A method for preparing 3-methylbutane-1,3-dithiol

Abstract

The present invention belongs to the field of organic synthesis and relates to a preparation method of 3-methylbutane-1,3-dithiol. Isoamyl glycol is subjected to a substitution reaction with hydrobromic acid to obtain 1,3-dibromo-3-methylbutane; 1,3-dibromo-3-methylbutane and sodium disulfide are subjected to a substitution cyclization reaction under the catalysis of a phase transfer catalyst 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. The preparation method provided by the present invention has the advantages of low material cost, simple process flow, green safety, high production efficiency, etc.

Description

Technical Field

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

[0002] Disclosing the information of this background art section is only intended to enhance the understanding of the overall background of the present invention, and it is not necessarily regarded as an admission or an implication in any form that this information constitutes the prior art already known to those of ordinary skill in the art.

[0003] 3-Methylbutane-1,3-dithiol is a spice with unique roast meat and coffee scents. It has excellent fragrance quality and long-lasting fragrance retention. It is an internationally recognized safe and harmless spice. This spice can be widely used in the fields of food and beverages, and with the economic development, 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] Currently, the synthesis method of 3-methylbutane-1,3-dithiol is as follows:

[0005]

[0006] This synthesis method uses 3-methyl-2-butenal as the raw material and synthesizes 3-methylbutane-1,3-dithiol through 4 steps. The total yield is only 16%. The starting material 3-methyl-2-butenal is relatively expensive (4000 yuan / kg), and other reagents used in the process such as sodium borohydride, sodium hydride, liquid ammonia, metallic sodium, etc. are highly dangerous and not suitable for industrial production. Summary of the Invention

[0007] 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.

[0008] To achieve the above purpose, the technical solution of the present invention is as follows:

[0009] A method for preparing 3-methylbutane-1,3-dithiol, in which isopentyl glycol reacts with hydrobromic acid to obtain 1,3-dibromo-3-methylbutane; 1,3-dibromo-3-methylbutane reacts with sodium disulfide under the catalytic action of a phase transfer catalyst 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.

[0010] The reaction route is as follows:

[0011]

[0012] In the reduction cleavage reaction of 3,3-dimethyl-1,2-dithiolane, there are various reduction systems, such as lithium aluminum hydride-tetrahydrofuran, sodium borohydride-methanol, etc. However, 3,3-dimethyl-1,2-dithiolane itself can form insoluble polymers through depolymerization and repolymerization. At the same time, it is also prone to produce insoluble polymers after cleavage, thus affecting subsequent cleavage. There is a problem that it is difficult to achieve complete cleavage. Research by the present invention shows that in the reduction cleavage 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 h, then complete cleavage can be achieved, with high efficiency and higher product yield.

[0013] 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.

[0014] In some embodiments, after the reduction cleavage reaction, filtration is carried out, tert-butylhydroquinone is added to the filtrate, acetic acid is removed by vacuum distillation, and then vacuum rectification is carried out. Specifically, the addition amount of tert-butylhydroquinone is 0.8-1.2% of the mass of 3-methylbutane-1,3-dithiol generated. Adding tert-butylhydroquinone can avoid the polymerization of 3-methylbutane-1,3-dithiol during subsequent treatment and ensure the yield of 3-methylbutane-1,3-dithiol.

[0015] In some embodiments, a phase transfer catalyst is added to the aqueous solution of sodium disulfide, 1,3-dibromo-3-methylbutane is then added dropwise, and then a substitution cyclization reaction is carried out. Since the aqueous solution of sodium disulfide is prone to chemical reactions after preparation, affecting its use effect, it is generally prepared and used immediately. After preparing the aqueous solution of sodium disulfide, the general operation step is to dropwise add the aqueous solution of sodium disulfide to the halide. However, when dropping the aqueous solution of sodium disulfide during the reaction process of the present invention, there is a problem of deterioration during its transfer, increasing the usage amount of the raw materials for preparing the aqueous solution of sodium disulfide. Therefore, in the present invention, 1,3-dibromo-3-methylbutane is added dropwise to the aqueous solution of sodium disulfide, which not only avoids the transfer process of the aqueous solution of sodium disulfide, simplifies the operation process, but also avoids the possible deterioration problem of the aqueous solution of sodium disulfide during the transfer process, and at the same time minimizes the usage amount of sodium sulfide and sulfur powder. Specifically, the phase transfer catalyst is tetrabutylammonium bromide.

[0016] Specifically, the preparation process of the sodium disulfide aqueous solution is as follows: heat the sodium sulfide solution to 65-75 °C, add sulfur powder, and carry out the reaction to obtain it. More specifically, the molar ratio of sodium sulfide to sulfur powder is 1:0.9-1.1.

[0017] Specifically, the reaction time after the addition of 1,3-dibromo-3-methylbutane is completed is 10-20 min.

[0018] In some embodiments, the temperature of the substitution cyclization reaction is 65-75 °C.

[0019] In some embodiments, the molar ratio of 1,3-dibromo-3-methylbutane to sodium disulfide is 1:0.9-1.1.

[0020] In some embodiments, the purification process after the substitution cyclization reaction is as follows: let it stand for liquid separation, dry the upper organic phase with anhydrous sodium sulfate, and filter.

[0021] In some embodiments, add isopentylene glycol to the acetic acid solution of hydrogen bromide, heat up to 75-85 °C, and react for 7-9 h to obtain 1,3-dibromo-3-methylbutane.

[0022] In some embodiments, after the substitution reaction, let it stand for liquid separation, and wash the lower layer liquid with saturated sodium bicarbonate aqueous solution until neutral to obtain 1,3-dibromo-3-methylbutane.

[0023] The beneficial effects of the present invention are as follows:

[0024] The present invention uses inexpensive isopentylene glycol as the raw material (100 yuan / kg), synthesizes 3-methylbutane-1,3-dithiol through 3-step reactions, the product purity is over 99%, and the total yield is 77%. This method has the advantages of low material cost, simple process flow, green safety, and high production efficiency. Specific Embodiments

[0025] 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 combination with specific examples and comparative examples.

[0026] Example 1

[0027] I. Preparation of 1,3-dibromo-3-methylbutane:

[0028] Add 100 g of isopentylene glycol and 560 g of 33% acetic acid solution of hydrogen bromide to the reaction flask, heat up to 80 °C, stir and react for 8 hours. Let the obtained reaction solution cool to room temperature, stand for liquid separation, and wash the lower layer liquid with saturated sodium bicarbonate aqueous solution until neutral to obtain 210 g of colorless clear liquid, the gas phase purity is 98.3%, and the yield is 95.1%.

[0029] II. Preparation of 3,3-dimethyl-1,2-dithiolane:

[0030] Add 210 g of water and 220 g of sodium sulfide nonahydrate to the reaction flask, heat up to 70 °C, and stir until dissolved and clear. Add 29.3 g of sulfur powder and stir again until dissolved and clear. Cool to room temperature, add 1 g of tetrabutylammonium bromide, and start to dropwise add 210 g of 1,3-dibromo-3-methylbutane obtained in Step I, controlling the dropping rate to keep the temperature of the reaction solution below 70 °C. After dropping, stir and react at 70 °C for 15 minutes. Stir the reaction solution to cool to room temperature, let it stand for liquid separation, dry the upper organic phase with anhydrous sodium sulfate overnight, filter, and obtain 121 g of a yellow clear liquid with a gas phase purity of 90.4% and a yield of 89.2%.

[0031] III. Preparation of 3-methylbutane-1,3-dithiol:

[0032] Add 294 g of zinc powder, 605 g of acetic acid, and 121 g of 3,3-dimethyl-1,2-dithiolane obtained in Step II to the reaction flask, heat up to 40 °C, stir and react for 12 hours, filter the reaction solution, add 1.2 g of tert-butylhydroquinone to the filtrate, distill off the solvent acetic acid under reduced pressure, and subject the concentrated solution to vacuum rectification. Collect the fraction at 80 - 86 °C under a pressure of 15 Torr to obtain 101 g of the finished product of 3-methylbutane-1,3-dithiol with a gas phase purity of 99.1% and a yield of 91.0%.

[0033] 1 H NMR(400MHz, CDCl 3 ) δppm: 2.51 - 2.57(m,2H), 1.77 - 1.81(m,2H), 1.40(s,6H). 13 C-NMR(100MHz, CDCl 3 ) δppm: 51.4, 44.2, 31.5, 19.5.

[0034] GC-MS m / z: 41(90), 47(52), 61(30), 69(100), 75(3), 87(2), 102(60),136(45).

[0035] Example 2

[0036] III. Preparation of 3-methylbutane-1,3-dithiol:

[0037] Prepare 1,3-dibromo-3-methylbutane and 3,3-dimethyl-1,2-dithiolane in sequence according to the method of Example 1.

[0038] 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 flask. Heat the temperature to 40 °C and stir for 12 hours. Filter the reaction solution. Add 1.2 g of tert-butylhydroquinone to the filtrate. Remove the solvent acetic acid by vacuum distillation. Subject the concentrated solution to vacuum rectification and collect the fraction at 80 - 86 °C under a pressure of 15 Torr to obtain 94 g of 3-methylbutane-1,3-dithiol as the finished product with a gas-phase purity of 99.0% and a yield of 84.6%.

[0039] Example 3

[0040] III. Preparation of 3-methylbutane-1,3-dithiol:

[0041] Prepare 1,3-dibromo-3-methylbutane and 3,3-dimethyl-1,2-dithiolane successively according to the method of Example 1.

[0042] Add 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 to the reaction flask. Heat the temperature to 40 °C and stir for 12 hours. Filter the reaction solution. Add 1.2 g of tert-butylhydroquinone to the filtrate. Remove the solvent acetic acid by vacuum distillation. Subject the concentrated solution to vacuum rectification and collect the fraction at 80 - 86 °C under a pressure of 15 Torr to obtain 100 g of 3-methylbutane-1,3-dithiol as the finished product with a gas-phase purity of 99.2% and a yield of 90.0%.

[0043] Example 4

[0044] II. Preparation of 3,3-dimethyl-1,2-dithiolane:

[0045] Add 210 g of water and 220 g of sodium sulfide nonahydrate to the reaction flask. Heat the temperature to 70 °C and stir until it becomes clear. Add 29.3 g of sulfur powder and stir again until it becomes clear. Cool to room temperature, add 2 g of tetrabutylammonium bromide, and start to dropwise add 210 g of 1,3-dibromo-3-methylbutane (gas-phase purity 98.6%) obtained in the previous step, controlling the dropping rate to keep the temperature of the reaction solution below 70 °C. After the dropping is complete, control the temperature at 70 °C and stir for 15 minutes. Stir the reaction solution and cool to room temperature, then let it stand for liquid separation. Dry the upper organic phase with anhydrous sodium sulfate overnight, filter, to obtain 122 g of a yellow liquid with a gas-phase purity of 89.8% and a yield of 89.3%.

[0046] Comparative Example 1

[0047] II. Preparation of 3,3-dimethyl-1,2-dithiolane:

[0048] Add 210 g of water and 220 g of sodium sulfide nonahydrate to the reaction flask, heat up to 70 °C, and stir until dissolved and clear. Add 29.3 g of sulfur powder and stir again until dissolved and clear. Cool down to room temperature and transfer the reaction solution to a constant-pressure dropping funnel. Take another reaction flask, add 1 g of tetrabutylammonium bromide and 210 g of 1,3-dibromo-3-methylbutane obtained in Step 1 of Example 1, and start dropping the prepared aqueous solution of disodium disulfide while stirring, controlling the dropping rate to keep the temperature of the reaction solution below 70 °C. After dropping, stir and react at 70 °C for 15 min. Stir the reaction solution and cool it down to room temperature, then let it stand for liquid separation. The upper organic phase is dried over anhydrous sodium sulfate overnight, filtered, to obtain 105 g of a yellow clear liquid, with a gas-phase purity of 90.1% and a yield of 77.1%.

[0049] Compared with Example 1, in this comparative example, only the feeding method was changed to dropping the aqueous solution of disodium disulfide, and the reaction yield decreased significantly.

[0050] Comparative Example 2

[0051] II. Preparation of 3,3-dimethyl-1,2-dithiolane:

[0052] Add 210 g of water and 220 g of sodium sulfide nonahydrate to the reaction flask, heat up to 70 °C, and stir until dissolved and clear. Add 29.3 g of sulfur powder and stir again until dissolved and clear. Cool down to room temperature and start dropping 210 g of 1,3-dibromo-3-methylbutane (gas-phase purity 98.6%) obtained in the previous step, controlling the dropping rate to keep the temperature of the reaction solution below 70 °C. After dropping, stir and react at 70 °C for 5 hours. Stir the reaction solution and cool it down to room temperature, then let it stand for liquid separation. The upper organic phase is dried over anhydrous sodium sulfate overnight, filtered, to obtain 113 g of a yellow liquid, with a gas-phase purity of 73.7% and a yield of 67.9%.

[0053] Compared with Example 1, in this comparative example, tetrabutylammonium bromide was not added as a phase transfer catalyst, not only the purity decreased, but also the yield decreased significantly.

[0054] Comparative Example 3

[0055] III. Preparation of 3-methylbutane-1,3-dithiol:

[0056] Add 34.3 g of lithium aluminum hydride and 605 g of anhydrous tetrahydrofuran to the reaction flask, stir and cool down to 10 °C. Slowly dropwise add 121 g of 3,3-dimethyl-1,2-dithiolane obtained in Step 2 of Example 1. After the addition is complete, warm up to 40 °C and stir the reaction for 24 hours. Cool down to 0 °C, and slowly dropwise add 240 g of saturated ammonium chloride aqueous solution to quench the reaction. Add 240 g of 20% hydrochloric acid, stir for 0.5 hour, and let it stand for liquid separation. Extract the aqueous phase with 120 g of methyl tert-butyl ether. After mixing the organic phases, add 1.2 g of tert-butylhydroquinone, distill off the solvent methyl tert-butyl ether under reduced pressure, and subject the concentrated solution to vacuum rectification. Collect the fraction at 80 - 86 °C under a pressure of 15 Torr to obtain 81 g of the finished product of 3-methylbutane-1,3-dithiol, with a gas phase purity of 98.7% and a yield of 67%.

[0057] Comparative Example 4

[0058] III. Preparation of 3-methylbutane-1,3-dithiol:

[0059] Add 34.2 g of sodium borohydride and 605 g of anhydrous methanol to the reaction flask, stir and cool down to 0 °C. Slowly dropwise add 121 g of 3,3-dimethyl-1,2-dithiolane obtained in Step 2 of Example 1. After the addition is complete, control the temperature at 10 °C and stir the reaction for 24 hours. Slowly dropwise add 240 g of saturated ammonium chloride aqueous solution to quench the reaction. Add 120 g of 10% hydrochloric acid, stir for 0.5 hour, then add 240 g of methyl tert-butyl ether, stir for 0.5 hour, and let it stand for liquid separation. Extract the aqueous phase with 240 g of methyl tert-butyl ether. After mixing the organic phases, add 1.2 g of tert-butylhydroquinone, distill off the solvent methyl tert-butyl ether under reduced pressure, and subject the concentrated solution to vacuum rectification. Collect the fraction at 80 - 86 °C under a pressure of 15 Torr to obtain 64 g of the finished product of 3-methylbutane-1,3-dithiol, with a gas phase purity of 98.2% and a yield of 53%.

[0060] Compared with Example 1, in Comparative Example 3 and Comparative Example 4, the reduction system was changed, and the yield of 3-methylbutane-1,3-dithiol decreased significantly.

[0061] The above are only the preferred embodiments of the present invention and are not used to limit the present invention. For those skilled in the art, the present invention can have various modifications and changes. 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 and hydrobromic acid are subjected to substitution reaction to obtain 1,3-dibromo-3-methylbutane; 1,3-dibromo-3-methylbutane and disodium disulfide are subjected to substitution cyclization reaction under the catalysis of a phase transfer catalyst to obtain 3,3-dimethyl-1,2-dithiolane; 3,3-dimethyl-1,2-dithiolane is heated to 35-45°C in a zinc powder-acetic acid system to undergo a reduction cracking reaction for 10-14 h to obtain 3-methylbutane-1,3-dithiol; The mass ratio of zinc powder, acetic acid and 3,3-dimethyl-1,2-dithiolane is 250-350:550-650:100-150; 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; The phase transfer catalyst is tetrabutylammonium bromide.

2. 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.

3. The method for preparing 3-methylbutane-1,3-dithiol as claimed in claim 2, 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.

4. The method for preparing 3-methylbutane-1,3-dithiol according to claim 1, 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.

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

6. 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 ℃.

7. 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.

8. 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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