CN109293478A - A method of preparing tetrafluorobenzyl alcohol - Google Patents
A method of preparing tetrafluorobenzyl alcohol Download PDFInfo
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- CN109293478A CN109293478A CN201811303725.2A CN201811303725A CN109293478A CN 109293478 A CN109293478 A CN 109293478A CN 201811303725 A CN201811303725 A CN 201811303725A CN 109293478 A CN109293478 A CN 109293478A
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- tetrafluorobenzyl alcohol
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- 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 kind of methods for preparing tetrafluorobenzyl alcohol, belong to technical field of organic synthesis.After reacting generation phenyl tetrafluoride formyl chloride with thionyl chloride using tetrafluorobenzoic aid, then again using phenyl tetrafluoride formyl chloride as raw material, the sodium borohydride after ether solvent activates restores in water obtains tetrafluorobenzyl alcohol.By being complexed containing ether solvent and sodium borohydride, to activate sodium borohydride, solvent is done using water and is restored, reaction yield is high, and reaction can be completed in reducing agent sodium borohydride catalyzing amount, and reaction process is more environmentally protective.
Description
Technical field
The present invention relates to the preparations of benzylalcohol, and in particular to a method of tetrafluorobenzyl alcohol is prepared, organic synthesis skill is belonged to
Art field.
Background technique
Tetrafluorobenzyl alcohol, molecular formula: C7H4F4O molecular weight: 180.10；Including 2,3,4,5- tetrafluorobenzyl alcohol CAS:
53072-18-7；2,4,5,6- tetrafluorobenzyl alcohols and 2,3,5,6- tetrafluorobenzyl alcohols, No. CAS: 4084-38-2, also known as tetrafluoro benzyl
, more or less all there are some defects in alcohol, the method for existing synthesis tetrafluorobenzyl alcohol, by taking 2,3,5,6- tetrafluorobenzyl alcohols as an example,
It is broadly divided into following several:
The first, tetrafluorobenzyl alcohol is directly reduced to using tetrafluorobenzoic aid
The process route and most classic process route that Bayer company uses, are restored using NaBH4, use sulfuric acid
Dimethyl ester does auxiliary agent direct-reduction tetrafluorobenzoic aid at tetrafluorobenzyl alcohol (with reference to DE3714602), and reaction equation is as follows:
This method yield is up to 96%, but reaction need using toxic articles dimethyl suflfate, purchase and using it is upper all by
To certain restrictions, and dimethyl suflfate usage amount is very big, and unit consumption reaches 0.6.
Second, it is restored using the sodium borohydride of activation
CN1900037, which is reported, to be added metal chloride and activates to NaBH4, right after NaBH4 reduction activation to enhance
Tetrafluorobenzoic aid is restored, and reaction equation is as follows:
This method is not necessarily to toxic articles dimethyl suflfate, but joined the metalloid of 2 times of weight ratios ZnCl2 or AlCl3
Chloride is collectively formed metal complex boride with triethylamine and NaBH4, is restored in organic solvent.Processing disadvantages are
The waste water that reaction generates contains a large amount of metal chlorides, it is not easy to handle.
The third, be reduced directly using acyl chlorides
CN2006101010646, which is reported, is first made into phenyl tetrafluoride formyl chloride for tetrafluorobenzoic aid, then uses excess NaBH4 again
It is restored, reaction equation is as follows:
This method needs to use ether organic solvent, and NaBH4 dosage is 10 times of moles of raw material, restores at high cost, post-processing
When generate bulk gas, there are certain security risks.
4th kind, restored under the conditions of activating sodium borohydride using methyl 4-fluorobenzene
Tang Yu, which is reported, is made into methyl 4-fluorobenzene for tetrafluorobenzoic aid, is then restored with NaBH4 and I2, reference: " has
Machine synthesis " 2005,25 (9), 1125. reaction equations are as follows:
This method reaction condition is relatively mild, but needs with a large amount of I2, and cost of material is very high.
Therefore, still need to look for the preparation method of a kind of more environmentally protective, economical and practical tetrafluorobenzyl alcohol at present.
Summary of the invention
In order to solve the above-mentioned technical problem, solvent is done using water the invention discloses a kind of, is restored using chlorobenzoyl chloride
To the technical solution of tetrafluorobenzyl alcohol.By being complexed containing ether solvent and sodium borohydride in reaction process, to activate hydroboration
Sodium makees solvent using water and is restored, and reaction yield is high, and reaction can be completed in reducing agent sodium borohydride catalyzing amount.
A method of preparing tetrafluorobenzyl alcohol, it is characterised in that: living through ether solvent using phenyl tetrafluoride formyl chloride as raw material
Sodium borohydride reduction obtains tetrafluorobenzyl alcohol after change.
Further, in the above-mentioned technical solutions, the tetrafluorobenzyl alcohol be selected from 2,3,5,6- tetrafluorobenzyl alcohols, 2,4,5,
6- tetrafluorobenzyl alcohol or 2,3,4,5- tetrafluorobenzyl alcohol.
Further, in the above-mentioned technical solutions, the ether solvent is selected from glycol dimethyl ether, diethylene glycol diformazan
Ether, triethylene glycol dimethyl ether, bis- (dimethylaminoethyl) ethers, preferably glycol dimethyl ether.
Further, in the above-mentioned technical solutions, the ether solvent is 2-6 times, preferably 3 times of NaBH4 weight ratio.
Further, in the above-mentioned technical solutions, the NaBH4 mole is 0.3-0.6 times of phenyl tetrafluoride formyl chloride, preferably
0.35-0.45 times.
Further, in the above-mentioned technical solutions, reduction reaction makees solvent using water, and water consumption is phenyl tetrafluoride formyl chloride weight
3-10 times, preferably 5.5 times for measuring ratio.
Further, in the above-mentioned technical solutions, a small amount of glycol dimethyl ether plays help in water and dissolves phenyl tetrafluoride first
The effect of acyl chlorides reduces the probability of phenyl tetrafluoride formyl chloride reaction hydrolysis.
Further, in the above-mentioned technical solutions, the phenyl tetrafluoride formyl chloride is restored with NaBH4 in water, if low
It is restored under temperature, reduction reaction is slow, and the product that phenyl tetrafluoride formyl chloride is easier and has generated --- tetrafluorobenzyl alcohol carries out ester
Change reaction.If carried out at relatively high temperatures, phenyl tetrafluoride formyl chloride is easy to happen hydrolytic side reactions, generates tetrafluorobenzoic aid.Often
Solution is exactly that excessive many times of NaBH4 is added, and increases the probability of reduction reaction.
Advantageous effect of the invention:
1. the present invention is added in a small amount of glycol dimethyl ether using NaBH4 and is activated, NaBH4 and glycol dimethyl ether shape
It is then reacted in water again at complex compound.NaBH4 activity is high after activation, can effectively facilitate phenyl tetrafluoride formyl chloride and quickly carry out
The probability of esterification side reaction occurs for reduction reaction, the tetrafluorobenzyl alcohol for reducing and having generated, and reaction yield is up to 98%.
2. reaction generates boric acid class inorganic salts and is not dissolved in water, can be removed by simple filter type.Ethylene glycol two
Methyl ether can use aromatic hydrocarbon solvent extraction and recovery, and waste water contains only a small amount of organic matter and inorganic salts, and waste water is easier to handle.
3. only using ether organic solvent, if glycol dimethyl ether carries out complex activation processing to NaBH4, enhance NaBH4
Activity avoids carrying out complex activation reaction using water-soluble inorganic salts such as ZnCl2 and AlCl3.
4. it replaces organic solvent to do using water to react, it is more environmentally protective.
Specific embodiment
Comparative example 1 synthesizes 2,3,5,6- tetrafluorobenzyl alcohol
2,3,5,6- tetrafluorobenzoic aid of 50g (0.258mol) is added in 150mL thionyl chloride, 3 drop DMF, heating are instilled
To 70 DEG C of progress back flow reactions, visual response terminates when solution, which becomes, clarifies the discharge of no gas.Chlorine is recycled in first air-distillation
Change sulfoxide, is then evaporated under reduced pressure, obtains 2,3,5,6- phenyl tetrafluoride formyl chloride 54.6g of colorless oil as product, yield 100%.
93.6g (2.53mol) NaBH4, water 300g are added in 500mL four-hole bottle, stirring and dissolving cools to 5 DEG C, nitrogen
Protection is lower to be added dropwise 54.6g 2,3,5,6- phenyl tetrafluoride formyl chloride.0~10 DEG C of reaction temperature of control is about added dropwise the used time 3 hours.Note
Meaning: exothermic heat of reaction is obvious, has gas and solid to generate.Insulation reaction 1 hour at such a temperature is added dropwise.
100g methylene chloride is added to stir 10 minutes, filters out undissolved inorganic salts, is filtered with 50g eluent methylene chloride
Cake, merging filtrate separate organic layer, are distilled to recover methylene chloride, obtain 2,3,5,6- tetrafluorobenzyl alcohol of 36.2g, and white is solid
Body.Two steps merge yield 78%.
Comparative example 2 synthesizes 2,3,5,6- tetrafluorobenzyl alcohol
37g (1mol) NaBH4, water 300g are added in 500mL four-hole bottle, stirring and dissolving cools to 5 DEG C, nitrogen protection
Lower 1 method of dropwise addition embodiment obtains 2,3,5,6- phenyl tetrafluoride formyl chloride 54.6g.0~10 DEG C of reaction temperature of control is about added dropwise and uses
When 3 hours.Note: exothermic heat of reaction is obvious, has gas and solid to generate.It is added dropwise and keeps the temperature 1 hour at such a temperature.
100g methylene chloride is added to stir 10 minutes, filters out undissolved inorganic salts, is filtered with 50g eluent methylene chloride
Cake, merging filtrate separate organic layer, are distilled to recover methylene chloride, obtain 2,3,5,6- tetrafluorobenzyl alcohol of 18.2g white solid,
Two steps merge yield 39.2%.
Embodiment 1 synthesizes 2,3,5,6- tetrafluorobenzyl alcohol
3.8g (0.1mol) NaBH4, glycol dimethyl ether 12g are added in 500mL four-hole bottle, stirred under nitrogen atmosphere adds
Heat is to 78~80 DEG C, back flow reaction 3 hours.
20~30 DEG C are cooled to after priming reaction, water 300g is added, and stirring and dissolving cools to 5 DEG C, under nitrogen protection
The 2,3,5,6- phenyl tetrafluoride formyl chloride 54.6g that 1 method of comparative example obtains is added dropwise.Strong reaction heat release has gas and solid to generate,
5~15 DEG C of reaction temperature of control is about added dropwise the used time 3 hours.It is added dropwise and keeps the temperature 1 hour at such a temperature.
100g methylene chloride is added to stir 10 minutes, filters out undissolved inorganic salts, is filtered with 50g eluent methylene chloride
Cake, merging filtrate separate organic layer, are distilled to recover methylene chloride, obtain 2,3,5,6- tetrafluorobenzyl alcohol of white solid product
45.5g, yield 98%, fusing point: 32-38 DEG C, HNMR (400MHz, CHCl3): 7.02 (s, 1H), 4.83 (s, 2H), 2.06 (s,
1H).Two steps merge yield 98%.
It is replaced when triethylene glycol dimethyl ether, bis- (dimethylaminoethyl) ethers is respectively adopted in glycol dimethyl ether according to above-mentioned condition
When changing, corresponding separation yield is 94% and 92%.
Embodiment 2 synthesizes 2,3,4,5- tetrafluorobenzyl alcohol
2,3,4,5- tetrafluorobenzoic aid of 50g (0.258mol) is added in 150mL thionyl chloride, 3 drop DMF, heating are instilled
To 70 DEG C of progress back flow reactions, visual response terminates when solution, which becomes, clarifies the discharge of no gas.Chlorine is recycled in first air-distillation
Change sulfoxide, is then evaporated under reduced pressure, obtains 2,3,4,5- phenyl tetrafluoride formyl chloride 54.1g of colorless oil as product, yield 99%.
4.16g (0.11mol) NaBH4, glycol dimethyl ether 10g, stirred under nitrogen atmosphere are added in 500mL four-hole bottle
It is heated to 78~80 DEG C, back flow reaction 3 hours.
20~30 DEG C are cooled to after priming reaction, water 300g is added, and stirring and dissolving cools to 5 DEG C, under nitrogen protection
2,3,4,5- phenyl tetrafluoride formyl chloride 54.1g is added dropwise.Strong reaction heat release has gas and solid to generate, controls reaction temperature 5~15
DEG C, about it is added dropwise the used time 3 hours.It is added dropwise and keeps the temperature 1 hour at such a temperature.
100g methylene chloride is added to stir 10 minutes, filters out undissolved inorganic salts, is filtered with 50g eluent methylene chloride
Cake, merging filtrate separate organic layer, are distilled to recover methylene chloride, obtain 2,3,4,5- tetrafluorobenzyl alcohol of white solid product
44.5g, yield 97%.Two steps merge yield 96.03%.
Embodiment 3 synthesizes 2,4,5,6- tetrafluorobenzyl alcohol
2,4,5,6- tetrafluorobenzoic aid of 50g (0.258mol) is added in 150mL thionyl chloride, 3 drop DMF, heating are instilled
To 70 DEG C of progress back flow reactions, visual response terminates when solution, which becomes, clarifies the discharge of no gas.Chlorine is recycled in first air-distillation
Change sulfoxide, is then evaporated under reduced pressure, obtains 2,4,5,6- phenyl tetrafluoride formyl chloride 54.1 of colorless oil as product, yield 99%.
4.44g (0.12mol) NaBH4, glycol dimethyl ether 13g, stirred under nitrogen atmosphere are added in 500mL four-hole bottle
It is heated to 78~80 DEG C, back flow reaction 3 hours.
20~30 DEG C are cooled to after priming reaction, water 300g is added, and stirring and dissolving cools to 5 DEG C, under nitrogen protection
2,4,5,6- phenyl tetrafluoride formyl chloride 54.1g is added dropwise.Strong reaction heat release has gas and solid to generate, controls reaction temperature 5~15
DEG C, about it is added dropwise the used time 3 hours.It is added dropwise and keeps the temperature 1 hour at such a temperature.
100g methylene chloride is added to stir 10 minutes, filters out undissolved inorganic salts, is filtered with 50g eluent methylene chloride
Cake, merging filtrate separate organic layer, are distilled to recover methylene chloride, obtain 2,4,5,6- tetrafluorobenzyl alcohol of white solid product
45.5g, yield 99%.Two steps merge yield 98.01%.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Any modifications, equivalent replacements, and improvements etc. done within mind and principle, should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of method for preparing tetrafluorobenzyl alcohol, which comprises the following steps: using phenyl tetrafluoride formyl chloride as raw material,
Tetrafluorobenzyl alcohol is obtained with the sodium borohydride reduction after ether solvent activates.
2. preparing the method for tetrafluorobenzyl alcohol according to claim 1, it is characterised 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. preparing the method for tetrafluorobenzyl alcohol according to claim 1, it is characterised in that: the ether solvent is selected from glycol dinitrate
Ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether or bis- (dimethylaminoethyl) ethers.
4. preparing the method for tetrafluorobenzyl alcohol according to claim 1, it is characterised in that: the ether solvent is NaBH4 weight ratio
2-6 times.
5. the method for preparing tetrafluorobenzyl alcohol according to claim 4, it is characterised in that: the ether solvent is NaBH4 weight ratio
3 times.
6. preparing the method for tetrafluorobenzyl alcohol according to claim 1, it is characterised in that: the NaBH4 mole is phenyl tetrafluoride first
0.3-0.6 times of acyl chlorides.
7. the method for preparing tetrafluorobenzyl alcohol according to claim 6, it is characterised in that: the NaBH4 mole is phenyl tetrafluoride first
0.35-0.45 times of acyl chlorides.
8. the method for tetrafluorobenzyl alcohol processed according to claim 1, it is characterised in that: reduction reaction makees solvent using water.
9. the method for preparing tetrafluorobenzyl alcohol according to claim 8, it is characterised in that: water consumption is phenyl tetrafluoride formyl chloride weight ratio
3-10 times.
10. the method for preparing tetrafluorobenzyl alcohol according to claim 9, it is characterised in that: water consumption is phenyl tetrafluoride formyl chloride weight
5.5 times of ratio.
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| CN201811303725.2A CN109293478B (en) | 2018-11-02 | 2018-11-02 | Method for preparing tetrafluorobenzyl alcohol |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115259996A (en) * | 2022-08-29 | 2022-11-01 | 浙江中欣氟材股份有限公司 | Synthetic method of transfluthrin intermediate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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2018
- 2018-11-02 CN CN201811303725.2A patent/CN109293478B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115259996A (en) * | 2022-08-29 | 2022-11-01 | 浙江中欣氟材股份有限公司 | Synthetic method of transfluthrin intermediate |
| CN115259996B (en) * | 2022-08-29 | 2024-02-02 | 浙江中欣氟材股份有限公司 | Synthesis method of 2,3,5, 6-tetrafluorobenzyl alcohol |
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