Paper
RSC Advances
DMSO. All the 19F NMR spectra were recorded on a Bruker DPX 65–66 ꢀC/64.9–66.4 ꢀC). 1H NMR (300 MHz, CDCl3) d 7.26 (d, J ¼
400 spectrometer in CDCl3. Melting points (uncorrected) were 8.3 Hz, 1H), 7.05 (s, 1H), 6.88 (d, J ¼ 8.4 Hz, 1H), 3.91 (s, 3H),
measured on a XT4 MP Apparatus (Taike Corp., Beijing, China). 3.88 (s, 3H). 13C NMR (151 MHz, CDCl3) d 152.84, 149.16,
126.48, 119.26, 113.88, 111.23, 103.85, 56.14, 56.11.
3-Hydroxybenzonitrile (9b). Slightly yellow crystal, 89% yield.
General procedure for preparation of compounds 1b–25b
Mp: 78.5–80.5 ꢀC (ref. mp: 74.8–77.2 ꢀC/57–59.5 ꢀC/78–80 ꢀC/68
A mixture of aromatic aldehydes (50 mmol) (1a–25a), hydroxyl- ꢀC/76–78 ꢀC). 1H NMR (300 MHz, CDCl3) d 8.06 (s, 1H), 7.30 (dd,
amine hydrochloride (62.5 mmol), sodium formate or sodium J ¼ 15.6, 7.7 Hz, 1H), 7.19 (d, J ¼ 7.6 Hz, 1H), 7.13 (d, J ¼ 2.9 Hz,
acetate (125 mmol) were dissolved in formic acid or acetic acid 1H), 6.63 (s, 1H). 13C NMR (151 MHz, CDCl3) d 156.70, 130.65,
solution and stirred at 80 ꢀC until TLC analysis indicated the 124.51, 121.11, 118.84, 118.72, 112.38.
disappearance of aromatic aldehydes. Then, aer the reaction
4-Hydroxybenzonitrile (10b). White crystal, 52% yield. Mp:
system cooled down to room temperature, it was immersed into 110.5–113.0 ꢀC (ref. mp: 110–113 ꢀC/111–112 ꢀC/109–111 ꢀC/
water to obtain the target compounds. Some desired products 108.8–110.2 ꢀC/100.7–103.2 ꢀC/107–109 ꢀC/111–112 ꢀC). 1H
dissolved in the formic acid or acetic acid solution could be ob- NMR (300 MHz, CDCl3) d 7.61–7.52 (m, 2H), 6.99–6.91 (m, 2H),
tained by salting out. Then, the solid target compounds were ob- 6.83 (s, 1H). 13C NMR (151 MHz, DMSO-d6) d 162.61, 135.22,
tained by ltration and recrystallized by alcohol, and then dried 120.53, 117.38, 101.96.
under vacuum. However, some target compounds were oily. These
2-Methylbenzonitrile (11b). Colorless liquid, 91% yield. 1H
oily compounds were obtained by extraction with ethyl acetate and NMR (300 MHz, CDCl3) d 7.56 (d, J ¼ 7.7 Hz, 1H), 7.46 (td, J ¼
the solvent was removed in vacuum to afford aryl nitriles (1b–25b). 7.6, 1.3 Hz, 1H), 7.34–7.16 (m, 2H), 2.52 (s, 3H). 13C NMR (151
Analytical data
MHz, CDCl3) d 141.92, 132.66, 132.50, 130.24, 126.23, 118.17,
2-Chlorobenzonitrile (1b). Light yellow needle crystal, 56% 112.73, 20.47.
1
3-Methylbenzonitrile (12b). Colorless liquid, 74% yield. 1H
ꢀ
ꢀ
yield. Mp: 43.6–45.5 C (ref. mp: 43–45 C, see ESI†). H NMR
(500 MHz, CDCl3) d 7.68 (d, J ¼ 8.2 Hz, 1H), 7.58–7.49 (m, 2H), NMR (300 MHz, CDCl3) d 7.46–7.40 (m, 2H), 7.38 (s, 1H), 7.36–
7.41–7.34 (m, 1H). 13C NMR (151 MHz, CDCl3) d 136.84, 134.02, 7.30 (m, 1H), 2.37 (s, 3H). 13C NMR (151 MHz, CDCl3) d 139.23,
133.91, 130.05, 127.18, 115.99, 113.36.
133.67, 132.48, 129.27, 129.00, 119.06, 112.20, 21.16.
4-Chlorobenzonitrile (2b). White ake crystals, 78% yield. Mp:
3-Aminobenzonitrile (13b). Brown crystal, 65% yield. Mp: 53.5–
90.6–92.8 ꢀC (ref. mp: 90–93 ꢀC/92–94 ꢀC/91.2–93.1 ꢀC). 1H NMR 54.5 ꢀC (ref. mp: 52–54 ꢀC/50–52 ꢀC/50–54 ꢀC). 1H NMR (300
(300 MHz, CDCl3) d 7.60 (d, J ¼ 8.4 Hz, 2H), 7.47 (d, J ¼ 8.5 Hz, MHz, CDCl3) d 7.22 (t, J ¼ 7.8 Hz, 1H), 7.01 (d, J ¼ 7.6 Hz, 1H),
2H). 13C NMR (151 MHz, CDCl3) d 139.55, 133.40, 129.70, 6.89 (t, J ¼ 5.8, 1.7 Hz, 1H), 3.89 (s, 2H). 13C NMR (151 MHz,
118.00, 110.75.
CDCl3) d 146.98, 130.06, 121.92, 119.24, 119.21, 117.40, 112.84.
4-Aminobenzonitrile (14b). White crystal, 70% yield. Mp: 83.5–
2,3-Dichlorobenzonitrile (3b). White needle crystals, 78% yield.
Mp: 61.5–62.4 ꢀC (ref. mp: 60–61 ꢀC/56–57 ꢀC/51–53.5 ꢀC). 1H 85.0 ꢀC (ref. mp: 83–85 ꢀC/83–86 ꢀC/85–87 ꢀC/85–86 ꢀC). 1H
NMR (300 MHz, CDCl3) d 8.57 (s, 1H), 7.76 (dd, J ¼ 7.9, 1.5 Hz, NMR (300 MHz, CDCl3) d 7.40 (dd, J ¼ 8.8, 2.0 Hz, 2H), 6.64 (d, J
1H), 7.49 (dd, J ¼ 8.0, 1.6 Hz, 1H). 13C NMR (151 MHz, DMSO-d6) ¼ 8.7 Hz, 2H), 4.19 (s, 2H). 13C NMR (151 MHz, DMSO) d 153.98,
d 145.61, 133.72, 133.27, 132.00, 131.11, 129.35, 126.36.
134.43, 121.68, 114.42, 96.49.
2,6-Dichlorobenzonitrile (4b). White needle crystals, 91%
2-Fluorobenzonitrile (15b). Colorless transparent liquid, 74%
yield. Mp: 143.5–145.0 ꢀC (ref. mp: 144–145 ꢀC/140–143 ꢀC/144– yield. 1H NMR (300 MHz, CDCl3) d 7.57–7.66 (m, 2H), 7.31 (d, J ¼
145 ꢀC). 1H NMR (300 MHz, CDCl3) d 7.52–7.46 (m, 1H), 7.44 (d, 3.0 Hz, 1H), 7.22 (dd, J ¼ 18.0, 9.0 Hz, 1H). 13C NMR (151 MHz,
J ¼ 4.9 Hz, 2H). 13C NMR (151 MHz, CDCl3) d 138.49, 133.90, CDCl3) d 164.13, 162.17, 135.08, 133.57, 124.87, 116.58, 113.90,
128.17, 114.38, 113.37.
101.27.
4-(Triuoromethoxy)benzonitrile (16b). Colorless liquid, 63%
2-Methoxybenzonitrile (5b). White needle crystals, 77% yiꢀeld.
Mp: 24.5–25.5 C (ref. mp: 59 C/21.5–22 C (ethanol)/24.5 C). yield. 1H NMR (300 MHz, CDCl3) d 7.76–7.68 (m, 2H), 7.35–7.28
1H NMR (500 MHz, CDCl3) d 7.55 (t, J ¼ 7.1 Hz, 2H), 7.04–6.95 (m, 2H). 13C NMR (151 MHz, CDCl3) d 152.36, 134.07, 121.19,
(m, 2H), 3.93 (s, 3H). 13C NMR (151 MHz, CDCl3) d 161.21, 117.73, 110.84.
ꢀ
ꢀ
ꢀ
134.53, 133.86, 120.80, 116.38, 111.70, 101.61, 56.03.
2-Fluoro-6-methoxybenzonitrile (17b). White crystal, 65% yield.
3-Methoxybenzonitrile (6b). Colorless transparent liquid, 68% Mp: 103.5–105.0 ꢀC (ref. mp: 93–95 ꢀC). 1H NMR (300 MHz,
yield. Mp: 20.0–22.0 ꢀC (ref. mp: 24–25 ꢀC/23 ꢀC). 1H NMR (300 CDCl3) d 7.52 (td, J ¼ 8.5, 6.6 Hz, 1H), 6.79 (t, J ¼ 8.1 Hz, 2H),
MHz, CDCl3) d 7.42–7.29 (m, 1H), 7.24 (t, J ¼ 7.3 Hz, 1H), 7.13 (s, 3.96 (s, 1H). 13C NMR (151 MHz, CDCl3) d 164.84, 163.14,
2H), 3.82 (t, J ¼ 0.7 Hz, 3H). 13C NMR (151 MHz, CDCl3) 162.39, 135.14, 111.63, 108.16, 106.97, 91.77, 56.70.
d 159.62, 130.35, 124.48, 119.31, 118.77, 116.83, 113.16, 55.54.
2-Chloro-4-uorobenzonitrile (18b). White crystal, 68% yield.
1
4-Methoxybenzonitrile (7b). White powder, 65% yield. Mp: Mp: 64.5–66.0 ꢀC (ref. mp: 63.0–65.0 ꢀC). H NMR (300 MHz,
57.5–59.5 ꢀC (ref. mp: 58–59 ꢀC/55–57 ꢀC/59.2–60.4 ꢀC/56–58 ꢀC/ chloroform-d) d 7.70 (dd, J ¼ 8.7, 5.6 Hz, 1H), 7.28 (dd, J ¼ 8.0,
59–60 ꢀC). 1H NMR (300 MHz, CDCl3) d 7.58 (d, J ¼ 8.8 Hz, 2H), 2.3 Hz, 1H), 7.12 (ddd, J ¼ 8.7, 7.7, 2.5 Hz, 1H). 13C NMR (151
6.94 (d, J ¼ 8.8 Hz, 2H), 3.85 (s, 3H). 13C NMR (151 MHz, CDCl3) MHz, CDCl3) d 165.61, 163.88, 138.76, 135.70, 118.08, 115.28,
d 162.85, 133.99, 119.28, 114.76, 103.89, 55.57.
115.21, 109.78.
3,4-Dimethoxybenzonitrile (8b). White crystal, 79% yield. Mp:
2-Fluoro-4-hydroxybenzonitrile (19b). White crystal, 45% yield.
ꢀ
67.5–70.5 ꢀC (ref. mp: 68.6–70.5 ꢀC/65–67 ꢀC/66–67 ꢀC/62–65 ꢀC/ Mp: 123.5–125.0 ꢀC (ref. mp: 124–125 ꢀC/123.5 C/117–118 ꢀC).
© 2021 The Author(s). Published by the Royal Society of Chemistry
RSC Adv., 2021, 11, 24232–24237 | 24235