CN100340538C - Method for preparing bromopentoic acid - Google Patents
Method for preparing bromopentoic acid Download PDFInfo
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- CN100340538C CN100340538C CNB2005101100027A CN200510110002A CN100340538C CN 100340538 C CN100340538 C CN 100340538C CN B2005101100027 A CNB2005101100027 A CN B2005101100027A CN 200510110002 A CN200510110002 A CN 200510110002A CN 100340538 C CN100340538 C CN 100340538C
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- valeric acid
- bromine valeric
- cycloalkane
- bromovaleric acid
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Abstract
The present invention relates to a 5-bromovaleric acid preparation method which belongs to the technical field of organic compound preparation. The dried hydrogen bromide gas is directly led into an organic solvent containing delta-valerolactone which easily carries out ring opening reaction, and the corresponding 5-bromovaleric acid is generated at high yield. As the 5-bromovaleric acid is difficult to dissolve in an alkane solvent, a naphthenic hydrocarbon solvent and a dutrex solvent, the 5-bromovaleric acid is cooled below 30 DEG C lower than the melting point of the 5-bromovaleric acid, the 5-bromovaleric acid forms a crystal, and the crystal is precipitated. Then, a high-purity 5-bromovaleric acid solid is separated by a filtration technology. The method has simple technology, is easy to form scale production, and has wide application prospects and favorable economic benefits.
Description
Technical field
The invention belongs to organic compound manufacturing technology field, be specially a kind of preparation method of 5-bromine valeric acid.
Background technology
5-bromine valeric acid is a kind of very important medicine intermediate, is widely used in medicine, in the manufacturing of veterinary drug.At present, domestic no any manufacturer production, its reason are to exist on the technology not enough, are difficult to obtain high purity product.Because the fusing point of 5-bromine valeric acid is lower, both fusing point 38-40 ℃, be not easy to form crystal, generally obtain 5-bromine valeric acid by distil process.But in the presence of water, 5-bromine valeric acid is easy to by the cyclisation engaging vibrating bromize hydrogen, generates δ-Wu Neizhi.Therefore, in still-process, the water reaction has become the raw material δ-Wu Neizhi in a part of 5-bromine valeric acid and the system, and this technology is difficult to obtain high purity 5-bromine valeric acid product.
G.A Olah (Synthesis, 1982, Page 963) the report use is in dichloromethane solvent, and boron tribromide and δ-Wu Neizhi react, and further hydrolysis generates corresponding 5-bromine valeric acid then, and productive rate is 88%.
(SU 1594169,1990 for G.I.Nikishin; SU 1268565,1986) etc. the people report and use cyclopentenone to be raw material that copper (II) is catalyzer, adds equivalent or excessive alkali metal bromide, by the hydrogen peroxide oxidation reaction, has synthesized corresponding 5-bromine valeric acid.
C.Ruppin people such as (FR 2835524,2003) report directly feeds the exsiccant bromize hydrogen gas in the δ-Wu Neizhi. and δ-Wu Neizhi generation ring-opening reaction, generating corresponding 5-bromine valeric acid productive rate is 97.4%.
G.L.Kad (Organic Process Research ﹠amp; Development, 2003,7, page 339) etc. the people be reported under the microwave irradiation, 48% Hydrogen bromide and δ-Wu Neizhi reaction generate corresponding 5-bromine valeric acid, productive rate is 85%.
Because the synthetic method of Olah need be used equimolar boron tribromide, has both needed the more expensive boron tribromide raw material of mass consumption price, causes the production cost height.And in process of production, produce a large amount of boron compounds.In the production process, the aftertreatment of a large amount of industrial waste boron compounds that given off is difficulty quite, and therefore, this method is in industrial no any use value.
The method of G.I.Nikishin uses a large amount of hydrogen peroxide as oxygenant, and copper (II) is catalyzer, causes the production cost height.Simultaneously and in process of production, produce the heavy metal copper refuse, still do not have suitable treatment process so far, the three wastes are handled quite difficulty.Because use a large amount of hydrogen peroxide as oxygenant in the reaction process, therefore, organo-peroxide is easy to residue in the thick product.As everyone knows, organo-peroxide is the explosive hazardous material, in thick product distil process, under the remaining situation of superoxide, the danger of blast is arranged, and present method is difficult to suitability for industrialized production.
Though the method for Ruppin has been used the direct and δ-Wu Neizhi reaction of exsiccant bromize hydrogen gas.But owing to do not describe detailed experimental implementation step in the patent, concrete separation method is not record also.The shortcoming of present method is not use any organic solvent, and material concentration is excessive in the system, and stirs difficulty, and Sheng Xia a part of raw material δ-Wu Neizhi is not easy to consume at last, residues in the system.Be difficult to obtain high purity product 5-bromine valeric acid, can not satisfy the high purity requirement to raw material of modern medicine industry.Therefore, also there is technologic where the shoe pinches in this method.
The method of G.L.Kad is used microwave reactor, only is used for research, can't carry out suitability for industrialized production at all.Therefore, this method is in industrial no any use value.
Summary of the invention
It is simple to the objective of the invention is to propose a kind of technology, is easy to the manufacture method of the high purity 5-bromine valeric acid of large-scale production.
The manufacture method of the high purity 5-bromine valeric acid that the present invention proposes, its step is as follows: the exsiccant bromize hydrogen gas is directly fed contain in the organic solvent of δ-Wu Neizhi, exsiccant bromize hydrogen gas usage quantity is δ-Wu Neizhi 1.0-2.0 doubly (mol ratio); Stir, ring-opening reaction takes place, temperature of reaction is-20 ℃ ~ 100 ℃, generates high purity 5-bromine valeric acid; Cooling, precipitation, filtering separation gets high purity 5-bromine valeric acid solid.
Employed organic solvent is an alkanes, cycloalkane, arene, the haloalkane hydro carbons, halo cycloalkane, one or more of halogenated aromatic hydro carbons and other organic solvents, wherein, alkane derivative such as butane, pentane, hexane, heptane, octane, nonane, certain herbaceous plants with big flowers alkane, 11 charcoal alkane, 12 charcoal alkane etc.; Cycloalkane chemical combination such as pentamethylene, hexanaphthene, suberane, cyclooctane etc.; Compound fragrant hydrocarbon such as benzene, toluene, ethylbenzene, isopropyl benzene, trimethylphenylmethane, dimethylbenzene etc.; Halo compound fragrant hydrocarbon such as fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, dichlorobenzene etc., halogenated alkane compounds such as methylene dichloride, trichloromethane, tetrachloro charcoal etc., ether compound such as curing charcoal, ether, propyl ether, butyl ether, methyl tertiary butyl ether, 1, the 4-dioxane, tetrahydrofuran (THF), methyl-phenoxide, phenyl ether etc.; Other are as second cyanogen, third cyanogen, fourth cyanogen, phenethyl cyanogen, oil of mirbane, methyl-sulphoxide etc.
Among the present invention, when the organic solvent that uses is alkanes, cycloalkane or arene, because 5-bromine valeric acid is insoluble in alkanes, in cycloalkane and the aromatic hydrocarbon solvent, after reaction generates 5-bromine valeric acid, be cooled to below 30 ℃, make 5-bromine valeric acid form crystal, obtain precipitation.Then, separate, obtain high purity 5-bromine valeric acid solid by filtration process.
Among the present invention, when the organic solvent that uses is the halo cycloalkane, when haloalkane hydro carbons or halogenated aromatic varsol, because 5-bromine valeric acid dissolves in the haloalkane hydro carbons, in halo cycloalkane and the halogenated aromatic varsol, after reaction generates 5-bromine valeric acid, pass through distil process, distill out employed solvent, add alkanes then, cycloalkane or aromatic hydrocarbon solvent are cooled to below 30 ℃, make 5-bromine valeric acid form crystal, precipitation; Then, obtain high purity 5-bromine valeric acid solid by the filtration process separation.
The inventive method technology is simple, is easy to form large-scale production, is with a wide range of applications.
Embodiment
In the three-necked bottle of embodiment 1:500 milliliter, thermometer is installed, agitator adds raw material δ-Wu Neizhi (1 mole, 100 grams), and normal hexane (200 milliliters) begins to stir then.Feed dry bromize hydrogen gas (1.1 moles, 89 grams), control reaction temperature is 20 ℃ ~ 30 ℃.After bromize hydrogen gas fed and finishes, restir was 5 hours under this temperature.Be cooled to 0 ~ 10 ℃ then, stirred 3 hours, a large amount of crystal generate.Filter, obtain light yellow 5-bromine valeric acid solid, weight 176 grams, productive rate 97%, purity 99.5% (gas chromatography analysis).
In the three-necked bottle of embodiment 2:500 milliliter, thermometer is installed, agitator adds raw material δ-Wu Neizhi (1 mole, 100 grams), and hexanaphthene (200 milliliters) begins to stir then.Feed dry bromize hydrogen gas (1.2 moles, 97 grams), control reaction temperature is 30 ℃ ~ 40 ℃.After bromize hydrogen gas fed and finishes, restir was 4 hours under this temperature.Be cooled to 5 ~ 15 ℃ then, stirred 2 hours, a large amount of crystal generate.Filter, obtain light yellow 5-bromine valeric acid solid, weight 178 grams, productive rate 98%, purity 99.2% (gas chromatography analysis).
In the three-necked bottle of embodiment 3:500 milliliter, thermometer is installed, agitator adds raw material δ-Wu Neizhi (1 mole, 100 grams), and toluene (200 milliliters) begins to stir then.Feed dry bromize hydrogen gas (1.5 moles, 121 grams), control reaction temperature is 40 ℃ ~ 50 ℃.After bromize hydrogen gas fed and finishes, restir was 6 hours under this temperature.Be cooled to 10 ~ 20 ℃ then, stirred 4 hours, a large amount of crystal generate.Filter, obtain light yellow 5-bromine valeric acid solid, weight 164 grams, productive rate 97%, purity 99.1% (gas chromatography analysis).
In the three-necked bottle of embodiment 4:500 milliliter, thermometer is installed, agitator adds raw material δ-Wu Neizhi (1 mole, 86 grams), and methylene dichloride (200 milliliters) begins to stir then.Feed dry bromize hydrogen gas (1.8 moles, 146 grams), control reaction temperature is 0 ℃ ~ 20 ℃.After bromize hydrogen gas fed and finishes, restir was 6 hours under this temperature.Air distillation goes out methylene dichloride then, adds normal hexane (200 milliliters) then, is cooled to-5 ~ 10 ℃, stirs 5 hours, and a large amount of crystal generate.Filter, obtain light yellow 5-bromine valeric acid solid, weight 171 grams, productive rate 94%, purity 99.0% (gas chromatography analysis).
Claims (1)
1, a kind of method of making 5-bromine valeric acid is characterized in that direct feeding of exsiccant bromize hydrogen gas contained in the organic solvent of δ-Wu Neizhi, counts in molar ratio, and exsiccant bromize hydrogen gas usage quantity is δ-Wu Neizhi 1.0-2.0 times; Stir, ring-opening reaction takes place, temperature of reaction is-20 ℃-100 ℃, generates high purity 5-bromine valeric acid; Wherein,
Described organic solvent is an alkanes, cycloalkane, and arene, the haloalkane hydro carbons, the halo cycloalkane, one of halogenated aromatic hydro carbons is planted or is several;
When the organic solvent that uses is alkanes, when cycloalkane or arene, after reaction generates 5-bromine valeric acid, be cooled to below 30 ℃, make 5-bromine valeric acid form crystal, precipitation; Then, obtain high purity 5-bromine valeric acid solid by the filtration process separation;
When the organic solvent that uses is the haloalkane hydro carbons, when halo cycloalkane or halogenated aromatic varsol, after reaction generates 5-bromine valeric acid, by distil process, distill out employed solvent, add alkanes again, cycloalkane or aromatic hydrocarbon solvent, be cooled to below 30 ℃, make 5-bromine valeric acid form crystal, precipitation; Then, separate, obtain high purity 5-bromine valeric acid solid by filtration process.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101100027A CN100340538C (en) | 2005-11-03 | 2005-11-03 | Method for preparing bromopentoic acid |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005101100027A CN100340538C (en) | 2005-11-03 | 2005-11-03 | Method for preparing bromopentoic acid |
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| CN1757624A CN1757624A (en) | 2006-04-12 |
| CN100340538C true CN100340538C (en) | 2007-10-03 |
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| CNB2005101100027A Expired - Fee Related CN100340538C (en) | 2005-11-03 | 2005-11-03 | Method for preparing bromopentoic acid |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101665427B (en) * | 2009-06-09 | 2019-12-13 | 大连九信精细化工有限公司 | Process for preparing 5-bromo-n-valeryl bromide |
| CN102010320A (en) * | 2010-11-18 | 2011-04-13 | 中国地质大学（武汉） | Solvent-free-pot synthesis method for 4-bromobutyl chloride and 5-bromovaleryl chloride |
| CN102153459B (en) * | 2011-03-22 | 2013-04-24 | 常州吉恩化工有限公司 | Method for preparing 5-chloro-valeryl chloride and adipoyl chloride simultaneously by one-pot method |
| CN102643188B (en) * | 2012-05-09 | 2014-04-16 | 岳阳亚王精细化工有限公司 | Method for preparing 5-bromovalerate |
| CN105712864B (en) * | 2016-01-21 | 2017-12-08 | 湖北相和精密化学有限公司 | A kind of preparation method of 5 bromine valeric acid |
| CN115028528A (en) * | 2022-08-04 | 2022-09-09 | 东莞理工学院 | Method for synthesizing 4-bromovaleric acid from gamma-valerolactone |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1131870A1 (en) * | 1983-01-03 | 1984-12-30 | Ордена Трудового Красного Знамени Институт Органического Синтеза Ан Латсср | Process for preparing bromovalerianic acid |
| JPH05155805A (en) * | 1991-12-05 | 1993-06-22 | Kao Corp | Production of halogenated carboxylic acid |
| FR2835524A1 (en) * | 2002-02-06 | 2003-08-08 | Atofina | PROCESS FOR THE PREPARATION OF OMEGA -BROMOALKYLCARBOXYLIC COMPOUNDS |
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2005
- 2005-11-03 CN CNB2005101100027A patent/CN100340538C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1131870A1 (en) * | 1983-01-03 | 1984-12-30 | Ордена Трудового Красного Знамени Институт Органического Синтеза Ан Латсср | Process for preparing bromovalerianic acid |
| JPH05155805A (en) * | 1991-12-05 | 1993-06-22 | Kao Corp | Production of halogenated carboxylic acid |
| FR2835524A1 (en) * | 2002-02-06 | 2003-08-08 | Atofina | PROCESS FOR THE PREPARATION OF OMEGA -BROMOALKYLCARBOXYLIC COMPOUNDS |
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