D
P. D. Parker, J. G. Pierce
Special Topic
Synthesis
1H NMR (400 MHz, DMSO): δ = 9.93 (s, 1 H), 8.38 (s, 1 H), 8.23 (s, 1 H),
7.52–7.28 (m, 7 H), 6.48 (s, 1 H), 4.18 (d, J = 6.3 Hz, 2 H).
13C NMR (100 MHz, DMSO): δ = 154.5, 148.2, 147.9, 136.3, 134.5,
132.4, 129.1, 128.3, 128.1, 123.4, 44.2.
ESI-MS: m/z = 228 [M + H]+.
N-(2,4-Dimethoxybenzyl)-N′-hydroxybenzimidamide (1f)
According to Typical Procedure 1, N-hydroxybenzimidoyl chloride
(0.075 g, 0.48 mmol), (2,4-dimethoxyphenyl)methanamine (0.10 g,
0.58 mmol), and Et3N (0.049 g, 0.48 mmol) were stirred in anhydrous
DMF (1.6 mL) for 2 h to afford 1f after purification by flash chroma-
tography (silica gel, hexanes–EtOAc, 5–35%); yield: 0.084 g (61%); yel-
low solid; mp 134–137 °C.
HRMS: m/z [M + H]+ calcd for C13H14N3O: 228.1131; found: 228.1131.
IR (neat): 3389, 3199, 2935, 1614, 1587, 1508, 1465, 1208, 1157 cm–1
.
N′-Hydroxy-N-[4-(trifluoromethyl)benzyl]benzimidamide (1c)
1H NMR (400 MHz, CDCl3): δ = 7.48–7.46 (m, 2 H), 7.41–7.37 (m, 3 H),
6.90 (d, J = 8.2 Hz, 1 H), 6.40 (d, J = 2.4 Hz, 1 H), 6.37 (dd, J = 8.2, 2.4 Hz,
1 H), 5.75 (t, J = 6.2 Hz, 1 H, NH), 4.12 (d, J = 6.2 Hz, 2 H), 3.78 (s, 3 H),
3.75 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 160.3, 158.4, 156.8, 131.8, 129.5,
129.0, 128.8, 128.4, 120.5, 103.8, 98.6, 55.5, 55.4, 43.1.
According to Typical Procedure 1, N-hydroxybenzimidoyl chloride
(0.20 g, 1.3 mmol), [4-(trifluoromethyl)phenyl]methanamine (0.27 g,
1.5 mmol), and Et3N (0.13 g, 1.3 mmol) were stirred in anhydrous
DMF (4.3 mL) for 2 h to afford 1c after purification by flash chroma-
tography (silica gel, hexanes–EtOAc, 10–40%); yield: 0.27 g (73%);
white solid; mp 122–123 °C.
IR (neat): 3384, 3192, 3061, 2939, 1627, 1575, 1496, 1327, 700 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.56–7.53 (m, 2 H), 7.45–7.34 (m, 5 H),
ESI-MS: m/z = 287 [M + H]+.
HRMS: m/z [M + H]+ calcd for C16H19N2O3: 287.1390; found: 287.1390.
.
7.33–7.26 (m, 2 H), 5.83 (s, 1 H), 4.29 (s, 2 H).
(Z)-N′-Hydroxy-N-(1-phenylethyl)benzimidamide (1g)
13C NMR (100 MHz, CDCl3): δ = 156.4, 143.9, 130.9, 130.0, 129.8,
According to Typical Procedure 1, N-hydroxybenzimidoyl chloride
(0.090 g, 0.58 mmol), 1-phenylethan-1-amine (0.084 g, 0.69 mmol),
and Et3N (0.059 g, 0.58 mmol) were stirred in anhydrous DMF (1.9
mL) for 2 h to afford 1g after purification by flash chromatography
(silica gel, hexanes–EtOAc, 5–35%); yield: 0.11 g (81%); clear oil.
129.4, 128.7, 128.6, 127.0, 125.7, 125.6, 125.6, 122.9, 94.6, 47.0.
ESI-MS: m/z = 295 [M + H]+.
HRMS: m/z [M
+
H]+ calcd for C15H14F3N2O: 295.1053; found:
295.1050.
IR (neat): 3203, 3061, 2967, 1631, 1571, 1493, 1378, 1142, 700 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.41–7.28 (m, 8 H), 7.13 (d, J = 7.2 Hz, 2
H), 5.69 (s, 1 H, NH), 4.47 (s, 1 H), 1.45 (d, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.0, 144.9, 131.8, 129.5, 128.6,
128.5, 128.3, 127.0, 125.6, 52.8, 24.6.
.
N′-Hydroxy-N-phenethylbenzimidamide (1d)
According to Typical Procedure 1, N-hydroxybenzimidoyl chloride
(0.090 g, 0.58 mmol), 2-phenylethan-1-amine (0.08 g, 0.06 mmol),
and Et3N (0.060 g, 0.58 mmol) were stirred in anhydrous DMF (1.9
mL) for 2 h to afford 1d after purification by flash chromatography
(silica gel, hexanes–EtOAc, 10–50%); yield: 0.12 g (85%); clear oil.
ESI-MS: m/z = 241 [M + H]+.
1H NMR (400 MHz, CDCl3): δ = 7.45–7.37 (m, 5 H), 7.30–7.20 (m, 3 H),
HRMS: m/z [M + H]+ calcd for C15H17N2O: 241.1335; found: 241.1334.
7.10–7.08 (m, 2 H), 5.50 (s, 1 H, NH), 3.28 (s, 2 H), 2.71 (t, J = 7.1 Hz, 2
H).
N′-Hydroxy-N-(1,2,3,4-tetrahydronaphthalen-1-yl)benzimid-
amide (1h)
13C NMR (100 MHz, CDCl3): δ = 156.3, 138.7, 131.5, 129.5, 128.9,
128.6, 128.6, 128.4, 126.5, 45.2, 38.0.
ESI-MS: m/z = 241 [M + H]+.
According to Typical Procedure 1, N-hydroxybenzimidoyl chloride
(0.080 g, 0.51 mmol), 1,2,3,4-tetrahydronaphthalen-1-amine (0.093
g, 0.62 mmol), and Et3N (0.052 g, 0.51 mmol) were stirred in anhy-
drous DMF (1.7 mL) for 2 h to afford 1h after purification by flash
chromatography (silica gel, hexanes–EtOAc, 5–35%); yield: 0.10 g
(73%); white solid; mp 120–123 °C.
N′-Hydroxy-N-(2-thienylmethyl)benzimidamide (1e)
According to Typical Procedure 1, N-hydroxybenzimidoyl chloride
(0.20 g, 1.3 mmol), 2-thienylmethanamine (0.17 g, 1.5 mmol), and
Et3N (0.13 g, 1.3 mmol) were stirred in anhydrous DMF (4.3 mL) for 2
h to afford 1e after purification by flash chromatography (silica gel,
hexanes–EtOAc, 5–35%); yield: 0.24 g (80%); white solid; mp 126–128
°C.
IR (neat): 3377, 3354, 3216, 2935, 1638, 1575, 1488, 1445, 1382 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.62–7.59 (m, 2H), 7.49–7.45 (m, 1 H),
7.44–7.39 (m, 3 H), 7.22–7.14 (m, 2 H), 7.07–7.06 (m, 1 H), 5.56 (d, J =
10.7 Hz, 1 H, NH), 4.44–4.42 (m, 1 H), 2.79–2.76 (m, 1 H), 2.71–2.65
(m, 1 H), 1.93–1.87 (m, 2 H), 1.71–1.64 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 156.4, 138.1, 137.4, 131.8, 129.8,
129.1, 128.7, 128.5, 128.1, 127.2, 126.3, 51.8, 29.3, 20.4.
IR (neat): 3401, 3188, 3105, 2935, 1631, 1575, 1484, 1445, 700 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.54–7.51 (m, 2 H), 7.43–7.39 (m, 3 H),
7.19 (dd, J = 5.1, 1.2 Hz, 1 H), 6.92 (dd, J = 5.1, 3.5 Hz, 1 H), 6.84 (dd, J =
3.3, 0.97 Hz, 1 H), 5.80 (s, 1 H, NH), 4.38 (s, 2 H).
ESI-MS: m/z = 267 [M + H]+.
13C NMR (100 MHz, CDCl3): δ = 156.4, 143.0, 131.0, 129.8, 128.6,
HRMS: m/z [M + H]+ calcd for C17H19N2O: 267.1492; found: 267.1490.
128.6, 126.9, 124.7, 124.7, 42.8.
ESI-MS: m/z = 233 [M + H]+.
N′-Hydroxy-N-isobutylbenzimidamide (1i)
+
H]+ calcd for C12H13N2OS: 233.0743; found:
According to Typical Procedure 1, N-hydroxybenzimidoyl chloride
(0.10 g, 0.64 mmol), 2-methylpropan-1-amine (0.056 g, 0.77 mmol),
and Et3N (0.065 g, 0.64 mmol) were stirred in anhydrous DMF (2.1
mL) for 2 h to afford 1i after purification by flash chromatography
(silica gel, hexanes–EtOAc, 10–40%); yield: 0.099 g (80%); clear solid;
mp 74–75 °C.
HRMS: m/z [M
233.0741.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H