CN103539666B - Preparation method of 2-methyl-3-butenoic acid ester - Google Patents
Preparation method of 2-methyl-3-butenoic acid ester Download PDFInfo
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- CN103539666B CN103539666B CN201310450735.XA CN201310450735A CN103539666B CN 103539666 B CN103539666 B CN 103539666B CN 201310450735 A CN201310450735 A CN 201310450735A CN 103539666 B CN103539666 B CN 103539666B
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- 0 CC(*)C(CBr)Br Chemical compound CC(*)C(CBr)Br 0.000 description 1
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
Abstract
The invention discloses a preparation method of 2-methyl-3-butenoic acid ester. The preparation method comprises the following steps: (1) under the effect of elemental iodine, carrying out reaction on 3-halogeneted butene and magnesium in an ether solvent to obtain a 3-halogeneted-butene Grignard reagent; and (2) dropwise adding the 3-halogeneted-butene Grignard reagent obtained in step (1) into carbonic ester for substitution reaction to obtain 2-methyl-3-butenoic acid ester. According to the preparation method which prepares the 3-halogeneted-butene Grignard reagent first by taking 3-halogeneted butene as an initial raw material and then carries out substitution reaction with carbonic ester, the reaction line is shortened, the product yield is improved and the post-treatment step is simplified, and meanwhile, use of virulent hydrocyanic acid is avoided in the line, so that the preparation method is more environment-friendly.
Description
Technical field
The invention belongs to chemical intermediate preparation method, be specifically related to a kind of preparation method of 2-methyl-3-butenoic acid ester.
Background technology
Carbon phosphonate ester (VII) is the important intermediate of synthesis A Piao β carotenoic acid ethyl ester and related compound, has its synthesis of a series of bibliographical information at present, wherein comparatively obvious with the synthetic route advantage that 2-methyl-3-butenoic acid ester is raw material.
US Patent No. 4937308 discloses a kind of synthetic route of carbon phosphonate ester (VII), first this route is under the effect of bromine simple substance, the double bond generation addition reaction of 2-methyl-3-butenoic acid ester (IV), generate corresponding dibromo product (V), dibromo product (V) sloughs hydrogen bromide generation bromination product (VI) of a part afterwards, and last bromination product (VI) and triethyl-phosphite react Formed phosphonate ester (VII).This synthetic route is shown below:
Starting raw material 2-methyl-3-butenoic acid ester (IV) in this synthetic route needs by 1,3-butadiene or reacts between 3-halo butylene and prussic acid and generate 2-methyl-3-butylene cyanogen (IX) (see in US4937308).2-methyl-3-butylene cyanogen (IX) generates 2-methyl-3-butenoic acid (X) through hydrolysis again, and last esterification obtains product.And prussic acid is well-known chemical industry drugs, all bring great hidden danger to operator and environment, the reaction formula of preparation 2-methyl-3-butenoic acid ester (IV) is as follows:
Summary of the invention
The invention provides a kind of preparation method of 2-methyl-3-butenoic acid ester, this preparation method avoids the use of chemical industry highly toxic product prussic acid, the environmental protection more of whole route, and low toxicity is with efficient.
A preparation method for 2-methyl-3-butenoic acid ester, comprises the steps:
(1) under the effect of elemental iodine, 3-halo butylene and magnesium react in ether solvents, obtain 3-halo-butylene Grignard reagent;
The structure of described 3-halo butylene is as shown in formula I:
The structure of described 3-halo-butylene Grignard reagent is as shown in formula II:
In formula I and formula II, X is Cl or Br;
(2) carry out substitution reaction in the 3-halo-butylene Grignard reagent dropwise to carbonic ether step (1) obtained, obtain described 2-methyl-3-butenoic acid ester;
The structure of described carbonic ether is as shown in formula III:
The structure of described 2-methyl-3-butenoic acid ester is as shown in formula IV:
In formula III and formula IV, R is C1 ~ C5 alkyl or phenyl.
In the present invention, with 3-halo butylene for starting raw material, be first prepared into 3-halo-butylene Grignard reagent, and then carry out substitution reaction with carbonic ether, adopt this route to avoid the prussic acid using severe toxicity, more friendly to environment; And adopt this route, obviously shorten reactions steps, operate simpler.
As preferably, in step (1), described ether solvents is ether, isopropyl ether or tetrahydrofuran (THF), adopts these ether solvents, and the yield preparing 3-halo-butylene Grignard reagent is high.Wherein, the consumption of solvent is without requirement strict especially, and generally can by under the prerequisite of material dissolution, consumption be not easily too much, to prevent from diluting the 3-halo-butylene Grignard reagent obtained, affects next step reaction.
As preferably, in step (1), temperature of reaction is 10 ~ 25 DEG C, and temperature of reaction is too low, and be unfavorable for the initiation of reacting and normally carry out, temperature of reaction is too high, and side reaction can be made to increase.
As preferably, in step (1), the mol ratio of described elemental iodine and described 3-halo butylene is 0.01% ~ 0.1%:1;
The mol ratio of described magnesium and described 3-halo butylene is 1:1.0 ~ 1.5, and wherein, elemental iodine is not easily too much, otherwise easily in system, introduces impurity.
Reaction times is long, and the 3-halo-butylene Grignard reagent generated can be made to decompose, as preferably, in step (1), the reaction times is 0.5 ~ 1 hour, in this time range, can react fully, the decomposition of described 3-halo-butylene Grignard reagent can have been avoided again.
As preferably, in step (2), described carbonic ether is methylcarbonate, diethyl carbonate or diphenyl carbonate, and the reactive behavior of these reagent is good, and the product obtained has important purposes.
In step (2), temperature of reaction is too low, low conversion rate, and temperature of reaction is too high, can obtain polysubstituted product, and as preferably, in step (2), temperature of reaction is 40 ~ 60 DEG C.
As preferably, the mol ratio of the carbonic ether in the 3-halo butylene in step (1) and step (2) is 1:0.9 ~ 1.1.
As further preferred, described ether solvents is anhydrous diethyl ether, and described X is Cl, and described carbonic ether is methylcarbonate, and now, yield and the purity of the 2-methyl-3-butenoic acid methyl esters obtained are high; As other preferred, described ether solvents is anhydrous diethyl ether, and described X is Br, and described carbonic ether is diethyl carbonate, and now, yield and the purity of the 2-methyl-3-butenoic acid ethyl ester obtained are high; As other preferred, described ether solvents is tetrahydrofuran (THF), and described X is Br, and described carbonic ether is diphenyl carbonate, and now, yield and the purity of the 2-methyl-3-butenoic acid phenyl ester obtained are high.
Compared with the existing technology, beneficial effect of the present invention is embodied in:
(1) with 3-halo butylene for starting raw material, be first prepared into 3-halo-butylene Grignard reagent, and then carry out substitution reaction with carbonic ether, shorten reaction scheme, improve the yield of product, simplify post-processing step;
(2) this preparation method avoids the use of the prussic acid of severe toxicity, more friendly to environment.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail.
Embodiment 1
In 50ml flask, add 24g magnesium sheet and 50ml anhydrous diethyl ether, then add 0.2g elemental iodine, and start slowly to stir.Be dissolved in 100ml anhydrous diethyl ether by 90.5g3-Cl-butylene and stir, be slowly added dropwise to reaction flask by constant pressure funnel, controlling temperature of reaction is 20 ± 2 DEG C.Stop after 0.5h stirring, reaction system dropwise added under normal temperature in the reaction flask filling 90g methylcarbonate, dropping limit, limit is stirred.After 0.5h dropwises, insulation reaction 3h at 50 ~ 60 DEG C, washes reaction system with water 3 times after reaction terminates, and collects oil reservoir, and steam low-boiling-point substances such as desolventizing, obtain the finished product 98.6g, GC content is 98.2%, and retention time is consistent with standard substance, and yield is 85%.
Embodiment 2
In 50ml flask, add 24g magnesium sheet and 50ml isopropyl ether, then add 0.2g elemental iodine, and start slowly to stir.Be dissolved in 100ml isopropyl ether by 90.5g3-Cl-butylene and stir, be slowly added dropwise to reaction flask by constant pressure funnel, controlling temperature of reaction is 20 ± 2 DEG C.Stop after 0.5h stirring, reaction system dropwise added under normal temperature in the reaction flask filling 90g methylcarbonate, dropping limit, limit is stirred.After 0.5h dropwises, insulation reaction 3h at 50 ~ 60 DEG C, washes reaction system with water 3 times after reaction terminates, and collects oil reservoir, and steam low-boiling-point substances such as desolventizing, obtain the finished product 97.5g, GC content is 98.0%, and retention time is consistent with standard substance, and yield is 83.9%.
Embodiment 3
In 50ml flask, add 24g magnesium sheet and 50ml anhydrous diethyl ether, then add 0.2g elemental iodine, and start slowly to stir.Be dissolved in 100ml anhydrous diethyl ether by 90.5g3-Cl-butylene and stir, be slowly added dropwise to reaction flask by constant pressure funnel, controlling temperature of reaction is 20 ± 2 DEG C.Stop after 0.5h stirring, reaction system dropwise added under normal temperature in the reaction flask filling 118g diethyl carbonate, dropping limit, limit is stirred.After 0.5h dropwises, insulation reaction 3h at 50 ~ 60 DEG C, washes reaction system with water 3 times after reaction terminates, and collects oil reservoir, and steam low-boiling-point substances such as desolventizing, obtain the finished product 102.5g, GC content is 98.0%, and retention time is consistent with standard substance, and yield is 78%.
Embodiment 4
In 50ml flask, add 24g magnesium sheet and 50ml anhydrous diethyl ether, then add 0.05g elemental iodine, and start slowly to stir.Be dissolved in 100ml anhydrous diethyl ether by 125g3-Br-butylene and stir, be slowly added dropwise to reaction flask by constant pressure funnel, controlling temperature of reaction is 15 ± 2 DEG C.Stop after 0.5h stirring, reaction system dropwise added under normal temperature in the reaction flask filling 118g diethyl carbonate, dropping limit, limit is stirred.After 0.5h dropwises, insulation reaction 2h at 50 ~ 60 DEG C, washes reaction system with water 3 times after reaction terminates, and collects oil reservoir, and steam low-boiling-point substances such as desolventizing, obtain the finished product 105.0g, GC content is 98.5%, and retention time is consistent with standard substance, and yield is 80.8%.
Embodiment 5
In 50ml flask, add 24g magnesium sheet and 50ml isopropyl ether, then add 0.05g elemental iodine, and start slowly to stir.Be dissolved in 100ml isopropyl ether by 125g3-Br-butylene and stir, be slowly added dropwise to reaction flask by constant pressure funnel, controlling temperature of reaction is 15 ± 2 DEG C.Stop after 0.5h stirring, reaction system dropwise added under normal temperature in the reaction flask filling 118g diethyl carbonate, dropping limit, limit is stirred.After 0.5h dropwises, insulation reaction 2h at 50 ~ 60 DEG C, washes reaction system with water 3 times after reaction terminates, and collects oil reservoir, and steam low-boiling-point substances such as desolventizing, obtain the finished product 100.0g, GC content is 97.5%, and retention time is consistent with standard substance, and yield is 76.2%.
Embodiment 6
In 50ml flask, add 24g magnesium sheet and 50ml tetrahydrofuran (THF), then add 0.05g elemental iodine, and start slowly to stir.Be dissolved in 100ml tetrahydrofuran (THF) by 125g3-Br-butylene and stir, be slowly added dropwise to reaction flask by constant pressure funnel, controlling temperature of reaction is 12 ± 2 DEG C.Stop after 0.5h stirring, and reaction system dropwise added in the reaction flask filling 214g diphenyl carbonate, dropping limit, limit is stirred.After 0.5h dropwises, insulation reaction 2h at 50 ~ 60 DEG C, washes reaction system with water 3 times after reaction terminates, and collects oil reservoir, and steam low-boiling-point substances such as desolventizing, obtain the finished product 152.4g, GC content is 98.8%, and retention time is consistent with standard substance, and yield is 86.4%.
Embodiment 7
In 50ml flask, add 24g magnesium sheet and 50ml isopropyl ether, then add 0.05g elemental iodine, and start slowly to stir.Be dissolved in 100ml tetrahydrofuran (THF) by 125g3-Br-butylene and stir, be slowly added dropwise to reaction flask by constant pressure funnel, controlling temperature of reaction is 12 ± 2 DEG C.Stop after 0.5h stirring, and reaction system dropwise added in the reaction flask filling 214g diphenyl carbonate, dropping limit, limit is stirred.After 0.5h dropwises, insulation reaction 2h at 50 ~ 60 DEG C, washes reaction system with water 3 times after reaction terminates, and collects oil reservoir, and steam low-boiling-point substances such as desolventizing, obtain the finished product 145.0g, GC content is 98.2%, and retention time is consistent with standard substance, and yield is 81.7%.
Claims (6)
1. a preparation method for 2-methyl-3-butenoic acid ester, is characterized in that, comprises the steps:
(1) under the effect of elemental iodine, 3-halo butylene and magnesium react in ether solvents, obtain 3-butylene Grignard reagent;
The structure of described 3-halo butylene is as shown in formula I:
The structure of described 3-butylene grignard reagent is as shown in formula II:
In formula I and formula II, X is Cl or Br;
In step (1), temperature of reaction is 10 ~ 25 DEG C;
(2) carry out substitution reaction in the 3-butylene Grignard reagent dropwise to carbonic ether step (1) obtained, obtain described 2-methyl-3-butenoic acid ester;
The structure of described carbonic ether is as shown in formula III:
The structure of described 2-methyl-3-butenoic acid ester is as shown in formula IV:
In formula III and formula IV, R is C
1~ C
5alkyl or phenyl;
In step (2), temperature of reaction is 50 ~ 60 DEG C.
2. the preparation method of 2-methyl-3-butenoic acid ester according to claim 1, is characterized in that, in step (1), described ether solvents is ether, isopropyl ether or tetrahydrofuran (THF).
3. the preparation method of 2-methyl-3-butenoic acid ester according to claim 1, is characterized in that, in step (1), the mol ratio of described elemental iodine and described 3-halo butylene is 0.01% ~ 0.1%:1;
The mol ratio of described magnesium and described 3-halo butylene is 1:1.0 ~ 1.5.
4. the preparation method of 2-methyl-3-butenoic acid ester according to claim 1, is characterized in that, in step (1), the reaction times is 0.5 ~ 1 hour.
5. the preparation method of 2-methyl-3-butenoic acid ester according to claim 1, is characterized in that, in step (2), described carbonic ether is methylcarbonate, diethyl carbonate or diphenyl carbonate.
6. the preparation method of 2-methyl-3-butenoic acid ester according to claim 1, is characterized in that, the mol ratio of the carbonic ether in the 3-halo butylene in step (1) and step (2) is 1:0.9 ~ 1.1.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1654452A (en) * | 2004-02-13 | 2005-08-17 | 大连绿源药业有限责任公司 | Method of producing carboxylate |
| CN102093396A (en) * | 2010-12-27 | 2011-06-15 | 浙江新和成股份有限公司 | Method for preparing Grignard reagent |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1654452A (en) * | 2004-02-13 | 2005-08-17 | 大连绿源药业有限责任公司 | Method of producing carboxylate |
| CN102093396A (en) * | 2010-12-27 | 2011-06-15 | 浙江新和成股份有限公司 | Method for preparing Grignard reagent |
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