10.1002/ejoc.201700981
European Journal of Organic Chemistry
FULL PAPER
injected as an internal standard for determining the yield by GC and the
reaction was quenched with saturated ammonium chloride solution (10
mL). The mixture was extracted with EtOAc (4 10 mL) and the
combined organic layers were concentrated and the residue purified by
flash column chromatography (70/30 pentane/CH2Cl2).
4-Cyclohexylbenzonitrile:[27] Table 1, Entry 1. Isolated as a colorless oil
in 94% yield (347 mg). 1H NMR (400 MHz, CDCl3): = 7.62–7.52 (m, 2H),
7.33–7.26 (m, 2H), 2.55 (tt, J = 9.1, 2.6 Hz, 1H), 1.90–1.83 (m, 4H),
1.82–1.76 (m, 1H), 1.44–1.36 (m, 4H), 1.33–1.17 (m, 1H) ppm. 13C NMR
(100 MHz, CDCl3): = 153.6, 132.3, 127.8, 119.4, 109.7, 44.9, 34.1, 26.8,
26.1 ppm. MS (EI): m/z = 185 [M]+.
2-Cyclohexylbenzonitrile:[34] Table 2, entry 8. Isolated as a colorless oil
in 91% yield (337 mg). 1H NMR (400 MHz, CDCl3): = 7.53–7.36 (m,
2H), 7.25 (dd, J = 8.0, 1.1 Hz, 1H), 7.14 (td, J = 7.6, 1.2 Hz, 1H), 2.93–
2.77 (m, 1H), 1.83–1.60 (m, 5H), 1.42–1.25 (m, 4H), 1.22–1.02 (m, 1H)
ppm. 13C NMR (100 MHz, CDCl3): = 151.3, 132.8, 132.7, 126.4, 126.2,
118.1, 111.7, 42.7, 33.5, 26.5, 25.8 ppm. MS (EI): m/z = 185 [M]+.
[1,1'-Biphenyl]-2-carbonitrile:[35] Table 2, entry 9. Isolated a as white
1
solid in 90% yield (321 mg). H NMR (400 MHz, CDCl3): = 7.75 (td, J =
6.3, 1.5 Hz, 1H), 7.63 (td, J = 7.8, 1.5 Hz, 1H), 7.57–7.40 (m, 7H) ppm.
13C NMR (100 MHz, CDCl3): = 145.7, 138.3, 133.9, 132.9, 130.2, 127.7,
118.9, 111.4 ppm. MS (EI): m/z = 179 [M]+.
Methyl 4-cyclohexylbenzoate:[27] Table 1, entry 2. Isolated as a white
solid (430 mg) containing about 25% of cyclohexyl p-cyclohexylphenyl
ketone which could not be separated. Yield 65%. 1H NMR (400 MHz,
CDCl3): = 7.98–7.90 (m, 2H), 7.30–7.21 (m, 2H), 3.87 (s, 3H), 2.60–
2.41 (m, 1H), 2.01–1.61 (m, 5H), 1.54–0.73 (m, 5H) ppm. 13C NMR (100
MHz, CDCl3): = 167.3, 153.6, 129.8, 127.8, 127.0, 52.0, 44.8, 34.6,
27.1, 26.4 ppm. MS (EI): m/z = 218 [M]+.
4'-Methoxy-[1,1'-biphenyl]-2-carbonitrile:[35] Table 2, entry 10.
Prepared according to the general procedure where the Grignard reagent
was added over 120 min at 0 °C to prevent a competing addition to the
cyano group. Isolated as a white solid in 80% yield (336 mg). 1H NMR
(400 MHz, CDCl3): = 7.74 (dd, J = 7.8, 1.3 Hz, 1H), 7.61 (td, J = 7.7,
1.4 Hz, 1H), 7.54–7.47 (m, 3H), 7.39 (td, J = 7.6, 1.2 Hz, 1H), 7.05–6.99
(m, 2H), 3.86 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): = 160.2, 145.3,
133.8, 132.9, 130.0, 127.1, 119.1, 114.3, 111.1, 55.5 ppm. MS (EI): m/z
= 209 [M]+.
4′-Chloro-[1,1'-biphenyl]-2-carbonitrile:[35] Table 2, entry 11. Prepared
according to the general procedure where the reaction mixture was
stirred for 2 h at 60 °C in an oil bath to ensure complete conversion of p-
chlorobenzonitrile. Isolated as a white solid in 79% yield (335 mg). 1H
NMR (400 MHz, CDCl3): = 7.77 (dd, J = 7.7, 1.3 Hz, 1H), 7.65 (td, J =
7.5, 1.3 Hz, 2H), 7.52–7.44 (m, 7H) ppm. 13C NMR (100 MHz, CDCl3):
= 144.3, 136.7, 135.2, 133.9, 133.1, 130.2, 128.0, 118.6, 111.4 ppm.
MS (EI): m/z = 213 [M]+.
4'-Methyl-[1,1'-biphenyl]-2-carbonitrile:[36] Table 2, entry 12. Prepared
according to the general procedure where the Grignard reagent was
added over 120 min at 0 °C to prevent a competing addition to the cyano
group. Isolated as a white solid in 78% yield (302 mg). 1H NMR (400 MHz,
CDCl3): = 7.70 (dd, J = 7.8, 1.3 Hz, 1H), 7.57 (td, J = 7.7, 1.4 Hz, 1H),
7.47–7.39 (m, 3H), 7.36 (td, J = 7.6, 1.3 Hz, 1H), 7.25 (d, J = 7.8 Hz, 2H),
2.37 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): = 145.6, 138.7, 135.3,
133.7, 132.8, 130.0, 129.5, 128.6, 127.3, 111.2, 21.4 ppm. MS (EI): m/z
= 193 [M]+.
4-Cyclohexyl-2-methylbenzonitrile (8):[34] Isolated as a colorless oil
(384 mg) which could not be obtained completely pure. Yield 88% as
estimated from the NMR spectrum. 1H NMR (400 MHz, CDCl3): = 7.66–
7.54 (m, 1H), 7.46–7.31 (m, 1H), 7.20 (d, J = 8.0 Hz, 1H), 2.80–2.35 (m,
4H), 2.02–1.75 (m, 5H), 1.71–1.15 (m, 5H) ppm. 13C NMR (100 MHz,
CDCl3): = 153.5, 141.9, 133.7, 132.6, 130.6, 129.0, 126.9, 125.0, 110.1,
44.8, 34.1, 26.8, 26.1, 20.6 ppm. MS (EI): m/z = 199 [M]+.
[1,1'-Biphenyl]-4-carbonitrile:[28] Table 2, entry 1. Isolated as
a
yellowish solid in 93% yield (334 mg). 1H NMR (400 MHz, CDCl3): =
7.76–7.65 (m, 4H), 7.63–7.55 (m, 2H), 7.53–7.44 (m, 2H), 7.47–7.38 (m,
1H) ppm. 13C NMR (100 MHz, CDCl3): = 145.8, 139.3, 132.7, 129.2,
128.8, 127.9, 127.4, 119.1, 111.1 ppm. MS (EI): m/z = 179 [M]+.
4'-Methoxy-[1,1'-biphenyl]-4-carbonitrile:[28] Table 2, entry 2. Prepared
according to the general procedure where the Grignard reagent was
added over 120 min at 0 °C to prevent a competing addition to the cyano
group. Isolated as a white solid in 83% yield (341 mg). 1H NMR (400
MHz, CDCl3): = 7.71–7.67 (m, 2H), 7.66–7.62 (m, 2H), 7.57–7.50 (m,
2H), 7.04–6.97 (m, 2H), 3.87 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3):
= 160.3, 145.3, 132.7, 131.6, 128.5, 127.2, 119.2, 114.7, 110.2, 55.5
ppm. MS (EI): m/z = 209 [M]+.
4'-Chloro-[1,1'-biphenyl]-4-carbonitrile:[29] Table 2, entry 3. Prepared
according to the general procedure where the reaction mixture was
stirred for 2 h at 60 °C in an oil bath to ensure complete conversion of p-
chlorobenzonitrile. Isolated as a white solid in 79% yield (335 mg). 1H
NMR (400 MHz, CDCl3): = 7.73 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 7.6 Hz,
2H), 7.52 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 7.6 Hz, 2H) ppm. 13C NMR
(100 MHz, CDCl3): = 144.5, 137.7, 135.1, 132.9, 129.5, 128.6, 127.7,
118.9, 111.4 ppm. MS (EI): m/z = 213 [M]+.
4'-Methyl-[1,1'-biphenyl]-4-carbonitrile:[30] Table 2, entry 4. Prepared
according to the general procedure where the Grignard reagent was
added over 120 min at 0 °C to prevent a competing addition to the cyano
group. Isolated as a white solid in 77% yield (296 mg). 1H NMR (400
MHz, CDCl3): = 7.63 (d, J = 8.5 Hz, 2H), 7.58 (d, J = 8.5 Hz, 2H), 7.43–
7.39 (m, 2H), 7.21 (d, J = 7.9 Hz, 2H), 2.34 (s, 3H) ppm. 13C NMR (100
MHz, CDCl3): = 145.7, 138.9, 136.4, 132.7, 130.0, 127.6, 127.2, 119.2,
110.7, 21.3 ppm. MS (EI): m/z = 193 [M]+.
4-Butylbenzonitrile:[31] Table 2, entry 5. Isolated as a colorless oil in
68% yield (217 mg). 1H NMR (400 MHz, CDCl3): = 7.52 (d, J = 7.5 Hz,
2H), 7.25 (d, J = 7.2 Hz, 2H), 2.64 (t, J = 7.8 Hz, 2H), 1.67–1.51 (p, J =
7.5 Hz, 2H), 1.33 (q, J = 7.4 Hz, 2H), 0.91 (t, J = 7.4 Hz, 3H) ppm. 13C
NMR (100 MHz, CDCl3): = 148.6, 132.0, 129.2, 119.1, 109.4, 35.8,
33.1, 22.2, 13.8 ppm. MS (EI): m/z = 159 [M]+.
4-Isobutylbenzonitrile:[32] Table 2, entry 6. Isolated as a colorless oil
(290 mg) which could not be obtained completely pure. Yield 63% as
estimated from the NMR spectrum. 1H NMR (400 MHz, CDCl3): = 7.42–
7.38 (m, 2H), 7.12–7.08 (m, 2H), 2.38 (d, J = 7.3 Hz, 2H), 1.74 (dt, J =
13.6, 6.8 Hz, 1H), 0.76 (d, J = 6.7 Hz, 6H) ppm. 13C NMR (100 MHz,
CDCl3): = 147.3, 131.9, 129.8, 129.7, 119.1, 109.5, 45.4, 30.0, 22.2
ppm. MS (EI): m/z = 159 [M]+.
5-Cyclohexyl-2-methylbenzonitrile (9): Isolated as a colorless oil in
62% yield (246 mg). 1H NMR (400 MHz, CDCl3): = 7.61 (d, J = 8.0 Hz,
1H), 7.29–7.15 (m, 2H), 2.66–2.60 (m, 4H), 2.10–1.75 (m, 5H), 1.63–1.26
(m, 5H) ppm. 13C NMR (100 MHz, CDCl3): = 153.4, 132.5, 128.9,
124.9, 118.6, 110.0, 44.8, 34.0, 26.7, 26.0, 20.6 ppm. HRMS: calcd for
C14H18N 200.1434 [M + H]+, found: 200.1436.
2-Cyclohexyl-6-methylbenzonitrile (10):[34] Isolated as a white solid in
81% yield (322 mg). 1H NMR (400 MHz, CDCl3): = 7.40 (t, J = 7.8 Hz,
1H), 7.17 (d, J = 7.9 Hz, 1H), 7.12 (d, J = 7.6 Hz, 1H), 2.98 (tt, J = 11.3,
3.1 Hz, 1H), 2.53 (s, 3H), 1.95–1.72 (m, 5H), 1.57–1.35 (m, 4H), 1.34–
1.17 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): = 151.9, 142.3, 132.4,
127.5, 123.7, 117.3, 112.5, 43.1, 33.9, 26.8, 26.1, 21.1 ppm. MS (EI):
m/z = 199 [M]+.
3-(Allyloxy)-4-chlorobenzonitrile (13):
A
mixture of 4-chloro-3-
hydroxybenzonitrile (1 g, 6.5 mmol), allyl bromide (0.6 mL, 7.1 mmol) and
K2CO3 (1 g, 7.2 mmol) in acetone (50 mL) was stirred under reflux. The
reaction was monitored by TLC and additional allyl bromide (0.6 mL, 7.1
mmol) and K2CO3 (1 g, 7.2 mmol) were added after 20 min. After two
hours, the reaction was diluted with water and extracted with diethyl ether.
The organic layers were concentrated to give 1.2 g (95%) of a brown
solid. 1H NMR (400 MHz, CDCl3): = 7.47 (d, J = 8.1 Hz, 1H), 7.20 (d, J
4-Isopropylbenzonitrile:[33] Table 2, entry 7. Isolated as a yellowish oil
in 58% yield (168 mg). 1H NMR (400 MHz, CDCl3): = 7.54–7.45 (m,
2H), 7.25 (d, J = 8.3 Hz, 2H), 2.88 (d, J = 6.9 Hz, 1H), 1.19 (d, J = 7.0 Hz,
6H) ppm. 13C NMR (100 MHz, CDCl3): = 154.4, 132.2, 127.3, 119.2,
109.6, 34.4, 23.5 ppm. MS (EI): m/z = 145 [M]+.
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