Silica-supported dichlorophosphate as a recoverable cyclodehydrant: Expeditious synthesis of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles under microwave irradiation

Article abstract of DOI:10.1080/00397910902838912

An expeditious novel approach to 3,6-disubstituted [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazoles using silica-supported dichlorophosphate as a recoverable cyclodehydrant, carboxylic acids and thiocarbohydrazide as starting materials, and microwave irradiatio

Full text of DOI:10.1080/00397910902838912

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Silica-Supported
Dichlorophosphate as a
Recoverable Cyclodehydrant:
Expeditious Synthesis of
[1,2,4]Triazolo[3,4-b]
[1,3,4]thiadiazoles Under
Microwave Irradiation
Zheng Li a & Yanlong Zhao a
a Gansu Key Laboratory of Polymer Materials,
College of Chemistry and Chemical Engineering,
Northwest Normal University , Lanzhou, Gansu,
China
Published online: 07 Oct 2009.
To cite this article: Zheng Li & Yanlong Zhao (2009) Silica-Supported
Dichlorophosphate as a Recoverable Cyclodehydrant: Expeditious Synthesis of
[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles Under Microwave Irradiation, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:21, 3816-3824, DOI: 10.1080/00397910902838912
To link to this article: http://dx.doi.org/10.1080/00397910902838912
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Synthetic Communications1, 39: 3816–3824, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902838912
Silica-Supported Dichlorophosphate
as a Recoverable Cyclodehydrant:
Expeditious Synthesis of [1,2,4]Triazolo
[3,4-b][1,3,4]thiadiazoles Under Microwave
Irradiation
Zheng Li and Yanlong Zhao
Gansu Key Laboratory of Polymer Materials, College of Chemistry
and Chemical Engineering, Northwest Normal University, Lanzhou,
Gansu, China
Abstract: An expeditious novel approach to 3,6-disubstituted [1,2,4]triazolo
[3,4-b][1,3,4]thiadiazoles using silica-supported dichlorophosphate as a recover-
able cyclodehydrant, carboxylic acids and thiocarbohydrazide as starting materi-
als, and microwave irradiation as thermal source was described. The protocol has
advantages of concise synthetic step, short time, good yield, easy workup
procedure, and no environmental pollution.
Keywords: Microwave irradiation, silica-supported dichlorophosphate, thiocar-
bohydrazide, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
INTRODUCTION
[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazole derivatives are important hetero-
cyclic compounds with a wide range of pharmaceutical and biological
activities, such as antibacterial,[1] fungicidal,[2] pesticidal,[3] and herbci-
dal[4] activities. Generally, 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]
thiadiazoles are synthesized by two routes[5] (Scheme 1): (i) 3-substituted
Received November 4, 2008.
Address correspondence to Zheng Li, College of Chemistry and Chemical
Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China.
E-mail: lizheng@nwnu.edu.cn
3816

[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles
3817
Scheme 1. Two routes for the synthesis of 3,6-disubstituted [1,2,4]triazolo[3,4-
b][1,3,4]thiadiazoles.
4-amino-5-mercapto-1,2,4-triazoles (1) reacted with carboxylic acids or
acid chlorides using phosphorus oxychloride as cyclodehydrant; (ii)
2-substituted 5-hydrazino-1,3,4-thiadiazoles (2) reacted with carboxylic
acids or acid chlorides using phosphorus oxychloride as cyclodehydrant.
However, the preparation of intermediates 1 and 2 requires long steps,
which often cause the poor overall yield of desired products. Further-
more, the resultant of liquid dehydrant, POCl3, is difficult to separate
and recover after the reactions, which usually causes heavy corrosive
and environmental pollution.
In this article, we report a novel and expeditious route to synthesize
3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles under microwave
irradiation using silica-supported dichlorophosphate as an efficient and
recoverable cyclodehydrant and carboxylic acids and thiocarbohydrazide
as starting materials.
RESULTS AND DISCUSSION
Silica-supported dichlorophosphate was prepared by reaction of silica gel
with phosphorus oxychloride under microwave irradiation (Scheme 2).
The reaction could be completed within 12 min to afford the desired
product in excellent yield. Figure 1 shows the infrared (IR) spectra of
silica-supported dichlorophosphate and silica gel. Both IR spectra show
the typical broad absorption peaks of Si-O-Si bond at 1103 cmꢀ1. Hydrogen-
bonded silanol groups give bands in the region of 3300–3600 cmꢀ1. In
particular, a new strong peak at 571 cmꢀ1 is exhibited in the spectrum of
silica-supported dichlorophosphate, which is attributable to the absorption

3818
Z. Li and Y. Zhao
Scheme 2. Synthesis of silica-supported dichlorophosphate.
of P-Cl. The silica-supporting capacity for POCl2 is ca. 2.81 mmol=g. The
specific surface area for the sample is ca. 82 m2=g.
To explore the availability of silica-supported dichlorophosphate as a
recoverable cyclodehydrant under microwave irradiation, the synthesis of
3,6-diphenyl [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4a) by reacting ben-
zoic acid with thiocarbohydrazide was selected as a model synthetic reac-
tion. The optimal reaction conditions including reactant ratio, reaction
time, and microwave power were investigated. It was found that when
the ratio of benzoic acid, thiocarbohydrazide, and silica-supported
dichlorophosphate was 2.2:1:2.2 and the microwave power was 650 W,
the reaction gave the best yield for 4a within 8 min. Using similar condi-
tions, a series of 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles
(4a–j) were synthesized in excellent yield (Table 1, Scheme 3). The differ-
ent substituents on the aromatic rings have no significant effect on the
reaction conditions and the reaction yields. After the reactions, the
Figure 1. IR spectra of silica gel and silica-supported dichlorophosphate.

[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles
3819
Table 1. Synthesis of 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles
(4a–j)
Compound
R
Product
Mp. (lit.) (ꢁC) Yield (%)a
200–202
88
4a
C6H5
(204–205)[6]
4b
4c
4-CH3OC6H4
160–162
120–122
84
83
2-CH3C6H4
4d
4e
3-CH3C6H4
124–126
220–222
84
80
2-ClC6H4
4f
3-ClC6H4
4-ClC6H4
196–194
81
81
4g
214–216
(235–236)[7]
(Continued )

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Z. Li and Y. Zhao
Table 1. Continued
Compound
R
Product
Mp. (lit.) (ꢁC) Yield (%)a
4h
4i
4j
3-FC6H4
190–192
160–162
79
3,5-((CH3)3C)2-4-
(OH)-C6H2
87
84
202–204
Fur-2-yl
(204–206)[8]
aThe yields refer to the isolated product.
resultant of silica-supported cyclodehydrant could be easily isolated and
recovered from the reaction system by only filtration, and this efficiently
avoided the corrosion and pollution caused by using liquid cyclodehy-
drant, such as phosphorus oxychloride. The pure product could be read-
ily obtained by evaporating off the solvent and washing with water.
In contrast, the synthesis of 4a was also tested by the traditional heat-
ing method. However, after 10 h reflux in ethanol, only 51% yield of 4a
was obtained.
In conclusion, we have developed an expeditious, novel method
to 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles by the
Scheme 3. Synthesis of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles.

[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles
3821
reactions of aromatic carboxylic acids with thiocarbohydrazide using
silica-supported dichlorophosphate as a recoverable cyclodehydrant
and microwave irradiation as thermal source. The features of short reac-
tion time, good reaction yield, no environmental pollution, and simple
workup procedure make this protocol a good alternative to the synthesis
of the corresponding heterocyclic compounds.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on a Digilab FTS 3000
Fourier transform (FT)-IR spectrophotometer and 1H NMR spectra
on a Mercury-400BB instrument using CDCl3 as solvent and Me4Si as
internal standard. Elemental analyses were performed on a Vario E1 ele-
mental analysis instrument. Melting points were observed in an electro-
thermal melting-point apparatus. Microwave reactions were conducted
in a modified microwave oven fitted with a condenser (LG-WP650,
China). Thiocarbohydrazide[9] and silica-supported dichlorophosphate[10]
were prepared according to the literature procedure.
General Procedure for the Preparation of 3,6-Disubstituted
[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles (4a–j)
Silica-supported dichlorophosphate (4.4 mmol) was added to the solution of
aromatic carboxylic acid (4.4 mmol) and thiocarbohydrazide (2mmol) in
25 mL of ethanol. The mixture was subjected to the microwave irradiation
at reflux condition for 8 min under the power of 650 W. The completion of
the reaction was monitored by thin-layer chromatography (TLC). Then the
resulting mixture was filtered to recover the silica-supported reagent, which
could be reused after regeneration, and the filtrate was evaporated off the
solvent. The resulting solid was washed with cold ethanol (5 mL) and water
(10mL) and recrystallized from DMF–EtOH–H2O (1:5:1) to give the
product. The analytical data for compounds 4a–j are given next.
Data
Compound 4a
1H NMR (CDCl3, 400 MHz): d 7.58–8.34 (m, 10H, Ar-H). IR (KBr, n,
cmꢀ1): 1676, 1514, 1466, 1380, 1237, 684. Anal. calcd. for C15H10N4S:
C, 64.73; H, 3.62; N, 20.13. Found: C, 64.60; H, 3.61; N, 20.18.

3822
Z. Li and Y. Zhao
Compound 4b
1H NMR (CDCl3, 400 MHz): d 7.02–8.35 (m, 8H, Ar-H), 3.89 (s, 6H,
CH3). IR (KBr, n, cmꢀ1): 1690, 1611, 1512, 1431, 1257, 693. Anal. calcd.
for C17H14N4O2S: C, 60.34; H, 4.17; N, 16.56. Found: C, 60.25; H, 4.16;
N, 16.51.
Compound 4c
1H NMR (CDCl3, 400 MHz): d 7.39–8.28 (m, 8H, Ar-H), 2.43 (s, 6H,
CH3). IR (KBr, n, cmꢀ1): 1650, 1608, 1519, 1461, 1269, 684. Anal. calcd.
for C17H14N4S: C, 66.64; H, 4.61; N, 18.29. Found: C, 66.77; H, 4.62; N,
18.24.
Compound 4d
1H NMR (CDCl3, 400 MHz): d 7.31–8.21 (m, 8H, Ar-H), 2.42 (s, 6H,
CH3). IR (KBr, n, cmꢀ1): 1651, 1607, 1514, 1462, 1261, 680. Anal. calcd.
for C17H14N4S: C, 66.64; H, 4.61; N, 18.29. Found: C, 66.72; H, 4.60; N,
18.35.
Compound 4e
1H NMR (CDCl3, 400 MHz): d 7.54–8.23 (m, 8H, Ar-H). IR (KBr, n,
cmꢀ1): 1606, 1540, 1496, 1448, 1243, 691. Anal. calcd. for C15H8Cl2N4S:
C, 51.89; H, 2.32; N, 16.14. Found: C, 51.78; H, 2.31; N, 16.20.
Compound 4f
1H NMR (CDCl3, 400 MHz): d 7.60–8.40 (m, 8H, Ar-H). IR (KBr, n,
cmꢀ1): 1608, 1496, 1472, 1460, 1248, 694. Anal. calcd. for C15H8Cl2N4S:
C, 51.89; H, 2.32; N, 16.14. Found: C, 52.00; H, 2.30; N, 16.09.
Compound 4g
1H NMR (CDCl3, 400 MHz): d 7.71–8.33 (m, 8H, Ar-H). IR (KBr, n,
cmꢀ1): 1626, 1595, 1472, 1468, 1259, 697. Anal. calcd. for
C15H8Cl2N4S: C, 51.89; H, 2.32; N, 16.14. Found: C, 51.98; H, 2.34;
N, 16.19.

[1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles
Compound 4h
3823
1H NMR (CDCl3, 400 MHz): d 7.41–8.21 (m, 8H, Ar-H). IR (KBr, n,
cmꢀ1): 1591, 1480, 1460, 1453, 1261, 692. Anal. calcd. for C15H8F2N4S:
C, 57.32; H, 2.57; N, 17.83. Found: C, 57.41; H, 2.56; N, 17.88.
Compound 4i
1H NMR (CDCl3, 400 MHz): d 8.33 (s, 2H, Ar-H), 7.75 (s, 2H, Ar-H),
5.76 (s, 1H, OH), 5.54 (s, 1H, OH), 1.51 (s, 36H, CH3). IR (KBr, n,
cmꢀ1): 1600, 1514, 1465, 1419, 1240, 700. Anal. calcd. for C31H42N4O2S:
C, 69.63; H, 7.92; N, 10.48. Found: C, 69.71; H, 7.93; N, 10.54.
Compound 4j
1H NMR (CDCl3, 400 MHz): d 6.79–8.12 (m, 6H, Fu-H). IR (KBr, n,
cmꢀ1): 1623, 1593, 1520, 1508, 1254, 699. Anal. calcd. for C11H6N4O2S:
C, 51.16; H, 2.34; N, 21.69. Found: C, 51.21; H, 2.35; N, 21.73.
ACKNOWLEDGMENTS
The authors thank the National Natural Science Foundation of China
(20772096) and Gansu Natural Science Foundation (3ZS061-A25-033)
for the financial support of this work.
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