CN101851180A - Chlorphenesin carbamate and preparation method thereof - Google Patents
Chlorphenesin carbamate and preparation method thereof Download PDFInfo
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- CN101851180A CN101851180A CN201010196505A CN201010196505A CN101851180A CN 101851180 A CN101851180 A CN 101851180A CN 201010196505 A CN201010196505 A CN 201010196505A CN 201010196505 A CN201010196505 A CN 201010196505A CN 101851180 A CN101851180 A CN 101851180A
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Abstract
The invention discloses chlorphenesin carbamate and a preparation method thereof. The preparation method comprises the step of mixing a compound shown in a formula (1) with ammonium reagent and alkali in an organic solvent in the presence of water at the temperature of 0-40 DEG C. The preparation method in the invention utilizes a raw material containing ammonium ions so as to avoid using of strong pungent ammonia water, improves production safety and is favor of environment protection.
Description
Technical field
The present invention relates to Chlorphenesin Carbamate and preparation method thereof.
Background technology
Chlorphenesin Carbamate (Chlorphenesin Carbamate) is as a kind of muscle relaxant, curative effect height, few side effects.The synthetic route of Chlorphenesin Carbamate mainly is to make adermykon and diethyl carbonate reaction at present, generates cyclic ethers, further with the ammoniacal liquor reaction, prepares Chlorphenesin Carbamate.
Chinese patent application CN10162435 discloses a kind of preparation method of Chlorphenesin Carbamate, being specially adermykon reacts with diethyl carbonate under a small amount of transesterification catalyst effect, add the trimethyl carbinol and dimethyl formamide and ammoniacal liquor then, get Chlorphenesin Carbamate.
Owing to use ammoniacal liquor, and ammoniacal liquor is volatile, has strong impulse, and respiratory tract and skin are had pungency in said synthesis route, and the damage central nervous system.If ammoniacal liquor is splashed into eyes, can cause keratohelcosis etc.Therefore, the production security of aforesaid method is low.
Summary of the invention
For solving problems of the prior art, the invention provides Chlorphenesin Carbamate and preparation method thereof.
Technical scheme provided by the present invention comprises:
The invention provides a kind of preparation method of Chlorphenesin Carbamate, comprise the steps: in the presence of water, make formula (I)
The compound of expression and ammonium reagent and alkali are in organic solvent, in 0～40 ℃ of mixing.
The compound of described formula (I) expression can be to utilize microwave radiation that adermykon and diethyl carbonate are reacted in the presence of transesterification catalyst and generate.The mol ratio of preferred adermykon and diethyl carbonate is 1: 1～1: 5.
Being used for transesterification catalyst of the present invention is the catalyzer that is generally used for transesterification reaction, can be basic catalyst, for example sodium methylate, alumina load list sodium oxide etc.; Also can be an acidic catalyst, for example toluenesulphonic acids, solid super-strong acid etc.
Ammonium reagent described in the present invention can or contain aqueous solution of ammonium ion etc. for ammonium chloride, volatile salt.Wherein preferably use ammonium chloride.
Described organic solvent can be alcohol or hexanaphthene etc.
Described alkali can be selected from one or more in sodium hydroxide, sodium methylate, sodium ethylate, triethylamine and the pyridine.Wherein preferably use sodium ethylate.
The present invention preferably carries out recrystallization at least one time to the Chlorphenesin Carbamate that obtains.Recrystallization solvent can be alcoholic solvent, and for example ethanol, propyl alcohol or butanols preferably use butanols; Also can be the aqueous alcohol solvent, for example aqueous ethanol, moisture propyl alcohol or moisture butanols wherein preferably use moisture butanols, especially preferably use the 70% butanols aqueous solution.
The present invention further provides the Chlorphenesin Carbamate that obtains by preparation method of the present invention.
Preparation method of the present invention contains the raw material of ammonium ion owing to using, thereby avoids using the ammoniacal liquor with strong and stimulating, and production security improves, and helps environmental protection.And owing to use microwave radiation to heat, thus the pyroreaction of avoiding, and shorten the reaction times, need not vaccum-pumping equipment, so simplified production technique, save energy.In addition, the raw material that uses among the preparation method of the present invention is easy to get, cost is low.When utilizing preparation method of the present invention to prepare Chlorphenesin Carbamate, yield and purity improve, and do not contain β-Chlorphenesin Carbamate (β-CPC).
Embodiment
Below utilize specific embodiment to describe the preparation method of Chlorphenesin Carbamate of the present invention in detail, but protection scope of the present invention is not limited to this.
Embodiment 1
In the reaction flask of the 500ml dried and clean that condensation reflux unit, whipping appts and thermometer are housed, add dry adermykon 202.6g (1mol), diethyl carbonate 200g (1.69mol), alumina load list sodium oxide (JAM-6 type) 4g that crosses, then reaction flask is put into microwave reactor, microwave irradiation power is set at 100W, radiation 150 minutes.
From microwave reactor, take out reaction flask, under reaction product ethanol is present in condition in the reaction flask, in reaction flask, add 100ml water, add ammonium chloride 60g (1.1mol), sodium hydroxide 44g (1.1mol) after being cooled to 30～20 ℃, be cooled to 15～5 ℃ then, stir 5h postcooling to 0 ℃, stop to stir, separate out crystallization.Utilize B to filter then, gained filter cake (being retained in the solid matter on the B) washs for three times with the pure moisture of 500ml, and it is the butanols recrystallization of 2 times of filter cake weight with weight that filter cake is filtered solid carbon dioxide branch back, obtains the 210.3g crystallization.Utilize high performance liquid chromatography (HPLC) to detect under the following conditions, the affirmation crystallization is a Chlorphenesin Carbamate, purity 99.9%, yield 85.6%.Do not see the chromatographic peak of β-Chlorphenesin Carbamate in the liquid chromatogram.
The HPLC condition:
Instrument: SHIMADZU island Tianjin 2010-A
Detector: 50UV/Vis
Chromatographic column: Kromasil-C
18(4.6 * 250mm, 5um)
Moving phase: normal hexane: Virahol: acetic acid=70: 30: 0.1
Flow velocity: 1.2ml/min
Detect wavelength: 281nm
The retention time of Chlorphenesin Carbamate is 9.09min under above-mentioned chromatographic condition, and the retention time of β-CPC is 9.74min.
Embodiment 2
In the reaction flask of the 500ml dried and clean that condensation reflux unit, whipping appts and thermometer are housed, add dry adermykon 202.6g (1mol), diethyl carbonate 200g (1.69mol), alumina load list sodium oxide (JAM-6 type) 4g that crosses, then reaction flask is put into microwave reactor, microwave irradiation power is set at 100W, radiation 150 minutes.
From microwave reactor, take out reaction flask, under reaction product ethanol is present in condition in the reaction flask, in reaction flask, add 100ml water, add volatile salt 100g (1.04mol), sodium hydroxide 44g (1.1mol) after being cooled to 30～20 ℃, be cooled to 15～5 ℃ then, stir 5h postcooling to 0 ℃, stop to stir, separate out crystallization.Utilize B to filter then, filter cake washs for three times with the pure moisture of 500ml, and it is the butanols recrystallization of 2 times of filter cake weight with weight that filter cake is filtered solid carbon dioxide branch back, obtains the 203.1g crystallization.Utilize the method identical with embodiment 1 to detect, the results verification crystallization is a Chlorphenesin Carbamate, purity 99.7%, yield 82.7%.And do not see the chromatographic peak of β-Chlorphenesin Carbamate in the liquid chromatogram.
Embodiment 3
In the reaction flask of the 500ml dried and clean that condensation reflux unit, whipping appts and thermometer are housed, add dry adermykon 202.6g (1mol), diethyl carbonate 200g (1.69mol), alumina load list sodium oxide (JAM-6 type) 4g that crosses, then reaction flask is put into microwave reactor, microwave irradiation power is set at 100W, radiation 150 minutes.
From microwave reactor, take out reaction flask, under reaction product ethanol is present in condition in the reaction flask, in reaction flask, add 100ml water, add ammonium chloride 60g (1.1mol), sodium methylate 59g (1.1mol) after being cooled to 30～20 ℃, be cooled to 15～5 ℃ then, stir 5h postcooling to 0 ℃, stop to stir, separate out crystallization.Utilize B to filter then, filter cake washs for three times with the pure moisture of 500ml, and it is the butanols recrystallization of 2 times of filter cake weight with weight that filter cake is filtered solid carbon dioxide branch back, obtains the 201.9g crystallization.Utilize the method identical with embodiment 1 to detect, the results verification crystallization is a Chlorphenesin Carbamate, purity 99.6%, yield 82.2%.And do not see the chromatographic peak of β-Chlorphenesin Carbamate in the liquid chromatogram.
Embodiment 4
In the reaction flask of the 500ml dried and clean that condensation reflux unit, whipping appts and thermometer are housed, add dry adermykon 202.6g (1mol), diethyl carbonate 200g (1.69mol), alumina load list sodium oxide (JAM-6 type) 4g that crosses, then reaction flask is put into microwave reactor, microwave irradiation power is set at 100W, radiation 150 minutes.
From microwave reactor, take out reaction flask, under reaction product ethanol is present in condition in the reaction flask, in reaction flask, add 100ml water, add ammonium chloride 60g (1.1mol), triethylamine 101g (1mol) after being cooled to 30～20 ℃, be cooled to 15～5 ℃ then, stir 5h postcooling to 0 ℃, stop to stir, separate out crystallization.Utilize B to filter then, filter cake washs for three times with the pure moisture of 500ml, and it is the butanols recrystallization of 2 times of filter cake weight with weight that filter cake is filtered solid carbon dioxide branch back, obtains the 196.4g crystallization.Utilize the method identical with embodiment 1 to detect, the results verification crystallization is a Chlorphenesin Carbamate, purity 99.2%, yield 79.9%.And do not see the chromatographic peak of β-Chlorphenesin Carbamate in the liquid chromatogram.
Embodiment 5
In the reaction flask of the 500ml dried and clean that condensation reflux unit, whipping appts and thermometer are housed, add dry adermykon 202.6g (1mol), diethyl carbonate 200g (1.69mol), alumina load list sodium oxide (JAM-6 type) 4g that crosses, then reaction flask is put into microwave reactor, microwave irradiation power is set at 100W, radiation 150 minutes.
From microwave reactor, take out reaction flask, under reaction product ethanol is present in condition in the reaction flask, in reaction flask, add 100ml water, add ammonium chloride 60g (1.1mol), sodium ethylate 70g (1mol) after being cooled to 30～20 ℃, be cooled to 15～5 ℃ then, stir 5h postcooling to 0 ℃, stop to stir, separate out crystallization.Utilize B to filter then, filter cake washs for three times with the pure moisture of 500ml, and it is the butanols recrystallization of 2 times of filter cake weight with weight that filter cake is filtered solid carbon dioxide branch back, obtains 219.8 g crystallizations.Utilize the method identical with embodiment 1 to detect, the results verification crystallization is a Chlorphenesin Carbamate, purity 99.9%, yield 89.5%.And do not see the chromatographic peak of β-Chlorphenesin Carbamate in the liquid chromatogram.
Embodiment 6
In the reaction flask of the 500ml dried and clean that condensation reflux unit, whipping appts and thermometer are housed, add dry adermykon 202.6g (1mol), diethyl carbonate 200g (1.69mol), alumina load list sodium oxide (JAM-6 type) 4g that crosses, then reaction flask is put into microwave reactor, microwave irradiation power is set at 100W, radiation 150 minutes.
From microwave reactor, take out reaction flask, under reaction product ethanol is present in condition in the reaction flask, in reaction flask, add 100ml water, add ammonium chloride 60g (1.1mol), pyridine 87g (1.1mol) after being cooled to 30～20 ℃, be cooled to 15～5 ℃ then, stir 5h postcooling to 0 ℃, stop to stir, separate out crystallization.Utilize B to filter then, filter cake washs for three times with the pure moisture of 500ml, and it is the butanols recrystallization of 2 times of filter cake weight with weight that filter cake is filtered solid carbon dioxide branch back, obtains the 189.3g crystallization.Utilize the method identical with embodiment 1 to detect, the results verification crystallization is a Chlorphenesin Carbamate, purity 99.1%, yield 76.9%.And do not see the chromatographic peak of β-Chlorphenesin Carbamate in the liquid chromatogram.
Embodiment 7
In the reaction flask of the 500ml dried and clean that condensation reflux unit, whipping appts and thermometer are housed, add dry adermykon 202.6g (1mol), the diethyl carbonate 590g (5mol) that crosses, sodium methylate 64.8g (1.2mol), then reaction flask is put into microwave reactor, microwave irradiation power is set at 150W, radiation 100min.
From microwave reactor, take out reaction flask, under reaction product ethanol is present in condition in the reaction flask, in reaction flask, add 100ml water, be cooled to 30～20 ℃, add ammonium chloride 60g (1.1mol), continue to be cooled to 15～5 ℃, stir 5h postcooling to 0 ℃, stop to stir, separate out crystallization.Utilize B to filter then, filter cake washs for three times with the pure moisture of 500ml, and it is 70% butanols aqueous solution recrystallization of 2 times of filter cake weight with weight that filter cake is filtered solid carbon dioxide branch back, obtains the 230.2g crystallization.Utilize the method identical with embodiment 1 to detect, the results verification crystallization is a Chlorphenesin Carbamate, purity 99.5%, yield 93.7%.And do not see the chromatographic peak of β-Chlorphenesin Carbamate in the liquid chromatogram.
Embodiment 8
In the reaction flask of the 500ml dried and clean that condensation reflux unit, whipping appts and thermometer are housed, add dry adermykon 202.6g (1mol), the diethyl carbonate 295g (2.5mol) that crosses, tosic acid 5g, then reaction flask is put into microwave reactor, microwave irradiation power is set at 300W, radiation 60min.
From microwave reactor, take out reaction flask, under reaction product ethanol is present in condition in the reaction flask, in reaction flask, add 100ml water, be cooled to 30～20 ℃, add solid ammonium chloride 60g (1.1mol), sodium hydroxide 45g (1.2mol), continue to be cooled to 15～5 ℃, stir 5h postcooling to 0 ℃, stop to stir, separate out crystallization.Utilize B to filter then, filter cake washs for three times with the pure moisture of 500ml, and it is 60% aqueous propanol solution recrystallization of 2 times of filter cake weight with weight that filter cake is filtered solid carbon dioxide branch back, obtains the 213.4g crystallization.Utilize the method identical with embodiment 1 to detect, the results verification crystallization is a Chlorphenesin Carbamate, purity 99.8%, yield 86.7%.And do not see the chromatographic peak of β-Chlorphenesin Carbamate in the liquid chromatogram.
Obviously, those skilled in the art can carry out various changes and modification to the present invention and not break away from design of the present invention and scope.If of the present invention these are revised and modification belongs within the scope of claim of the present invention and equivalent technologies thereof, then the present invention also is intended to comprise these changes and modification interior.
Claims (10)
1. the preparation method of Chlorphenesin Carbamate is characterized in that, described method comprises, in the presence of water, makes formula (I)
The compound of expression and ammonium reagent and alkali are in organic solvent, in 0～40 ℃ of mixing.
2. preparation method according to claim 1 is characterized in that, the compound of described formula (I) expression is to utilize microwave radiation that adermykon and diethyl carbonate are reacted in the presence of transesterification catalyst to generate.
3. preparation method according to claim 2 is characterized in that, the mol ratio of described adermykon and diethyl carbonate is 1: 1～1: 5.
4. according to each described preparation method in the claim 1～3, it is characterized in that described ammonium reagent is ammonium chloride or volatile salt.
5. according to each described preparation method in the claim 1～3, it is characterized in that described organic solvent is an alcohol.
6. according to each described preparation method in the claim 1～3, it is characterized in that described alkali is selected from one or more in sodium hydroxide, sodium methylate, sodium ethylate, triethylamine and the pyridine.
7. according to each described preparation method in the claim 1～3, it is characterized in that, described Chlorphenesin Carbamate is carried out recrystallization at least one time.
8. preparation method according to claim 7 is characterized in that, recrystallization solvent is alcoholic solvent or aqueous alcohol solvent.
9. preparation method according to claim 8 is characterized in that, described recrystallization solvent is butanols or moisture butanols.
10. Chlorphenesin Carbamate is obtained by each described preparation method in the claim 1～3.
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| CN201010196505A CN101851180A (en) | 2010-06-10 | 2010-06-10 | Chlorphenesin carbamate and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108432749A (en) * | 2018-03-28 | 2018-08-24 | 方建波 | A kind of preparation method of orchard bird repellent |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3161567A (en) * | 1963-05-29 | 1964-12-15 | Upjohn Co | Process for relieving pain with 3-p-chlorophenoxy-2-hydroxy-propyl carbamate |
| CN101624354A (en) * | 2009-08-17 | 2010-01-13 | 朱岩安 | Preparation method of chlorphenesin carbamate |
-
2010
- 2010-06-10 CN CN201010196505A patent/CN101851180A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3161567A (en) * | 1963-05-29 | 1964-12-15 | Upjohn Co | Process for relieving pain with 3-p-chlorophenoxy-2-hydroxy-propyl carbamate |
| CN101624354A (en) * | 2009-08-17 | 2010-01-13 | 朱岩安 | Preparation method of chlorphenesin carbamate |
Non-Patent Citations (2)
| Title |
|---|
| 柴兰琴 等: ""微波促进有机化学反应应用研究"", 《兰州铁道学院学报(自然科学版)》 * |
| 邢爱华: "碳酸二甲酯与苯酚酯交换反应合成碳酸二苯酯的研究", 《中国博士学位论文全文数据库 工程科技I辑》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108432749A (en) * | 2018-03-28 | 2018-08-24 | 方建波 | A kind of preparation method of orchard bird repellent |
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Application publication date: 20101006 |