A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether

Abstract

The invention discloses a continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether, and belongs to the technical field of organic synthesis. The present invention reacts 2,6-di-tert-butylphenol, paraformaldehyde and methanol under the action of dimethylamine methanol and piperazine mixed catalyst, and after methanol is recovered by rectification, 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether is obtained by crystallization suction filtration and drying; the crystallization filtrate recovered secondly can be directly circulated for the recovery of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether and methanol. The present invention uses dimethylamine methanol and piperazine as catalysts, synergistic catalysis, effectively reducing the generation of by-products, and the product yield can reach 95.75%, and the purity can reach 96.6%. The crystallization filtrate of the synthesis method of the present invention is circulated, and the product and solvent can be fully recovered, and the loss and cost saving can be reduced; continuous production is adopted, there is no purification section, the operation steps and energy consumption are reduced, and the production requirements of green chemical industry are met.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether. Background Art

[0002] Antioxidant 330 is an antioxidant widely used in rubber, plastic, lubricant and other fields. It can effectively prevent the performance degradation of materials due to oxidation during processing, storage and use. At present, the mainstream industrial synthesis scheme of antioxidant 330 is: firstly react 2,6-di-tert-butylphenol and polyformaldehyde in the presence of alkaline catalyst to generate 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether (i.e. benzyl ether intermediate), and then react the benzyl ether intermediate with mesitylene to obtain antioxidant 330.

[0003] 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether is a key precursor for the synthesis of antioxidant 330, and the choice of its synthesis reaction directly determines the yield of antioxidant 330 products. However, the traditional preparation method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether has problems such as long reaction time, low product purity, large amount of solvent, and environmental pollution, which limits its application in large-scale production. Studies have found that the choice of catalyst largely determines the product quality of benzyl ether intermediates. The existing technology mostly uses organic bases as reaction catalysts, which usually have problems of low product yield and low purity; there is also a problem of high content of by-product 4,4'-methylenebis(2,6-di-tert-butylphenol) (antioxidant 702), which can reach about 5%. Because its properties are similar to those of benzyl ether intermediates, it is difficult to separate. Reducing the production of by-products can further improve the purity of benzyl ether intermediates. Therefore, screening more efficient catalysts, improving the synthesis process, and continuously improving purity and yield are important for the industrial production of benzyl ether intermediates.

[0004] CN114181054A discloses a method for synthesizing 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether, using potassium tert-butoxide as a catalyst, first depolymerizing polyformaldehyde, then dropping methanol and 2,6-di-tert-butylphenol solution under normal pressure for synthesis reaction, cooling, crystallization, filtering and drying, to obtain a product yield of 82.4%, and the purity is not mentioned. The conversion rate of 2,6-di-tert-butylphenol by the alkaline catalyst is only about 90%, the selectivity for 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether is low, and the by-product 4,4'-methylenebis (2,6-di-tert-butylphenol) is difficult to separate, resulting in low product purity. Secondly, the solvent methanol volatilization amount is large under normal pressure, resulting in a large amount of solvent loss, intermittent production, and the catalyst is difficult to recycle.

[0005] CN101665416A discloses a method for synthesizing 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether, which uses a polyamine with a high boiling point and low volatility as a catalyst to catalyze the reaction of 2,6-di-tert-butylphenol, formaldehyde and methanol to synthesize 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether. In this method, the conversion rate of the catalyst to 2,6-di-tert-butylphenol reaches 99%, and the selectivity is also above 90%, but the production is intermittent, and the purity and yield of the benzyl ether are not mentioned.

[0006] Yin Zhenyan (Yin Zhenyan, Li Yanyun, Zhu Jiudi. Synthesis of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether at atmospheric pressure [J]. Chemical Reagents, 2009, 31(04): 280-282.) used 33% dimethylamine aqueous solution as a catalyst for the synthesis reaction, and the yield was only 83.8%. Studies have found that water enrichment will have a certain inhibitory effect on the synthesis, and dimethylamine is highly volatile in aqueous solution, which is easy to cause environmental pollution. Summary of the invention

[0007] The present invention aims at the deficiencies of the above-mentioned prior art and provides a continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether. 2,6-di-tert-butylphenol, paraformaldehyde and methanol are reacted under the action of a mixed catalyst of dimethylamine methanol and piperazine. After methanol is recovered by rectification, 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether is obtained by crystallization, suction filtration and drying. The recovered crystallization filtrate can be directly circulated to recover 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether and methanol. The synthesis method of the present invention is simple to operate, can significantly improve the purity and yield of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether, effectively reduce the generation of by-products, and the crystallization filtrate is circulated and applied, which can maximize the product yield and recover the solvent, reduce production loss, save production costs, and meet the production requirements of green chemical industry.

[0008] In order to achieve the above objectives, this scheme adopts the following technical solutions:

[0009] A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether specifically comprises the following steps:

[0010] (1) Mixing 2,6-di-tert-butylphenol, methanol and paraformaldehyde in a high-pressure reactor, and then adding a dimethylamine methanol solution and a piperazine mixed catalyst to react at a reaction temperature of 70-90° C. and a reactor pressure of 0.12-0.16 Mpa to obtain a reaction liquid;

[0011] (2) distilling the reaction solution obtained in step (1) to recover methanol and obtain a concentrated mother liquor;

[0012] (3) The concentrated mother liquor obtained in step (2) is filtered through crystallization, and after the crystallization filtrate is recovered, the filter cake obtained is dried to prepare 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether.

[0013] Furthermore, in step (1), the weight ratio of 2,6-di-tert-butylphenol, methanol and paraformaldehyde is 20-30:100:5.5-7.

[0014] Furthermore, in step (1), the mass ratio of the mixed catalyst to 2,6-di-tert-butylphenol is 1:2-3.

[0015] Furthermore, in step (1), the mass ratio of the dimethylamine methanol solution to piperazine is 100:4-6; and the concentration of the dimethylamine methanol solution is 1.5-2.5 mol / L.

[0016] Furthermore, the reaction time of step (1) is 4-7 h.

[0017] Furthermore, the distillation conditions in step (2) are normal pressure and the tower temperature is 60-80° C.; and the amount of methanol recovered is 55-65% of the initial amount added.

[0018] Furthermore, in step (3), the crystallization temperature is 15-25°C and the time is 1-2 h.

[0019] Furthermore, in step (3), the drying temperature is 70-90° C. and the drying time is 1.5-4 h.

[0020] Furthermore, the crystallization filtrate in step (3) can be subjected to steps (2) and (3) in sequence, and the filtrate can be utilized in a continuous cycle.

[0021] Beneficial effects:

[0022] (1) The present invention uses a methanol solution of dimethylamine as a catalyst, without adding water, so that volatility is improved and catalytic effect is enhanced. Moreover, the reaction solvent is methanol, and dimethylamine can be recovered and reused in the methanol recovery process. Meanwhile, piperazine is added as a catalyst, and its cyclic secondary amine structure forms a field effect that promotes the synthesis of surrounding molecules. In addition, piperazine itself is non-volatile, so the volatility of dimethylamine can be reduced, and a synergistic effect is exhibited in catalysis, which significantly improves the yield and purity of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether. The product yield can reach 95.75%, and the purity can reach 96.6%.

[0023] (2) The synthesis of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether will inevitably produce a by-product, 4,4'-methylenebis(2,6-di-tert-butylphenol). The catalyst reaction system used in this process is mild, which greatly reduces the output of 4,4'-methylenebis(2,6-di-tert-butylphenol), has little effect on the synthesis of antioxidant 330, and is easy to separate in the post-treatment section of antioxidant 330.

[0024] (3) Methanol as a solvent produces a large amount of waste liquid in the crystallization stage. The crystallization filtrate of this process can be recycled to recover the solvent to the maximum extent, reduce losses and save costs.

[0025] (4) This process adopts continuous production, omitting the intermediate benzyl ether purification stage, minimizing energy consumption and meeting the production requirements of green chemical industry. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The figure is a schematic diagram of the continuous synthesis process of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether. DETAILED DESCRIPTION

[0027] The following will combine the contents in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Example 1

[0029] A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether specifically comprises the following steps:

[0030] (1) In a 250 ml autoclave, 24.76 g of 2,6-di-tert-butylphenol, 100 ml of methanol and 5.7 g of paraformaldehyde were mixed, and then 10 ml of a 2 mol / L dimethylamine methanol solution and 0.5 g of piperazine were added respectively. The temperature was adjusted to 80°C, and the autoclave pressure was maintained at an autogenerated pressure of 0.145 MPa. After reacting for 5.5 h, a reaction solution was obtained.

[0031] (2) adding the reaction solution obtained in step (1) into a methanol distillation tower to distill and recover 60% of the methanol at 75° C. under normal pressure to obtain a concentrated mother liquor;

[0032] (3) adding the concentrated mother liquor obtained in step (2) into a crystallization kettle, cooling to 20° C., crystallizing for 1 hour, and filtering by suction. After the crystallization filtrate is recovered, the filter cake is dried in a forced air drying oven at 80° C. for 2 hours to obtain 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether;

[0033] (4) The crystallization filtrate obtained in step (3) was subjected to steps (2) and (3) in sequence for 5 consecutive cycles to obtain 6 batches of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether in total.

[0034] The above-synthesized 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether was sampled respectively, and the purity and yield were analyzed by liquid chromatography. The purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether are shown in Table 1. The present invention uses dimethylamine methanol solution as a catalyst, anhydrous addition, improved volatility, improved catalytic effect, and the reaction solvent is methanol, and dimethylamine can be recycled and reused with the methanol recovery process; at the same time, piperazine is added as a catalyst, and its cyclic secondary amine structure forms a field effect to promote the synthesis of surrounding molecules. In addition, piperazine itself is non-volatile, which can reduce the volatility of dimethylamine, and shows a synergistic effect in catalysis, significantly improving the yield and purity of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether, and the synthesis process of the present invention is stable, and the obtained product can be directly used for the synthesis of antioxidant 330.

[0035] The content of by-product 4,4'-methylenebis(2,6-di-tert-butylphenol) in each batch of products was determined with reference to Q / FSJYH 0005-2017 "Antioxidant JY-702". The content of by-product 4,4'-methylenebis(2,6-di-tert-butylphenol) in each batch of products was determined as shown in Table 1. Compared with the existing synthesis method, the process reaction system of the present invention is mild, the content of 4,4'-methylenebis(2,6-di-tert-butylphenol) is reduced, and the purity of the product 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether is further improved.

[0036] Table 1 Indices of different batches of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether

[0037]

[0038] Comparative Example 1

[0039] A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether specifically comprises the following steps:

[0040] (1) In a 250 ml autoclave, 24.76 g of 2,6-di-tert-butylphenol, 100 ml of methanol and 5.7 g of paraformaldehyde were mixed, and then 10 ml of a 2 mol / L dimethylamine methanol solution was added. The temperature was adjusted to 80°C, and the autoclave pressure was maintained at an autogenerated pressure of 0.145 MPa. After reacting for 5.5 h, a reaction solution was obtained.

[0041] (2) adding the reaction solution obtained in step (1) into a methanol distillation tower and distilling at 75° C. at normal pressure to recover 60% methanol to obtain a concentrated mother liquor;

[0042] (3) adding the concentrated mother liquor obtained in step (2) into a crystallization kettle, cooling to 20° C., crystallizing for 1 hour, and filtering by suction. After the crystallization filtrate is recovered, the filter cake is dried in a forced air drying oven at 80° C. for 2 hours to obtain 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether;

[0043] (4) The crystallization filtrate obtained in step (3) was subjected to steps (2) and (3) in sequence for 5 consecutive cycles to obtain 6 batches of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether in total.

[0044] The above-synthesized 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether was sampled and analyzed by liquid chromatography for purity and yield. The purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether are shown in Table 2. It can be seen that the yield and purity of the product decreased to varying degrees by removing the use of piperazine as a catalyst.

[0045] Table 2 Purity and yield of different batches of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether

[0046]

[0047] Comparative Example 2

[0048] A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether specifically comprises the following steps:

[0049] (1) In a 250 ml autoclave, 24.76 g of 2,6-di-tert-butylphenol, 100 ml of methanol and 5.7 g of paraformaldehyde were mixed, and then 0.27 g of sodium methoxide was added respectively. The temperature was adjusted to 80°C, and the autoclave pressure was maintained at an autogenerated pressure of 0.145 MPa. After reacting for 5.5 h, a reaction solution was obtained.

[0050] (2) adding the reaction solution obtained in step (1) into a methanol distillation tower and distilling at 75° C. at normal pressure to recover 60% methanol to obtain a concentrated mother liquor;

[0051] (3) adding the concentrated mother liquor obtained in step (2) into a crystallization kettle, cooling to 20° C., crystallizing for 1 hour, and filtering by suction. After the crystallization filtrate is recovered, the filter cake is dried in a forced air drying oven at 80° C. for 2 hours to obtain 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether;

[0052] (4) The crystallization filtrate obtained in step (3) was subjected to steps (2) and (3) in sequence for 5 consecutive cycles to obtain 6 batches of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether in total.

[0053] The above-synthesized 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether was sampled and analyzed for purity and yield using liquid chromatography, and the purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether are shown in Table 3. It can be seen that the use of sodium methoxide as a catalyst alone can significantly improve the yield of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether, but it will greatly reduce the purity of the product.

[0054] Table 3 Purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether

[0055]

[0056] Comparative Example 3

[0057] A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether specifically comprises the following steps:

[0058] (1) In a 250 ml autoclave, 24.76 g of 2,6-di-tert-butylphenol, 100 ml of methanol and 5.7 g of paraformaldehyde were mixed, and then 10 ml of dimethylamine methanol solution and 0.5 g of piperazine were added respectively. The temperature was adjusted to 70°C, and the autoclave pressure was maintained at an autogenerated pressure of 0.145 MPa. After reacting for 5.5 h, a reaction solution was obtained.

[0059] (2) adding the reaction solution obtained in step (1) into a methanol distillation tower and distilling at 75° C. at normal pressure to recover 60% methanol to obtain a concentrated mother liquor;

[0060] (3) adding the concentrated mother liquor obtained in step (2) into a crystallization kettle, cooling to 20° C., crystallizing for 1 h, and filtering by suction. After the crystallization filtrate is recovered, the filter cake is dried in a forced air drying oven at 80° C. for 2 h to obtain 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether;

[0061] (4) The crystallization filtrate obtained in step (3) was subjected to steps (2) and (3) in sequence for 5 consecutive cycles to obtain 6 batches of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether in total.

[0062] The above-synthesized 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether was sampled separately, and the purity and yield were tested and analyzed by liquid chromatography. The purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether are shown in Table 4. The appropriate temperature is conducive to the full progress of the reaction.

[0063] Table 4 Purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether

[0064]

[0065] Comparative Example 4

[0066] A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether specifically comprises the following steps:

[0067] (1) In a 250 ml glass flask, 24.76 g of 2,6-di-tert-butylphenol, 100 ml of methanol and 5.7 g of paraformaldehyde were mixed, and then 10 ml of dimethylamine methanol solution and 0.5 g of piperazine were added respectively. The temperature was adjusted to 80°C, and the mixture was refluxed at normal pressure for 5.5 h to obtain a reaction solution.

[0068] (2) adding the reaction solution obtained in step (1) into a methanol distillation tower and distilling at 75° C. at normal pressure to recover 60% methanol to obtain a concentrated mother liquor;

[0069] (3) adding the concentrated mother liquor obtained in step (2) into a crystallization kettle, cooling to 20° C., crystallizing for 1 hour, and filtering by suction. After the crystallization filtrate is recovered, the filter cake is dried in a forced air drying oven at 80° C. for 2 hours to obtain 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether;

[0070] (4) The crystallization filtrate obtained in step (3) was subjected to steps (2) and (3) in sequence for 5 consecutive cycles to obtain 6 batches of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether in total.

[0071] The above-synthesized 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether was sampled separately, and the purity and yield were tested and analyzed by liquid chromatography. The purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether are shown in Table 5. Changing the reaction vessel and reducing the reaction pressure will reduce the product purity and yield.

[0072] Table 5 Purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether

[0073]

[0074] Comparative Example 5

[0075] A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether specifically comprises the following steps:

[0076] (1) In a 250 ml autoclave, 24.76 g of 2,6-di-tert-butylphenol, 100 ml of methanol and 5.04 g of paraformaldehyde were mixed, and then 10 ml of dimethylamine methanol solution and 0.5 g of piperazine were added respectively. The temperature was adjusted to 80°C, and the autoclave pressure was maintained at an autogenerated pressure of 0.145 MPa. After reacting for 5.5 h, a reaction solution was obtained.

[0077] (2) adding the reaction solution obtained in step (1) into a methanol distillation tower and distilling at 75° C. at normal pressure to recover 60% methanol to obtain a concentrated mother liquor;

[0078] (3) adding the concentrated mother liquor obtained in step (2) into a crystallization kettle, cooling to 20° C., crystallizing for 1 hour, and filtering by suction. After the crystallization filtrate is recovered, the filter cake is dried in a forced air drying oven at 80° C. for 2 hours to obtain 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether;

[0079] (4) The crystallization filtrate obtained in step (3) was subjected to steps (2) and (3) in sequence for 5 consecutive cycles to obtain 6 batches of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether in total.

[0080] The above-synthesized 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether was sampled and analyzed by liquid chromatography for purity and yield. The purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether are shown in Table 6. It can be seen that reducing the amount of paraformaldehyde added will reduce the purity and yield of the product.

[0081] Table 6 Purity and yield of each batch of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether

[0082]

Claims

1. A continuous synthesis method of 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether, characterized in that: The method comprises the following steps: (1) Mixing 2,6-di-tert-butylphenol, methanol and polyformaldehyde in a high-pressure reactor, then adding dimethylamine methanol solution and piperazine mixed catalyst to react, the reaction temperature is 80° C., the reactor pressure is 0.12-0.16 Mpa, and a reaction liquid is obtained; the weight ratio of the 2,6-di-tert-butylphenol, methanol and polyformaldehyde is 20-30:100:5.5-7; the mass ratio of the mixed catalyst to 2,6-di-tert-butylphenol is 1:2-3; the mass ratio of the dimethylamine methanol solution to piperazine is 100:4-6; the concentration of the dimethylamine methanol solution is 1.5-2.5 mol / L; (2) distilling the reaction solution obtained in step (1) to recover methanol and obtain a concentrated mother liquor; (3) The concentrated mother liquor obtained in step (2) is filtered through crystallization, and after the crystallization filtrate is recovered, the filter cake obtained is dried to prepare 3,5-di-tert-butyl-4-hydroxybenzyl methyl ether; the crystallization filtrate can be sequentially subjected to steps (2) and (3), and the filtrate can be continuously circulated for utilization.

2. The continuous synthesis method according to claim 1, characterized in that: The reaction time of step (1) is 4-7 h.

3. The continuous synthesis method according to claim 1, characterized in that: The distillation conditions in step (2) are normal pressure and the tower temperature is 60-80°C.

4. The continuous synthesis method according to claim 1, characterized in that: The amount of methanol recovered in step (2) is 55-65% of the initial amount added.

5. The continuous synthesis method according to claim 1, characterized in that: In step (3), the crystallization temperature is 15-25°C and the crystallization time is 1-2 h; the drying temperature is 70-90°C and the drying time is 1.5-4 h.

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