CN109293478B - Method for preparing tetrafluorobenzyl alcohol - Google Patents
Method for preparing tetrafluorobenzyl alcohol Download PDFInfo
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- CN109293478B CN109293478B CN201811303725.2A CN201811303725A CN109293478B CN 109293478 B CN109293478 B CN 109293478B CN 201811303725 A CN201811303725 A CN 201811303725A CN 109293478 B CN109293478 B CN 109293478B
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- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
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Abstract
The invention discloses a method for preparing tetrafluorobenzyl alcohol, belonging to the technical field of organic synthesis. Tetrafluorobenzoic acid reacts with thionyl chloride to generate tetrafluorobenzoyl chloride, and then tetrafluorobenzoyl chloride is used as a raw material, and sodium borohydride activated by an ether solvent is reduced in water to obtain tetrafluorobenzyl alcohol. The ether-containing solvent is complexed with sodium borohydride to activate the sodium borohydride, water is used as the solvent for reduction, the reaction yield is high, the reaction can be completed by the catalytic amount of the reducing agent sodium borohydride, and the reaction process is more green and environment-friendly.
Description
Technical Field
The invention relates to preparation of benzyl alcohol, in particular to a method for preparing tetrafluorobenzyl alcohol, and belongs to the technical field of organic synthesis.
Background
Tetrafluorobenzyl alcohol, molecular formula: C7H4F4O molecular weight: 180.10, respectively; comprises 2,3,4, 5-tetrafluorobenzyl alcohol CAS: 53072-18-7; 2,4,5, 6-tetrafluorobenzyl alcohol and 2,3,5, 6-tetrafluorobenzyl alcohol, CAS No.: 4084-38-2, also known as tetrafluorobenzyl alcohol, the existing method for synthesizing tetrafluorobenzyl alcohol has some defects, such as 2,3,5, 6-tetrafluorobenzyl alcohol, which is mainly classified into the following:
first, adopting tetrafluorobenzoic acid to directly reduce into tetrafluorobenzyl alcohol
The process route adopted by Bayer, also the most classical one, uses NaBH4 for reduction, using dimethyl sulfate as an auxiliary agent to directly reduce tetrafluorobenzoic acid to tetrafluorobenzyl alcohol (DE 3714602), and the reaction equation is as follows:
the yield of the method is up to 96%, but the reaction needs to use highly toxic dimethyl sulfate, the purchase and the use are limited to a certain extent, the usage amount of the dimethyl sulfate is large, and the unit consumption reaches 0.6.
Second, reduction with activated sodium borohydride
CN1900037 reports the activation of NaBH4 by adding metal chloride to enhance the reduction activity of NaBH4, and then the reduction of tetrafluorobenzoic acid, the reaction equation is as follows:
the method does not need highly toxic dimethyl sulfate, but adds 2 times of metal chloride such as ZnCl2 or AlCl3 by weight ratio, forms metal complex boride together with triethylamine and NaBH4, and reduces the metal complex boride in an organic solvent. The process has the defect that the wastewater generated by the reaction contains a large amount of metal chloride and is not easy to treat.
Thirdly, direct reduction by acyl chloride
CN2006101010646 reports the preparation of tetrafluorobenzoic acid into tetrafluorobenzoyl chloride, followed by reduction with excess NaBH4, the reaction equation is as follows:
the method needs ether organic solvent, the NaBH4 dosage is 10 times of the molar weight of the raw material, the reduction cost is high, a large amount of gas is generated during the post-treatment, and certain potential safety hazard exists.
Fourthly, reducing methyl tetrafluorobenzoate under the condition of activating sodium borohydride
Tangyu reported making methyl tetrafluorobenzoate from tetrafluorobenzoic acid followed by reduction with NaBH4 and I2, reference: organic Synthesis 2005,25(9),1125, the reaction equation is as follows:
the method has relatively mild reaction conditions, but needs a large amount of I2, and has high raw material cost.
Therefore, there is still a need for a more environmentally friendly, economical and practical method for preparing tetrafluorobenzyl alcohol.
Disclosure of Invention
In order to solve the technical problems, the invention discloses a technical scheme for obtaining tetrafluorobenzyl alcohol by adopting water as a solvent and benzoyl chloride for reduction. In the reaction process, the ether-containing solvent is complexed with sodium borohydride to activate the sodium borohydride, water is used as the solvent for reduction, the reaction yield is high, and the reducing agent sodium borohydride can complete the reaction in a catalytic amount.
A method for preparing tetrafluorobenzyl alcohol is characterized in that: tetrafluorobenzoyl chloride is used as a raw material, and is activated by an ether solvent and then reduced by sodium borohydride to obtain tetrafluorobenzyl alcohol.
Further, in the above technical solution, the tetrafluorobenzyl alcohol is selected from 2,3,5, 6-tetrafluorobenzyl alcohol, 2,4,5, 6-tetrafluorobenzyl alcohol or 2,3,4, 5-tetrafluorobenzyl alcohol.
Further, in the above technical solution, the ether solvent is selected from the group consisting of ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, and bis (dimethylaminoethyl) ether, and ethylene glycol dimethyl ether is preferred.
Further, in the above technical solution, the ether solvent is 2 to 6 times, preferably 3 times the weight ratio of NaBH 4.
Further, in the technical scheme, the molar amount of NaBH4 is 0.3-0.6 times, preferably 0.35-0.45 times that of tetrafluorobenzoyl chloride.
Furthermore, in the technical scheme, water is used as a solvent in the reduction reaction, and the amount of the water is 3-10 times, preferably 5.5 times of the weight ratio of the tetrafluorobenzoyl chloride.
Further, in the technical scheme, a small amount of ethylene glycol dimethyl ether plays a role in helping to dissolve tetrafluorobenzoyl chloride in water, and the probability of hydrolysis reaction of tetrafluorobenzoyl chloride is reduced.
Further, in the above technical solution, the tetrafluorobenzoyl chloride is reduced by NaBH4 in water, if the reduction is performed at low temperature, the reduction reaction is slow, and the tetrafluorobenzoyl chloride is easier to perform esterification with tetrafluorobenzyl alcohol which is a product already generated. If the reaction is carried out at a higher temperature, tetrafluorobenzoyl chloride is easy to generate hydrolysis side reaction to generate tetrafluorobenzoic acid. The solution commonly used is to add a large excess of NaBH4 to increase the probability of reduction.
The invention has the beneficial effects that:
1. the method adopts NaBH4 added into a small amount of glycol dimethyl ether for activation, and NaBH4 and the glycol dimethyl ether form a complex and then react in water. The activated NaBH4 has high activity, can effectively promote tetrafluorobenzoyl chloride to rapidly carry out reduction reaction, reduces the probability of esterification side reaction with the generated tetrafluorobenzyl alcohol, and has the reaction yield up to 98 percent.
2. The boric acid inorganic salt generated by the reaction is insoluble in water and can be removed by a simple filtration method. The glycol dimethyl ether can be extracted and recovered by an aromatic hydrocarbon solvent, and the wastewater only contains a small amount of organic matters and inorganic salts and is easier to treat.
3. Only ether organic solvents such as ethylene glycol dimethyl ether are used for carrying out complexing activation treatment on NaBH4, the activity of NaBH4 is enhanced, and water-soluble inorganic salts such as ZnCl2 and AlCl3 are not used for carrying out complexing activation reaction.
4. Water is adopted to replace an organic solvent for reaction, so that the method is more environment-friendly.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
Comparative example 1 Synthesis of 2,3,5, 6-tetrafluorobenzyl alcohol
50g (0.258mol) of 2,3,5, 6-tetrafluorobenzoic acid was added to 150mL of thionyl chloride, 3 drops of DMF were added dropwise, the temperature was raised to 70 ℃ to carry out a reflux reaction, and the reaction was considered to be completed when the solution became clear and no gas was emitted. Atmospheric distillation is firstly carried out to recover thionyl chloride, then reduced pressure distillation is carried out to obtain 54.6g of colorless oily product 2,3,5, 6-tetrafluorobenzoyl chloride, and the yield is 100%.
93.6g (2.53mol) NaBH4 and 300g of water are added into a 500mL four-mouth bottle, stirred and dissolved, cooled to 5 ℃, and 54.6g of 2,3,5, 6-tetrafluorobenzoyl chloride is added dropwise under the protection of nitrogen. The reaction temperature is controlled to be 0-10 ℃, and the dropwise addition is carried out for about 3 hours. Note that: the reaction is exothermic and gas and solid are generated. After the addition, the reaction was kept at this temperature for 1 hour.
100g of dichloromethane was added and stirred for 10 minutes, insoluble inorganic salts were filtered off, the filter cake was rinsed with 50g of dichloromethane, the filtrates were combined, the organic layer was separated, and dichloromethane was recovered by distillation to give 36.2g of 2,3,5, 6-tetrafluorobenzyl alcohol as a white solid. The combined yield of the two steps was 78%.
Comparative example 2 Synthesis of 2,3,5, 6-tetrafluorobenzyl alcohol
37g (1mol) of NaBH4 and 300g of water are added into a 500mL four-mouth bottle, stirred and dissolved, the temperature is reduced to 5 ℃, and 54.6g of 2,3,5, 6-tetrafluorobenzoyl chloride obtained by the method in example 1 is dropwise added under the protection of nitrogen. The reaction temperature is controlled to be 0-10 ℃, and the dropwise addition is carried out for about 3 hours. Note that: the reaction is exothermic and gas and solid are generated. After the addition, the temperature was maintained at this temperature for 1 hour.
100g of dichloromethane was added and stirred for 10 minutes, insoluble inorganic salts were filtered off, the filter cake was rinsed with 50g of dichloromethane, the filtrates were combined, the organic layer was separated, and dichloromethane was recovered by distillation to give 18.2g of 2,3,5, 6-tetrafluorobenzyl alcohol as a white solid, the combined yield in the two steps being 39.2%.
EXAMPLE 1 Synthesis of 2,3,5, 6-tetrafluorobenzyl alcohol
3.8g (0.1mol) of NaBH4 and 12g of ethylene glycol dimethyl ether are added into a 500mL four-mouth bottle, stirred and heated to 78-80 ℃ under the protection of nitrogen, and then reflux reaction is carried out for 3 hours.
And after the activation reaction is finished, cooling to 20-30 ℃, adding 300g of water, stirring for dissolving, cooling to 5 ℃, and dropwise adding 54.6g of 2,3,5, 6-tetrafluorobenzoyl chloride obtained by the method in the comparative example 1 under the protection of nitrogen. The reaction is strongly exothermic, gas and solid are generated, the reaction temperature is controlled to be 5-15 ℃, and the dropping time is about 3 hours. After the addition, the temperature was maintained at this temperature for 1 hour.
Adding 100g of dichloromethane, stirring for 10 minutes, filtering out insoluble inorganic salts, leaching filter cakes by using 50g of dichloromethane, combining filtrates, separating out an organic layer, and distilling to recover dichloromethane to obtain 45.5g of white solid product 2,3,5, 6-tetrafluorobenzyl alcohol, wherein the yield is 98 percent, and the melting point is as follows: 32-38 ℃ and HNMR (400MHz, CHCl3), 7.02(s,1H),4.83(s,2H),2.06(s, 1H). The combined yield of the two steps is 98%.
When the ethylene glycol dimethyl ether is replaced by triethylene glycol dimethyl ether and bis (dimethylaminoethyl) ether respectively according to the conditions, the corresponding separation yield is 94% and 92%.
Example 2 Synthesis of 2,3,4, 5-tetrafluorobenzyl alcohol
50g (0.258mol) of 2,3,4, 5-tetrafluorobenzoic acid was added to 150mL of thionyl chloride, 3 drops of DMF were added dropwise, the temperature was raised to 70 ℃ to carry out a reflux reaction, and the reaction was considered to be complete when the solution became clear and no gas was emitted. Atmospheric distillation is firstly carried out to recover thionyl chloride, then reduced pressure distillation is carried out to obtain 54.1g of colorless oily product 2,3,4, 5-tetrafluorobenzoyl chloride, and the yield is 99%.
4.16g (0.11mol) of NaBH4 and 10g of ethylene glycol dimethyl ether are added into a 500mL four-mouth bottle, stirred and heated to 78-80 ℃ under the protection of nitrogen, and then reflux reaction is carried out for 3 hours.
And after the activation reaction is finished, cooling to 20-30 ℃, adding 300g of water, stirring for dissolving, cooling to 5 ℃, and dropwise adding 54.1g of 2,3,4, 5-tetrafluorobenzoyl chloride under the protection of nitrogen. The reaction is strongly exothermic, gas and solid are generated, the reaction temperature is controlled to be 5-15 ℃, and the dropping time is about 3 hours. After the addition, the temperature was maintained at this temperature for 1 hour.
Adding 100g of dichloromethane, stirring for 10 minutes, filtering out insoluble inorganic salts, leaching filter cakes by using 50g of dichloromethane, combining filtrates, separating an organic layer, and recovering dichloromethane by distillation to obtain a white solid product, namely 44.5g of 2,3,4, 5-tetrafluorobenzyl alcohol, with the yield of 97%. The combined yields in both steps are 96.03%.
EXAMPLE 3 Synthesis of 2,4,5, 6-tetrafluorobenzyl alcohol
50g (0.258mol) of 2,4,5, 6-tetrafluorobenzoic acid was added to 150mL of thionyl chloride, 3 drops of DMF were added dropwise, the temperature was raised to 70 ℃ to carry out a reflux reaction, and the reaction was considered to be completed when the solution became clear and no gas was emitted. Atmospheric distillation is firstly carried out to recover thionyl chloride, then reduced pressure distillation is carried out to obtain colorless oily product 2,4,5, 6-tetrafluorobenzoyl chloride 54.1, and the yield is 99%.
Adding 4.44g (0.12mol) NaBH4 and 13g ethylene glycol dimethyl ether into a 500mL four-mouth bottle, stirring and heating to 78-80 ℃ under the protection of nitrogen, and carrying out reflux reaction for 3 hours.
And after the activation reaction is finished, cooling to 20-30 ℃, adding 300g of water, stirring for dissolving, cooling to 5 ℃, and dropwise adding 54.1g of 2,4,5, 6-tetrafluorobenzoyl chloride under the protection of nitrogen. The reaction is strongly exothermic, gas and solid are generated, the reaction temperature is controlled to be 5-15 ℃, and the dropping time is about 3 hours. After the addition, the temperature was maintained at this temperature for 1 hour.
Adding 100g of dichloromethane, stirring for 10 minutes, filtering out insoluble inorganic salts, leaching filter cakes by using 50g of dichloromethane, combining filtrates, separating out an organic layer, and recovering dichloromethane by distillation to obtain 45.5g of white solid product 2,4,5, 6-tetrafluorobenzyl alcohol with the yield of 99%. The combined yield of the two steps is 98.01 percent.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (7)
1. A method for preparing tetrafluorobenzyl alcohol, which is characterized by comprising the following steps: using tetrafluorobenzoyl chloride as a raw material, and reducing by using sodium borohydride activated by an ether solvent to obtain tetrafluorobenzyl alcohol; the ether solvent is selected from glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether or bis (dimethylaminoethyl) ether; the NaBH4The molar weight is 0.3 to 0.6 times of that of tetrafluorobenzoyl chloride; the reduction reaction adopts water as a solvent.
2. The method of preparing tetrafluorobenzyl alcohol according to claim 1, characterized in that: the tetrafluorobenzyl alcohol is selected from 2,3,5, 6-tetrafluorobenzyl alcohol, 2,4,5, 6-tetrafluorobenzyl alcohol or 2,3,4, 5-tetrafluorobenzyl alcohol.
3. The method of preparing tetrafluorobenzyl alcohol according to claim 1, characterized in that: the ether solvent is NaBH42-6 times of the weight ratio.
4. A method of preparing tetrafluorobenzyl alcohol according to claim 3, characterized in that: the ether solvent is NaBH43 times of the weight ratio.
5. The method of preparing tetrafluorobenzyl alcohol according to claim 1, characterized in that: the NaBH4The molar weight is 0.35-0.45 times of that of tetrafluorobenzoyl chloride.
6. The method of preparing tetrafluorobenzyl alcohol according to claim 1, characterized in that: the water consumption is 3-10 times of the weight ratio of the tetrafluorobenzoyl chloride.
7. The method of preparing tetrafluorobenzyl alcohol according to claim 6, characterized in that: the amount of water used was 5.5 times the weight ratio of tetrafluorobenzoyl chloride.
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| CN1900037A (en) * | 2006-07-09 | 2007-01-24 | 常州康美化工有限公司 | Preparation method of 2, 3, 5, 6-tetrafluorobenzyl alcohol |
| US20100179194A1 (en) * | 2007-04-10 | 2010-07-15 | Bayer Corpscience Ag | Insecticidal aryl isoxazoline derivatives |
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| CN1900037A (en) * | 2006-07-09 | 2007-01-24 | 常州康美化工有限公司 | Preparation method of 2, 3, 5, 6-tetrafluorobenzyl alcohol |
| US20100179194A1 (en) * | 2007-04-10 | 2010-07-15 | Bayer Corpscience Ag | Insecticidal aryl isoxazoline derivatives |
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Inventor after: Yuanfeng Inventor after: Jiang Dianbao Inventor after: Zhang Hongxue Inventor after: Sun Liqin Inventor before: Yuanfeng Inventor before: Jiang Dianping Inventor before: Zhang Hongxue Inventor before: Sun Liqin |
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