A kind of synthetic method of 4-biphenylmethanol

Abstract

The invention provides a method for synthesizing 4-biphenylmethanol: biphenyl is used as a raw material, and formaldehyde and HCl are subjected to a Blank chloromethylation reaction under the action of a Lewis acid to generate 4-chloromethylbiphenyl, which is then reacted with sodium benzoate to generate an intermediate 4-biphenylmethanol benzoate, and the 4-biphenylmethanol benzoate is hydrolyzed to generate 4-biphenylmethanol. The method has cheap and readily available raw materials, mild conditions, high production safety, reduced reaction costs, is easy to scale up, and has high industrial application value.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a method for synthesizing 4-biphenylmethanol. Background Art

[0002] The synthesis methods of 4-biphenylmethanol reported in the literature are mainly the following:

[0003] 1. The first synthesis method is to use 4-chlorobenzyl alcohol and phenylboric acid as raw materials, and synthesize 4-biphenylmethanol through Suzuki reaction under the action of palladium catalyst. The synthesis route is:

[0004]

[0005] The specific operation steps are as follows: using toluene as solvent, adding phenylboric acid and 4-chlorobenzyl alcohol into toluene, stirring and mixing, then adding a catalyst and potassium carbonate, refluxing, cooling after the raw materials react completely, filtering, extracting, evaporating the solvent, and recrystallizing to obtain the product.

[0006] This synthesis method uses 4-chlorobenzyl alcohol, phenylboric acid and a relatively expensive palladium catalyst, which has a high production cost and is not suitable for industrial production.

[0007] The second synthesis method is to use biphenyl, polyformaldehyde, and concentrated hydrochloric acid as raw materials, produce 4-chloromethylbiphenyl under the action of phosphoric acid and a catalyst, and then hydrolyze to produce 4-biphenylmethanol. The synthesis route is:

[0008]

[0009] The specific operation steps are as follows: add biphenyl, paraformaldehyde, phosphoric acid, concentrated hydrochloric acid and catalyst into a reaction bottle, heat to 100°C, and stir for 24 hours. Cool, separate the organic layer, and then add water to the organic layer. Reflux for 12 hours. After the reaction is complete, cool, filter, and dry to obtain a crude product, which is then recrystallized to obtain the final product.

[0010] Although the raw materials of this synthesis method are cheap and easily available, the second step is carried out in a closed environment, which poses a safety hazard. In addition, direct hydrolysis in the second step will cause the generated 4-biphenylmethanol to react with the unreacted raw materials to form ether, thereby greatly affecting the yield.

[0011] The third synthesis method is to use 4-biphenylcarboxylic acid as a raw material, react with methanol under the action of concentrated sulfuric acid to generate 4-biphenylcarboxylic acid methyl ester. 4-biphenylcarboxylic acid methyl ester is then reacted with sodium borohydride or palladium carbon to generate 4-biphenylmethanol, and its synthesis route is.

[0012]

[0013] This method uses expensive palladium carbon as a catalyst, which is costly and not suitable for industrial production. Therefore, it is urgent to develop a synthetic route that is simple to operate, has cheap raw materials, is easily available, and is environmentally friendly and suitable for industrial production. Summary of the invention

[0014] The invention aims to provide a new synthesis method of 4-biphenylmethanol, which has the advantages of cheap and readily available raw materials, mild reaction conditions, suitability for industrial production and the like.

[0015] The invention provides a method for synthesizing a 4-biphenylmethanol compound. The method uses biphenyl as a raw material, utilizes Blank chloromethylation reaction to generate an intermediate 4-chloromethylbiphenyl (I), and then reacts with sodium benzoate to generate a compound 4-biphenylmethanol benzoate (II), and finally hydrolyzes to obtain a product 4-biphenylmethanol (III).

[0016] The structure of 4-chloromethylbiphenyl (I):

[0017]

[0018] The structure of 4-biphenylmethanol benzoate (II) is as follows:

[0019]

[0020] The structure of 4-biphenylmethanol (III) is as follows:

[0021]

[0022] In the present invention, the preparation method of 4-biphenylmethanol is carried out according to the following reaction route:

[0023]

[0024] In the present invention, the molar ratio of 4-chloromethylbiphenyl to paraformaldehyde is 1:1-4, and the molar ratio of biphenyl to HCl gas is 1:1-5.

[0025] The weight ratio of biphenyl to phosphoric acid in the present invention is 1:5-15, the concentration of phosphoric acid used is 65%-85%, and the volume ratio of phosphoric acid to acetic acid is 1:0.5-5.

[0026] The catalyst used in the present invention is one or more of cupric chloride, ferrous chloride, ferric chloride, nickel chloride, zinc chloride, and aluminum chloride, and the mass ratio of biphenyl to the catalyst is 10 to 40:1.

[0027] In the present invention, the molar ratio of 4-chloromethylbiphenyl to sodium benzoate is 1:1-4.

[0028] The solvent used in the present invention is one or more of toluene, ethyl acetate, ethylene glycol dimethyl ether, dioxane, N,N-dimethylformamide (DMF) and tetrahydrofuran.

[0029] The alkali used in the present invention is one or more of KOH, NaOH and LiOH, and the mass concentration of the aqueous solution thereof is 5% to 50%.

[0030] The solvent used for recrystallization in the present invention is one or more of toluene, ethyl acetate, carbon tetrachloride, ethanol and n-hexane.

[0031] The specific steps are as follows:

[0032] Add biphenyl, paraformaldehyde, phosphoric acid, acetic acid and catalyst to the reaction bottle, heat to 60 ° C, and slowly introduce HCl gas while stirring. After 6 hours of reaction, point the plate, gas phase analysis, cool the raw material after reaction, extract with toluene, dry with anhydrous sodium sulfate, and concentrate under reduced pressure. Add reaction solvent and sodium benzoate to the concentrated reaction solution, heat to 90 ° C, stir for 4 hours, point the plate for analysis, after the raw material is completely reacted, cool to room temperature, add water, extract with ethyl acetate, dry with anhydrous sodium sulfate, and concentrate under reduced pressure. Residues are recrystallized from toluene to separate the disubstituted by-products, collect the filtrate, add toluene and alkaline solution to the concentrated reaction solution, react for 2 hours, point the plate, add water and ether extraction after the raw material is completely reacted, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and recrystallize.

[0033] The present invention has the following advantages:

[0034] 1. The raw materials used are cheap and easily available.

[0035] 2. Mild reaction conditions and high yield.

[0036] 3. Compared with traditional methods, this method greatly reduces the generation of by-products.

[0037] 4. The solvent has low toxicity and is environmentally friendly.

[0038] 5. In the second step, sodium benzoate and 4-chloromethylbiphenyl are used for esterification, which can better separate the disubstituted by-products generated in the first step and improve the purity of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 The hydrogen nuclear magnetic resonance spectrum of 4-chloromethylbiphenyl (I) prepared in Examples 1 and 2;

[0040] Figure 2 The hydrogen nuclear magnetic resonance spectrum of 4-biphenylmethanol benzoate (II) prepared in Example 3;

[0041] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of 4-biphenylmethanol (III) prepared in Example 4. DETAILED DESCRIPTION

[0042] The following examples will further illustrate the present invention, but are not intended to limit the present invention. Nuclear magnetic resonance was measured by a Bruker 400 nuclear magnetic resonance instrument, and gas chromatography (GC) was measured by an Agilent 7820 chromatograph.

[0043] Example 1

[0044] Synthesis of 4-Chloromethylbiphenyl (I)

[0045]

[0046] 62g biphenyl, 45g paraformaldehyde, 500ml 85% phosphoric acid, 500ml glacial acetic acid, 5g CuCl2 were added to the reaction bottle, heated to 60°C, and 55g HCl gas was slowly introduced while stirring. After 6h of reaction, the plate was observed and the gas phase analysis showed that the raw material content was 4% and the content of the by-product was 11%. After the reaction of the raw material, it was cooled to room temperature, extracted with toluene, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized by adding 300ml ethanol. After filtering and drying, 66.2g of the product was obtained with a yield of 81%. Its NMR data are as follows:

[0047] 1 H NMR (400MHz, CDCl3) δ4.61~4.64(m,2H), 7.32~7.38(m,1H), 7.40~7.48(m,4H), 7.54~7.61(m,4H).

[0048] Example 2

[0049] 62g biphenyl, 45g paraformaldehyde, 500ml 85% phosphoric acid, 500ml glacial acetic acid, 5g ZnCl2 were added to the reaction bottle, heated to 60℃, and 55g HCl gas was slowly introduced while stirring. After 6h of reaction, the plate was observed and the gas phase analysis showed that the raw material content was 4.2% and the by-product content was 11.5%. After the reaction of the raw material, it was cooled, extracted with toluene, dried, concentrated, and recrystallized by adding 300ml ethanol. After filtering and drying, 64.3g of the product was obtained with a yield of 78.8%. Its NMR data are as follows:

[0050] 1 H NMR (400MHz, CDCl3) δ4.61~4.64(m,2H), 7.32~7.38(m,1H), 7.40~7.48(m,4H), 7.54~7.61(m,4H).

[0051] Example 3

[0052] Synthesis of 4-Biphenylmethanol benzoate (II)

[0053]

[0054] 66g of 4-chloromethylbiphenyl was added to the reaction bottle, 200ml of ethylene glycol dimethyl ether was added to dissolve, and 129g of sodium benzoate was added. After the addition, the temperature was raised to 80°C, stirred, and the plate was observed every 30 minutes. After the raw materials were completely reacted, the temperature was lowered, 400ml of water was added, and ethyl acetate was extracted, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized from 300ml of toluene to obtain 90.7g of the product with a yield of 96.6%. The NMR data are as follows:

[0055] 1H NMR (400MHz, CDCl3) δ5.43~5.48(m,2H),7.31~7.37(m,1H),7.40~7.46(m,4H) ,7.40~7.47(m,4H),7.49~7.58(m,3H),7.58~7.64(m,4H),8.06~8.13(m,2H).

[0056] Example 4

[0057] Synthesis of 4-Biphenylmethanol (III)

[0058]

[0059] 71.8g of raw material was added to the reaction bottle, 200g of 15% KOH solution was slowly added at room temperature, and stirred for 1h after the addition was completed. The plate was checked to see whether the raw material was completely reacted. After the reaction was complete, 300ml of water and 200ml of ether were added for extraction, dried, concentrated, and recrystallized from 300ml of n-hexane to obtain 44.6g of 4-biphenylmethanol, with a yield of 97.3%. The NMR data are as follows:

[0060] 1 H NMR (400MHz, CDCl3) δ1.77~1.85(m,1H), 4.70~4.77(m,2H), 7.31~7.37(m,1H), 7.40~7.46(m,4H), 7.55~7.61(m,4H).

[0061] The above-mentioned implementation cases only express the implementation methods of the present invention, but they cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A method for synthesizing 4-biphenylmethanol, characterized in that , comprising the reaction steps: (1) biphenyl, paraformaldehyde, acetic acid, phosphoric acid and a catalyst are mixed, HCl gas is introduced, heated to 40-100° C., reacted for 4-24 hours, cooled to room temperature, extracted with toluene, dried with anhydrous sodium sulfate, and dried under reduced pressure to obtain a product, 4-chloromethylbiphenyl; (2) adding a solvent and sodium benzoate to the product of step (1), heating to 70-120° C., reacting for 4-8 hours, cooling to room temperature, adding water, extracting with ethyl acetate, drying with anhydrous sodium sulfate, drying under reduced pressure, and recrystallizing with toluene to separate the disubstituted byproduct to obtain the product 4-biphenylmethanol benzoate; (3) adding alkali to the product of step (2) for hydrolysis, reacting for 3-6 hours, adding water, extracting, drying, and drying under reduced pressure to obtain a crude product, which is then recrystallized to obtain 4-biphenylmethanol; The solvent used in step (2) is one or more of toluene, ethyl acetate, ethylene glycol dimethyl ether, dioxane, N,N-dimethylformamide, and tetrahydrofuran; the molar ratio of 4-chloromethylbiphenyl to sodium benzoate in step (2) is 1:1-4; The catalyst used in step (1) is one or more of copper chloride and zinc chloride, and the mass ratio of biphenyl to the catalyst is 10 to 40:

1.

2. A method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The structure of the product 4-chloromethylbiphenyl in step (1) is shown in Formula I: The product structure of step (2) is shown in Formula II: The product structure of step (3) is shown in formula III:

3. A method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: In the step (1), the molar ratio of biphenyl to paraformaldehyde is 1:1-4, the molar ratio of biphenyl to HCl gas is 1:1-5, and the weight ratio of biphenyl to phosphoric acid is 1:5-15.

4. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The concentration of phosphoric acid used in step (1) is 65% to 85%, and the volume ratio of phosphoric acid to acetic acid is 1:0.5 to 5.

5. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The alkali used in step (3) is one or more of KOH, NaOH, and LiOH, and the mass concentration of the aqueous solution thereof is 5% to 50%.

6. The method for synthesizing 4-biphenylmethanol according to claim 1, characterized in that: The solvent used for recrystallization in step (3) is one or more of toluene, ethyl acetate, carbon tetrachloride, ethanol, and n-hexane; the extraction is performed using ether extraction, and the drying is performed using anhydrous sodium sulfate drying.

Images