CN107793292A - To the preparation method of trifluoromethyl benzyl chloride - Google Patents
To the preparation method of trifluoromethyl benzyl chloride Download PDFInfo
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- CN107793292A CN107793292A CN201610770184.9A CN201610770184A CN107793292A CN 107793292 A CN107793292 A CN 107793292A CN 201610770184 A CN201610770184 A CN 201610770184A CN 107793292 A CN107793292 A CN 107793292A
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- trifluoromethyl benzyl
- preparation
- benzyl chloride
- hydrochloric acid
- tetrahydrofuran
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
- C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/38—Separation; Purification; Stabilisation; Use of additives
- C07C17/383—Separation; Purification; Stabilisation; Use of additives by distillation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
- C07C29/80—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by distillation
Abstract
The present invention relates to a kind of preparation method to trifluoromethyl benzyl chloride, specific steps include：A. appropriate tetrahydrofuran, magnesium, iodine, bromoethane and p-chloro benzo trifluoride-99 are added in a kettle, nitrogen is passed through, stirring is warming up to backflow, and flow back 20min~40min, then temperature control is at 40 DEG C~60 DEG C, p-chloro benzo trifluoride-99 is added dropwise, insulation reaction 1.5h~3h after completion of dropwise addition, is consequently cooled to 5 DEG C~15 DEG C, add appropriate paraformaldehyde, temperature control is reacted into 5h~7h at 0 DEG C~60 DEG C again, then reclaims tetrahydrofuran, rectification under vacuum is obtained to trifluoromethyl benzyl alcohol；B. appropriate hydrochloric acid is added in another reactor and are warming up to by backflow, insulation reaction 20h~30h, is cooled to room temperature for trifluoromethyl benzyl alcohol, stirring, is layered, dehydration, vacuum distillation is obtained to trifluoromethyl benzyl chloride.The preparation method route to trifluoromethyl benzyl chloride of the present invention is succinct and yield is high.
Description
Technical field
The present invention relates to a kind of preparation method of compound, especially a kind of preparation method to trifluoromethyl benzyl chloride.
Background technology
It is organic synthesis intermediate important in agricultural chemicals, medical industry to trifluoromethyl benzyl chloride, in agricultural chemicals, medicine, chemical industry
Had a very wide range of applications in industry.At present, although having industrial method of a variety of synthesis to trifluoromethyl benzyl chloride, greatly
All there is the defects of cost is higher or less efficient in majority, how to provide that a kind of route is succinct and production efficiency is high to fluoroform
The preparation method of base benzyl chloride is those skilled in the art's technical issues that need to address.
The content of the invention
The high system to trifluoromethyl benzyl chloride of succinct and yield the technical problem to be solved in the present invention is to provide a kind of route
Preparation Method.
The present invention is to solve a kind of technical scheme that above-mentioned technical problem proposes to be：A kind of preparation to trifluoromethyl benzyl chloride
Method, specific steps include：
A. appropriate tetrahydrofuran, magnesium, iodine, bromoethane and p-chloro benzo trifluoride-99 are added in a kettle, is passed through nitrogen, are stirred
It is warming up to backflow, flow back 20min~40min so that RMgBr triggers successfully, and then temperature control is at 40 DEG C~60 DEG C, by
P-chloro benzo trifluoride-99 is added dropwise to, insulation reaction 1.5h~3h after completion of dropwise addition, 5 DEG C~15 DEG C is consequently cooled to, adds appropriate
Paraformaldehyde, then temperature control is reacted into 5h~7h at 0 DEG C~60 DEG C, tetrahydrofuran is then reclaimed, residue is cooled to room temperature
After be put into frozen water, be layered after hydrolysis, the water layer got is with the toluene organic matter that once obtains afterwards of extraction and the organic layer got
Merge, then reclaim tetrahydrofuran at ambient pressure, residue is transferred to rectifying still, and rectification under vacuum is obtained to trifluoromethyl benzyl alcohol；
B. appropriate hydrochloric acid is added in another reactor and to trifluoromethyl benzyl alcohol, stirring is warming up to backflow, and insulation is anti-
20h~30h is answered, is cooled to room temperature, is layered, is taken organic layer, be dehydrated with anhydrous sodium sulfate, vacuum distillation is obtained to trifluoromethyl chlorine
Benzyl.
The parts by weight of the p-chloro benzo trifluoride-99 of the initiation are 1~2, the parts by weight of the tetrahydrofuran are 250~
350, the parts by weight 7~15 of the magnesium, the parts by weight of the bromoethane are 2~4, the p-chloro benzo trifluoride-99 being added dropwise
Parts by weight are 88~89.
The quality of the iodine is the 0.05%~0.1% of p-chloro benzo trifluoride-99 gross mass.
The quality of the paraformaldehyde is the 50%~60% of p-chloro benzo trifluoride-99 gross mass.
The quality of the frozen water is 5 times~8 times of p-chloro benzo trifluoride-99 gross mass.
Contain hydrochloric acid in the frozen water, the quality of the hydrochloric acid accounts for frozen water quality 5%~8%.
The mass ratio of hydrochloric acid and trifluoromethyl benzyl alcohol is the ︰ 2 of 1 ︰ 1~3 in the step B.
The hydrochloric acid is the aqueous hydrochloric acid solution that concentration is 35%.
The present invention has positive effect：The present invention the preparation method to trifluoromethyl benzyl chloride using p-chloro benzo trifluoride-99 as
Raw material, tetrahydrofuran are solvent, carry out RMgBr initiation by magnesium, iodine, bromoethane, are then added dropwise to chlorine fluoroform
Benzene, raw material route is succinct, and reaction process is short, can effectively improve yield by the strict control to reaction condition and production is imitated
Rate, suitable for industrialized production.Tetrahydrofuran is easily recycled, and can be utilized with iterative cycles, be advantageously reduced cost.Pair of the present invention
The preparation method of trifluoromethyl benzyl chloride is suitable to industrial mass production.
Embodiment
Embodiment 1
The specific steps of the preparation method to trifluoromethyl benzyl chloride of the present embodiment include：
A. pretreated tetrahydrofuran 150kg, dried magnesium grain 7.3kg, iodine 30g, bromoethane are added in a kettle
1kg and p-chloro benzo trifluoride-99 0.5kg, is slowly passed through nitrogen, and stirring is warming up to backflow, maintains the reflux for 30min so that grignard is tried
Agent triggers successfully, and then p-chloro benzo trifluoride-99 44.5kg, insulation reaction after completion of dropwise addition is added dropwise at 50 DEG C in temperature control
2h, 10 DEG C are consequently cooled to, add paraformaldehyde 25kg, then temperature control is reacted into 6h at 30 DEG C, then reclaim tetrahydrofuran,
Residue is put into 300kg frozen water after being cooled to room temperature（The aqueous hydrochloric acid solution that concentration is 35% has been previously added in frozen water
18.5kg）.It is layered after being fully hydrolyzed, the organic matter that the water layer got once is obtained afterwards with 50L toluene extraction has with what is got
Machine is laminated simultaneously, then reclaims tetrahydrofuran at ambient pressure, and residue is transferred to rectifying still, and rectification under vacuum is obtained to trifluoromethylbenzene first
Alcohol, actual measurement yield are 84.7%, content 98.5%.Step A reaction equation（1）It is as follows：
B. addition concentration is 35% aqueous hydrochloric acid solution 150kg and to trifluoromethyl benzyl alcohol 50kg in another reactor, is stirred
Mix and be warming up to backflow, insulation reaction 24h, be cooled to room temperature, be layered, take organic layer, be dehydrated with anhydrous sodium sulfate, is evaporated under reduced pressure to
To trifluoromethyl benzyl chloride, content 98.8%.Step B reaction equation（2）It is as follows：
Embodiment 2
The specific steps of the preparation method to trifluoromethyl benzyl chloride of the present embodiment include：
A. pretreated tetrahydrofuran 150kg, dried magnesium grain 7.3kg, iodine 30g, bromoethane are added in a kettle
1kg and p-chloro benzo trifluoride-99 0.5kg, is slowly passed through nitrogen, and stirring is warming up to backflow, maintains the reflux for 40min so that grignard is tried
Agent triggers successfully, and then p-chloro benzo trifluoride-99 44.5kg, insulation reaction after completion of dropwise addition is added dropwise at 40 DEG C in temperature control
1.5h, 9 DEG C are consequently cooled to, add paraformaldehyde 25kg, then temperature control is reacted into 7h at 20 DEG C, then reclaim tetrahydrochysene furan
Mutter, residue is put into 300kg frozen water after being cooled to room temperature（The aqueous hydrochloric acid solution that concentration is 35% has been previously added in frozen water
18.5kg）.It is layered after being fully hydrolyzed, the organic matter that the water layer got once is obtained afterwards with 50L toluene extraction has with what is got
Machine is laminated simultaneously, then reclaims tetrahydrofuran at ambient pressure, and residue is transferred to rectifying still, and rectification under vacuum is obtained to trifluoromethylbenzene first
Alcohol, actual measurement yield are 82.3%, content 99.0%.
B. addition concentration is 35% aqueous hydrochloric acid solution 150kg and to trifluoromethyl benzyl alcohol in another reactor
50kg, stirring are warming up to backflow, insulation reaction 22h, are cooled to room temperature, are layered, take organic layer, be dehydrated with anhydrous sodium sulfate, subtracted
Pressure distillation is obtained to trifluoromethyl benzyl chloride, content 99.2%.
Embodiment 3
The specific steps of the preparation method to trifluoromethyl benzyl chloride of the present embodiment include：
A. pretreated tetrahydrofuran 150kg, dried magnesium grain 7.3kg, iodine 30g, bromoethane are added in a kettle
1kg and p-chloro benzo trifluoride-99 0.5kg, is slowly passed through nitrogen, and stirring is warming up to backflow, maintains the reflux for 20min so that grignard is tried
Agent triggers successfully, and then p-chloro benzo trifluoride-99 44.5kg, insulation reaction after completion of dropwise addition is added dropwise at 60 DEG C in temperature control
2.5h, 11 DEG C are consequently cooled to, add paraformaldehyde 25kg, then temperature control is reacted into 5h at 40 DEG C, then reclaim tetrahydrochysene furan
Mutter, residue is put into 300kg frozen water after being cooled to room temperature（The aqueous hydrochloric acid solution that concentration is 35% has been previously added in frozen water
18.5kg）.It is layered after being fully hydrolyzed, the organic matter that the water layer got once is obtained afterwards with 50L toluene extraction has with what is got
Machine is laminated simultaneously, then reclaims tetrahydrofuran at ambient pressure, and residue is transferred to rectifying still, and rectification under vacuum is obtained to trifluoromethylbenzene first
Alcohol, actual measurement yield are 81.2%, content 97.8%.
B. addition concentration is 35% aqueous hydrochloric acid solution 150kg and to trifluoromethyl benzyl alcohol in another reactor
50kg, stirring are warming up to backflow, insulation reaction 25h, are cooled to room temperature, are layered, take organic layer, be dehydrated with anhydrous sodium sulfate, subtracted
Pressure distillation is obtained to trifluoromethyl benzyl chloride, content 98.2%.
Raw materials used in the present invention is bought-in article unless otherwise specified, and concentration is that chemistry is pure.
Obviously, above-described embodiment is only intended to clearly illustrate example of the present invention, and is not to the present invention
The restriction of embodiment.For those of ordinary skill in the field, it can also be made on the basis of the above description
Its various forms of changes or variation.There is no necessity and possibility to exhaust all the enbodiments.And these belong to this hair
Among the obvious changes or variations that bright spirit is extended out is still in protection scope of the present invention.
Claims (8)
1. a kind of preparation method to trifluoromethyl benzyl chloride, it is characterised in that specific steps include：
A. appropriate tetrahydrofuran, magnesium, iodine, bromoethane and p-chloro benzo trifluoride-99 are added in a kettle, is passed through nitrogen, are stirred
It is warming up to backflow, flow back 20min~40min so that RMgBr triggers successfully, and then temperature control is at 40 DEG C~60 DEG C, by
P-chloro benzo trifluoride-99 is added dropwise to, insulation reaction 1.5h~3h after completion of dropwise addition, 5 DEG C~15 DEG C is consequently cooled to, adds appropriate
Paraformaldehyde, then temperature control is reacted into 5h~7h at 0 DEG C~60 DEG C, tetrahydrofuran is then reclaimed, residue is cooled to room temperature
After be put into frozen water, be layered after hydrolysis, the water layer got is with the toluene organic matter that once obtains afterwards of extraction and the organic layer got
Merge, then reclaim tetrahydrofuran at ambient pressure, residue is transferred to rectifying still, and rectification under vacuum is obtained to trifluoromethyl benzyl alcohol；
B. appropriate hydrochloric acid is added in another reactor and to trifluoromethyl benzyl alcohol, stirring is warming up to backflow, and insulation is anti-
20h~30h is answered, is cooled to room temperature, is layered, is taken organic layer, be dehydrated with anhydrous sodium sulfate, vacuum distillation is obtained to trifluoromethyl chlorine
Benzyl.
2. the preparation method according to claim 1 to trifluoromethyl benzyl chloride, it is characterised in that：The initiation to chlorine
The parts by weight of benzotrifluoride are 1~2, and the parts by weight of the tetrahydrofuran are 250~350, the parts by weight 7~15 of the magnesium, institute
The parts by weight for stating bromoethane are 2~4, and the parts by weight of the p-chloro benzo trifluoride-99 being added dropwise are 88~89.
3. the preparation method according to claim 2 to trifluoromethyl benzyl chloride, it is characterised in that：The quality of the iodine is pair
The 0.05%~0.1% of chlorobenzotrifluoride gross mass.
4. the preparation method according to claim 3 to trifluoromethyl benzyl chloride, it is characterised in that：The matter of the paraformaldehyde
Amount is the 50%~60% of p-chloro benzo trifluoride-99 gross mass.
5. the preparation method according to claim 1 to trifluoromethyl benzyl chloride, it is characterised in that：The quality of the frozen water is
5 times of p-chloro benzo trifluoride-99 gross mass~8 times.
6. according to the preparation method to trifluoromethyl benzyl chloride any one of claim 1 to 5, it is characterised in that：The ice
Contain hydrochloric acid in water, the quality of the hydrochloric acid accounts for frozen water quality 5%~8%.
7. the preparation method according to any one of claim 1 to 5 to trifluoromethyl benzyl chloride, it is characterised in that：It is described
The mass ratio of hydrochloric acid and trifluoromethyl benzyl alcohol is the ︰ 2 of 1 ︰ 1~3 in step B.
8. the preparation method according to claim 7 to trifluoromethyl benzyl chloride, it is characterised in that：The hydrochloric acid is that concentration is
35% aqueous hydrochloric acid solution.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610770184.9A CN107793292A (en) | 2016-08-31 | 2016-08-31 | To the preparation method of trifluoromethyl benzyl chloride |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610770184.9A CN107793292A (en) | 2016-08-31 | 2016-08-31 | To the preparation method of trifluoromethyl benzyl chloride |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002088058A1 (en) * | 2001-04-23 | 2002-11-07 | Ishihara Sangyo Kaisha, Ltd. | Process for the preparation of benzyl alcohols |
| CN1935761A (en) * | 2006-09-27 | 2007-03-28 | 荆和祥 | Method for preparing 2-methyl-3-phenyl benzil alcohol |
| CN105085194A (en) * | 2015-08-28 | 2015-11-25 | 江西力田维康科技有限公司 | Preparing method of 3-alkoxy phenylcarbinol |
-
2016
- 2016-08-31 CN CN201610770184.9A patent/CN107793292A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002088058A1 (en) * | 2001-04-23 | 2002-11-07 | Ishihara Sangyo Kaisha, Ltd. | Process for the preparation of benzyl alcohols |
| CN1935761A (en) * | 2006-09-27 | 2007-03-28 | 荆和祥 | Method for preparing 2-methyl-3-phenyl benzil alcohol |
| CN105085194A (en) * | 2015-08-28 | 2015-11-25 | 江西力田维康科技有限公司 | Preparing method of 3-alkoxy phenylcarbinol |
Non-Patent Citations (1)
| Title |
|---|
| VOLKER HESSEL 等: "Continuous-Flow Multistep Synthesis of Cinnarizine,Cyclizine, and a Buclizine Derivative from Bulk Alcohols", 《CHEMSUSCHEM》 * |
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Application publication date: 20180313 |