388 JOURNAL OF CHEMICAL RESEARCH 2011
Table 1 Comparison of the synthesis of compounds 6a–k between microwave irradiation and conventional heating
Compounds
Conventional method
Microwave method
TC/TMW
Time/min
Yield/%
Time/min
Yield/%
6a
6b
6c
6d
6e
6f
6g
6h
6i
R = C6H5
540
600
600
540
540
600
540
540
480
600
540
63
59
65
52
64
47
56
51
53
43
58
10
9
88
85
87
80
90
81
83
84
82
83
80
54
67
75
60
49
50
54
60
69
50
49
R = 4-CH3C6H4
R = 3-CH3C6H4
R = 4-FC6H4
8
9
R = 4-ClC6H4
R = 3-ClC6H4
R = 4-BrC6H4
R = 4-NO2C6H4
R = 3,5-(NO2)2C6H3
R = 4-CH3OC6H4
R = 1-naphthyl
11
12
10
9
7
12
11
6j
6k
TC, conventional method time; TMW, microwave method time.
Microwave method for the preparation of 6a–k
1,3-Bis{(6-(3-chlorophenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}benzene (6f): Pale yellow solid, yield 81%, m.p. 165–
167 °C. IR (KBr) (νmax/cm−1): 3062, 2959, 1597, 1461, 1283, 1029,
678; 1H NMR (400 MHz, DMSO-d6): δ 7.92 (d, J = 7.6 Hz, 2H, ArH),
7.75–7.71 (m, 2H, ArH), 7.68–7.60 (m, 4H, ArH), 7.28 (t, J = 8.4 Hz,
1H, ArH), 7.01 (s, 1H, ArH), 6.80 (d, J = 8.0 Hz, 2H, ArH), 5.59
(s, 4H, OCH2). ESI-MS m/z (%): 629 [(M+23)+, 100]. Anal. Calcd
for C26H16Cl2N8O2S2: C, 51.40; H, 2.65; N, 18.45. Found: C, 51.52;
H, 2.63; N, 18.39%.
Compound 5 (1 mmol), a substituted benzoic acid (2.2 mmol) and
phosphorus oxychloride (10 mL) were mixed thoroughly in a 50 mL
flask. The flask with a reflux condenser was placed in the microwave
oven and irradiated at 450 W for 7–12 min. After completion of the
reaction, the mixture was cooled to ambient temperature. Excess
phosphorus oxychloride was removed under reduced pressure and an
ice–water mixture was poured onto the residue with vigorous stirring.
The reaction mixture was neutralised with concentrated sodium
hydroxide solution and allowed to stand overnight. The solid precipi-
tate formed was filtered and washed with cold water, dilute NaHCO3
solution and dried in air. The crude product was purified by column
chromatography on silica gel H using methanol-ethyl acetate as
eluent. The physical and spectra data of title compounds 6a–k are as
follows.
1,3-Bis{(6-phenyl-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-3-yl)-
methoxy}benzene (6a): Pale yellow solid, yield 88%, m.p. 199–
201 °C. IR (KBr) (νmax/cm−1): 3075, 2930, 1596, 1462, 1278, 1038,
684; 1H NMR (400 MHz, DMSO-d6): δ 7.96 (d, J = 7.2 Hz, 4H, ArH),
7.67 (t, J = 7.2 Hz, 2H, ArH), 7.60 (t, J = 8.0 Hz, 4H, ArH), 7.29 (t,
J = 8.4 Hz, 1H, ArH), 6.99 (s, 1H, ArH), 6.80 (dd, J = 8.0, 8.0 Hz, 2H,
ArH), 5.57 (s, 4H, OCH2). HRMS (ESI) m/z Calcd for C26H18N8O2S2:
538.0994. Found: 539.1074[M+H]+.
1,3-Bis{(6-(4-methylphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}benzene (6b): Pale yellow solid, yield 85%, m.p. 214–
216 °C. IR (KBr) (νmax/cm−1): 3033, 2921, 1600, 1458, 1253, 1007,
680; 1H NMR (400 MHz, DMSO-d6): δ 7.84 (d, J = 8.4 Hz, 4H, ArH),
7.39 (d, J = 8.4 Hz, 4H, ArH), 7.28 (t, J = 8.4 Hz, 1H, ArH), 7.00
(s, 1H, ArH), 6.79 (dd, J = 8.4, 8.0 Hz, 2H, ArH), 5.56 (s, 4H, OCH2),
2.39 (s, 6H, CH3). ESI-MS m/z (%): 567 [(M+1)+, 100]. Anal. Calcd
for C28H22N8O2S2: C, 59.35; H, 3.91; N, 19.77. Found: C, 59.22;
H, 3.89; N, 19.84%.
1,3-Bis{(6-(3-methylphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}benzene (6c): Pale yellow solid, yield 87%, m.p. 202–
204 °C. IR (KBr) (νmax/cm−1): 3046, 2923, 1596, 1461, 1276, 1028,
686; 1H NMR (400 MHz, DMSO-d6): δ 7.74 (t, J = 4.4 Hz, 4H, ArH),
7.47 (d, J = 5.2 Hz, 4H, ArH), 7.28 (t, J = 8.4 Hz, 1H, ArH), 7.01
(s, 1H, ArH), 6.79 (dd, J = 8.4, 8.4 Hz, 2H, ArH), 5.57 (s, 4H, OCH2),
2.39 (s, 6H, CH3). ESI-MS m/z (%): 589 [(M+23)+, 100]. Anal. Calcd
for C28H22N8O2S2: C, 59.35; H, 3.91; N, 19.77. Found: C, 59.52;
H, 3.90; N, 19.71%.
1,3-Bis{(6-(4-bromophenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}ben-zene (6g): Yellow solid, yield 83%, m.p. 222–
224 °C. IR (KBr) (νmax/cm−1): 3082, 2929, 1589, 1461, 1246, 1005,
689; 1H NMR (400 MHz, DMSO-d6): δ 7.90 (d, J = 8.4 Hz, 4H, ArH),
7.80 (d, J = 8.4 Hz, 4H, ArH), 7.28 (t, J = 8.4 Hz, 1H, ArH), 6.99
(s, 1H, ArH), 6.79 (dd, J = 8.0, 8.4 Hz, 2H, ArH), 5.57 (s, 4H, OCH2).
ESI-MS m/z (%): 697 [(M+1)+, 100].Anal. Calcd for C26H16Br2N8O2S2:
C, 44.84; H, 2.32; N, 16.09. Found: C, 44.71; H, 2.33; N, 16.04%.
1,3-Bis{(6-(4-nitrophenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}benzene (6h): Yellow solid, yield 84%, m.p. 144–
146 °C. IR (KBr) (νmax/cm−1): 3061, 2957, 1598, 1462, 1348, 1283,
1025, 684; 1H NMR (400 MHz, DMSO-d6): δ 8.40 (d, J = 8.8 Hz, 4H,
ArH), 8.23 (d, J = 8.8 Hz, 4H, ArH), 7.29 (t, J = 8.4 Hz, 1H, ArH),
6.99 (s, 1H, ArH), 6.81 (d, J = 8.0 Hz, 2H, ArH), 5.60 (s, 4H, OCH2).
ESI-MS m/z (%): 629 [(M+1)+, 100]. Anal. Calcd for C26H16N10O6S2:
C, 49.68; H, 2.57; N, 22.28. Found: C, 49.56; H, 2.59; N, 22.23%.
1,3-Bis{(6-(3,5-dinitrophenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}ben-zene (6i): Yellow solid, yield 82%, m.p. 153–
155 °C. IR (KBr) (νmax/cm−1): 3087, 2930, 1595, 1473, 1345, 1283,
1009, 732; 1H NMR (400 MHz, DMSO-d6): δ 9.02 (t, J = 2.0 Hz, 2H,
ArH), 8.99 (d, J = 2.0 Hz, 4H, ArH), 7.30 (t, J = 8.4 Hz, 1H, ArH),
7.00 (s, 1H, ArH), 6.82 (dd, J = 8.4, 8.4 Hz, 2H, ArH), 5.65 (s, 4H,
OCH2). ESI-MS m/z (%): 719 [(M+1)+, 100]. Anal. Calcd for
C26H14N12O10S2: C, 43.46; H, 1.96; N, 23.39. Found: C, 43.40; H, 1.97;
N, 23.47%.
1,3-Bis{(6-(4-methoxyphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}ben-zene (6j): Pale yellow solid, yield 83%, m.p. 183–
185 °C. IR (KBr) (νmax/cm−1): 3041, 2932, 1601, 1461, 1259, 1033,
683; 1H NMR (400 MHz, DMSO-d6): δ 7.89 (d, J = 8.8 Hz, 4H, ArH),
7.28 (t, J = 8.4 Hz, 1H, ArH), 7.12 (d, J = 8.4 Hz, 4H, ArH), 7.01
(s, 1H, ArH), 6.79 (d, J = 8.0 Hz, 2H, ArH), 5.55 (s, 4H, OCH2), 3.86
(s, 6H, OCH3). ESI-MS m/z (%): 1219 [(2M+23)+, 100]. Anal. Calcd
for C28H22N8O4S2: C, 56.18; H, 3.70; N, 18.72. Found: C, 56.32;
H, 3.72; N, 18.67%.
1,3-Bis{(6-(1-naphthyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-3-yl)-
methoxy}benzene (6k): Pale yellow solid, yield 80%, m.p. 195–
197 °C. IR (KBr) (νmax/cm−1): 3049, 2953, 1596, 1465, 1283, 1021,
679; 1H NMR (400 MHz, DMSO-d6): δ 8.62 (t, J = 5.6 Hz, 2H, ArH),
8.24 (d, J = 8.0 Hz, 2H, ArH), 8.08 (t, J = 5.2 Hz, 2H, ArH), 7.97
(d, J = 7.2 Hz, 2H, ArH), 7.69 (t, J = 8.0 Hz, 2H, ArH), 7.64-7.59
(m, 4H, ArH), 7.29 (t, J = 8.4 Hz, 1H, ArH), 6.99 (s, 1H, ArH), 6.82
(dd, J = 8.0, 8.0 Hz, 2H, ArH), 5.63 (s, 4H, OCH2). ESI-MS m/z (%):
639 [(M+1)+, 100]. Anal. Calcd for C34H22N8O2S2: C, 63.93; H, 3.47;
N, 17.54. Found: C, 63.79; H, 3.48; N, 17.60%.
1,3-Bis{(6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}benzene (6d): White solid, yield 80%, m.p. 203–
205 °C. IR (KBr) (νmax/cm−1): 3037, 2971, 1594, 1462, 1236, 1003,
687; 1H NMR (400 MHz, DMSO-d6): δ 8.04 (dd, J = 8.8, 8.8 Hz, 4H,
ArH), 7.46 (t, J = 8.8 Hz, 4H, ArH), 7.28 (t, J = 8.4 Hz, 1H, ArH), 6.98
(s, 1H, ArH), 6.79 (dd, J = 8.4, 8.0 Hz, 2H, ArH), 5.57 (s, 4H, OCH2).
ESI-MS m/z (%): 575 [(M+1)+, 100]. Anal. Calcd for C26H16F2N8O2S2:
C, 54.35; H, 2.81; N, 19.50. Found: C, 54.46; H, 2.82; N, 19.45%.
1,3-Bis{(6-(4-chlorphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-
3-yl)-methoxy}benzene (6e): Yellow solid, yield 90%, m.p. 214–
216 °C. IR (KBr) (νmax/cm−1): 3051, 2926, 1594, 1462, 1254, 1011,
1
678; H NMR (400 MHz, DMSO-d6): δ 8.00–7.96 (m, 4H, ArH),
7.69–7.66 (m, 4H, ArH), 7.28 (t, J = 8.4 Hz, 1H, ArH), 6.99 (s, 1H,
ArH), 6.79 (dd, J = 8.4, 8.4 Hz, 2H, ArH), 5.57 (s, 4H, OCH2).
ESI-MS m/z (%): 607 [(M+1)+, 100].Anal. Calcd for C26H16Cl2N8O2S2:
C, 51.40; H, 2.65; N, 18.45. Found: C, 51.59; H, 2.63; N, 18.41%.
Conventional method for the preparation of 6a–k
Compound 5 (1 mmol), a substituted benzoic acid (2.2 mmol) and
phosphorus oxychloride (10 mL) were mixed thoroughly in a 50 mL