The Journal of Organic Chemistry
Article
1H), 4.12 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ. 186.6,
147.5, 139.2, 133.0, 129.1, 128.7, 127.7, 127.3, 113.8, 29.3.
3-(Naphthalen-1-yl)-3-oxopropanenitrile (3h). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3h. White solid (29.6 mg, 76%), mp 96−97 °C. Lit.15 98−100
°C. 1H NMR (400 MHz, CDCl3): δ 8.82 (d, J = 8.4 Hz, 1H), 8.11 (d,
J = 8.0 Hz, 1H), 7.88−7.92 (m, 2H), 7.68−7.65 (m, 1H), 7.61−7.52
(m, 2H), 4.21 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 189.5,
135.2, 134.1, 131.6, 130.4, 129.5, 129.2, 128.7, 127.1, 125.6, 124.2,
114.0, 31.8.
3-(Naphthalen-2-yl)-3-oxopropanenitrile (3i). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3i. White solid (36.3 mg, 93%), mp 107−108 °C. Lit.15 97−
101 °C. 1H NMR (500 MHz, CDCl3): δ 8.42 (s, 1H), 8.00−7.90 (m,
4H), 7.69−7.66 (m, 1H), 7.63−7.60 (m, 1H), 4.22 (s, 2H); 13C{1H}
NMR (125 MHz, CDCl3): δ 186.9, 136.2, 132.3, 131.7, 130.7, 129.7,
129.5, 129.2, 127.9, 127.4, 123.4, 113.8, 29.4.
3-(4-Iodophenyl)-3-oxopropanenitrile (3q). Flash column chro-
matography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to afford 3q.
White solid (38.5 mg, 71%), mp 173−174 °C. Lit.13 173−175 °C. 1H
NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4
Hz, 2H), 4.03 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 186.5,
138.6, 133.6, 129.6, 113.3, 103.2, 29.3.
3-(4-Methoxyphenyl)-3-oxopropanenitrile (3r). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3r. White solid (23.5 mg, 67%), mp 126−127 °C. Lit.8e 129.2−
1
131.1 °C. H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.8 Hz, 2H),
6.97 (d, J = 8.8 Hz, 2H), 4.03 (s, 2H), 3.88 (s, 3H); 13C{1H} NMR
(125 MHz, CDCl3): δ 185.4, 164.7, 130.9, 127.3, 114.3, 114.1, 55.6,
29.0.
3-Oxo-3-(4-phenoxyphenyl)propanenitrile (3s). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3s. White solid (35.5 mg, 75%). mp 98−100 °C. Lit.8a 1H
NMR (500 MHz, CDCl3): δ 7.89 (d, J = 8.5 Hz, 2H), 7.43−7.40 (m,
2H), 7.25−7.22 (m, 1H), 7.08 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 9.0
Hz, 2H), 4.04 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 185.6,
163.4, 154.8, 130.9, 130.2, 128.7, 125.1, 120.4, 117.4, 113.9, 29.1.
3-Oxo-3-(4-(trifluoromethoxy)phenyl)propanenitrile (3t). Flash
column chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/
v) to afford 3t. White solid (40.3 mg, 88%), mp 88−89 °C. 1H NMR
(400 MHz, CDCl3): δ 8.01−7.98 (m, 2H), 7.35 (d, J = 8.0 Hz, 2H),
4.08 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 185.6, 153.8,
3-(2-Fluorophenyl)-3-oxopropanenitrile (3j). Flash column chro-
matography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to afford 3j.
White solid (3.9 mg, 12%), mp 54−56 °C. Lit.18 60−61 °C. 1H NMR
(400 MHz, CDCl3): δ 8.00−7.95 (m, 1H), 7.65−7.63 (m, 1H),
7.33−7.29 (m, 1H), 7.23−7.18 (m, 1H), 4.10 (s, 2H); 13C{1H} NMR
4
(125 MHz, CDCl3): δ 185.0 (C−F, JC−F = 3.8 Hz), 162.2 (C−F,
1JC−F = 252.5 Hz), 136.6 (C−F, 3JC−F = 8.8 Hz), 131.2 (C−F, 4JC−F
=
2.5 Hz), 125.2 (C−F, 4JC−F = 2.5 Hz), 122.7 (C−F, 3JC−F = 12.5 Hz),
1
2
4
132.3, 130.7, 120.2 (C−F, JC−F = 257.5 Hz), 120.7, 113.3, 29.4.
116.9 (C−F, JC−F = 22.5 Hz), 113.4 (C−F, JC−F = 5.0 Hz), 33.7
HRMS (ESI): calcd for C10H6F3NO2 [M + Na]+, 252.0249; found,
252.0239.
3
(C−F, JC−F = 12.5 Hz).
3-(3-Fluorophenyl)-3-oxopropanenitrile (3k). Flash column chro-
matography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to afford 3k.
3-(4-Acetylphenyl)-3-oxopropanenitrile (3u). Flash column chro-
matography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to afford 3u.
Yellow solid (6.4 mg, 17%), mp 121−123 °C. Lit.8e 121.7−122.8 °C.
1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.0 Hz, 2H), 8.01 (d, J =
8.4 Hz, 2H), 4.13 (s, 2H), 2.66 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3): δ 196.9, 186.7, 141.4, 137.2, 128.9, 128.7, 113.3, 29.7, 26.9.
Ethyl 4-(2-Cyanoacetyl)benzoate (3v). Flash column chromatog-
raphy on silica gel (eluent: PE/EtOAc = 6/1, v/v) to afford 3v.
Orange oil (6.4 mg, 17%). 1H NMR (400 MHz, CDCl3): δ 8.18 (d, J
= 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 4.42 (q, J = 7.2 Hz, 2H), 4.11
(s, 2H), 1.42 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3):
δ 186.7, 165.2, 137.2, 135.8 130.2, 128.4, 113.3, 61.8, 29.7, 14.2.
HRMS (ESI): calcd for C12H11NO3 [M + Na]+, 240.0637; found,
240.0638.
White solid (24.2 mg, 75%), mp 69−71 °C. Lit.18 71−72 °C. H
1
NMR (400 MHz, CDCl3): δ 7.70−7.68 (m, 1H), 7.63−7.60 (m, 1H),
7.55−7.50 (m, 1H), 7.39−7.35 (m, 1H), 4.10 (s, 2H); 13C{1H} NMR
1
(125 MHz, CDCl3): δ 186.1, 162.9 (C−F, JC−F = 248.8 Hz), 136.2
3
3
(C−F, JC−F = 6.3 Hz), 130.9 (C−F, JC−F = 7.5 Hz), 124.2 (C−F,
4JC−F = 3.8 Hz), 121.9 (C−F, 2JC−F = 21.3 Hz), 115.2 (C−F, 2JC−F
=
22.5 Hz), 113.4, 29.6.
3-(4-Fluorophenyl)-3-oxopropanenitrile (3l). Flash column chro-
matography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to afford 3l.
White solid (22.8 mg, 76%), mp 72−74 °C. Lit.13 75−77 °C. H
1
NMR (400 MHz, CDCl3): δ 7.99−7.95 (m, 2H), 7.23−7.19 (m, 2H),
4.06 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 185.6, 166.6 (C−
1
3
F, JC−F = 256.3 Hz), 131.3 (C−F, JC−F = 10.0 Hz), 130.8 (C−F,
3-Oxo-3-(4-(trifluoromethyl)phenyl)propanenitrile (3w). Flash
column chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/
v) to afford 3w. Yellow solid (6.4 mg, 17%), mp 141−143 °C. Lit.18
4JC−F = 3.0 Hz), 116.4(C−F, JC−F = 22.5 Hz), 113.6, 29.3.
2
3-(3-Chlorophenyl)-3-oxopropanenitrile (3m). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3m. White solid (21.4 mg, 60%), mp 80−81 °C. Lit.13 72−73
°C. 1H NMR (400 MHz, CDCl3): δ 7.90 (s, 1H), 7.80 (d, J = 8.0 Hz,
1H), 7.64 (d, J = 8.0 Hz, 1H), 7.50−7.46 (m, 1H), 4.07 (s, 2H);
13C{1H} NMR (125 MHz, CDCl3): δ 186.0, 135.7, 135.6, 134.7,
130.5, 128.5, 126.5, 113.3, 29.5.
1
143−144 °C. H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.0 Hz,
2H), 7.80 (d, J = 8.0 Hz, 2H), 4.12 (s, 2H); 13C{1H} NMR (125
2
MHz, CDCl3): δ 186.3, 135.9 (C−F, JC−F = 32.5 Hz), 128.8, 126.3
4
1
(C−F, JC−F = 3.8 Hz), 123.2 (C−F, JC−F = 271.3 Hz), 113.2, 29.7.
3-Oxo-3-(thiophen-2-yl)propanenitrile (3x). Flash column chro-
matography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to afford 3x.
Yellow solid (8.9 mg, 30%), mp 137−138 °C. Lit.8e 136.3−138.3 °C.
1H NMR (500 MHz, CDCl3): δ 7.80−7.78 (m, 2H), 7.21−7.19 (m,
1H), 4.01 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 179.5,
140.9, 133.7, 128.7, 113.4, 29.6.
3-(4-Chlorophenyl)-3-oxopropanenitrile (3n). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3n. White solid (25.8 mg, 72%), mp 123−125 °C. Lit.13 121−
1
123 °C. H NMR (500 MHz, CDCl3): δ 7.86 (d, J = 8.5 Hz, 2H),
7.50 (d, J = 8.5 Hz, 2H), 4.09 (s, 2H); 13C{1H} NMR (125 MHz,
CDCl3): δ 186.0, 141.4, 132.6, 129.8, 129.5, 113.5, 29.4.
3-(3-Bromophenyl)-3-oxopropanenitrile (3o). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3o. Yellow solid (28.3 mg, 64%), mp 91−93 °C. Lit.19 92−94
°C. 1H NMR (400 MHz, CDCl3): δ 8.04 (s, 1H), 7.81 (dd, 1J = 21.6,
2J = 7.2 Hz, 2H), 7.43−7.39 (m, 1H), 4.08 (s, 2H); 13C{1H} NMR
(125 MHz, CDCl3): δ 186.0, 137.5, 135.8, 131.4, 130.7, 126.9, 123.4,
113.3, 29.5.
3-(Benzo[b]thiophen-2-yl)-3-oxopropanenitrile (3y). Flash col-
umn chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3y. Yellow solid (14.3 mg, 36%), mp 136−137 °C. Lit.8e
1
118.4−125.6 °C. H NMR (500 MHz, CDCl3): δ 8.04 (s, 1H), 7.91
(dd, J1 = 23.5 Hz, J2 = 8.0 Hz, 2H), 7.55−7.52 (m, 1H), 7.47−7.44
(m, 1H), 4.11 (s, 2H); 13C{1H} NMR (126 MHz, CDCl3): δ 181.1,
143.1, 140.1, 138.6, 131.1, 128.5, 126.4, 125.6, 123.0, 113.3, 29.5.
2,2-Dimethyl-3-oxo-3-phenylpropanenitrile (4a).16 Flash column
chromatography on silica gel (eluent: PE/EtOAc = 16/1, v/v) to
afford 4a. Pale-yellow oil (32.9 mg, 95%). Lit.16 1H NMR (500 MHz,
CDCl3): δ 8.17−8.15 (m, 2H), 7.63−7.60 (m, 1H), 7.52−7.49 (m,
2H), 1.72 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3): δ 193.9,
133.7, 133.6, 129.3, 128.7, 122.6, 40.8, 25.6.
3-(4-Bromophenyl)-3-oxopropanenitrile (3p). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 6/1, v/v) to
afford 3p. White solid (30.9 mg, 70%), mp 153−155 °C. Lit.13 156−
1
157 °C. H NMR (400 MHz, CDCl3): δ 7.78 (d, J = 8.4 Hz, 2H),
7.67 (d, J = 8.4 Hz, 2H), 4.06 (s, 2H); 13C{1H} NMR (125 MHz,
CDCl3): δ 186.2, 133.0, 132.6, 130.3, 129.9, 113.4, 29.3.
2,2-Dimethyl-3-oxo-3-(p-tolyl)propanenitrile (4b). Flash column
chromatography on silica gel (eluent: PE/EtOAc = 16/1, v/v) to
E
J. Org. Chem. XXXX, XXX, XXX−XXX