10.1002/cmdc.201800238
ChemMedChem
FULL PAPER
1
Off-white powder; yield: 49%; 1H NMR (400 MHz, DMSO) δ 10.64 (s, 1H,
NHOH), 8.94 (s, 1H, NHOH), 7.50 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 15.7
Hz, 1H, Hβ), 6.97 (d, J = 8.6 Hz, 1H), 6.31 (d, J = 15.8 Hz, 1H, Hα), 3.78
(s, 1H). MS (ESI_, MeOH) m/z (%):194.05 (100) [M+H]+, 192.24 (100)
[M+H]+. HRMS-ESI m/z [M+H]+ calcd for C10H12NO3+: 194.0817, found:
194.0812.
Off-white powder; yield: 57%; H NMR (400 MHz, DMSO-d6) δ 10.62 (s,
1H, NHOH), 8.94 (s, 1H, NHOH), 7.46 – 7.31 (m, 6H, Hβ, 5Ar’H), 7.18 (s,
1H, H2), 7.09 (d, J = 8.7 Hz, 1H, H6), 7.06 (d, J = 8.3 Hz, 1H, H5), 6.34
(d, J = 15.7 Hz, 1H, Hα), 5.12 (s, 2H, CH2), 3.81 (s, 3H, CH3). MS (ESI_,
MeOH) m/z (%): 382.19 (100) [M-H]-. HRMS-ESI m/z [M+H]+ calcd for
C17H18NO4+: 300.1236, found: 300.1232.
(2E)-N-Hydroxy-3-(3-methoxyphenyl)-2-propenamide (19c)
(2E)-N-Hydroxy-3-[2-(benzyloxy)phenyl]-2-propenamide (27c)
1
1
Off-white powder; yield: 37%; H NMR (400 MHz, DMSO-d6) δ 10.73 (s,
Off-white powder; yield: 12%; H NMR (400 MHz, DMSO-d6) δ 10.72 (s,
1H, NHOH), 9.03 (s, 1H, NHOH), 7.43 (d, J = 15.8 Hz, 1H, Hβ ), 7.32 (t, J
= 7.9 Hz, 1H, H5), 7.13 (d, J = 7.9 Hz, 1H, H6), 7.11 (s, 1H, H2), 6.94 (dd,
J = 8.2, 2.1 Hz, 1H, H4), 6.46 (d, J = 15.8 Hz, 1H, Hα), 3.78 (s, 3H, CH3).
MS (ESI_, MeOH) m/z (%): 192.27 (100) [M-H]- 194.04 (100) [M+H]+.
1H, NHOH), 8.96 (s, 1H, NHOH), 7.75 (d, J = 16.0 Hz, 1H, Hβ), 7.53 (d, J
= 7.0 Hz, 1H, H6), 7.47 (d, J = 7.0 Hz, 2H, H2’, H6’), 7.43 – 7.37 (m, 2H,
H3’, H5’), 7.37 – 7.29 (m, 2H, H4, H4’), 7.14 (d, J = 8.2 Hz, 1H, H3), 6.98
(t, J = 7.4 Hz, 1H, H5), 6.48 (d, J = 16.0 Hz, 1H, Hα), 5.21 (s, 2H, CH2).
MS (ESI_, MeOH) m/z (%): 268.20 (100) [M-H]-. HRMS-ESI m/z [M+H]+
calcd for C16H16NO3+: 270.1130, found: 270.1128.
(2E)-3-(2-Ethoxyphenyl)-N-hydroxy-2-propenamide (20c)
1
Off-white powder; yield: 62%; H NMR (400 MHz, DMSO-d6) δ 10.72 (s,
1H, NHOH), 8.96 (s, 1H, NHOH), 7.67 (d, J = 15.9 Hz, 1H, Hβ), 7.49 (d, J
= 6.5 Hz, 1H, H6), 7.36 – 7.30 (m, 1H, H4), 7.05 (d, J = 7.9 Hz, 1H, H5),
6.96 (m, J = 7.5 Hz, 1H, H3), 6.51 (d, J = 15.9 Hz, 1H, Hα), 4.11 (q, J =
7.0 Hz, 2H, CH2), 1.39 (t, J = 7.0 Hz, 3H, CH3). HRMS-ESI m/z [M+H]+
calcd for C11H14NO3+: 208.0974, found: 208.0971.
(2E)-3-[2-Benzyloxy-3-methoxyphenyl]-N-hydroxy-2-propenamide
(28c)
1
Off-white powder; yield: 59%; H NMR (400 MHz, DMSO-d6) δ 10.72 (s,
1H, NHOH), 9.00 (s, 1H, NHOH), 7.71 (d, J = 16.1 Hz, 1H, Hβ), 7.45 (d, J
= 6.8 Hz, 2H, H2’, H6’), 7.41 – 7.31 (m, 3H, H6, H3’, H5’), 7.11 (t, J = 6.7
Hz, 3H, H4, H5, H4’), 6.43 (d, J = 15.9 Hz, 1H, Hα), 4.96 (s, 2H, CH2),
3.85 (s, 3H, CH3). MS (ESI_, MeOH) m/z (%): 298.25 (100) [M-H]- 322.07
(100) [M+Na]+. HRMS-ESI m/z [M+H]+ calcd for C17H18NO4+: 300.1236,
found: 300.1230.
(2E)-3-(4-Ethoxyphenyl)-N-hydroxy-2-propenamide (21c)
1
Off-white powder; yield: 35%; H NMR (400 MHz, DMSO-d6) δ 10.63 (s,
1H, NHOH), 8.93 (s, 1H, NHOH), 7.48 (d, J = 8.5 Hz, 2H, H3, H5), 7.39
(d, J = 15.8 Hz, 1H, Hβ), 6.95 (d, J = 8.7 Hz, 2H, H2, H6), 6.30 (d, J =
15.6 Hz, 1H, Hα), 4.05 (q, J = 6.9 Hz, 2H, CH2), 1.33 (t, J = 7.0 Hz, 3H,
CH3). MS (ESI_, MeOH) m/z (%): 206.28 (100) [M-H]-. HRMS-ESI m/z
[M+H]+ calcd for C11H14NO3+: 208.0974, found: 208.0968.
(2E)-3-[2-(4-Chlorobenzyloxy)phenyl]-N-hydroxy-2-propenamide
(29c)
1
Off-white powder; yield: 55%; H NMR (400 MHz, DMSO-d6) δ 10.72 (s,
1H, NHOH), 8.98 (s, 1H, NHOH), 7.73 (d, J = 16.0 Hz, 1H, Hβ), 7.53 (d, J
= 6.9 Hz, 1H, H6), 7.51 – 7.44 (m, 4H, H2’, H3’, H5’, H6’), 7.33 (t, J = 7.2
Hz, 1H, H5), 7.12 (d, J = 8.2 Hz, 1H, H3), 6.99 (t, J = 7.5 Hz, 1H, H4),
6.49 (d, J = 15.9 Hz, 1H, Hα), 5.21 (s, 2H, CH2). MS (ESI_, MeOH) m/z
(%): 302.19 (100) [M-H]- 304.10 (100) [M+H]+. HRMS-ESI m/z [M+H]+
calcd for C16H15ClNO3+: 304.0740, found: 304.0734.
(2E)-3-(3-Methoxy-4-hydroxyphenyl)-N-hydroxy-2-propenamide (22c)
1
Off-white powder; yield: 43%; H NMR (400 MHz, DMSO-d6) δ 10.58 (s,
1H, NHOH), 9.40 (s, 1H, NHOH), 7.35 (d, J = 15.7 Hz, 1H, Hβ), 7.12 (s,
1H, H6), 6.99 (d, J = 8.1 Hz, 1H, H2), 6.78 (d, J = 8.1 Hz, 1H, H3), 6.27
(d, J = 15.7 Hz, 1H, Hα), 3.80 (s, 3H, CH3). MS (ESI_, MeOH) m/z (%):
+
208.22 (100) [M-H]-. HRMS-ESI m/z [M+H]+ calcd for C10H12NO4
:
210.0766, found: 210.0763 .
(2E)-3-[2-(2,4-Dichlorobenzyloxy)phenyl]-N-hydroxy-2-propenamide
(30c)
(2E)-3-(3-Ethoxy-4-hydroxyphenyl)-N-hydroxy-2-propenamide (23c)
1
Off-white powder; yield: 49%; H NMR (400 MHz, DMSO-d6) δ 10.70 (s,
1
Pale red powder; yield: 33%; H NMR (500 MHz, DMSO-d6) δ 10.57 (s,
1H, NHOH), 9.34 (s, 1H, NHOH), 7.33 (d, J = 15.8 Hz, 1H, Hβ), 7.09 (s,
1H, H2), 6.98 (d, J = 8.2 Hz, 1H, H6), 6.79 (d, J = 8.1 Hz, 1H, H5), 6.25 (t,
J = 12.3 Hz, 1H, Hα), 4.09 – 4.01 (m, 2H, CH2), 1.34 (t, J = 7.0 Hz, 3H,
CH3). MS (ESI_, MeOH) m/z (%): 222.23 (100) [M-H]-, 224.03 (100)
[M+H]+. HRMS-ESI m/z [M+H]+ calcd for C11H14NO4+: 224.0923, found:
224.0921.
1H, NHOH), 8.97 (s, 1H, NHOH), 7.74 – 7.68 (m, 2H, Hβ, H3’), 7.60 (d, J
= 8.3 Hz, 1H, H6), 7.55 (d, J = 7.7 Hz, 1H, H6’), 7.50 (dd, J = 8.3, 2.1 Hz,
1H, H5’), 7.36 (t, J = 7.8 Hz, 1H, H4), 7.15 (d, J = 8.3 Hz, 1H, H3), 7.02 (t,
J = 7.4 Hz, 1H, H5), 6.45 (d, J = 15.9 Hz, 1H, Hα), 5.24 (s, 2H, CH2). MS
(ESI_, MeOH) m/z (%): 336.12 (100) [M-H]- 338.06 (100) [M+H]+. HRMS-
ESI m/z [M+H]+ calcd for C16H14Cl2NO3+: 338.0351, found: 338.0347.
(2E)-3-[2-(2,6-Dichlorobenzyloxy)phenyl]-N-hydroxy-2-propenamide
(2E)-N-Hydroxy-3-[4-(benzyloxy)phenyl]-2-propenamide (24c)
(31c)
1
Pale pink powder; yield 16%; H NMR (400 MHz, DMSO-d6) δ 10.62 (s,
1
Off-white powder; yield: 61%; H NMR (400 MHz, DMSO-d6) δ 10.67 (s,
1H, NHOH), 8.94 (s, 1H, NHOH), 7.54 – 7.29 (m, J = 24.6, 17.1, 7.7 Hz,
8H, Hβ, H3, H5, H2’, H3’, H4’, H5’, H6’), 7.04 (d, J = 8.6 Hz, 2H, H2, H6),
6.31 (d, J = 15.9 Hz, 1H, Hα), 5.14 (s, 2H, CH2). MS (ESI_, MeOH) m/z
(%): 268.17 (100) [M-H]-, 270.07 (100) [M+H]+.
1H, NHOH), 8.93 (s, 1H, NHOH), 7.65 – 7.47 (m, 5H, Hβ, H6, H3’, H4’,
H5’), 7.41 (dd, J = 12.0, 4.9 Hz, 1H, H4), 7.31 (d, J = 8.1 Hz, 1H, H3),
7.05 (t, J = 7.4 Hz, 1H, H5), 6.37 (d, J = 15.9 Hz, 1H, Hα), 5.30 (s, J =
11.7 Hz, 2H, CH2). MS (ESI_, MeOH) m/z (%):338.46 (100) [M+H]+.
+
HRMS-ESI m/z [M+H]+ calcd for C16H14Cl2NO3
: 338.0351, found:
(2E)-N-Hydroxy-3-[4-benzyloxy-3-chlorphenyl]-2-propenamide (25c)
Off-white powder; yield: 38%; 1H NMR (400 MHz, DMSO-d6) δ 10.66 (s,
1H, NHOH), 9.00 (s, 1H, NHOH), 7.67 (d, J = 1.8 Hz, 1H, H2), 7.50 (dd, J
= 8.6, 1.7 Hz, 1H, H6), 7.49 – 7.38 (m, 5H, Hβ, H2’, H3’, H5’, H6’), 7.37 –
7.32 (m, 1H, H4’), 7.27 (d, J = 8.6 Hz, 1H, H5), 6.37 (d, J = 15.8 Hz, 1H,
Hα), 5.25 (s, 2H, CH2). MS (ESI_, MeOH) m/z (%): 304.15 (100) [M+H]+,
338.0345.
(2E)-3-[2-(4-Chlorophenoxy)phenyl]-N-hydroxy-2-propenamide (32c)
1
Off-white powder; yield: 89%; H NMR (400 MHz, DMSO-d6) δ 10.78 (s,
1H,NHOH), 9.02 (s, 1H, NHOH), 7.73 – 7.67 (m, 1H, H6), 7.58 (d, J =
15.9 Hz, 1H, Hβ), 7.46 – 7.37 (m, 3H, H6, H3’, H5’), 7.25 (t, J = 7.3 Hz,
1H, H4), 7.01 – 6.95 (m, 3H, H5, H2’, H6’), 6.55 (d, J = 15.9 Hz, 1H, Hα).
MS (ESI_, MeOH) m/z (%): 288.26 (100) [M-H]-. HRMS-ESI m/z [M+H]+
calcd for C15H13NO3+: 290.0584, found: 290.0585.
-
302.15 (100) [M-H]-. HRMS-ESI m/z [M-H]- calcd for C16H13ClNO3 :
302.0584, found: 302.0584.
(2E)-N-Hydroxy-3-[4-benzyloxy-3-methoxyphenyl]-2-propenamide
(26c)
9
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