CN109384693A - (S) preparation method of -1- ethoxy carbonyl -3- bromopropyl methyl carbamate - Google Patents
(S) preparation method of -1- ethoxy carbonyl -3- bromopropyl methyl carbamate Download PDFInfo
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- CN109384693A CN109384693A CN201811303492.6A CN201811303492A CN109384693A CN 109384693 A CN109384693 A CN 109384693A CN 201811303492 A CN201811303492 A CN 201811303492A CN 109384693 A CN109384693 A CN 109384693A
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- Prior art keywords
- methyl carbamate
- ethoxy carbonyl
- preparation
- bromopropyl
- bromopropyl methyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
Abstract
The present invention relates to field of agricultural herbicide, for the lower problem of yield, provide the preparation method of one kind (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate, the technical solution is as follows: in organic solvent, utilize alcohol and bromating agent collective effect, (S) -2- oxa- tetrahydrofuran base -3- methyl carbamate open loop, esterification, obtains (R) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate；Utilize alcohol and bromating agent collective effect, so that 2- oxo-tetrahydrofuran base is in neutral conditions, stable (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate is formed, the activity of 2- oxo-tetrahydrofuran base is higher in the synthetic route, so that conversion ratio improves, the yield of final product is higher.
Description
Technical field
The present invention relates to field of agricultural herbicide, more particularly, to one kind (S) -1- ethoxy carbonyl -3- bromopropyl amino
The preparation method of methyl formate.
Background technique
Typically, the different isomer of amino acid has different bioactivity, and more situation is only a kind of hand
Property isomers amino acid to have bioactivity be effective body, and another chiral isomer is then without bioactivity or activity
It is very weak.
Glufosinate-ammonium is the amino acids steriland herbicide of German Hirst company exploitation, in the world extensively
Using.
The L-glufosinate-ammonium that Japanese Mingzhi Fruit company develops accordingly is single L- chiral isomer, and through testing
Card, the D body of glufosinate-ammonium are not no bioactivity, and L body bioactivity is 2 times of raceme.
For a long time being prepared by the production technology of L-glufosinate-ammonium, many enterprises are carrying on technical development always in field,
It is split including biological enzyme synthesis, biological enzyme and isomers conversion, chiral catalysis synthesis, chemical resolution and isomers turns
Change etc., and have numerous patents report, but the method for biological enzyme does not have report or the practice of any industrialization so far.
The chiral chemistry catalyst synthesis L-GAP of Mingzhi Fruit company exploitation realizes industrialization in China, but
It is that its manufacturing cost is still not ideal enough.
German Hirst company reports in Tetrahedron Letters, Vol33, No19, pp2669-2672 within 1992
Road one kind is using (S) -2- amino butyrolactone as the method for Material synthesis L-glufosinate-ammonium, (S) -1- ethoxy carbonyl -3- chloropropyl
Methyl carbamate is one of its core intermediate, and key intermediate process route is as follows:
Under study for action, it is found that it is next that (S) -1- ethoxy carbonyl -3- chloropropyl methyl carbamate of amido protecting carries out
When step reaction, reactivity is inadequate, and the reaction time is long, and converts incomplete.Then expect with (S) -1- ethoxy carbonyl -3- bromine third
Ylcarbamic acid methyl ester replaces (S) -1- ethoxy carbonyl -3- chloropropyl methyl carbamate.
Sravan Kumar Patel a, Timothy E.Long is equal to 2009 in Tetrahedron Letters
Synthesis (S) -1- ethoxy carbonyl -3- bromopropyl carbamic acid first is reported in Vol 50, No 36, pp 5067-5070
The route of ester.
Although the synthetic route can synthesize (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate, practical study
When middle discovery (S) -2- amino butyrolactone hydrochloride reacts realization open loop bromination in acetic acid with hydrobromic acid, since butyrolactone is in acid
Property under the conditions of it is very stable, open loop is highly difficult, causes reactivity inadequate, and then cause yield lower, therefore, empty there are also improving
Between.
Summary of the invention
In view of the deficiencies of the prior art, the present invention intends to provide one kind (S) -1- ethoxy carbonyl -3- bromine
The preparation method of propylcarbamate has the advantages that yield is higher.
To achieve the above object, the present invention provides the following technical scheme that
The preparation method of one kind (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate utilizes in organic solvent
Alcohol and bromating agent collective effect, (S) -2- oxa- tetrahydrofuran base -3- methyl carbamate open loop, esterification obtain (R) -1- second
Epoxide carbonyl -3- bromopropyl methyl carbamate.
By using above-mentioned technical proposal, using alcohol and bromating agent collective effect, so that 2- oxa- tetrahydrofuran base is in
Property under the conditions of, by bromide ion the C-O key of 2- oxa- tetrahydrofuran base is broken and ring-opening reaction occurs generates bromopropyl, and lead to
The hydroxyl and carboxyl for crossing ethyl alcohol occur esterification and generate ethoxy carbonyl, to form stable (S) -1- ethoxy carbonyl -3-
Bromopropyl methyl carbamate, the activity of 2- oxa- tetrahydrofuran base is higher in the synthetic route, so that conversion ratio improves, finally
The yield of product is higher.
The present invention is further arranged to: the alcohol is one kind of C1-C4 alcohol.
By using above-mentioned technical proposal, because the carbochain of alcohol is shorter, esterification is easier, so that final product
Yield it is higher.
The present invention is further arranged to: the alcohol is methanol or ethyl alcohol.
By using above-mentioned technical proposal, since the carbochain of methanol and ethyl alcohol is shorter, so that esterification activity is higher,
Conversion ratio is improved, so that the yield of final product is higher.
The present invention is further arranged to: the organic solvent is toluene, dimethylbenzene, trimethylbenzene, methylene chloride, chloroform
Or dichloroethanes.
By using above-mentioned technical proposal, so that organic solvent is easy to (S) -2- oxa- tetrahydrofuran base -3- amino first
Sour methyl esters stabilizing dissolved guarantees that stable reaction carries out, keeps higher reaction rate.
The present invention is further arranged to: the organic solvent is dichloroethanes.
By using above-mentioned technical proposal, (S) -2- oxa- tetrahydrofuran base -3- carbamic acid is dissolved using dichloroethanes
Effect is preferable when methyl esters, guarantees that stable reaction carries out, keeps higher reaction rate.
The present invention is further arranged to: the reaction temperature is 0-100 DEG C.
By using above-mentioned technical proposal, so that reaction temperature is suitable for, reactivity is improved, improves conversion ratio and reaction
Rate.
The present invention is further arranged to: the reaction temperature is 20-50 DEG C.
By using above-mentioned technical proposal, so that reaction temperature is more suitable, improve reactivity, improve conversion ratio and
Reaction rate.
The present invention is further arranged to: the bromating agent is that dry hydrogen bromide, tribromo oxygen phosphorus, phosphorus tribromide or dibromo are sub-
Sulfone.
By using above-mentioned technical proposal so that bromating agent dissolution easily generate afterwards in organic solvent free bromine from
Son, and then the activity of ring-opening reaction is improved, conversion ratio is improved, and then improve the yield of final product.
The present invention is further arranged to: the bromating agent is hydrogen bromide, phosphorus tribromide.
By using above-mentioned technical proposal, the characteristic of organic solvent is soluble in using hydrogen bromide and phosphorus tribromide, so that
Faster, bromide ion concentration is higher, and then preferably improves the activity of ring-opening reaction for the free bromide ion rate of production, improves conversion
Rate, and then improve the yield of final product.
In conclusion the invention has the following advantages:
1. being formed stable using alcohol and bromating agent collective effect so that 2- oxa- tetrahydrofuran base is in neutral conditions
(S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate, the activity of 2- oxa- tetrahydrofuran base is higher in the synthetic route,
So that conversion ratio improves, the yield of final product is higher；
2. the carbochain by methanol and ethyl alcohol is shorter, so that esterification activity is higher, conversion ratio is improved, so that
The yield of final product is higher；
3. it is preferable using effect when dichloroethanes dissolution (S) -2- oxa- tetrahydrofuran base -3- methyl carbamate, guarantee
Stable reaction carries out, and keeps higher reaction rate；
4. the characteristic of organic solvent is soluble in using hydrogen bromide and phosphorus tribromide, so that bromide ion concentration is higher, in turn
The activity for preferably improving ring-opening reaction improves conversion ratio, and then improves the yield of final product.
Specific embodiment
With reference to embodiments, invention is further described in detail.
Embodiment 1
The preparation method of one kind (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate, in 250 milliliters of four-hole bottles plus
Enter 16 grams of (S) -2- oxa--tetrahydrofuran base -3- methyl carbamates, 18 grams of dehydrated alcohols, 80 grams of dichloroethanes are heated to 40
Degree, 20 grams of phosphorus tribromides of dropwise addition in 1-2 hours, insulation reaction 5 hours.Raw material conversion finishes.
Precipitation is depressurized, obtains light yellow oil, as (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate.Column
Chromatography, petroleum ether: ethyl acetate=4:1, as solvent.Obtain 24.2 grams of products.Yield 91%.
Reaction equation is as follows:
Embodiment 2
The preparation method of one kind (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate, in 250 milliliters of four-hole bottles plus
Enter 16 grams of (S) -2- oxa--tetrahydrofuran base -3- methyl carbamates, 18 grams of dehydrated alcohols, 80 grams of dichloroethanes are heated to 60
Degree, is slowly added dropwise 20 grams of phosphorus tribromides, and insulation reaction 5 hours.Raw material conversion finishes.
Precipitation is depressurized, obtains light yellow oil, as (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate.Column
Chromatography, petroleum ether: ethyl acetate=4:1, as solvent.Obtain 22.8 grams of products.Yield 85%.
Reaction equation is as follows:
Embodiment 3
The preparation method of one kind (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate, in 250 milliliters of four-hole bottles plus
Enter 16 grams of (S) -2- oxa--tetrahydrofuran base -3- methyl carbamates, 18 grams of dehydrated alcohols, 80 grams of dichloroethanes are heated to 40
Degree, is continually fed into bromination hydrogen, and insulation reaction 15 hours.Raw material conversion finishes.
Precipitation is depressurized, obtains light yellow oil, as (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate.Column
Chromatography, petroleum ether: ethyl acetate=4:1, as solvent.Obtain 21.4 grams of products.Yield 80%.
Reaction equation is as follows:
Embodiment 4
The preparation method of one kind (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate, in 250 milliliters of four-hole bottles plus
Enter 16 grams of (S) -2- oxa--tetrahydrofuran base -3- methyl carbamates, 18 grams of dehydrated alcohols, 80 grams of dichloroethanes are heated to 60
Degree, is continually fed into bromination hydrogen, and insulation reaction 15 hours.Raw material conversion finishes.
Precipitation is depressurized, obtains light yellow oil, as (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate.Column
Chromatography, petroleum ether: ethyl acetate=4:1, as solvent.Obtain 25.9 grams of products.Yield 93%.
Reaction equation is as follows:
It can be obtained according to embodiment 1- embodiment 4, the yield of final product will be made obvious using synthetic route of the invention
It is promoted.
When bromating agent uses phosphorus tribromide, optimal reaction temperature is 40 DEG C.
When bromating agent uses bromination hydrogen, optimal reaction temperature is 60 DEG C.
The embodiment of present embodiment is presently preferred embodiments of the present invention, not limits protection of the invention according to this
Range, therefore: the equivalence changes that all structures under this invention, shape, principle are done, should all be covered by protection scope of the present invention it
It is interior.
Claims (9)
1. the preparation method of one kind (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate, it is characterized in that: in organic solvent
In, using alcohol and bromating agent collective effect, (S) -2- oxa--tetrahydrofuran base -3- methyl carbamate open loop, esterification is obtained
(R) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate.
2. the preparation method of (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate according to claim 1, special
Sign is: the alcohol is one kind of C1-C4 alcohol.
3. the preparation method of (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate according to claim 2, special
Sign is: the alcohol is methanol or ethyl alcohol.
4. the preparation method of (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate according to claim 1, special
Sign is: the organic solvent is toluene, dimethylbenzene, trimethylbenzene, methylene chloride, chloroform or dichloroethanes.
5. the preparation method of (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate according to claim 4, special
Sign is: the organic solvent is dichloroethanes.
6. the preparation method of (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate according to claim 1, special
Sign is: the reaction temperature is 0-100 DEG C.
7. the preparation method of (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate according to claim 6, special
Sign is: the reaction temperature is 20-50 DEG C.
8. the preparation method of (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate according to claim 1, special
Sign is: the bromating agent is dry hydrogen bromide, tribromo oxygen phosphorus, phosphorus tribromide or dibromo sulfoxide.
9. the preparation method of (S) -1- ethoxy carbonyl -3- bromopropyl methyl carbamate according to claim 8, special
Sign is: the bromating agent is hydrogen bromide, phosphorus tribromide.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110386882A (en) * | 2019-08-12 | 2019-10-29 | 利尔化学股份有限公司 | (S) preparation method of the chloro- 2- of -4- ((ethoxy carbonyl) amino) ethyl butyrate |
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2018
- 2018-11-02 CN CN201811303492.6A patent/CN109384693A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110386882A (en) * | 2019-08-12 | 2019-10-29 | 利尔化学股份有限公司 | (S) preparation method of the chloro- 2- of -4- ((ethoxy carbonyl) amino) ethyl butyrate |
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