CN104496949A - Preparation method of 3-bromophthalide - Google Patents
Preparation method of 3-bromophthalide Download PDFInfo
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- CN104496949A CN104496949A CN201410708314.7A CN201410708314A CN104496949A CN 104496949 A CN104496949 A CN 104496949A CN 201410708314 A CN201410708314 A CN 201410708314A CN 104496949 A CN104496949 A CN 104496949A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
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Abstract
The invention discloses a preparation method of 3-bromophthalide. The method comprises the following steps: (1) after heating o-methyl benzoic acid to 126-134 DEG C, continuously and dropwisely adding liquid bromine, heating to 135-145 DEG C to react, after finishing adding the liquid bromine, detecting the content of the o-methyl benzoic acid in the reaction solution to judge the reaction end point, adjusting to 130-140 DEG C, and keeping the temperature for 1-2 hours to obtain the reaction product; and (2) cooling the reaction product to 80-84 DEG C, and adding sym-tetrachloroethane to recrystallize, thereby obtaining the 3-bromophthalide. According to the method, the o-methyl benzoic acid and liquid bromine react to obtain the 3-bromophthalide. The specific reaction temperature is 135-145 DEG C, and the feeding mode is continuous and dropwise addition of liquid bromine. The reaction product is recrystallized by using the sym-tetrachloroethane as the solvent, and the specific temperature of 80-84 DEG C is selected to enhance the recrystallization effect, thereby obtaining the 3-bromophthalide product with high yield and higher purity.
Description
Technical field
The present invention relates to technical field prepared by 3-bromo phthalide, particularly relate to a kind of preparation method of 3-bromo phthalide.
Background technology
3-bromo phthalide has another name called 3-bromo-2-benzo [C] furanone, or 3-bromo-2-benzo [C] furanone, and its molecular weight is 213.03, No. CAS is 6940-49-4, and it is a kind of faint yellow solid, and fusing point is 80 ~ 83 DEG C, boiling point is 306.9 DEG C, and flash-point is 139.4 DEG C.The technological deficiency that the yield of preparation technology's existence of prior art 1-cyclohexenyl acetic acid is lower and product purity is lower.
Summary of the invention
In view of this, the invention provides a kind of 1-cyclohexenyl acetic acid preparation method, the purity of the product of this preparation method is higher, yield is higher.
A preparation method for 3-bromo phthalide, comprises the following steps:
(1) after o-toluic acid (formula A) is heated to 126 ~ 134 DEG C, drip bromine continuously wherein, make o-toluic acid and bromine constant be 135 ~ 145 DEG C of heating conditions under react, after bromine dropwises, when the content detection by o-toluic acid in the reaction solution of this reaction is to judge that reaction is reached home, reaction solution to be regulated at 130 ~ 140 DEG C and constant temperature 1 ~ 2h, obtain reaction product;
(2) in described reaction product, be cooled to 80 ~ 84 DEG C, add acetylene tetrachloride wherein and carry out recrystallization, obtain 3-bromo phthalide (formula B); The reaction formula of wherein said reaction is as follows,
In above-mentioned preparation method, the reaction mechanism of o-toluic acid and bromine can be divided into two benches, and the first stage is, the methyl on the phenyl ring of a part o-toluic acid and bimolecular bromine generation bromo-reaction, generates dibrominated o-toluic acid; Subordinate phase is, in the hydroxyl initial ring of the bromine in dibrominated o-toluic acid and carboxyl, HBr is sloughed in substitution reaction, generates phenyl ring and the 3-bromo phthalide of five-ring fused structure.Substitution reaction due to subordinate phase is reversible reaction, therefore product HBr can have influence on the transformation efficiency of this elementary reaction.Thus, removing HBr gas will be constantly separated in whole reaction process.Tail gas unit can be set in reaction unit to remove HBr gas, the tail gas removing device that the such as concrete structure of this tail gas removing device can adopt this area general, such as tail gas removing device can comprise for the condenser by tail gas (HBr gas) condensation, connect condenser and absorption unit (certainly also can adopt absorption tower) is set, this absorption unit built with absorption liquid, such as alkali lye (sodium hydroxide or sodium carbonate etc.).In order to strengthen the effect that tail gas is absorbed by Liquid soap, the sprinkling equipment that absorption liquid can be sprayed can be set in absorption unit, increase the contact with tail gas by spray like this, ensure that absorption is more abundant.
The temperature of above-mentioned reaction plays vital effect to the yield of reaction product and the purity of product.135 ~ 145 DEG C can be brought the optimum yield of reaction product and the purity of product.
The mass ratio of o-toluic acid and bromine is preferably 1:(2 ~ 3), be 1:2.6 better.The stoichiometric mole ratio 1:2 of o-toluic acid and bromine reaction.The preferred 1:2.6 of the present invention can ensure that bromine is excessive a little, thus improves the level of response of o-toluic acid.Except this, the too much or very few purity that all can reduce product of bromine.
Bromine feed way adopts the mode dripped continuously.The time for adding of bromine is preferably 4 ~ 6h, more preferably 5.5h.The gas such as nitrogen or nitrogen peroxide that passes into more of the prior art realizes bromine vapor to take conversion unit, and continuous dropping of the present invention obviously can reduce the dropping required time of bromine.
When the content of o-toluic acid is account for reaction solution total mass 0.02%, judge that reaction is reached home.To the analytical instrument that the content of o-toluic acid can adopt this area conventional, such as chromatographic technique etc.Do not repeat them here.
Recrystallization is adopted to purify to reaction product in step (2).Take acetylene tetrachloride as the solvent of recrystallization.The volume ratio 0.6 ~ 1.5 of acetylene tetrachloride and reaction product, is preferably 1.The concrete operations of recrystallization are known technology, do not repeat them here.
The present invention is obtained by reacting 3-bromo phthalide with o-toluic acid and bromine.Select 135 ~ 145 DEG C to be the specified temp reacted, the mode dripped continuously with bromine is feed way.Reaction product is that solvent carries out recrystallization with acetylene tetrachloride, and selects 80 ~ 84 DEG C of specified temps, to improve the effect of recrystallization, has obtained the 3-bromo phthalide that product yield is high, purity is higher thus.
Embodiment
Technical scheme of the present invention is further illustrated below in conjunction with embodiment.
Below implement involved industrial chemicals to be mode commercially available or well-known to those skilled in the art and to obtain.As space is limited, below eliminate the concrete available sources of these industrial chemicals, should not be considered as the query to the present invention program's embodiment to this.
Embodiment 1
In bromination still, add 100g o-toluic acid, open chuck steam heating, be warming up to o-toluic acid fusing, start and stir, temperature is raised to 126 DEG C and starts to drip 200g bromine equably continuously and make it reaction.Bromine rate of addition controls to take out of without bromine at reaction end gas, and the time controlling to drip is at 4h.Temperature of reaction controls at 145 DEG C.Reaction end gas, after condenser, enters HBr falling liquid film water absorption tower, reclaims HBr, then emptying after the process of alkali lye spray column.After bromine dropwises, adopt o-toluic acid content in gas-chromatography sampling detection reaction liquid, if o-toluic acid content is the 0.02wt% being no more than reaction solution total mass, then constant temperature 2h at 130 DEG C, and continue to stir, obtain reaction product.
In reaction product, pass into nitrogen to remove hydrogen bromide, be cooled to 80 DEG C simultaneously.Logical complete, add acetylene tetrachloride stirring and dissolving, device filters brilliant still after filtration, crystallisation by cooling, is separated and obtains wet finished product, then obtain finished product 3-bromo phthalide through vacuum-drying through whizzer.
Embodiment 2
In bromination still, add 100g o-toluic acid, open chuck steam heating, be warming up to o-toluic acid fusing, start and stir, temperature is raised to 134 DEG C and starts to drip 300g bromine equably continuously and make it reaction.Bromine rate of addition controls to take out of without bromine at reaction end gas, and the time controlling to drip is at 6h.Temperature of reaction controls at 135 DEG C.Reaction end gas, after condenser, enters HBr falling liquid film water absorption tower, reclaims HBr, then emptying after the process of alkali lye spray column.After bromine dropwises, adopt o-toluic acid content in gas-chromatography sampling detection reaction liquid, if o-toluic acid content is the 0.02wt% being no more than reaction solution total mass, then constant temperature 1h at 130 ~ 140 DEG C, and continue to stir, obtain reaction product.
In reaction product, pass into nitrogen to remove hydrogen bromide, be cooled to 84 DEG C simultaneously.Logical complete, add acetylene tetrachloride stirring and dissolving, device filters brilliant still after filtration, crystallisation by cooling, is separated and obtains wet finished product, then obtain finished product 3-bromo phthalide through vacuum-drying through whizzer.
Embodiment 3
In bromination still, add 100g o-toluic acid, open chuck steam heating, be warming up to o-toluic acid fusing, start and stir, temperature is raised to 130 DEG C and starts to drip 260g bromine equably continuously and make it reaction.Bromine rate of addition controls to take out of without bromine at reaction end gas, and the time controlling to drip is at 5.5h.Temperature of reaction controls at 140 DEG C.Reaction end gas, after condenser, enters HBr falling liquid film water absorption tower, reclaims HBr, then emptying after the process of alkali lye spray column.After bromine dropwises, adopt o-toluic acid content in gas-chromatography sampling detection reaction liquid, if o-toluic acid content is the 0.02wt% being no more than reaction solution total mass, then constant temperature 1.5h at 135 DEG C, and continue to stir, obtain reaction product.
In reaction product, pass into nitrogen to remove hydrogen bromide, be cooled to 82 DEG C simultaneously.Logical complete, add acetylene tetrachloride stirring and dissolving, device filters brilliant still after filtration, crystallisation by cooling, is separated and obtains wet finished product, then obtain finished product 3-bromo phthalide through vacuum-drying through whizzer.
Embodiment 4
In bromination still, add 100g o-toluic acid, open chuck steam heating, be warming up to o-toluic acid fusing, start and stir, temperature is raised to 128 DEG C and starts to drip 250g bromine equably continuously and make it reaction.Bromine rate of addition controls to take out of without bromine at reaction end gas, and the time controlling to drip is at 5h.Temperature of reaction controls at 140 DEG C.Reaction end gas, after condenser, enters HBr falling liquid film water absorption tower, reclaims HBr, then emptying after the process of alkali lye spray column.After bromine dropwises, adopt o-toluic acid content in gas-chromatography sampling detection reaction liquid, if o-toluic acid content is the 0.02wt% being no more than reaction solution total mass, then constant temperature 1.5h at 132 DEG C, and continue to stir, obtain reaction product.
In reaction product, pass into nitrogen to remove hydrogen bromide, be cooled to 80 DEG C simultaneously.Logical complete, add acetylene tetrachloride stirring and dissolving, device filters brilliant still after filtration, crystallisation by cooling, is separated and obtains wet finished product, then obtain finished product 3-bromo phthalide through vacuum-drying through whizzer.
Embodiment 5
In bromination still, add 100g o-toluic acid, open chuck steam heating, be warming up to o-toluic acid fusing, start and stir, temperature is raised to 130 DEG C and starts to drip 280g bromine equably continuously and make it reaction.Bromine rate of addition controls to take out of without bromine at reaction end gas, and the time controlling to drip is at 5.5h.Temperature of reaction controls at 140 DEG C.Reaction end gas, after condenser, enters HBr falling liquid film water absorption tower, reclaims HBr, then emptying after the process of alkali lye spray column.After bromine dropwises, adopt o-toluic acid content in gas-chromatography sampling detection reaction liquid, if o-toluic acid content is the 0.02wt% being no more than reaction solution total mass, then constant temperature 2h at 135 DEG C, and continue to stir, obtain reaction product.
In reaction product, pass into nitrogen to remove hydrogen bromide, be cooled to 80 DEG C simultaneously.Logical complete, add acetylene tetrachloride stirring and dissolving, device filters brilliant still after filtration, crystallisation by cooling, is separated and obtains wet finished product, then obtain finished product 3-bromo phthalide through vacuum-drying through whizzer.
1-cyclohexenyl acetic acid embodiment 1 ~ 5 obtained carries out transformation efficiency and yield is tested, and what deserves to be explained is, these tests the means of testing be familiar with by those skilled in the art, concrete testing method does not repeat at this.Its test result is as following table:
Table 1
Applicant states, the present invention illustrates detailed process equipment and process flow process of the present invention by above-described embodiment, but the present invention is not limited to above-mentioned detailed process equipment and process flow process, namely do not mean that the present invention must rely on above-mentioned detailed process equipment and process flow process and could implement.Person of ordinary skill in the field should understand, any improvement in the present invention, to equivalence replacement and the interpolation of ancillary component, the concrete way choice etc. of each raw material of product of the present invention, all drops within protection scope of the present invention and open scope.
Claims (5)
1. a preparation method for 3-bromo phthalide, is characterized in that, comprises the following steps:
(1) after o-toluic acid (formula A) is heated to 126 ~ 134 DEG C, drip bromine continuously wherein, make o-toluic acid and bromine constant be 135 ~ 145 DEG C of heating conditions under react, after bromine dropwises, when the content detection by o-toluic acid in the reaction solution of this reaction is to judge that reaction is reached home, reaction solution to be regulated at 130 ~ 140 DEG C and constant temperature 1 ~ 2h, obtain reaction product;
(2) in described reaction product, be cooled to 80 ~ 84 DEG C, add acetylene tetrachloride wherein and carry out recrystallization, obtain 3-bromo phthalide (formula B); The reaction formula of wherein said reaction is as follows,
2. preparation method according to claim 1, is characterized in that, described in step (1), the mass ratio of o-toluic acid and bromine is 1:(2 ~ 3).
3. preparation method according to claim 1, is characterized in that, described in step (1), the time for adding of bromine is 4 ~ 6h.
4. preparation method according to claim 1, is characterized in that, in step (1), when the content of o-toluic acid is account for reaction solution total mass 0.02%, judges that reaction is reached home.
5. preparation method according to claim 1, is characterized in that, the volume ratio 0.6 ~ 1.5 of acetylene tetrachloride and reaction product described in step (2).
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110498783A (en) * | 2019-08-02 | 2019-11-26 | 成都蓝蜻蜓生物技术有限公司 | A method of his intermediate of synthesis Luo Shasi |
| CN110615734A (en) * | 2018-06-20 | 2019-12-27 | 福建博诺安科医药科技有限公司 | Industrialized synthesis method of o-aldehyde phenyl fatty acid |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4211710A (en) * | 1977-05-11 | 1980-07-08 | Dynamit Nobel Aktiengesellschaft | Process of preparing 3-bromophthalide |
| CN101735041A (en) * | 2009-12-17 | 2010-06-16 | 太仓市运通化工厂 | Preparation method of 2-carboxybenzaldehyde |
| CN102675271A (en) * | 2012-05-10 | 2012-09-19 | 常州大学 | Continuous preparation method for phthalide and derivatives thereof |
-
2014
- 2014-11-27 CN CN201410708314.7A patent/CN104496949A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4211710A (en) * | 1977-05-11 | 1980-07-08 | Dynamit Nobel Aktiengesellschaft | Process of preparing 3-bromophthalide |
| CN101735041A (en) * | 2009-12-17 | 2010-06-16 | 太仓市运通化工厂 | Preparation method of 2-carboxybenzaldehyde |
| CN102675271A (en) * | 2012-05-10 | 2012-09-19 | 常州大学 | Continuous preparation method for phthalide and derivatives thereof |
Non-Patent Citations (1)
| Title |
|---|
| 金克强，等: "3-溴苯酞合成工艺的研究", 《浙江化工》, vol. 44, no. 12, 31 December 2013 (2013-12-31) * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110615734A (en) * | 2018-06-20 | 2019-12-27 | 福建博诺安科医药科技有限公司 | Industrialized synthesis method of o-aldehyde phenyl fatty acid |
| CN110498783A (en) * | 2019-08-02 | 2019-11-26 | 成都蓝蜻蜓生物技术有限公司 | A method of his intermediate of synthesis Luo Shasi |
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Application publication date: 20150408 |