A method for synthesizing 4-tert-butyl-2,6-diformylphenol

Abstract

The invention provides a synthesis method of 4-tert-butyl-2,6-diformylphenol, and relates to the technical field of electronic material synthesis. The method comprises the following steps: S1, placing chlorosulfonic acid in a reaction bottle 1, connecting an air guide tube, adding 4-tert-butylphenol, CuCl, anhydrous AlCl3 and benzene into a reaction bottle 2, reacting to obtain a mixed reaction liquid, and connecting a tail gas absorption device; S2, placing formic acid in a constant drop, and dropping the acid into the reaction bottle 1 at a constant rate; S3, quenching, filtering and extracting the mixed reactants to obtain a crude 4-tert-butyl-2,6-diformylphenol product; and S4, using a solution for recrystallization comprising cyclohexane, wherein the volume-to-mass ratio of the solution used in the recrystallization to the crude 4-tert-butyl-2,6-diformylphenol product is 10-13:1. The present invention adopts the above-mentioned synthesis method of 4-tert-butyl-2,6-diformylphenol, which solves the problems of low yield and low purity in the synthesis process of 4-tert-butyl-2,6-diformylphenol in the related art.

Description

Technical Field

[0001] The present invention relates to the technical field of electronic material synthesis, in particular to a method for synthesizing 4-tert-butyl-2,6-diformylphenol. Background Art

[0002] 4-tert-Butyl-2,6-diformylphenol can serve as an important organic synthesis intermediate, used to construct more complex organic compounds. For example, by reacting its formyl or phenolic hydroxyl groups with other compounds, multifunctional compounds with specific structures and functions can be synthesized, such as in fields such as pharmaceutical synthesis and materials chemistry. In pharmaceutical synthesis, it can serve as a building block for constructing bioactive molecules. By modifying the formyl or phenolic hydroxyl groups, various pharmacophores can be introduced to develop new drug molecules. In materials chemistry, it can be used to prepare polymers or small molecule materials with special properties. For example, by reacting it with amino-containing compounds, it forms polymer materials with specific functions, which can be used to prepare sensors, catalyst supports, and more.

[0003] Numerous organic synthesis methods for synthesizing 4-tert-butyl-2,6-diformylphenol have been developed. Among them, Jones, Rebecca, et al., and Li Fan, et al., from Hong Kong Baptist University, used trifluoroacetic acid as a protonic acid to prepare 4-tert-butyl-2,6-diformylphenol. However, trifluoroacetic acid is highly corrosive, which greatly limits its application in industrial production. Huang Wei et al. used (5-(tert-butyl)-2-hydroxy-1,3-phenyl)dimethanol as a raw material for synthesis, which resulted in high economic costs. To address this issue, researchers and industry have been exploring safer, more environmentally friendly, and more economically viable synthetic pathways.

[0004] In Organic Journal, Jones, Rebecca et al. heated phenol (1.0 eq) and hexamethylenetetramine (2.0 eq) in trifluoroacetic acid (TFA) (15.0 eq) to 145°C and refluxed for 18 hours. The resulting hot solution was poured into 4N hydrochloric acid (115 mL). Stirred at room temperature for 2 hours. Stored at 5°C overnight. The precipitate was isolated by filtration. The crude product was washed with ice-cold distilled water (3 × 50 mL) and -78°C methanol (3 × 20 mL) to obtain the product. The TFA used in the reaction is a highly corrosive proton acid and poses a significant risk to the experimenter, so this method was not adopted for safety reasons.

[0005] Li Fan et al. at Hong Kong Baptist University synthesized 4-tert-butyl-2,6-diformylphenol. A solution of 4-tert-butylphenol (2.0 g, 13.3 mmol) and hexamethylenetetramine (3.9 g, 27.8 mmol) were added to TFA (25 mL), and the mixture was heated under reflux for 24 h under a nitrogen atmosphere. The reaction mixture was poured into 6 M HCl (80 mL) and stirred for 20 min. The aqueous phase was extracted with dichloromethane (60 mL), and the combined organic phases were washed sequentially with 4 M HCl (80 mL), water (80 mL), and brine (80 mL), then dried over NaSO. After solvent removal, the residue was purified by column chromatography on silica gel (PE:EA = 40:1) to yield a pale yellow product. TFA proton acid was also used in the reaction, so this synthesis method was not adopted for safety reasons.

[0006] Huang Wei et al. developed an improved oxidation method for preparing 4-tert-butyl-2,6-diformylphenol by manganese dioxide, using (5-(tert-butyl)-2-hydroxy-1,3-phenyl)dimethanol as the raw material. Activated MnO2 (40 g) was added to CHCl3 (200 mL) in a 500 mL round-bottom culture flask. The mixture was heated to reflux and stirred for about 15 minutes. A tert-butyl derivative powder (5.0 g) was added. The reaction mixture was refluxed for 8 hours. The reaction mixture was cooled to room temperature and filtered. The solid was washed with CHCl3 (40 mL x 5) until the filtrate became colorless. The filtrate was concentrated on a rotary evaporator to obtain the product. Due to the high price of (5-(tert-butyl)-2-hydroxy-1,3-phenyl)dimethanol used in the reaction process, the economic cost of the entire reaction process remained high, so this method was not suitable from an economic point of view.

[0007] Wu Xibing et al. synthesized 4-biphenylaldehyde using the Gattermann-Koch reaction with chlorobenzene as the solvent and anhydrous aluminum chloride and cuprous chloride as the catalyst. The reaction required a 24-hour gaseous flow of CO and HCl. This experiment referenced their synthesis method and optimized the process. Large-scale industrial production could yield good economic benefits. Therefore, developing this high-yield, high-purity synthesis method for 4-tert-butyl-2,6-diformylphenol is highly desirable. Summary of the Invention

[0008] The present invention aims to provide a method for synthesizing 4-tert-butyl-2,6-diformylphenol, which solves the problems of safety, environmental protection and economic cost in the synthesis process of 4-tert-butyl-2,6-diformylphenol in the related art by utilizing the Gattermann-Koch reaction.

[0009] To achieve the above object, the present invention provides a method for synthesizing 4-tert-butyl-2,6-diformylphenol, comprising the following steps:

[0010] S1, placing chlorosulfonic acid in reaction flask 1, connecting reaction flask 1 and reaction flask 2 with an air guide tube, adding 4-tert-butylphenol, CuCl, anhydrous AlCl3 and benzene to reaction flask 2 to react to obtain a mixed reaction liquid, and further connecting reaction flask 2 to a tail gas absorption device to form a reaction system, and evacuating the reaction system;

[0011] S2, formic acid is placed in a constant drop and added to reaction flask 1 at a constant rate to produce dry HCl and CO, and a mixed product is produced in reaction flask 2;

[0012] S3, quenching, filtering, and extracting the mixed product in reaction flask 2 to obtain a crude product of 4-tert-butyl-2,6-diformylphenol;

[0013] S4. After the crude product of 4-tert-butyl-2,6-diformylphenol is recrystallized, 4-tert-butyl-4,6-diformylphenol is obtained. The solution used in the recrystallization includes cyclohexane, and the volume mass ratio of the solution used in the recrystallization to the crude product is 10 to 13:1.

[0014] Preferably, in S1, the volume ratio of benzene to 4-tert-butylphenol is 15-20:1, the molar ratio of 4-tert-butylphenol to chlorosulfonic acid is 1:8-10, the molar ratio of 4-tert-butylphenol to CuCl is 1:0.3-0.5, and the molar ratio of 4-tert-butylphenol to anhydrous AlCl3 is 1:1.5-2.

[0015] Preferably, in S1, the reaction temperature is 20-30°C, and the reaction time is 10-14 hours.

[0016] Preferably, in S2, the solution used for extraction is a hydrocarbon solution, which includes one or more of dichloromethane, 1,2-dichloroethane, chloroform, toluene, benzene, and trichloroethane, and the extraction is performed at least once.

[0017] Preferably, in S3, the quenching step, the solution used is an ice-water mixture.

[0018] Preferably, in S3, diatomaceous earth is used for filtration.

[0019] Preferably, in S4, recrystallization is performed at least once, and the same solution is used in each recrystallization.

[0020] Preferably, in S4, the solution used for recrystallization further comprises one or more of petroleum ether, n-hexane, and n-heptane, and the volume ratio of cyclohexane to petroleum ether is 4 to 7:10.

[0021] Preferably, in S1 , a gas scrubber is further provided between the reaction flask 1 and the reaction flask 2 .

[0022] Therefore, the present invention adopts the above-mentioned synthesis method of 4-tert-butyl-2,6-diformylphenol. The raw material 4-tert-butylphenol used in the preparation is cheap and easily available, the reaction conditions are mild, and the production safety is high. This not only reduces the reaction cost, but also improves the yield and purity of 4-tert-butyl-2,6-diformylphenol, and has high industrial application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a synthetic route for 4-tert-butyl-2,6-diformylphenol of Example 1 of the present invention;

[0024] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of 4-tert-butyl-2,6-diformylphenol prepared in Example 1 of the present invention;

[0025] Figure 3 This is a gas phase spectrum of 4-tert-butyl-2,6-diformylphenol prepared in Example 1 of the present invention; Figure 3 (a) is the response with retention time between 0 and 4.5 s; Figure 3 (b) is the response after the retention time is 4.5s. DETAILED DESCRIPTION

[0026] The technical solution of the present invention is further described below with reference to the accompanying drawings and embodiments.

[0027] Unless otherwise defined, technical or scientific terms used in the present invention shall have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs.

[0028] The gas phase method was as follows: injection port temperature 260°C, column box initial temperature 50°C, 30°C / min, gradient temperature increase to 200°C, holding time 5 min, detector temperature 300°C, sample boiling point 310°C, sample solvent: dichloromethane.

[0029] Example 1

[0030] A method for synthesizing 4-tert-butyl-2,6-diformylphenol comprises the following steps:

[0031] S1. At 2°C, chlorosulfonic acid (6.2105g, 0.0530mol, 8eq) was placed in reaction flask 1. A gas scrubber was provided between reaction flask 1 and reaction flask 2. A gas guide tube was used to connect reaction flask 1 and reaction flask 2. 15mL of benzene, 4-tert-butylphenol (1.005g, 0.0067mol, 1eq), cuprous chloride (0.1979g, 0.0020mol, 0.3eq), and anhydrous aluminum chloride (1.3325g, 0.0100mol, 1.5eq) were added to reaction flask 2 to obtain a mixed reaction liquid. Reaction flask 2 was also connected to a tail gas absorption device (configured with 200mL of 10% sodium hydroxide solution) to form a reaction system. The reaction system was evacuated and stirring was then started.

[0032] S2 and formic acid (2.4528 g, 0.0533 mol, 8 eq) were placed in a constant drip and added dropwise to reaction flask 1 at a constant rate to produce dry HCl and CO; after continuing the reaction for 11 h, a mixed product was obtained.

[0033] S3. The mixed product was quenched with ice water, filtered with celite, and extracted with 20 mL of dichloromethane. The organic phases were combined, dried and filtered using anhydrous MgSO4, and then spin-dried at 45°C to obtain a crude product of 4-tert-butyl-2,6-diformylphenol.

[0034] S4. 15.4 mL of cyclohexane was added to the crude 4-tert-butyl-2,6-diformylphenol each time recrystallization was performed. After recrystallization twice, the crude product was filtered and dried to obtain 1.0133 g of 4-tert-butyl-2,6-diformylphenol with a yield of 73.82% and a purity of 99.64%.

[0035] The synthetic route of 4-tert-butyl-2,6-diformylphenol prepared in Example 1 is as follows: Figure 1 The nuclear magnetic resonance hydrogen spectrum of the 4-tert-butyl-2,6-diformylphenol is as follows: Figure 2 shown.

[0036] Example 2

[0037] A method for synthesizing 4-tert-butyl-2,6-diformylphenol comprises the following steps:

[0038] S1. At 25°C, chlorosulfonic acid (7.7631 g, 0.0666 mol, 10 eq) was placed in reaction flask 1. A gas scrubber was provided between reaction flask 1 and reaction flask 2. A gas guide tube was used to connect reaction flask 1 and reaction flask 2. 16 mL of benzene, 4-tert-butylphenol (1.014 g, 0.0067 mol, 1 eq), cuprous chloride (0.3298 g, 0.0033 mol, 0.5 eq), and anhydrous aluminum chloride (1.5102 g, 0.01133 mol, 1.7 eq) were added to reaction flask 2 to obtain a mixed reaction liquid. Reaction flask 2 was also connected to a tail gas absorption device (configured with 200 mL of 10% sodium hydroxide solution) to form a reaction system. The reaction system was evacuated and stirring was then started.

[0039] S2 and formic acid (3.0700 g, 0.0667 mol, 10 eq) were placed in a constant drip and added dropwise to reaction flask 1 at a constant rate to produce dry HCl and CO; after continuing the reaction for 12 h, a mixed product was obtained.

[0040] S3. The mixed product was quenched with ice water, filtered with celite, and extracted with 20 mL of dichloromethane. The organic phases were combined, dried and filtered using anhydrous MgSO4, and then spin-dried at 45°C to obtain a crude product of 4-tert-butyl-2,6-diformylphenol.

[0041] S4. 18 mL of cyclohexane was added to the crude 4-tert-butyl-2,6-diformylphenol each time recrystallization was performed. After recrystallization twice, the crude product was filtered and dried to obtain 1.0476 g of 4-tert-butyl-2,6-diformylphenol with a yield of 76.30% and a purity of 99.55%.

[0042] Example 3

[0043] A method for synthesizing 4-biphenylaldehyde comprises the following steps:

[0044] S1. At 25°C, chlorosulfonic acid (7.7631 g, 0.0666 mol, 10 eq) was placed in reaction flask 1. A gas scrubber was provided between reaction flask 1 and reaction flask 2. A gas guide tube was used to connect reaction flask 1 and reaction flask 2. 16 mL of benzene, 4-tert-butylphenol (1.007 g, 0.0067 mol, 1 eq), cuprous chloride (0.3957 g, 0.0040 mol, 0.6 eq), and anhydrous aluminum chloride (1.7767 g, 0.0133 mol, 2 eq) were added to reaction flask 2 to obtain a mixed reaction liquid. Reaction flask 2 was also connected to a tail gas absorption device (configured with 200 mL of 10% sodium hydroxide solution) to form a reaction system. The reaction system was evacuated and stirring was then started.

[0045] S2 and formic acid (3.0700 g, 0.0667 mol, 10 eq) were placed in a constant drip and added dropwise to reaction flask 1 at a constant rate to produce dry HCl and CO; after continuing the reaction for 11 h, a mixed product was obtained.

[0046] S3. The mixed product was quenched with ice water, filtered with celite, and extracted with 20 mL of dichloromethane. The organic phases were combined, dried and filtered using anhydrous MgSO4, and then spin-dried at 45°C to obtain a crude product of 4-tert-butyl-2,6-diformylphenol.

[0047] S4. 22 mL of cyclohexane was added to the crude 4-tert-butyl-2,6-diformylphenol each time recrystallization was performed. After recrystallization twice, the crude product was filtered and dried to obtain 1.0750 g of 4-tert-butyl-2,6-diformylphenol with a yield of 79.20% and a purity of 99.63%.

[0048] Example 4

[0049] Compared with Example 1, the difference of Example 4 is that cyclohexane is replaced by an equal volume of n-hexane;

[0050] 1.0741 g of 4-tert-butyl-2,6-diformylphenol was obtained with a yield of 78.23% and a purity of 99.64%.

[0051] Example 5

[0052] Compared with Example 4, the difference of Example 5 is that n-hexane is replaced by cyclohexane and petroleum ether in a volume ratio of 4:6;

[0053] 1.1703 g of 4-tert-butyl-2,6-diformylphenol was obtained with a yield of 85.24% and a purity of 99.51%.

[0054] Example 6

[0055] Compared with Example 4, the difference of Example 6 is that n-hexane is replaced by cyclohexane and petroleum ether with a volume ratio of 3:7; 1.2449 g of 4-tert-butyl-2,6-diformylphenol is obtained with a yield of 90.67% and a purity of 99.64%.

[0056] Example 7

[0057] Compared with Example 4, Example 7 is different in that n-hexane is replaced by cyclohexane and petroleum ether in a volume ratio of 3:7;

[0058] 1.0898 g of 4-tert-butyl-2,6-diformylphenol was obtained with a yield of 79.37% and a purity of 99.47%.

[0059] Example 8

[0060] Compared with Example 6, the difference in Example 8 is that dichloromethane is replaced by an equal amount of chloroform;

[0061] 1.2578 g of 4-tert-butyl-2,6-diformylphenol was obtained with a yield of 91.61% and a purity of 99.53%.

[0062] Example 9

[0063] Compared with Example 6, the difference in Example 9 is that dichloromethane is replaced by an equal amount of toluene;

[0064] 1.2235 g of 4-tert-butyl-2,6-diformylphenol was obtained with a yield of 89.11% and a purity of 99.70%.

[0065] Comparative Example 1

[0066] Compared with Example 1, the difference of Comparative Example 1 is that cyclohexane is not used for recrystallization;

[0067] 0.9585 g of 4-tert-butyl-2,6-diformylphenol was obtained with a yield of 69.81% and a purity of 99.37%.

[0068] Comparative Example 2

[0069] Compared with Example 6, the difference in Comparative Example 2 is that cyclohexane is replaced by an equal volume of chloroform;

[0070] 1.1525 g of 4-tert-butyl-2,6-diformylphenol was obtained with a yield of 83.94% and a purity of 99.47%.

[0071] Compared with Comparative Example 1, Example 1 added cyclohexane for recrystallization. As a result, the yield and purity of Example 1 were better than those of Comparative Example 1, indicating that when cyclohexane was used for recrystallization, the yield and purity of 4-tert-butyl-2,6-diformylphenol could be improved.

[0072] Compared with Comparative Example 2 and Examples 1, 4, and 7, Examples 5 and 6 simultaneously added a solution consisting of cyclohexane and petroleum ether for recrystallization. As a result, the yield and purity of Examples 5 and 6 were better than those of Comparative Example 2 and Examples 1, 4, and 7, indicating that cyclohexane and petroleum ether exerted a synergistic effect, which could further improve the yield and purity of 4-tert-butyl-2,6-diformylphenol.

[0073] Compared with Example 6, Examples 8 and 9 added different types of hydrocarbon solutions for extraction. The yield and purity of Example 6 were better than those of Examples 8 and 9, indicating that when the added hydrocarbon solution was dichloromethane, the yield and purity of the obtained 4-tert-butyl-2,6-diformylphenol were higher.

[0074] Therefore, the present invention adopts the above-mentioned synthesis method of 4-tert-butyl-2,6-diformylphenol to solve the problems of low yield and low purity in the synthesis process of 4-tert-butyl-2,6-diformylphenol in the related art.

[0075] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the same. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solutions of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A method for synthesizing 4-tert-butyl-2,6-diformylphenol, characterized in that: The following steps are involved: S1, placing chlorosulfonic acid in reaction flask 1, connecting reaction flask 1 and reaction flask 2 with an air guide tube, adding 4-tert-butylphenol, CuCl, anhydrous AlCl3 and benzene to reaction flask 2 to react to obtain a mixed reaction liquid, and further connecting reaction flask 2 to a tail gas absorption device to form a reaction system, and evacuating the reaction system; S2, formic acid is placed in a constant drop and added to reaction flask 1 at a constant rate to produce dry HCl and CO, and a mixed product is produced in reaction flask 2; S3, quenching, filtering, and extracting the mixed product in reaction flask 2 to obtain a crude product of 4-tert-butyl-2,6-diformylphenol; S4. After the crude product of 4-tert-butyl-2,6-diformylphenol is recrystallized, 4-tert-butyl-4,6-diformylphenol is obtained. The solution used in the recrystallization includes cyclohexane, and the volume mass ratio of the solution used in the recrystallization to the crude product is 10 to 13:

1.

2. A method for synthesizing 4-tert-butyl-2,6-diformylphenol according to claim 1, characterized in that: In S1, the volume ratio of benzene to 4-tert-butylphenol is 15-20:1, the molar ratio of 4-tert-butylphenol to chlorosulfonic acid is 1:8-10, the molar ratio of 4-tert-butylphenol to CuCl is 1:0.3-0.5, and the molar ratio of 4-tert-butylphenol to anhydrous AlCl3 is 1:1.5-2.

3. A method for synthesizing 4-tert-butyl-2,6-diformylphenol according to claim 1, characterized in that: In S1, the reaction temperature is 20-30°C, and the reaction time is 10-14 hours.

4. A method for synthesizing 4-tert-butyl-2,6-diformylphenol according to claim 1, characterized in that: In S2, the solution used for extraction is a hydrocarbon solution, which includes one or more of dichloromethane, 1,2-dichloroethane, chloroform, toluene, benzene, and trichloroethane, and the extraction is performed at least once.

5. A method for synthesizing 4-tert-butyl-2,6-diformylphenol according to claim 1, characterized in that: In S3, the quenching step, the solution used is an ice-water mixture.

6. A method for synthesizing 4-tert-butyl-2,6-diformylphenol according to claim 1, characterized in that: In S3, filter using celite.

7. A method for synthesizing 4-tert-butyl-2,6-diformylphenol according to claim 1, characterized in that: In S4, recrystallization is performed at least once, and the same solution is used in each recrystallization.

8. A method for synthesizing 4-tert-butyl-2,6-diformylphenol according to claim 1, characterized in that: In S4, the solution used in the recrystallization further comprises one or more of petroleum ether, n-hexane, and n-heptane.

9. A method for synthesizing 4-tert-butyl-2,6-diformylphenol according to claim 1, characterized in that: In S1 , a gas scrubber is provided between reaction flask 1 and reaction flask 2 .

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