Synthesis method of 3, 3 '-disulfanediyl bis (N, N-dimethyl-1H-1, 2, 4-triazole-1-sulfonamide)
By performing the coupling reaction in a dichloromethane solvent, using dimethylamine sulfonyl chloride, potassium carbonate, compound A and triethylamine as raw materials, the problem of lack of efficient synthesis methods in the prior art was successfully solved, and the production of 3,3'-disulfanyldiylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) with high yield and high purity was achieved.
Patent Information
- Application Number
- CN202311224465.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-09-21
- Publication Date
- 2025-03-21
AI Technical Summary
There is a lack of a safe, efficient and suitable synthesis method for 3,3'-disulfanyldiylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) in the prior art.
Dichloromethane was used as solvent, dimethylamine sulfonyl chloride, potassium carbonate, compound A, and triethylamine were added, and the coupling reaction was carried out by controlling the temperature to obtain 3,3'-disulfanyldiylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide).
The synthesis of 3,3'-disulfanyldiylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) with high yield and high purity is achieved, and is suitable for productive production.
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Figure CN119661454A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide). Background Art
[0002] A five-membered aromatic heterocyclic compound containing three nitrogen atoms is called a triazole. According to the adjacent relationship of the nitrogen atoms, it can be divided into two categories: 1,2,3-triazole 1 and 1,2,4-triazole 2, each of which has its own isomers (Scheme 1). Since their discovery, 1,2,4-triazole compounds have been highly valued by medicinal chemists and biochemists, and a large number of studies have been conducted on this type of compound at home and abroad. Years of research have shown that this type of compound has broad application prospects in many fields such as organic chemistry, organometallic chemistry, medicinal chemistry and material chemistry due to its unique structure and chemical properties.
[0003] 3,3'-Disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) is a derivative of 1,2,4-triazole compounds, which can be used in the fields of pesticides, industrial preservatives, fungicides, disinfectants, etc. It is also used as an organic synthesis intermediate for the preparation of other biologically active compounds. It is also a nitrogen heterocyclic compound containing sulfur, which can inhibit the biosynthesis of proteins, thereby affecting the growth and development of plant or human cells.
[0004] However, there is no corresponding synthesis route or production process for 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) in the prior art. There is an urgent need for a corresponding synthesis route for 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) with high production efficiency and suitable for production. Summary of the invention
[0005] The technical problem to be solved by the present invention is: how to provide a safe, efficient and production-suitable synthesis method of 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide).
[0006] To solve the above problems, the technical solution adopted by the present invention is:
[0007] A method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide), characterized in that it comprises the following steps: using dichloromethane as a solvent, adding dimethylaminosulfonyl chloride, potassium carbonate, compound A, and triethylamine, controlling the temperature, and performing a coupling reaction to obtain 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide), the chemical formula of which is:
[0008]
[0009] Preferably, the mass ratio of dimethylaminosulfonyl chloride, potassium carbonate, compound A and triethylamine is 120:7:67:100-110.
[0010] Preferably, the temperature is 20-30°C.
[0011] The present invention also provides a synthesis of compound A comprising:
[0012] (1) Formic acid and thiosemicarbazide are subjected to a ring-closing reaction at 50-55°C to obtain mercaptotriazole
[0013] (2) Using methanol as solvent, adding mercaptotriazole and hydrogen peroxide, and performing coupling reaction at 40-50° C. to obtain compound A
[0014]
[0015] Preferably, the mass ratio of formic acid to thiosemicarbazide is 10:3-5.
[0016] Preferably, the mass ratio of the mercaptotriazole to hydrogen peroxide is 4:1-2.
[0017] Beneficial effects:
[0018] The invention provides a method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) by using compound A, dimethylaminosulfonyl chloride, potassium carbonate, triethylamine and the like as raw materials through coupling reaction. The method has high product yield, is easy to operate, and is suitable for commercial production. The invention also provides a synthetic route for preparing compound A by using formic acid and thiosemicarbazide as basic raw materials through ring-closing reaction and coupling reaction. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Attached Figure 1 This is the H-NMR spectrum of 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) prepared in Example 13. DETAILED DESCRIPTION
[0020] The present application is described below in the form of specific examples, and its purpose is to better understand the content of the present application. It should be understood that these examples are merely illustrative and non-restrictive. The reagents used in the examples are conventionally purchased from the market unless otherwise specified. The methods and conditions used in the examples are conventional methods and conditions unless otherwise specified.
[0021] The molar yield is calculated by the formula: (product mass: product molecular weight) / (raw material mass: raw material molecular weight)×100%. Synthesis method of compound A:
[0022] (1) Formic acid is placed in a reactor, the temperature is controlled at 50-55°C, and then thiosemicarbazide is added, and the reaction is kept warm for 1.5 hours. Then water is added, the temperature is raised to 80-85°C, and the temperature is kept warm and stirred for 30 minutes. The temperature is lowered to 0-5°C, and the wet product is filtered and centrifuged to obtain a wet product. Water, sodium hydroxide, and the wet product are mixed, the temperature is controlled to 40-45°C, and the temperature is kept warm and stirred for 1 hour. The temperature is lowered to 5-10°C, hydrochloric acid is added dropwise to adjust the pH to 5-6, and the mercaptotriazole is obtained by suction filtration;
[0023] (2) Methanol and mercaptotriazole are placed in a reactor, the temperature is raised to 45-50°C, hydrogen peroxide is added dropwise under temperature control, the addition is completed over 6-8 hours, the temperature is kept for reaction for 4 hours, and then the temperature is lowered to 0-5°C, filtered, and dried to obtain compound A.
[0024] Example 1
[0025] Synthesis of mercaptotriazole:
[0026] Put 100g of formic acid into the reactor, control the temperature at 50-55°C, add 30g of thiosemicarbazide, keep the temperature for reaction for 1.5h, then add water, raise the temperature to 80-85°C, keep the temperature and stir for 30min, cool to 0-5°C, filter, centrifuge to get the wet product, mix 150g of water, 15g of sodium hydroxide and the wet product, control the temperature to 40-45°C, keep the temperature and stir for 1h, cool to 5-10°C, add hydrochloric acid dropwise to adjust the pH to 5-6, filter to get mercaptotriazole, and the molar yield is 93.8%.
[0027] Example 7
[0028] Synthesis of compound A: Add 150g methanol and 40g mercaptotriazole into a reactor, raise the temperature to 40-50°C, and add 50g of 20% hydrogen peroxide solution under temperature control. The addition is completed in about 6-8h, and the reaction is kept warm for 4 hours. Then, the temperature is lowered to 0-5°C, filtered, and dried to obtain compound A with a molar yield of 96.7%.
[0029] From the above experiments, it can be seen that the yield of compound A obtained according to the experimental conditions is the highest. At the same time, when the temperature increases or decreases, the yield decreases rapidly.
[0030] Example 13
[0031] Compound A
[0032] A method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide): 340g of dichloromethane, 7g of potassium carbonate, 67g of compound A and 100g of triethylamine are added into a reactor, the temperature is controlled at 20-30°C, 120g of dimethylaminosulfonyl chloride is added dropwise, the addition is completed within 2h, the reaction is carried out by heat preservation for 3h, the temperature is lowered to 20°C, dilute hydrochloric acid is added, the mixture is stirred for 30min, the mixture is allowed to stand, the mixture is separated into layers, the lower layer is concentrated, the concentrated material is mixed and dissolved with methanol, the mixture is stirred, the temperature is lowered to 0-5°C, the mixture is filtered by suction and dried to obtain 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide), and the molar yield is 97.5%.
[0033] The above experiments show that the yield of 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) obtained under the experimental conditions is the highest, and the purity reaches 99.6%. At the same time, when the temperature increases or decreases, the yield decreases rapidly.
Claims
1. A method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide), characterized in that: The method comprises the following steps: using dichloromethane as a solvent, adding dimethylaminosulfonyl chloride, potassium carbonate, compound A, and triethylamine, controlling the temperature, and performing a coupling reaction to obtain 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide), the chemical formula of which is: 。 2. The method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) according to claim 1, characterized in that: The mass ratio of dimethylaminosulfonyl chloride, potassium carbonate, compound A and triethylamine is 120:7:67:100-110.
3. The method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) according to claim 2, characterized in that: The temperature is 20-30°C.
4. The method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) according to any one of claims 1 to 3, characterized in that: The synthesis of compound A comprises: (1) Formic acid and thiosemicarbazide are subjected to a ring-closing reaction at 50-55°C to obtain mercaptotriazole; (2) Using methanol as solvent, adding mercaptotriazole and hydrogen peroxide, and carrying out coupling reaction at 40-50°C to obtain compound A.
5. The method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) according to claim 4, characterized in that: The mass ratio of the formic acid to thiosemicarbazide is 10:3-5.
6. The method for synthesizing 3,3'-disulfanediylbis(N,N-dimethyl-1H-1,2,4-triazole-1-sulfonamide) according to claim 4, characterized in that: The mass ratio of the mercaptotriazole to the hydrogen peroxide is 4:1-2.