Preparation method of 1-methylbenzocyclobutene

Abstract

The invention belongs to the technical field of dielectric material monomer synthesis, and discloses a preparation method of 1-methylbenzocyclobutene, which comprises the following steps: reacting 1-hydroxybenzocyclobutene serving as a raw material with paratoluensulfonyl chloride (TsCl) to generate 1-paratoluensulfonyloxy benzocyclobutene, then reacting with methylmagnesium chloride under the action of a catalyst to obtain 1-paratoluensulfonyloxy benzocyclobutene; the target product 1-methylbenzocyclobutene is synthesized mainly by controlling the reaction temperature, the feeding sequence and the feeding proportion under the relatively mild condition, and the method is simple in technological operation, mild in experimental condition, high in product yield and suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of dielectric material monomer synthesis, and in particular to a method for preparing 1-methylbenzocyclobutene. Background Art

[0002] 1-Methylbenzocyclobutene is a dielectric material monomer with excellent physical properties, chemical stability, high temperature stability and other characteristics, and can be widely used in the fields of electronics, microelectronics industry manufacturing, etc. At present, there are generally two methods for preparing 1-methylbenzocyclobutene, one is to use 1-hydroxymethylbenzocyclobutene and p-toluenesulfonyl chloride and then use lithium aluminum hydride reduction, or to use 1-vinylbenzocyclobutene hydrogenation reduction preparation, both of which involve reduction reactions, have high industrial scale-up risk factors, are inconvenient to prepare, and have low production efficiency. Summary of the invention

[0003] The present invention is intended to provide a method for preparing 1-methylbenzocyclobutene to solve the technical problems raised in the above background technology.

[0004] In order to achieve the above object, the present invention provides the following technical solutions: A method for preparing 1-methylbenzocyclobutene comprises the following steps: S1: prepare raw materials; The raw materials include 1-hydroxybenzocyclobutene, dichloromethane, triethylamine, p-toluenesulfonyl chloride, tetrahydrofuran, ferric acetylacetonate, methylmagnesium chloride THF solution, saturated ammonium chloride solution and ethyl acetate; S2: Preparation of 1-p-toluenesulfonyloxybenzocyclobutene; Prepare a reaction bottle, add 1-hydroxybenzocyclobutene and dichloromethane into the reaction bottle, stir the solution to make 1-hydroxybenzocyclobutene completely dissolved in dichloromethane, then add triethylamine, then add p-toluenesulfonyl chloride, and then keep warm for 1-2 hours to obtain a reaction solution, detect whether the chemical reaction is completely completed, pour the reaction solution after the chemical reaction is completely completed into ice water, stir for 30 minutes, stand and separate, extract the reaction solution after separation to obtain an organic phase and an aqueous phase, wash, dry, filter and concentrate the organic phase to obtain 1-toluenesulfonyloxybenzocyclobutene.

[0005] S3: Preparation of 1-methylbenzocyclobutene; Prepare a three-necked flask, add the 1-toluenesulfonyloxybenzocyclobutene obtained in step S2 into the flask, then add tetrahydrofuran, then stir to completely dissolve the 1-toluenesulfonyloxybenzocyclobutene, then add ferric acetylacetonate, cool the system to -20°C, then drop methylmagnesium chloride THF solution into the flask, wait for it to react for 2 hours under an environment of -30°C to -20°C to obtain a preliminary product, detect whether the chemical reaction is completely completed, pour the preliminary product after the chemical reaction is completely completed into a saturated ammonium chloride solution for acidification, wait for the preliminary product to be completely acidified, add ethyl acetate to the preliminary product, stir and then stand, wait for the solution to be layered to obtain an organic phase and an aqueous phase, separate the organic phase and the aqueous phase, extract the obtained aqueous phase with ethyl acetate to obtain an organic phase remaining in the aqueous phase, combine the obtained organic phases, wash, dry, concentrate and distill the organic phases to obtain 1-methylbenzocyclobutene.

[0006] Preferably, in step S2, the mass volume ratio of 1-hydroxybenzocyclobutene to dichloromethane is 1 g:5-10 mL, and the molar ratio of 1-hydroxybenzocyclobutene, triethylamine, and p-toluenesulfonyl chloride is 1:1.2-1.7:1-1.4.

[0007] Preferably, in step S3, the mass volume ratio of 1-toluenesulfonyloxybenzocyclobutene to tetrahydrofuran is 1 g: 5-8 mL, and the molar ratio of 1-toluenesulfonyloxybenzocyclobutene, ferric acetylacetonate, and methylmagnesium chloride THF solution is 1: 0.005-0.01: 1.0-1.5.

[0008] Preferably, in step S2, p-toluenesulfonyl chloride is added in batches, and the temperature during the addition process is -10°C to -5°C.

[0009] Preferably, in step S2, the organic phase is first washed with HCl, then washed with a saturated sodium bicarbonate aqueous solution, and finally washed with saturated brine, and dried over anhydrous magnesium sulfate.

[0010] Preferably, in step S3, the methylmagnesium chloride THF solution is dripped into the flask using a constant pressure dropping funnel, and the temperature of the reaction system is -30°C to -20°C when the methylmagnesium chloride THF solution is added.

[0011] Preferably, in step S2 and step S3, thin layer chromatography is used to detect whether the reaction is completely completed.

[0012] Preferably, in step S3, the organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, and purified by reduced pressure distillation using a high vacuum oil pump.

[0013] The beneficial effects of this technical solution are: (1) This technical solution changes the preparation raw materials, using 1-hydroxybenzocyclobutene as the raw material, reacting with p-toluenesulfonyl chloride and other substances to generate the target product (1-methylbenzocyclobutene). By setting the reaction temperature and the feeding steps, 1-methylbenzocyclobutene is synthesized under relatively mild conditions. The raw materials used are low-cost and easy to obtain, which greatly reduces the production cost; the experimental conditions are mild, the process operation is simple, the industrial scale-up risk factor is greatly reduced, and it is suitable for industrial production; the input ratio of each substance is optimized, which greatly improves the product generation rate and improves the preparation efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 The hydrogen nuclear magnetic resonance spectrum of 1-methylbenzocyclobutene synthesized by the present invention; DETAILED DESCRIPTION

[0015] The applicant will further explain the present invention in detail below in conjunction with specific examples, with the aim of enabling those skilled in the art to more clearly understand the present invention, but the following content should not be construed in any way as limiting the scope of protection sought in the claims of this application. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used can all be obtained from commercial channels: Example 1

[0016] A method for preparing 1-methylbenzocyclobutene comprises the following steps: S1: prepare raw materials; The raw materials include 1-hydroxybenzocyclobutene, dichloromethane, triethylamine, p-toluenesulfonyl chloride, tetrahydrofuran, ferric acetylacetonate, methylmagnesium chloride THF solution, saturated ammonium chloride solution and ethyl acetate; the remaining experimental instruments such as reaction bottles, flasks, etc. are also prepared before starting the operation. The raw materials prepared in S1 of this application are the substances required for the chemical reaction of preparing the target product; S2: Preparation of 1-p-toluenesulfonyloxybenzocyclobutene; Prepare a 250ml reaction bottle, add 12.0g (100mmol) of 1-hydroxybenzocyclobutene into the reaction bottle, then add 100ml of dichloromethane, stir the solution to make 1-hydroxybenzocyclobutene completely dissolved in dichloromethane, then add 20.85ml of triethylamine (150mmol), then add 22.88g of p-toluenesulfonyl chloride (120mmol), add p-toluenesulfonyl chloride into the reaction bottle in batches, control the feeding temperature at -10°C, that is, the solution in the reaction bottle is lowered to -10°C, then add toluenesulfonyl chloride into the reaction bottle, keep the temperature of the reaction system at -10°C when adding toluenesulfonyl chloride, then make the substances in the reaction bottle heat-insulated in an ice-salt bath at -10°C for 1-2 hours, detect whether the reaction is complete by thin layer chromatography, and obtain a reaction solution after the chemical reaction is complete; The reaction solution was poured into 200 ml of ice water, stirred for 30 minutes, and allowed to stand for stratification. The stratified reaction solution was extracted to obtain an organic phase and an aqueous phase, and then the organic phase was washed with 100 ml of 1N HCl, 100 ml of a saturated sodium bicarbonate aqueous solution and saturated brine in sequence. The washed organic phase was then dried over anhydrous magnesium sulfate, filtered, concentrated and the solvent removed to obtain 1-toluenesulfonyloxybenzocyclobutene.

[0017] S3: Preparation of 1-methylbenzocyclobutene; Prepare a three-necked flask, add 13.72 g (50 mmol) of 1-toluenesulfonyloxybenzocyclobutene obtained in step S2 into the flask, then add 60 ml of tetrahydrofuran, then stir to dissolve the 1-toluenesulfonyloxybenzocyclobutene, then add 0.088 g of ferric acetylacetonate (0.25 mmol), cool the reaction system to -20°C, that is, cool the reaction material in the flask to -20°C, then add 32.5 ml of 2M methylmagnesium chloride THF solution (65 mmol) into the flask, and use a constant pressure dropping funnel to drop the methylmagnesium chloride THF solution into the flask during the addition of the methylmagnesium chloride THF solution. The temperature of the reaction system is maintained at -20°C during the addition of the methylmagnesium chloride THF solution; then wait for the solution to react for 2 hours at -20°C, and detect whether the chemical reaction is completely completed by thin layer chromatography. After the reaction is completely completed, a preliminary product is obtained; Then the preliminary product was slowly poured into 100 ml of saturated ammonium chloride solution for acidification. After the acidification was completed, the acidified preliminary product was obtained. 60 ml of ethyl acetate was added to the acidified preliminary product, stirred and then allowed to stand, waiting for the solution to separate, and then extracted to obtain an organic phase and an aqueous phase. The obtained aqueous phase was extracted again with 100 ml of ethyl acetate, and the organic phases obtained from the two extractions were combined. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to remove the solvent to obtain a crude product, which was then distilled under reduced pressure by a high vacuum oil pump to obtain the target product 1-methylbenzocyclobutene, and 4.72 g of an oily liquid was obtained, with a total yield of 70%.

[0018] The temperature control of the reaction system is all controlled by an ice-salt bath. Controlling the temperature of the reaction system by an ice-salt bath is a common conventional technique in the art and will not be described in detail here. Example 2

[0019] A method for preparing 1-methylbenzocyclobutene comprises the following steps: S1: prepare raw materials; The raw materials include 1-hydroxybenzocyclobutene, dichloromethane, triethylamine, p-toluenesulfonyl chloride, tetrahydrofuran, ferric acetylacetonate, methylmagnesium chloride THF solution, saturated ammonium chloride solution and ethyl acetate; the remaining experimental instruments such as reaction bottles, flasks, etc. are also prepared before starting the operation. The raw materials prepared in S1 of this application are the substances required for the chemical reaction of preparing the target product; S2: Preparation of 1-p-toluenesulfonyloxybenzocyclobutene; Prepare a 250ml reaction bottle, add 12.0g (100mmol) of 1-hydroxybenzocyclobutene to the reaction bottle, then add 100ml of dichloromethane, stir the solution to make 1-hydroxybenzocyclobutene completely dissolved in dichloromethane, then add 20.85ml of triethylamine (150mmol), then add 22.88g of p-toluenesulfonyl chloride (115mmol), add p-toluenesulfonyl chloride to the reaction bottle in batches, control the feeding temperature at -10°C, that is, the solution in the reaction bottle is lowered to -10°C, then add p-toluenesulfonyl chloride to the reaction bottle, keep the temperature of the reaction system at -10°C when adding p-toluenesulfonyl chloride, then make the substances in the reaction bottle heat-insulated in an ice-salt bath at -10°C for 1-2 hours, detect whether the reaction is complete by thin layer chromatography, and obtain a reaction solution after the chemical reaction is complete; The reaction solution was poured into 200 ml of ice water, stirred for 30 minutes, and allowed to stand for stratification. The stratified reaction solution was extracted to obtain an organic phase and an aqueous phase, and then the organic phase was washed with 100 ml of 1N HCl, 100 ml of a saturated sodium bicarbonate aqueous solution and saturated brine in sequence. The washed organic phase was then dried over anhydrous magnesium sulfate, filtered, concentrated and the solvent removed to obtain 1-toluenesulfonyloxybenzocyclobutene.

[0020] S3: Preparation of 1-methylbenzocyclobutene; Prepare a three-necked flask, add 13.72 g (50 mmol) of 1-toluenesulfonyloxybenzocyclobutene obtained in step S2 into the flask, then add 60 ml of tetrahydrofuran, then stir to dissolve the 1-toluenesulfonyloxybenzocyclobutene, then add 0.088 g of ferric acetylacetonate (0.25 mmol), cool the reaction system to -20°C, that is, cool the reaction material in the flask to -20°C, then add 32.5 ml of 2M methylmagnesium chloride THF solution (65 mmol) into the flask, and use a constant pressure dropping funnel to drop the methylmagnesium chloride THF solution into the flask during the addition of the methylmagnesium chloride THF solution. The temperature of the reaction system is maintained at -20°C during the dropwise addition of the methylmagnesium chloride THF solution; then reduce the temperature of the reaction system to -25°C, and then react the reaction system at -25°C for 2 hours, and detect whether the chemical reaction is completely completed by thin layer chromatography, and obtain a preliminary product after the reaction is completely completed; Then the preliminary product was slowly poured into 100 ml of saturated ammonium chloride solution for acidification. After the acidification was completed, the acidified preliminary product was obtained. 60 ml of ethyl acetate was added to the acidified preliminary product, stirred and then allowed to stand, waiting for the solution to separate, and then extracted to obtain an organic phase and an aqueous phase. The obtained aqueous phase was extracted again with 100 ml of ethyl acetate, and the organic phases obtained from the two extractions were combined. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to remove the solvent to obtain a crude product, which was then distilled under reduced pressure by a high vacuum oil pump to obtain the target product 1-methylbenzocyclobutene, and 4.59 g of an oily liquid was obtained, with a total yield of 68%.

[0021] According to the comparison between Example 2 and Example 1, when the reaction temperature changes, it will affect the chemical reaction of the substance, thereby affecting the finished product conversion rate. Example 3

[0022] A method for preparing 1-methylbenzocyclobutene comprises the following steps: S1: prepare raw materials; The raw materials include 1-hydroxybenzocyclobutene, dichloromethane, triethylamine, p-toluenesulfonyl chloride, tetrahydrofuran, ferric acetylacetonate, methylmagnesium chloride THF solution, saturated ammonium chloride solution and ethyl acetate; the remaining experimental instruments such as reaction bottles, flasks, etc. are also prepared before starting the operation. The raw materials prepared in S1 of this application are the substances required for the chemical reaction of preparing the target product; S2: Preparation of 1-p-toluenesulfonyloxybenzocyclobutene; Prepare a 250ml reaction bottle, add 12.0g (100mmol) of 1-hydroxybenzocyclobutene to the reaction bottle, then add 100ml of dichloromethane, stir the solution to make 1-hydroxybenzocyclobutene completely dissolved in dichloromethane, then add 22.24ml of triethylamine (160mmol), then add 24.80g of p-toluenesulfonyl chloride (130mmol), add p-toluenesulfonyl chloride to the reaction bottle in batches, control the feeding temperature at -10°C, that is, the solution in the reaction bottle is lowered to -10°C, then add p-toluenesulfonyl chloride to the reaction bottle, keep the temperature of the reaction system at -10°C when adding p-toluenesulfonyl chloride, then make the substances in the reaction bottle heat-insulated in an ice-salt bath at -10°C for 1-2 hours, detect whether the reaction is complete by thin layer chromatography, and obtain a reaction solution after the chemical reaction is complete; The reaction solution was poured into 200 ml of ice water, stirred for 30 minutes, and allowed to stand for stratification. The stratified reaction solution was extracted to obtain an organic phase and an aqueous phase, and then the organic phase was washed with 100 ml of 1N HCl, 100 ml of a saturated sodium bicarbonate aqueous solution and saturated brine in sequence. The washed organic phase was then dried over anhydrous magnesium sulfate, filtered, concentrated and the solvent removed to obtain 1-toluenesulfonyloxybenzocyclobutene.

[0023] S3: Preparation of 1-methylbenzocyclobutene; Prepare a three-necked flask, add 13.72 g (50 mmol) of 1-toluenesulfonyloxybenzocyclobutene obtained in step S2 into the flask, then add 60 ml of tetrahydrofuran, then stir to dissolve the 1-toluenesulfonyloxybenzocyclobutene, then add 0.088 g of ferric acetylacetonate (0.25 mmol), cool the reaction system to -20°C, that is, cool the reaction material in the flask to -20°C, then add 30 ml of 2M methylmagnesium chloride THF solution (60 mmol) into the flask, and use a constant pressure dropping funnel to drop the methylmagnesium chloride THF solution into the flask during the addition of the methylmagnesium chloride THF solution. The temperature of the reaction system is maintained at -20°C during the addition of the methylmagnesium chloride THF solution; then wait for the solution to react for 2 hours at -20°C, and detect whether the chemical reaction is completely completed by thin layer chromatography. After the reaction is completely completed, a preliminary product is obtained; Then the preliminary product was slowly poured into 100 ml of saturated ammonium chloride solution for acidification. After the acidification was completed, the acidified preliminary product was obtained. 60 ml of ethyl acetate was added to the acidified preliminary product, stirred and then allowed to stand, waiting for the solution to separate, and then extracted to obtain an organic phase and an aqueous phase. The obtained aqueous phase was extracted again with 100 ml of ethyl acetate, and the organic phases obtained from the two extractions were combined. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to remove the solvent to obtain a crude product, which was then distilled under reduced pressure with a high vacuum oil pump to obtain the target product 1-methylbenzocyclobutene, and 4.63 g of an oily liquid was obtained, with a total yield of 68.7%.

[0024] The technical solution proposed in the present application changes the raw materials and methods for preparing the target product, and completes the preparation of the target product with a completely new method. By limiting the reaction temperature and the addition steps, as well as the ratio of the reaction raw materials, 1-methylbenzocyclobutene is synthesized under relatively mild conditions. The raw materials used are low-cost and easy to obtain, which greatly reduces the production cost; the experimental conditions are mild, the process operation is simple, the industrial scale-up risk factor is greatly reduced, and it is suitable for industrial production; the input ratio of each substance is optimized, which greatly improves the product generation rate and improves the preparation efficiency.

[0025] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions and / or characteristics in the solution is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several modifications and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A method for preparing 1-methylbenzocyclobutene, characterized in that: The following steps are involved: S1: prepare raw materials; The raw materials include 1-hydroxybenzocyclobutene, dichloromethane, triethylamine, p-toluenesulfonyl chloride, tetrahydrofuran, ferric acetylacetonate, methylmagnesium chloride THF solution, saturated ammonium chloride solution and ethyl acetate; S2: Preparation of 1-p-toluenesulfonyloxybenzocyclobutene; Prepare a reaction bottle, add the 1-hydroxybenzocyclobutene and dichloromethane into the reaction bottle, stir the solution to make the 1-hydroxybenzocyclobutene completely dissolved in the dichloromethane, then add triethylamine, then add p-toluenesulfonyl chloride, then keep warm at a temperature of -10°C to -5°C for 1-2 hours to obtain a reaction solution, detect whether the chemical reaction is completely completed, pour the reaction solution after the chemical reaction is completely completed into ice water, stir for 30 minutes, stand and separate, extract the reaction solution after separation to obtain an organic phase and an aqueous phase, wash, dry, filter and concentrate the organic phase to obtain 1-toluenesulfonyloxybenzocyclobutene; S3: Preparation of 1-methylbenzocyclobutene; Prepare a three-necked flask, add the 1-toluenesulfonyloxybenzocyclobutene obtained in step S2 into the flask, then add tetrahydrofuran, stir to dissolve the 1-toluenesulfonyloxybenzocyclobutene, then add ferric acetylacetonate, cool the reaction system to -20°C, then drop a methylmagnesium chloride THF solution into the flask, wait for it to react for 2 hours at -30°C to -20°C to obtain a preliminary product, detect whether the chemical reaction is completely completed, pour the preliminary product after the chemical reaction is completely completed into a saturated ammonium chloride solution for acidification, wait for the preliminary product to be completely acidified, add ethyl acetate to the preliminary product, stir and then stand, wait for the solution to be layered to obtain an organic phase and an aqueous phase, separate the organic phase and the aqueous phase, extract the obtained aqueous phase with ethyl acetate to obtain an organic phase remaining in the aqueous phase, combine the obtained organic phases, wash, dry, concentrate and distill the organic phases to obtain 1-methylbenzocyclobutene.

2. The method for preparing 1-methylbenzocyclobutene according to claim 1, wherein: In the step S2, the mass volume ratio of 1-hydroxybenzocyclobutene to dichloromethane is 1 g: 5-10 mL, and the molar ratio of 1-hydroxybenzocyclobutene, triethylamine, and p-toluenesulfonyl chloride is 1: 1.2-1.7: 1-1.

4.

3. A method for preparing 1-methylbenzocyclobutene as claimed in claim 1, characterized in that: In step S3, the mass volume ratio of 1-toluenesulfonyloxybenzocyclobutene to tetrahydrofuran is 1 g: 5-8 mL, and the molar ratio of 1-toluenesulfonyloxybenzocyclobutene, ferric acetylacetonate, and methylmagnesium chloride THF solution is 1: 0.005-0.01: 1.0-1.

5.

4. The method for preparing 1-methylbenzocyclobutene according to claim 1, wherein: In step S2, p-toluenesulfonyl chloride is added in batches, and the temperature of the reaction system during the addition process is -10°C to -5°C.

5. A method for preparing 1-methylbenzocyclobutene as claimed in claim 1, characterized in that: In the step S2, the organic phase is first washed with HCl, then washed with a saturated sodium bicarbonate aqueous solution, and finally washed with saturated brine, and dried over anhydrous magnesium sulfate.

6. The method for preparing 1-methylbenzocyclobutene according to claim 1, characterized in that: In the step S3, the methylmagnesium chloride THF solution is dripped into the flask using a constant pressure dropping funnel, and the temperature of the reaction system is -30°C to -20°C when the methylmagnesium chloride THF solution is dripped.

7. The method for preparing 1-methylbenzocyclobutene according to claim 1, characterized in that: In step S2 and step S3, thin layer chromatography is used to detect whether the reaction is completely completed.

8. The method for preparing 1-methylbenzocyclobutene according to claim 1, characterized in that: In the step S3, the organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, and purified by reduced pressure distillation using a high vacuum oil pump.

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