The Journal of Organic Chemistry
NOTE
3
δ 55.7, 61.5, 61.9, 113.4, 117.7, 124.2, 126.0, 144.5, 147.9, 152.8. HRMS/
EI: calcd for C10H13NO3 195.0895, found 195.0900.
diastereoisomer (Z) δ 3.95 (s, 3H), 7.18 (d, 1H, J = 7.8 Hz), 7.39
(t, 1H, 3J = 8.8 Hz), 7.42 (s, 1H), 7.51 (d, 1H, 3J = 8.8 Hz). 1H NMR
(400 MHz, CDCl3), diastereoisomer (E) δ 4.03 (s, 3H), 7.13 (d, 1H,
3J = 7.8 Hz,), 7.39 (t, 1H, 3J = 8.8 Hz), 7.54 (d, 1H, 3J = 7.8 Hz), 8.21
(s, 1H). 13C NMR (100 MHz, CDCl3) δ 62.4, 62.4, 122.4, 124.2, 128.3,
129.3, 130.5, 130.6, 130.8, 131.8, 132.1, 133.5, 133.9, 134.9, 143.2, 145.8.
HRMS/EI: calcd for C8H7NOBrCl 246.9399, found 246.9401.
General Procedure for the Synthesis of Substituted 2-
Bromobenzaldehyde O-Methyloximes 1bÀ14b. In a sealed
flask, substituted benzaldehyde O-methyloxime 1aÀ15a (1 equiv) was
added to a solution of N-bromosuccinimide (see Table 2), silver
trifluoroacetate (10 mol %), palladium acetate (10 mol %), and acetic
acid (see Table 2) in 1,2-dichloroethane (2 mL/0.60 mmol of oxime).
The resulting mixture was stirred and heated at 120 °C (see Table 2 for
conditions), partitioned between water and dichloromethane, and
filtered through a pad of Celite. The aqueous layer was extracted with
dichloromethane. The combined organic layers were dried on MgSO4,
filtered, evaporated in vacuo, and purified by silica gel chromatography.
(E)-2-Bromobenzaldehyde O-Methyloxime 1b. Starting from
benzaldehyde O-methyloxime 1a (500 mg, 3.70 mmol), 1b was obtained
as a colorless oil (403 mg, 51%, cyclohexane as eluent). (E)-2-Bromo-
benzaldehyde O-methyloxime 1b: IR (KBr) ν cmÀ1) 3434, 2935, 1591,
1438, 1468, 1059, 924, 753. 1H NMR (400 MHz, CDCl3) δ 4.00 (s, 3H),
7.22 (dt, 1H, 3J = 7.8 Hz, 4J = 2.0 Hz), 7.30 (t, 1H, 3J = 6.8 Hz), 7.56 (dd,
1H, 3J = 7.8 Hz, 4J = 2.0 Hz), 7.87 (dd, 1H, 3J = 7.8 Hz, 4J = 2.0 Hz), 8.45
(s, 1H). 13C NMR (100 MHz, CDCl3) δ 62.3, 123.8, 127.5, 127.6, 131.0,
131.5, 133.1, 147.9. HRMS/EI: calcd for C8H8NOBr 212.9789, found
212.9790. (E)-2,6-Dibromobenzaldehyde O-methyloxime 1c: Ob-
tained as a byproduct during the screening of conditions. White solid,
mp 78À80 °C. IR (KBr) (cmÀ1) 3074, 2940, 1547, 1423, 1189, 1054,
923, 772. 1H NMR(400 MHz, CDCl3) δ4.03(s, 3H), 7.06(t, 1H, 3J =8.8
Hz), 7.58 (d, 2H, 3J =8.8 Hz), 8.15(s, 1H). 13CNMR(125 MHz, CDCl3)
δ 62.5, 124.1 (2C), 130.9, 132.4 (2C), 147.3. HRMS/EI: calcd for
C8H7NOBr2 290.8894, found 290.8885.
(E)-2-Bromo-6-methoxybenzaldehyde O-Methyloxime 2b.
Starting from 2-methoxybenzaldehyde O-methyloxime 2a (495 mg,
3.00 mmol), 2b was obtained as a colorless oil (470 mg, 64%, petroleum
ether/diethyl ether 98/2 as eluent). IR (KBr) ν cmÀ1) 3004, 2935, 2837,
1586, 1563, 1459, 1429, 1261, 1032, 918. 1H NMR (400 MHz, CDCl3)
δ 3.83 (s, 3H), 4.01 (s, 3H), 6.87 (d, 1H, 3J = 7.8 Hz), 7.14À7.23 (m, 2H),
8.27 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 56.2, 62.1, 110.2, 111.7,
124.1, 125.5, 130.7, 145.8, 158.9. HRMS/EI: calcd for C9H10NO2Br
242.9895, found 242.9889.
(E)-2-Bromo-6-methylbenzaldehyde O-Methyloxime 3b.
Starting from 2-methylbenzaldehyde O-methyloxime 3a (448 mg, 3.00
mmol), 3b was obtained as a colorless oil (306 mg, 45%, petroleum ether
as eluent). IR (KBr) ν (cmÀ1) 3435, 2934, 1449, 1052, 925, 771.
1H NMR (500 MHz, CDCl3) δ 2.50(s, 3H), 4.00 (s, 3H), 7.09 (t, 1H,
3J = 7.8 Hz), 7.18 (d, 1H, 3J = 6.8 Hz), 7.43 (d, 1H, 3J = 7.8 Hz), 8.41
(s, 1H). 13C NMR (125 MHz, CDCl3) δ 22.2, 62.2, 124.9, 129.8, 130.2,
130.5, 139.9, 149.0. HRMS/EI: calcd for C9H10NOBr 226.9946, found
226.9953.
(E)-2-Bromo-5-chlorobenzaldehyde O-Methyloxime 6b. Start-
ing from 3-chlorobenzaldehyde O-methyloxime 6a (529 mg, 3.12 mmol),
6b was obtained as a white solid (284 mg, 37%, petroleum ether as eluent).
Mp 70À72 °C. IR (KBr) ν (cmÀ1) 3084, 2938, 1461, 1394, 1059, 1027,
1
931, 896, 884, 808. H NMR (400 MHz, CDCl3) δ 4.01 (s, 3H), 7.19
(dd, 1H, 3J = 8.8 Hz, 4J = 2.9 Hz), 7.47 (d, 1H, 3J = 8.8 Hz), 7.86 (d, 1H, 4J =
2.0 Hz), 8.36 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 62.5, 121.4, 127.2,
130.8, 132.9, 133.8, 134.1, 146.7. HRMS/EI: calcd for C8H7NOClBr
246.9399, found 246.9404.
(E)-2-Bromo-5-nitrobenzaldehyde O-Methyloxime 7b. Starting
from 3-nitrobenzaldehyde O-methyloxime 7a (500 mg, 1.93 mmol), 7b was
obtained as a white solid (230 mg, 32%, cyclohexane/diethyl ether 99/1 as
eluent). Mp 117À119 °C. IR(KBr) ν(cmÀ1) 3097, 3078, 2937, 1560, 1594,
1
1523, 1345, 1054, 1029, 918, 740. H NMR (400 MHz, CDCl3) δ 4.06
(s, 3H), 7.75(d, 1H, 3J=8.8Hz), 8.05(dd, 1H, 3J=8.8Hz, 4J= 2.0 Hz), 8.44
(s, 1H), 8.72 (d, 1H, 4J = 2.0 Hz). 13C NMR (100 MHz, CDCl3) δ 62.9,
122.3, 124.7, 129.9, 133.3, 134.2, 145.8, 147.3. HRMS/EI: calcd for
C8H7N2O3Br 257.9640, found 257.9637.
(E)-2,5-Dibromobenzaldehyde O-Methyloxime 8b. Starting
from 5-bromobenzaldehyde O-methyloxime 8a (500 mg, 2.34 mmol),
8b was obtained as a white solid (270 mg, 40%, petroleum ether/acetone
99/1 as eluent). Mp 80À82 °C. IR (KBr) ν (cmÀ1) 3080, 2937, 1458,
1
1388, 1198, 1059, 1025, 930. H NMR (400 MHz, CDCl3) δ 4.01
(s, 3H), 7.33 (dd, 1H, 3J = 8.8 Hz, 4J = 2.9 Hz), 7.42 (d, 1H, 3J = 8.8 Hz),
8.01 (d, 1H, 4J = 2.9 Hz), 8.35 (s, 1H). 13C NMR (100 MHz, CDCl3) δ
62.5, 121.5, 122.1, 130.1, 133.2, 133.7, 134.3, 146.6. HRMS/EI: calcd for
C8H7NOBr2 290.8894, found 290.8890.
(E)-2-Bromo-5-fluorobenzaldehyde O-Methyloxime 9b.
Starting from 3-fluorobenzaldehyde O-methyloxime 9a (518 mg, 3.38
mmol), 9b was obtained as a white solid (67 mg, 18%, petroleum ether as
eluent). 2,6-dibromo-3-fluorobenzaldehyde O-methyloxime 9c as a
byproduct was obtained in a 1:1 Z:E ratio as a white solid (440 mg,
42%). (E)-2-Bromo-5-fluorobenzaldehyde O-methyloxime 9b: Mp <
50 °C. IR (KBr) ν (cmÀ1) 2932, 1599, 1568, 1460, 1417, 1263, 1158,
1058, 1031, 917. 1H NMR (400 MHz, CDCl3) δ 4.01 (s, 3H), 6.95 (dt,
1H, 3J = 7.8 Hz, 4J = 2.9 Hz), 7.51 (dd, 1H, 3J = 8.8 Hz, 4J = 8.8 Hz), 7.60
(dd, 1H, 3J = 9.8 Hz, 4J = 2.9 Hz), 8.38 (d, 1H, 5J = 1.9 Hz). 13C NMR
(100 MHz, CDCl3) δ 62.5, 114.0 (d, 2J = 25 Hz), 117.8 (d, J = 2 Hz),
118.3 (d, 2J = 23 Hz), 133.2 (d, J = 8 Hz), 134.3 (d, J = 8 Hz), 147.0
(d, J = 2 Hz), 161.8 (d, 1J = 246 Hz). HRMS/EI: calcd for C8H7NOFBr
232.9675, found 232.9679. (Z,E)-2,6-Dibromo-3-fluorobenzaldehyde
O-methyloxime 9c: Mp < 50 °C. IR (KBr) ν (cmÀ1) 2938, 2820, 1564,
2-Bromo-6-fluorobenzaldehyde O-Methyloxime 4b40. Starting
from 2-fluorobenzaldehyde O-methyloxime 4a (310 mg, 2.02 mmol), 4b
was obtained as a colorless oil in a 1:0.9 Z:E ratio (334 mg, 71%, petroleum
ether/acetone 99/1 as eluent). IR (KBr) ν (cmÀ1) 3085, 2938, 2820, 1599,
1564, 1460, 1443, 1251, 1051, 925, 874, 780. 1H NMR (400 MHz, CDCl3)
δ 3.96 (s, 3H), 4.04 (s, 3H), 7.05À7.10 (m, 2H), 7.12À7.25 (m, 2H),
7.39À7.42 (m, 3H), 8.30 (s, 1H). 13C NMR (100 MHz, CDCl3) (E) δ62.6,
115.7 (d, 2J = 22 Hz), 120.6 (d, 2J = 14 Hz), 124.4 (d, J = 4 Hz), 129.1 (d, J =
1
1443, 1400, 1271, 1194, 1056, 998, 897, 813. H NMR (400 MHz,
CDCl3) δ 3.94 (s, 3H), 4.04 (s, 3H), 7.00 (dt, 2H, 3J = 7.8 Hz, 4J = 2.9 Hz),
7.34 (s, 1H), 7.48À7.56 (m, 2H), 8.11 (s, 1H). 13C NMR (100 MHz,
CDCl3) δ 62.4, 62.5, 110.0 (d, 2J = 22 Hz), 111.7 (d, 2J = 22 Hz), 116.3
(d, J = 3 Hz), 117.3 (d, J = 11 Hz), 117.6 (d, J = 11 Hz), 118.1
(d, J = 4 Hz), 132.3 (d, J = 7 Hz), 132.9 (d, J = 7 Hz), 133.7, 135.8,
143.4 (d, J= 2 Hz), 146.4 (d, J= 2 Hz), 158.4 (d, 1J= 248 Hz), 158.6 (d, 1J=
246 Hz). HRMS/EI: calcd for C8H6NOFBr2 308.8800, found 308.8808.
(E)-2-Bromo-4-trifluoromethylbenzaldehyde O-Methyloxime
10b. Starting from 4-trifluoromethylbenzaldehyde O-methyloxime 10a
(406 mg, 2.00 mmol), 10b was obtained as a white solid (230 mg, 41%,
petroleum ether as eluent). Mp < 50 °C. IR (KBr) ν (cmÀ1) 3080, 2949,
1597, 1466, 1399, 1325, 1171, 1038, 925, 863, 836. 1H NMR (400 MHz,
4 Hz), 131.1 (d, J = 9 Hz), 144.6 (d, J = 4 Hz), 160.8 (d, 1J = 258 Hz). 13
C
NMR (100 MHz, CDCl3) (Z) δ 62.6, 114.8 (d, 2J = 22 Hz), 121.0 (d, 2J =
21 Hz), 122.5 (d, J=5Hz), 128.2(d, J= 4 Hz), 131.4 (d, J= 9 Hz), 140.5 (d,
J = 2 Hz), 159.7 (d, 1J = 255 Hz).
2-Bromo-6-chlorobenzaldehyde O-Methyloxime 5b. Start-
ing from 2-chlorobenzaldyde O-methyloxime 5a (500 mg, 2.95 mmol),
5b was obtained as a colorless oil in a 1:2 E:Z ratio (591 mg, 81%,
cyclohexane as eluent). IR (KBr) ν (cmÀ1) 2968, 2938, 1577, 1554,
1427, 1189, 1078, 1058, 920, 776. 1H NMR (400 MHz, CDCl3),
3
CDCl3) δ 4.03 (s, 3H), 7.55 (d, 1H, J = 8.8 Hz), 7.83 (s, 1H), 8.00
(d, 1H, 3J = 7.8 Hz), 8.44 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 62.5,
6417
dx.doi.org/10.1021/jo200853j |J. Org. Chem. 2011, 76, 6414–6420