PAPER
Electrophilic Bromination of Anilines
1307
The compounds were isolated and purified either by flash chroma-
tography or preparative HPLC, and characterized by 1H NMR spec-
troscopy, MS, and, when not already reported or commercially
available, by 13C NMR spectroscopy (three cases only). Because of
the different adsorption coefficients of isomers 2, 3, and 4, the rela-
tive percentages obtained directly by HPLC are not correct. Correc-
tion factors for each isomer were obtained by comparing results
from HPLC of the CHCl3 reaction mixture to the corresponding 1H
NMR spectra. The resulting correction factors multiplied by the
HPLC area gave the correct percentages for each reaction mixture.
Methyl 5-Amino-2-bromobenzoate (3d)
1H NMR (400 MHz, CDCl3): d = 7.38 (d, J = 9.0 Hz, 1 H), 7.10 (d,
J = 3.0 Hz, 1 H), 6.65 (dd, J = 9.0, 3.0 Hz, 1 H), 3.91 (s, 3 H), 3.50
(br s, 2 H).
MS (ES): m/z = 230 [M + H]+, 232 [M + H]+.
Methyl 3-Amino-4-bromobenzoate (4d)
1H NMR (400 MHz, CDCl3): d = 7.48 (d, J = 8.5 Hz, 1 H), 7.44 (d,
J = 2.0 Hz, 1 H), 7.28 (dd, J = 8.5, 2.0 Hz, 1 H), 4.23 (br s), 3.91 (s,
3 H).
MS (ES): m/z = 230 [M + H]+, 232 [M + H]+.
2-Bromo-3-nitroaniline (2a)
1H NMR (400 MHz, CDCl3): d = 7.23 (t, J = 8.0 Hz, 1 H), 7.11 (dd,
J = 8.0, 1.0 Hz, 1 H), 6.93 (dd, J = 8.0, 1.0 Hz, 1 H), 4.48 (br s, 2 H).
1-(3-Amino-2-bromophenyl)ethanone (2e)
1H NMR (400 MHz, CDCl3): d = 7.15 (t, J = 8.0 Hz, 1 H), 6.84 (d,
J = 8.0 Hz, 1 H), 6.78 (d, J = 8.0 Hz, 1 H), 4.10 (br s), 2.62 (s, 3 H).
MS (ES): m/z = 217 [M + H]+, 219 [M + H]+.
13C NMR (100 MHz, CDCl3): d = 204.6, 145.3, 143.2, 128.5, 118.0,
4-Bromo-3-nitroaniline (3a)
1H NMR (400 MHz, CDCl3): d = 7.45 (d, J = 8.0 Hz, 1 H), 7.15 (d,
J = 2 Hz, 1 H), 6.72 (dd, J = 8.0, 2.0 Hz, 1 H), 3.98 (br s, 2 H).
117.6, 105.1, 30.8.
MS (ES): m/z = 214 [M + H]+, 216 [M + H]+.
MS (ES): m/z = 217 [M + H]+, 219 [M + H]+.
1-(5-Amino-2-bromophenyl)ethanone (3e)
1H NMR (400 MHz, CDCl3): d = 7.32 (d, J = 8.0 Hz, 1 H), 6.73 (d,
J = 1.5 Hz, 1 H), 6.61 (dd, J = 8.0, 1.5 Hz, 1 H), 3.78 (br s, 2 H),
2.62 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 204.8, 146.3, 142.5, 134.8, 118.8,
115.4, 106.6, 30.8.
2-Bromo-5-nitroaniline (4a)
1H NMR (400 MHz, CDCl3): d = 7.60–7.50 (m, 2 H), 7.18 (dd,
J = 8.0, 2.0 Hz, 1 H), 5.95 (br s, 2 H).
MS (ES): m/z = 217 [M + H]+, 219 [M + H]+.
MS (ES): m/z = 214 [M + H]+, 216 [M + H]+.
2-Bromo-3-(trifluoromethyl)aniline (2b)
1H NMR (400 MHz, CDCl3): d = 7.20 (t, J = 8.0 Hz, 1 H), 7.10 (dd,
J = 8.0, 2.0 Hz, 1 H), 6.93 (dd, J = 8.0, 2 Hz, 1 H), 4.40 (br s, 2 H).
1-(3-Amino-4-bromophenyl)ethanone (4e)
1H NMR (400 MHz, CDCl3): d = 7.50 (d, J = 8.0 Hz, 1 H), 7.34 (d,
J = 1.0 Hz, 1 H), 7.18 (dd, J = 8.0, 1.0 Hz, 1 H), 4.20 (br s), 2.62 (s,
3 H).
13C NMR (100 MHz, CDCl3): d = 205.1, 144.7, 137.7, 133.2, 119.6,
115.0, 105.9, 27.1.
MS (ES): m/z = 240 [M + H]+, 242 [M + H]+.
4-Bromo-3-(trifluoromethyl)aniline (3b)
1H NMR (400 MHz, CDCl3): d = 7.42 (d, J = 9.0 Hz, 1 H), 6.99 (d,
J = 3.0 Hz, 1 H), 6.68 (dd, J = 9.0, 3.0 Hz, 1 H), 3.85 (br s, 2 H).
MS (ES): m/z = 240 [M + H]+, 242 [M + H]+.
MS (ES): m/z = 214 [M + H]+, 216 [M + H]+.
2-Bromo-5-(trifluoromethyl)aniline (4b)
4-Bromo-3-fluoroaniline (3f)
1H NMR (400 MHz, CDCl3): d = 7.52 (d, J = 8.0 Hz, 1 H), 7.00 (d,
J = 2.0 Hz, 1 H), 6.86 (dd, J = 8.0, 2.0 Hz, 1 H), 4.33 (br s, 2 H).
1H NMR (400 MHz, CDCl3): d = 7.24 (t, J = 9.0 Hz, 1 H), 6.47 (dd,
J = 10.0, 2.0 Hz, 1 H), 6.37 (dd, J = 9.0, 2.0 Hz, 1 H), 3.62 (br s, 2
H).
MS (ES): m/z = 240 [M + H]+, 242 [M + H]+.
MS (ES): m/z = 190 [M + H]+, 192 [M + H]+
3-Amino-2-bromobenzonitrile (2c)
1H NMR (400 MHz, CDCl3): d = 7.20 (t, J = 8.0 Hz, 1 H), 7.07 (dd,
J = 8.0, 1.5 Hz, 1 H), 6.97 (dd, J = 8.0, 1.5 Hz, 1 H), 4.35 (br s, 2 H).
2-Bromo-5-fluoroaniline (4f)
1H NMR (400 MHz, CDCl3): d = 7.34 (dd, J = 9.0, 6.0 Hz, 1 H),
6.48 (d, J = 10.0, 3.0 Hz, 1 H), 6.37 (dd, J = 9.0, 3.0 Hz, 1 H), 4.18
(br s, 2 H).
MS (ES): m/z = 197 [M + H]+, 199 [M + H]+.
MS (ES): m/z = 190 [M + H]+, 192 [M + H]+
5-Amino-2-bromobenzonitrile (3c)
1H NMR (400 MHz, CDCl3) d = 7.39 (d, J = 8.0 Hz, 1 H), 6.91 (d,
J = 1.5 Hz, 1 H), 6.76 (dd, J = 8.0, 1.5 Hz, 1 H), 3.97 (br s, 2 H).
2-Bromo-3-chloroaniline (2g)
1H NMR (400 MHz, CDCl3): d = 7.03 (t, J = 8.0 Hz, 1 H), 6.85 (d,
J = 8.0, 1 H), 6.65 (dd, J = 8.0, 1 H), 3.93 (br s, 2 H).
MS (ES): m/z = 197 [M + H]+, 199 [M + H]+.
MS (ES): m/z = 206 [M + H]+, 208 [M + H]+, 210 [M + H]+.
3-Amino-4-bromobenzonitrile (4c)
1H NMR (400 MHz, CDCl3): d = 7.50 (d, J = 8.0 Hz, 1 H), 6.99 (s,
1 H), 6.87 (d, J = 8.0 Hz, 1 H), 4.35 (br s, 2 H).
4-Bromo-3-chloroaniline (3g)
1H NMR (400 MHz, CDCl3): d = 7.33 (d, J = 9.0 Hz, 1 H), 6.79 (d,
J = 2.5 Hz, 1 H), 6.45 (dd, J = 9.0, 2.5 Hz, 1 H), 3.75 (br s, 2 H).
MS (ES): m/z = 197 [M + H]+, 199 [M + H]+.
MS (ES): m/z = 206 [M + H]+, 208 [M + H]+, 210 [M + H]+.
Methyl 3-Amino-2-bromobenzoate (2d)
1H NMR (400 MHz, CDCl3): d = 7.13 (t, J = 7.5 Hz, 1 H), 7.09 (dd,
J = 7.5, 1.5 Hz, 1 H), 6.87 (dd, J = 7.5, 1.5 Hz, 1 H), 4.22 (br s, 2
H), 3.90 (s, 3 H).
2-Bromo-5-chloroaniline (4g)
1H NMR (400 MHz, CDCl3): d = 7.31 (d, J = 8.5 Hz, 1 H), 6.76 (d,
J = 2.0 Hz, 1 H), 6.60 (dd, J = 8.5, 2.0 Hz, 1 H), 4.15 (br s, 2 H).
MS (ES): m/z = 230 [M + H]+, 232 [M + H]+.
MS (ES): m/z = 206 [M + H]+, 208 [M + H]+, 210 [M + H]+.
Synthesis 2009, No. 8, 1305–1308 © Thieme Stuttgart · New York