Study on synthesis of 1,2,3-triazole
Xiao Guomin, Yang Weihua
(Department of Chemistry and Chemical Engineering, Southeast University, Nanjing, 210096)
Received Sep. 13, 2001
Abstract 1,2,3-triazole was
prepared by the reaction of tosylhydrazine with glyoxal followed by treatment with
ammonia. Experiments were done under different conditions of reaction, and the optimal
condition for synthesis of 1,2,3-triazole was obtained. Under the optimal condition, the
yield of 1,2,3-triazole was 66.8%.
Keyword 1,2,3-triazole,
tosylhydrazide, synthesis, b-lactam antibiotics
1H-1,2,3-triazole is used
widely in the preparation of important pharmaceutical compounds, especially useful as an
intermediate for b-lactam antibiotics
such as tazobactam[1]. It can also be used as intermediate for some
bactericides and pesticides. Sometimes, it plays an important role in polymer industry. So
it is valuable to study the procedures for preparation of 1H-1,2,3-triazole.
1. VARIOUS PROCEDURES FOR PREPARATION OF
1,2,3-TRIAZOLE
1H-1,2,3-triazole can be prepared by the following methods:
One method utilizes the
reaction of Cl2CHCH=NNHSO2C6H4CH3
with NH3. A solvent of 41.5g p-MeC6H4SO2NHNH2
in MeCH2CO2H was treated with 25g Cl2CHCHO at 15°C for ~1h to give 37.2g Cl2CHCH=NNHSO2C6H4CH3,
which was treated with NH3-saturated.MeOH at 22±5°C for
2h to give 50.5% 1,2,3-triazole [2].
Another
method: 2,2-dichloroacetaldehyde was treated with hydroxylamine hydrochloride to give
80.5% 2,2-dichloroacetaldoxime, which was treated with hydrazine to give 70.1% glyoxal
monoxime hydrazon. Stirring it in CHCl3 in the presence of SOCl2 and
Et3N gave 61.6% 1,2,3-triazole [3].
The third method: 1H-1,2,3-triazole was prepared by adding
tosylhydrazide to a mixture of ammonia and glyoxal in methanol and water in a sealed
container, and the reaction mixture was stirred for 15h at room temperature to give 53.4%
1,2,3-triazole, which was isolated by the residue distillation[4, 5].
The fourth method: 538g MeCONHN=CHCH=NOH and 74.8g AcONa
were dissolved in 2.4L toluene, followed by adding 930.2g Ac2O, and the
reaction mixture was stirred at 90-93°CC for 4h,cooled,and filtered to give a filtrate solvent. MeOH(730g) was added
drop-wise to the latter solvent at <40°C and the resulting mixture was stirred for
4h, concentrated in vacuum, and distillated to give 80% 1,2,3-triazole[6, 7].
The fifth method: Autoclaving benzyltriazole with 5% Pd/C in AcOH at 50°C and
6kg/cm2 for 4h gave 89.8% 1,2,3-triazole, whereas hydrogenation in EtOH was
unsuccessful[4].
In view of price of
raw materials, conditions demanded and yield of the product in the concerned procedures,
we selected the third method as the most suitable procedure for preparation of
1,2,3-triazole for study.
2. EXPERIMENTAL
2.1 Preparation of tosylhydrazine
Scheme 1
As shown in scheme 1,
tosylhydrazide was prepared by the reaction of tosylchloride with hydrazine. Thus, 85% H2NNH2·H2O
(30ml) was added drop-wise into a stirred solution of tosylchloride in benzene (80ml) for
40 minutes. The reaction mixture was left stirring at 60-70°C for additional 50 minutes followed by laying up.
The product, tosylhydrazide, precipitating from the reaction mixture was isolated by
filtration, and was dried at 56°C. It
was washed with water until free from H2NNH2·HCl, then redrying at 50°C for 5h. The product(15g,80.6%) is a white crystalline solid, mp 105°C(decomposition) as
the literature[8] reported.
Anal. IR (KBr), v=3400,
3255, 1650, 1230, 820cm-1, which is same as Sadtler standard spectrogram.
2.2 Synthesis of 1,2,3-triazole
Scheme 2
As shown in scheme 2,
1,2,3-triazole was prepared by the reaction of tosylhydrazide with glyoxal followed by
treatment with ammonia. Thus, a solution of tosylhydrazine (20g) and acetic acid(1ml) in
methanol(180ml) was added drop-wise into a stirred solution of glyoxal(31ml of 40%
solution) in methanol(100ml). Some solid was separated out during the addition. The
reaction mixture was then stirred for additional 15 minutes. A stream of ammonia was
bubbled through the reaction mixture for 45 minutes .During the ammonia addition the
reaction temperature rose to 55°C, and then slowly dropped to 30°C. The reaction mixture was left stirring at room
temperature overnight. The reaction mixture was concentrated, and diluted with 25%
methanol in ether(250ml).The separated solid was removed by filtration, the filtrate
concentrated and the residue distilled to isolate 1,2,3-triazole(5.0g,66.8%).The fraction
collected at 42°C(0.25mm) was
identified as 1,2,3-triazole, a pale yellow liquid.
2.3 Product analysis
Found: mp, 23-24°C; NMR (CDCl3), d=2.33ppm(1H), 7.75ppm (2H);
IR (CCl4), v=3131,2942,1521,1455,1223,1186,
1092,1079, 947,789,701cm-1
Requires: mp, 23°C; NMR (CDCl3), d=2.34ppm(1H),
7.76ppm (2H);
IR (CCl4), v=3130,2940,1520,1450,1220,1180,
1090,1080, 950,790,700cm-1
3. RESULTS AND DISCUSSION
In industry, tosylhydrazide is produced from
40% H2NNH2路H2O, the yield is 76% and the purity is 95%. As
the product tends to be hydrolyzed, the product is thermolability and unfit to be material
of preparing 1,2,3-triazole. The yield and purity of the product can be raised through
properly increasing the dosage of H2NNH2·H2O, thus, high concentration (85%) of H2NNH2·H2O was used as
material. The reaction of preparing tosylhydrazine is mainly affected by such factors as
mole ratio among materials and reaction temperature. As far as reaction temperature is
concerned, 60-70°C is optimal for this reaction. Otherwise,
it is inadvisable to lengthen reaction time, since we have obtained high yield (80.6%) of
the product after reacting for 1.5h (see Table 1).
While synthesizing 1,2,3-triazole, many experiments to study the
influencing factors on the reaction were performed. In experiments, for example, we
selected different mole ratios of tosylhydrazide (A) and glyoxal (B). Otherwise, we took
three various manners of materials addition: the first, A and B were simultaneously added
into a stirred solvent of methanol followed by bubbling a stream of ammonia; the second, a
solution of glyoxal in methanol was added into a stirred solution of tosylhydrazide in
methanol followed by bubbling a stream of ammonia; the third, a solution of tosylhydrazide
in methanol was added drop-wise into a stirred solution of glyoxal in methanol followed by
bubbling a stream of ammonia. The results of experiments are shown in table 2.
Table 1. The yield of tosylhydrazide
at different reaction time
Reaction time/h |
1.0 |
1.5 |
2.0 |
3.0 |
5.0 |
Yield/% |
68.3 |
80.6 |
76.8 |
75.3 |
70.2 |
Table 2. The yield of 1,2,3-triazole at
various adding manner and different mole ratio of A and B
Manner
Ratio |
First |
Second |
Third |
Output(g) |
Yield |
Output(g) |
Yield |
Output(g) |
Yield |
1.3 |
2.1 |
28.1% |
2.3 |
30.7% |
3.2 |
42.8% |
2.0 |
2.8 |
37.4% |
3.2 |
42.8% |
4.3 |
57.4% |
2.7 |
3.6 |
48.1% |
3.8 |
50.8% |
5.0 |
66.8% |
3.5 |
2.9 |
38.7% |
3.4 |
45.4% |
4.1 |
54.8% |
5.0 |
2.7 |
36.1% |
3.2 |
42.8% |
3.8 |
50.8% |
Consequently, we have
found out the optimal condition for synthesis of 1,2,3-triazole. The ratio of (A) and
glyoxal(B) 1:2.7 should be selected, and the third manner of materials addition is the
best.
By the way, 1,2,3-triazole should be isolated by vacuum distillation because of
its thermolability at >200 °C.
4.CONCLUSIONS
A preparation method of tosylhydrazide with
high purity was established, by the reaction of MeC6H4SO2Cl
(I) with H2NNH2·H2O(II) in presence of benzene as solvent and
mole ratio of I-II 1:2 at 60-70°C for 1.5h, with the yield of80.6%
product was obtained. It is a white crystalline solid after being purified, mp 105°C(decomposition).
The effective process for the production of 1,2,3-triazole
is summarized as follows: A solution of tosylhydrazide and acetic acid in methanol was
added drop-wise into a stirred solution of glyoxal in methanol followed by bubbling a
stream of ammonia. The reaction mixture was stirred for 15h at room temperature, the
product was isolated by the residue distillation. When the mole ratio of tosylhydrazide
and glyoxal is 1:2.7, it gives the yield of 66.8% for 1H-1,2,3-triazole. The pure product
is a pale yellow liquid, mp.23-25°C.
The total yield of
1,2,3-triazole is up to 53.8% in the procedure from MeC6H4SO2Cl
as one material. So the procedure is advisable for its economy benefit.
REFERENCES
[1]Torii S, Tanaka H, Nakai A et al. Japan, EP331394, 1989.
[2]Hardas K, Oda M, Matsushita A. Japan, JP05140121, 1993.
[3]Hardas K, Oda M. Japan, JP06 41092 , 1994-02-15.
[4]Singh I P, Spevak P, Spevak P et al. Canada, US5478947, 1995.
[5]Hardas K, Oda M. Japan, JP07278121, 1995.
[6]Harda, K. Synlett, 1998 , (4): 431-3.
[7]Hardas K, Matsushita A, Oda M. Japan, JP07126257,1995.
[8]Dragutan V, Dragutan I. Bucuresti, Ro100922, 1991.
|