Xiao Guomin, Yang Weihua
(Department of Chemistry and Chemical Engineering, Southeast University, Nanjing, 210096)
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%.
1H-1,2,3-triazole is used widely in the preparation of important pharmaceutical compounds, especially useful as an intermediate for-lactam antibiotics such as tazobactam. 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 ClCHCH=NNHSOCH with NH. A solvent of 41.5g p-MeCSONHNH in MeCHCOH was treated with 25g ClCHCHO at 15°Cfor ~1h to give 37.2g ClCHCH=NNHSOCH, which was treated with NH-saturated.MeOH at 22±5°Cfor 2h to give 50.5% 1,2,3-triazole 
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 CHCl in the presence of SOCl and EtN gave 61.6% 1,2,3-triazole 
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 AcO, and the reaction mixture was stirred at 90-93°Cfor 4h,cooled,and filtered to give a filtrate solvent. MeOH(730g) was added drop-wise to the latter solvent at <40°Cand the resulting mixture was stirred for 4h, concentrated in vacuum, and distillated to give 80% 1,2,3-triazole
The fifth method: Autoclaving benzyltriazole with 5% Pd/C in AcOH at 50°Cand 6kg/cm for 4h gave 89.8% 1,2,3-triazole, whereas hydrogenation in EtOH was unsuccessful
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.
2.1 Preparation of tosylhydrazine
As shown in scheme 1, tosylhydrazide was prepared by the reaction of tosylchloride with hydrazine. Thus, 85% HNNH·HO (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 HNNH·HCl, then redrying at 50°Cfor 5h. The product(15g,80.6%) is a white crystalline solid, mp 105°C(decomposition) as the literature 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
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 (CDCl),=2.33ppm(1H), 7.75ppm (2H);
IR (CCl), v=3131,2942,1521,1455,1223,1186, 1092,1079, 947,789,701cm-1
Requires: mp, 23°C; NMR (CDCl),=2.34ppm(1H), 7.76ppm (2H);
IR (CCl), v=3130,2940,1520,1450,1220,1180, 1090,1080, 950,790,700cm-1
3. RESULTS AND DISCUSSION
In industry, tosylhydrazide is produced from 40% HNNH路O, 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 HNNH·O, thus, high concentration (85%) of HNNH·O 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°Cis 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
Table 2. The yield of 1,2,3-triazole at various adding manner and different mole ratio of A and B
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
A preparation method of tosylhydrazide with high purity was established, by the reaction of MeCSOCl (I) with HNNH·O(II) in presence of benzene as solvent and mole ratio of I-II 1:2 at 60-70°Cfor 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 MeCSOCl as one material. So the procedure is advisable for its economy benefit.