Synthesis method of 4-biphenylcarbinol

Abstract

The present invention relates to the technical field of chemical synthesis, and provides a 4-biphenylmethanol synthesis method, which comprises: S1, uniformly mixing biphenyl, a solvent and a catalyst I, adding methyl chloroformate in an inert atmosphere, and carrying out a reaction to obtain 4-methyl bibenzoate; s2, mixing the methyl 4-bibenzoate, an alcoholic solution and a catalyst II, reacting, and recrystallizing to obtain the 4-biphenylcarbinol, a solution used during recrystallization in S2 comprises ethyl acetate. According to the technical scheme, the problems of low yield and low purity in the synthesis process of 4-biphenylcarbinol 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-biphenylmethanol. Background Art

[0002] As an organic compound, 4-biphenylmethanol is widely used in medicine, dyes, optics and other fields. The synthesis methods of 4-biphenylmethanol reported in the literature are mainly as follows: The first synthesis method is to synthesize 4-biphenylmethanol by hydrolysis of benzyl halide. In 2020, Wang Zhusheng et al. disclosed in CN111470970 A that a hydrolyzing agent is added to a water solvent, and an alkaline solution is added dropwise to generate an ester and undergo a hydrolysis reaction, thereby finally preparing benzyl alcohol. The synthesis route is:

[0003] This synthetic route generally uses water as the reaction solvent for the hydrolysis of substituted benzyl halides, and high-temperature hydrolysis is performed in the presence of an inorganic base to obtain the target product. However, this method is prone to produce impurities such as disubstituted benzyl ethers, resulting in low product yield and poor purity.

[0004] The second synthesis method is the Suzuki coupling of aromatic compounds and aromatic boronic acid derivatives. In 2003, Coccia et al. published a synthesis method for 4-biphenylmethanol in the Journal of Inorganic Chemistry. The synthesis route is:

[0005] This synthesis method uses 4-hydroxymethylphenylboronic acid and iodobenzene as starting materials, and undergoes Suzuki reaction under the catalysis of K2CO3 and Pd-ZnNPs to finally synthesize the product 4-biphenylmethanol. The Pd-ZnNPs used in the reaction are expensive and difficult to obtain.

[0006] The third synthesis method is to use biphenyl substrate as raw material to synthesize 4-biphenyl formaldehyde and then reduce it to synthesize 4-biphenyl methanol. In 2011, Wu Xibing et al. used chlorobenzene as solvent and anhydrous aluminum chloride and cuprous chloride as catalysts to synthesize 4-biphenyl formaldehyde. The synthesis route is:

[0007] The specific operation steps of this method are: biphenyl, anhydrous aluminum chloride, cuprous chloride and chlorobenzene are mixed in a weight ratio of 1:1.2:0.1:0.2:2, HCl gas is introduced at 30°C for 10 minutes, and then CO and HCl mixed gas is introduced for 24 hours. TLC monitors the reaction process, and the gas introduced for reaction is toxic and difficult to control.

[0008] Therefore, different synthesis methods have significant differences in yield, purity, etc. A synthesis method with low yield and purity often means increased cost and decreased product quality. Therefore, it is necessary to propose a synthesis method for 4-biphenylmethanol with high yield and high purity. Summary of the invention

[0009] The invention provides a method for synthesizing 4-biphenylmethanol, which solves the problems of low yield and low purity in the synthesis process of 4-biphenylmethanol in the related art.

[0010] The technical solution of the present invention is as follows: The present invention provides a method for synthesizing 4-biphenylmethanol, comprising the following steps: S1, biphenyl, solvent and catalyst I are mixed evenly, and methyl chloroformate is added under an inert atmosphere, and after reaction, methyl 4-biphenylformate is obtained; S2, mixing the methyl 4-biphenylcarboxylate, the alcohol solution and the catalyst II, and performing the reaction and recrystallization to obtain 4-biphenylmethanol; The solution used in the recrystallization in S2 includes ethyl acetate.

[0011] As a further technical solution, the molar ratio of biphenyl in S1 to the catalyst I is 1:1-4.

[0012] As a further technical solution, the molar ratio of biphenyl in S1 to the catalyst I is 1:2-4.

[0013] As a further technical solution, the mass volume ratio of biphenyl to the solvent in S1 is 1g:5~10mL.

[0014] As a further technical solution, the mass volume ratio of biphenyl to the solvent in S1 is 1g:8~10mL.

[0015] As a further technical solution, the molar ratio of biphenyl to methyl chloroformate in S1 is 1:1-5.

[0016] As a further technical solution, the molar ratio of biphenyl to methyl chloroformate in S1 is 1:3-5.

[0017] As a further technical solution, the solution used in the recrystallization in S2 also includes n-hexane, and the volume ratio of the ethyl acetate to the n-hexane is 3-5:2.

[0018] In the present invention, ethyl acetate and n-hexane are added simultaneously for recrystallization, and the synergistic effect of the two is brought into play, thereby further improving the yield and purity of 4-biphenylmethanol.

[0019] As a further technical solution, the volume mass ratio of the solution used in the recrystallization in S2 to the biphenyl is 10 mL:1 g.

[0020] As a further technical solution, the solvent in S1 includes one or more of dichloromethane, 1,2-dichloroethane, toluene, and chlorobenzene.

[0021] As a further technical solution, the catalyst I in S1 is a Lewis acid catalyst, and the Lewis acid catalyst includes one or more of aluminum chloride, ferric chloride, nickel chloride, and zinc chloride.

[0022] As a further technical solution, the reaction temperature in S1 is 25-45° C., and the reaction time is 4-8 hours.

[0023] As a further technical solution, the reaction temperature in S1 is 30-40° C., and the reaction time is 4-6 hours.

[0024] As a further technical solution, after the reaction in S1, quenching, extraction, drying, reduced pressure concentration and recrystallization are carried out in sequence to obtain methyl 4-bibenzoate, and the solution used for recrystallization in S1 includes one or more of chloroform, acetone and n-hexane.

[0025] As a further technical solution, the number of recrystallizations in S1 is 2 times, and the solutions for the 2 recrystallizations are the same.

[0026] As a further technical solution, the volume mass ratio of the total solution used in the recrystallization in S1 to the biphenyl is 5 mL:1 g.

[0027] As a further technical solution, the desiccant used for drying in S1 is anhydrous magnesium sulfate.

[0028] As a further technical solution, the extraction solution is an ester solution, and the ester solution includes one or more of ethyl acetate, butyl acetate, and isopropyl acetate.

[0029] As a further technical solution, the extraction solution is preferably isopropyl acetate.

[0030] As a further technical solution, the extraction is performed twice, and the solutions of the two extractions are the same.

[0031] As a further technical solution, the volume mass ratio of the total extracted solution to the biphenyl is 16mL:1g.

[0032] As a further technical solution, the alcohol solution in S2 includes one or more of methanol, ethanol, and isopropanol.

[0033] As a further technical solution, the mass volume ratio of the methyl 4-bibenzoate to the alcohol solution is 1 g:5-10 mL.

[0034] As a further technical solution, the mass volume ratio of the methyl 4-bibenzoate to the alcohol solution is 1 g:8~10 mL.

[0035] As a further technical solution, the catalyst II in S2 is an alloy catalyst, and the alloy catalyst includes one or more of a Ni-Al alloy catalyst, a Pd-Ag alloy catalyst, a Pt-Sn alloy catalyst, and a Cu-Zn alloy catalyst.

[0036] As a further technical solution, the catalyst II is preferably a Cu-Zn alloy catalyst.

[0037] As a further technical solution, the amount of catalyst II added is 5% to 10% of the mass of methyl 4-bibenzoate.

[0038] As a further technical solution, the reaction temperature in S2 is 20-40° C., and the reaction time is 12-16 hours.

[0039] As a further technical solution, the reaction temperature in S2 is 25-35° C., and the reaction time is 12-14 h.

[0040] As a further technical solution, the reaction in S2 is carried out under a hydrogen atmosphere.

[0041] As a further technical solution, the reaction pressure in S2 is 5~10MPa.

[0042] As a further technical solution, the reaction pressure in S2 is 7~10MPa.

[0043] The working principle and beneficial effects of the present invention are: In the present invention, biphenyl is used as a raw material, biphenyl and methyl chloroformate undergo Friedel-Crafts acylation reaction under the action of Lewis acid to generate an intermediate 4-biphenylcarboxylic acid methyl ester, which is then subjected to catalyst hydrogenation reduction and recrystallization to generate 4-biphenylmethanol. The method has cheap and readily available raw materials, mild catalytic conditions, high production safety, and uses ethyl acetate as a recrystallization solution to improve the yield and purity of 4-biphenylmethanol. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0045] Figure 1 The hydrogen nuclear magnetic resonance spectrum of methyl 4-bibenzoate prepared in Example 4 of the present invention; Figure 2The gas chromatogram of methyl 4-bibenzoate prepared in Example 4 of the present invention; Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of 4-biphenylmethanol prepared in Example 4 of the present invention; Figure 4 This is a gas chromatogram of 4-biphenylmethanol prepared in Example 4 of the present invention. DETAILED DESCRIPTION

[0046] 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.

[0047] In the following examples and comparative examples: Cu-Zn alloy catalyst: particle size is 30 nm, element content: 30wt% Cu, 70wt% Zn; Pt-Sn alloy catalyst: particle size is 5 nm, element content: 50wt% Pt, 50wt% Sn.

[0048] Example 1 A method for synthesizing 4-biphenylmethanol comprises the following steps: S1. Add 10.1272 g (64.85 mmol) of biphenyl, 50 mL of toluene, and 8.6575 g (64.85 mmol) of anhydrous aluminum chloride into a reaction flask, evacuate with nitrogen protection, heat to 25°C, add 6 mL of methyl chloroformate (64.85 mmol) while stirring, react for 8 h, quench with ice water, add 80 mL × 2 of isopropyl acetate for extraction, dry over anhydrous magnesium sulfate, concentrate under reduced pressure, add 25 mL × 2 of chloroform for recrystallization, and dry to obtain 4-biphenylcarboxylic acid methyl ester; S2. Add 10.1076 g (47.12 mmol) of methyl 4-biphenylcarboxylate, 50 mL of methanol and 0.8236 g of Cu-Zn alloy catalyst into an autoclave. After sealing and installing the autoclave, replace the air in the autoclave with hydrogen and fill it with hydrogen to 5 MPa. After reacting at 20°C for 16 h, filter and concentrate under reduced pressure, add ethyl acetate for recrystallization to obtain 7.9206 g of 4-biphenylmethanol with a yield of 91.24% and a purity of 99.25%.

[0049] Example 2 A method for synthesizing 4-biphenylmethanol comprises the following steps: S1. Add 10.1272 g (64.85 mmol) of biphenyl, 80 mL of chlorobenzene, and 17.315 g (129.7 mmol) of anhydrous ferric chloride into a reaction flask, evacuate with nitrogen protection, heat to 35°C, add 18 mL of methyl chloroformate (184.55 mmol) while stirring, react for 6 h, quench with ice water, add 80 mL × 2 of isopropyl acetate for extraction, dry over anhydrous magnesium sulfate, concentrate under reduced pressure, add 25 mL × 2 of chloroform for recrystallization, and dry to obtain methyl 4-biphenylcarboxylate; S2. Add 10.1021 g (47.12 mmol) of methyl 4-biphenylcarboxylate, 80 mL of ethanol and 0.9215 g of Cu-Zn alloy catalyst into an autoclave. After sealing and installing the autoclave, replace the air in the autoclave with hydrogen and fill it with hydrogen to 7 MPa. After reacting at 25 °C for 14 h, filter and concentrate under reduced pressure, add ethyl acetate for recrystallization to obtain 7.9302 g of 4-biphenylmethanol with a yield of 91.35% and a purity of 99.33%.

[0050] Example 3 A method for synthesizing 4-biphenylmethanol comprises the following steps: S1. Add 10.1272 g (64.85 mmol) of biphenyl, 100 mL of 1,2-dichloroethane, and 34.63 g (259.4 mmol) of anhydrous nickel chloride into a reaction flask, evacuate with nitrogen protection, heat to 45°C, add 30 mL of methyl chloroformate (324.25 mmol) while stirring, react for 4 h, quench with ice water, add 80 mL × 2 of isopropyl acetate for extraction, dry over anhydrous magnesium sulfate, concentrate under reduced pressure, add 25 mL × 2 of chloroform for recrystallization, and dry to obtain methyl 4-biphenylcarboxylate; S2. Add 10.1007 g (47.12 mmol) of methyl 4-biphenylcarboxylate, 100 mL of isopropanol, and 1.0237 g of Cu-Zn alloy catalyst into an autoclave. After sealing and installing the autoclave, replace the air in the autoclave with hydrogen and fill it with hydrogen to 10 MPa. After reacting at 40°C for 12 h, filter and concentrate under reduced pressure, add ethyl acetate for recrystallization to obtain 7.9015 g of 4-biphenylmethanol with a yield of 91.02% and a purity of 99.26%.

[0051] Example 4 A method for synthesizing 4-biphenylmethanol comprises the following steps: S1. Add 10.1272 g (64.85 mmol) of biphenyl, 80 mL of dichloromethane, and 17.315 g (129.7 mmol) of anhydrous zinc chloride into a reaction flask, evacuate with nitrogen protection, heat to 40°C, add 18 mL of methyl chloroformate (184.55 mmol) while stirring, react for 6 h, quench with ice water, add 80 mL × 2 of isopropyl acetate for extraction, dry over anhydrous magnesium sulfate, concentrate under reduced pressure, add 25 mL × 2 of chloroform for recrystallization, and dry to obtain methyl 4-biphenylcarboxylate; S2. Add 10.1046 g (47.12 mmol) of methyl 4-biphenylcarboxylate, 80 mL of methanol and 0.9215 g of Cu-Zn alloy catalyst into an autoclave. After sealing and installing the autoclave, replace the air in the autoclave with hydrogen and fill it with hydrogen to 7 MPa. After reacting at 35 °C for 14 h, filter and concentrate under reduced pressure, add ethyl acetate for recrystallization to obtain 7.8764 g of 4-biphenylmethanol with a yield of 90.73% and a purity of 99.23%.

[0052] The hydrogen nuclear magnetic resonance spectrum of methyl 4-bibenzoate prepared in Example 4 is as follows: Figure 1 As shown, the gas chromatogram of methyl 4-bibenzoate is as follows Figure 2 As shown, the nuclear magnetic resonance hydrogen spectrum of 4-biphenylmethanol is as follows Figure 3 As shown, the gas chromatogram of 4-biphenylmethanol is as follows Figure 4 shown.

[0053] Example 5 Compared with Example 4, the difference of Example 5 is that ethyl acetate is replaced by an equal amount of n-hexane; 8.1107 g of 4-biphenylmethanol was obtained with a yield of 93.43% and a purity of 99.45%.

[0054] Example 6 Compared with Example 4, the difference of Example 6 is that ethyl acetate is replaced by ethyl acetate and n-hexane in a volume ratio of 3:2; 8.3582 g of 4-biphenylmethanol was obtained with a yield of 96.28% and a purity of 99.86%.

[0055] Example 7 Compared with Example 4, the difference of Example 7 is that ethyl acetate is replaced by ethyl acetate and n-hexane in a volume ratio of 5:2; 8.1811 g of 4-biphenylmethanol was obtained with a yield of 94.24% and a purity of 99.72%.

[0056] Example 8 Compared with Example 6, the difference in Example 8 is that isopropyl acetate is replaced by an equal amount of ethyl acetate; 7.9206 g of 4-biphenylmethanol was obtained with a yield of 91.24% and a purity of 99.26%.

[0057] Example 9 Compared with Example 6, the difference in Example 9 is that isopropyl acetate is replaced by an equal amount of butyl acetate; 8.0257 g of 4-biphenylmethanol was obtained with a yield of 92.45% and a purity of 99.41%.

[0058] Example 10 Compared with Example 6, the difference of Example 10 is that the Cu-Zn alloy catalyst is replaced with an equal amount of Pt-Sn alloy catalyst; 7.9710 g of 4-biphenylmethanol was obtained with a yield of 91.82% and a purity of 99.33%.

[0059] Embodiment 11 Compared with Example 6, the difference of Example 11 is that chloroform is replaced by an equal amount of acetone; 8.0135 g of 4-biphenylmethanol was obtained with a yield of 92.31% and a purity of 99.39%.

[0060] Example 12 Compared with Example 6, Example 11 is different in that chloroform is replaced by an equal amount of toluene.

[0061] 7.9675 g of 4-biphenylmethanol was obtained with a yield of 91.78% and a purity of 99.30%.

[0062] Comparative Example 1 Compared with Example 1, the difference of Comparative Example 1 is that no ethyl acetate is added for recrystallization; 7.800 g of 4-biphenylmethanol was obtained with a yield of 89.62% and a purity of 99.26%.

[0063] Compared with Comparative Example 1, ethyl acetate 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 the use of ethyl acetate for recrystallization can improve the yield and purity of 4-biphenylmethanol.

[0064] Compared with Examples 4 and 5, Examples 6 and 7 simultaneously added ethyl acetate and n-hexane for recrystallization, and the yield and purity of Examples 6 and 7 were better than those of Examples 4 and 5, indicating that ethyl acetate and n-hexane play a synergistic role and can further improve the yield and purity of 4-biphenylmethanol. In Examples 6 and 7, ethyl acetate and n-hexane in different volume ratios were added for recrystallization, and the yield and purity of Example 6 were better than those of Example 7, indicating that when the volume ratio of ethyl acetate to n-hexane is 3:2, the yield and purity of the obtained 4-biphenylmethanol are higher.

[0065] Compared with Example 6, Examples 8 and 9 used different types of ester 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 isopropyl acetate was used for extraction, the yield and purity of 4-biphenylmethanol could be further improved.

[0066] Compared with Example 6, Example 10 added a Pt-Sn alloy catalyst. As a result, the yield and purity of Example 6 were better than those of Example 10, indicating that when the added catalyst was a Cu-Zn alloy, the yield and purity of the obtained 4-biphenylmethanol were higher.

[0067] Compared with Example 6, Examples 11 and 12 used different solvents for recrystallization in S1. As a result, the yield and purity of Example 6 were better than those of Examples 11 and 12, indicating that when chloroform was used for recrystallization in S1, the yield and purity of 4-biphenylmethanol were higher.

[0068] 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-biphenylmethanol, characterized in that: The following steps are involved: S1, biphenyl, solvent and catalyst I are mixed evenly, and methyl chloroformate is added under an inert atmosphere, and after reaction, methyl 4-biphenylformate is obtained; S2, mixing the methyl 4-biphenylcarboxylate, the alcohol solution and the catalyst II, and performing the reaction and recrystallization to obtain 4-biphenylmethanol; The solution used in the recrystallization in S2 includes ethyl acetate.

2. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The solution used in the recrystallization in S2 also includes n-hexane, and the volume ratio of the ethyl acetate to the n-hexane is 3-5:

2.

3. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The solvent in S1 includes one or more of dichloromethane, 1,2-dichloroethane, toluene, and chlorobenzene.

4. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The catalyst I in S1 is a Lewis acid catalyst, and the Lewis acid catalyst includes one or more of aluminum chloride, ferric chloride, nickel chloride, and zinc chloride.

5. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The reaction temperature in S1 is 25-45° C., and the reaction time is 4-8 hours.

6. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: After the reaction in S1, quenching, extraction, drying, concentration under reduced pressure and recrystallization are performed in sequence to obtain methyl 4-bibenzoate. The solution used for recrystallization in S1 includes one or more of chloroform, acetone, n-hexane and toluene.

7. The method for synthesizing 4-biphenylmethanol according to claim 6, characterized in that: The extraction solution is an ester solution, and the ester solution includes one or more of ethyl acetate, butyl acetate, and isopropyl acetate.

8. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The alcohol solution in S2 includes one or more of methanol, ethanol, and isopropanol.

9. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The catalyst II in S2 is an alloy catalyst, and the alloy catalyst includes one or more of a Ni-Al alloy catalyst, a Pd-Ag alloy catalyst, a Pt-Sn alloy catalyst, and a Cu-Zn alloy catalyst.

10. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The reaction temperature in S2 is 20-40° C., and the reaction time is 12-16 h.

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