2454 J . Org. Chem., Vol. 63, No. 8, 1998
Wang et al.
HRMS exact mass calcd for C19H13NO2 287.0946, found
287.0945. Anal. Calcd for C19H13NO2: C, 79.43; H, 4.56; N,
4.87. Found: C, 79.55; H, 4.63; N, 4.98.
Exp er im en ta l Section
Gen er a l Da ta / Melting points were taken on an electro-
chemical apparatus and are uncorrected. IR spectra were
3-Ben zyl-2-cyan o-4-m eth oxyben zoic acid (4e): mp 185-
186 °C; 1H NMR (acetone-d6) δ 3.65 (s, 3 Η), 4.10 (s, 2 H), 6.90
(d, J ) 8.4 Hz, 1 H), 7.08-7.20 (m, 5 H), 8.20 (d, J ) 8.4 Hz,
1 H); 13C NMR δ 34.5, 56.3, 118.6, 126.9, 129.0, 129.4, 133.3,
134.5, 140.3, 146.7, 160.1, 176.4; IR 3412 (OH), 2235 (CN)
cm-1; HRMS exact mass calcd for C16H13NO3 267.0895, found
267.0891. Anal. Calcd for C16H13NO3: C, 71.90; H, 4.90; N,
5.24.
obtained from a FTIR spectrometer, and the H and 13C NMR
1
spectra were recorded on a 200 or 400 MHz spectrometer;
chemical shifts were related to TMS as internal standard.
Elemental analyses were obtained from E + R Microanalytical
Laboratories, Inc., Corona, NY. High-resolution mass spectra
were performed by the Washington University Mass Spec-
trometry Resource, an NIH Research Resource (Grant No.
P41RR0954). Chemicals were purchased from Aldrich Chemi-
cal Co. Diisopropylamine was refluxed over and distilled from
calcium hydride. Tetrahydrofuran (THF) was distilled from
Na/benzophenone immediately prior to use. n-Butyllithium
(n-BuLi) was purchased from Aldrich Chemical Co. as a
solution in hexanes. The glassware was heated at 125 °C in
an oven overnight prior to use. All the benzyne reactions were
done under an atmosphere of dry O2-free N2 contained in a
balloon.
2-Cya n o-4-m eth oxy-3-[(4-m eth oxyp h en yl)m eth yl]ben -
1
zoic a cid (4f): mp 190-192 °C; H NMR (DMSO-d6) δ 3.73
(s, 3 Η), 4.01 (s, 2 H), 4.22 (s, 2 H), 6.82 (d, J ) 8.8 Hz, 2 H),
7.24 (d, J ) 8.8 Hz, 2 H), 7.41 (d, J ) 8.8 Hz, 1 H), 8.11 (d, J
) 8.8 Hz, 1 H); 13C NMR δ 33.7, 55.4, 56.8, 114.6, 115.0, 117.0,
125.5, 129.4, 130.4, 131.8, 132.5, 137.1, 138.1, 159.3, 161.8,
165.5; IR 3412 (OH), 2266 (CN) cm-1; HRMS exact mass calcd
for C17H15NO4 297.1001, found 297.1003. Anal. Calcd for
C
17H15NO4: C, 68.28; H, 5.09; N, 4.71. Found: C, 68.53; H,
Gen er a l P r oced u r e for Ar yn e Rea ction s. In a flame-
dried flask flushed with nitrogen, fresh LDA (15 mmol) was
prepared by adding n-butyllithium (15 mmol, 2.5 M in hexane)
to a solution of diisopropylamine (15 mmol) in THF (30 mL)
at -70 °C. After the mixture was stirred for 10 min, the
appropriate bromobenzoic acid (5 mmol) in THF (30 mL) was
added dropwise over 20 min, and the stirring was continued
for 10 min at -70 °C. The appropriate arylacetonitrile then
was added, during which time the solution developed a deep
red color. The resulting solution was stirred for an additional
30 min and then was allowed to warm to room temperature
and immediately quenched with 30 mL of saturated NH4Cl in
the case of 1a ,b,d or stirred overnight in the case of 1c before
quenching. The THF was evaporated under reduced pressure,
and the remaining residue was extracted with methylene
chloride (3 × 20 mL). The combined extracts were washed
with dilute HCl (1 × 20 mL) and NaCl brine (2 × 20 mL),
dried (Na2SO4), and concentrated (rotary evaporator) to pro-
vide a crude solid material. The mixture was subjected to flash
column chromatography (silica gel) using a mixture of hexane/
acetone (6:4) as the eluent to give a solid product that was
recrystallized from EtOAc. The mp, elemental analyses, and
NMR spectral data of isolated compounds are given below.
2-Cya n o-3-ben zylben zoic a cid (4a ): mp 189-191 °C; 1H
NMR (acetone-d6) δ 4.34 (s, 2 H), 7.24 (m, 1 H), 7.32 (m, 4 H),
7.74 (m, 2H), 8.05 (m, 1 H); 13C NMR δ 40.5, 116.8, 126.8,
127.5, 129.5, 130.0, 133.3, 134.7, 140.0, 148.0, 165.8; IR 3412
(OH), 2235 (CN) cm-1; HRMS exact mass calcd for C15H11NO2
237.0790, found 237.0791. Anal. Calcd for C15H11NO2: C,
75.94; H, 4.67; N, 5.90. Found: C, 76.02; H, 4.75; N, 5.99.
5.23; N, 4.52.
2-Cya n o-4-m eth oxy-3-[(2-m eth oxyp h en yl)m eth yl]ben -
zoic a cid (4g): mp 202-204 °C; 1H NMR (acetone-d6) δ 3.87
(s, 3 Η), 3.90 (s, 3 H), 4.25 (s, 2 H), 6.59 (d, J ) 7.2 Hz, 1 H),
6.76 (t, J ) 7.2 Hz, 1 H), 6.97 (d, J ) 8.0 Hz, 1 H), 7.16 (t, J
) 8.0 Hz, 1 H), 7.35 (d, J ) 8.8 Hz, 1 H), 8.15 (d, J ) 8.8 Hz,
1 H); 13C NMR δ 39.3, 54.3, 55.3, 105.5, 108.8, 109.7, 113.2,
119.5, 126.7, 127.3, 131.0, 133.1, 138.6, 153.2, 158.5, 163.4,
174.2; IR 3454 (OH), 2224 (CN) cm-1; HRMS exact mass calcd
for C17H15NO4 297.1001, found 297.1001. Anal. Calcd for
C
17H15NO4: C, 68.68; H, 5.09, N, 4.71. Found: C, 68.87; H,
5.17; N, 4.84.
2-Cya n o-3-(1-n a p h th ylm eth yl)-4-m eth oxyben zoic a cid
(4h ): mp 235-237 °C; H NMR (acetone-d6) δ 3.89 (s, 3 Η),
1
4.79 (s, 2 H), 6.68 (d, J ) 7.2 Hz, 1 H), 7.32 (m, 1 H), 7.51 (d,
J ) 8.8 Hz, 1 H), 7.57 (t, J ) 8.0 Hz, 1 H), 7.65 (t, J ) 8.0 Hz,
1 H), 7.78 (d, J ) 8.8 Hz, 1 H), 7.96 (d, J ) 8.0 Hz, 1 H), 8.25
(d, J ) 8.8 Hz, 1 H), 8.37 (d, J ) 8.0 Hz, 1 H); 13C NMR δ
30.1, 55.4, 55.3, 113.6, 115.0, 122.8, 123.0, 124.3, 124.9, 125.2,
125.6, 126.3, 127.7, 128.1, 131.5, 133.3, 133.8, 134.1, 161.0,
164.1, 175.0; IR 3398 (OH), 2266 (CN) cm-1; HRMS exact mass
calcd for C20H15NO3 317.1052, found 317.1049. Anal. Calcd
for C20H15NO3: C, 75.70; H, 4.76; N, 4.41. Found: C, 75.79;
H, 4.85; N, 4.32.
3-Ben zyl-2-cya n o-4-m eth ylben zoic a cid (4i): mp 128-
130 °C; 1H NMR (acetone-d6) δ 2.37 (s, 3 Η), 4.43 (s, 2 H), 7.15
(d, J ) 7.6 Hz, 1 H), 7.28 (m, 2 H), 7.63 (d, J ) 8.0 Hz, 1 H),
8.20 (d, J ) 8.0 Hz, 1 H); 13C NMR δ 20.3, 37.8, 115.0, 117.0,
127.2, 129.0, 129.4, 130.5, 135.0, 139.4, 143.0, 144.0, 145.5,
175.5; IR 3412 (OH), 2235 (CN) cm-1; HRMS calcd for C16H13
-
2-Cya n o-3-[4-m et h oxyp h en yl)m et h yl]b en zoic
a cid
NO2 251.0946, found 251.0948. Anal. Calcd for C16H13NO2:
C, 76.48; H, 5.21; N, 5.57. Found: C, 76.50; H, 5.23; N, 5.67.
2-Cya n o-3-[(4-m et h oxyp h en yl)m et h yl]-4-m et h ylb en -
(4b): mp 295-297 °C; 1H NMR (DMSO-d6) δ 3.70 (s, 3 Η),
4.10 (s, 2 H), 6.85 (d, J ) 8.6 Hz, 2 H), 7.17 (d, J ) 8.6 Hz, 2
H), 7.37 (d, J ) 7.2 Hz, 1 H), 7.48 (t, J ) 7.2 Hz, 1 H), 7.80 (d,
J ) 7.2 Hz, 1 H); 13C NMR δ 31.2, 56.4, 112.3, 115.3, 119.3,
129.0, 129.4, 131.0, 131.6, 132.8, 144.9, 146.9, 159.2, 170.2;
IR 3412 (OH), 2235. Anal. Calcd for C16H13NO3: C, 71.90;
H, 4.90; N, 5.24. Found: C, 71.85; H, 4.97; N, 5.17.
1
zoic a cid (4j): mp 146-137 °C; H NMR (acetone-d6) δ 2.47
(s, 3 Η), 3.88 (s, 2 H), 4.21 (s, 2 H), 6.74 (d, J ) 6.4 Hz, 2 H),
6.94 (d, J ) 6.4 Hz, 2 H), 7.21 (d, J ) 8.4 Hz, 1 H), 8.11 (d, J
) 8.4 Hz, 1 H); 13C NMR δ 17.9, 27.4, 50.3, 109.1, 109.5, 113.5,
124.8, 126.0, 126.6, 128.7, 133.0, 138.2, 140.7, 154.0, 167.0;
IR 3412 (OH), 2235 (CN) cm-1; HRMS exact mass calcd for
2-Cya n o-3-[(2-m et h oxyp h en yl)m et h yl]b en zoic a cid
1
(4c): mp 190-192 °C; H NMR (acetone-d6) δ 3.82 (s, 3 Η),
C
C
17H15NO3 281.1052, found 281.1053. Anal. Calcd for
17H15NO3: C, 72.58; H, 5.37; N, 4.98. Found: C, 72.51; H,
4.28 (s, 2 H), 6.92 (t, J ) 7.6 Hz, 1 H), 7.02 (d, J ) 8.0 Hz, 1
H), 7.21 (d, J ) 7.6 Hz, 1 H), 7.27 (t, J ) 7.6 Hz, 1 H), 7.54 (d,
J ) 8.0 Hz, 1 H), 7.67 (t, J ) 8.0 Hz, 1 H), 8.03 (d, J ) 7.6 Hz,
1 H); 13C NMR δ 33.7, 54.3, 110.2, 115.3, 120.0, 126.5, 127.8,
128.2, 129.8, 131.4, 133.1, 146.4, 157.0, 158.4, 164.5, 175.0;
IR (CN) cm-1; HRMS exact mass calcd for C16H13NO3 267.0895,
found 267.0894. Anal. Calcd for C16H13NO3: C, 71.90; H, 4.90;
N, 5.24. Found: C, 71.99; H, 4.82; N, 5.20.
5.33; N, 5.02.
2-Cya n o-4-m eth oxy-3-[(2-m eth oxyp h en yl)m eth yl]ben -
zoic a cid (4k ): mp 202-204 °C; 1H NMR (acetone-d6) δ 3.87
(s, 3 Η), 3.90 (s, 3 H), 4.25 (s, 2 H), 6.59 (d, J ) 7.2 Hz, 1 H),
6.76 (t, J ) 7.2 Hz, 1 H), 6.97 (d, J ) 8.0 Hz, 1 H), 7.16 (t, J
) 8.0 Hz, 1 H), 7.35 (d, J ) 8.8 Hz, 1 H), 8.15 (d, J ) 8.8 Hz,
1 H); 13C NMR δ 39.3, 54.3, 55.3, 105.5, 108.8, 109.7, 113.2,
119.5, 126.7, 127.3, 131.0, 133.1, 138.6, 153.2, 158.5, 163.4,
174.2; IR 3454 (OH), 2224 (CN) cm-1; HRMS exact mass calcd
for C17H15NO4 297.1001, found 297.1001. Anal. Calcd for
2-Cya n o-3-(1-n a p h th ylm eth yl)ben zoic a cid (4d ): mp
205-207 °C; 1H NMR (acetone-d6) δ 4.81 (s, 2 Η), 7.31 (d, J )
6.8 Hz, 1 H), 7.37 (d, J ) 8.0 Hz, 1 H), 7.47-7.55 (m, 3 H),
7.65 (t, J ) 8.0 Hz, 1 H), 7.90 (d, J ) 8.0 Hz, 1 H), 7.97 (m, 1
H), 8.01-8.08 (m, 2 H); 13C NMR δ 36.0, 105.5, 115.2, 123.2,
125.1, 125.3, 125.9, 126.9, 127.2, 128.3, 128.5, 131.7, 133.0,
C
17H15NO4: 68.68; H, 5.09; 4.71. Found: C, 68.69; H, 5.14;
N, 4.64.
3-Ben zyl-2-cya n o-4,5-d im eth oxyben zoic a cid (4l): mp
133.5, 134.0, 145.2, 146.0, 164.4, 175.0; IR 2238 (CN) cm-1
;
230-231 C dec; 1H NMR (DMSO-d6) δ 3.62 (s, 3 Η), 3.86 (s, 3
o