Communication
mixture was stirred at 100 °C for 12 h. After the reaction completed,
the mixture was quenched with saturated Na2S2O3 solution (50 mL),
extracted with EtOAc (3 × 50 mL). The combined organic layers
were washed with brine, dried over anhydrous Na2SO4, filtered and
then concentrated under reduced pressure. The residue was puri-
fied by column chromatography on silica gel (petroleum ether/
EtOAc = 3:1) to yield the desired product .
5-Phenyl-1,3,4-thiadiazol-2-amine[30] (4a): Yield: 83 % ; Colorless
solid, m.p. 213–214 °C; 1H NMR (400 MHz, [D6]DMSO) δ = 7.71 (d,
J = 6.9 Hz, 2H), 7.41 (m, 5H). 13C NMR (101 MHz, [D6]DMSO) δ =
168.97, 156.87, 131.41, 129.97, 129.52, 126.73.
5-(p-Tolyl)-1,3,4-thiadiazol-2-amine[34] (4b): Yield: 79 %; Colorless
solid, m.p. 215–217 °C; 1H NMR (400 MHz, [D6]DMSO) δ = 7.60 (d,
J = 8.1 Hz, 2H), 7.34 (br s, 2H), 7.23 (d, J = 8.0 Hz, 2H), 2.30 (s, 3H).
13C NMR (101 MHz, [D6]DMSO) δ = 168.61, 156.89, 139.72, 130.07,
128.72, 126.66, 21.32.
5-(4-Methoxyphenyl)-1,3,4-thiadiazol-2-amine[34] (4c): Yield:
70 %; Colorless solid, m.p. 191–193 °C; 1H NMR (400 MHz,
[D6]DMSO) δ = 7.64 (d, J = 8.8 Hz, 2H), 7.25 (br s, 2H), 6.98 (d, J =
8.8 Hz, 2H), 3.76 (s, 3H).13C NMR (101 MHz, [D6]DMSO) δ = 168.30,
160.68, 156.69, 128.22, 124.04, 114.91, 55.73.
7.89 (d, J = 7.9 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.50 (br s, 2H), 7.43
(t, J = 8.0 Hz, 1H). 13C NMR (101 MHz, [D6]DMSO) δ = 170.84, 151.66,
133.27, 132.40, 131.68, 129.60, 129.16, 128.98. HRMS (ESI-TOF) m/z:
[M + H]+ calcd. for C8H5Cl2N3S 245.9654; Found: 245.9652; IR (KBr,
cm-1): ν = 3466 (NH2), 1530 (C=N), 618 (C-S).
˜
5-(2-Methoxy-5-nitrophenyl)-1,3,4-thiadiazol-2-amine(4l): Yield:
63 %; Colorless solid, m.p. 234–236 °C; 1H NMR (400 MHz,
[D6]DMSO) δ = 8.83 (d, J = 2.8 Hz, 1H), 8.24 (dd, J = 9.2, 2.8 Hz, 1H),
7.38 (br s, 2H), 7.35 (s, 1H), 4.03 (s, 3H). 13C NMR (101 MHz,
[D6]DMSO) δ = 171.09,159.24, 148.88, 141.51, 126.18, 122.15, 120.71,
113.46, 57.54. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for C9H8O3N4S
253.0390; Found: 253.0400; IR (KBr, cm–1): ν = 3500 (NH ), 1542 (C=
˜
2
N), 761 (C-S).
5-(Furan-2-yl)-1,3,4-thiadiazol-2-amine[28] (4m): Yield: 54 %;
brown solid, m.p. 201–202 °C; 1H NMR (400 MHz, [D6]DMSO) δ =
7.80–7.77 (m, 1H), 7.39 (br s, 2H), 6.90 (d, J = 2.9 Hz, 1H), 6.61 (dd,
J = 3.3, 1.7 Hz, 1H). 13C NMR (101 MHz, [D6]DMSO) δ = 168.41,
147.47, 145.98, 144.66, 112.67, 109.36.
5-(Thiophen-2-yl)-1,3,4-thiadiazol-2-amine[30] (4n): Yield: 64 %;
brown solid, m.p. 205–207 °C; 1H NMR (400 MHz, [D6]DMSO) δ =
7.58 (d, J = 5.0 Hz, 1H), 7.42 (br s, 2H), 7.37 (d, J = 2.8 Hz, 1H), 7.10–
5-(4-Nitrophenyl)-1,3,4-thiadiazol-2-amine[34] (4d): Yield: 79 %;
brown solid, m.p. 250–252 °C; 1H NMR (400 MHz, [D6]DMSO) δ =
8.23 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 8.4 Hz, 2H), 7.67 (br s, 2H). 13C
NMR (101 MHz, [D6]DMSO) δ = 170.42, 154.52, 147.78, 137.42,
127.49, 124.81.
7.06 (m, 1H). 13C NMR (101 MHz, [D6]DMSO)
151.05,138.60, 133.64, 128.38, 128.02.
δ = 168.52,
5-(Pyridin-3-yl)-1,3,4-thiadiazol-2-amine[10] (4o): Yield: 49 %;
brown solid, m.p. 230–232 °C; 1H NMR (400 MHz, [D6]DMSO) δ =
8.91 (d, J = 2.0 Hz, 1H), 8.57 (d, J = 4.6 Hz, 1H), 8.10 (m, 1H), 7.53
(br s, 2H), 7.46 (dd, J = 7.9, 4.8 Hz, 1H). 13C NMR (101 MHz,
[D6]DMSO) δ = 169.53, 153.68, 150.66, 147.33, 133.96, 124.56,121.35.
5-(4-Fluorophenyl)-1,3,4-thiadiazol-2-amine[24] (4e): Yield:86 %;
1
Colorless solid, m.p. 211–213 °C; H NMR (400 MHz, [D6]DMSO) δ =
7.76 (dd, J = 8.7, 5.4 Hz, 2H), 7.38 (br s, 2H), 7.26 (dd, J = 8.8 Hz,
2H). 13C NMR (101 MHz, [D6]DMSO) δ = 169.03, 163.12(JC-F = 247.45
Hz), 155.65, 128.87 (JC-F = 9.09Hz), 128.01 (JC-F = 22.22 Hz), 116.55
(JC-F = 4.04Hz).
5-(Naphthalen-1-yl)-1,3,4-thiadiazol-2-amine[34] (4p): Yield:
51 %; Colorless solid, m.p. 207–208 °C; 1H NMR (400 MHz,
[D6]DMSO) δ = 8.75 (d, J = 8.0 Hz, 1H), 7.98 (t, J = 7.3 Hz, 2H), 7.70 (d,
J = 7.2 Hz, 1H), 7.62–7.52 (m, 3H), 7.44 (br s, 2H). 13C NMR (101 MHz,
[D6]DMSO) δ = 169.15, 156.00, 134.00, 130.42, 130.19, 129.15,
128.92, 127.81, 127.77, 126.05, 125.93, 125.88.
5-(4-Chlorophenyl)-1,3,4-thiadiazol-2-amine[34] (4f): Yield: 88 %;
1
Colorless solid, m.p. 224–225 °C; H NMR (400 MHz, [D6]DMSO) δ =
7.73 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 8.5 Hz, 2H), 7.45 (br s, 2H). 13C
NMR (101 MHz, [D6]DMSO) δ = 169.25, 155.51, 134.37, 130.24,
129.57, 128.31.
(E)-5-Styryl-1,3,4-thiadiazol-2-amine[34] (4q) Yield: 68 %; Colorless
solid, m.p. 230–232 °C; 1H NMR (400 MHz, [D6]DMSO) δ = 7.60 (d,
J = 7.4 Hz, 2H), 7.40 (br s, 2H), 7.35 (d, J = 7.2 Hz, 1H), 7.32 (s, 1H),
7.28 (t, J = 3.4 Hz, 2H), 7.02 (d, J = 16.4 Hz, 1H). 13C NMR (101 MHz,
[D6]DMSO) δ = 167.99, 157.19, 136.21, 134.67, 129.22, 129.01,
127.32, 119.98.
5-(4-Bromophenyl)-1,3,4-thiadiazol-2-amine[24] (4g): Yield: 84 %;
1
Colorless solid, m.p. 219–220 °C; H NMR (400 MHz, [D6]DMSO) δ =
7.66 (d, J = 8.6 Hz, 2H), 7.61 (d, J = 8.6 Hz, 2H), 7.45 (br s, 2H).13
C
NMR (101 MHz, [D6]DMSO) δ = 169.26, 155.61, 132.48, 130.59,
128.53, 123.04.
(E)-5-(1-Phenylprop-1-en-2-yl)-1,3,4-thiadiazol-2-amine
(4r):
Yield: 58 %; Colorless solid, m.p. 215–217 °C; 1H NMR (400 MHz,
[D6]DMSO) δ = 7.40 (m, J = 12.5, 4H), 7.35 (br s, 2H), 7.29 (t, J =
12.0, J = 4.0, 1H), 6.92 (s, 1H), 2.24 (s, 3H).13C NMR (101 MHz,
[D6]DMSO) δ = 168.27, 160.62, 136.50, 131.72, 130.05, 129.70,
128.81, 127.90, 15.97. HRMS (ESI-TOF) m/z: [M + H]+ calcd. for
5-(3-Methoxyphenyl)-1,3,4-thiadiazol-2-amine[28] (4h): Yield:
69 %; Colorless solid, m.p. 199–201 °C; 1H NMR (400 MHz,
[D6]DMSO) δ = 7.40 (br s, 2H), 7.33 (t, J = 7.9 Hz, 1H), 7.29–7.21 (m,
2H), 6.98 (s, 1H), 3.77 (s, 3H). 13C NMR (101 MHz, [D6]DMSO) δ =
169.01, 159.96, 156.56, 132.64, 130.73, 119.45, 115.93, 111.21, 55.64.
5-(3-Bromophenyl)-1,3,4-thiadiazol-2-amine[10] (4i): Yield: 64 %;
Colorless solid, m.p. 217–220 °C; H NMR (400 MHz, [D6]DMSO) δ =
C11H11N3S 218.0746; Found: 218.0752; IR (KBr, cm–1): ν = 3490 (NH2),
˜
1610 (C=C) Alkene, 1530 (C=N), 635 (C-S).
1
7.89 (s, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.61–7.56 (m, 1H), 7.52 (br s,
2H), 7.40 (s, 1H). 13C NMR (101 MHz, [D6]DMSO) δ = 169.49, 155.01,
133.50, 132.59, 131.72, 128.63, 125.90, 122.70.
5-(2,3-Dimethoxyphenyl)-1,3,4-thiadiazol-2-amine[35] (4j): Yield:
54 %; Colorless solid, m.p. 204–206 °C; 1H NMR (400 MHz,
[D6]DMSO) δ = 7.64 (dd, J = 7.7, 1.6 Hz, 1H), 7.23 (br s, 2H), 7.15–
7.06 (m, 2H), 3.82 (s, 3H), 3.77 (s, 3H). 13C NMR (101 MHz, [D6]DMSO)
δ = 170.61, 153.16, 150.57, 144.97, 125.09, 124.86, 118.33, 113.84,
60.60, 56.32.
Acknowledgments
We thank the National Natural Science Foundation of China (No.
21362022) and the Natural Science Foundation of Jiangxi Prov-
ince (No. 20192BAB203006) for financial support.
Keywords: Three-component reaction · Iodine-promoted
reaction · Metal-free condition · 2-Aminothiadiazole ·
Potassium thiocyanate
5-(2,3-Dichlorophenyl)-1,3,4-thiadiazol-2-amine(4k): Yield: 84 %;
1
Colorless solid, m.p. 197–198 °C; H NMR (400 MHz, [D6]DMSO) δ =
Eur. J. Org. Chem. 2019, 6561–6565
6564
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim