Preparation method of 2, 2-dimethyl-1-oxa-4-thia-2-silaheterohexane-6-ketone

Abstract

The invention discloses a preparation method of 2, 2-dimethyl-1-oxa-4-thia-2-silaheterohexane-6-ketone, which comprises the following steps: (1) under the protection of nitrogen atmosphere, mixing sodium chloroacetate and tert-butyl methyl ether, adding a phase transfer catalyst, then dropwise adding chloromethyl dimethyl chlorosilane, carrying out esterification reaction, and after the reaction is completed, carrying out reduced pressure distillation to obtain 2, 2-dimethyl-1-oxa-4-thia-2-silaheterohexane-6-ketone; the reaction liquid takes chloromethyl dimethyl silicon chloroacetate as a main substance; (2) adding sodium sulfide into the reaction liquid, and carrying out cyclization reaction to obtain a crude product after the reaction is completed; and (3) purifying the crude product, so as to obtain a 2, 2-dimethyl-1-oxa-4-thia-2-silaheterohexane-6-ketone product, namely the 2, 2-dimethyl-1-oxa-4-thia-2-silaheterohexane-6-ketone. According to the invention, the problems that a large amount of organic alkali is used and organic amine salt is generated in the prior art are avoided, the use of mercaptoacetic acid with special odor and toxicity is also avoided, and the yield and content of the product are improved.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and specifically relates to a method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one. Background Art

[0002] 2,2-Dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one is a complex organic compound, a type of heterocyclic compound, and is widely used in pharmaceutical intermediates and rubber modifiers. As a rubber modifier, it can introduce silicon carboxylate groups into diene rubber, modify the rubber, and thus improve the weather resistance of the rubber (see CN118215687A, EP4444762A1, US9969833B2, etc.).

[0003] Chinese patent CN104725411A discloses a method for synthesizing 2,2-dimethyl-2-silicon-1,4-thioxane-6-one, comprising the following steps: uniformly mixing thioglycolic acid with a hydrogen chloride absorbent and an inert aprotic solvent, adding chloromethyldimethylsilyl chloride dropwise under stirring to cause an esterification reaction; filtering the precipitate; heating the filtrate to reflux, and performing a ring-closing reaction, thereby reacting to obtain 2,2-dimethyl-2-silicon-1,4-thioxane-6-one. Although the above-mentioned synthesis method can prepare the product, it is necessary to add triethylamine, pyridine, morpholine or N-methylmorpholine and other hydrogen chloride absorbents and dichloromethane, benzene, toluene, cyclohexane, furan or 2-methylfuran and other inert aprotic solvents during the synthesis process. These substances are harmful to the environment to a certain extent, and the raw material thioglycolic acid is also toxic. In addition, the yield of the product in the above-mentioned synthesis method is also less than 80%, and the yield is low. Summary of the invention

[0004] The purpose of the present invention is to provide a method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one, so as to solve the problems of needing to use toxic raw materials and a large amount of organic base and low yield in the above-mentioned synthesis process.

[0005] To achieve the above object, the present invention provides a method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one, comprising the following steps: (1) Under the protection of nitrogen atmosphere, sodium chloroacetate and tert-butyl methyl ether are mixed, a phase transfer catalyst is added, and then chloromethyldimethylsilyl chloride is added dropwise to carry out esterification reaction. After the reaction is completed, a reaction liquid containing chloromethyldimethylsilyl chloride as the main substance is obtained; (2) adding sodium sulfide to the reaction solution to carry out a cyclization reaction, and after the reaction is completed, a crude product is obtained; (3) The crude product is purified to obtain 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one.

[0006] The reaction formula of step (1) in the present invention is:

[0007] The reaction formula of step (2) in the present invention is:

[0008] Preferably, in step (1), the phase transfer catalyst is one or more of tetra-n-butylammonium bromide, benzyltrimethylammonium chloride, and benzyltriethylammonium chloride.

[0009] Preferably, in step (1), the mass ratio of sodium chloroacetate to tert-butyl methyl ether is 1:(8-10).

[0010] Preferably, the amount of phase transfer catalyst added in step (1) is 2-2.5% of the mass of sodium chloroacetate.

[0011] Preferably, in step (1), the amount of chloromethyldimethylsilyl chloride added is 1.1 to 1.5 times the mass of sodium chloroacetate.

[0012] Preferably, in step (1), the temperature of the esterification reaction is below 50° C., and the reaction is continued to be stirred for 3 to 6 hours after the dropwise addition is completed.

[0013] Preferably, in step (2), the amount of sodium sulfide added is 30-40% of the mass of sodium chloroacetate.

[0014] Preferably, in step (2), the reaction solution is heated to 60-70° C. before adding sodium sulfide, and sodium sulfide is added to the reaction solution in batches.

[0015] Preferably, in step (3), the purification process of the crude product is: Add water to the crude product and stir to dissolve the sodium chloride in the crude product at room temperature. When all the salt is completely dissolved, stop stirring and let it stand for 20 to 40 minutes to separate the lower brine phase. The upper organic phase is distilled to obtain the product.

[0016] Preferably, in step (3), the amount of water added is 50-80% of the mass of tert-butyl methyl ether.

[0017] Therefore, the present invention adopts the above-mentioned method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one, which has the following beneficial effects: (1) Traditional synthesis methods require a large amount of organic bases to promote the reaction, and these organic bases and the organic amine salts they produce are often difficult to handle and easily cause environmental pollution. The synthesis method of the present invention reduces the use of organic bases by selecting specific reaction conditions and raw material ratios, such as using sodium chloroacetate as a raw material, and significantly reduces such pollution sources.

[0018] (2) Although thioglycolic acid can participate in the synthesis reaction, its strong pungent odor and toxicity limit its application range. The present invention does not use thioglycolic acid, but uses sodium chloroacetate as the raw material, thereby avoiding these adverse effects.

[0019] (3) The present invention improves the yield and purity of the product by setting specific raw material ratios and reaction conditions.

[0020] (4) The post-processing steps such as purification of the present invention are simple to operate. An appropriate amount of water is added to the crude product to dissolve the generated sodium chloride, and the brine phase and the organic phase are separated after standing. Finally, the pure product is obtained by distillation. This method is simple and easy to operate and does not require complicated separation equipment and technology.

[0021] (5) The raw materials used in the present invention, such as sodium chloroacetate, tert-butyl methyl ether, chloromethyldimethylsilyl chloride, etc., are relatively cheap and easily available chemicals, which reduces the cost of raw materials.

[0022] (6) The raw materials and catalysts selected in the present invention are low-toxic or non-toxic substances, such as tetra-n-butylammonium bromide, benzyltrimethylammonium chloride, etc. These substances are less harmful to the human body during use. At the same time, the entire reaction process is carried out under mild conditions without the need for high temperature and high pressure, which reduces the operational risks and improves the safety of the chemical reaction.

[0023] The technical solution of the present invention is further described in detail below through embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is the H NMR spectrum of the product prepared in Example 1. DETAILED DESCRIPTION

[0025] The present invention will be further described below. It should be noted that this embodiment is based on the technical solution and provides a detailed implementation method and a specific operation process, but the present invention is not limited to this embodiment.

[0026] Example 1 A method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one comprises the following steps: (1) A 100L reactor was used as a reaction vessel, and the vacuum was evacuated and replaced with nitrogen for 3 times. Under nitrogen protection, 40 kg of tert-butyl methyl ether, 4.7 kg of sodium chloroacetate, and 0.1 kg of tetra-n-butylammonium bromide were added into the reactor. Stirring was started at room temperature, and 5.7 kg of chloromethyldimethylsilyl chloride was added dropwise from the dropping tank. The temperature was kept below 50°C. After the addition was completed, stirring was continued for 5 hours. The reaction was controlled by GC until the chloromethyldimethylsilyl chloride was completely reacted to generate chloromethyldimethylsilyl chloride; (2) After the above reaction is complete, the temperature is raised to 65°C, and 1.6 kg of sodium sulfide is added in batches from the solid feeding port. After the addition is completed, the temperature is maintained and the reaction continues. Through GC control, when the chloromethyl dimethyl chloroacetic acid silyl ester is less than 0.5%, the reaction is completed and the temperature is lowered to room temperature; (3) 28 kg of water was added dropwise through the water adding tank, and the sodium chloride in the reaction system was stirred and dissolved at room temperature. When all the salt in the system was completely dissolved, stirring was stopped, and the mixture was left to stand for 30 minutes. The lower salt water phase was separated, and the upper organic phase was distilled to obtain 5.8 kg of colorless oil, which was 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one, with a yield of 90% and a content of more than 98%. The H NMR spectrum of 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one is shown in Figure 1 .

[0027] Example 2 A method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one comprises the following steps: (1) A 100L reactor was used as a reaction vessel, and the vacuum was evacuated and replaced with nitrogen for 3 times. Under nitrogen protection, 40 kg of tert-butyl methyl ether, 4.7 kg of sodium chloroacetate, and 0.1 kg of benzyltrimethylammonium chloride were added into the reactor. Stirring was started at room temperature. 6 kg of chloromethyldimethylsilyl chloride was added dropwise from the dropping tank. The temperature was kept below 50°C. After the addition was completed, stirring was continued for 5 hours. The reaction was controlled by GC until the chloromethyldimethylsilyl chloride was completely reacted to generate chloromethyldimethylsilyl chloride; (2) After the above reaction is complete, the temperature is raised to 65°C, and 1.6 kg of sodium sulfide is added in batches from the solid feeding port. After the addition is completed, the temperature is maintained and the reaction continues. Through GC control, when the chloromethyl dimethyl chloroacetic acid silyl ester is less than 0.5%, the reaction is completed and the temperature is lowered to room temperature; (3) 28 kg of water was added dropwise through a water adding tank, and the sodium chloride in the reaction system was dissolved by stirring at room temperature. When all the salt in the system was completely dissolved, stirring was stopped, and the mixture was allowed to stand for 30 minutes. The lower salt water phase was separated, and the upper organic phase was distilled to obtain 5.5 kg of a colorless oily substance, namely 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one, with a yield of 85% and a content of more than 98%.

[0028] Example 3 A method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one comprises the following steps: (1) A 100L reactor was used as a reactor, and the vacuum was evacuated and replaced with nitrogen for 3 times. Under nitrogen protection, 40 kg of cyclopentyl methyl ether, 5 kg of sodium chloroacetate, and 0.1 kg of benzyltriethylammonium chloride were added into the reactor. Stirring was started at room temperature, and 5.7 kg of chloromethyldimethylsilyl chloride was added dropwise from the dropping tank. The temperature was kept below 50°C. After the addition was completed, stirring was continued for 5 hours. The reaction was controlled by GC until the chloromethyldimethylsilyl chloride was completely reacted to generate chloromethyldimethylsilyl chloride; (2) After the above reaction is complete, the temperature is raised to 65°C, and 1.6 kg of sodium sulfide is added in batches from the solid feeding port. After the addition is completed, the temperature is maintained and the reaction continues. Through GC control, when the chloromethyl dimethyl chloroacetic acid silyl ester is less than 0.5%, the reaction is completed and the temperature is lowered to room temperature; (3) 28 kg of water was added dropwise through a water adding tank, and the sodium chloride in the reaction system was dissolved by stirring at room temperature. When all the salt in the system was completely dissolved, stirring was stopped, and the mixture was allowed to stand for 30 min. The lower salt water phase was separated, and the upper organic phase was distilled to obtain 5.6 kg of a colorless oily substance, namely 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one, with a yield of 87% and a content of more than 98%.

[0029] Comparative Example 1 A method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one comprises the following steps: Add 200g 2-methylfuran (anhydrous) and 50.5g (0.5mol) N-methylmorpholine (anhydrous) into a 500ml three-necked flask, and cool to 10°C under nitrogen protection. At 10°C, add 18.4g (0.2mol) thioglycolic acid dropwise, and control the temperature not to exceed 20°C. After the addition is complete, stir rapidly for 1 hour to obtain a colorless transparent liquid; The mixture was cooled to 10°C again, and 28.6 g (0.2 mol) of chloromethyldimethylsilyl chloride was added dropwise, and the temperature was controlled not to exceed 20°C. After the addition was completed, the mixture was stirred at room temperature for 8 hours. The mixture was sampled and tested by GC to see if there was any residual raw material. The mixture was filtered and the filter cake was washed twice with 2-methylfuran, 30 ml each time. The filtrate was heated to reflux for reaction for 10 hours (nitrogen protection). The mixture was sampled and tested by GC to see if there was any residual intermediate material. The mixture was cooled to room temperature, filtered and the filter cake was washed twice with 2-methylfuran, 20 ml each time. The filtrate was concentrated to dryness under reduced pressure, and the remaining material was distilled under reduced pressure by a distillation device to collect 24.3 g of product with a purity greater than 98% and a yield of 75%.

[0030] Comparative Example 2 A method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one comprises the following steps: Add 200g 2-methylfuran (anhydrous) and 60.7g (0.6mol) triethylamine (anhydrous) into a 500ml three-necked flask, and cool to 10°C under nitrogen protection. At 10°C, add 20.24g (0.22mol) thioglycolic acid dropwise, and control the temperature not to exceed 20°C. After the addition is complete, stir rapidly for 1 hour to obtain a colorless transparent liquid; The mixture was cooled to 20°C again, and 28.6 g (0.2 mol) of chloromethyldimethylsilyl chloride was added dropwise, and the temperature was controlled not to exceed 20°C. After the addition was completed, the mixture was stirred at room temperature for 8 hours. The mixture was sampled and tested by GC to see if there was any residual raw material. The mixture was filtered and the filter cake was washed twice with 2-methylfuran, 30 ml each time. The filtrate was heated to reflux for reaction (nitrogen protection). The mixture was sampled and tested by GC to see if there was any residual intermediate material. The mixture was cooled to room temperature, filtered and the filter cake was washed twice with 2-methylfuran, 20 ml each time. The filtrate was concentrated to dryness under reduced pressure, and the remaining material was distilled under reduced pressure by a distillation device at a vacuum degree of 10 mm Hg and a temperature of 160°C. 25 g of the product was collected with a purity greater than 98% and a yield of 77%.

[0031] Therefore, the present invention adopts a preparation method of 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one of the above structure, which avoids the problem of large-scale use of organic bases and the generation of organic amine salts in the existing process, and also avoids the use of thioglycolic acid with special odor and toxicity, and improves the yield and content of the product.

[0032] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one, characterized in that: The following steps are involved: (1) Under the protection of nitrogen atmosphere, sodium chloroacetate and tert-butyl methyl ether are mixed, a phase transfer catalyst is added, and then chloromethyldimethylsilyl chloride is added dropwise to carry out esterification reaction. After the reaction is completed, a reaction liquid containing chloromethyldimethylsilyl chloride as the main substance is obtained; (2) adding sodium sulfide to the reaction solution to carry out a cyclization reaction, and after the reaction is completed, a crude product is obtained; (3) The crude product is purified to obtain 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one.

2. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 1, characterized in that: In step (1), the phase transfer catalyst is one or more of tetra-n-butylammonium bromide, benzyltrimethylammonium chloride, and benzyltriethylammonium chloride.

3. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 1, characterized in that: In step (1), the mass ratio of sodium chloroacetate to tert-butyl methyl ether is 1:(8-10).

4. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 1, characterized in that: The amount of phase transfer catalyst added in step (1) is 2-2.5% of the mass of sodium chloroacetate.

5. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 1, characterized in that: In step (1), the amount of chloromethyldimethylsilyl chloride added is 1.1 to 1.5 times the mass of sodium chloroacetate.

6. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 1, characterized in that: In step (1), the temperature of the esterification reaction is below 50° C. After the dropwise addition is completed, the reaction is continued to be stirred for 3 to 6 hours.

7. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 1, characterized in that: In step (2), the amount of sodium sulfide added is 30-40% of the mass of sodium chloroacetate.

8. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 1, characterized in that: In step (2), the reaction solution is heated to 60-70° C. before adding sodium sulfide, and sodium sulfide is added to the reaction solution in batches.

9. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 1, characterized in that: In step (3), the purification process of the crude product is as follows: Add water to the crude product and stir to dissolve the sodium chloride in the crude product at room temperature. When all the salt is completely dissolved, stop stirring and let it stand for 20 to 40 minutes to separate the lower brine phase. The upper organic phase is distilled to obtain the product.

10. The method for preparing 2,2-dimethyl-1-oxa-4-thia-2-silacyclohexane-6-one according to claim 9, characterized in that: In step (3), the amount of water added is 50-80% of the mass of tert-butyl methyl ether.

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