CN107619405A - It is a kind of（R）The preparation method of single thiocarbonic acid propylene - Google Patents
It is a kind of（R）The preparation method of single thiocarbonic acid propylene Download PDFInfo
- Publication number
- CN107619405A CN107619405A CN201710874356.1A CN201710874356A CN107619405A CN 107619405 A CN107619405 A CN 107619405A CN 201710874356 A CN201710874356 A CN 201710874356A CN 107619405 A CN107619405 A CN 107619405A
- Authority
- CN
- China
- Prior art keywords
- expoxy propane
- preparation
- acid propylene
- thiocarbonic acid
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The present invention relates to one kind（R）The preparation method of single thiocarbonic acid propylene, including：(1) expoxy propane, epoxide hydrolase ECU1040 are mixed with water, after 0~5 DEG C is reacted 10~40 hours, stops reaction, air-distillation goes out (R) expoxy propane；(2) (R) expoxy propane of above-mentioned gained is mixed with organic solvent, add quinine and organic amine, stirring is passed through carbonyl sulfide gas at 10~30 DEG C, untill carbonyl sulfide gas does not absorb, total reaction time is 15~30 hours, produces (R) single thiocarbonic acid propylene.The preparation method atmospheric operation of the present invention, high income is simple and practical, and dangerous low, equipment investment is few, and optical purity of products reaches more than 99%e.e values, has good industrial prospect.
Description
Technical field
The present invention relates to technical field of pharmaceuticals, and in particular to a kind of preparation field of pharmaceutical intermediate, it is more particularly to a kind of
(R) preparation method of-mono- thiocarbonic acid propylene.
Background technology
(R)-mono- thiocarbonic acid propylene is the intermediate of synthetic drug, is also used for preparing high refractive index resin
The polymerized monomer of Polythiocarbonate, therefore there is important practical value.According to the inventors knowledge, it there is no work both at home and abroad at present
Industry is combined to the technique and method of the compound.Inventor realizes the epoxidation of carbonyl sulfide and all kinds of different structures under study for action
Thing carries out coupling open loop addition generation ring-type small molecule and copolymerization generation polymer under catalyst action.At present in laboratory
Synthesis (R)-mono- thiocarbonic acid propylene needs high pressure carbonyl sulfide gas to couple generation at high temperature with (R)-expoxy propane, should
Method is carried out under high pressure, therefore high to equipment requirement, there is certain danger, and conversion ratio is relatively low causes cost higher.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of preparation method of (R)-mono- thiocarbonic acid propylene, we
Method selectivity is high, it is low to operate facility, simple general-purpose, cost, is easy to industrialized production.
In order to solve the above technical problems, a kind of technical scheme provided by the invention is a kind of (R)-mono- thiocarbonic acid propylene
Preparation method, its step is as follows：
(1) by expoxy propane, epoxide hydrolase ECU1040 and water in mass ratio 1:0.005~0.02:0.2~2 mixing,
Reacted, finally distill out (R)-expoxy propane；
(2) (R)-expoxy propane of above-mentioned gained is mixed with organic solvent, adds quinine and organic amine, stirring is logical
Enter carbonyl sulfide gas, untill carbonyl sulfide gas does not absorb, produce (R)-mono- thiocarbonic acid propylene；(R)-epoxy third
The mass ratio of alkane and quinine is 100:0.3~3.0, the mass ratio of (R)-expoxy propane and organic amine is 100:1~10.
Its synthetic route is as follows：
Preferably, in step (1), after 0~5 DEG C is reacted 10~40 hours, reaction is stopped.
Preferably, the step (2), total reaction time are 15~30 hours, wherein, (R)-expoxy propane and organic solvent
Mass volume ratio be 100g:300~500mL.
Preferably, the organic solvent in the step (2) is selected from methanol, ethanol, isopropanol, the tert-butyl alcohol, ethyl acetate, two
One or more mixing of chloromethanes, tetrahydrofuran or propane diols.
Preferably, the organic amine in the step (2) is selected from one kind of triethylamine, ethylenediamine, tert-butylamine or diethylamine
Or a variety of mixing.
The preparation method of (R)-mono- thiocarbonic acid propylene of the invention, its step are as follows：
(1) by expoxy propane, epoxide hydrolase ECU1040 and water in mass ratio 1:0.005~0.02:0.2~2 mixing,
After 0~5 DEG C is reacted 10~40 hours, stop reaction, air-distillation goes out (R)-expoxy propane；
(2) (R)-expoxy propane of above-mentioned gained is mixed with organic solvent, adds quinine and organic amine, 10~
Stirring is passed through carbonyl sulfide gas at 30 DEG C, and untill carbonyl sulfide gas does not absorb, total reaction time is 15~30 hours,
Produce (R)-mono- thiocarbonic acid propylene；Wherein, the mass volume ratio of (R)-expoxy propane and organic solvent is 100g:300~
The mass ratio of 500mL, (R)-expoxy propane and quinine is 100:0.3~3.0, the quality of (R)-expoxy propane and organic amine
Than for 100:1~10.
The present invention technology path be：
Fractionation is hydrolyzed to racemization expoxy propane, prepares (R)-expoxy propane；
Under conditions of catalyst quinine, normal pressure is passed through carbonyl sulfide, directly generates target product (R)-mono- thio
Propene carbonate；
To increase solubility of the carbonyl sulfide in reaction solution, the organic amine of catalytic amount is added.
The preparation method atmospheric operation of the present invention, high income is simple and practical, and dangerous low, equipment investment is few, product optics
Purity reaches more than 99%e.e values, has good industrial prospect.
Embodiment
Such scheme is described further below in conjunction with specific embodiment.It should be understood that these embodiments are to be used to illustrate
The present invention and be not limited to limit the scope of the present invention.The implementation condition used in embodiment can be done according to the condition of specific producer
Further adjustment, unreceipted implementation condition is usually the condition in normal experiment.
Introduce and summarize
The present invention by way of example rather than provides the mode of limitation to illustrate.It should be noted that in present disclosure
Described " one " or " one kind " embodiment is not necessarily referring to same embodiment, and refers at least a kind of.
Various aspects of the invention are described below.However, as will be readily apparent to one of skill in the art, can
Implement the present invention according to the only some or all of aspects of the present invention.For purposes of illustration, provide herein specific numbering, material and
Configuration, enables one to thoroughly understand the present invention.However, be evident that for those of skill in the art,
The present invention can be implemented without concrete details.In other examples, not make the present invention is obscure many institutes have been omitted or simplified
Known feature.
Various operations are described successively as multiple discrete steps, and with most helpful in the side for understanding the present invention
Formula illustrates；However, in-order description should not be construed as to imply that these operations are necessarily dependent on order.
Reactant according to type species is illustrated to various embodiments.To show for those of skill in the art and
It is clear to, any number of different types of reactant can be used to implement for the present invention, and be more than those for the purpose of illustration
And the reactant provided herein.In addition, also it is evident that, the invention is not limited in any specific mixing is shown
Example.
Specific embodiment
Embodiment 1
By 58g racemic epoxides propane and 0.5 gram of epoxide hydrolase ECU1040 input reaction bulb, ice-water bath is cooled to 5 DEG C,
25 grams of water are added dropwise.Temperature is controlled to be no more than 5 DEG C.Drop, which finishes, removes ice-water bath, warms naturally to room temperature.Stop after continuing reaction 24 hours
Only react.Air-distillation goes out 30 grams of (R)-expoxy propane, chemical purity 99.8%, optical voidness 99.5%e.e.Yield 91.8%.
25g (R)-expoxy propane of above-mentioned gained and 100 milliliters of ethanol input 250mL reaction bulbs, are cooled to 16 DEG C, successively
0.3 gram of quinine and 0.9 gram of triethylamine are added, stirring is passed through carbonyl sulfide gas after 15 minutes, keeping temperature is not higher than 20
℃.After reaction 20 hours, carbonyl sulfide gas does not reabsorb.Air-distillation recovery alcohol solvent is heated, high vacuum distillation is produced
Product (R) -40.6 grams of mono- thiocarbonic acid propylene.Gas chromatographic analysis chemical purity 99.7%, chiral purity：99.6%e.e, receive
Rate 97.5%.
Embodiment 2
By 58 grams of racemic epoxide propane and 1.7 grams of epoxide hydrolase ECU1040 input reaction bulbs, ice-water bath is cooled to 0 DEG C
Hereinafter, 11 grams of water are added dropwise.Temperature is controlled to be no more than 5 DEG C.Drop, which finishes, removes ice-water bath, warms naturally to room temperature.It is small to continue reaction 24
When after stop reaction.Air-distillation goes out 29 grams of (R)-expoxy propane, chemical purity 99.7%, optical purity 99.6%e.e.Yield
92.3%.
25g (R)-expoxy propane of above-mentioned gained and 90 ml methanols are put into 250mL reaction bulbs, are cooled to 12 DEG C,
0.5 gram of quinine and 1.3 grams of ethylenediamines are successively added, stirring is passed through carbonyl sulfide gas after 15 minutes, and keeping temperature is not high
In 20 DEG C.After reaction 24 hours, carbonyl sulfide gas does not reabsorb.Normal pressure recovery methanol solvate is heated, high vacuum distillation is produced
Product (R) -42.2 grams of mono- thiocarbonic acid propylene, gas chromatographic analysis chemical purity 99.6%, chiral purity：99.5%e.e, receive
Rate 96.1%.
Embodiment 3
By 58 grams of racemic epoxide propane and 0.6 gram of epoxide hydrolase ECU1040 input reaction bulb, ice-water bath is cooled to 0~5
At DEG C, 115 grams of water are added dropwise.Temperature is controlled to be no more than 5 DEG C.Drop, which finishes, removes ice-water bath, warms naturally to room temperature.It is small to continue reaction 24
When after stop reaction.Air-distillation goes out 27 grams of (R)-expoxy propane, chemical purity 99.7%, optical purity 99.6%e.e, yield
92.3%.
By 25g (R)-expoxy propane of above-mentioned gained and 100 milliliters of tert-butyl alcohol input 250mL reaction bulbs, 10 DEG C are cooled to
0.6 gram of quinine and 1.8 grams of diethylamine are successively added, stirring is passed through carbonyl sulfide gas after 15 minutes, and keeping temperature is not high
In 20 DEG C.Reaction 15 hours, until carbonyl sulfide gas does not reabsorb.T-butanol solvent, high vacuum distillation is recovered under reduced pressure in heating
Go out product (R) -44.3 grams of mono- thiocarbonic acid propylene, gas chromatographic analysis chemical purity 99.6%, chiral purity：99.5%
E.e, yield 96.1%.
Embodiment 4
By 58 grams of racemic epoxide propane and 0.5 gram of epoxide hydrolase ECU1040 input reaction bulb, ice-water bath is cooled to 0~5
At DEG C, 25 grams of water are added dropwise.Temperature is controlled to be no more than 5 DEG C.Drop, which finishes, removes ice-water bath, warms naturally to room temperature.It is small to continue reaction 24
When after stop reaction.Air-distillation goes out 27 grams of (R)-expoxy propane, chemical purity 99.7%, optical purity 99.6%e.e, yield
92.2%.
By 25g (R)-expoxy propane of above-mentioned gained and 90 milliliters of dichloromethane input 250mL reaction bulbs, 14 are cooled to
DEG C, 0.75 gram of quinine and 2.0 grams of tert-butylamines are successively added, stirring is passed through carbonyl sulfide gas, keeping temperature after 15 minutes
Not higher than 20 DEG C, react 30 hours, until carbonyl sulfide gas does not reabsorb.Heat normal pressure recovery dichloromethane solvent, Gao Zhen
Sky distills out product (R) -42.3 grams of mono- thiocarbonic acid propylene, gas chromatographic analysis chemical purity 99.6%, chiral purity：
99.4%e.e, yield 95.9%.
Comparative example 1
25g (R)-expoxy propane of the gained of embodiment 1 is put into 250mL reaction bulbs with 100 milliliters of ethanol, it is cooled to 12~
16 DEG C, stirring is passed through carbonyl sulfide gas after 15 minutes, and keeping temperature is not higher than 20 DEG C.Reaction 20~25 hours, sample gas phase
Chromatogram detects, no product (R)-mono- thiocarbonic acid propylene generation.Illustrating the catalytic reaction of no quinine can not be carried out.
Comparative example 2
25g (R)-expoxy propane of the gained of embodiment 1 is put into 250mL reaction bulbs with 100 milliliters of ethanol, it is cooled to 12~
16 DEG C, 0.3 gram of quinine is added, stirring is passed through carbonyl sulfide gas after 15 minutes, keeping temperature is not higher than 20 DEG C.Reaction 20
~25 hours, gas chromatographic detection, raw material (R)-expoxy propane residue 83% are sampled, product (R)-mono- thiocarbonic acid propylene contains
Amount only 17%, reaction rate is very low.Illustrate the catalytic action of no organic amine, carbonyl sulfide meltage is very low to cause reaction speed
It is slower.
Specific embodiment described above is only the preferred embodiment of the present invention, it is noted that for the art
For those of ordinary skill, under the premise without departing from the principles of the invention, some improvement or replacement can also be made, these improvement
Or replace and should also be as being considered as protection scope of the present invention.
Claims (6)
1. a kind of preparation method of (R)-mono- thiocarbonic acid propylene, its step are as follows：
(1) by expoxy propane, epoxide hydrolase ECU1040 and water in mass ratio 1:0.005~0.02:0.2~2 mixing, is carried out
Reaction, finally distills out (R)-expoxy propane；
(2) (R)-expoxy propane of above-mentioned gained is mixed with organic solvent, adds quinine and organic amine, stirring is passed through oxygen
Nitric sulfid gas, untill carbonyl sulfide gas does not absorb, produce (R)-mono- thiocarbonic acid propylene；(R)-expoxy propane with
The mass ratio of quinine is 100:0.3~3.0, the mass ratio of (R)-expoxy propane and organic amine is 100:1~10.
2. preparation method according to claim 1, it is characterised in that in step (1), reacted 10~40 hours in 0~5 DEG C
Afterwards, reaction is stopped.
3. preparation method according to claim 1, it is characterised in that in step (2), total reaction time is 15~30 small
When.
4. preparation method according to claim 1, it is characterised in that in step (2), (R)-expoxy propane and organic solvent
Mass volume ratio be 100g:300~500mL.
5. preparation method according to claim 1, it is characterised in that in step (2), the organic solvent be selected from methanol,
One or more mixing in ethanol, isopropanol, the tert-butyl alcohol, ethyl acetate, dichloromethane, tetrahydrofuran or propane diols.
6. preparation method according to claim 1, it is characterised in that in step (2), the organic amine be selected from triethylamine,
One or more mixing of ethylenediamine, tert-butylamine or diethylamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710874356.1A CN107619405A (en) | 2017-09-25 | 2017-09-25 | It is a kind of（R）The preparation method of single thiocarbonic acid propylene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710874356.1A CN107619405A (en) | 2017-09-25 | 2017-09-25 | It is a kind of（R）The preparation method of single thiocarbonic acid propylene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107619405A true CN107619405A (en) | 2018-01-23 |
Family
ID=61090330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710874356.1A Pending CN107619405A (en) | 2017-09-25 | 2017-09-25 | It is a kind of（R）The preparation method of single thiocarbonic acid propylene |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107619405A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102391239A (en) * | 2011-09-14 | 2012-03-28 | 上海科利生物医药有限公司 | Preparation method of (R)-propene carbonate |
| CN104277027A (en) * | 2014-09-24 | 2015-01-14 | 扬州三友合成化工有限公司 | Preparation method of (R)-propylene carbonate |
-
2017
- 2017-09-25 CN CN201710874356.1A patent/CN107619405A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102391239A (en) * | 2011-09-14 | 2012-03-28 | 上海科利生物医药有限公司 | Preparation method of (R)-propene carbonate |
| CN104277027A (en) * | 2014-09-24 | 2015-01-14 | 扬州三友合成化工有限公司 | Preparation method of (R)-propylene carbonate |
Non-Patent Citations (2)
| Title |
|---|
| M. LUO ET AL.: "Synthesis of cyclic monothiocarbonates via the coupling reaction of carbonyl sulfide (COS) with epoxides", 《CATAL. SCI. TECHNOL》 * |
| 刘尚长等主编: "《一氧化碳》", 31 July 1994 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103787883B (en) | A kind of preparation method of 4-chloroacetyl acetacetic ester | |
| CN114957193B (en) | Method for green synthesis of vinylene carbonate | |
| CN109053460B (en) | Method for catalyzing amination of benzyl alcohol compound | |
| CN107619405A (en) | It is a kind of（R）The preparation method of single thiocarbonic acid propylene | |
| CN108822012A (en) | A kind of preparation method of 3,7- dimethyl -3- acetylthio -6- matsutake alcohol | |
| CN113582807A (en) | Method for synthesizing 2, 6-dichlorobenzyl chloride | |
| CN102391239B (en) | Preparation method of (R)-propene carbonate | |
| CN103896979B (en) | Compound synthetic method | |
| CN116768709B (en) | Efficient synthesis method of 2-hydroxy stilbene compounds | |
| EP1284256A1 (en) | Process of the preparation of high-purity alkyladamantyl esters | |
| CN114539068B (en) | Preparation method of N, N, N ', N' -tetra-N-butyl-1, 6-hexamethylenediamine | |
| CN113816917B (en) | Preparation method of wibeled intermediate | |
| CN115974722B (en) | Synthesis method of cyflumetofen | |
| CN104262383B (en) | Method for synthesizing compound | |
| CN115246857B (en) | Preparation method of L-glufosinate-ammonium | |
| CN112624968B (en) | Synthetic method of 5-amino-3-cyanopyridine methyl formate hydrochloride | |
| CN115707691A (en) | Phenoxymethyl-1,4,2-dioxazole-5-ketone and preparation method thereof | |
| CN110642818B (en) | Method for preparing benzofuran-2-carboxamide compound | |
| ES2613982T3 (en) | Procedure and assembly to produce alkylene oxides and glycol ethers | |
| CN108623496A (en) | The preparation method of 3- ethyl -4- fluorobenzonitriles | |
| CN112521341A (en) | Novel method for high-selectivity synthesis of 2, 4-bis (4-biphenyl) -6-chloro-1, 3, 5-s-triazine | |
| CN115650843A (en) | Synthesis of cyclopropyl formic acid | |
| KR20230059118A (en) | A manufacturing method of cycloaliphatic epoxy compound | |
| CN104529881B (en) | 2-chloro-5-ethyl pyridine preparation method | |
| CN114685362A (en) | Separation method of 2-methylpyridine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180123 |
|
| RJ01 | Rejection of invention patent application after publication |