C. Gallardo-Garrido, et al.
ToxicologyandAppliedPharmacology401(2020)115104
3456 (N–H), 3278 (N–H), 1705 (C=O), 1589 (N–H), 1427 (C=N).
M.p. 186–188 °C. HRMS [M+]: C6H6ClN3O2: calc 188.0227. Found
188.0229.
115.76, 109.83, 49.30. Ir ν (cm−1): 1813 (C=O), 1760 (C=O),
1442 (C=N), 1350 (CH2). M.p. 198–200 °C. HRMS [M+]:
C8H6ClN3O3 calc 228.0176. Found 228.0179.
2-((5-Nitrofuran-2-yl)methylene)hydrazine-1-carboxamide
(ni-
1-((5-Nitrofuran-2-ylmethylene)amino)imidazolidine-2,4-dione (ni-
trofurantoin) (3e, NHT). Yellow solid (95%, yield). 1H NMR
(400 MHz, DMSO-d6) δ 11.46 (s, 1H, NH), 7.78 (s, 1H, H-6), 7.77 (d,
J = 3.9 Hz, 1H, H-4), 7.13 (d, J = 3.9 Hz, 1H, H-3), 4.35 (s, 2H,
CH2). 13C NMR (101 MHz, DMSO-d6) δ 169.1, 153.7, 152.3, 152.2,
131.6, 115.2, 115.0, 49.5. HRMS [M+]: C8H6N4O5 calc 239.0411.
Found 239.1626.
N′-(Furan-2-ylmethylene)benzohydrazide (4a). White solid (47%
yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.79 (s, 1H, NH), 8.36
(s, 1H, H-6), 7.94–7.87 (m, 2H, H-11), 7.85 (d, J = 1.8 Hz, 1H, H-5),
7.59 (t, J = 7.3 Hz, 1H, H-13), 7.52 (t, J = 7.3 Hz, 2H, H-12), 6.93
(d, J = 3.5 Hz, 1H, H-3), 6.64 (dd, J = 3.5, 1.8 Hz, 1H, C-4). 13C
NMR (101 MHz, DMSO-d6) δ ppm 163.1, 149.5, 145.2, 137.6, 133.4,
131.8, 128.5, 127.6, 113.5, 112.2. Ir ν (cm−1): 3240 (N–H), 3055
(N–H), 1651 (C=O), 1473 (C=N). M.p. 180–182 °C. HRMS [M+]:
trofurazone) (1d, NFZ). Yellow solid (97% yield). 1H NMR
(400 MHz, DMSO-d6) δ ppm 10.78 (s, 1H, NH), 7.79 (s, 1H, H-6),
7.76 (d, J = 4.0 Hz, 1H, H-3), 7.22 (d, J = 4.0 Hz, 1H, H-4), 6.61 (s,
2H, NH2). 13C NMR (101 MHz, DMSO-d6) δ 156.4, 153.6, 151.7,
127.9, 115.7, 112.6. Ir ν (cm−1): 3464–3294 (N–H), 1720 (C=O),
1581(C=N), 1512 (NO2), 1388 (NO2). HRMS [M+]: C6H6N4O4 calc
198.1366. Found 198.1366.
1-(Furan-2-ylmethylene)-2-phenylhydrazine (2a). Brown solid (97%
yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.31 (s, 1H, NH), 7.79
(s, 1H, H-6), 7.70 (d, J = 1.8 Hz, 1H, H-5), 7.22 (t, J = 7.7 Hz, 2H,
H-11), 7.02 (d, J = 7.7 Hz, 2H, H-10), 6.75 (t, J = 7.7 Hz, 1H, H-
12), 6.64 (d, J = 3.4 Hz, 1H, H-3), 6.55 (dd, J = 3.4, 1.8 Hz, 1H, H-
4). 13C NMR (101 MHz, DMSO-d6) δ 151.3, 145.5, 143.5, 129.6,
127.7, 119.3, 112.4, 112.3, 109.3, 60.2. Ir ν (cm−1): 3317 (N–H),
1481 (C=N), 1512 (C=C), 1442 (C=C). M.p. dec. 86 °C. HRMS
[M+]: C11H10N2O calc 186.2104. Found 186.2106.
1-(5-Bromofuran-2-ylmethylene)-2-phenylhydrazine (2b). Brown
solid (50% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.39 (s,
1H, NH), 7.68 (s, 1H, H-6), 7.21 (t, 2H, H-11), 7.00 (d, J = 7.9 Hz,
2H, H-10), 6.76 (t, J = 7.2 Hz, 1H, H-12), 6.67 (d, J = 3.5 Hz, 1H,
H-3), 6.66 (d, J = 3.4 Hz, 1H, H-4). 13C NMR (101 MHz, DMSO- d6)
δ ppm 152.9, 144.8, 129.1, 126.0, 121.7, 119.1, 113.8, 112.0,
111.2. Ir ν (cm−1): 3302 (N–H), 1442 (C=N). M.p. > 300 °C. HRMS
[M+]: C11H9BrN2O calc 265.1060. Found 265.1066.
C
12H10N2O2 calc 214.2205. Found 214.2215.
N′-(5-Methylfuran-2-ylmethylene)benzohydrazide (4b). White solid
(98% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H, NH),
8.26 (s, 1H, H-6), 7.89 (d, J = 7.0 Hz, 2H, H-11), 7.58 (t,
J = 7.3 Hz, 1H, H-13), 7.51 (t, J = 7.3 Hz, 2H, H-12), 6.81 (d,
J = 3.2 Hz, 1H, H-3), 6.26 (d, J = 3.2 Hz, 1H, H-4), 2.34 (s, 3H,
CH3). 13C NMR (101 MHz, DMSO-d6) δ 163.0, 154.6, 147.9, 137.4,
133.4, 131.7, 128.4, 127.5, 115.3, 108.6, 13.5. Ir ν (cm−1): 3210
(N–H), 3051 (N–H), 1641 (C=O), 1485 (C=N). M.p. 161–163 °C.
HRMS [M+]: C13H12N2O2 calc 228.2472. Found 228.2477.
1-(5-Nitrofuran-2-ylmethylene)-2-phenylhydrazine (2c). Red nee-
dles (98% yield). 1H NMR (400 MHz, DMSO- d6) δ ppm 11.12 (s, 1H,
NH), 7.78 (s, 1H, H-6), 7.73 (d, J = 4.0 Hz, 1H, H-4), 7.27 (t,
J = 7.7 Hz, 2H, H-11), 7.12 (t, J = 7.7 Hz, 2H, H-10), 6.98 (d,
J = 4.0 Hz, 1H, H-3), 6.86 (t, J = 7.7 Hz, 1H, H-12). 13C NMR
(101 MHz, DMSO- d6) δ 156.0, 151.4, 144.2, 129.7, 124.4, 121.0,
116.3, 113.3, 111.2. Ir ν (cm−1): 3302 (N–H), 1597 (C=N), 1566
(NO2), 1365 (NO2), 1465 (C=C). M.p. 190–192 °C. HRMS [M+]:
N′-(5-Bromofuran-2-ylmethylene)benzohydrazide (4c) White solid
(94% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.86 (s, 1H,
NH), 8.27 (s, 1H, H-6), 7.89 (d, J = 7.2 Hz, 2H, H-11), 7.59 (t,
J = 7.5 Hz, 1H, H-13), 7.52 (t, J = 7.5 Hz, 2H, H-12), 6.98 (d,
J = 3.5 Hz, 1H, H-4), 6.76 (d, J = 3.5 Hz, 1H, H-3). 13C NMR
(101 MHz, DMSO-d6) δ ppm 163.1, 151.4, 136.3, 133.2, 131.8,
128.5, 127.6, 124.6, 116.2, 114.2. Ir ν (cm−1): 3240 (N–H), 3058
(N–H), 1649 (C=O), 1475 (C=N). M.p. dec. 164 °C. HRMS [M+]:
C
11H9N3O3 calc 231.2080. Found 231.2088.
C12H9BrN2O2 calc 293.1161. Found 293.1156.
1-((Furan-2-ylmethylene)amino)imidazolidine-2,4-dione
(3a).
N′-(5-Chlorofuran-2-ylmethylene)benzohydrazide (4d) White solid
(yield 95%). 1H NMR (400 MHz, DMSO-d6) δ 11.87 (s, 1H, NH),
8.28 (s, 1H, H-6), 7.90 (d, J = 7.2 Hz, 2H, H-11), 7.65–7.57 (m, 1H,
H-13), 7.53 (dd, J = 8.2, 6.5 Hz, 2H, H-12), 7.03 (d, J = 3.5 Hz, 1H,
H-4), 6.68 (d, J = 3.5 Hz, 1H, H-3). 13C NMR (101 MHz, DMSO-d6)
δ 163.60, 149.71, 137.81, 136.83, 133.70, 132.32, 128.97, 128.07,
116.41, 109.92. Ir ν (cm−1): 3425 (N–H), 3224 (N–H), 1650 (C=O),
1489 (C=N). M.p. 170–171 °C. HRMS [M+]: C12H9ClN2O2 calc
249.0431. Found 249.0435.
N′-(5-Nitrofuran-2-ylmethylene)benzohydrazide (4e). Yellow solid
(78% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.23 (s, 1H,
NH), 8.41 (s, 1H, H-6), 7.92 (d, J = 7.3 Hz, 2H, H-11), 7.79 (d,
J = 3.9 Hz, 1H, H-4), 7.62 (t, J = 7.3 Hz, 1H, H-13), 7.55 (t,
J = 7.3 Hz, 2H, H-12), 7.27 (d, J = 4.0 Hz, 1H, H-3). 13C NMR
(101 MHz, DMSO-d6) δ ppm 163.5, 151.9, 151.8, 135.5, 132.8,
132.2, 128.6, 127.8, 115.3, 114.7. Ir ν (cm−1): 3248 (N–H), 3016
(N–H), 1654 (C=O), 1475 (C=N). M.p. 221–224 °C. HRMS [M+]:
White solid (90% yield). 1H NMR (400 MHz, DMSO- d6) δ ppm
11.23 (s, 1H, NH), 7.81 (d, J = 1.8 Hz, 1H, H-5), 7.69 (s, 1H, H-6),
6.83 (d, J = 3.4 Hz, 1H, H-3), 6.62 (dd, J = 3.4, 1.8 Hz, 1H, H-4),
4.32 (s, 2H, CH2). 13C NMR (101 MHz, DMSO-d6) δ 169.0, 153.4,
149.5, 144.9, 133.3, 113.0, 112.2, 48.9. Ir ν (cm−1): 1782 (C=O),
1720 (C=O), 1481 (C=N), 1442 (CH2). M.p. dec. 220 °C. HRMS
[M+]: C8H7N3O3 calc 194.0560. Found 194.1872
1-((5-Methylfuran-2-ylmethylene)amino)imidazolidine-2,4-dione
(3b). White solid (88% yield). 1H NMR (400 MHz, DMSO- d6) δ ppm
11.20 (s, 1H, NH), 7.61 (s, 1H, H-6), 6.70 (d, J = 3.3 Hz, 1H, H-3),
6.23 (d, J = 3.3 Hz, 1H, H-4), 4.30 (s, 2H, CH2), 2.33 (s, 3H, CH3);
13C NMR (101 MHz, DMSO- d6) δ 169.4, 154.5, 153.7, 148.4, 133.7,
115.2, 108.9, 49.3, 13.9. Ir ν (cm−1): 11782 (C=O), 1720 (C=O),
1527 (C=N), 1442 (CH2). M.p. dec. 230 °C. HRMS [M+]: C9H9N3O3
calc 208.0717. Found 208.1800.
1-((5-Bromofuran-2-ylmethylene)amino)imidazolidine-2,4-dione
(3c). White solid (64% yield). 1H NMR (400 MHz, DMSO- d6) δ ppm
11.27 (s, 1H, NH), 7.63 (s, 1H, H-6), 6.85 (d, J = 3.5 Hz, 1H, H-3),
6.74 (d, J = 3.5 Hz, 1H, H-4), 4.30 (s, 2H, CH2). 13C NMR
(101 MHz, DMSO-d6) δ ppm 168.8, 153.3, 151.4, 132.1, 124.1,
115.5, 114.2, 48.9. Ir ν (cm−1): 1789 (C=O), 1712 (C=O), 1481
(C=N), 1442 (CH2). M.p. dec. 220 °C. HRMS [M+]: C8H6BrN3O3
calc 271.9665. Found 272.0049.
C
12H9N3O4 calc 259.2181. Found 259.2188.
N′-(Furan-2-ylmethylene)-4-hydroxybenzohydrazide (5a). White
solid (88% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.58 (s,
1H, NH), 10.12 (s, 1H, OH), 8.33 (s, 1H, H-6), 7.82 (d, J = 1.8 Hz,
1H, H-5), 7.81–7.75 (m, 2H, H-11), 6.89 (d, J = 3.4 Hz, 1H, H-3),
6.87–6.82 (m, 2H, H-12), 6.62 (t, J = 3.4, 1.8 Hz, 1H, H-4). 13C
NMR (101 MHz, DMSO-d6) δ ppm 162.7, 160.7, 149.6, 144.9, 136.7,
129.7, 123.8, 115.0, 113.0, 112.2. Ir ν (cm−1): 1666 (C=O), 1435
(C=N). M.p. 230–234 °C. HRMS [M+]: C12H10N2O3 calc 230.2199.
Found 230.2211.
1-((5-Chlorofuran-2-ylmethylene)amino)imidazolidine-2,4-dione
(3d). White solid (89% yield). 1H NMR (400 MHz, DMSO-d6) δ
11.29 (s, 1H, NH), 7.63 (s, 1H, H-6), 6.90 (d, J = 3.5 Hz, 1H, H-4),
6.65 (dd, J = 3.5, 1.2 Hz, 1H, H-3), 4.31 (s, 2H). 13C NMR
(101 MHz, DMSO) δ 169.30, 153.77, 149.73, 137.43, 132.57,
4-Hydroxy-N′-((5-methylfuran-2-yl)methylene)benzohydrazide
(5b). White solid (97% yield). 1H NMR (400 MHz, DMSO-d6) δ
3