CN102311356A - Synthetic method of ethyl p-aminobenzoate - Google Patents
Synthetic method of ethyl p-aminobenzoate Download PDFInfo
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- CN102311356A CN102311356A CN201110263348A CN201110263348A CN102311356A CN 102311356 A CN102311356 A CN 102311356A CN 201110263348 A CN201110263348 A CN 201110263348A CN 201110263348 A CN201110263348 A CN 201110263348A CN 102311356 A CN102311356 A CN 102311356A
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- benzoic acid
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Abstract
The invention discloses a synthetic method of ethyl p-aminobenzoate, comprising the following steps: using alcohol to dissolve para amino benzoic acid, preparing a para amino benzoic acid solution with the mass fraction of 5-30 %, adding thionyl chloride dropwisely in the para amino benzoic acid solution at the temperature of 0-50 DEG C for esterification reaction for 4-10 hours, after adding dropwisely, heating until reflux; after the reaction ends, cooling the reaction materials, after the solid substance is dissolved out, carrying out filtering, using water to dissolve the solid substance, adding weak base to neutralize the pH to 7-8, after the solid substance is dissolved out, carrying out filtering again, and then washing and drying to obtain the product of ethyl p-aminobenzoate. The method adopts para amino benzoic acid as raw material, uses thionyl chloride as desiccant for esterification reaction to prepare ethyl p-aminobenzoate, the advantages of rapid reaction speed, high yield, and high product purity are achieved, and the method has a good application prospect in industry.
Description
Technical field
The present invention relates to a kind of amino organic acid esterification process that contains, relate in particular to a kind of compound method for preparing parathesin by para-amino benzoic acid.
Background technology
Parathesin (Benzocaine claims Benzocaine again) is a kind of colourless, odorless, tasteless crystal, is insoluble in water, is soluble in alcohol, ether, chloroform.Parathesin can be used as the local anesthetic of skin and mucous membrane, also can be used for covering the protective agent of daylight, also is the midbody of cough medicine benzonatate simultaneously.
Synthesizing of parathesin mainly contains two kinds of working methods at present.A kind of method is to be raw material with the p-Nitrobenzenecarboxylic acid, is under the situation of catalyzer with sulfuric acid etc., carries out esterification with ethanol to obtain ethyl p-nitrobenzoate, obtains parathesin through iron powder reducing again.Another kind method is to be raw material with the para-amino benzoic acid, is under the situation of catalyzer with sulfuric acid etc., directly carries out esterification with ethanol and obtains parathesin.First method is that the compound method of raw material exists complex process, transformation efficiency is low, product purity is not high shortcoming with the p-Nitrobenzenecarboxylic acid.Second method is that the compound method of raw material exists the shortcoming that transformation efficiency is low, product purity is not high equally with the para-amino benzoic acid.
Summary of the invention
The objective of the invention is to overcome the shortcomings and deficiencies that exist in the prior art; Providing a kind of is raw material with the para-amino benzoic acid; Use sulfur oxychloride to carry out esterification and prepare parathesin as dewatering agent; The product purity that makes is compared all with traditional method with yield and is significantly improved, and production efficiency is high, and good application prospects is arranged in industry.
A kind of compound method of parathesin is characterized in that, may further comprise the steps:
A) with alcohol dissolving para-amino benzoic acid, the preparation massfraction is the para-amino benzoic acid solution of 5-30%;
B) under 0-50 ℃ temperature of reaction in the para-amino benzoic acid solution dripping thionyl chloride carry out esterification, be warming up to backflow after dripping, reacted 4-10 hour;
C) after reaction finished, the cooling reaction material treated that solid matter separates out after-filtration, and water dissolved solids material adds weak base and is neutralized to pH7-8, refiltered after solid matter is separated out, washes, dried and obtain the parathesin product.
Further, the alcohol among the step a is selected from ethanol, Virahol, the trimethyl carbinol, propyl carbinol, defends a kind of in the alcohol.
The 1-1.2 that the consumption of sulfur oxychloride is preferably the para-amino benzoic acid mole number among the step b doubly.The temperature of reaction that dripping thionyl chloride is carried out esterification in the para-amino benzoic acid solution is preferably 5-15 ℃.
Weak base described in the step c is preferably yellow soda ash, sodium hydrogencarbonate, triethylamine or ammoniacal liquor.Reflux time is preferably 5 ~ 7 hours.
The generation of one of product water is arranged in the esterification reaction process, the speed and the transformation efficiency of esterification had material impact.For fast reaction speed and transformation efficiency, must in time remove the moisture content that esterification produces, carry out to the direction of esterification to impel reaction.The present invention is a dewatering agent through dripping thionyl chloride; The water that esterification produces generates sulfurous gas and hydrogenchloride with the sulfur oxychloride reaction immediately; Hydrogenchloride can be reacted into hydrochloride with amino simultaneously, can play the amino effect of protection, and sulfur dioxide gas can absorb the preparation sodium sulfite anhy 96 through alkali lye.Its reaction equation is following.
After reaction finished among the step c, cold filtration gained filtrating can reuse, turned back among the step a to recycle as alcohol.
The present invention is a raw material with the para-amino benzoic acid, uses sulfur oxychloride to carry out esterification as dewatering agent and prepares parathesin, and speed of response is fast, productive rate is high, product purity is high, and good application prospects is arranged in industry.
Embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage of the present invention and characteristics will be more clear along with description.But these embodiment only are exemplary, scope of the present invention are not constituted any restriction.It will be understood by those skilled in the art that and down can make amendment with form and replace without departing from the spirit and scope of the present invention the details of technical scheme of the present invention, but these modifications and replace and all list in protection scope of the present invention.
Embodiment 1
Stirring is being housed, and TM in the 2000ml four-hole boiling flask of condensing surface, adds para-amino benzoic acid 274g; Absolute ethyl alcohol 1500ml adds sulfur oxychloride 160ml in the 250ml constant voltage separating funnel, begin to stir to be cooled to 10 ℃, slowly dripping thionyl chloride; The control reacting liquid temperature is at 8～14 ℃, and the condensation mouth of pipe inserts device for absorbing tail gas, and sulfur oxychloride dropwised in 4 hours, under nitrogen protection, began slowly to be warming up to backflow; Reaction solution has silvery white chip solid to occur gradually, 74～78 ℃ of reflux temperatures, and return time 6.5 hours, cooling is filtered; Solid with absolute ethanol washing is once used deionized water dissolving, transfers pH7～8 with 10% aqueous sodium carbonate, and filtration, washing, vacuum-drying get product: 289g; Purity (HPLC): 99.7%, fusing point: 90～91 ℃, yield: 95.8%.
Embodiment 2
Stirring is being housed, and TM in the 2000ml four-hole boiling flask of condensing surface, adds para-amino benzoic acid 274g; Absolute ethyl alcohol 1500ml adds sulfur oxychloride 140ml in the 250ml constant voltage separating funnel, begin to stir to be cooled to 10 ℃, slowly dripping thionyl chloride; The control reacting liquid temperature is at 8～10 ℃, and the condensation mouth of pipe inserts device for absorbing tail gas, and sulfur oxychloride dropwised in 5 hours, under nitrogen protection, began slowly to be warming up to backflow; Reaction solution has silvery white chip solid to occur gradually, 70～75 ℃ of reflux temperatures, and return time 5 hours, cooling is filtered; Solid with absolute ethanol washing is once used deionized water dissolving, transfers pH7～8 with 10% sodium bicarbonate aqueous solution, and filtration, washing, vacuum-drying get product: 270g; Purity (HPLC): 99.7%, fusing point: 90～91 ℃, yield: 89.4%.
Embodiment 3
Stirring is being housed, and TM in the 2000ml four-hole boiling flask of condensing surface, adds para-amino benzoic acid 274g; Absolute ethyl alcohol 1800ml adds sulfur oxychloride 150ml in the 250ml constant voltage separating funnel, begin to stir to be cooled to 10 ℃, slowly dripping thionyl chloride; The control reacting liquid temperature is at 8～14 ℃, and the condensation mouth of pipe inserts device for absorbing tail gas, and sulfur oxychloride dropwised in 4 hours, under nitrogen protection, began slowly to be warming up to backflow; Reaction solution has silvery white chip solid to occur gradually, 72～78 ℃ of reflux temperatures, and return time 6 hours, cooling is filtered; Solid with absolute ethanol washing is once used deionized water dissolving, transfers pH7～8 with 10% aqueous sodium carbonate, and filtration, washing, vacuum-drying get product: 280g; Purity (HPLC): 99.9%, fusing point: 90～91 ℃, yield: 92.7%.
Embodiment 4
Stirring is being housed, and TM in the 2000ml four-hole boiling flask of condensing surface, adds para-amino benzoic acid 274g; Instance 3 filters the ethanol filtrating that obtains, and is supplemented to 1500ml with absolute ethyl alcohol, adds sulfur oxychloride 150ml in the 250ml constant voltage separating funnel, begins to stir to be cooled to 10 ℃; Slowly dripping thionyl chloride is controlled reacting liquid temperature at 6～10 ℃, and the condensation mouth of pipe inserts device for absorbing tail gas, and sulfur oxychloride dropwised in 4 hours; Under nitrogen protection, begin slowly to be warming up to backflow, reaction solution has silvery white chip solid 71～76 ℃ of reflux temperatures to occur gradually; Return time 6 hours, cooling is filtered, and solid is with absolute ethanol washing once; Use deionized water dissolving, transfer pH7～8 with 10% aqueous sodium carbonate, filtration, washing, vacuum-drying get product: 279g; Purity (HPLC): 99.8%, fusing point: 90～91 ℃, yield: 92.4%.
Embodiment 5
Stirring is being housed, and TM in the 2000ml four-hole boiling flask of condensing surface, adds para-amino benzoic acid 274g; Virahol 1500ml adds sulfur oxychloride 160ml in the 250ml constant voltage separating funnel, begin to stir to be cooled to 0 ℃, slowly dripping thionyl chloride; The control reacting liquid temperature is at 0～5 ℃, and the condensation mouth of pipe inserts device for absorbing tail gas, and sulfur oxychloride dropwised in 4 hours, under nitrogen protection, began slowly to be warming up to backflow; Reaction solution has silvery white chip solid to occur gradually, 82～85 ℃ of reflux temperatures, and return time 6 hours, cooling is filtered; Solid with washed with isopropyl alcohol is once used deionized water dissolving again, transfers pH7～8 with ammonia soln, and filtration, washing, vacuum-drying get product: 302g; Purity (HPLC): 99.6%, fusing point: 84～85 ℃, yield: 95.6%.
Embodiment 6
Stirring is being housed, and TM in the 2000ml four-hole boiling flask of condensing surface, adds para-amino benzoic acid 274g; Trimethyl carbinol 1600ml adds sulfur oxychloride 150ml in the 250ml constant voltage separating funnel, begin to stir to be cooled to 25 ℃, slowly dripping thionyl chloride; The control reacting liquid temperature is at 25～30 ℃, and the condensation mouth of pipe inserts device for absorbing tail gas, and sulfur oxychloride dropwised in 5 hours, under nitrogen protection, began slowly to be warming up to backflow; Reaction solution has silvery white chip solid to occur gradually, 83～85 ℃ of reflux temperatures, and return time 5 hours, cooling is filtered; Solid with trimethyl carbinol washing is once used deionized water dissolving, transfers pH7～8 with ammonia soln, and filtration, washing, vacuum-drying get product: 308g; Purity (HPLC): 99.5%, fusing point: 108～110 ℃, yield: 91.5%.
Embodiment 7
Stirring is being housed, and TM in the 2000ml four-hole boiling flask of condensing surface, adds para-amino benzoic acid 274g; Propyl carbinol 1800ml adds sulfur oxychloride 160ml in the 250ml constant voltage separating funnel, be warming up to 50 ℃, slowly dripping thionyl chloride; The control reacting liquid temperature is at 50～55 ℃, and the condensation mouth of pipe inserts device for absorbing tail gas, and sulfur oxychloride dropwised in 4 hours, under nitrogen protection, began slowly to be warming up to backflow; Reaction solution has silvery white chip solid to occur gradually, 117～119 ℃ of reflux temperatures, and return time 5 hours, cooling is filtered; Solid with the propyl carbinol washing is once used deionized water dissolving, transfers pH7～8 with 10% aqueous sodium carbonate, and filtration, washing, vacuum-drying get product: 296g; Purity (HPLC): 99.2%, fusing point: 57～59 ℃, yield: 89.7%.
Embodiment 8
Stirring is being housed, and TM in the 2000ml four-hole boiling flask of condensing surface, adds para-amino benzoic acid 274g; Just defending pure 1600ml, adding sulfur oxychloride 150ml in the 250ml constant voltage separating funnel, beginning stirring and be cooled to 25 ℃, slowly dripping thionyl chloride; The control reacting liquid temperature is at 25～30 ℃, and the condensation mouth of pipe inserts device for absorbing tail gas, and sulfur oxychloride dropwised in 4 hours, under nitrogen protection, began slowly to be warming up to backflow; Reaction solution has silvery white chip solid to occur gradually, 136～138 ℃ of reflux temperatures, and return time 4 hours, cooling is filtered; Solid is used deionized water dissolving with just defending the alcohol washing once, transfers pH7～8 with 10% aqueous sodium carbonate, and filtration, washing, vacuum-drying get product: 306g; Purity (HPLC): 99.1%, fusing point: 51～53 ℃, yield: 89.0%.
Claims (6)
1. the compound method of a parathesin is characterized in that, may further comprise the steps:
A) with alcohol dissolving para-amino benzoic acid, the preparation massfraction is the para-amino benzoic acid solution of 5-30%;
B) under 0-50 ℃ temperature of reaction in the para-amino benzoic acid solution dripping thionyl chloride carry out esterification, be warming up to backflow after dripping, reacted 4-10 hour;
C) after reaction finished, the cooling reaction material treated that solid matter separates out after-filtration, and water dissolved solids material adds weak base and is neutralized to pH7-8, refiltered after solid matter is separated out, washes, dried and obtain the parathesin product.
2. compound method as claimed in claim 1 is characterized in that, the alcohol among the step a is selected from ethanol, Virahol, the trimethyl carbinol, propyl carbinol, defend a kind of in the alcohol.
3. compound method as claimed in claim 1 is characterized in that, among the step b, the consumption of sulfur oxychloride is 1-1.2 a times of para-amino benzoic acid mole number.
4. compound method as claimed in claim 1 is characterized in that, among the step b, to carry out the temperature of reaction of esterification be 5-15 ℃ to dripping thionyl chloride in the para-amino benzoic acid solution.
5. compound method as claimed in claim 1 is characterized in that, among the step b, reflux time is 5 ~ 7 hours.
6. compound method as claimed in claim 1 is characterized in that, weak base described in the step c is yellow soda ash, sodium hydrogencarbonate, triethylamine or ammoniacal liquor.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201110263348A CN102311356A (en) | 2011-09-07 | 2011-09-07 | Synthetic method of ethyl p-aminobenzoate |
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| CN201110263348A CN102311356A (en) | 2011-09-07 | 2011-09-07 | Synthetic method of ethyl p-aminobenzoate |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675137A (en) * | 2012-05-29 | 2012-09-19 | 济南诚汇双达化工有限公司 | Method for preparing N-butyl p-amino benzoic acid |
| CN109336767A (en) * | 2018-11-26 | 2019-02-15 | 山东永浩新材料科技有限公司 | A kind of dehydration synthetic method of ethyl difluoro |
| CN110003035A (en) * | 2018-12-28 | 2019-07-12 | 中国水产科学研究院 | Stable isotope labeling 3- benzocaine-D5And preparation method thereof |
-
2011
- 2011-09-07 CN CN201110263348A patent/CN102311356A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| 张斌 等: "苯佐卡因合成方法的改进", 《浙江工业大学学报》 * |
| 杨双花: "间氨基苯甲酸甲酯的合成研究", 《化工中间体》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675137A (en) * | 2012-05-29 | 2012-09-19 | 济南诚汇双达化工有限公司 | Method for preparing N-butyl p-amino benzoic acid |
| CN102675137B (en) * | 2012-05-29 | 2013-10-23 | 济南诚汇双达化工有限公司 | Method for preparing N-butyl p-amino benzoic acid |
| CN109336767A (en) * | 2018-11-26 | 2019-02-15 | 山东永浩新材料科技有限公司 | A kind of dehydration synthetic method of ethyl difluoro |
| CN110003035A (en) * | 2018-12-28 | 2019-07-12 | 中国水产科学研究院 | Stable isotope labeling 3- benzocaine-D5And preparation method thereof |
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Application publication date: 20120111 |