CN103304403A - Method for synthesizing 4-benzene-1-butyric acid - Google Patents
Method for synthesizing 4-benzene-1-butyric acid Download PDFInfo
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- CN103304403A CN103304403A CN2013101955867A CN201310195586A CN103304403A CN 103304403 A CN103304403 A CN 103304403A CN 2013101955867 A CN2013101955867 A CN 2013101955867A CN 201310195586 A CN201310195586 A CN 201310195586A CN 103304403 A CN103304403 A CN 103304403A
- Authority
- CN
- China
- Prior art keywords
- benzene
- butyric acid
- butyrolactone
- organic layer
- gamma
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title abstract description 9
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims abstract description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 27
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 11
- 239000012044 organic layer Substances 0.000 claims abstract description 10
- 230000007062 hydrolysis Effects 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000010410 layer Substances 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 8
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 238000004821 distillation Methods 0.000 claims abstract description 3
- 239000003208 petroleum Substances 0.000 claims description 12
- 238000010189 synthetic method Methods 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- 230000000630 rising effect Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 229930188620 butyrolactone Natural products 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 238000005580 one pot reaction Methods 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- 229910000497 Amalgam Inorganic materials 0.000 description 1
- BFJDTNSWCVCHKJ-UHFFFAOYSA-N C(=O)=C1CC(=CC=C1)CCCC(=O)O Chemical compound C(=O)=C1CC(=CC=C1)CCCC(=O)O BFJDTNSWCVCHKJ-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for synthesizing 4-benzene-1-butyric acid. The method comprises the steps of adding pure benzene and aluminum chloride to a reactor, dropwise adding gamma-butyrolactone while controlling the temperature to be 0-40 DEG C, heating up to reflux for 3-5 hours after the adding is completed, cooling, pouring a reacted mixture into dilute hydrochloric acid for hydrolysis, separating a lower water layer after the hydrolysis is completed, collecting an organic layer, adding water to clean the organic layer, and then carrying out reduced-pressure distillation until the cleaned organic layer is dried, thereby obtaining the 4-benzene-1-butyric acid, wherein the mole ratio of pure benzene to aluminum chloride to gamma-butyrolactone is (3.23-5.82): (0.97-1.5): 1 preferably. According to the method, the 4-benzene-1-butyric acid is prepared from butyrolactone and pure benzene directly through one-step reaction, the reaction steps are simple, the raw materials are obtained easily, the cost is low, the industrial production is facilitated, the synthesis yield is high, and the product quality is good, so that a more excellent way is provided for the preparation of the 4-benzene-1-butyric acid.
Description
Technical field
The present invention relates to the synthetic method of organic compound, specifically, is the synthetic method of a kind of 4-benzene-1-butyric acid.
Background technology
4-benzene-1-butyric acid is a kind of important intermediate of the general Leinster of synthetic treatment asthma medicine, the relevant report of synthetic this material is for adopting Succinic anhydried and purified petroleum benzin Friedel-Crafts reaction to obtain 3-carbonyl benzenebutanoic acid, then be methylene radical through Wollf-Kishner or zinc-amalgam with carbonyl reduction, get 4-benzene-1-butyric acid, the building-up reactions formula is:
But this synthetic route process is complicated, severe reaction conditions, and material cost is high.Therefore need that a kind of reactions steps is simple, synthesis yield is high, starting material are easy to get and new preparation method cheap, good product quality badly, but yet there are no report about these class methods at present.
Summary of the invention
The objective of the invention is for deficiency of the prior art, the method for a kind of 4-of preparation benzene-1-butyric acid is provided.
For achieving the above object, the technical scheme taked of the present invention is:
A kind of method for preparing 4-benzene-1-butyric acid, it is that purified petroleum benzin, aluminum chloride are added reaction unit, temperature control 0-40 ℃ drips gamma-butyrolactone, finish temperature rising reflux 4-5 hour, cooling is poured in the dilute hydrochloric acid and is hydrolyzed, tell lower aqueous layer after the hydrolysis fully, underpressure distillation was to doing to get 4-benzene-1-butyric acid after collected organic layer added water washing.Reaction equation is as follows:
Preferably, the mol ratio of described purified petroleum benzin, aluminum chloride and gamma-butyrolactone is 3.23-5.82: 0.97-1.5: 1.
Described dilute hydrochloric acid is concentrated hydrochloric acid with the quality ratio is 1: 2 solution.
Preferably, the temperature of described hydrolysis reaction is 5-30 ℃.
Need to prove, described purified petroleum benzin is benzene, molecular formula C
6H
6, molecular weight 78.11; Described gamma-butyrolactone molecular formula: C
4H
6O
2, molecular weight 86.09.
The invention has the advantages that: the present invention adopts butyrolactone and the direct 4-benzene-1-butyric acid that gets of purified petroleum benzin single step reaction, reactions steps is simple, starting material are easy to get, cheap, be convenient to suitability for industrialized production, and synthesis yield is high, good product quality, for the preparation of 4-benzene-1-butyric acid provides a kind of better approach.
Embodiment
The below elaborates to embodiment provided by the invention.
Embodiment 1
With purified petroleum benzin 400g(5.13mol), aluminum chloride 200g(1.50mol) add reaction flask, temperature control 35-40 ℃ drips gamma-butyrolactone 100 grams (1.16mol), adding heats up is incubated 3 hours under reflux state, be cooled to 20 ℃, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control is (25-30 ℃) below 30 ℃, tell lower aqueous layer after the hydrolysis fully, collected organic layer adds entry 200g washing, anhydrous magnesium sulfate drying, through being evaporated to dried white solid 175.2g, yield 92%.Purity 99.32%(HPLC).
Embodiment 2
With purified petroleum benzin 500g(6.40mol), aluminum chloride 220g(1.65mol) add reaction flask, temperature control 20-25 ℃ drips gamma-butyrolactone 95g(1.10mol), adding heats up is incubated 4 hours under reflux state, be cooled to 20 ℃, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control is (20-25 ℃) below 30 ℃, tell lower aqueous layer after the hydrolysis fully, collected organic layer adds entry 200g washing, anhydrous magnesium sulfate drying, through being evaporated to dried white solid 170.1g, yield 94.2%.Purity 99.55%(HPLC).
Embodiment 3
With purified petroleum benzin 350g(4.49mol), aluminum chloride 180g(1.35mol) add reaction flask, temperature control 0-5 ℃ drips gamma-butyrolactone 120g(1.39mol), adding heats up is incubated 5 hours under reflux state, be cooled to 20 ℃, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control is (15-20 ℃) below 30 ℃, tell lower aqueous layer after the hydrolysis fully, collected organic layer adds entry 200g washing, anhydrous magnesium sulfate drying, through being evaporated to dried white solid 214.1g, yield 93.8%.Purity 99.32%(HPLC).
Embodiment 4
With purified petroleum benzin 450g(5.77mol), aluminum chloride 220g(1.65mol) add reaction flask, temperature control 10-15 ℃ drips gamma-butyrolactone 120g(1.39mol), adding heats up is incubated 5 hours under reflux state, be cooled to 20 ℃, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control is (10-15 ℃) below 30 ℃, tell lower aqueous layer after the hydrolysis fully, collected organic layer adds entry 200g washing, anhydrous magnesium sulfate drying, through being evaporated to dried white solid 202.3g, yield 94.0%.Purity 99.51%(HPLC).
Embodiment 5
With purified petroleum benzin 400g(5.13mol), aluminum chloride 200g(1.50mol) add reaction flask, temperature control 30-35 ℃ drips gamma-butyrolactone 95g(1.10mol), adding heats up is incubated 5 hours under reflux state, be cooled to 20 ℃, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control is (5-10 ℃) below 30 ℃, tell lower aqueous layer after the hydrolysis fully, collected organic layer adds entry 200g washing, anhydrous magnesium sulfate drying, through being evaporated to dried white solid 171.3g, yield 91.5%.Purity 99.35%(HPLC).
The above only is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the inventive method; can also make some improvement and replenish, these improvement and replenish and also should be considered as protection scope of the present invention.
Claims (4)
1. the synthetic method of 4-benzene-1-butyric acid, it is characterized in that, it is that purified petroleum benzin, aluminum chloride are added reaction unit, temperature control 0-40 ℃ drips gamma-butyrolactone, finish temperature rising reflux 4-5 hour, cooling is poured in the dilute hydrochloric acid and is hydrolyzed, and tells lower aqueous layer after the hydrolysis fully, and underpressure distillation was to doing to get 4-benzene-1-butyric acid after collected organic layer added water washing.
2. the synthetic method of 4-benzene according to claim 1-1-butyric acid is characterized in that, the mol ratio of described purified petroleum benzin, aluminum chloride and gamma-butyrolactone is 3.23-5.82: 0.97-1.5: 1.
3. the synthetic method of 4-benzene according to claim 1-1-butyric acid is characterized in that, described dilute hydrochloric acid is concentrated hydrochloric acid with the quality ratio is 1: 2 solution.
4. the synthetic method of 4-benzene according to claim 1-1-butyric acid is characterized in that, the temperature of described hydrolysis reaction is 5-30 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310195586.7A CN103304403B (en) | 2013-05-24 | 2013-05-24 | Method for synthesizing 4-benzene-1-butyric acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310195586.7A CN103304403B (en) | 2013-05-24 | 2013-05-24 | Method for synthesizing 4-benzene-1-butyric acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103304403A true CN103304403A (en) | 2013-09-18 |
| CN103304403B CN103304403B (en) | 2015-04-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310195586.7A Active CN103304403B (en) | 2013-05-24 | 2013-05-24 | Method for synthesizing 4-benzene-1-butyric acid |
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| Country | Link |
|---|---|
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1511133A (en) * | 2001-05-21 | 2004-07-07 | R������˹�� ˹̹��˹�� | Synthesis of 4-phenylbutyric acid |
-
2013
- 2013-05-24 CN CN201310195586.7A patent/CN103304403B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1511133A (en) * | 2001-05-21 | 2004-07-07 | R������˹�� ˹̹��˹�� | Synthesis of 4-phenylbutyric acid |
Non-Patent Citations (1)
| Title |
|---|
| 陈华奇等: "4-苯基丁醇的制备", 《中国医药工业杂志》 * |
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| CN103304403B (en) | 2015-04-22 |
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