CN105837438A - Preparation method of high-purity triethyl citrate - Google Patents
Preparation method of high-purity triethyl citrate Download PDFInfo
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- CN105837438A CN105837438A CN201610291215.2A CN201610291215A CN105837438A CN 105837438 A CN105837438 A CN 105837438A CN 201610291215 A CN201610291215 A CN 201610291215A CN 105837438 A CN105837438 A CN 105837438A
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- triethyl citrate
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- ethyl alcohol
- high purity
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of high-purity triethyl citrate .The preparation method comprises the steps that citric acid monohydrate or anhydrous citric acid and ethyl alcohol are adopted as raw materials, catalytic esterification, ethyl alcohol azeotropy water entraining, activated carbon decoloration, distillation ethyl alcohol removal, filtering, filtrate washing/water distribution and oil layer drying are performed to obtain the high-purity triethyl citrate .Crude triethyl citrate with the small content of impurities can be obtained through a proper catalyst and the addition amount of the catalyst, the reaction balance can be broken through the specific technology, the high yield can be obtained, and the reaction time can be shortened .Meanwhile, an inventor further finds that the reaction charge rate and the reaction temperature can affect the reaction rate and the product quality .
Description
Technical field
The present invention relates to pharmaceutical technology field, specifically, relate to the preparation method of a kind of Triethyl Citrate with High Purity.
Background technology
Plasticizer is also referred to as plasticiser, plasticizer, is a kind of material softness or additive making material liquefy of increasing, extensively
It is applied to food, medicine, cosmetics, commodity, toy for children etc..Plasticiser is of a great variety, but uses most common adjacent benzene two
Formate ester plasticizer has potential carcinogenicity, and countries in the world the most strictly control it and use.China has also worked out relevant
Laws and rules, by superseded phthalate compound in food and medicine packaging material, medicine equipment, toy for children, day
The application in the fields such as articles for use.
Citric acid ester plasticizer is the green generally acknowledged the most both at home and abroad, nontoxic, the product of environmental protection, wherein, citric acid three
Ethyl ester is widely used in food and medicine, cosmetics, toy for children etc..It is good that triethyl citrate has compatibility, and plasticizing efficiency is high,
Easily it is biodegradable, light resistance and the advantage such as have excellent water-resistance, resinae packaging material has good shock resistance, it is possible to suppression
The growth and breeding of mould.It is clear that citrate series products is the ideal substitute of phthalic ester plasticizer.
At present, triethyl citrate mainly by citric acid and absolute ethyl alcohol as reactant, logical under the effect of catalyst
Over-churning reaction and obtain crude product, loaded down with trivial details isolated and purified obtaining purer triethyl citrate through complicated.By difference
In triethyl citrate crude product prepared by method, impurity content is different, and product quality also has bigger difference.Chinese patent
Ethanol gasification is passed through by application 201010233849.5 as a vapor, adds production cost, and uses high boiling
Tetraethyl titanate, as catalyst, is unfavorable for industrialized production.Chinese patent application 201510350758.2 with niter cake or its
Hydrate is as catalyst, and catalytic efficiency is low, and the reaction time is long, and production cost is high, is unfavorable for that heavy industrialization is applied.China
Using sulfuric acid in patent 201110034137.5 is catalyst, and the reaction time is long, complex operation, and may generate citric acid and take off
Aquatic products thing and sulfation product.Therefore, find suitable reaction condition, meet, to obtain, the product that pharmaceutical quality requires, and
And economical, it is simple to industrialized production.
Based on requirements above, the present invention proposes the preparation method of a kind of Triethyl Citrate with High Purity.
Summary of the invention
The object of the invention is contemplated to make up the defect of prior art, it is provided that the preparation of a kind of Triethyl Citrate with High Purity
Method.
Carry out during esterification prepares triethyl citrate at citric acid and ethanol, because of the difference of reaction condition,
In product, the kind of impurity is also very different with content, is difficult to obtain the product meeting pharmaceutical quality requirement.Esterification is made
For typical reversible reaction, if can not promote in time, reacting the direction towards generating triethyl citrate moves, then can drop significantly
Low production efficiency and productivity.
The present invention is achieved by the following technical solutions:
A kind of preparation method of Triethyl Citrate with High Purity, including: monohydrate potassium or anhydrous citric acid and absolute ethyl alcohol
Condensing reflux reaction under the effect of catalyst, after reaching balance, utilizes second alcohol and water azeotropic principles to steam second alcohol and water, then
Adding absolute ethyl alcohol, carry out back flow reaction, finally carry out limit distillation ethanol and absolute ethyl alcohol is added in waterside, the phase adds in the reaction
Or addition activated carbon decolours at the end of reaction, after decolouring terminates, decompression suction filtration removes activated carbon, and second alcohol and water is evaporated off,
To water white transparency triethyl citrate crude product；Gained triethyl citrate crude product, through isolated and purified, obtains highly purified lemon
Triethylenetetraminehexaacetic acid ester.
The invention have the advantage that
The present invention can obtain, by suitable catalyst and addition, the triethyl citrate crude product that impurity content is few；Can lead to
Cross specific technique and break molecular balance, it is thus achieved that higher productivity, shorten the reaction time.And inventor also finds that reaction feeds intake
Ratio, reaction temperature can affect speed and the product quality of reaction.
Detailed description of the invention
Embodiment 1
In the reactor, 63.04g monohydrate potassium, 61mL absolute ethyl alcohol, 1.89g boric acid, 1.89g benzene sulfonic acid, machinery are added
Stirring, oil bath heating, 85 DEG C～90 DEG C carry out the 1h of condensing reflux reaction for the first time, second alcohol and water are evaporated off；Add 42.7mL anhydrous
Ethanol, 85 DEG C～90 DEG C carry out second time condensing reflux reaction 1h, second alcohol and water are evaporated off；Addition 24.4mL absolute ethyl alcohol, 85 DEG C
～90 DEG C carry out third time condensing reflux reaction 1h, start distillation, add the absolute ethyl alcohol of equal in quality simultaneously, react 3～5h
After, add 0.68g activated carbon, 100 DEG C of stirring 0.5h～1.0h, after being cooled to room temperature, use 0.45 μm organic membrane filter, be evaporated off
Solvent, obtains water white triethyl citrate crude product, saturated sodium bicarbonate solution 3 times (each 30mL) of washing, fully divides
After Ceng, separatory obtains organic layer purified water 3 times (each 30mL) of washing, and fully after layering, separatory obtains triethyl citrate.With
Buck layer and water layer are extracted by 50mL ethyl acetate, concentrate, and are dried, amount to obtain 77.31g colourless transparent liquid, and yield is
93.26%。
Claims (9)
1. the preparation method of a Triethyl Citrate with High Purity, it is characterised in that include with monohydrate potassium or anhydrous lemon
Lemon acid and ethanol as raw material, through catalytic esterification, ethanol azeotropic band water, activated carbon decolorizing, distillation removing ethanol, filtration,
Filtrate washing/point water, oil reservoir are dried, and obtain highly purified triethyl citrate.
The preparation method of a kind of Triethyl Citrate with High Purity the most according to claim 1, it is characterised in that the present invention by
Stirred autoclave equipped with destilling tower constitutes the device of catalytic reaction distillation synthesizing citric acid triethyl；In course of reaction, in batches
Or add absolute ethyl alcohol entrance stirred autoclave continuously, the water that reaction generates separates through destilling tower with ethanol azeotropic, and tower top distillates
The alcohol reflux of content big 99%, to reactor, overflows hydrous ethanol at the bottom of tower.
The preparation method of a kind of Triethyl Citrate with High Purity the most according to claim 1, it is characterised in that described urges
Agent is the one in boric acid, borate, borate, or its compound with benzene sulfonic acid, benzene sulfonate, sulfuric acid, phosphoric acid etc., two
The mass ratio of person is 1:0～1；Quality that the inventory of catalyst is monohydrate potassium or anhydrous citric acid feeds intake 0.3%～
6.0%。
The preparation method of a kind of Triethyl Citrate with High Purity the most according to claim 1, it is characterised in that described urges
Changing reaction temperature is 80 DEG C～110 DEG C.
The preparation method of a kind of Triethyl Citrate with High Purity the most according to claim 1, it is characterised in that described urges
The change reaction time is 4.5h～10h.
The preparation method of a kind of Triethyl Citrate with High Purity the most according to claim 2, it is characterised in that specifically,
Add the operation of absolute ethyl alcohol in batches, press 1:1.5 for the first time～5.5 mol ratios put into metering monohydrate potassium or anhydrous lemon
Acid and absolute ethyl alcohol, react after 1 ~ 2h, add absolute ethyl alcohol, and additional amount is put into amount of alcohol for the first time 0.5 ~ 1 times；Even
The continuous operation adding absolute ethyl alcohol, presses 1:1 ~ 2 mol ratio for the first time and puts into metering monohydrate potassium or anhydrous citric acid and nothing
Water-ethanol, after reaction 1 ~ 2h, starts to drip continuously absolute ethyl alcohol, the speed of dropping absolute ethyl alcohol and the speed about phase of distillation
Deng.
The preparation method of a kind of Triethyl Citrate with High Purity the most according to claim 1, it is characterised in that activated carbon exists
Reaction adds or adds at the end of reaction mid-term, and bleaching time is no less than 0.5h.
The preparation method of a kind of Triethyl Citrate with High Purity the most according to claim 1, it is characterised in that described preparation
Method also includes: filtrate washing gained aqueous layer with ethyl acetate organic solvent extraction, through reduced pressure concentration, concentrate closes with oil reservoir
And.
The preparation method of a kind of Triethyl Citrate with High Purity the most according to claim 1, it is characterised in that described oil reservoir
Drying means is water absorbing agent dehydration under normal temperature；Water absorbing agent used can be anhydrous sodium sulfate, anhydrous magnesium sulfate, molecular sieve and silica gel
Deng, consumption is equivalent to the 5% ~ 15% of triethyl citrate quality.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610291215.2A CN105837438A (en) | 2016-05-05 | 2016-05-05 | Preparation method of high-purity triethyl citrate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610291215.2A CN105837438A (en) | 2016-05-05 | 2016-05-05 | Preparation method of high-purity triethyl citrate |
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| Publication Number | Publication Date |
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| CN105837438A true CN105837438A (en) | 2016-08-10 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610291215.2A Pending CN105837438A (en) | 2016-05-05 | 2016-05-05 | Preparation method of high-purity triethyl citrate |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557800A (en) * | 2004-02-06 | 2004-12-29 | 江南大学 | Process for preparing ethyl citrate suitable for industrialized production |
| CN102584590A (en) * | 2011-12-21 | 2012-07-18 | 蚌埠丰原医药科技发展有限公司 | Method for synthesizing triethyl citrate |
| CN104311419A (en) * | 2014-09-29 | 2015-01-28 | 湖南尔康制药股份有限公司 | Method for catalytically synthesizing medicinal triethyl citrate by using mesoporous molecular sieve loaded heteropoly acid |
-
2016
- 2016-05-05 CN CN201610291215.2A patent/CN105837438A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557800A (en) * | 2004-02-06 | 2004-12-29 | 江南大学 | Process for preparing ethyl citrate suitable for industrialized production |
| CN102584590A (en) * | 2011-12-21 | 2012-07-18 | 蚌埠丰原医药科技发展有限公司 | Method for synthesizing triethyl citrate |
| CN104311419A (en) * | 2014-09-29 | 2015-01-28 | 湖南尔康制药股份有限公司 | Method for catalytically synthesizing medicinal triethyl citrate by using mesoporous molecular sieve loaded heteropoly acid |
Non-Patent Citations (1)
| Title |
|---|
| 孙玉婧: "柠檬酸酯化反应催化剂的评选", 《兰州教育学院学报》 * |
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Application publication date: 20160810 |