Preparation method of 4-hydroxybenzaldehyde
By generating an intermediate from cyclohexanone-4-carboxaldehyde under a Lewis acid catalyst, and then converting it to 4-hydroxybenzaldehyde using a palladium-on-carbon catalyst and potassium tert-butoxide, the problems of unavailable raw materials and complex steps in existing technologies are solved, and an efficient and economical synthetic route is realized.
Patent Information
- Application Number
- CN202411516379.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-29
- Publication Date
- 2025-02-07
AI Technical Summary
Existing synthetic routes for 4-hydroxybenzaldehyde suffer from problems such as the scarcity of raw materials, complex procedures, and high costs, making it difficult to meet market demand.
The intermediate is generated by cyclohexanone-4-carboxaldehyde under Lewis acid catalyst, and then reacted under palladium on carbon catalyst, potassium tert-butoxide and argon gas. Finally, it is acidified to generate 4-hydroxybenzaldehyde, which is simplified to a two-step synthesis process.
It improves reaction yield, reduces costs, uses readily available raw materials, and features a simple, safe, and stable process, making it suitable for industrial production.
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Abstract
Description
Technical Field
[0001] The invention relates to a preparation method of 4-hydroxybenzaldehyde, and belongs to the technical field of organic synthesis. Background Art
[0002] 4-Hydroxybenzaldehyde is an important organic compound with a wide range of uses. It is an important intermediate in the pharmaceutical industry, the fragrance industry and liquid crystal materials. It is also used abroad in the synthesis of the pesticide herbicides bromoxynil and hydroxydichlorvos, as well as in the production of fungicides and photographic emulsions.
[0003] There are relatively many methods for the synthesis of 4-hydroxybenzaldehyde, and the representative routes include: [Journal of the Iranian Chemical Society, 2015, 12, 81; RSC Advances, 2021, 11, 35988; Advanced Synthesis and Catalysis, 2007, 349, 846] Using 4-hydroxybenzyl alcohol as a raw material, 4-hydroxybenzaldehyde is obtained by oxidation reaction. The chemical reaction equation is as follows:
[0004]
[0005] [Molecules, 2017, 22, 1952; Tetrahedron Letters, 2008, 49, 5024] 4-bromophenol and N,N'-dimethylformamide (DMF) are used as raw materials to obtain 4-hydroxybenzaldehyde under the action of Grignard reagent or lithium reagent. The chemical reaction equation is as follows:
[0006]
[0007] [New Journal of Chemistry, 2019, 43, 9802; Organic Letters, 2017, 19, 4235; Synthesis, 2021, 53, 1962] 4-iodophenol and formaldehyde are used as raw materials to obtain 4-hydroxybenzaldehyde under the action of palladium catalyst. The chemical reaction equation is as follows:
[0008]
[0009] In view of the defects of the above technical routes, it is necessary to conduct in-depth research on the synthesis route of 4-hydroxybenzaldehyde 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
[0010] In order to overcome the above technical defects, the present invention provides a method for preparing 4-hydroxybenzaldehyde. Cyclohexanone-4-carboxaldehyde is used to generate an intermediate under the action of a Lewis acid catalyst; the intermediate is reacted under the action of a palladium carbon catalyst, potassium tert-butoxide and argon gas, and the target compound 4-hydroxybenzaldehyde is generated after acid hydrolysis. The route of the present invention is overall reasonable and is carried out in two steps, providing a simple and effective new path for the preparation of 4-hydroxybenzaldehyde.
[0011] The preparation method of 4-hydroxybenzaldehyde of the present invention is represented by the following reaction equation:
[0012]
[0013] The steps include:
[0014] A. reacting cyclohexanone-4-carboxaldehyde in the presence of a Lewis acid catalyst to generate an intermediate;
[0015] B. The intermediate, palladium-carbon catalyst, potassium tert-butoxide and organic solvent are mixed, argon is introduced, reacted at elevated temperature, and then acidified to obtain 4-hydroxybenzaldehyde.
[0016] Furthermore, in the above step A, the catalyst is selected from anhydrous ferric chloride, anhydrous zinc chloride or anhydrous cupric chloride.
[0017] Furthermore, in the above step A, the molar ratio of cyclohexanone-4-carboxaldehyde to Lewis acid catalyst is 1:0.03-0.1.
[0018] Furthermore, in the above step B, the palladium-carbon catalyst is selected from 5% palladium-carbon or 10% palladium-carbon.
[0019] Furthermore, in the above step B, the organic solvent is selected from sulfolane, DMSO or DMF.
[0020] Furthermore, in the above step B, the acid is selected from hydrochloric acid or sulfuric acid.
[0021] Furthermore, in the above step B, the molar ratio of the intermediate, the palladium-carbon catalyst and potassium tert-butoxide is 1:0.04-0.07:0.1-0.2.
[0022] Compared with the synthesis method reported in the literature, the present invention has the following beneficial effects:
[0023] 1. The Lewis acid catalyst is used to catalyze cyclohexanone-4-carboxaldehyde to generate 1,3,5-trioxacyclic intermediates, and the reaction yield is high. The Lewis catalyst is used to catalyze the generation of 1,3,5-trioxacyclic intermediates, avoiding the use of other protecting groups to protect the aldehyde group and then deprotecting it, reducing the use of protecting groups, reducing costs, and achieving good economic benefits.
[0024] 2. Cyclohexanone is converted into phenol using palladium-carbon catalyst, potassium tert-butoxide and argon. The route is novel and feasible, and the palladium-carbon catalyst can be recycled to reduce costs.
[0025] 3. The raw materials of this process are easily available in the market, the process is simple, safe and stable, and is suitable for industrial scale expansion. Specific embodiments
[0026] The present invention is 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 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.
[0027] Example 1
[0028] Under nitrogen protection, 12.6 g (0.1 mol) of cyclohexanone-4-carboxaldehyde and 0.8 g (0.005 mol) of anhydrous ferric chloride were mixed and reacted at room temperature for 1 hour. 80 mL of tetrahydrofuran was added and filtered. The filtrate was washed twice with 20 mL of saturated sodium bisulfite aqueous solution to obtain an organic layer, which was concentrated and directly recrystallized in tetrahydrofuran to obtain 9.0 g of an intermediate with a yield of 71% and a GC of 99.2%. 1 HNMR (400MHz, CDCl3): 4.62 (d, 3H), 2.31-2.35 (m, 12H), 2.22-2.24 (m, 3H), 1.96-2.02 (m, 6H), 1.42-1.46 (m, 6H).
[0029] Under nitrogen protection, in an autoclave, intermediate 1 (37.8 g, 0.1 mol), 5.3 g of 10% palladium carbon, 1.7 g of potassium tert-butoxide (0.015 mol) and 80 mL of cyclopentane were mixed, replaced with argon three times, and then filled with argon to a pressure of 0.2 MPa, and the autoclave was sealed, heated to 100-105° C., reacted for 12 hours, and GC detected that intermediate 1 was completely converted, cooled to room temperature, filtered, and the filtrate was concentrated. Subsequently, 50 mL of hydrochloric acid (2N) was added, the temperature was raised to 50° C., reacted for 3 hours, cooled to room temperature, extracted twice with 150 mL of ethyl acetate, and the ethyl acetate solution was concentrated to obtain a crude product, which was recrystallized from ethanol to obtain 31.1 g of 4-hydroxybenzaldehyde with a yield of 85% and a GC of 99.3%. 1 HNMR(400MHz, DMSO-d6):10.6(s,1H),9.8(s,1H),7.74-7.78(m,2H),6.91-6.95(m,2H).
[0030] Example 2
[0031] Under nitrogen protection, 12.6 g (0.1 mol) of cyclohexanone-4-carboxaldehyde, 1.1 g (0.008 mol) of anhydrous zinc chloride and 0.4 g of boron trifluoride-ether were mixed and reacted at room temperature for 1 hour. 80 mL of tetrahydrofuran was added and filtered. The filtrate was washed twice with 20 mL of saturated sodium bisulfite aqueous solution to obtain an organic layer, which was concentrated and directly recrystallized in tetrahydrofuran to obtain 11.6 g of an intermediate with a yield of 92% and a GC of 99.3%.
[0032] Under nitrogen protection, in an autoclave, intermediate 1 (37.8 g, 0.1 mol), 8.5 g of 5% palladium carbon, 2.2 g of potassium tert-butoxide (0.02 mol) and 100 mL of cyclopentane were mixed, replaced with argon three times, and then filled with argon to a pressure of 0.15 MPa, and the autoclave was sealed. The temperature was raised to 105-110° C. and reacted for 10 hours. GC detected that the intermediate was completely converted, cooled to room temperature, filtered, and the filtrate was concentrated. Subsequently, 50 mL of hydrochloric acid (2N) was added, the temperature was raised to 50° C., reacted for 3 hours, cooled to room temperature, extracted twice with 150 mL of ethyl acetate, and the ethyl acetate solution was concentrated to obtain a crude product, which was recrystallized from ethanol to obtain 29.7 g of 4-hydroxybenzaldehyde with a yield of 81% and a GC of 99.2%.
[0033] Example 3
[0034] Under nitrogen protection, 12.6 g (0.1 mol) of cyclohexanone-4-carboxaldehyde and 1.3 g (0.01 mol) of anhydrous cupric chloride were mixed and reacted at room temperature for 3 hours. 80 mL of tetrahydrofuran was added and filtered. The filtrate was washed twice with 20 mL of saturated sodium bisulfite aqueous solution to obtain an organic layer, which was concentrated and directly recrystallized in tetrahydrofuran to obtain 8.2 g of an intermediate with a yield of 65% and a GC of 99.1%.
[0035] Under nitrogen protection, in an autoclave, intermediate 1 (37.8 g, 0.1 mol), 10% palladium-calcium carbonate 7.4 g, potassium tert-butoxide 1.1 g (0.01 mol) and 80 mL of cyclopentane were mixed, replaced with argon three times, and then filled with argon to a pressure of 0.1 MPa, and the autoclave was sealed, heated to 105-110 ° C, reacted for 14 hours, and GC detected that the intermediate was completely converted. The mixture was cooled to room temperature, filtered, and the filtrate was concentrated. Subsequently, 50 mL of sulfuric acid (1N) was added, the temperature was raised to 40 ° C, reacted for 3 hours, cooled to room temperature, extracted twice with 150 mL of ethyl acetate, and the ethyl acetate solution was concentrated to obtain a crude product, which was recrystallized from ethanol to obtain 29.3 g of 4-hydroxybenzaldehyde with a yield of 80% and GC 99.1%.
[0036] 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 4-hydroxybenzaldehyde, characterized in that: The steps include: A. reacting cyclohexanone-4-carboxaldehyde in the presence of a Lewis acid catalyst to generate an intermediate; B. The intermediate, palladium-carbon catalyst, potassium tert-butoxide and organic solvent are mixed, argon is introduced, reacted at elevated temperature, and then acidified to obtain 4-hydroxybenzaldehyde.
2. The method for preparing 4-hydroxybenzaldehyde according to claim 1, characterized in that: In step A, the Lewis acid catalyst is selected from ferric chloride, zinc chloride or cupric chloride.
3. The method for preparing 4-hydroxybenzaldehyde according to claim 1, characterized in that: In step A, the molar ratio of cyclohexanone-4-carboxaldehyde to Lewis acid catalyst is 1:0.03-0.
1.
4. The method for preparing 4-hydroxybenzaldehyde according to claim 1, characterized in that: In step B, the palladium catalyst is selected from 5% palladium carbon or 10% palladium carbon.
5. The method for preparing 4-hydroxybenzaldehyde according to claim 1, characterized in that: In step B, the organic solvent is DMSO or DMF.
6. The method for preparing 4-hydroxybenzaldehyde according to claim 1, characterized in that: In step B, the acid is selected from hydrochloric acid or sulfuric acid.
7. The method for preparing 4-hydroxybenzaldehyde according to claim 1, characterized in that: In step B, the molar ratio of the intermediate, palladium-carbon catalyst and potassium tert-butoxide is 1:0.04-0.07:0.1-0.2.