Preparation method of 3, 5-di-tert-butyl benzyl alcohol

Abstract

The invention discloses a preparation method of 3, 5-di-tert-butyl benzyl alcohol, and belongs to the technical field of organic synthesis. According to the method, 1, 3, 5-tri-tert-butylbenzene and formaldehyde are taken as raw materials, and the 3, 5-di-tert-butyl benzyl alcohol is synthesized by a one-step method under the action of two lewis acid catalysts, namely a boron-containing lewis acid catalyst and a thiourea catalyst, and a salt auxiliary agent, namely anhydrous zinc acetate. The yield of the 3, 5-di-tert-butyl benzyl alcohol prepared by the method disclosed by the invention is 71-83%, and the product purity is gt; the content is 99.0%.

Description

Technical Field

[0001] The invention relates to a preparation method of 3,5-di-tert-butylbenzyl alcohol and belongs to the technical field of organic synthesis. Background Art

[0002] 3,5-Di-tert-butylbenzyl alcohol is a widely used chemical raw material. It can be used as a pharmaceutical intermediate, a pesticide intermediate, and can also be used to synthesize a variety of polymer additives. In addition, this compound is also used for foreign trade exports and has certain demand and applications in the international market.

[0003] Due to its specific chemical properties, the 3,5-di-tert-butylbenzene ring has a large steric hindrance. When two 3,5-di-tert-butylbenzyl alcohols are connected by linear organic molecules, large steric hindrances at both ends are formed, which can be used as excellent template compounds. The linear molecule in the middle can directly graft active groups on the linear chain, or coat a variety of cyclic molecules on the linear chain (the cyclic molecules can translate on the linear chain) to synthesize a variety of supramolecular structure compounds for applications such as drugs, dyes, and molecular probes (Angewandte Chemie-International Edition, 2004, 43, 3260-3264).

[0004] The synthesis process of 3,5-di-tert-butylbenzyl alcohol reported at home and abroad mainly includes: reduction reaction of 3,5-di-tert-butylbenzaldehyde (Chemical Communications, 2019, 55, 4427-4430; Chemical Science, 2017, 8, 4739-4749) or reduction of 3,5-di-tert-butylbenzoic acid / 3,5-di-tert-butylbenzoate (Organic Letters, 2001, 3, 2485-2487; Chemical Communications, 2014, 50, 11378-11381; Angewandte Chemie-International Edition, 2004, 43, 3260-3264) or hydrolysis reaction of 3,5-di-tert-butylbenzyl chloride / bromine (Journal of Organic Chemistry, 2003, 43, 3260-3264). Chemistry, 2011, 76, 6264-6270); the above synthesis method has the defects of generating a large amount of hydrogen when the reducing agent is quenched, which has certain safety hazards, and the chlorine / brombenzyl raw materials have irritating tastes.

[0005] In view of the defects of the above technical route, it is necessary to conduct in-depth research on the synthesis route of 3,5-di-tert-butylbenzyl alcohol to provide a better, easy-to-obtain raw material, simple, safe, stable and economical process route to meet the growing market demand. Summary of the invention

[0006] In order to overcome the above technical defects, the present invention provides a method for preparing 3,5-di-tert-butylbenzyl alcohol. 1,3,5-s-tri-tert-butylbenzene and formaldehyde are used as raw materials, and 3,5-di-tert-butylbenzyl alcohol is synthesized in one step under the action of two Lewis acid catalysts, a boron-containing Lewis acid catalyst and a thiourea catalyst and a salt auxiliary anhydrous zinc acetate. The yield of preparing 3,5-di-tert-butylbenzyl alcohol by the method of the present invention is 71-83%, and the product purity is >99.0%.

[0007] The preparation method of 3,5-di-tert-butylbenzyl alcohol of the present invention comprises the following steps:

[0008]

[0009] 1,3,5-tri-tert-butylbenzene and formaldehyde are used as raw materials, and the temperature is increased in an organic solvent in the presence of a mixed catalyst and a salt auxiliary agent. After the reaction is completed, the filtrate is filtered and distilled under reduced pressure to obtain 3,5-di-tert-butylbenzyl alcohol.

[0010] Furthermore, in the above technical solution, the organic solvent is selected from toluene, xylene or anisole, preferably anisole.

[0011] Furthermore, in the above technical solution, the formaldehyde is selected from triformaldehyde or paraformaldehyde, preferably paraformaldehyde.

[0012] Furthermore, in the above technical solution, the mixed catalyst is a combination of a boron-containing Lewis acid catalyst and a thiourea catalyst.

[0013] Furthermore, in the above technical solution, the boron-containing Lewis acid catalyst is selected from triphenylborane or tri(pentafluorophenyl)borane; preferably tri(pentafluorophenyl)borane.

[0014] Furthermore, in the above technical solution, the thiourea catalyst is selected from N,N'-diphenylthiourea, N,N'-di-o-tolylthiourea or 1,3-di(p-tolyl)thiourea; preferably N,N'-diphenylthiourea.

[0015] Furthermore, in the above technical solution, the salt auxiliary agent is selected from anhydrous sodium acetate, anhydrous potassium acetate or anhydrous zinc acetate; preferably anhydrous zinc acetate.

[0016] Furthermore, in the above technical solution, the molar ratio of the 1,3,5-tri-tert-butylbenzene, formaldehyde, boron-containing Lewis acid catalyst, thiourea catalyst and salt additive is 1: 1.1-1.8: 0.05-0.12: 0.03-0.07: 0.05-0.10.

[0017] Furthermore, in the above technical solution, the temperature of the temperature-raising reaction is selected from 60-90° C. The present invention has the following beneficial effects:

[0018] The present invention adopts a one-step synthesis method and adopts a dual catalyst for synergistic catalysis. While catalyzing the deisobutylene, the addition reaction of formaldehyde is carried out to generate a benzyl alcohol product, thereby reducing the occurrence of side reactions and improving the catalytic efficiency. At the same time, the raw materials of 1,3,5-tri-tert-butylbenzene and formaldehyde are cheap and easily available, which has certain cost advantages.

[0019] The mechanism of action of the salt additive is speculated to be: it assists the catalyst to form a better and more stable catalytic intermediate state for synergistic catalysis, improves the catalytic effect, has good reaction parallelism, and has high parallelism of multiple test data. Specific embodiments

[0020] The present invention will be further described below by specific examples. These embodiments should be understood to be only used to illustrate the present invention and not to limit the scope of protection of the present invention. After reading the content of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

[0021] Example 1

[0022] Under nitrogen protection, 24.6 g (0.1 mol) of 1,3,5-tri-tert-butylbenzene and 130 mL of anisole were added to the reaction bottle, and then 3.7 g (0.12 mol) of polyformaldehyde, 3.1 g (0.006 mol) of tri(pentafluorophenyl)borane, 1.14 g (0.005 mol) of N,N'-diphenylthiourea and 1.28 g (0.007 mol) of anhydrous zinc acetate were added. After stirring and mixing, the reaction system was heated to 60 ° C for 7 h. GC detection showed that 1,3,5-tri-tert-butylbenzene was completely converted. The mixture was cooled to room temperature, the reaction solution was filtered, and the filtrate was distilled under reduced pressure to obtain 18.3 g of product 3,5-di-tert-butylbenzyl alcohol, which became solid after cooling. The yield was 83%, and the GC was 99.3%. 1 HNMR(400MHz, CDCl3):7.21-7.35(m,3H),4.65(m,2H),1.36(s,18H).

[0023] Example 2

[0024] Under nitrogen protection, 24.6 g (0.1 mol) of 1,3,5-tri-tert-butylbenzene and 130 mL of toluene were added to the reaction bottle, and then 4.3 g (0.14 mol) of paraformaldehyde, 2.9 g (0.012 mol) of triphenylborane, 1.8 g (0.007 mol) of N,N'-di-o-tolylthiourea and 1.28 g (0.007 mol) of anhydrous zinc acetate were added. After stirring and mixing, the reaction system was heated to 80°C for 10 h. GC detection showed that 1,3,5-tri-tert-butylbenzene was completely converted. The temperature was cooled to room temperature, the reaction solution was filtered, and the filtrate was distilled under reduced pressure to obtain 17.2 g of 3,5-di-tert-butylbenzyl alcohol, which became solid after cooling. The yield was 78%, and the GC was 99.1%.

[0025] Example 3

[0026] Under nitrogen protection, 24.6 g (0.1 mol) of 1,3,5-tri-tert-butylbenzene and 130 mL of xylene were added to the reaction bottle, and then 3.4 g (0.11 mol) of paraformaldehyde, 2.6 g (0.005 mol) of tri(pentafluorophenyl)borane, 0.8 g (0.003 mol) of 1,3-di(p-tolyl)thiourea and 0.8 g (0.01 mol) of anhydrous sodium acetate were added. After stirring and mixing, the reaction system was heated to 80°C for 10 h. GC detection showed that 1,3,5-tri-tert-butylbenzene was completely converted. The temperature was cooled to room temperature, the reaction solution was filtered, and the filtrate was distilled under reduced pressure to obtain 16.2 g of 3,5-di-tert-butylbenzyl alcohol, which became solid after cooling. The yield was 74%, and the GC was 99.2%.

[0027] Example 4

[0028] Under nitrogen protection, 24.6 g (0.1 mol) of 1,3,5-tri-tert-butylbenzene and 130 mL of anisole were added to the reaction bottle, and then 4.3 g (0.14 mol) of paraformaldehyde, 2.4 g (0.01 mol) of triphenylborane, 1.6 g (0.007 mol) of N,N'-diphenylthiourea and 1.0 g (0.01 mol) of anhydrous potassium acetate were added. After stirring and mixing, the reaction system was heated to 70 ° C for 7 h. GC detection showed that 1,3,5-tri-tert-butylbenzene was completely converted. The temperature was cooled to room temperature, the reaction solution was filtered, and the filtrate was distilled under reduced pressure to obtain 15.6 g of 3,5-di-tert-butylbenzyl alcohol, which became solid after cooling. The yield was 71%, and the GC was 99.1%.

[0029] The operation of Example 1 was adopted, 24.6 g (0.1 mol) of 1,3,5-tri-tert-butylbenzene, 130 mL of anisole and 3.7 g (0.12 mol) of paraformaldehyde were added, and the amounts of catalyst and salt auxiliary agent were adjusted. The reaction results were as follows:

[0030]

[0031]

[0032] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for preparing 3,5-di-tert-butylbenzyl alcohol, characterized in that: The method comprises the following steps: taking 1,3,5-tri-tert-butylbenzene and formaldehyde as raw materials, heating and reacting in an organic solvent in the presence of a mixed catalyst and a salt auxiliary agent, filtering after the reaction is completed, and distilling the filtrate under reduced pressure to obtain 3,5-di-tert-butylbenzyl alcohol.

2. The method for preparing 3,5-di-tert-butylbenzyl alcohol according to claim 1, characterized in that: The organic solvent is selected from toluene, xylene or anisole, preferably anisole.

3. The method for preparing 3,5-di-tert-butylbenzyl alcohol according to claim 1, characterized in that: The formaldehyde is selected from triformaldehyde or polyformaldehyde, preferably polyformaldehyde.

4. The method for preparing 3,5-di-tert-butylbenzyl alcohol according to claim 1, characterized in that: The mixed catalyst is a combination of a boron-containing Lewis acid catalyst and a thiourea catalyst.

5. The method for preparing 3,5-di-tert-butylbenzyl alcohol according to claim 4, characterized in that: The boron-containing Lewis acid catalyst is selected from triphenylborane or tri(pentafluorophenyl)borane; preferably tri(pentafluorophenyl)borane.

6. The method for preparing 3,5-di-tert-butylbenzyl alcohol according to claim 1, characterized in that: The thiourea catalyst is selected from N,N'-diphenylthiourea, N,N'-di-o-tolylthiourea or 1,3-di(p-tolyl)thiourea; preferably N,N'-diphenylthiourea.

7. The method for preparing 3,5-di-tert-butylbenzyl alcohol according to claim 1, characterized in that: The salt auxiliary agent is selected from anhydrous sodium acetate, anhydrous potassium acetate or anhydrous zinc acetate; preferably anhydrous zinc acetate.

8. The method for preparing 3,5-di-tert-butylbenzyl alcohol according to claim 4, characterized in that: The molar ratio of the 1,3,5-s-tri-tert-butylbenzene, formaldehyde, boron-containing Lewis acid catalyst, thiourea catalyst and salt auxiliary agent is 1: 1.1-1.8: 0.05-0.12: 0.03-0.07: 0.05-0.

10.

9. The method for preparing 3,5-di-tert-butylbenzyl alcohol according to claim 1, characterized in that: The temperature of the temperature-raising reaction is selected from 60-90°C.

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