(
)-2-[Hydroxy(p-nitrophenyl)methyl]acrylonitrile (2)
p-Nitrobenzaldehyde (1 mmol), acrylonitrile (0.4 mL) and
DABCO (1 mmol) were reacting at 0 ◦C under 30 min. After the
complete reaction, the mixture was brought to room tempera-
ture and was directly filtered through silica gel, using 7/3 ethyl
acetate/hexane as eluent and the reaction products were con-
centrated under reduced pressure producing ( )-2 in 99% yield:
IR (KBr) cm−1 3481, 2225, 1523, 1350 cm−1; NMR 1H (200 MHz,
CDCl3) ı (ppm): 8.19 (dd, J = 8.8/4.0 Hz, 2H, ArorthoNO2); 7.55 (dd,
(R)-1 – [␣]D = +37 (C = 1.6 g/100 mL,CHCl3, 25 ◦C).
(S)-3 – [␣]D = −7 (C = 1.6 g/100 mL, CHCl3, 25 ◦C).
4.2.4. Synthesis of
J = 8.8/4.0 Hz, 2H ArmetaNO2); 6.14 (dd, J = 4.0/1.0 Hz, 1H C
C
Htrans);
In a 25 mL glass round bottom flask a solution of (S)-2-cyano-
1-(m-nitrophenyl)allyl acetate (38.1 mg, 0.15 mmol) in methanol
(2 mL) was added potassium carbonate (40 mg, 0.3 mmol). This
mixture was stirred for 6 h at 0 ◦C [18], and then the solution was
diluted with dichloromethane. The aqueous solution was extracted
twice with dichloromethane and dried with sodium sulfate. After
concentration, the crude material was subjected to flash column
chromatography on silica gel with 7/3 ethyl acetate/hexane as elu-
ent. The (S)-1 was obtained with quantitative yield (31.5 mg).
6.05 (dd, J = 4.0/1.2 Hz, 1H C
C Hcis); 5.39 (s, 1H, CHOH); 3.03 (s, 1H,
CHOH). NMR 13C (50 MHz, CDCl3) ı (ppm): 73.13 (H COH), 116.20
(CN), 123.97 (CHAr), 125.23 (CH2 C), 127.27 (CHAr), 131.03 (CH2 ),
145.93 (CAr), 147.88 (CAr). GC–MS(m/z) = 204 (3%-M+), 152 (100%),
105-(28.4%), 77 (60.0%), 51 (35.1%).
4.2.7. Synthesis of racemic ( )-2-cyano-1-(p-nitrophenyl)allyl
acetate (4)
2-[Hydroxy(p-nitrophenyl)methyl]acrylonitrile
( )-2
(2.1146 g, 10.3 mmol), triethylamine (1.5 mL), acetyl chloride
(2.0 mL) in 50 mL of dichloromethane were reacted at 0 ◦C for
3 h. After the complete reaction, the mixture was brought to
room temperature. The aqueous solution was extracted twice
with dichloromethane and dried under sodium sulfate. After
concentration, the crude material was subjected to flash column
chromatography on silica gel in 10/90 Ethyl acetate/hexane as
eluent producing quantitative yield of ( )4: IR (KBr) cm−1: 1751,
2229, 1523, 1350 cm−1; NMR 1H (200 MHz, CDCl3) ı (ppm): 8.27
(dd, J = 7.6/4.0 Hz, 2 H, 2ArHorthoNO2); 7.78 (dd, J = 7.5/4.0 Hz, 2H,
4.2.5. Determination of absolute configuration of (R)-1 by
Mosher method
4.2.5.1. With (R)-MTPA. In a 25 mL glass round bottom flask, alco-
hol (R)-1 (20 mg, 0.041 mmol), (R)-MTPA (30 mg, 0.13 mmol), DCC
(20 mg, 0.097 mmol) and DMAP (2.0 mg, 0.016 mmol) were added
to 4 mL of dry dichloromethane. This mixture was stirred at room
temperature for 8 h. The aqueous solution was extracted three
times with dichloromethane, and dried with sodium sulfate. After
concentration, the crude material was subjected to flash column
chromatography on silica gel firstly with hexane to remove DCU
(1,3-dicyclohexylurea) and then with 15/85 ethyl acetate/hexane
as eluent. The (R)-[(R)-2-cyano-1-(3-nitrophenyl) allyl] 3,3,3-
trifluoro-2-methoxy-2 phenylpropanoate (5) was obtained with
2ArHmetaNO2); 6.40 (m, 1H, H COH); 6.16 (s, 1H, C
C Htrans);
6.13 (s, 1H, C Hcis); 2.21 (s, 3H, CH3
C
C
O). NMR 13C (50 MHz,
CDCl3) ı (ppm): 20.99 (CH3 CO), 73.62 (HC O), 115.5 (CN),
122.0 (2CHArparaNO2), 124.2 (C ), 127.8 (2CHArmetaNO2), 133.2
(CH2 ), 142.4 (CAripsoC O ), 148.3 (CAripsoNO2), 169.0, (C O).