CN107935985A - A kind of synthetic method of 2 bromothiophene - Google Patents
A kind of synthetic method of 2 bromothiophene Download PDFInfo
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- CN107935985A CN107935985A CN201711420420.5A CN201711420420A CN107935985A CN 107935985 A CN107935985 A CN 107935985A CN 201711420420 A CN201711420420 A CN 201711420420A CN 107935985 A CN107935985 A CN 107935985A
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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 discloses a kind of synthetic method of 2 bromothiophene of technical field of chemical synthesis, this method comprises the following steps that：S1：Reactant is made in raw material addition mixing back flow reaction；S2：Add reaction promoter and carry out temperature reaction；S3：Filtration washing obtains solid crystal after reaction；S4：Reactant is mixed with solid crystal adjusts pH value；S5：Liquid separation merges organic dry concentration finished product that is concerned with, and raw material of the invention is cheap and easy to get, its small toxicity, the high selectivity of chemical reaction, high income, and obtained finished product purity is high, and product quality is stablized, and is adapted to the use of large-scale production of batch production.
Description
Technical field
The invention discloses a kind of synthetic method of 2- bromothiophenes, is specially technical field of chemical synthesis.
Background technology
2- bromothiophenes are the important intermediates in organic synthesis, are widely used in the fields such as medicine, pesticide, high molecular material,
Especially in field of medicaments, 2- bromothiophenes are the raw materials of synthesizing thiofuran ethamine, its demand is increasing.Existing 2- bromothiophenes
Synthetic method method, is synthesized using glacial acetic acid solvent method, carbon tetrachloride solvent method, direct bromination, high spot reviews plus bromine mode,
Add influence of the factors such as bromine time, raw material proportioning, reaction temperature to direct bromination production technology, itself test result indicates that, ice second
Sour solvent method and carbon tetrachloride solvent method are not appropriate for industrialized production, and direct bromination is that thiophene is dissolved in acetic acid
In, the glacial acetic acid solution of bromine is added at 10 DEG C, then add water to reaction mixture, oily liquids is separated out, and extracted with ether,
But the yield of this method is very low, and product purity is not high.A kind of for this reason, synthetic method throwing we have proposed 2- bromothiophenes
Enter to use, to solve the above problems.
The content of the invention
It is proposed in the above background technology to solve it is an object of the invention to provide a kind of synthetic method of 2- bromothiophenes
Problem.
To achieve the above object, the present invention provides following technical solution：A kind of synthetic method of 2- bromothiophenes, this method
Comprise the following steps that：
S1：The brominated waste water of 40~60ml and the anhydrous ether of 10~20ml are added in three-neck flask, is heated to
It is uniformly mixed after 30~40 DEG C with the aqueous solution of hydrogen bromide of 80~100g, is continuously heating to slight boiling condition, 1~2h of back flow reaction,
Reactant is made, places spare；
S2：6~8g n-hexanes and 4~6g dimethyl oxalates are added in reaction vessel, after stirring evenly, in 20min
15~20g monoxones are added dropwise, control 4~6 DEG C of temperature, then add the anhydrous cupric sulfate of 40~50g, temperature reaction；
S3：After reaction, 60~70 DEG C are continuously heating to, 1~2h of back flow reaction is up to no longer releasing gas, filtering,
Filtrate is washed with detergent, is dried with after activated carbon decolorizing by anhydrous calcium chloride, is obtained solid crystal；
S4：Reactant into solid crystal in a dropping step S1, after 2~3h of heating reflux reaction, then in ice
Salt acid for adjusting pH is added dropwise under water-bath to 3~4, solid is all dissolved；
S5：Liquid separation, water are mutually extracted with ether, merge organic phase, and are washed with solvent, and anhydrous sodium sulfate is done under elevated pressure
Dry, concentration, re-crystallizing in ethyl acetate, obtains 2- bromothiophene finished products.
Preferably, in the step S1, dropping funel and thermometer are installed in three-neck flask.
Preferably, in the step S2, the temperature of temperature reaction is 20~30 DEG C, 15~30min of reaction time.
Preferably, in the step S3, detergent is saturated sodium bicarbonate solution and the mixture of water, is heated up in reaction
Cheng Zhong, heating rate are 2 DEG C/min.
Preferably, in the step S4, the dropwise addition of reactant is added dropwise in 15min, and the temperature of temperature reaction is 50
~60 DEG C.
Preferably, in the step S5, solvent is saturation sodium hydroxide solution and the mixed liquor of saturated salt solution.
Compared with prior art, the beneficial effects of the invention are as follows：The raw material of the present invention is cheap and easy to get, its small toxicity, chemistry
The high selectivity of reaction, high income, and obtained finished product purity are high, and product quality is stablized, and are adapted to the large-scale production of batch production
Use.
Brief description of the drawings
Fig. 1 is synthetic method flow chart of the present invention.
Embodiment
Below in conjunction with the attached drawing in the embodiment of the present invention, the technical solution in the embodiment of the present invention is carried out clear, complete
Site preparation describes, it is clear that described embodiment is only part of the embodiment of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, those of ordinary skill in the art are obtained every other without making creative work
Embodiment, belongs to the scope of protection of the invention.
Embodiment one
A kind of synthetic method of 2- bromothiophenes, this method comprise the following steps that：
S1：The brominated waste water of 40ml and the anhydrous ether of 10ml are added in three-neck flask, after being heated to 30 DEG C with
The aqueous solution of hydrogen bromide of 80g is uniformly mixed, and is continuously heating to slight boiling condition, and back flow reaction 1h, is made reactant, and placement is spare,
Dropping funel and thermometer are installed in three-neck flask；
S2：6g n-hexanes and 4g dimethyl oxalates are added in reaction vessel, after stirring evenly, by 15g chlorine in 20min
Acetic acid is added dropwise, and controls 4 DEG C of temperature, then adds the anhydrous cupric sulfate of 40g, temperature reaction, the temperature of temperature reaction is 20
DEG C, reaction time 15min；
S3：After reaction, 60 DEG C are continuously heating to, back flow reaction 1h is filtered until no longer release gas, and filtrate is with washing
Agent washing is washed, is dried with after activated carbon decolorizing by anhydrous calcium chloride, obtains solid crystal, detergent is molten for saturated sodium bicarbonate
The mixture of liquid and water, in temperature-rise period is reacted, heating rate is 2 DEG C/min；
S4：Reactant into solid crystal in a dropping step S1, after heating reflux reaction 2h, then in ice-water bath
Lower dropwise addition salt acid for adjusting pH makes solid all dissolve, the dropwise addition of reactant is added dropwise in 15min, temperature reaction to 3~4
Temperature be 50 DEG C；
S5：Liquid separation, water are mutually extracted with ether, merge organic phase, and are washed with solvent, and anhydrous sodium sulfate is done under elevated pressure
Dry, concentration, re-crystallizing in ethyl acetate obtains 2- bromothiophene finished products, and solvent is saturation sodium hydroxide solution and saturated salt solution
Mixed liquor.
Embodiment two
A kind of synthetic method of 2- bromothiophenes, this method comprise the following steps that：
S1：The brominated waste water of 60ml and the anhydrous ether of 20ml are added in three-neck flask, after being heated to 40 DEG C with
The aqueous solution of hydrogen bromide of 100g is uniformly mixed, and is continuously heating to slight boiling condition, and back flow reaction 2h, is made reactant, and placement is spare,
Dropping funel and thermometer are installed in three-neck flask；
S2：8g n-hexanes and 6g dimethyl oxalates are added in reaction vessel, after stirring evenly, by 20g chlorine in 20min
Acetic acid is added dropwise, and controls 6 DEG C of temperature, then adds the anhydrous cupric sulfate of 50g, temperature reaction, the temperature of temperature reaction is 30
DEG C, reaction time 30min；
S3：After reaction, 70 DEG C are continuously heating to, back flow reaction 2h is filtered until no longer release gas, and filtrate is with washing
Agent washing is washed, is dried with after activated carbon decolorizing by anhydrous calcium chloride, obtains solid crystal, detergent is molten for saturated sodium bicarbonate
The mixture of liquid and water, in temperature-rise period is reacted, heating rate is 2 DEG C/min；
S4：Reactant into solid crystal in a dropping step S1, after heating reflux reaction 3h, then in ice-water bath
Lower dropwise addition salt acid for adjusting pH makes solid all dissolve, the dropwise addition of reactant is added dropwise in 15min, temperature reaction to 3~4
Temperature be 60 DEG C；
S5：Liquid separation, water are mutually extracted with ether, merge organic phase, and are washed with solvent, and anhydrous sodium sulfate is done under elevated pressure
Dry, concentration, re-crystallizing in ethyl acetate obtains 2- bromothiophene finished products, and solvent is saturation sodium hydroxide solution and saturated salt solution
Mixed liquor.
Embodiment three
A kind of synthetic method of 2- bromothiophenes, this method comprise the following steps that：
S1：The brominated waste water of 50ml and the anhydrous ether of 15ml are added in three-neck flask, after being heated to 35 DEG C with
The aqueous solution of hydrogen bromide of 90g is uniformly mixed, and is continuously heating to slight boiling condition, and back flow reaction 2h, is made reactant, and placement is spare,
Dropping funel and thermometer are installed in three-neck flask；
S2：7g n-hexanes and 5g dimethyl oxalates are added in reaction vessel, after stirring evenly, by 17g chlorine in 20min
Acetic acid is added dropwise, and controls 5 DEG C of temperature, then adds the anhydrous cupric sulfate of 45g, temperature reaction, the temperature of temperature reaction is 25
DEG C, reaction time 25min；
S3：After reaction, 65 DEG C are continuously heating to, back flow reaction 2h is filtered until no longer release gas, and filtrate is with washing
Agent washing is washed, is dried with after activated carbon decolorizing by anhydrous calcium chloride, obtains solid crystal, detergent is molten for saturated sodium bicarbonate
The mixture of liquid and water, in temperature-rise period is reacted, heating rate is 2 DEG C/min；
S4：Reactant into solid crystal in a dropping step S1, after heating reflux reaction 3h, then in ice-water bath
Lower dropwise addition salt acid for adjusting pH makes solid all dissolve, the dropwise addition of reactant is added dropwise in 15min, temperature reaction to 3~4
Temperature be 55 DEG C；
S5：Liquid separation, water are mutually extracted with ether, merge organic phase, and are washed with solvent, and anhydrous sodium sulfate is done under elevated pressure
Dry, concentration, re-crystallizing in ethyl acetate obtains 2- bromothiophene finished products, and solvent is saturation sodium hydroxide solution and saturated salt solution
Mixed liquor.
In summary described in embodiment, highly preferred embodiment of the present invention is embodiment three, and raw material of the invention is cheap and easy to get,
Its small toxicity, the high selectivity of chemical reaction, high income, and obtained finished product purity are high, and product quality is stablized, and are adapted to batch production
Use of large-scale production.
Although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
Understanding without departing from the principles and spirit of the present invention can carry out these embodiments a variety of changes, modification, replace
And modification, the scope of the present invention is defined by the appended.
Claims (6)
- A kind of 1. synthetic method of 2- bromothiophenes, it is characterised in that：This method comprises the following steps that：S1：The brominated waste water of 40~60ml and the anhydrous ether of 10~20ml are added in three-neck flask, it is heated to 30~ It is uniformly mixed after 40 DEG C with the aqueous solution of hydrogen bromide of 80~100g, is continuously heating to slight boiling condition, 1~2h of back flow reaction, is made Reactant, is placed spare；S2：6~8g n-hexanes and 4~6g dimethyl oxalates are added in reaction vessel, after stirring evenly, by 15 in 20min ~20g monoxones are added dropwise, and control 4~6 DEG C of temperature, then add the anhydrous cupric sulfate of 40~50g, temperature reaction；S3：After reaction, 60~70 DEG C are continuously heating to, 1~2h of back flow reaction is filtered, filtrate up to no longer releasing gas Washed with detergent, dried with after activated carbon decolorizing by anhydrous calcium chloride, obtain solid crystal；S4：Reactant into solid crystal in a dropping step S1, after 2~3h of heating reflux reaction, then in ice-water bath Lower dropwise addition salt acid for adjusting pH makes solid all dissolve to 3~4；S5：Liquid separation, water are mutually extracted with ether, merge organic phase, and are washed with solvent, and anhydrous sodium sulfate is dried under elevated pressure, dense Contracting, re-crystallizing in ethyl acetate, obtains 2- bromothiophene finished products.
- A kind of 2. synthetic method of 2- bromothiophenes according to claim 1, it is characterised in that：In the step S1, three necks Dropping funel and thermometer are installed in flask.
- A kind of 3. synthetic method of 2- bromothiophenes according to claim 1, it is characterised in that：In the step S2, heating The temperature of reaction is 20~30 DEG C, 15~30min of reaction time.
- A kind of 4. synthetic method of 2- bromothiophenes according to claim 1, it is characterised in that：In the step S3, washing Agent is saturated sodium bicarbonate solution and the mixture of water, and in temperature-rise period is reacted, heating rate is 2 DEG C/min.
- A kind of 5. synthetic method of 2- bromothiophenes according to claim 1, it is characterised in that：In the step S4, reaction The dropwise addition of agent is added dropwise in 15min, and the temperature of temperature reaction is 50~60 DEG C.
- A kind of 6. synthetic method of 2- bromothiophenes according to claim 1, it is characterised in that：In the step S5, solvent For saturation sodium hydroxide solution and the mixed liquor of saturated salt solution.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591328A (en) * | 2009-05-04 | 2009-12-02 | 浙江燎原药业有限公司 | The chemical synthesis process of a kind of 2-bromothiophene and derivative thereof |
| CN102363614A (en) * | 2011-11-14 | 2012-02-29 | 连云港宏业化工有限公司 | Method for synthesizing 2-bromothiophene |
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- 2017-12-25 CN CN201711420420.5A patent/CN107935985A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591328A (en) * | 2009-05-04 | 2009-12-02 | 浙江燎原药业有限公司 | The chemical synthesis process of a kind of 2-bromothiophene and derivative thereof |
| CN102363614A (en) * | 2011-11-14 | 2012-02-29 | 连云港宏业化工有限公司 | Method for synthesizing 2-bromothiophene |
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Application publication date: 20180420 |