Preparation method of 3-methylbutane-1, 3-dithiol

Abstract

The invention belongs to the field of organic synthesis, and relates to a preparation method of 3-methyl butane-1, 3-dithiol. The preparation method comprises the following steps: carrying out substitution reaction on isoprene glycol and hydrobromic acid to obtain 1, 3-dibromo-3-methyl butane; the preparation method comprises the following steps: carrying out a substitution cyclization reaction on 1, 3-dibromo-3-methyl butane and disodium disulfide under the catalytic action of a phase transfer catalyst to obtain 3, 3-dimethyl-1, 2-dithiocyclopentane; the method comprises the following steps: in a zinc powder-acetic acid system, heating 3, 3-dimethyl-1, 2-dithiolane to 35-45 DEG C, and carrying out reduction cracking reaction for 10-14 hours, so as to obtain the 3-methylbutane-1, 3-dithiol. The preparation method provided by the invention has the advantages of low material cost, simple process flow, greenness, safety, high production efficiency and the like.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis and relates to a method for preparing 3-methylbutane-1,3-dithiol. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] 3-Methylbutane-1,3-dithiol is a spice with a unique aroma of roasted meat and coffee. It has excellent aroma quality and lasting fragrance. It is internationally recognized as safe and harmless. This spice can be widely used in the field of food and beverages. With the development of the economy, its usage will continue to increase. It is a very promising spice product. However, the preparation method of 3-methylbutane-1,3-dithiol is rarely reported in the literature. Therefore, it is of great significance to develop an efficient and low-cost preparation method.

[0004] The current synthesis method of 3-methylbutane-1,3-dithiol is as follows:

[0005] This synthesis method uses 3-methyl-2-butenal as raw material and synthesizes 3-methylbutane-1,3-dithiol through four steps of reaction. The total yield is only 16%. The starting material 3-methyl-2-butenal is relatively expensive (4,000 yuan / kg). Other reagents used in the process, such as sodium borohydride, sodium hydride, liquid ammonia, and metallic sodium, are highly dangerous and are not suitable for industrial production. Summary of the invention

[0006] In order to solve the deficiencies of the prior art, the purpose of the present invention is to provide a method for preparing 3-methylbutane-1,3-dithiol, which has the advantages of low material cost, simple process flow, green safety, high production efficiency, etc.

[0007] In order to achieve the above object, the technical solution of the present invention is: A preparation method of 3-methylbutane-1,3-dithiol comprises the following steps: subjecting isopentyl glycol and hydrobromic acid to a substitution reaction to obtain 1,3-dibromo-3-methylbutane; subjecting 1,3-dibromo-3-methylbutane and disodium disulfide to a substitution cyclization reaction under the catalytic action of a phase transfer catalyst to obtain 3,3-dimethyl-1,2-dithiolane; and in a zinc powder-acetic acid system, heating 3,3-dimethyl-1,2-dithiolane to 35-45° C. to perform a reduction cracking reaction for 10-14 h to obtain 3-methylbutane-1,3-dithiol.

[0008] The reaction route is as follows:

[0009] In the reduction cracking reaction of 3,3-dimethyl-1,2-dithiolane, there are a variety of reduction systems, such as lithium aluminum hydroxide-tetrahydrofuran, sodium borohydride-methanol, etc. However, 3,3-dimethyl-1,2-dithiolane itself can form insoluble polymers by depolymerization and repolymerization. At the same time, it is easy to produce insoluble polymers after cracking, thereby affecting subsequent cracking, and there is a problem of difficulty in complete cracking. The present invention has shown through research that in the reduction cracking reaction of 3,3-dimethyl-1,2-dithiolane, a zinc powder-acetic acid reduction system is used, and the reaction is carried out at 35-45°C for 10-14 hours, and the cracking can be complete, the efficiency is high, and the product yield is higher.

[0010] In some embodiments, the mass ratio of zinc powder, acetic acid and 3,3-dimethyl-1,2-dithiolane is 250-350:550-650:100-150.

[0011] In some embodiments, after the reduction cleavage reaction, filtration is performed, tert-butyl hydroquinone is added to the filtrate, acetic acid is removed by vacuum distillation, and then vacuum distillation is performed. Specifically, the amount of tert-butyl hydroquinone added is 0.8-1.2% of the mass of the generated 3-methylbutane-1,3-dithiol. Adding tert-butyl hydroquinone can avoid the polymerization of 3-methylbutane-1,3-dithiol in the subsequent treatment process, thereby ensuring the yield of 3-methylbutane-1,3-dithiol.

[0012] In some embodiments, a phase transfer catalyst is added to the sodium disulfide aqueous solution, and then 1,3-dibromo-3-methylbutane is added dropwise, and then a substitution ring-closure reaction is carried out. Since the sodium disulfide aqueous solution is prone to chemical reactions after preparation, which affects its use effect, it is generally prepared on the spot. After preparing the sodium disulfide aqueous solution, the general operating procedure is to drop the sodium disulfide aqueous solution into the halide. However, when the sodium disulfide aqueous solution is added dropwise during the reaction process of the present invention, it has a deterioration problem during the transfer process, which increases the amount of raw materials used to prepare the sodium disulfide aqueous solution. Therefore, the present invention adds 1,3-dibromo-3-methylbutane to the sodium disulfide aqueous solution, which not only avoids the transfer process of the sodium disulfide aqueous solution, simplifies the operation process, and avoids the deterioration problem that the sodium disulfide aqueous solution may have during the transfer process, but also minimizes the use of sodium sulfide and sulfur powder. Specifically, the phase transfer catalyst is tetrabutylammonium bromide.

[0013] Specifically, the preparation process of the disodium disulfide aqueous solution is: heating the sodium sulfide solution to 65-75°C, adding sulfur powder, and reacting to obtain the disodium disulfide aqueous solution. More specifically, the molar ratio of sodium sulfide to sulfur powder is 1:0.9-1.1.

[0014] Specifically, the reaction time after the dropwise addition of 1,3-dibromo-3-methylbutane is completed is 10 to 20 minutes.

[0015] In some embodiments, the temperature of the substitution ring-closure reaction is 65-75 °C.

[0016] In some embodiments, the molar ratio of 1,3-dibromo-3-methylbutane to disodium disulfide is 1:0.9-1.1.

[0017] In some embodiments, the purification process after the substitution ring-closure reaction is: standing to separate the liquid, drying the upper organic phase with anhydrous sodium sulfate, and filtering.

[0018] In some embodiments, isopentyl glycol is added to a solution of hydrogen bromide in acetic acid, the temperature is raised to 75-85° C., and the reaction is carried out for 7-9 hours to obtain 1,3-dibromo-3-methylbutane.

[0019] In some embodiments, after the substitution reaction, the liquid is allowed to stand and separated, and the lower layer of liquid is washed with a saturated sodium bicarbonate aqueous solution until it becomes neutral, namely 1,3-dibromo-3-methylbutane.

[0020] The beneficial effects of the present invention are: The present invention uses low-priced isopentyl glycol as a raw material (100 yuan / kg) and synthesizes 3-methylbutane-1,3-dithiol through three steps of reaction. The purity of the product is as high as more than 99%, and the total yield is 77%. The method has the advantages of low material cost, simple process flow, green safety, high production efficiency, etc. DETAILED DESCRIPTION

[0021] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments and comparative examples.

[0022] Example 1 1. Preparation of 1,3-dibromo-3-methylbutane: Add 100 g of isopentyl glycol and 560 g of 33% hydrogen bromide in acetic acid solution to the reaction flask, heat to 80 ° C, stir and react for 8 hours, cool the reaction solution to room temperature, stand and separate, wash the lower layer with saturated sodium bicarbonate aqueous solution until neutral, and obtain 210 g of colorless clear liquid with gas phase purity of 98.3% and yield of 95.1%.

[0023] 2. Preparation of 3,3-dimethyl-1,2-dithiolane: Add 210g of water and 220g of sodium sulfide nine hydrate to the reaction bottle, heat to 70°C, and stir until dissolved. Add 29.3g of sulfur powder and stir again until dissolved. Cool to room temperature, add 1g of tetrabutylammonium bromide, and start dripping 210g of 1,3-dibromo-3-methylbutane obtained in step 1, and control the dripping rate to make the reaction liquid temperature below 70°C. After dripping, control the temperature at 70°C and stir the reaction for 15 minutes. Stir the reaction liquid to room temperature, let it stand and separate, dry the upper organic phase with anhydrous sodium sulfate overnight, filter, and obtain 121g of yellow clear liquid, gas phase purity 90.4%, yield 89.2%.

[0024] 3. Preparation of 3-methylbutane-1,3-dithiol: Add 294 g of zinc powder, 605 g of acetic acid and 121 g of 3,3-dimethyl-1,2-dithiolane obtained in step 2 to the reaction bottle, heat to 40 ° C, stir and react for 12 hours, filter the reaction solution, add 1.2 g of tert-butylhydroquinone to the filtrate, distill under reduced pressure to remove the solvent acetic acid, distill the concentrate under reduced pressure, collect the fraction at 80-86 ° C at a pressure of 15 Torr, and obtain 101 g of 3-methylbutane-1,3-dithiol finished product with a gas phase purity of 99.1% and a yield of 91.0%.

[0025] 1 H NMR (400MHz, CDCl3) δppm: 2.51-2.57(m,2H), 1.77-1.81(m,2H), 1.40(s,6H). 13 C-NMR (100MHz, CDCl3) δppm: 51.4, 44.2, 31.5, 19.5. GC-MS m / z: 41(90), 47(52), 61(30), 69(100), 75(3), 87(2), 102(60),136(45).

[0026] Example 2 3. Preparation of 3-methylbutane-1,3-dithiol: According to the method of Example 1, 1,3-dibromo-3-methylbutane and 3,3-dimethyl-1,2-dithiolane were prepared in sequence.

[0027] Add 235 g of zinc powder, 605 g of acetic acid and 121 g of 3,3-dimethyl-1,2-dithiolane (gas phase purity 90.5%) obtained in the previous step to the reaction bottle, heat to 40 ° C, stir and react for 12 hours, filter the reaction solution, add 1.2 g of tert-butylhydroquinone to the filtrate, distill under reduced pressure to remove the solvent acetic acid, distill the concentrated solution under reduced pressure, collect the fraction at 80-86 ° C at a pressure of 15 Torr, and obtain 94 g of 3-methylbutane-1,3-dithiol finished product with a gas phase purity of 99.0% and a yield of 84.6%.

[0028] Example 3 3. Preparation of 3-methylbutane-1,3-dithiol: According to the method of Example 1, 1,3-dibromo-3-methylbutane and 3,3-dimethyl-1,2-dithiolane were prepared in sequence.

[0029] To the reaction flask, 353 g of zinc powder, 605 g of acetic acid and 121 g of 3,3-dimethyl-1,2-dithiolane (gas phase purity 90.5%) obtained in the previous step were added, the temperature was raised to 40°C, the reaction was stirred for 12 hours, the reaction solution was filtered, 1.2 g of tert-butylhydroquinone was added to the filtrate, the solvent acetic acid was removed by vacuum distillation, the concentrated solution was vacuum distilled, and the fractions at 80-86°C were collected at a pressure of 15 Torr to obtain 100 g of 3-methylbutane-1,3-dithiol finished product with a gas phase purity of 99.2% and a yield of 90.0%.

[0030] Example 4 2. Preparation of 3,3-dimethyl-1,2-dithiolane: Add 210g of water and 220g of sodium sulfide nine hydrate to the reaction bottle, heat to 70°C, and stir until dissolved. Add 29.3g of sulfur powder and stir again until dissolved. Cool to room temperature, add 2g of tetrabutylammonium bromide, and start dripping 210g of 1,3-dibromo-3-methylbutane (gas phase purity 98.6%) obtained in the previous step, and control the dripping rate to make the reaction liquid temperature below 70°C. After dripping, control the temperature at 70°C and stir the reaction for 15 minutes. Stir the reaction liquid to room temperature, let it stand and separate, dry the upper organic phase with anhydrous sodium sulfate overnight, filter, and obtain 122g of yellow liquid, gas phase purity 89.8%, yield 89.3%.

[0031] Comparative Example 1 2. Preparation of 3,3-dimethyl-1,2-dithiolane: Add 210g of water and 220g of sodium sulfide nine hydrate to the reaction bottle, heat to 70°C, and stir until dissolved. Add 29.3g of sulfur powder and stir again until dissolved. Cool to room temperature and transfer the reaction solution to a constant pressure dropping funnel. Take another reaction bottle and add 1g of tetrabutylammonium bromide and 210g of 1,3-dibromo-3-methylbutane obtained in step 1 of Example 1. Start dripping the prepared disodium disulfide aqueous solution under stirring, and control the dripping rate so that the temperature of the reaction solution is lower than 70°C. After the dripping, control the temperature at 70°C and stir the reaction for 15min. Stir the reaction solution and cool it to room temperature, let it stand for separation, dry the upper organic phase with anhydrous sodium sulfate overnight, filter, and obtain 105g of yellow clear liquid, gas phase purity 90.1%, yield 77.1%.

[0032] Compared with Example 1, the only difference in the addition method was the dropwise addition of a disodium disulfide aqueous solution, and the reaction yield was significantly reduced.

[0033] Comparative Example 2 2. Preparation of 3,3-dimethyl-1,2-dithiolane: Add 210g of water and 220g of sodium sulfide nine hydrate to the reaction bottle, heat to 70°C, and stir until dissolved. Add 29.3g of sulfur powder and stir again until dissolved. Cool to room temperature, start dripping 210g of 1,3-dibromo-3-methylbutane (gas phase purity 98.6%) obtained in the previous step, and control the dripping rate to make the reaction liquid temperature below 70°C. After dripping, control the temperature at 70°C and stir the reaction for 5 hours. Stir the reaction liquid to room temperature, let it stand and separate the liquids, dry the upper organic phase with anhydrous sodium sulfate overnight, filter, and obtain 113g of yellow liquid with a gas phase purity of 73.7% and a yield of 67.9%.

[0034] Compared with Example 1, this comparative example does not add tetrabutylammonium bromide as a phase transfer catalyst, which not only reduces the purity but also significantly reduces the yield.

[0035] Comparative Example 3 3. Preparation of 3-methylbutane-1,3-dithiol: Add 34.3g of lithium aluminum tetrahydride and 605g of anhydrous tetrahydrofuran to the reaction bottle, stir and cool to 10°C. Slowly drip 121g of 3,3-dimethyl-1,2-dithiocyclopentane obtained in step 2 of Example 1, heat to 40°C after dripping, and stir to react for 24 hours. Cool to 0°C, slowly drip 240g of saturated ammonium chloride aqueous solution to quench the reaction. Add 240g of 20% hydrochloric acid, stir for 0.5 hours, and stand for separation. The aqueous phase is extracted with 120g of methyl tert-butyl ether. After the organic phase is mixed, 1.2g of tert-butyl hydroquinone is added, and the solvent methyl tert-butyl ether is removed by vacuum distillation. The concentrate is vacuum distilled, and the fraction of 80~86°C is collected at a pressure of 15Torr to obtain 81g of 3-methylbutane-1,3-dithiol finished product, with a gas phase purity of 98.7% and a yield of 67%.

[0036] Comparative Example 4 3. Preparation of 3-methylbutane-1,3-dithiol: Add 34.2g of sodium borohydride and 605g of anhydrous methanol to the reaction bottle, stir and cool to 0°C. Slowly drip 121g of 3,3-dimethyl-1,2-dithiocyclopentane obtained in step 2 of Example 1, control the temperature at 10°C after dripping, and stir the reaction for 24 hours. Slowly drip 240g of saturated ammonium chloride aqueous solution to quench the reaction. Add 120g of 10% hydrochloric acid, stir for 0.5 hour, then add 240g of methyl tert-butyl ether, stir for 0.5 hour, and stand for separation. The aqueous phase is extracted with 240g of methyl tert-butyl ether. After the organic phase is mixed, 1.2g of tert-butyl hydroquinone is added, and the solvent methyl tert-butyl ether is removed by vacuum distillation. The concentrate is vacuum distilled, and the fraction of 80~86°C is collected at a pressure of 15Torr to obtain 64g of 3-methylbutane-1,3-dithiol finished product, with a gas phase purity of 98.2% and a yield of 53%.

[0037] Compared with Example 1, Comparative Examples 3 and 4 changed the reduction system, and the yield of 3-methylbutane-1,3-dithiol was significantly reduced.

[0038] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing 3-methylbutane-1,3-dithiol, characterized in that: Isopentyldiol is reacted with hydrobromic acid to obtain 1,3-dibromo-3-methylbutane; 1,3-dibromo-3-methylbutane is reacted with disodium disulfide under the catalysis of a phase transfer catalyst to undergo a substitution cyclization reaction to obtain 3,3-dimethyl-1,2-dithiolane; in a zinc powder-acetic acid system, 3,3-dimethyl-1,2-dithiolane is heated to 35-45°C for a reduction cleavage reaction for 10-14 h to obtain 3-methylbutane-1,3-dithiol.

2. The method for preparing 3-methylbutane-1,3-dithiol according to claim 1, characterized in that: The mass ratio of zinc powder, acetic acid and 3-dimethyl-1,2-dithiolane is 250~350:550~650:100~150.

3. The method for preparing 3-methylbutane-1,3-dithiol according to claim 1, characterized in that: After the reduction cleavage reaction, the product is filtered, tert-butylhydroquinone is added to the filtrate, acetic acid is removed by vacuum distillation, and then vacuum rectification is performed.

4. The method for preparing 3-methylbutane-1,3-dithiol as claimed in claim 3, characterized in that: The amount of tert-butylhydroquinone added is 0.8-1.2% of the mass of the generated 3-methylbutane-1,3-dithiol.

5. The method for preparing 3-methylbutane-1,3-dithiol according to claim 1, characterized in that: A phase transfer catalyst is added to a disodium disulfide aqueous solution, and then 1,3-dibromo-3-methylbutane is added dropwise, and then a substitution ring-closure reaction is carried out.

6. The method for preparing 3-methylbutane-1,3-dithiol as claimed in claim 5, characterized in that: The preparation process of disodium disulfide aqueous solution is as follows: heat the sodium sulfide solution to 65~75 ℃, add sulfur powder, and react to obtain the product.

7. The method for preparing 3-methylbutane-1,3-dithiol as claimed in claim 5, characterized in that: The reaction time after the completion of 1,3-dibromo-3-methylbutane is 10~20 min.

8. The method for preparing 3-methylbutane-1,3-dithiol according to claim 1, characterized in that: The temperature of the substitution ring-closure reaction is 65~75 ℃.

9. The method for preparing 3-methylbutane-1,3-dithiol according to claim 1, characterized in that: The molar ratio of 1,3-dibromo-3-methylbutane to disodium disulfide is 1:0.9~1.

1.

10. The method for preparing 3-methylbutane-1,3-dithiol according to claim 1, characterized in that: Add isopentyl glycol to the acetic acid solution of hydrogen bromide, raise the temperature to 75-85 °C, and react for 7-9 hours to obtain 1,3-dibromo-3-methylbutane.

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