A. Nakhai, B. Stensland, P. H. Svensson, J. Bergman
FULL PAPER
151.5 (s), 144.4 (s), 122.7 (d), 117.7 (s), 117.1 (d), 114.5 (d), 95.9
(s), 55.8 (q) ppm.
NMR ([D6]DMSO): δ = 151.9 (s), 141.2 (s), 133.2 (d), 117.1 (s),
116.8 (d), 112.4 (d), 94.6 (s), 20.3 (q) ppm.
2-Amino-6-chlorobenzonitrile (6j):[41] This compound was prepared
from 2-chloro-6-nitrobenzonitrile (6.57 g, 36.0 mmol) according to
ref.[41] The product was obtained as a yellow solid (5.04 g, 92%),
2-Amino-5-methylbenzonitrile (6c):[28] This compound was prepared
from p-toluidine in two steps according to ref.[28] The total yield of
the desired product was (83%). IR (neat): ν = 3456, 3364, 3240,
˜
m.p. 132–134 °C (ref.[41] 132–136 °C). IR (neat): ν = 3402, 3335,
2210, 1630, 1504, 1260, 807 cm–1. 1H NMR ([D6]DMSO): δ = 7.17–
7.08 (m, 2 H), 6.71 (d, J = 8.4 Hz, 1 H), 5.78 (br. s, 2 H), 2.12 (s,
3 H) ppm. 13C NMR ([D6]DMSO): δ = 149.5 (s), 135.0 (d), 131.6
(d), 124.7 (s), 118.2 (s), 115.4 (d), 93.4 (s), 19.4 (q) ppm.
˜
1
3230, 2219, 1646, 1598, 1471, 777 cm–1. H NMR ([D6]DMSO): δ
= 7.26 (t, J = 8.2 Hz, 1 H), 6.78–6.66 (m, 2 H), 6.40 (s, 2 H) ppm.
13C NMR ([D6]DMSO): δ = 153.6 (s), 135.0 (s), 134.4 (d), 115.8
(d), 115.3 (s), 113.8 (d), 93.8 (s) ppm.
2-Amino-3,5-dimethylbenzonitrile (6d):[29] This compound was pre-
pared from 2,4-dimethylaniline (9.8 g, 80.9 mmol) in two steps ac-
cording to ref.[29] The product was obtained as a dark-brown oil
3,4-Dihydro-4-imino-3-methyl-1,2,3-benzotriazine (7a): 2-Azido-
benzonitrile (4a; 1.0 g, 6.94 mmol) was dissolved in dry THF
(20 mL) and methylmagnesium bromide (3.0 m, 13.89 mmol) was
added dropwise at room temperature. After stirring for 1 h, the
reaction mixture was quenched with NH4Cl (20% aq.) and the mix-
ture was stirred for 20 min. The solvent was separated and the
aqueous phase extracted with diethyl ether (3ϫ50 mL). The com-
bined organic solvents were dried (Na2SO4), evaporated and the
crude product was purified by column chromatography on silica
(heptane/EtOAc) to give of product 7a (0.87 g, 78%) as a pale-
(4.8 g, 41%). IR (neat): ν = 3428, 3347, 2215, 1625, 1483, 1286,
˜
1
1248, 855 cm–1. H NMR ([D6]DMSO): δ = 7.04 (s, 1 H), 5.48 (s,
1 H), 2.11 (s, 3 H), 2.07 (s, 3 H) ppm. 13C NMR ([D6]DMSO): δ =
147.4 (s), 135.9 (d), 129.3 (d), 124.8 (s), 123.0 (s), 118.6 (s), 93.4
(s), 19.5 (q), 17.5 (q) ppm.
2-Amino-5-chlorobenzonitrile (6e):[30] This compound was prepared
from 2-aminobenzonitrile (6a; 5.0 g, 42.4 mmol) and N-chlorosuc-
cinimide (NCS; 5.93 g, 44.4 mmol) according to ref.[30] The product
was obtained as a pale-yellow solid (4.3 g, 67%), m.p. 95–96 °C
yellow solid, m.p. 108.9–111.7 °C. IR (neat): ν = 3313, 3031, 1609,
˜
1454, 1250, 1169, 1009, 769 cm–1. 1H NMR ([D6]DMSO): δ = 8.72
(br. s, 1 H), 8.30 (d, J = 7.47 Hz, 1 H), 7.89–7.85 (m, 1 H), 7.83–
7.77 (m, 1 H), 7.75–7.68 (m, 1 H), 3.82 (s, 3 H) ppm. 13C NMR
([D6]DMSO): δ = 149.6 (s), 140.1 (s), 133.1 (d), 131.7 (d), 127.6
(d), 123.5 (d), 117.9 (s), 38.6 (q) ppm. C8H8N4 (160.07): calcd. C
59.99, H 5.03, N 34.98; found C 60.4, H 5.5, N 35.0.
(ref.[45] 95.0–96.3 °C). IR (neat): ν = 3449, 3356, 2218, 1615, 1488,
˜
1411, 878, 816 cm–1. 1H NMR ([D6]DMSO): δ = 7.48 (d, J =
2.5 Hz, 1 H), 7.31 (dd, J = 9.0, 2.5 Hz, 1 H), 6.79 (d, J = 9.0 Hz,
1 H), 6.23 (br. s, 2 H) ppm. 13C NMR ([D6]DMSO): δ = 150.7 (s),
134.0 (d), 131.1 (d), 118.5 (s), 117.0 (d), 116.9 (s), 94.3 (s) ppm.
2-Amino-5-bromobenzonitrile (6f):[31] This compound was prepared
from 2-aminobenzonitrile (6a; 5.0 g, 42.4 mmol) and bromine
(2.26 mL, 43.8 mmol) according to ref.[31] The product was ob-
tained as a white solid (5.68 g, 68%), m.p. 94–95 °C (ref.[46] 96–
3,4-Dihydro-4-imino-6-methoxy-3-methyl-1,2,3-benzotriazine (7b):
This compound was prepared from 2-azido-5-methoxybenzonitrile
(4b; 0.50 g, 2.87 mmol) and methylmagnesium bromide (3.0 m,
5.74 mmol) according to the procedure given for compound 7a.
The crude product was purified by column chromatography on sil-
ica (heptane/EtOAc) to yield the product 7b (0.39 g, 71%) as a
97 °C). IR (neat): ν = 3434, 3351, 2218, 1629, 1485, 1303, 1255,
˜
828 cm–1. 1H NMR ([D6]DMSO): δ = 7.58 (d, J = 2.4 Hz, 1 H),
7.41 (dd, J = 9.0, 2.4 Hz, 1 H), 6.74 (d, J = 9.0 Hz, 1 H), 6.26 (br.
s, 2 H) ppm. 13C NMR ([D6]DMSO): δ = 151.0 (s), 136.7 (d), 133.9
(d), 117.3 (d), 116.8 (s), 105.2 (s), 95.0 (s) ppm.
yellow solid, m.p. 169.7–172–8 °C. IR (neat): ν = 3282, 3033, 1607,
˜
1487, 1361, 1245, 1009, 738 cm–1. 1H NMR ([D6]DMSO): δ = 8.58
(br. s, 1 H), 7.85–7.72 (m, 2 H), 7.34 (dd, J = 8.83, 2.55 Hz, 1 H),
3.90 (s, 3 H), 3.79 (s, 3 H) ppm. 13C NMR ([D6]DMSO): δ = 161.7
(s), 149.6 (s), 135.0 (s), 129.8 (d), 121.4 (d), 119.5 (s), 104.9 (d),
56.2 (q), 38.5 (q) ppm. HRMS (ESI): calcd. for C9H10N4O [M +
H]+ 191.0933; found 191.0931.
2-Amino-3,5-dibromobenzonitrile (6g):[33] Bromine (6.5 mL,
127.1 mmol) was added dropwise to a solution of 2-aminobenzoni-
trile (6a; 5.0 g, 42.4 mmol) in acetic acid (100 mL). The reaction
mixture was stirred at room temperature overnight and the white
precipitate was collected by filtration. The solid was dried at room
temperature to afford the title product 6g (11.4 g, 98%), m.p.
3,4-Dihydro-4-imino-3,6-dimethyl-1,2,3-benzotriazine (7c): This
compound was prepared from 2-azido-5-methylbenzonitrile (4c;
0.50 g, 3.16 mmol) and methylmagnesium bromide (3.0 m,
6.33 mmol) according to the procedure given for compound 7a.
The crude product was purified by column chromatography on sil-
ica (heptane/EtOAc) to yield the product 7c (0.27 g, 49%) as a
156 °C (ref.[33] 156–156.5 °C). IR (neat): ν = 3470, 3359, 2225, 1635,
˜
1
1470, 1237, 1174, 870 cm–1. H NMR ([D6]DMSO): δ = 7.88 (d, J
= 2.3 Hz, 1 H), 7.74 (d, J = 2.3 Hz, 1 H), 6.27 (br. s, 2 H) ppm.
13C NMR ([D6]DMSO): δ = 147.5 (s), 139.0 (d), 134.2 (d), 115.9
(s), 109.3 (s), 105.6 (s), 96.6 (s) ppm.
yellow solid, m.p. 101.6–103.8 °C. IR (neat): ν = 3282, 1608, 1572,
˜
1
1246, 1227, 1023, 998, 833 cm–1. H NMR ([D6]DMSO): δ = 8.55
2-Amino-4,6-dimethylbenzonitrile (6h):[39] This compound was pre-
(br. s, 1 H), 8.11 (s, 1 H), 7.75 (d, J = 8.19 Hz, 1 H), 7.60 (dd, J =
8.19, 1.27 Hz, 1 H), 3.80 (s, 3 H), 2.44 (s, 3 H) ppm. 13C NMR
([D6]DMSO): δ = 149.7 (s), 142.2 (s), 138.3 (s), 134.0 (d), 127.6 (d),
123.0 (d), 117.6 (s), 38.6 (q), 21.3 (q) ppm. HRMS (ESI): calcd. for
C9H10N4 [M + H]+ 175.0984; found 175.0981.
pared according to ref.[39], m.p. 64–65 °C (ref.[39] 62–63 °C). IR
1
(neat): ν = 3446, 3365, 3351, 2201, 1636, 1610, 1294, 837 cm–1. H
˜
NMR ([D6]DMSO): δ = 6.41 (s, 1 H), 6.31 (s, 1 H), 5.83 (s, 2 H),
2.26 (s, 3 H), 2.14 (s, 3 H) ppm. 13C NMR ([D6]DMSO): δ = 151.9
(s), 143.5 (s), 141.0 (s), 118.3 (d), 117.5 (s), 112.5 (d), 92.0 (s), 21.4
(q), 20.2 (q) ppm.
3,4-Dihydro-4-imino-3,6,8-trimethyl-1,2,3-benzotriazine (7d): This
compound was prepared from 2-azido-3,5-dimethylbenzonitrile
(4d; 0.45 g, 2.61 mmol) and methylmagnesium bromide (3.0 m,
5.23 mmol) according to the procedure given for compound 7a.
The crude product was purified by column chromatography on sil-
ica (heptane/EtOAc) to yield the product 7d (0.27 g, 56%) as a
2-Amino-6-methylbenzonitrile (6i):[40,41] This compound was pre-
pared from 2-methyl-6-nitrobenzonitrile (2.0 g, 12.3 mmol) as ac-
cording to ref.[40] The product was obtained as a yellow solid
(1.04 g, 64%), m.p. 125–127 °C (ref.[40] 127–129 °C). IR (neat): ν =
˜
3403, 3338, 3232, 2211, 1645, 1474, 1167, 778 cm–1. 1H NMR ([D6]- yellow solid, m.p. 83.7–85.0 °C. IR (neat): ν = 3260, 2920, 1606,
˜
1
DMSO): δ = 7.15 (t, J = 7.9 Hz, 1 H), 6.60 (d, J = 8.3 Hz, 1 H),
1578, 1464, 1227, 974, 773 cm–1. H NMR ([D6]DMSO): δ = 8.26
6.47 (d, J = 7.9 Hz, 1 H), 5.90 (br. s, 2 H), 2.31 (s, 3 H) ppm. 13C (br. s, 1 H), 7.90 (s, 1 H), 7.42 (s, 1 H), 3.79 (s, 3 H), 2.56 (s, 3 H),
6596 Eur. J. Org. Chem. 2010, 6588–6599
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim