Synthesis method of 4-biphenyl formaldehyde

Abstract

The invention relates to the technical field of chemical synthesis, and provides a synthesis method of 4-biphenyl formaldehyde, which comprises the following steps: S1, mixing trifluoroacetic acid and biphenyl, adding urotropine, and reacting to obtain a mixed reaction solution; s2, quenching, neutralizing and extracting the mixed reaction liquid to obtain a 4-biphenyl formaldehyde crude product; and S3, the 4-biphenyl formaldehyde crude product and the sodium hydrogen sulfite solution are subjected to addition to obtain a sodium hydrogen sulfite adduct, the sodium hydrogen sulfite adduct is subjected to alkaline hydrolysis and recrystallization to obtain 4-biphenyl formaldehyde, the solution used during recrystallization comprises acetone, and the volume mass ratio of the solution used during recrystallization to the 4-biphenyl formaldehyde crude product is 10-13 mL: 1 g. According to the technical scheme, the problems of low yield and low purity in the synthesis process of 4-biphenyl formaldehyde in related technologies are solved.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a method for synthesizing 4-biphenylcarboxaldehyde. Background Art

[0002] 4-Biphenylcarboxaldehyde is an important biphenyl derivative and an important organic chemical intermediate. It is widely used in medicine, polymer liquid crystals, dyes, etc. For example, 4-biphenylcarboxaldehyde can be used to synthesize the non-steroidal anti-inflammatory drug fenbufen, which is used to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout and other diseases.

[0003] At present, there have been many organic synthesis methods for synthesizing 4-biphenyl formaldehyde. Among them, U.S. Patent No. 5068450 adopts formic acid ester to react in hydrofluoric acid-boron trifluoride to prepare 4-biphenyl formaldehyde, and U.S. Patent No. 4368336 adopts the method for the formylation reaction of biphenyl and carbon monoxide by hydrofluoric acid-boron trifluoride to prepare 4-biphenyl formaldehyde. However, hydrofluoric acid-boron trifluoride has strong toxicity and has strong corrosiveness to equipment, which greatly limits its application in industrial production. In view of this problem, scientific researchers and the industry have been exploring safer, more environmentally friendly and economically feasible synthetic paths.

[0004] Zhang Yingxue et al. used the Suzuki coupling reaction, that is, the coupling reaction of bromo (or chlorine, iodine) benzaldehyde and phenylboronic acid under the catalysis of transition metals to obtain 4-biphenylaldehyde. Since the phenylboric acid and Pd (palladium) nanoparticle catalyst used in the reaction are relatively expensive, the economic cost of the entire reaction process remains high. Therefore, this method is not suitable from an economic point of view.

[0005] Wu Xibing et al. synthesized 4-biphenylcarboxaldehyde using chlorobenzene as solvent and anhydrous aluminum chloride and cuprous chloride as catalysts. The reaction required the introduction of a mixed gas of CO and HCl for 24 hours. However, the experiment did not further optimize the experimental conditions, resulting in a low yield and poor economic benefits in large-scale industrial production. Therefore, it is necessary to propose a method for synthesizing 4-biphenylcarboxaldehyde with high yield and high purity. Summary of the invention

[0006] The invention provides a method for synthesizing 4-biphenylcarboxaldehyde, which solves the problems of low yield and low purity in the synthesis process of 4-biphenylcarboxaldehyde in the related art.

[0007] The technical solution of the present invention is as follows: The present invention provides a method for synthesizing 4-biphenylcarboxaldehyde, comprising the following steps: S1, mixing trifluoroacetic acid and biphenyl, adding urotropine, and reacting to obtain a mixed reaction liquid; S2, the mixed reaction liquid is quenched, neutralized and extracted to obtain a crude 4-biphenylcarboxaldehyde product; S3, the crude 4-biphenylformaldehyde product and the sodium bisulfite solution are added to obtain a sodium bisulfite adduct, which is then subjected to alkaline hydrolysis and recrystallization to obtain 4-biphenylformaldehyde; The solution used in the recrystallization includes acetone, and the volume mass ratio of the solution used in the recrystallization to the crude 4-biphenylcarboxaldehyde is 10-13 mL:1 g.

[0008] As a further technical solution, the recrystallization is carried out twice, and the solution used in the recrystallization is the same twice.

[0009] As a further technical solution, the solution used in the recrystallization also includes n-hexane, and the volume ratio of the acetone to the n-hexane is 4-7:10.

[0010] In the present invention, acetone and n-hexane are used as recrystallization solutions at the same time, and the synergistic effect of the two is brought into play, thereby further improving the yield and purity of 4-biphenylcarboxaldehyde.

[0011] As a further technical solution, the volume ratio of trifluoroacetic acid to biphenyl in S1 is 15-20:1, and the molar ratio of biphenyl to hexamethylenetetramine is 1:1.5-2.5.

[0012] As a further technical solution, the mixing temperature in S1 is 70°C.

[0013] As a further technical solution, the reaction temperature in S1 is 70-100° C., and the reaction time is 8-12 h.

[0014] As a further technical solution, the solution used for quenching in S2 is a 4-6M hydrochloric acid solution, and the volume mass ratio of the hydrochloric acid solution to the biphenyl is 20mL:1g.

[0015] As a further technical solution, the solution used for neutralization is a 3wt% sodium hydroxide solution, and the pH of the neutralization is 7.

[0016] As a further technical solution, the concentration of the sodium bisulfite solution in S3 is 29.6wt%, and the volume mass ratio of the sodium bisulfite solution to the biphenyl is 13-15mL:1g.

[0017] As a further technical solution, the solution used for alkaline hydrolysis in S3 is a 24.8wt% sodium carbonate solution, and the volume mass ratio of the sodium carbonate solution to the biphenyl is 13-15mL:1g.

[0018] As a further technical solution, the solution used for extraction in S2 is a hydrocarbon solution, and the hydrocarbon solution includes one or more of 1,2-dichloroethane, chloroform, toluene, benzene, and trichloroethane.

[0019] As a further technical solution, the volume mass ratio of the hydrocarbon solution used for extraction in S2 to the biphenyl is 20mL:1g.

[0020] As a further technical solution, after the extraction in S2, the organic phases are combined, dried and filtered using anhydrous MgSO4, and then spin-dried to obtain a crude 4-biphenyl formaldehyde product.

[0021] As a further technical solution, the spin drying temperature is 45°C.

[0022] As a further technical solution, the mixed reaction liquid is concentrated under reduced pressure before quenching in S2.

[0023] As a further technical solution, the concentration temperature is 50°C, and the concentrated state is an oily solid.

[0024] The working principle and beneficial effects of the present invention are: In the present invention, biphenyl is used as a raw material, and the Duff reaction (hexamethylenetetramine formylation reaction) mechanism is adopted to generate an iminium ion through the reaction of hexamethylenetetramine (HMTA) and a strong proton acid, and an affinity substitution reaction occurs with an electron-rich benzene ring, and 4-biphenyl formaldehyde is obtained through hydrolysis. The raw materials for preparing 4-biphenyl formaldehyde in the present invention are cheap and easy to obtain, the reaction conditions are mild, and the production safety is high, which not only reduces the reaction cost, but also improves the yield and purity of 4-biphenyl formaldehyde, and has high industrial application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0026] Figure 1 The synthetic route of 4-biphenylcarboxaldehyde of Example 1 of the present invention is shown in FIG. Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of 4-biphenylaldehyde prepared in Example 1 of the present invention; Figure 3 The gas chromatogram of 4-biphenylaldehyde prepared in Example 1 of the present invention; Figure 4 This is a gas chromatographic standard curve of 4-biphenylaldehyde prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0027] The following will be combined with 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] In the following examples and comparative examples: The gas phase method is as follows: injection port temperature 260°C, column box initial temperature 50°C, 30°C / min, gradient temperature increase to 200°C, holding time 5min, detector temperature 300°C, sample boiling point 340°C, sample solvent: dichloromethane.

[0029] Example 1 A method for synthesizing 4-biphenylcarboxaldehyde comprises the following steps: S1. Mix 15 mL of trifluoroacetic acid and 1.0014 g of biphenyl (4.48 mmol), heat to 70°C, add 0.9421 g of urotropine (6.72 mmol) after the biphenyl is completely dissolved, and continue the reaction for 12 hours to obtain a mixed reaction solution; S2, the mixed reaction liquid was concentrated under reduced pressure at 50°C, quenched by adding 20 mL of 4M hydrochloric acid solution, adjusted to pH 7 with 3 wt% sodium hydroxide solution, extracted with 20 mL of 1,2-dichloroethane, combined the organic phases, dried and filtered with anhydrous MgSO4, and dried at 45°C to obtain 1.4 g of crude 4-biphenylcarboxaldehyde; S3. To the crude 4-biphenylcarboxaldehyde, 13 mL of 29.6 wt% sodium bisulfite solution was added, and the mixture was stirred and filtered to obtain a sodium bisulfite adduct of the aldehyde. Then, 13 mL of 24.8 wt% sodium carbonate solution was added, and the mixture was heated under reflux with stirring. After filtration, an alkaline hydrolysis product was obtained. Then, 15.4 mL of acetone was added twice, and the mixture was recrystallized twice, and then filtered and dried to obtain 0.8723 g of 4-biphenylcarboxaldehyde, with a yield of 73.82% and a purity of 99.34%.

[0030] The synthetic route of 4-biphenyl carboxaldehyde prepared in Example 1 is as follows Figure 1 As shown, the nuclear magnetic resonance hydrogen spectrum of 4-biphenylaldehyde is as follows Figure 2 As shown in the gas chromatogram of 4-biphenylaldehyde Figure 3 As shown in the figure, the gas chromatography standard curve of 4-biphenylaldehyde is as follows Figure 4 shown.

[0031] Example 2 A method for synthesizing 4-biphenylcarboxaldehyde comprises the following steps: S1. Mix 16 mL of trifluoroacetic acid and 1.0014 g of biphenyl (4.48 mmol), heat to 70°C, add 1.2561 g of urotropine (8.96 mmol) after the biphenyl is completely dissolved, heat to 90°C, react for 11 hours, and obtain a mixed reaction liquid; S2, the mixed reaction liquid was concentrated under reduced pressure at 50°C, 20 mL of 5M hydrochloric acid solution was added for quenching, the pH was adjusted to 7 with 3 wt% sodium hydroxide solution, 20 mL of 1,2-dichloroethane was added for extraction, the organic phases were combined, dried and filtered with anhydrous MgSO4, and dried at 45°C to obtain 1.5 g of crude 4-biphenylcarboxaldehyde; S3. Add 14 mL of 29.6 wt% sodium bisulfite solution to the crude 4-biphenylcarboxaldehyde, stir and filter to obtain the sodium bisulfite adduct of the aldehyde, then add 14 mL of 24.8 wt% sodium carbonate solution, heat under reflux and stir, filter to obtain the alkaline hydrolysis product, add 21 mL of acetone × 2, recrystallize twice, filter and dry to obtain 0.9016 g of 4-biphenylcarboxaldehyde, with a yield of 76.30% and a purity of 99.34%.

[0032] Example 3 A method for synthesizing 4-biphenylcarboxaldehyde comprises the following steps: S1. Mix 20 mL of trifluoroacetic acid and 1.0014 g of biphenyl (4.48 mmol), heat to 70°C, add 1.5701 g of urotropine (11.20 mmol) after the biphenyl is completely dissolved, heat to 100°C, react for 8 hours, and obtain a mixed reaction liquid; S2, the mixed reaction liquid was concentrated under reduced pressure at 50°C, quenched by adding 20 mL of 6M hydrochloric acid solution, adjusted to pH 7 with 3 wt% sodium hydroxide solution, extracted with 20 mL of 1,2-dichloroethane, combined the organic phases, dried and filtered with anhydrous MgSO4, and dried at 45°C to obtain 1.6 g of crude 4-biphenylcarboxaldehyde; S3. Add 15 mL of 29.6 wt% sodium bisulfite solution to the crude 4-biphenylcarboxaldehyde, stir and filter to obtain the sodium bisulfite adduct of the aldehyde, then add 15 mL of 24.8 wt% sodium carbonate solution, heat under reflux and stir, filter to obtain the alkaline hydrolysis product, add 24 mL of acetone × 2, recrystallize twice, filter and dry to obtain 0.9245 g of 4-biphenylcarboxaldehyde, with a yield of 78.24% and a purity of 99.46%.

[0033] Example 4 Compared with Example 1, the difference of Example 4 is that acetone is replaced by an equal volume of n-hexane; 0.9114 g of 4-biphenylcarboxaldehyde was obtained with a yield of 77.13% and a purity of 99.21%.

[0034] Example 5 Compared with Example 4, the difference of Example 5 is that n-hexane is replaced with acetone and n-hexane in a volume ratio of 4:6; 1.1018 g of 4-biphenylcarboxaldehyde was obtained with a yield of 93.24% and a purity of 99.51%.

[0035] Example 6 Compared with Example 4, the difference of Example 6 is that n-hexane is replaced with acetone and n-hexane in a volume ratio of 3:7; 1.1422 g of 4-biphenylcarboxaldehyde was obtained with a yield of 96.67% and a purity of 99.64%.

[0036] Example 7 Compared with Example 4, the difference of Example 7 is that n-hexane is replaced by acetone and chloroform in a volume ratio of 3:7; 0.9378 g of 4-biphenylcarboxaldehyde was obtained with a yield of 79.37% and a purity of 99.36%.

[0037] Example 8 Compared with Example 6, the difference in Example 8 is that 1,2-dichloroethane is replaced by an equal amount of chloroform; 1.0825 g of 4-biphenylcarboxaldehyde was obtained with a yield of 91.61% and a purity of 99.25%.

[0038] Example 9 Compared with Example 6, the difference of Example 9 is that 1,2-dichloroethane is replaced by an equal amount of toluene; 1.0529 g of 4-biphenylcarboxaldehyde was obtained with a yield of 89.11% and a purity of 99.13%.

[0039] Comparative Example 1 Compared with Example 1, the difference of Comparative Example 1 is that acetone is not used for recrystallization; 0.8249 g of 4-biphenylcarboxaldehyde was obtained with a yield of 69.81% and a purity of 99.07%.

[0040] Comparative Example 2 Compared with Example 6, the difference in Comparative Example 2 is that acetone is replaced by an equal volume of chloroform; 0.9918 g of 4-biphenylcarboxaldehyde was obtained with a yield of 83.94% and a purity of 99.47%.

[0041] Compared with Comparative Example 1, acetone was added to Example 1 for recrystallization. As a result, the yield and purity of Example 1 were better than those of Comparative Example 1, indicating that when acetone was used for recrystallization, the yield and purity of 4-biphenylcarboxaldehyde could be improved.

[0042] Compared with Comparative Example 2 and Examples 1, 4, and 7, Examples 5 and 6 simultaneously added a solution consisting of acetone and n-hexane 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 acetone and n-hexane play a synergistic role and can further improve the yield and purity of 4-biphenylcarboxaldehyde.

[0043] Compared with Example 6, Examples 8 and 9 added different types of hydrocarbon solutions for extraction. As a result, the yield and purity of Example 6 were better than those of Examples 8 and 9, indicating that when the added hydrocarbon solution was 1,2-dichloroethane, the yield and purity of the obtained 4-biphenylcarboxaldehyde were higher.

[0044] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing 4-biphenylcarboxaldehyde, characterized in that: The following steps are involved: S1, mixing trifluoroacetic acid and biphenyl, adding urotropine, and reacting to obtain a mixed reaction liquid; S2, the mixed reaction liquid is quenched, neutralized and extracted to obtain a crude 4-biphenylcarboxaldehyde product; S3, the crude 4-biphenylformaldehyde product and the sodium bisulfite solution are added to obtain a sodium bisulfite adduct, which is then subjected to alkaline hydrolysis and recrystallization to obtain 4-biphenylformaldehyde; The solution used in the recrystallization includes acetone, and the volume mass ratio of the solution used in the recrystallization to the crude 4-biphenylcarboxaldehyde is 10-13 mL:1 g.

2. The method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The recrystallization is performed twice, and the solution used in the recrystallization is the same twice.

3. A method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The solution used in the recrystallization also includes n-hexane, and the volume ratio of the acetone to the n-hexane is 4-7:

10.

4. The method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The volume ratio of trifluoroacetic acid to biphenyl in S1 is 15-20:1, and the molar ratio of biphenyl to hexamethylenetetramine is 1:1.5-2.

5.

5. The method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The reaction temperature in S1 is 70-100° C., and the reaction time is 8-12 hours.

6. The method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The solution used for quenching in S2 is a 4-6M hydrochloric acid solution, and the volume mass ratio of the hydrochloric acid solution to the biphenyl is 20mL:1g.

7. The method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The solution used in the neutralization is a 3wt% sodium hydroxide solution, and the neutralization is performed to adjust the pH to 7.

8. The method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The concentration of the sodium bisulfite solution in S3 is 29.6wt%, and the volume mass ratio of the sodium bisulfite solution to the biphenyl is 13-15mL:1g.

9. The method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The solution used for alkaline hydrolysis in S3 is a 24.8wt% sodium carbonate solution, and the volume mass ratio of the sodium carbonate solution to the biphenyl is 13-15mL:1g.

10. The method for synthesizing 4-biphenylcarboxaldehyde according to claim 1, characterized in that: The solution used for extraction in S2 is a hydrocarbon solution, and the hydrocarbon solution includes one or more of 1,2-dichloroethane, chloroform, toluene, benzene, and trichloroethane.

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