E
O. Khoumeri et al.
Paper
Synthesis
1H NMR (250 MHz, CDCl3): δ = 2.24 (br, 1 H, OH), 2.95 (dd, J = 13.7, 5.8
Hz, 1 H, CH2), 3.02 (dd, J = 13.7, 7.2 Hz, 1 H, CH2), 4.86 (dd, J = 7.2, 5.8
Hz, 1 H, CH), 7.57 (d, J = 8.5 Hz, 2 H, ArH), 7.57 (d, J = 8.5 Hz, 2 H, ArH),
7.53–7.58 (m, 2 H, ArH), 7.53–7.58 (m, 2 H, ArH).
13C NMR (62.5 MHz, CDCl3): δ = 45.0, 74.1, 112.1, 118.8, 127.1 (2 C),
128.6 (2 C), 129.0, 130.3, 133.0, 133.5, 134.2, 139.2, 141.7.
1H NMR (250 MHz, CDCl3): δ = 2.23 (br, 1 H, OH), 3.13 (dd, J = 13.7, 8.4
Hz, 1 H, CH2), 3.25 (dd, J = 13.7, 4.6 Hz, 1 H, CH2), 5.10 (dd, J = 8.8, 4.6
Hz, 1 H, CH), 7.30 (dd, J = 7.6, 1.0 Hz, 1 H, ArH), 7.37 (dd, J = 7.6, 1.3 Hz,
1 H, ArH), 7.49 (d, J = 8.5 Hz, 2 H, ArH), 7.53 (dt, J = 7.7, 1.4 Hz, 1 H,
ArH), 7.62 (d, J = 8.5 Hz, 2 H, ArH), 7.64 (dt, J = 7.3, 1.1 Hz, 1 H, ArH).
13C NMR (62.5 MHz, CDCl3): δ = 44.4, 73.5, 111.4, 112.9, 118.0, 118.7,
126.4 (2 C), 127.4, 131.1, 132.3 (2 C), 132.7, 132.8, 141.2, 148.4.
HRMS (ESI): m/z [M + Na]+ calcd for C16H12N2ONa: 271.0842; found:
HRMS (ESI): m/z [M + NH4]+ calcd for C15H12BrNO: 319.0441; found:
319.0444.
271.0844.
3-[2-(2-Bromophenyl)-2-hydroxyethyl]benzonitrile (6h)
2-[2-Hydroxy-2-(p-tolyl)ethyl]benzonitrile (7e)
Yield: 110 mg (30%); white solid; mp 102 °C.
Yield: 85 mg (30%); beige solid; mp 89 °C.
1H NMR (250 MHz, CDCl3): δ = 2.22 (br, 1 H, OH), 2.84 (dd, J = 13.9, 8.7
Hz, 1 H, CH2), 3.15 (dd, J = 13.9, 3.3 Hz, 1 H, CH2), 5.25 (dd, J = 8.7, 3.3
Hz, 1 H, CH), 7.16 (dt, J = 7.6, 1.7 Hz, 1 H, ArH), 7.35 (dt J = 7.7, 0.7 Hz,
1 H, ArH), 7.42 (dd J = 7.2, 0.7 Hz, 1 H, ArH), 7.49–7.56 (m, 5 H, ArH).
13C NMR (62.5 MHz, CDCl3): δ = 43.3, 73.4, 112.1, 118.9, 121.5, 127.2,
127.8, 129.0, 129.1, 130.2, 132.6, 133.1, 134.2, 139.7, 142.3.
1H NMR (250 MHz, CDCl3): δ = 2.14 (br, 1 H, OH), 2.35 (s, 3 H, CH3),
3.17 (dd, J = 13.7, 7.9 Hz, 1 H, CH2), 3.25 (dd, J = 13.7, 2.2 Hz, 1 H, CH2),
4.96 (dd, J = 7.9, 2.2 Hz, 1 H, CH), 7.17 (d, J = 7.9 Hz, 2 H, ArH), 7.28 (d,
J = 7.9 Hz, 2 H, ArH), 7.30–7.36 (m, 2 H, ArH), 7.51 (dt, J = 7.7, 1.4 Hz, 1
H, ArH), 7.63 (dd, J = 7.7, 1.1 Hz, 1 H, ArH).
13C NMR (62.5 MHz, CDCl3): δ = 21.0, 44.3, 74.2, 112.9, 118.1, 125.6 (2
C), 126.9, 129.1 (2 C), 130.9, 132.4, 132.6, 137.5, 140.3, 142.3.
HRMS (ESI): m/z [M + NH4]+ calcd for C15H12BrNO: 319.0441; found:
319.0437.
HRMS (ESI): m/z [M + NH4]+ calcd for C16H15NO: 255.1492; found:
255.1493.
2-[2-(4-Chlorophenyl)-2-hydroxyethyl]benzonitrile (7a)
Yield: 116 mg (37%); white solid; mp 87 °C.
2-[2-(3-Bromophenyl)-2-hydroxyethyl]benzonitrile (7f)
1H NMR (250 MHz, CDCl3): δ = 2.13 (br, 1 H, OH), 3.15 (dd, J = 13.7, 8.1
Hz, 1 H, CH2), 3.24 (dd, J = 13.7, 5.0 Hz, 1 H, CH2), 5.00 (dd, J = 8.1, 5.0
Hz, 1 H, CH), 7.27–7.31 (m, 5 H, ArH), 7.34 (dt, J = 7.6, 1.1 Hz, 1 H,
ArH), 7.51 (dt J = 7.6, 1.4 Hz, 1 H, ArH), 7.63 (d J = 7.6 Hz, 1 H, ArH).
13C NMR (62.5 MHz, CDCl3): δ = 44.4, 73.7, 112.9, 118.1, 127.1 (2 C),
127.2, 128.6 (2 C), 131.0, 132.6, 132.8, 133.5, 141.7, 141.8.
Yield: 155 mg (42%); colorless oil.
1H NMR (250 MHz, CDCl3): δ = 2.13 (br, 1 H, OH), 3.14 (dd, J = 13.9, 8.5
Hz, 1 H, CH2), 3.255 (dd, J = 13.9, 4.6 Hz, 1 H, CH2), 4.98 (dd, J = 8.5, 4.6
Hz, 1 H, CH), 7.18–7.32 (m, 3 H, ArH), 7.36 (dd, J = 7.6, 1.3 Hz, 1 H,
ArH), 7.44 (dt, J = 7.7, 1.9 Hz, 1 H, ArH), 7.49–7.55 (m, 2 H, ArH), 5.65
(dd, J = 7.7, 1.3 Hz, 1 H, ArH).
13C NMR (62.5 MHz, CDCl3): δ = 44.4, 73.6, 112.9, 118.1, 122.6, 124.4,
127.2, 128.8, 130.1, 130.9, 131.1, 132.6, 132.8, 141.7, 145.5.
HRMS (ESI): m/z [M + Na]+ calcd for C15H12ClNONa: 280.0500; found:
280.0500.
HRMS (ESI): m/z [M + NH4]+ calcd for C15H12BrNO: 319.0441; found:
319.0441.
2-(2-Hydroxy-2-phenylethyl)benzonitrile (7b)
Yield: 130 mg (48%); white solid; mp 75 °C.
1H NMR (250 MHz, CDCl3): δ = 2.04 (br, 1 H, OH), 3.08 (dd, J = 13.7, 8.2
Hz, 1 H, CH2), 3.15 (dd, J = 13.7, 5.5 Hz, 1 H, CH2), 4.90 (dd, J = 8.2, 5.5
Hz, 1 H, CH), 7.16–7.27 (m, 7 H, ArH), 7.40 (dt, J = 7.4, 1.4 Hz, 1 H,
ArH), 7.52 (dd, J = 7.4, 1.4 Hz, 1 H, ArH).
13C NMR (62.5 MHz, CDCl3): δ = 44.3, 74.3, 112.9, 118.1, 125.7 (2 C),
127.0, 127.8, 128.5 (2 C), 131.0, 132.5, 132.7, 142.2, 143.2.
2-[2-(4-Bromophenyl)-2-hydroxyethyl]benzonitrile (7g)
Yield: 140 mg (38%); white solid; mp 72 °C.
1H NMR (250 MHz, CDCl3): δ = 2.12 (br, 1 H, OH), 3.14 (dd, J = 13.9, 8.2
Hz, 1 H, CH2), 3.255 (dd, J = 13.9, 5.0 Hz, 1 H, CH2), 4.98 (dd, J = 8.2, 5.0
Hz, 1 H, CH), 7.25 (d, J = 8.4 Hz, 2 H, ArH), 7.34 (dt, J = 7.6, 1.1 Hz, 2 H,
ArH), 7.46 (d, J = 8.4 Hz, 2 H, ArH), 7.51 (dt, J = 7.6, 1.4 Hz, 1 H, ArH),
7.63 (dd, J = 7.7, 1.3 Hz, 1 H, ArH).
HRMS (ESI): m/z [M + NH4]+ calcd for C15H13NO: 241.1335; found:
241.1341.
13C NMR (62.5 MHz, CDCl3): δ = 44.3, 73.6, 112.8, 118.0, 121.5, 127.1,
127.4 (2 C), 131.0, 131.5 (2 C), 132.6, 132.7, 141.7, 142.2.
HRMS (ESI): m/z [M + NH4]+ calcd for C15H12BrNO: 319.0441; found:
319.0443.
2-[2-(2-Chlorophenyl)-2-hydroxyethyl]benzonitrile (7c)
Yield: 120 mg (38%); white solid; mp 84 °C.
1H NMR (250 MHz, CDCl3): δ = 2.14 (br, 1 H, OH), 3.10 (dd, J = 13.9, 8.0
Hz, 1 H, CH2), 3.22 (dd, J = 13.9, 4.3 Hz, 1 H, CH2), 5.34 (dd, J = 8.0, 4.3
Hz, 1 H, CH), 7.10–7.26 (m, 5 H, ArH), 7.38–7.57 (m, 3 H, ArH).
13C NMR (62.5 MHz, CDCl3): δ = 42.0, 70.8, 113.5, 118.1, 127.0, 127.1,
127.2, 128.8, 129.3, 130.8, 131.7, 132.4, 132.7, 140.4, 141.6.
2-[2-(2-Bromophenyl)-2-hydroxyethyl]benzonitrile (7h)
Yield: 170 mg (46%); white solid; mp 100 °C.
1H NMR (250 MHz, CDCl3): δ = 2.45 (br, 1 H, OH), 3.12 (dd, J = 14.0, 8.2
Hz, 1 H, CH2), 3.22 (dd, J = 14.0, 4.4 Hz, 1 H, CH2), 5.32 (dd, J = 8.2, 44
Hz, 1 H, CH), 7.09 (dt, J = 7.6, 1.7 Hz, 1 H, ArH), 7.24–7.32 (m, 3 H,
ArH), 7.42–7.48 (m, 3 H, ArH), 7.52 (dt, J = 8.0, 1.6 Hz, 1 H, ArH).
HRMS (ESI): m/z [M + NH4]+ calcd for C15H12ClNO: 275.0946; found:
275.0943.
13C NMR (62.5 MHz, CDCl3): δ = 41.9, 72.8, 113.8, 118.1, 121.7, 126.9,
127.5, 126.7, 129.1, 130.7, 132.4, 132.5, 132.6, 141.5, 141.9.
HRMS (ESI): m/z [M + NH4]+ calcd for C15H12BrNO: 319.0441; found:
2-[2-(4-Cyanophenyl)-2-hydroxyethyl]benzonitrile (7d)
Yield: 96 mg (32%); white solid; mp 118 °C.
319.0442.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G