CN104529997A - Method for producing 3-bromothiophene by reducing 2,3,5-three bromine thiophene by using acid-metal system - Google Patents
Method for producing 3-bromothiophene by reducing 2,3,5-three bromine thiophene by using acid-metal system Download PDFInfo
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- CN104529997A CN104529997A CN201410850683.XA CN201410850683A CN104529997A CN 104529997 A CN104529997 A CN 104529997A CN 201410850683 A CN201410850683 A CN 201410850683A CN 104529997 A CN104529997 A CN 104529997A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/28—Halogen atoms
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Abstract
The invention relates to a method for producing 3-bromothiophene by reducing 2,3,5-three bromine thiophene by using an acid-metal system. The method is characterized by comprising the following specific steps that strong phosphoric acid or hydrochloric acid, zinc powder or reduced iron powder or magnesium powder and the 2,3,5-three bromine thiophene are put into a reaction still 1, and the mole ratio of strong phosphoric acid or hydrochloric acid to zinc powder or reduced iron powder or magnesium powder to 2,3,5-three bromine thiophene is 3:6:2; water with the volume two times of the strong phosphoric acid or the hydrochloric acid is added in the reaction still 1, heating reflux is performed on reaction mixture under stirring, and the reaction mixture reacts for three to seven hours. After reaction is completed, steam distillation is performed, distillate is extracted by adding ethyl acetate with the same volume of the water, water phases are released, organic phases are dried by adding an anhydrous sodium sulfate drying agent into an extraction dying still 3, the dried organic phases are put into a distillation still 4 to be distilled, and the colourless liquid 3-bromothiophene is obtained by distilling and collecting distillate at the temperature ranging from 159 DEG C to 161 DEG C. The method has the advantages that the purity of a product is high, the content is higher than 99.0% (GC), the productive rate of a by-product 2-bromothiophene is less than 5%, the production cost is low, the post-processing is simple, and the environmental pollution is small.
Description
Technical field
The present invention relates to a kind of method of producing 3 bromo thiophene, more specifically to a kind of acid-metal system reductase 12,3,5-tri-bromothiophene produces the method for 3 bromo thiophene.
Background technology
3 bromo thiophene is a kind of important organic intermediate, and the derivative as a kind of β-thiophene has important using value in thiophen polymer synthesis and new drug synthesis etc.
The main production process of 3 bromo thiophene has isomerate process, reduction method etc.
(1) isomerate process
Be that raw material first synthesizes 2-bromothiophene with thiophene, then the isomerization of 2-bromothiophene is obtained 3 bromo thiophene, this technique synthesis step is few, and yield is higher, but in product, unreacted 2-bromothiophene is difficult to be separated with 3 bromo thiophene.
(2) reduction method
2,3,5-tri-bromothiophene in the presence of a reducing agent debrominate obtains 3 bromo thiophene.Be first raw material and bromine Reactive Synthesis 2,3,5-tri-bromothiophene with thiophene, then make reductive agent with zinc be obtained by reacting 3 bromo thiophene in acetic acid solvent.Various production technique respectively has relative merits (seeing the following form).
| Isomerate process | Reduction method | |
| Raw materials for production | Thiophene, bromine | Thiophene, bromine, zinc |
| Route length | Short | Long |
| Production cost | Low | High |
| Facility investment | High | Low |
Summary of the invention
The technical problem to be solved in the present invention is: provide a kind of acid-metal system reductase 12, and 3,5-tri-bromothiophene produces the method for 3 bromo thiophene, with 2,3,5-tri-bromothiophene for raw material, debrominate obtains 3 bromo thiophene in the presence of a reducing agent, improves the selectivity of reaction, reduces the method that 2-bromothiophene generates.
Feature of the present invention is that the method comprises following concrete steps:
A, acid, metal and 2,3,5-tri-bromothiophene are dropped in reactor, its mol ratio is 3:6:2, in reactor, then add the water of 2 gallic acid volumes, is heated to backflow under stirring, gas passes back in reactor after reflux exchanger condensation, and reflux time is 3 ~ 6 hours.Wherein said acid is strong phosphoric acid or hydrochloric acid; Described metal is zinc powder or reduced iron powder or magnesium powder.
B, react complete mixture in reactor is put into wet distillation still, then in wet distillation still, pass into overheated steam carry out steam distillation.
C, overhead product are collected in extraction drying kettle after wet distillation condenser condenses, with adding the extraction into ethyl acetate with aqueous phase same volume, release aqueous phase, and the anhydrous sodium sulfate drying agent that organic phase adds ethyl acetate quality 7% in extraction drying kettle is dry.
D, dried organic phase squeezed in still kettle and distills, gas enters condensation in distiller condenser I, distiller condenser II successively, collect solvent after condensation and front-end volatiles enter in solvent collection tank, collect 159 DEG C ~ 161 DEG C fractions and to enter in product-collecting tank to obtain colourless liquid 3 bromo thiophene.
Accompanying drawing explanation
Below in conjunction with the drawings and specific embodiments, the present invention is described in further detail.
Fig. 1 is a kind of acid-metal system reductase 12 of the present invention, and 3,5-tri-bromothiophene produces the schematic flow sheet of 3 bromo thiophene method.
Embodiment
First 500L glassed steel reaction vessels 1 is connected with reflux exchanger 5, wet distillation still 2 respectively, wet distillation still 2 is connected with wet distillation condenser 6, wet distillation condenser 6 is connected with extraction drying kettle 3, extraction drying kettle 3 is connected with still kettle 4, still kettle 4 is connected with distiller condenser I 7, distiller condenser II 8 successively, and distiller condenser I 7, distiller condenser II 8 are connected with solvent collection tank 9, product-collecting tank 10.
Embodiment 1
A, by 80L water, 24.5kg 85% strong phosphoric acid, 32.0kg zinc powder, 52.6kg 2,3,5-tri-bromothiophene drops in reactor 1, and be heated to backflow under stirring, gas passes back in reactor 1 after reflux exchanger 5 condensation, and reflux time is 6 hours.
B, react complete mixture in reactor 1 is put into wet distillation still 2, in wet distillation still 2, pass into overheated steam carry out steam distillation.
C, overhead product are collected in extraction drying kettle 3 after wet distillation condenser 6 condensation, use 80L extraction into ethyl acetate, release aqueous phase, organic phase 5kg anhydrous sodium sulfate drying.
D, dried organic phase squeezed in still kettle 4 and distills, gas is successively through distiller condenser I7, distiller condenser II 8, collection solvent and front-end volatiles enter in solvent collection tank 9, collect 159 DEG C ~ 161 DEG C fractions and enter in product-collecting tank 10 to obtain 23.7kg colourless liquid 3 bromo thiophene.
Embodiment 2
A, by 80L water, 60kg 31% hydrochloric acid, 32.0kg zinc powder, 52.6kg 2,3,5-tri-bromothiophene drops in reactor 1, and stir lower heating, gas passes back in reactor 1 after reflux exchanger 5 condensation, and reflux time is 3 hours.
B, react complete mixture in reactor 1 is put into wet distillation still 2, in wet distillation still 2, pass into overheated steam carry out steam distillation.
C, overhead product are collected in extraction drying kettle 3 after wet distillation condenser 6 condensation, use 80L extraction into ethyl acetate, release aqueous phase, organic phase 5kg anhydrous sodium sulfate drying.
D, dried organic phase squeezed in still kettle 4 and distills, gas is successively through distiller condenser I 7, distiller condenser II 8, collection solvent and front-end volatiles enter in solvent collection tank 9, collect 159 DEG C ~ 161 DEG C fractions and enter in product-collecting tank 10 to obtain 17.4kg colourless liquid 3 bromo thiophene.
Embodiment 3
A, 80L water, 24.5kg 85% strong phosphoric acid, 30kg reduced iron powder and 52.6kg 2,3,5-tri-bromothiophene are dropped in reactor 1, stir lower heating, gas passes back in reactor 1 after reflux exchanger 5 condensation, and reflux time is 7 hours.
B, react complete mixture in reactor 1 is put into wet distillation still 2, in wet distillation still 2, pass into overheated steam carry out steam distillation.
C, overhead product are collected in extraction drying kettle 3 after wet distillation condenser 6 condensation, use 80L extraction into ethyl acetate, release aqueous phase, organic phase 5kg anhydrous sodium sulfate drying;
D, dried organic phase squeezed in still kettle 4 and distills, gas is successively through distiller condenser I 7, distiller condenser II 8, collection solvent and front-end volatiles enter in solvent collection tank 9, collect 159 DEG C ~ 161 DEG C fractions and enter in product-collecting tank 10 to obtain 21.4kg colourless liquid 3 bromo thiophene.
Embodiment 4
A, 80L water, 24.5kg 85% strong phosphoric acid, 13kg magnesium powder and 52.6kg 2,3,5-tri-bromothiophene are dropped in reactor 1, stir lower heating, gas passes back in reactor 1 after reflux exchanger 5 condensation, and reflux time is 6 hours.
B, react complete mixture in reactor 1 is put into wet distillation still 2, in wet distillation still 2, pass into overheated steam carry out steam distillation.
C, overhead product are collected in extraction drying kettle 3 after wet distillation condenser 6 condensation, use 80L extraction into ethyl acetate, release aqueous phase, organic phase 5kg anhydrous sodium sulfate drying.
D, dried organic phase squeezed in still kettle 4 and distills, gas is successively through distiller condenser I7, distiller condenser II 8, collection solvent and front-end volatiles enter in solvent collection tank 9, collect 159 DEG C ~ 161 DEG C fractions and enter in product-collecting tank 10 to obtain 16.0kg colourless liquid 3 bromo thiophene.
In sum: the acid added by proportioning, metal and 2,3,5-tri-bromothiophene, react, all can obtain 3 bromo thiophene under heated reflux condition.Raw material is simple, reaction time is short, product purity reaches more than 99%.
Claims (1)
1. acid-metal system reductase 12,3,5-tri-bromothiophene produces the method for 3 bromo thiophene, it is characterized in that the method comprises following concrete steps:
A, by acid, metal and 2,3,5-tri-bromothiophene drops in reactor (1), its mol ratio is 3:6:2, then in reactor (1), add the water of 2 gallic acid volumes, be heated to backflow under stirring, gas passes back in reactor (1) after reflux exchanger (5) condensation, and reflux time is 3 ~ 7 hours; Wherein said acid is strong phosphoric acid or hydrochloric acid; Described metal is zinc powder or reduced iron powder or magnesium powder;
B, react complete mixture in reactor (1) is put into wet distillation still (2), then in wet distillation still (2), pass into overheated steam carry out steam distillation;
C, overhead product are collected in extraction drying kettle (3) after wet distillation condenser (6) condensation, with adding the extraction into ethyl acetate with aqueous phase same volume, release aqueous phase, the anhydrous sodium sulfate drying agent that organic phase adds ethyl acetate quality 7% in extraction drying kettle (3) is dry;
D, dried organic phase squeezed in still kettle (4) and distills, gas enters condensation in distiller condenser I (7), distiller condenser II (8) successively, collect solvent after condensation and front-end volatiles enter in solvent collection tank (9), collect 159 DEG C ~ 161 DEG C fractions and to enter in product-collecting tank (10) to obtain colourless liquid 3 bromo thiophene.
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| CN201410850683.XA CN104529997A (en) | 2014-12-30 | 2014-12-30 | Method for producing 3-bromothiophene by reducing 2,3,5-three bromine thiophene by using acid-metal system |
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| CN201410850683.XA CN104529997A (en) | 2014-12-30 | 2014-12-30 | Method for producing 3-bromothiophene by reducing 2,3,5-three bromine thiophene by using acid-metal system |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63250385A (en) * | 1987-04-04 | 1988-10-18 | Tokuyama Soda Co Ltd | Production of halogenated heterocyclic compound |
| US4889940A (en) * | 1987-07-14 | 1989-12-26 | Shell Internationale Research Maatschappij B.V. | Process for preparing thiophene derivatives |
| US5100520A (en) * | 1989-02-06 | 1992-03-31 | Hoechst Aktiengesellschaft | Process for the preparation of thiophene derivatives |
| CN102020663A (en) * | 2010-11-24 | 2011-04-20 | 山东鑫泉医药中间体有限公司 | Tazobactam synthesis method |
-
2014
- 2014-12-30 CN CN201410850683.XA patent/CN104529997A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63250385A (en) * | 1987-04-04 | 1988-10-18 | Tokuyama Soda Co Ltd | Production of halogenated heterocyclic compound |
| US4889940A (en) * | 1987-07-14 | 1989-12-26 | Shell Internationale Research Maatschappij B.V. | Process for preparing thiophene derivatives |
| US5100520A (en) * | 1989-02-06 | 1992-03-31 | Hoechst Aktiengesellschaft | Process for the preparation of thiophene derivatives |
| CN102020663A (en) * | 2010-11-24 | 2011-04-20 | 山东鑫泉医药中间体有限公司 | Tazobactam synthesis method |
Non-Patent Citations (3)
| Title |
|---|
| SVENOLOV LAWESSON: "Dehalogenation of Bromothiophenes with Butyllithium", 《ACTA CHEMICA SCANDINAVICA》 * |
| 谢湘华等: "从噻吩合成3- (3-噻吩酮)噻吩", 《华东理工大学学报》 * |
| 黄宪等: "《新编有机合成化学》", 31 January 2003 * |
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Application publication date: 20150422 |