Preparation method of aromatic alcohol

Abstract

The invention provides a preparation method of aromatic alcohol. The preparation method provided by the invention comprises the step of reacting aromatic acid shown in a formula I with potassium borohydride in the presence of a catalyst to obtain aromatic alcohol shown in a formula II. The preparation method disclosed by the invention is simple, mild in condition, high in product purity and high in reaction yield. # imgabs0 #

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing aromatic alcohol. Background Art

[0002] p-Methoxyphenylethanol is an important intermediate for the synthesis of chiral drugs, fine chemicals, pesticides and other special materials. Biocatalytic asymmetric reactions have the advantages of being environmentally friendly, mild conditions and high selectivity. As a preferred route for the green and efficient preparation of chiral compounds, they are increasingly used in the production of some high value-added chiral compounds.

[0003] p-Methoxyphenylethanol is mainly used to synthesize p-methylstyrene. p-Methoxystyrene, also known as 4-methoxystyrene or 4-vinylphenyl ether, belongs to aromatic vinyl compounds. Since the side chain is a C=C double bond, the chemical properties are relatively active. The compound can slowly polymerize at room temperature and requires the addition of an inhibitor (stabilizer) for storage. It can self-polymerize (homopolymerize) and can also copolymerize with other unsaturated compounds. It is a very important chemical raw material and is widely used in materials, pharmaceutical intermediates, adhesives, coatings, sunscreens and other fields. The polymer of p-methoxystyrene has a protective group that is easily acid-lyzed by light. It is an excellent anti-corrosion material and has been widely used in the information industry.

[0004] There are mainly the following methods for synthesizing p-methoxyphenylethanol: (i) using toluene, p-chlorophenol, dimethyl sulfate, and ethylene oxide as raw materials for synthesis. This route is relatively complicated, the process is long, and more polluting materials are used in the process, and the yield is low; (ii) using methoxybenzene as a raw material to synthesize 4-methoxybromobenzene, and then preparing a Grignard reagent and introducing ethylene oxide to finally obtain methoxyphenylethanol. This process has a lower yield and is highly dangerous. Therefore, it is particularly important to study a method for synthesizing p-methoxyphenylethanol with high yield and greater safety. Summary of the invention

[0005] In order to solve one of the above technical problems existing in the prior art, the present invention provides a method for preparing aromatic alcohol, which has the characteristics of simple process, mild and safe reaction conditions and high reaction yield.

[0006] The technical solution of the present invention is as follows:

[0007] The present invention provides a method for preparing an aromatic alcohol, the preparation method comprising the following steps:

[0008] The aromatic acid represented by formula I is reacted with potassium borohydride in the presence of a catalyst to obtain the aromatic alcohol represented by formula II;

[0009]

[0010] Wherein, in Formula I and Formula II, R1 is selected from C 1-6 A straight or branched alkyl group; R2 is selected from hydrogen or C 1-6 A straight chain or branched alkylene group.

[0011] According to some embodiments of the present invention, in Formula I and Formula II, R1 is selected from C 1-4 A straight chain or branched alkyl group.

[0012] According to some embodiments of the present invention, in Formula I and Formula II, R1 is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl.

[0013] According to some embodiments of the present invention, in Formula I and Formula II, R1 is selected from methyl or ethyl.

[0014] According to some embodiments of the present invention, in Formula I and Formula II, R1 is methyl.

[0015] According to some embodiments of the present invention, the aromatic acid represented by Formula I has a structure represented by Formula I-1:

[0016]

[0017] Wherein, R1 and R2 are defined as in Formula I.

[0018] According to some embodiments of the present invention, in Formula I and Formula II, R2 is selected from hydrogen or C 1-4 A straight chain or branched alkylene group.

[0019] According to some embodiments of the present invention, in Formula I and Formula II, R2 is selected from hydrogen, methylene, ethylene, propylene, isopropylene, butylene, isobutylene or tert-butylene.

[0020] According to some embodiments of the present invention, in Formula I and Formula II, R2 is hydrogen, methylene or ethylene.

[0021] According to some embodiments of the present invention, in Formula I and Formula II, R2 is methylene.

[0022] According to some embodiments of the present invention, the aromatic alcohol shown in Formula II has a structure shown in Formula II-1:

[0023]

[0024] wherein R1 and R2 are as defined in formula II.

[0025] According to some embodiments of the present invention, the method for preparing the aromatic alcohol comprises the following steps:

[0026] The aromatic acid represented by formula I-1 is reacted with potassium borohydride in the presence of a catalyst to obtain the aromatic alcohol represented by formula II-1;

[0027]

[0028] According to some embodiments of the present invention, the aromatic acid represented by formula I is p-methoxyphenylacetic acid, and the aromatic alcohol represented by formula II is p-methoxyphenylethanol.

[0029] According to some embodiments of the present invention, the catalyst includes boron trihalide and / or boron trihalide ether. The boron trihalide of the present invention includes but is not limited to: boron trifluoride, boron trichloride, etc.

[0030] According to some embodiments of the invention, the catalyst comprises boron trifluoride etherate.

[0031] According to some embodiments of the invention, the catalyst comprises boron trichloride etherate solution.

[0032] According to some embodiments of the present invention, the molar ratio of the aromatic acid represented by Formula I to potassium borohydride is (1-1.5):1, for example, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1 or any value therebetween.

[0033] According to some embodiments of the present invention, the molar ratio of the aromatic acid represented by Formula I to the catalyst is 1:(1.2-1.5), for example, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or any value therebetween.

[0034] According to some embodiments of the present invention, the reaction is carried out in an organic solvent. The organic solvent of the present invention includes but is not limited to oxygen-containing heterocyclic solvents, such as tetrahydrofuran. According to some embodiments of the present invention, the molar ratio of the aromatic acid shown in Formula I to the organic solvent is 1:(10-30), for example, 1:10, 1:12, 1:15, 1:18, 1:20, 1:22, 1:25, 1:30 or any value therebetween, preferably 1:(15-20).

[0035] According to some embodiments of the present invention, the reaction temperature is 0-10°C, such as 0°C, 3°C, 5°C, 8°C, 10°C or any value therebetween. According to some embodiments of the present invention, the reaction time is 2-8 hours.

[0036] According to some embodiments of the present invention, the preparation method further comprises a post-processing step. In some embodiments, the post-processing comprises the following steps:

[0037] After the reaction is completed, water is added to the reaction solution and the pH is adjusted, and then the solution is extracted with an ester organic solvent to obtain an organic phase;

[0038] The organic phase is dried and concentrated to obtain the aromatic alcohol shown in formula II.

[0039] In some embodiments, the mass ratio of the volume of added water to the reaction solution is 1 mL: (1.5-10) g.

[0040] In some embodiments, the pH is adjusted to 6-7.

[0041] In some embodiments, the ester organic solvent used for extraction includes ethyl acetate.

[0042] In some embodiments, the volume ratio of the ethyl acetate extraction amount to the material after adding water is 1:(1-3).

[0043] According to some embodiments of the present invention, the preparation method comprises the following steps:

[0044] The aromatic acid represented by Formula I, potassium borohydride, a catalyst and an organic solvent are mixed and reacted to obtain a reaction solution containing the aromatic alcohol represented by Formula II;

[0045] The reaction solution containing the aromatic alcohol represented by formula II is mixed with water, the pH is adjusted to 6-7, and then extracted with ethyl acetate to obtain an organic phase; the organic phase is dried and concentrated to obtain the aromatic alcohol represented by formula II.

[0046] According to some embodiments of the present invention, the temperature of the organic solvent is 0-5°C.

[0047] According to some embodiments of the present invention, the mixing is performed at 0-5°C.

[0048] According to some embodiments of the present invention, the reaction temperature is 5-10°C.

[0049] According to some embodiments of the present invention, there is provided a method for preparing p-methoxyphenylethanol, comprising the following steps: reacting p-methoxyphenylacetic acid with potassium borohydride in the presence of a catalyst to obtain p-methoxyphenylethanol. In some embodiments, the catalyst comprises boron trichloride etherate solution.

[0050] Compared with the prior art, the present invention has the following beneficial effects:

[0051] The invention uses para-aromatic carboxylic acid as a raw material, potassium borohydride as a reducing agent, and a suitable catalyst to reduce the carboxylic acid to a corresponding primary alcohol in one step. The process is simple, the conditions are mild, the safety is high, and the reaction rate is high. In particular, when para-methoxyphenylacetic acid is used as a raw material to prepare para-methoxyphenylethanol, the reaction yield can be as high as more than 98%, and an unexpected technical effect is achieved. DETAILED DESCRIPTION

[0052] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with embodiments. The specific embodiments described herein are only used to explain the present invention and are not intended to constitute any limitation to the present invention.

[0053] The term "alkyl" as used herein includes carbon-containing, saturated, straight-chain or branched hydrocarbon groups. In one embodiment, the alkyl group contains 1 to 6 carbon atoms, i.e., C 1-6 In one embodiment, the alkyl group contains 1-4 carbon atoms, i.e., C 1-4 Alkyl. "C 1-6 "Alkyl" refers to a straight-chain or branched saturated monovalent hydrocarbon group having 1, 2, 3, 4, 5 or 6 carbon atoms, such as C 1-5 Alkyl, C 1-4 Alkyl, C 1-3 Alkyl, C 2-5 Alkyl, C 2-4 Alkyl, C 2-3Alkyl. Among them, including but not limited to methyl, ethyl, n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t-Bu, -C(CH3)3), n-pentyl (-CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1-butyl (-CH2 ), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH(CH3)CH2CH3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3).

[0054] The reagents used in the following experiments of the present invention, unless otherwise specified, are all conventional commercial products or reagents prepared by conventional methods, and the methods used in the experiments, unless otherwise specified, are all conventional experimental methods. The instruments used in the experiments, unless otherwise specified, can all be obtained through commercial channels.

[0055] The p-methoxyphenylacetic acid used in the following experiments of the present invention has the structural formula: The CAS number is 104-01-8.

[0056] The boron trichloride ether solution used in the following experiments of the present invention is a commercially available Macklin reagent, and the mass concentration of boron trichloride is 50%.

[0057] Example 1

[0058] After adding 700g of tetrahydrofuran into the reaction bottle, the temperature was lowered. After the temperature dropped to 0°C, 90g of p-methoxyphenylacetic acid, 23g of potassium borohydride, and 220g of a 50% boron trichloride ether solution were added step by step. The temperature was controlled at 0-5°C. After the materials were added, the temperature was controlled at 5-10°C to start the reaction. The reaction was stopped after 6h of reaction. After the reaction, 2000ml of pure water was added and the pH was finely adjusted to between 6 and 7. After the pH was adjusted, 4000ml of ethyl acetate was prepared and extracted three times. After the extraction was completed, the organic phase was collected and added to a dryer to remove water, and the organic phase was vacuum recovered to obtain 81.3g of p-methoxyphenylethanol as a colorless oil with a purity of 99.9% and a comprehensive yield of 98.6%.

[0059] Example 2

[0060] After adding 700g of tetrahydrofuran into the reaction bottle, the temperature was lowered. After the temperature dropped to 0°C, 90g of p-methoxyphenylacetic acid, 21g of potassium borohydride, and 220g of a 50% boron trichloride ether solution were added step by step. The temperature was controlled at 0-5°C. After the addition of the materials, the temperature was controlled at 5-10°C to start the reaction. The reaction was stopped after 6h of reaction. After the reaction, 2000ml of pure water was added and the pH was finely adjusted to between 6 and 7. After the pH was adjusted, 4000ml of ethyl acetate was prepared and extracted three times. After the extraction was completed, the organic phase was collected and added to a dryer to remove water, and the organic phase was vacuum recovered to obtain 80.6g of p-methoxyphenylethanol as a colorless oil with a purity of 99.3% and a comprehensive yield of 97.7%.

[0061] Example 3

[0062] After adding 700g of tetrahydrofuran into the reaction bottle, the temperature was lowered. After the temperature dropped to 0°C, 90g of p-methoxyphenylacetic acid, 23g of potassium borohydride, and 210g of a 50% boron trichloride ether solution were added step by step. The temperature was controlled at 0-5°C. After the materials were added, the temperature was controlled at 5-10°C to start the reaction. The reaction was stopped after 6h of reaction. After the reaction, 2000ml of pure water was added and the pH was finely adjusted to between 6 and 7. After the pH was adjusted, 4000ml of ethyl acetate was prepared and extracted three times. After the extraction was completed, the organic phase was collected and added to a dryer to remove water, and the organic phase was vacuum recovered to obtain 80.3g of p-methoxyphenylethanol as a colorless oil with a purity of 99.6% and a comprehensive yield of 97.3%.

[0063] Comparative Example 1

[0064] After adding 700g of tetrahydrofuran into the reaction bottle, the temperature was lowered. After the temperature dropped to 0°C, 90g of p-methoxyphenylacetic acid, 16.2g of sodium borohydride, and 220g of a 50% boron trichloride ether solution were added step by step. The temperature was controlled at 0-5°C. After the materials were added, the temperature was controlled at 5-10°C to start the reaction. The reaction was stopped after 6h of reaction. After the reaction, 2000ml of pure water was added and the pH was finely adjusted to between 6 and 7. After the pH was adjusted, 4000ml of ethyl acetate was prepared and extracted three times. After the extraction was completed, the organic phase was collected and added to a dryer to remove water, and the organic phase was vacuum recovered to obtain 71.5g of p-methoxyphenylethanol as a colorless oil with a purity of 93.6% and a comprehensive yield of 79.3%.

[0065] Comparative Example 2

[0066] After adding 700g of tetrahydrofuran into the reaction bottle, the temperature was lowered. After the temperature dropped to 0°C, 90g of p-methoxyphenylacetic acid, 9.3g of lithium aluminum hydride, and 220g of a 50% boron trichloride ether solution were added step by step. The temperature was controlled at 0-5°C. After the materials were added, the temperature was controlled at 5-10°C to start the reaction. The reaction was stopped after 6h of reaction. After the reaction, 2000ml of pure water was added and the pH was finely adjusted to between 6 and 7. After the pH was adjusted, 4000ml of ethyl acetate was prepared and extracted three times. After the extraction was completed, the organic phase was collected and added to a dryer to remove water, and the organic phase was vacuum recovered to obtain 53.2g of p-methoxyphenylethanol as a colorless oil with a purity of 86.3% and a comprehensive yield of 51.3%.

[0067] Comparative Example 3

[0068] After adding 700g of tetrahydrofuran into the reaction bottle, the temperature was lowered. After the temperature dropped to 0°C, 90g of p-methoxyphenylacetic acid, 23g of potassium borohydride, and 220g of ZnCl2 were added step by step. The temperature was controlled at 0-5°C. After the materials were added, the temperature was controlled at 5-10°C to start the reaction. The reaction was stopped after 6h of reaction. After the reaction, 2000ml of pure water was added and the pH was fine-tuned to between 6-7. After the pH was adjusted, 4000ml of ethyl acetate was prepared and extracted three times. After the extraction was completed, the organic phase was collected and added to the dryer to remove water, and the organic phase was vacuum recovered to obtain 60.6g of p-methoxyphenylethanol as a colorless oil with a purity of 38.6% and a comprehensive yield of 16.3%.

[0069] The results of Examples 1 to 3 show that the p-methoxyphenylethanol prepared in the present application using p-methoxyphenylacetic acid as a raw material, boron trichloride etherate as a catalyst, and potassium borohydride as a reducing agent has a purity of more than 99% and a yield of more than 97%.

[0070] The results of Example 1 and Comparative Examples 1 and 2 show that in the reaction of reducing p-methoxyphenylacetic acid to p-methoxyphenylethanol, when boron trichloride ethyl ether is used as a catalyst, potassium borohydride is selected as a reducing agent, which has a higher reaction yield and product purity than when sodium borohydride or lithium aluminum hydride is used as a reducing agent.

[0071] Furthermore, the results of Example 1 and Comparative Example 3 show that in the reaction of reducing p-methoxyphenylacetic acid to p-methoxyphenylethanol, when potassium borohydride is used as a reducing agent, boron trichloride etherate is selected as a catalyst, which has a higher reaction yield and product purity than when ZnCl2 is used as a catalyst.

[0072] The technical solution of the present invention is not limited to the above-mentioned specific embodiments. All technical variations made according to the technical solution of the present invention fall within the protection scope of the present invention.

Claims

1. A method for preparing an aromatic alcohol, comprising the following steps: The aromatic acid represented by formula I is reacted with potassium borohydride in the presence of a catalyst to obtain the aromatic alcohol represented by formula II; in, In formula I and formula II, R1 is selected from C 1-6 A straight or branched alkyl group; R2 is selected from hydrogen or C 1-6 A straight chain or branched alkylene group.

2. The preparation method according to claim 1, characterized in that: R1 is selected from C 1-4 A straight chain or branched alkyl group; Preferably, R1 is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl; More preferably, R1 is methyl.

3. The preparation method according to claim 1 or 2, characterized in that: R2 is selected from hydrogen or C 1-4 A straight chain or branched alkylene group; Preferably, R2 is selected from hydrogen, methylene, ethylene, propylene, isopropylene, butylene, isobutylene or tert-butylene; More preferably, R2 is methylene.

4. The preparation method according to any one of claims 1 to 3, characterized in that: The aromatic acid shown in formula I has the structure shown in formula I-1, and the aromatic alcohol shown in formula II has the structure shown in formula II-1: Wherein, the definitions of R1 and R2 are the same as those in any one of claims 1 to 3; Preferably, the aromatic acid represented by formula I is p-methoxyphenylacetic acid, and the aromatic alcohol represented by formula II is p-methoxyphenylethanol.

5. The preparation method according to any one of claims 1 to 4, characterized in that: The catalyst comprises boron trihalide and / or boron trihalide ethyl ether; preferably, the boron trihalide comprises boron trifluoride and / or boron trichloride; Preferably, the catalyst comprises boron trichloride in ether.

6. The preparation method according to any one of claims 1 to 5, characterized in that: The molar ratio of the aromatic acid shown in formula I to potassium borohydride is (1-1.5):1; and / or the molar ratio of the aromatic acid shown in formula I to the catalyst is 1:(1.2-1.5).

7. The preparation method according to any one of claims 1 to 6, characterized in that: The reaction is carried out in an organic solvent, and the organic solvent preferably includes an oxygen-containing heterocyclic solvent, and more preferably includes tetrahydrofuran.

8. The preparation method according to claim 7, characterized in that: The molar ratio of the aromatic acid represented by formula I to the organic solvent is 1:(10-30).

9. The preparation method according to any one of claims 1 to 8, characterized in that: The reaction temperature is 0-10° C.; and / or the reaction time is 2-8 hours.

10. The preparation method according to any one of claims 1 to 9, characterized in that: The following steps are also included: After the reaction is completed, water is added to the reaction solution and the pH is adjusted, and then the solution is extracted with an ester organic solvent to obtain an organic phase; The organic phase is dried and concentrated to obtain the aromatic alcohol shown in Formula II; Preferably, the pH is adjusted to 6-7; Preferably, the ester organic solvent comprises ethyl acetate.

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