CN107324969A - A kind of method that utilization cyclopropyl-carbinol synthesizes chloromethyl cyclopropane - Google Patents
A kind of method that utilization cyclopropyl-carbinol synthesizes chloromethyl cyclopropane Download PDFInfo
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- CN107324969A CN107324969A CN201710577379.6A CN201710577379A CN107324969A CN 107324969 A CN107324969 A CN 107324969A CN 201710577379 A CN201710577379 A CN 201710577379A CN 107324969 A CN107324969 A CN 107324969A
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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
- C07C29/132—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 present invention relates to organic synthesis field, a kind of method that utilization cyclopropyl-carbinol synthesizes chloromethyl cyclopropane is disclosed, is comprised the following steps：A）Cyanuric Chloride is dissolved in solvent orange 2 A, solution is configured to；B）Cyclopropyl-carbinol is added drop-wise in the solution of above-mentioned preparation and reacted；C）The reaction solution for completing reaction is added in aqueous slkali and is quenched；D）Target product is extracted using solvent B, dried, rectifying obtains product.The inventive method is using cyclopropyl-carbinol and Cyanuric Chloride as raw material, and raw material is easy to get, and cost is low, pollutes small, and its reaction condition is gentle, and post processing is simple, suitable for industrial production.
Description
Technical field
The side of chloromethyl cyclopropane is synthesized the present invention relates to organic synthesis field, more particularly to a kind of utilization cyclopropyl-carbinol
Method.
Background technology
The method of production chloromethyl cyclopropane has a variety of now, and topmost is by the use of cyclopropyl-carbinol as raw material, together
When replace with the use of chlorinating agent.Current main method has：1, chlorination reagent is used as using tetrachloro Phenylphosphine.Its advantage
It is higher according to relevant document this method yield, but it has the disadvantage that tetrachloro Phenylphosphine price is expensive, supplier is few, and easily produces
Isomerized products, it is difficult to realize industrialized production.2, chlorinating agent is used as using the acetone of chlordene two and triphenyl phosphorus.This method is same
There is triphenyl phosphorus consumption big, the problem of price is expensive, and this method post processing is cumbersome.
It follows that the synthetic method of existing chloromethyl cyclopropane has its respective distinct disadvantage, therefore have must
A kind of new synthetic method in place is developed, to solve above-mentioned technical problem.
The content of the invention
In order to solve the above-mentioned technical problem, the invention provides the side that a kind of utilization cyclopropyl-carbinol synthesizes chloromethyl cyclopropane
Method.The inventive method is using cyclopropyl-carbinol and Cyanuric Chloride as raw material, and raw material is easy to get, and cost is low, pollutes small, and its reaction condition temperature
With post processing is simple, suitable for industrial production.
The present invention concrete technical scheme be：A kind of method that utilization cyclopropyl-carbinol synthesizes chloromethyl cyclopropane, including with
Lower step：
A）Cyanuric Chloride is dissolved in solvent orange 2 A, solution is configured to.
B）Cyclopropyl-carbinol is added drop-wise in the solution of above-mentioned preparation and reacted.
C）The reaction solution for completing reaction is added in aqueous slkali and is quenched.
D）Target product is extracted using solvent B, dried, rectifying obtains product.
Preferably, step A）In, the solvent orange 2 A is DMF, DMA, DMSO, two
At least one of chloromethanes, toluene, chloroform, acetonitrile, dioxane.
Preferably, step A）In, the weight proportion of the solvent orange 2 A and solute is 2 ~ 7：1.
Preferably, step B）In, reaction temperature is less than 0 DEG C, and the reaction time is 1-8h, the cyclopropyl-carbinol and trimerization
The mol ratio of chlorine cyanogen is 0.2-2：1.
Preferably, step C）In, the aqueous slkali is that the mixing of potassium hydroxide solution, sodium hydroxide solution or both is molten
Liquid.
Preferably, step C）In, the alkaline concentration is less than 50wt%.
Preferably, step C）In, temperature control is quenched below 20 DEG C.
Preferably, step D）In, the solvent B is dichloromethane, ethyl acetate, methyl tertiary butyl ether(MTBE), toluene, hexamethylene
At least one of alkane, n-hexane, chloroform, dichloroethanes.
Preferably, step D）In, the rectifying is normal pressure or rectification under vacuum.
Preferably, the preparation method of the cyclopropyl-carbinol, comprises the following steps：
1）Reactor is subjected to deactivation.
2）The ester and alcohols that are synthesized by cyclopropanecarboxylic acid and alcohols are put into reactor, heating stirring.
3）Put into metallic sodium in batches into reactor, make to maintain the reflux in whole course of reaction reactor.
4）After metallic sodium addition is finished, continue to flow back, treat that metallic sodium is completely dissolved reaction, sampling detection cyclopropanecarboxylic acid methyl esters
Content, cools after the completion of reaction.
5）Acid is added into reactor, adjusts pH to neutrality, filtering, filtrate rectifying obtains product.
Preferably, step 2）In, the ester synthesized by cyclopropanecarboxylic acid and alcohols is selected from cyclopropanecarboxylic acid methyl esters, the first of ring third
Acetoacetic ester, cyclopropanecarboxylic acid propyl ester, cyclopropanecarboxylic acid isopropyl ester；The alcohols is selected from methanol, ethanol, propyl alcohol, isopropanol and butanol.
Preferably, step 2）In, the ester synthesized by cyclopropanecarboxylic acid and alcohols is cyclopropanecarboxylic acid methyl esters；The alcohols
For methanol.
Preferably, step 2）In, the mass ratio of the methanol and cyclopropanecarboxylic acid methyl esters is 4 ~ 8：1.
Preferably, step 2）In, temperature elevating range is at 30-120 DEG C, and mixing speed is in 40-120rpm.
Preferably, step 3）In, the mol ratio of the metallic sodium and cyclopropanecarboxylic acid methyl esters is 1 ~ 6：1.
Preferably, step 3）In, the reaction time is 8-20h, and reflux temperature is at 60-120 DEG C.
Preferably, step 4）In, the content of the cyclopropanecarboxylic acid methyl esters is not more than 10wt% after methanol is deducted.
Preferably, step 4）In, detection method is vapor detection, and reaction is completed after cooling below 50 DEG C.
Preferably, step 5）In, the acid is at least one of organic acid, inorganic acid；PH detection methods are extensive examination
Paper, precision test paper measurement or pH meter measurement；The rectifying is rectification under vacuum or atmospheric distillation.
Preferably, the acid is formic acid, organic acid and the watery hydrochloric acid such as acetic acid, dilute sulfuric acid, in the inorganic acid such as phosphoric acid,diluted
It is at least one.
The method of production cyclopropyl-carbinol has a variety of at present, but is usually by the use of cyclopropanecarboxylic acid as substrate, with the use of also
Original reagent obtains product to reduce.Existing main method has：1, using cyclopropanecarboxylic acid as main material, using strong reductant
LAH is reduced.The shortcoming of this method is that cyclopropanecarboxylic acid and LAH cost are higher, and LAH is easily and air, water
Vapour can react, dangerous higher.General factory is difficult to reach working condition.2, although some can substitute cyclopropanecarboxylic acid at present
Main material, can avoid the high cost brought using cyclopropanecarboxylic acid to a certain extent, but equally must be strong using LAH
Reducing agent, it is impossible to the high risk for avoiding LAH from bringing.
The present invention using the esters such as cyclopropanecarboxylic acid methyl esters as main material, and using metallic sodium as reducing agent, not only
Cost of material, and the high risk that strong reductant LAH can be avoided to bring can effectively be reduced.
It is compared with the prior art, the beneficial effects of the invention are as follows：
1st, the inventive method, using cyclopropyl-carbinol and Cyanuric Chloride as raw material, raw material is cheap and easily-available, and cost is low, pollutes small, purity can
Up to more than 99.5%.Yield is up to more than 90%, and reaction condition is gentle, and post processing is simple.
2nd, the present invention is using main material of the esters such as cyclopropanecarboxylic acid methyl esters as synthesis cyclopropyl-carbinol, and raw material is cheap, can
Effectively reduce cost.
3rd, in the inventive method cyclopropyl-carbinol synthetic method, method more of the prior art, using metallic sodium as also
Former agent, reduces danger, and reaction condition is gentle.Purity is up to more than 99%.Yield is up to more than 80%, and post processing is simple.
Embodiment
With reference to embodiment, the invention will be further described.
Embodiment 1：
A）1.5kg DMF are added in four-hole bottle, stirring is cooled to -12 DEG C；Temperature control adds in batches below 0 DEG C in 30min
Enter 613g TCT, stir 5min, temperature control is added dropwise to 721g CPMO below 0 DEG C in 3 hours；Completion of dropping, is stirred at 0 DEG C
Mix 1 hour, stop refrigeration, 25 DEG C are risen to naturally, controlled in sampling, when CPMO reacts completely, reaction terminates.
B）30% sodium hydroxide 4kg solution is prepared, and is cooled to 5 DEG C or so.Control no more than 10 DEG C feelings of dropping temperature
Under condition, reaction solution is added dropwise in liquid caustic soda, 2 hours completion of dropping.Stir 30min.
C）Take 2kg dichloromethane extracted products in two times, combined dichloromethane, dichloromethane layer 300ml water washings 3
It is secondary.
D）Dichloromethane layer atmospheric distillation obtains product：760.6g, purity 99.1%：Yield：84%.
Wherein, the preparation method of cyclopropyl-carbinol is：
1）Ensure reactor, condenser, the equipment such as head tank is clean, dries；Checking each valve opening situation of reaction system is
It is no normal.Ensure that Materials Solvents etc. meet feedstock specifications.To reactor deactivation twice.
2）250kg cyclopropanecarboxylic acid methyl esters and 1200kg methanol are pumped under nitrogen protection, is stirred, and are opened steam and are warming up to 45
DEG C, stop heating.
3）1.8kg sodium is put into reactor, a large amount of backflows occurs, records capacity of returns.Continue to feed intake, until kettle temperature is reached
65℃.Every 15 minutes input 5.4kg sodium.Keep remaining reflux state in reactor simultaneously.Until 200kg sodium input
Finish.Continue to be incubated backflow 2 hours, the sodium reaction completely of input is finished.
4）Sampling, enters the content of vapor detection cyclopropanecarboxylic acid methyl esters, if the content of cyclopropanecarboxylic acid methyl esters is less than 5%, stops
Only react, start cooling, otherwise continue to react.
5）Material is cooled to 0 DEG C, by the slow low price of formic acid into reactor, process control temp is added dropwise and is less than 10 DEG C,
Completion of dropping, is surveyed between pH=6.5-7.5.Continue to stir 1 hour, filtering, filtrate is collected.It is warming up to 65 DEG C of recovery methanol.Methanol
After recovery is finished, material is cooled to less than 40 DEG C, using low vacuum rectifying, slow rise kettle temperature to top distillates product.Most
Product is obtained eventually：150kg, purity：99.6%, yield：83.1%.
Embodiment 2：
A）1.5kg DMAs are added in four-hole bottle, stirring is cooled to -12 DEG C；Temperature control is below 0 DEG C
920g TCT are added in 30min in batches, 5min is stirred, temperature control is added dropwise to 721g CPMO below 0 DEG C in 3 hours；
Completion of dropping, is stirred 4 hours at 0 DEG C, is stopped refrigeration, is warmed to room temperature naturally, is controlled in sampling, when CPMO reacts completely, reaction knot
Beam.
B）30% sodium hydroxide 6kg solution is prepared, and is cooled to 5 DEG C or so.Control no more than 10 DEG C feelings of dropping temperature
Under condition, reaction solution is added dropwise in liquid caustic soda, 2 hours completion of dropping.Stir 30min.
C）Take 3kg dichloromethane extracted products in two times, combined dichloromethane, dichloromethane layer 500ml water washings 3
It is secondary.
D）Dichloromethane layer atmospheric distillation obtains product：824g, purity 99.5%：Yield：91%.
Wherein, the preparation method of cyclopropyl-carbinol is：
1）Ensure reactor, condenser, the equipment such as head tank is clean, dries；Checking each valve opening situation of reaction system is
It is no normal.Ensure that Materials Solvents etc. meet feedstock specifications.To reactor deactivation twice.
2）285.3kg cyclopropanecarboxylic acid ethyl ester and 1200kg ethanol are pumped under nitrogen protection, is stirred, and are opened steam and are warming up to
45 DEG C, stop heating.
3）1.8kg sodium is put into reactor, a large amount of backflows occurs, records capacity of returns.Continue to feed intake, until kettle temperature is reached
80℃.Every 15 minutes input 5.4kg sodium.Keep remaining reflux state in reactor simultaneously.Until 200kg sodium input
Finish.Continue to be incubated backflow 2 hours, the sodium reaction completely of input is finished.
4）Sampling, enters the content of vapor detection cyclopropanecarboxylic acid ethyl ester, if the content of cyclopropanecarboxylic acid ethyl ester is less than 5%, stops
Only react, start cooling, otherwise continue to react.
5）Material is cooled to 0 DEG C, by the slow low price of formic acid into reactor, process control temp is added dropwise and is less than 10 DEG C,
Completion of dropping, is surveyed between pH=6.5-7.5.Continue to stir 1 hour, filtering, filtrate is collected.It is warming up to 85 DEG C of recovery ethanol.Ethanol
After recovery is finished, material is cooled to less than 40 DEG C, using low vacuum rectifying, slow rise kettle temperature to top distillates product.Most
Product is obtained eventually：144kg, purity：99.1%, yield：80%.
Embodiment 3：
A）3kg acetonitriles are added in four-hole bottle, stirring is cooled to -10 DEG C；Temperature control adds in batches below 0 DEG C in 30min
Enter 1216g TCT, stir 5min, temperature control is added dropwise to 721g CPMO below 0 DEG C in 2 hours；Completion of dropping, at 0 DEG C
Stirring 3 hours, stops refrigeration, 25 DEG C is risen to naturally, is controlled in sampling, when CPMO reacts completely, reaction terminates.
B）30% sodium hydroxide 4kg solution is prepared, and is cooled to 5 DEG C or so.Control no more than 10 DEG C feelings of dropping temperature
Under condition, reaction solution is added dropwise in liquid caustic soda, 2 hours completion of dropping.Stir 30min.
C）Take 2kg dichloromethane extracted products in two times, combined dichloromethane, dichloromethane layer 300ml water washings 3
It is secondary.
D）Dichloromethane layer atmospheric distillation obtains product：851g, purity 99.6%：Yield：94%.
Wherein, the preparation method of cyclopropyl-carbinol is：
1）Ensure reactor, condenser, the equipment such as head tank is clean, dries；Checking each valve opening situation of reaction system is
It is no normal.Ensure that Materials Solvents etc. meet feedstock specifications.To reactor deactivation twice.
2）250kg cyclopropanecarboxylic acid methyl esters and 1000kg methanol are pumped under nitrogen protection, is stirred, and are opened steam and are warming up to 45
DEG C, stop heating.
3）1.8kg sodium is put into reactor, a large amount of backflows occurs, records capacity of returns.Continue to feed intake, until kettle temperature is reached
65℃.Every 15 minutes input 5.4kg sodium.Keep remaining reflux state in reactor simultaneously.Until 250kg sodium input
Finish.Continue to be incubated backflow 2 hours, the sodium reaction completely of input is finished.
4）Sampling, enters the content of vapor detection cyclopropanecarboxylic acid methyl esters, if the content of cyclopropanecarboxylic acid methyl esters is less than 5%, stops
Only react, start cooling, otherwise continue to react.
5）Material is cooled to 0 DEG C, by the slow low price of formic acid into reactor, process control temp is added dropwise and is less than 10 DEG C,
Completion of dropping, is surveyed between pH=6.5-7.5.Continue to stir 1 hour, filtering, filtrate is collected.It is warming up to 65 DEG C of recovery methanol.Methanol
After recovery is finished, material is cooled to less than 40 DEG C, using low vacuum rectifying, slow rise kettle temperature to top distillates product.Most
Product is obtained eventually：158.6kg, purity：99.5%, yield：88%.
Raw materials used in the present invention, equipment, is the conventional raw material, equipment of this area unless otherwise noted；In the present invention
Method therefor, is the conventional method of this area unless otherwise noted.
It is described above, only it is presently preferred embodiments of the present invention, not the present invention is imposed any restrictions, it is every according to the present invention
Any simple modification, change and equivalent transformation that technical spirit is made to above example, still fall within the technology of the present invention side
The protection domain of case.
Claims (10)
1. a kind of method that utilization cyclopropyl-carbinol synthesizes chloromethyl cyclopropane, it is characterised in that comprise the following steps：
A）Cyanuric Chloride is dissolved in solvent orange 2 A, solution is configured to；
B）Cyclopropyl-carbinol is added drop-wise in the solution of above-mentioned preparation and reacted；
C）The reaction solution for completing reaction is added in aqueous slkali and is quenched；
D）Target product is extracted using solvent B, dried, rectifying obtains product.
2. the method that a kind of utilization cyclopropyl-carbinol as claimed in claim 1 synthesizes chloromethyl cyclopropane, it is characterised in that step
A）In, the solvent orange 2 A be DMF, DMA, DMSO, dichloromethane, toluene, chloroform, acetonitrile,
At least one of dioxane.
3. the method that a kind of utilization cyclopropyl-carbinol as claimed in claim 1 or 2 synthesizes chloromethyl cyclopropane, it is characterised in that
Step A）In, the weight proportion of the solvent orange 2 A and solute is 2 ~ 7：1.
4. the method that a kind of utilization cyclopropyl-carbinol as claimed in claim 1 synthesizes chloromethyl cyclopropane, it is characterised in that step
B）In, reaction temperature is less than 0 DEG C, and the reaction time is 1-8h, and the mol ratio of the cyclopropyl-carbinol and Cyanuric Chloride is 0.2-2：
1。
5. the method that a kind of utilization cyclopropyl-carbinol as claimed in claim 1 synthesizes chloromethyl cyclopropane, it is characterised in that step
C）In, the aqueous slkali is the mixed solution of potassium hydroxide solution, sodium hydroxide solution or both.
6. the method that a kind of utilization cyclopropyl-carbinol as claimed in claim 5 synthesizes chloromethyl cyclopropane, it is characterised in that step
C）In, the alkaline concentration is less than 50wt%.
7. the method that a kind of utilization cyclopropyl-carbinol as described in claim 1 or 5 or 6 synthesizes chloromethyl cyclopropane, its feature exists
In step C）In, temperature control is quenched below 20 DEG C.
8. the method that a kind of utilization cyclopropyl-carbinol as claimed in claim 1 synthesizes chloromethyl cyclopropane, it is characterised in that step
D）In, the solvent B is dichloromethane, ethyl acetate, methyl tertiary butyl ether(MTBE), toluene, hexamethylene, n-hexane, chloroform, two chloroethenes
At least one of alkane.
9. the method that a kind of utilization cyclopropyl-carbinol as described in claim 1 or 8 synthesizes chloromethyl cyclopropane, it is characterised in that
Step D）In, the rectifying is normal pressure or rectification under vacuum.
10. the method that a kind of utilization cyclopropyl-carbinol as claimed in claim 1 synthesizes chloromethyl cyclopropane, it is characterised in that step
Rapid B）In, the preparation method of the cyclopropyl-carbinol is as follows：
1）Reactor is subjected to deactivation；
2）The ester and alcohols that are synthesized by cyclopropanecarboxylic acid and alcohols are put into reactor, heating stirring；
3）Put into metallic sodium in batches into reactor, make to maintain the reflux in whole course of reaction reactor；
4）After metallic sodium addition is finished, continue to flow back, treat that metallic sodium is completely dissolved reaction, sampling detection cyclopropanecarboxylic acid methyl esters contains
Amount, cools after the completion of reaction；
5）Acid is added into reactor, adjusts pH to neutrality, filtering, filtrate rectifying obtains product.
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| CN201710577379.6A CN107324969A (en) | 2017-07-14 | 2017-07-14 | A kind of method that utilization cyclopropyl-carbinol synthesizes chloromethyl cyclopropane |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4739057A (en) * | 1986-06-30 | 1988-04-19 | Stauffer Chemical Co. | Process for converting organo-hydroxyl compounds to halides |
| CN102126925A (en) * | 2011-01-12 | 2011-07-20 | 浙江联盛化学工业有限公司 | Preparation method of hydroxymethyl cyclane |
| CN106187674A (en) * | 2016-07-27 | 2016-12-07 | 上饶师范学院 | A kind of method being prepared chlorohydrocarbon by alcohol using aryl chloride as chlorinating agent |
-
2017
- 2017-07-14 CN CN201710577379.6A patent/CN107324969A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4739057A (en) * | 1986-06-30 | 1988-04-19 | Stauffer Chemical Co. | Process for converting organo-hydroxyl compounds to halides |
| CN102126925A (en) * | 2011-01-12 | 2011-07-20 | 浙江联盛化学工业有限公司 | Preparation method of hydroxymethyl cyclane |
| CN106187674A (en) * | 2016-07-27 | 2016-12-07 | 上饶师范学院 | A kind of method being prepared chlorohydrocarbon by alcohol using aryl chloride as chlorinating agent |
Non-Patent Citations (1)
| Title |
|---|
| LIDIA DE LUCA等: "An Efficient Route to Alkyl Chlorides from Alcohols Using the Complex TCT/DMF", 《ORGANIC LETTERS》 * |
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