CN103304402B - Method for preparing 4-benzene-1-butyric acid - Google Patents
Method for preparing 4-benzene-1-butyric acid Download PDFInfo
- Publication number
- CN103304402B CN103304402B CN201310195564.0A CN201310195564A CN103304402B CN 103304402 B CN103304402 B CN 103304402B CN 201310195564 A CN201310195564 A CN 201310195564A CN 103304402 B CN103304402 B CN 103304402B
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- CN
- China
- Prior art keywords
- benzene
- butyric acid
- butyrolactone
- organic layer
- temperature control
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 14
- 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 24
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 11
- 239000012044 organic layer Substances 0.000 claims abstract description 11
- 230000007062 hydrolysis Effects 0.000 claims abstract description 10
- 239000010410 layer Substances 0.000 claims abstract description 9
- 238000010992 reflux Methods 0.000 claims abstract description 9
- 239000003208 petroleum Substances 0.000 claims description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 229930188620 butyrolactone Natural products 0.000 abstract description 2
- 238000001816 cooling Methods 0.000 abstract description 2
- 238000004821 distillation Methods 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
- 239000000463 material Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 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
- 0 CO*(CCC1)O[C@]1OC Chemical compound CO*(CCC1)O[C@]1OC 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
- 230000000630 rising effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for preparing 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 process 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. 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 preparation method of organic compound, specifically, is a kind of method preparing 4-benzene-1-butyric acid.
Background technology
4-benzene-1-butyric acid is a kind of important intermediate of the synthesis treatment general Leinster of asthma medicine, the relevant report of synthesizing this material obtains 3-carbonyl benzenebutanoic acid for adopting Succinic anhydried and purified petroleum benzin Friedel-Crafts reaction, then be methylene radical through Wollf-Kishner or zinc-amalgam by carbonyl reduction, obtain 4-benzene-1-butyric acid, building-up reactions formula is:
But this synthetic route process is complicated, and severe reaction conditions, material cost is high.Therefore need that a kind of reactions steps is simple, synthesis yield is high, starting material are easy to get badly and new preparation method that is cheap, good product quality, but have not been reported about these class methods at present.
Summary of the invention
The object of the invention is for deficiency of the prior art, a kind of method preparing 4-benzene-1-butyric acid is provided.
For achieving the above object, the technical scheme that the present invention takes is:
A kind of method preparing 4-benzene-1-butyric acid, it is that purified petroleum benzin, aluminum chloride are added reaction unit, temperature control 0-40 DEG C drips gamma-butyrolactone, finish temperature rising reflux 3-5 hour, cooling is poured in dilute hydrochloric acid and is hydrolyzed, separate lower aqueous layer after hydrolysis completely, after collected organic layer adds water washing, underpressure distillation is to doing to obtain 4-benzene-1-butyric acid.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 is the solution of 1: 2 with quality ratio.
Preferably, the temperature of described hydrolysis reaction is 5-30 DEG C.
It should be noted that, described purified petroleum benzin and 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 adopt butyrolactone and purified petroleum benzin single step reaction direct 4-benzene-1-butyric acid, 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 more excellent approach.
Embodiment
Below embodiment provided by the invention is elaborated.
embodiment 1
By purified petroleum benzin 400g(5.13mol), aluminum chloride 200g(1.50mol) add reaction flask, temperature control 35-40 DEG C drips gamma-butyrolactone 100 grams (1.16mol), add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control less than 30 DEG C (25-30 DEG C), lower aqueous layer is separated after hydrolysis completely, collected organic layer adds water 200g and washs, anhydrous magnesium sulfate drying, through being evaporated to dry white solid 175.2g, yield 92%.Purity 99.32%(HPLC).
embodiment 2
By purified petroleum benzin 500g(6.40mol), aluminum chloride 220g(1.65mol) add reaction flask, temperature control 20-25 DEG C drips gamma-butyrolactone 95g(1.10mol), add intensification and be incubated 4 hours at reflux, be cooled to 20 DEG C, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control less than 30 DEG C (20-25 DEG C), lower aqueous layer is separated after hydrolysis completely, collected organic layer adds water 200g and washs, anhydrous magnesium sulfate drying, through being evaporated to dry white solid 170.1g, yield 94.2%.Purity 99.55%(HPLC).
embodiment 3
By purified petroleum benzin 350g(4.49mol), aluminum chloride 180g(1.35mol) add reaction flask, temperature control 0-5 DEG C drips gamma-butyrolactone 120g(1.39mol), add intensification and be incubated 5 hours at reflux, be cooled to 20 DEG C, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control less than 30 DEG C (15-20 DEG C), lower aqueous layer is separated after hydrolysis completely, collected organic layer adds water 200g and washs, anhydrous magnesium sulfate drying, through being evaporated to dry white solid 214.1g, yield 93.8%.Purity 99.32%(HPLC).
embodiment 4
By purified petroleum benzin 450g(5.77mol), aluminum chloride 220g(1.65mol) add reaction flask, temperature control 10-15 DEG C drips gamma-butyrolactone 120g(1.39mol), add intensification and be incubated 5 hours at reflux, be cooled to 20 DEG C, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control less than 30 DEG C (10-15 DEG C), lower aqueous layer is separated after hydrolysis completely, collected organic layer adds water 200g and washs, anhydrous magnesium sulfate drying, through being evaporated to dry white solid 202.3g, yield 94.0%.Purity 99.51%(HPLC).
embodiment 5
By purified petroleum benzin 400g(5.13mol), aluminum chloride 200g(1.50mol) add reaction flask, temperature control 30-35 DEG C drips gamma-butyrolactone 95g(1.10mol), add intensification and be incubated 5 hours at reflux, be cooled to 20 DEG C, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control less than 30 DEG C (5-10 DEG C), lower aqueous layer is separated after hydrolysis completely, collected organic layer adds water 200g and washs, anhydrous magnesium sulfate drying, through being evaporated to dry white solid 171.3g, yield 91.5%.Purity 99.35%(HPLC).
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite not departing from the inventive method; can also make some improvement and supplement, these improve and supplement and also should be considered as protection scope of the present invention.
Claims (2)
1. prepare the method for 4-benzene-1-butyric acid for one kind, it is characterized in that, it is by purified petroleum benzin 5.13mol, aluminum chloride 1.50mol adds reaction flask, temperature control 35-40 DEG C drips gamma-butyrolactone 1.16mol, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control is at 25-30 DEG C, lower aqueous layer is separated after hydrolysis completely, collected organic layer adds water 200g and washs, anhydrous magnesium sulfate drying, through being evaporated to dry white solid 175.2g, namely described 4-benzene-1-butyric acid, yield 92%, it is 99.32% that HPLC detects purity.
2. prepare the method for 4-benzene-1-butyric acid for one kind, it is characterized in that, it is by purified petroleum benzin 5.13mol, aluminum chloride 1.50mol adds reaction flask, temperature control 30-35 DEG C drips gamma-butyrolactone 1.10mol, add intensification and be incubated 5 hours at reflux, be cooled to 20 DEG C, slowly pour in the mixing solutions of 250g concentrated hydrochloric acid and 500g water and be hydrolyzed, temperature control is at 5-10 DEG C, lower aqueous layer is separated after hydrolysis completely, collected organic layer adds water 200g and washs, anhydrous magnesium sulfate drying, through being evaporated to dry white solid 171.3g, namely described 4-benzene-1-butyric acid, yield 91.5%, it is 99.35% that HPLC detects purity.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310195564.0A CN103304402B (en) | 2013-05-24 | 2013-05-24 | Method for preparing 4-benzene-1-butyric acid |
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|---|---|---|---|
| CN201310195564.0A CN103304402B (en) | 2013-05-24 | 2013-05-24 | Method for preparing 4-benzene-1-butyric acid |
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|---|---|
| CN103304402A CN103304402A (en) | 2013-09-18 |
| CN103304402B true CN103304402B (en) | 2015-04-22 |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2850391A1 (en) | 2011-09-30 | 2013-04-04 | Hyperion Therapeutics, Inc. | Methods of therapeutic monitoring of nitrogen scavenging drugs |
| US9914692B2 (en) | 2016-05-25 | 2018-03-13 | Horizon Therapeutics, Llc | Procedure for the preparation of 4-phenyl butyrate and uses thereof |
| US10668040B2 (en) | 2017-09-11 | 2020-06-02 | Horizon Therapeutics, Llc | Treatment of urea cycle disorders in neonates and infants |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6372938B1 (en) * | 2001-05-21 | 2002-04-16 | Stanislaw R. Burzynski | Synthesis of 4-phenylbutyric acid |
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