A method for preparing 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole

Abstract

This invention discloses a method for preparing 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole, comprising the following steps: at a certain temperature, 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole is reacted in a reaction mixture containing acetic acid, water, and toluene, and chlorine gas is introduced to obtain a thiadiazole sulfoxide compound with high purity. This reaction is mild, simple to operate, highly selective, uses economical raw materials, and is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole. Background Technology

[0002] 2-Methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole is an important heterocyclic intermediate, mainly used in the preparation of fluthiamethoxam pesticide.

[0003] The main preparation methods are as follows:

[0004] US6437189 discloses a method for synthesizing 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole. This method selectively oxidizes 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole to the target product using sodium perborate or sodium percarbonate. This method has a high yield (98.9%) and high selectivity (99.1%), but the oxidants sodium perborate or sodium percarbonate are expensive, unstable, unsafe to use, and generate large amounts of industrial waste salt, making them unsuitable for industrial production.

[0005] CN103288776 discloses a method for preparing 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole. This method uses potassium persulfate as an oxidant and methylenebenzenesulfonamide as a catalyst. By controlling the amount and feeding rate of potassium persulfate, 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole can be oxidized to 2-sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole with high selectivity. The yield is 95%, and the purity is 99%. Using other catalysts, such as benzyltriethylammonium chloride, the product yield and purity are reduced (yield 94%, purity 96%). Although potassium persulfate can be used in large quantities, its price is high, and the large amount of sulfate waste it generates is a significant environmental problem.

[0006] CN104327013 discloses another method for preparing 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole. This method uses hydrogen peroxide as an oxidant and boric acid and hydrochloric acid as catalysts to selectively oxidize 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole to 2-sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole. The product yield is 97.2%, and the purity is 99.4%. This method also discloses the use of other catalysts (such as phosphorus trihalides and phosphorus trihalides). Compared with the two methods mentioned above, the hydrogen peroxide used in this method is more economical and readily available, but the oxidation reaction needs to be carried out at a relatively high temperature (40–80°C) and requires an excess of hydrogen peroxide (2.5 eq). Using large amounts of hydrogen peroxide at high temperatures poses a significant safety hazard. Furthermore, the catalysts boric acid, phosphorus trihalides, and phosphorus trihalides used cannot be recovered and are lost into wastewater, increasing wastewater treatment costs.

[0007] DE4005225 reports a method for preparing 2-methylsulfinyl-5-chlorofluoromethyl-1,3,4-thiadiazole compounds. This method involves reacting chlorine gas and 2-methylthio-5-chlorofluoromethyl-1,3,4-thiadiazole in water to generate 2-methylsulfinyl-5-chlorofluoromethyl-1,3,4-thiadiazole in 50% yield. Summary of the Invention

[0008] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for the industrial preparation of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole with mild reaction conditions, high yield, high selectivity, and low waste.

[0009] A method for preparing 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole (I) involves using 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) as a raw material, and passing chlorine gas through a system containing acetic acid, water, and toluene as solvents to generate 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole (I); the reaction formula is as follows:

[0010]

[0011] in,

[0012] The mass ratio of toluene to the raw material 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 0.1 to 20:1, preferably 2 to 10:1, and more preferably 4 to 8:1.

[0013] The mass ratio of acetic acid to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 0.2 to 5:1, preferably 0.2 to 2:1, and more preferably 0.3 to 1:1.

[0014] The mass ratio of water to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 0.5 to 5:1, preferably 1 to 2:1, and more preferably 1.2 to 1.5:1.

[0015] The molar ratio of chlorine gas to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 1 to 1.5:1, preferably 1 to 1.2:1.

[0016] The reaction temperature is -10 to 30°C, preferably 10 to 20°C.

[0017] This invention discloses a novel method for preparing 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole. This method solves the safety and environmental problems existing in the prior art for preparing 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole, and has the advantages of mild reaction conditions, simple operation, high selectivity, atom economy, and suitability for industrial production. Detailed Implementation

[0018] The following embodiments clearly and completely describe the technical solutions of the present invention; obviously, the embodiments described are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0019] Example 1: Preparation of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole

[0020] 20 g of 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole was dissolved in a mixed solvent of 40 g toluene, 15 g acetic acid, and 25 g water. 8.2 g of chlorine gas was bubbled through the solution at 20 °C for 20 min. The layers were separated. The aqueous layer was extracted twice with toluene, and the organic layer was washed with 5% sodium bicarbonate solution. The solvent was removed to obtain 21.5 g of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole, with a purity of 99% (yield: 98.54%). (Product) 1 H NMR (500MHz, CDCl3) δ3.21 (s, 3H)).

[0021] Example 2 Preparation of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole

[0022] 100g of 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole was dissolved in a mixed solvent of 200g toluene, 30g acetic acid, and 150g water. 41g of chlorine gas was introduced at 15°C for 1.5 hours. The mixture was allowed to separate into layers. The aqueous layer was extracted twice with 100g of toluene, and the organic layer was washed with 5% sodium bicarbonate solution. The solvent was removed to obtain 108g of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole with a purity of 99% (yield: 99%).

[0023] Comparative Example 1

[0024] 20 g of 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole was dissolved in a mixed solvent of 40 g toluene and 25 g water. 8.2 g of chlorine gas was introduced at 0 °C for 1 h. The mixture was separated into layers. The aqueous layer was extracted twice with toluene, and the organic layer was washed with 5% sodium bicarbonate solution. The solvent was removed to obtain 19.8 g of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole with a purity of 98% (Y: 89.8%).

[0025] Comparative Example 2

[0026] 20 g of 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole was dissolved in a mixed solvent of 40 g toluene and 25 g water. 8.2 g of chlorine gas was introduced at 15 °C for 1 h. The mixture was separated into layers. The aqueous layer was extracted twice with toluene, and the organic layer was washed with 5% sodium bicarbonate solution. The solvent was removed to obtain 19.8 g of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole with a purity of 98% (yield: 80%).

[0027] Comparative Example 3

[0028] 20 g of 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole was dissolved in a mixed solvent of 10 g acetic acid and 25 g water. 8.2 g of chlorine gas was introduced at 20 °C for 1 h. The mixture was separated into layers. The aqueous layer was extracted twice with toluene, and the organic layer was washed with 5% sodium bicarbonate solution. The solvent was removed to obtain 18 g of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole with a purity of 97% (yield: 80.8%).

[0029] Comparative Example 4

[0030] 20 g of 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole was dissolved in a mixed solvent of 10 g acetic acid and 40 g toluene. 8.2 g of chlorine gas was passed through the solution at 0 °C for 1 h. The mixture was separated into layers. The organic layer was washed with 5% sodium bicarbonate solution and the solvent was removed to obtain 18.5 g of 2-methyl sulfoxide-5-trifluoromethyl-1,3,4-thiadiazole with a purity of 96% (yield: 82%).

[0031] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A process for the preparation of 2-methylsulfinyl-5-trifluoromethyl-1,3,4- thiadiazole (I) characterized in that, Using 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) as a starting material, chlorine gas is passed through a system containing acetic acid, water, and toluene as solvents to generate 2-methylsulfoxide-5-trifluoromethyl-1,3,4-thiadiazole (I); the reaction formula is as follows:

2. The method of claim 1, wherein, The mass ratio of toluene to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) used is 0.01 to 20:1; the mass ratio of acetic acid to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 0.2 to 5:1; the mass ratio of water to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 0.5 to 5:1; the molar ratio of chlorine gas to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 1 to 1.5:1; and the reaction temperature is -10 to 30°C.

3. The method of claim 2, wherein, The mass ratio of toluene to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) used is 2 to 10:1; the mass ratio of acetic acid to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 0.2 to 2:1; the mass ratio of water to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 1 to 2:1; the molar ratio of chlorine gas to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 1 to 1.2:1; and the reaction temperature is 10 to 20°C.

4. The method of claim 3, wherein, The mass ratio of toluene to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) used is 4 to 8:1; the mass ratio of acetic acid to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 0.3 to 1:1; and the mass ratio of water to 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole (II) is 1.2 to 1.5:1.

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