Synthesis and biological activity of 3-(2-furanyl)-6-aryl-1,2,4-triazolo[3, 4-b]-1,3,4-thiadiazoles

Article abstract of DOI:10.3390/70800681

3-(2-Furanyl)-4-amino-5-mercapto-1,2,4-triazole (1) was prepared from 2-furoic acid through a multi-step reaction sequence. Compound 1 reacted with aromatic acids in the presence of phosphorus oxychloride to give 3-(2-furanyl)-6-aryl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (2). The structures of all the newly synthesized compounds have been confirmed by elemental analysis, IR, ¹H-NMR, ¹³C-NMR and mass spectra. The bioassay indicated most of the title compounds possess significant growth promoting effects on mung bean radicles.

Full text of DOI:10.3390/70800681

Molecules 2002, 7, 681-689
molecules
ISSN 1420-3049
http://www.mdpi.org
Synthesis and Biological Activity of 3-(2-Furanyl)-6-Aryl-1,2,4-
Triazolo[3,4-b]-1,3,4 –Thiadiazoles
Li-Xue Zhang *,1, An-Jiang Zhang 1, Xian-Xing Chen 1, Xin-Xiang Lei 1, Xiang-Yun Nan 1,
Dong-Yong Chen 1 and Zi-Yi Zhang 2
1 Department of Chemistry, Wenzhou Normal College, Wenzhou 325003, P.R. China.
2 Department of Chemistry, Lanzhou University, Lanzhou 730000, P.R. China.
* Author to whom correspondence should be addressed; E-mail: zhanglixuelz@yahoo.com.cn;
Tel: (+86) 577-81972027, Fax: (+86) 577-88339081
Abstract: 3-(2-Furanyl)-4-amino-5-mercapto-1,2,4-triazole (1) was prepared from
2-furoic acid through a multi-step reaction sequence. Compound 1 reacted with aromatic
acids in the presence of phosphorus oxychloride to give 3-(2-furanyl)-6-aryl-1,2,4-
triazolo[3,4-b]-1,3,4-thiadiazoles (2). The structures of all the newly synthesized
1
compounds have been confirmed by elemental analysis, IR, H-NMR, 13C-NMR and
mass spectra. The bioassay indicated most of the title compounds possess significant
growth promoting effects on mung bean radicles.
Keywords: Furan ring; triazolothiadiazoles; synthesis; spectral characterization;
biological activity
Introduction
Various substituted 1,2,4-triazolo[3,4-b]-1,3,4–thiadiazoles are associated with diverse
pharmacological activities, such as antimicrobial, bactericidal, antiinflammatory, antiviral,
antihypertensive, anthelmintic and analgesic effects [1-3]. Prompted by these observations and as a
continuation of our work on the synthesis of biologically active nitrogen and sulfur containing
heterocycles, we report herein the reaction of aromatic acids with 3-furoyl-4-amino-
5-mercapto-1,2,4-triazole in the presence of phosphoryl chloride to give 3-(2-furanyl)-6-aryl-

Molecules 2002, 7
682
1,2,4-triazolo-[3,4-b]-1,3,4–thiadiazoles. The structures of all the synthesized compounds were
1
confirmed by elemental analysis, IR, H-NMR, 13C-NMR, and mass spectral data. The bioassay
indicated most of the title compounds possess significant growth promoting effects on mung bean
(Vigna radiata) radicles, giving up to 40% increases in growth in the case of some compounds.
Results And Discussion
Synthetic route and improvement of synthetic methods
The synthetic route used is shown in Scheme 1. 2-Furoic hydrazide is a needle-like crystalline
compound, but often exists in form liquid when prepared according to literature methods. Sometimes
the crystals only appear after standing for up to three months. The liquid form of 2-furoic hydrazide
was reacted with carbon disulphide and potassium hydroxide in ethanol, successfully giving potassium
furoic hydrazide dithioformate.
Scheme 1. The synthetic route to the title compounds
C2H5OH, H+
CONHNH2
O
O
COOH
COOC2H5
O
CS2, KOH, C2H5OH
NH2NH2
O
NH2NH2
-
CONHNHCSSK+
N
Ar
ArCOOH
POCl3
N
N
O
O
N
N
SH
S
N
N
2a-r
NH2
1
Ar = a. 4-NH2C6H4
b. 3-pyridinyl
f. 3-ClC6H4
g . 2-NO2C6H4 CH2
k. C6H5OCH2
l. . 2-CH3OC6H4
m. C6H5
p. 4- NO2C6H4
q. 2-NH2C6H4
r. 4-CH3OC6H4
c. 1-naphthylmethyl h. 2-ClC6H4
d. 3,5-(NO2)2C6H3
e. C6H5CH2
i. 2-HOC6H4
j. 2-furanyl
n. 2,4-Cl2C6H3OCH2
o. 2-quinolyl
After the ring-closure of compound 1 with aromatic acids in the presence of phosphorus
oxychloride, the literature procedure calls for the removal of excess phosphorus oxychloride under
reduced pressure, but this can result in damage to the rotatory evaporator and vacuum pump due to the
strong acidity and high boiling point of phosphorus oxychloride. An improvement was made in our

Molecules 2002, 7
683
experiments, in that the reaction mixture was gradually poured onto crushed ice with stirring, some
solid potassium carbonate and then the appropriate amount of solid potassium hydroxide was added till
the pH value was 8. The separated solid after standing overnight was filtered and thoroughly washed
with cold water. Little product is lost because of its insolubility in water. This is a simple and
convenient method of removing excess phosphorus oxychloride.
IR spectra of the title compounds
In the IR spectrum of compound 1 there are absorption bands at 3335, 3269 cm-1 due to the N-H
stretching vibration, 1634, 1523, 1494, 1467, 1420 cm-1 due to furan and triazole ring skeleton
vibrations, and 1109 cm-1 due to the C-O-C stretching vibration of the furan ring. Of course, the bands
at 3335, 3269 cm-1 had disappeared in the IR spectra of compounds 2a-r. Furthermore, the strongest
band in the IR of compound 1 is at 1457cm-1, while in the IR of compounds 2a-r it appears at around
1470 cm-1. The peaks at 1634 and 1109 cm –1 are also shifted to 1620 and 1125 cm –1, respectively. The
C-S-C bending vibration bands of compounds 2a-r are observed around 700 cm –1.
1H-NMR spectra of the title compounds
The signals of the three furan ring hydrogens of 1 appear at δ 7.91, 6.70 and 7.36 ppm, attributed to
1
H-5, H-4 and H-3, respectively. In the H-NMR spectra of the title compounds, the δ values of the
5-position hydrogens are noted to have shifted to 7.98-8.19, decreasing in the order of Ar =2-HOC6H4
> 2-ClC6H4 > 1-naphthylmethyl > 3-ClC6H4 > 2-furanyl > 2-NO2C6H4CH2 > C6H5 > 3,5-(NO2)2C6H3 >
4-NO2C6H4 > 3-pyridinyl > 2-CH3OC6H4 > 2,4-Cl2C6H3OCH2 > 4-NH2C6H4 > C6H5CH2 > C6H5OCH2
> 2-NH2C6H4 > 4-CH3OC6H4 and 2-quinolyl (where Ar is the substituent group at the 6 position of the
triazolothiadiazoles). Moreover, the δ values of the 4-position hydrogens have increased to 6.71-6.85.
Only the δ values of the 3-position hydrogens do not show a similar trend, as they go both up and
down, varying between 7.21-7.58. When an active methylene group is attached to the 6 position of the
triazolothiadiazoles, the δ values of the benzyl, o-nitrobenzyl and 1- naphthylmethyl methylene
hydrogen is 4.50, 4.82 and 4.98 respectively, while the corresponding δ values of the phenoxymethyl
and 2,4-dichlorophenoxymethyl methylene hydrogen are 5.59 and 5.71, respectively.
13C-NMR spectra of the title compounds
The δ values of the C-2 and C-3 carbons of the furan are 142.6 and 109.6, respectively. In the
13C-NMR spectrum of the intermediate compound 1, there are peaks at 142.84, 139.91, 113.99 and
111.89 ppm, which can be attributed to 2, 5, 4 and 3 position carbons of the furan ring, respectively;
the two triazole carbons have δ values of 166.56 and 145.22. In the 13C-NMR spectra of the title
compounds, the C-4 and C-3 carbons still have δ values at 111 and 112 or so, while the chemical shifts
of the C-2 and C-5 carbons vary between 135 and 145. When an active methylene group is attached to
6 position of the triazolothiadiazoles, the δ values of benzyl and 1- naphthylmethyl methylene carbons
are 37.30 and 34.95 respectively, which is different from the quantitative order seen in the 1H-NMR.

Molecules 2002, 7
684
Mass spectra
All the title compounds display molecular ion peaks. In the mass spectrum of a representative
compound such as 2r the molecular ion peak is also the base peak. This is probably because both
substituted benzene and furan ring form a well conjugated system with the triazolothiadiazole, which
makes the molecular ion especially stable. The peak at m/z 151, i.e. 3-(2-furyl)-4-amino-1,2,4-triazole,
is very strong, its intensity being second only to the base peak.
Biological Activity
The effect of the title compounds on sprouting of mung bean seeds has been investigated. After
treating with culture solution of 10.0µgL-3 of the title compounds for 48 hours, the lengths of mung
bean radicles with reference of distilled water, the growth promoting percentage has been calculated.
The data of biological activity test are presented in Table 1. From the data it can be seen that 2h, 2l, 2o
increase mung bean sprout growth by 40% at 10 •g·L-3. Even those compounds which inhibit mung
bean sprout growth at 10 •g·L-3 can show promoting effect at lower concentrations.
Table 1. Effect of the title compounds on mung bean radicle growth
Length of mung
Growth
Compd.
bean radicles (cm) promotion (%)
2.45
3.34
1.26
2.485
2.35
3.08
2.52
3.41
2.64
3.005
0.73
3.40
2.38
2.445
3.40
2.79
2.01
2.26
1.87
38.88
- 49.27
3.33
-2.29
28.07
4.78
2a
2b
2c
2d
2e
2f
2g
2h
2i
41.79
9.77
24.95
30.35
41.37
-6.17
1.66
41.37
16.01
-16.42
-6.3
2j
2k
2l
2m
2n
2o
2p
2q
2r

Molecules 2002, 7
685
Acknowledgements
This work was financially supported by the National Science Foundation of China (grant No.
29802004), the University Backbone Teachers Foundation of the Education Ministry of China, and the
Education Department of Zhejiang Province.
Experimental
General
All melting points were determined on an XT-4A apparatus and are uncorrected. The IR spectra
1
(KBr disks) were taken on a Bruker Quinox 55 spectrophotometer. The H-NMR and 13C-NMR
spectra were measured on a Bruker Advance 300 spectrometer for DMSO-d6 solutions using TMS as
internal reference. The mass spectra were recorded on an HP 5988 spectrometer. Elemental analyses
were carried out with a CE 1112 elemental analyzer. All the reagents used were AR grade.
Preparation of 3-(2-furyl)-4-amino-5-mercapto-1,2,4-triazole (1).
Ethyl 2-furoate [4], was treated with 85% NH2NH2·H2O. Reaction with CS2 and KOH in ethanol
gave potassium 2-furoic hydrazide dithioformate [5]. The salt underwent ring-closure in 85%
hydrazine monohydrate, giving 3-(2-furyl)-4-amino-5-mercapto-1,2,4-triazole (1), which was
recrystallized from absolute ethanol: 1H-NMR δ: 13.89 (s, 1H, SH), 7.91 (d, 1H), 7.36 (d, 1H), 6.70 (q,
1H), 5.80 (s, 2H, NH2); 13C-NMR δ: 166.56, 145.22, 142.84, 139.91, 113.99, 111.89.
General method for the preparation of 3-(2-furanyl)-6-aryl-1,2,4-triazolo[3,4-b]-1,3,4–thiadiazoles
(2a-r).
A mixture of 1 (5.0mmol) and an aromatic acid (5.5mmol) in POCl3 (20mL) was refluxed for 7hr.
The reaction mixture was gradually poured onto crushed ice with stirring. Some solid K2CO3 was
added to the mixture with stirring, then an appropriate amount of solid KOH was added till the pH
value was 8. The solid which separated after standing overnight was filtered, washed with cold water,
dried, and recrystallized from absolute alcohol to afford the title compounds 2a-r. The physical and
spectral data of the title compounds are as follows:
3-(2-furanyl)-6-(4-aminophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2a): Yield 48 %; M.p.
229-231°C; IR ν/cm-1: 3422, 3220 (N-H), 1603 (C=N), 1518, 1496, 1470 (aromatic skeleton), 1226
(N-N=C), 988, 952, 903, 841,739 (Ar-H bending vibration), 699 (C-S-C); 1H-NMR δ: 8.00, 6.78, 7.34
(3H, furan H), 6.69, 7.68 (4H,dd, J=8.7Hz, Ar-H); 13C-NMR δ: 167.80, 153.72, 145.25, 140.39,
139.10, 129.04, 128.04, 115.12, 113.72, 112.18, 111.56; MS (m/z, %): 283 (M+, 72.23), 136 (100), 118
(54.09), 109 (37.86), 93 (31.77), 91 (22.78), 83 (15.41), 79 (11.59), 77 (6.80), 51 (19.23), 39 (22.78).
Calcd. for C13H9N5OS (%): C 55.11, H 3.20, N 24.73; Found (%): C 54.87, H 3.22 , N 24.51.

Molecules 2002, 7
686
3-(2-furanyl)-6-(3-pyridyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2b): Yield 57 %; Mp. 189-191°C;
IR (KBr) ν/cm-1: 3128, 3063 (Ar-H), 1624 (C=N), 1588, 1574, 1517, 1473, 1459 (aromatic skeleton)
1249 (N-N=C), 1224 (furan C-O-C), 989, 960, 904, 885 ,809, 739 (Ar-H bending vibration), 700
(C-S-C); 1H-NMR δ: 8.02, 6.80, 7.44 (3H, furan H), 9.23, 8.83, 8.43, 7.68 (4H, pyridine H); 13C-NMR
δ: 164.99, 153.62, 153.43, 147.88, 145.57, 140.00, 139.45, 135.17, 125.54, 124.59, 112.31, 112.13;
MS (m/z, %): 269 (M+, 100), 137 (11.09), 122 (66.52), 109 (70.65), 93 (52.69), 78 (12.90), 77 (17.61),
65 (20.96), 51 (35.28), 39 (18.84). Calcd. for C12H7N5OS (%): C 53.52, H 2.62, N 26.01; Found (%):
C 53.33, H 2.59, N 26.24.
3-(2-furanyl)-6-(1-naphthylmethyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2c): Yield 64 %; Mp.
146-148°C; IR (KBr) ν/cm-1: 3128, 3063 (Ar-H), 1626 (C=N), 1598, 1517, 1473, 1427 (aromatic
1
skeleton), 1262 (N-N=C), 1226 (furan C-O-C), 696 (C-S-C); H-NMR δ: 8.13, 6.77, 7.54 (3H, furan
H), 7.18-8.00 (7H, m, naphthalene H), 4.98 (2H, s, CH2); 13C-NMR δ : 171.50, 153.96, 145.43, 140.21,
138.95, 133.69, 131.41, 128.89, 128.54, 128.34, 126.96, 126.33, 125.87, 125.63, 123.76, 112.21,
111.51, 34.95; MS (m/z, %): 332 (M+, 98.94), 185 (3.65), 167 (40.18), 166 (53.24), 152 (30.31), 141
(78.44), 137 (20.09), 115 (32.29), 109 (100), 93 (46.53), 83 (13.49), 65 (14.72), 63 (24.02), 51 (18.48),
39 (15.87). Calcd. for C18H12N4OS (%): C 65.04, H 3.64, N 16.86; Found (%): C 64.81, H 3.60, N
16.99.
3-(2-furanyl)-6-(3,5-dinitrophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2d): Yield 55 %; Mp.
290-292°C; IR (KBr) ν/cm-1: 3136, 3059 (Ar-H), 1628 (C=N), 1595, 1551, 1519, 1477, 1456, 1425
(aromatic skeleton), 1252 (N-N=C), 1224 (furan C-O-C), 981, 916, 903, 886 ,799, 756, 737 (Ar-H
1
bending vibration), 696 (C-S-C); H-NMR δ: 8.06, 6.83, 7.47 (3H, furan H), 9.06 (2H, s, Ar-H), 9.02
(1H, s, Ar-H); 13C-NMR δ: 163.86, 154.00, 148.87, 145.76, 139.86, 139.62, 131.73, 127.57, 121.84,
112.41, 112.39; MS (m/z, %): 358 (M+, 64.41), 266 (11.32), 211 (13.03), 165 (16.64), 137 (18.72), 119
(23.84), 111 (15.60), 109 (100), 93 (21.46), 75 (24.95), 57 (50.33), 43 (38.35). Calcd. for C13H6N6O5S
(%): C 43.58, H 1.69, N 23.46; Found (%): C 43.23, H 1.60, N 23.66.
3-(2-furanyl)-6-benzyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2e): Yield 62 %; Mp.111-113°C; IR
(KBr) ν/cm-1: 3133, 3061, 3029 (Ar-H), 1625 (C=N), 1536, 1518, 1495, 1474, 1456, 1425 (aromatic
1
skeleton), 1265 (N-N=C), 1224 (furan C-O-C), 705 (C-S-C); H-NMR δ: 8.00, 6.76, 7.21 (3H, furan
H), 7.31-7.44 (5H, m, Ar-H), 4.50 (2H, s, CH2); 13C-NMR δ: 171.16, 154.15, 145.40, 142.23, 138.95,
135.41, 129.36, 129.08, 127.83, 112.20, 111.51, 37.30; MS (m/z, %): 282 (M+, 55.07), 137 (15.15),
135 (4.07), 109 (100), 103 (18.82), 93 (46.41), 91 (47.94), 77 (22.82), 65 (39.07), 51 (42.84), 39
(45.75). Calcd. for C14H10N4OS (%): C 59.56, H 3.57, N 19.85; Found (%): C 59.28, H 3.65, N 20.07.
3-(2-furanyl)-6-(3-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole
(2f):
Yield
66
%;
M.p.207-209°C; IR (KBr) ν/cm-1: 3108, 3066 (Ar-H), 1626 (C=N), 1573, 1518, 1478, 1474, 1459,
1
1423 (aromatic skeleton), 1266 (N-N=C), 1226 (furan C-O-C), 694 (C-S-C); H-NMR δ: 8.13, 6.80,
13
7.45 (3H, furan H), 7.65-8.03 (4H, m, Ar-H); C-NMR δ: 165.89, 153.56, 145.56, 140.01, 139.48,
134.52, 132.84, 131.69, 130.95, 126.75, 126.34, 112.31, 112.17; MS (m/z, %): 304 (M++2, 24.00), 303

Molecules 2002, 7
687
(M++1, 10.76), 302 (M+, 65.31), 160 (1.43), 158 (3.76), 157 (22.49), 155 (63.07), 139 (11.46), 137
(32.33), 109 (100), 93 (66.16), 75 (29.66), 65 (27.80), 51 (39.10), 39 (29.85); Calcd. for C13H7ClN4OS
(%): C 51.57, H 2.33, N 18.51; Found (%): C 51.84, H 2.40, N 18.27.
3-(2-furanyl)-6-(2-nitrophenylmethyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2g): Yield 59 %;
M.p.187-189°C; IR (KBr) ν/cm-1: 3128 (Ar-H), 1620 (C=N), 1578, 1524, 1461, 1428 (aromatic
1
skeleton), 1262 (N- N=C), 1225 (furan C-O-C), 695 (C-S-C); H-NMR δ: 8.09, 6.74, 7.34 (3H, furan
H), 6.84-8.15 (4H, m, Ar-H), 4.82 (2H, s, CH2); MS (m/z, %): 327 (M+, 34.73), 282 (41.91), 137
(21.79), 135 (33.08), 119 (10.19), 109 (100), 77 (25.59), 64 (84.11), 51 (44.52), 39 (49.63); Calcd. for
C14H9N5O3S (%): C 51.37, H 2.77, N 21.40; Found (%): C 51.66, H 2.74, N 21.16.
3-2-furanyl-6-(2-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole
(2h):
Yield
54
%;
M.p.169-171°C; IR (KBr) ν/cm-1: 3130, 3073, 3013 (Ar-H), 1628 (C=N), 1592, 1517, 1477, 1454,
1
1427 (aromatic skeleton), 1277 (N-N=C), 1227 (furan C-O-C), 695 (C-S-C); H-NMR δ: 8.14, 6.79,
7.34 (3H, furan H), 7.71-8.02 (4H, m, Ar-H); MS (m/z, %): 304 (M++2, 23.52), 303 (M++1, 10.71),
302 (M+, 60.98), 160 (1.17), 158 (3.13), 157 (18.19), 155 (49.15), 137 (27.81), 109 (100), 93 (59.72),
75 (22.51), 64 (41.34), 51 (30.21), 39 (20.59); Calcd. for C13H7ClN4OS (%): C 51.57, H 2.33, N 18.51;
Found (%): C 51.33, H 2.40, N 18.23.
3-(2-furanyl)-6-(2-hydroxyphenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2i): Yield 49 %; M.p.
273-275°C; IR (KBr) ν/cm-1: 3423 (O-H), 3126, 3070 (Ar-H), 1602 (C=N), 1519, 1477, 1460, 1425
(aromatic skeleton), 1254 (N-N=C), 1224 (furan C-O-C), 699 (C-S-C); 1H-NMR δ: 11.70 (1H, s, OH),
8.19, 6.79, 7.39 (3H, furan H), 7.01-8.00 (4H, m, Ar-H); 13C-NMR δ: 163.44, 156.50, 155.16, 145.23,
140.49, 138.72, 127.69, 120.43, 117.03, 115.55, 112.23, 112.07, 111.53; MS (m/z, %): 284 (M+,
93.85), 137 (100), 119 (15.97), 109 (94.61), 93 (61.71), 77 (14.55), 64 (89.09), 51 (34.40), 39 (44.46);
Calcd. for C13H8N4O2S (%): C 54.92, H 2.84, N 19.71; Found (%): C 54.68, H 2.91, N 19.98.
3,6-di(2-furanyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2j): Yield 55 %; M.p. 204-206°C; IR (KBr)
ν/cm-1: 3120, 3092 (Ar-H), 1623 (C=N), 1593, 1520, 1508, 1481, 1445, 1429 (aromatic skeleton),
1254 (N-N=C), 1224 (furan C-O-C), 990, 960, 904, 886, 818, 754 (Ar-H bending vibration), 699
1
(C-S-C). H-NMR δ: 8.12, 8.01, 7.58, 7.28, 6.85, 6.79 (6H, m, furan H); 13C-NMR δ: 157.05, 153.03,
147.94, 145.50, 143.07, 140.12, 139.45, 115.38, 113.54, 112.24, 111.78; Calcd. for C11H6N4O2S (%): C
51.15, H 2.34, N 21.70; Found (%): C 51.26, H 2.44, N 21.51.
3-(2-furanyl)-6-phenyloxymethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole
(2k):
Yield
62
%;
M.p.115-117°C; IR (KBr) ν/cm-1: 3115, 3070 (Ar-H), 1624 (C=N), 1589, 1519, 1496, 1475, 1452,
1
1427 (aromatic skeleton), 1243 (N-N=C), 692 (C-S-C); H-NMR δ: 8.00, 6.77, 7.37 (3H, furan H),
7.00-7.34 (5H, m, Ar-H), 5.59 (2H, s, OCH2); MS (m/z, %): 298 (M+, 46.92), 205 (30.84), 109 (24.13),
84 (100), 77 (27.61), 65 (66.98), 57 (72.70), 51 (25.10), 39 (51.15); Calcd. for C14H10N4O2S (%): C
56.36, H 3.38, N 18.79; Found (%): C 56.09, H 3.36, N 19.04.

Molecules 2002, 7
688
3-(2-furanyl)-6-(2-methoxyphenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2l): Yield 58 %; M.p.
162-164°C; IR (KBr) ν/cm-1: 3111, 3012 (Ar-H), 1622 (C=N), 1584, 1506, 1462, 1435, 1422 (aromatic
1
skeleton), 1255 (N-N=C), 1223 (furan C-O-C), 699 (C-S-C); H-NMR δ: 8.01, 6.80, 7.40 (3H, furan
H), 7.21-8.33 (4H, m, Ar-H), 4.04 (3H, s, OCH3); MS (m/z, %): 298 (M+, 100), 149 (33.42), 109
(84.92), 93 (59.71), 77 (23.86), 64 (68.84), 51 (35.38), 39 (48.20); Calcd. for C14H10N4O2S (%):
56.36, H 3.38, N 18.79; Found (%): C 56.10, H 3.41, N 18.51.
C
3-(2-furanyl)-6-phenyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2m): Yield 53 %; M.p. 203-205°C; IR
(KBr) ν/cm-1: 3131, 3078, 3024 (Ar-H), 1624 (C=N), 1518, 1469, 1444, 1426 (aromatic skeleton),
1
1240 (N-N=C), 1224 (furan C-O-C), 691 (C-S-C); H-NMR δ: 8.07, 6.78, 7.40 (3H, furan H),
7.65-8.04 (5H, m, Ar-H); MS (m/z, %): 268 (M+, 100), 137 (15.84), 121 (88.23), 109 (77.76), 93
(52.23), 51 (41.26), 39 (26.39); Calcd. for C13H8N4OS (%): C 58.19, H 3.00, N 20.89; Found (%): C
58.44, H 2.98, N 20.67.
3-(2-furanyl)-6-(2,4-dichlorophenoxymethyl ) -1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2n): Yield 51 %;
M.p.193-195°C; IR (KBr) ν/cm-1: 3096, 3030 (Ar-H), 1625 (C=N), 1586, 1520, 1481, 1428 (aromatic
1
skeleton), 1249 (N-N=C), 1224 (furan C-O-C), 687 (C-S-C); H-NMR δ: 8.01, 6.78, 7.46 (3H, furan
H), 7.20-7.66 (3H, m, Ar-H), 5.71 (2H, s, OCH2); MS (m/z, %): 370 (M++4, 1.82), 368 (M++2, 8.86),
366 (M+, 12.83), 205 (58.79), 133 (12.64), 109 (22.09), 94 (45.70), 84 (100), 75 (6.40), 64 (19.66), 39
(9.28); Calcd. for C14H8Cl2N4O2S (%): C 45.79, H 2.19, N 15.26; Found (%): C 45.83, H 2.17, N
15.50.
3-(2-furanyl)-6-(2-quinolyl ) -1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2o):Yield 48 %; M.p. 267-269°C;
IR (KBr) ν/cm-1: 3128, 3069 (Ar-H), 1622 (C=N), 1585, 1561, 1519, 1474, 1445, 1427 (aromatic
1
skeleton), 1288 (N-N=C), 1225 (furan C-O-C), 695 (C-S-C); H-NMR δ: 7.98, 6.71, 7.54 (3H, furan
H), 6.22-9.05 (6H, m, quinoline H); Calcd. for C16H9 N5OS (%): C 60.17, H 2.84, N 21.94; Found (%):
C 60.43, H 2.88, N 21.81.
3-(2-furanyl)-6-(4-nitrophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2p): Yield 59 %; M.p.
304-306°C; IR (KBr) ν/cm-1: 3099, 3061 (Ar-H), 1622 (C=N), 1527, 1486, 1469, 1428 (aromatic
1
skeleton), 1283 (N-N=C), 1228 (furan C-O-C), 688 (C-S-C); H-NMR δ: 8.05, 6.83, 7.39 (3H, furan
H), 8.34-8.43 (4H, dd, J=9.0Hz, Ar-H); MS (m/z, %): 313 (M+, 78.32), 166 (29.75), 137 (19.97), 120
(34.58), 109 (100), 93 (71.97), 76 (22.26), 67 (14.30), 64 (72.07), 57 (39.21); Calcd. for C13H7 N5O3S
(%): C 49.83, H 2.25, N 22.36; Found(%): C 50.10, H 2.27, N 22.12.
3-(2-furanyl)-6-(2-aminophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2q): Yield 46 %; M.p.
144-146°C; R (KBr) ν/cm-1: 3448, 3346 (N-H), 3123, 3030 (Ar-H), 1621 (C=N), 1563, 1510, 1475,
1
1440, 1424 (aromatic skeleton), 1273 (N-N=C), 1232 (furan C-O-C), 697 (C-S-C); H-NMR δ: 8.01,
13
6.79, 7.50 (3H, furan H), 6.81-7.27 (4H, m, Ar-H), 6.70 (2H, s, NH2 ); C-NMR δ: 168.01, 152.43,
147.50, 145.45, 140.34, 139.49, 133.41, 129.53, 127.08, 116.52, 112.29, 111.53, 109.95; MS (m/z, %):
283(M+, 100), 136 (91.75), 118 (64.48), 109 (50.94), 93 (43.32), 91 (37.30), 77 (16.05), 64 (71.60), 51

Molecules 2002, 7
689
(31.91), 39 (34.01); Calcd. for C13H9N5OS (%): C 55.11, H 3.20, N 24.73; Found (%): C 54.85, H 3.22,
N 24.96.
3-(2-furanyl)-6-(4-methoxyphenyl )-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (2r): Yield 61 %; M.p.
177-179°C; IR (KBr) ν/cm-1: 3102, 3003 (Ar-H), 1607 (C=N), 1576, 1518, 1496, 1473, 1420
1
(aromatic skeleton), 1264 (N-N=C), 1225 (furan C-O-C), 702 (C-S-C); H-NMR δ: 8.01, 6.79, 7.38
13
(3H, furan H), 7.15-8.00 (4H, dd, J=9.0Hz, Ar-H), 3.86 (3H, s, OCH3); C-NMR δ: 167.05, 163.07,
153.40, 145.44, 140.22, 139.34, 129.27, 121.31, 115.21,112.28, 111.86, 55.85; MS (m/z, %): 298
(M+,100), 177 (8.45), 151 (98.97), 137 (28.18), 133 (21.33), 93 (35.40); Calcd. for C14H10N4O2S (%):
C 56.36, H 3.38, N 18.79; Found (%): C 56.64, H 3.48, N 18.57.
References
1. Zhang Z.Y.; Chen X. Synthesis and Antibacterial Activity of 3-(4-Pyridyl)-6-aryl-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles. Acta Chim. Sinica, 1991, 49, 513-520
2. Zhang Z.Y.; Li M.; Zhao L.; Li Z.M.; Liao R.A. Synthesis of 3-Alkyl/Aryl-6-
(3-pyridyl)-s-triazolo[3,4-b]-1,3,4-thiadiazoles. Chin. J. Org. Chem., 1993, 13, 397-402
3. Gupta R.; Sudan S.; Mengi V.; Kachroo P. L. Indian J. Chem., Sect. B, 1996, 35, 621-623
4. Zhang L.X.; Zhang Z.Y.; Zeng F.L. Studies on Synthesis and Spectral Properties of
1-Nicotinyl-4-arylaminosemicarbazides and Substituted-1,2,4-triazoles. Chem. J. Chin. Univ., 1990,
11, 148-153
5. Reid J. R.; Heindel N. D. J. Heterocyclic Chem., 1976, 13, 925-928
Sample Availability: Not available.
© 2002 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.