CN104086418A - Method for preparing acetyl salicylic acid - Google Patents
Method for preparing acetyl salicylic acid Download PDFInfo
- Publication number
- CN104086418A CN104086418A CN201410332975.4A CN201410332975A CN104086418A CN 104086418 A CN104086418 A CN 104086418A CN 201410332975 A CN201410332975 A CN 201410332975A CN 104086418 A CN104086418 A CN 104086418A
- Authority
- CN
- China
- Prior art keywords
- acetylsalicylic acid
- acetyl chloride
- product
- preparing
- chloride 98min
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 20
- 239000000047 product Substances 0.000 claims abstract description 16
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000012346 acetyl chloride Substances 0.000 claims abstract description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 238000000967 suction filtration Methods 0.000 claims description 10
- 238000009413 insulation Methods 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 239000007795 chemical reaction product Substances 0.000 claims description 5
- 239000013078 crystal Substances 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000011017 operating method Methods 0.000 claims description 2
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 238000012805 post-processing Methods 0.000 abstract description 2
- JYRBKUGRRUQXNQ-UHFFFAOYSA-N 6,6-dihydroxycyclohexa-2,4-diene-1-carboxylic acid Chemical compound OC(=O)C1C=CC=CC1(O)O JYRBKUGRRUQXNQ-UHFFFAOYSA-N 0.000 abstract 1
- 239000012345 acetylating agent Substances 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 239000012043 crude product Substances 0.000 abstract 1
- 238000005265 energy consumption Methods 0.000 abstract 1
- 239000012535 impurity Substances 0.000 abstract 1
- 229910000029 sodium carbonate Inorganic materials 0.000 abstract 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 239000006227 byproduct Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/14—Preparation of carboxylic acid esters from carboxylic acid halides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing acetyl salicylic acid. The method specifically comprises the following steps of reacting o-hydroxy salicylic acid with acetyl chloride as an acetylating agent to generate an acetyl salicylic acid crude product, then removing impurities with sodium carbonate and finally recrystallizing to obtain the final target product. According to method, the energy consumption is low; no catalyst is required, the cost is reduced, the post-processing difficulty is also reduced, the purity of the product is improved and can reach above 99.9%; the yield of the method disclosed by the invention can reach about 90%.
Description
Technical field
The invention belongs to fine chemical product field, a kind of method for preparing acetylsalicylic acid is provided.
Background technology
Acetylsalicylic acid (being commonly called as acetylsalicylic acid) is a kind of time-honored antipyretic and analgesic, is born on March 6th, 1899.Be used for curing cold, generate heat, headache, toothache, arthrodynia, rheumatosis, can also anticoagulant, for preventing and treat ischemic heart disease, stenocardia, cardiopulmonary infraction, cerebral thrombosis, be applied to revascularization and bypass graft also effective, it is a kind of conventional safe and effective, inexpensive medicine.As far back as Xia Er in 1853, you (Gerhardt) just synthesized acetylsalicylic acid with Whitfield's ointment and aceticanhydride Frederick Taylor hot-drawn, but could not cause people's attention; Within 1897, Germanization scholar Felix Huffman synthesizes again, and for his father treats rheumatic arthritis, curative effect is fabulous; Within 1899, by Dierser, made referrals to clinically, and be named as acetylsalicylic acid (Aspirin).Till today, acetylsalicylic acid has been applied a century, becomes one of three large classical medicines in medical history.
Traditional preparation method be take the vitriol oil as catalyzer, and acetic anhydride and Whitfield's ointment add thermal synthesis.The method by product is many, and productive rate is low, contaminate environment.Acetysalicylic for realizing " green production ", finds the focus that new catalyzer becomes present research, tosic acid, sodium acetate, trichlorine rare earth, tungstosilicic acid, potassium aluminium sulfate etc., also useful Microwave Radiation Synthesis Method.
Acetylsalicylic acid synthesis technique used is all to utilize acetic anhydride to do acetylation reagent at present, heats acidylate synthetic with Whitfield's ointment under the effect of catalyzer.The consumption of catalyzer is many, have up to 30% of Whitfield's ointment quality, and be difficult to separation, not only cause cost to increase, and product purity caused to detrimentally affect.
Summary of the invention
In conjunction with the weak point of existing technique, the present invention has studied a kind of industrial by-product Acetyl Chloride 98Min. that utilizes and has done acylating reagent, and under the condition without catalyzer, acidylate generates highly purified method for preparing acetylsalicylic acid.
Preparation technology of the present invention has following reaction equation
In order to realize the concrete operating procedure that above formula reaction takes, be:
(1) Acetyl Chloride 98Min. of metering and Whitfield's ointment are joined in there-necked flask, slowly heating, to occurring backflow, after Whitfield's ointment all dissolves, insulation reaction;
(2) reaction finishes, and reclaims excessive Acetyl Chloride 98Min.;
(3) reaction product is added in frozen water, separate out white crystals, with cold water washing, suction filtration, obtains the thick product of acetylsalicylic acid;
(4) add saturated sodium carbonate solution, be stirred to without bubble, remove by filter insolubles;
(5) filtrate is poured in concentrated hydrochloric acid, stir, separate out white solid, suction filtration;
(6) with alcohol-water mixing solutions recrystallization, obtain target product.
Above-mentioned (1) described Acetyl Chloride 98Min. and salicylic mol ratio is 1.5 ~ 3:1.
The time of the insulation reaction that above-mentioned (1) is described is 0.5 ~ 3h.
Above-mentioned (6) the described ethanol of alcohol-water mixing solutions and volume ratio of water is 3 ~ 10:1.
Research of the present invention is acetysalicylic synthetic a kind of " green production " method that provides, and the power consumption of this processing method is low; Do not need to use catalyzer, not only reduced cost, and reduced post-processing difficulty, improve product purity and can reach more than 99.9%; Process yield high energy of the present invention reaches 90% left and right.The present invention is highly suitable for the high value added product utilization of by-product Acetyl Chloride 98Min. producer, for company brings great economic benefit.
Embodiment
Embodiment 1(most preferred embodiment)
A kind of method for preparing acetylsalicylic acid is synthetic by following principle:
Concrete operation steps is:
(1) 117.8g Acetyl Chloride 98Min. and 138g Whitfield's ointment are joined in there-necked flask, slowly heating, to occurring backflow, after Whitfield's ointment all dissolves, insulation reaction 2h;
(2) reaction finishes, and reclaims excessive Acetyl Chloride 98Min.;
(3) reaction product is added in frozen water, separate out white crystals, with cold water washing, suction filtration, obtains the thick product of acetylsalicylic acid;
(4) add saturated sodium carbonate solution, be stirred to without bubble, remove by filter insolubles;
(5) filtrate is poured in concentrated hydrochloric acid, stir, separate out white solid, suction filtration;
(6) with the alcohol-water mixing solutions recrystallization of volume ratio 8:1, obtain target product.
Embodiment 2
A kind of method for preparing acetylsalicylic acid is synthetic by following principle:
Concrete operation steps is:
(1) 157g Acetyl Chloride 98Min. and 138g Whitfield's ointment are joined in there-necked flask, slowly heating, to occurring backflow, after Whitfield's ointment all dissolves, insulation reaction 2h;
(2) reaction finishes, and reclaims excessive Acetyl Chloride 98Min.;
(3) reaction product is added in frozen water, separate out white crystals, with cold water washing, suction filtration, obtains the thick product of acetylsalicylic acid;
(4) add saturated sodium carbonate solution, be stirred to without bubble, remove by filter insolubles;
(5) filtrate is poured in concentrated hydrochloric acid, stir, separate out white solid, suction filtration;
(6) with volume ratio 5:1 alcohol-water mixing solutions recrystallization, obtain target product.
Embodiment 3
A kind of method for preparing acetylsalicylic acid is synthetic by following principle:
Concrete operation steps is:
(1) 117.8g Acetyl Chloride 98Min. and 138g Whitfield's ointment are joined in there-necked flask, slowly heating, to occurring backflow, after Whitfield's ointment all dissolves, insulation reaction 3h;
(2) reaction finishes, and reclaims excessive Acetyl Chloride 98Min.;
(3) reaction product is added in frozen water, separate out white crystals, with cold water washing, suction filtration, obtains the thick product of acetylsalicylic acid;
(4) add saturated sodium carbonate solution, be stirred to without bubble, remove by filter insolubles;
(5) filtrate is poured in concentrated hydrochloric acid, stir, separate out white solid, suction filtration;
(6) with the alcohol-water mixing solutions recrystallization of volume ratio 10:1, obtain target product.
Claims (4)
1. a method for preparing acetylsalicylic acid, is characterized in that, acetysalicylic synthesizing completes by following formula technological principle
Concrete operating procedure is:
The Acetyl Chloride 98Min. of metering and Whitfield's ointment are joined in there-necked flask, slowly heating, to occurring backflow, after Whitfield's ointment all dissolves, insulation reaction;
Reaction finishes, and reclaims excessive Acetyl Chloride 98Min.;
Reaction product is added in frozen water, separate out white crystals, with cold water washing, suction filtration, obtains the thick product of acetylsalicylic acid;
Add saturated sodium carbonate solution, be stirred to without bubble, remove by filter insolubles;
Filtrate is poured in concentrated hydrochloric acid, stir, separate out white solid, suction filtration;
With alcohol-water mixing solutions recrystallization, obtain target product.
2. a kind of method for preparing acetylsalicylic acid according to claim 1, is characterized in that, described Acetyl Chloride 98Min. and the salicylic mol ratio of step (1) is 1.5 ~ 3:1.
3. a kind of method for preparing acetylsalicylic acid according to claim 1, is characterized in that, the time of the insulation reaction that step (1) is described is 0.5 ~ 3h.
4. a kind of method for preparing acetylsalicylic acid according to claim 1, is characterized in that, the described ethanol of alcohol-water mixing solutions and the volume ratio of water of step (6) is 3 ~ 10:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410332975.4A CN104086418A (en) | 2014-07-14 | 2014-07-14 | Method for preparing acetyl salicylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410332975.4A CN104086418A (en) | 2014-07-14 | 2014-07-14 | Method for preparing acetyl salicylic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104086418A true CN104086418A (en) | 2014-10-08 |
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ID=51634209
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410332975.4A Pending CN104086418A (en) | 2014-07-14 | 2014-07-14 | Method for preparing acetyl salicylic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104086418A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106187772A (en) * | 2015-04-30 | 2016-12-07 | 苗怡文 | A kind of prepare antipyretic, analgesia, the method for anti-inflammatory drug aspirin crystal compound |
| CN106966899A (en) * | 2017-03-01 | 2017-07-21 | 山东裕欣药业有限公司 | A kind of preparation method of guacetisal |
| CN107868001A (en) * | 2017-11-03 | 2018-04-03 | 山东泰和水处理科技股份有限公司 | A kind of novel processing step of acetylsalicylic acid |
| CN111620915A (en) * | 2020-07-07 | 2020-09-04 | 华中科技大学 | Stannous chloride catalyzed hydroxyl high-selectivity acylation protection method |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5944M (en) * | 1966-01-26 | 1968-05-13 | ||
| CN102180792A (en) * | 2011-03-23 | 2011-09-14 | 沈阳化工大学 | Method for preparing aspirin |
| CN103880663A (en) * | 2012-12-24 | 2014-06-25 | 青岛康地恩动物药业有限公司 | Aspirin preparation method |
-
2014
- 2014-07-14 CN CN201410332975.4A patent/CN104086418A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR5944M (en) * | 1966-01-26 | 1968-05-13 | ||
| CN102180792A (en) * | 2011-03-23 | 2011-09-14 | 沈阳化工大学 | Method for preparing aspirin |
| CN103880663A (en) * | 2012-12-24 | 2014-06-25 | 青岛康地恩动物药业有限公司 | Aspirin preparation method |
Non-Patent Citations (2)
| Title |
|---|
| 吴文婷等: "乙酰氯合成阿司匹林工艺研究", 《山东化工》, vol. 42, 31 December 2013 (2013-12-31) * |
| 谭伟等: "阿司匹林合成实验改进", 《广东化工》, vol. 39, 31 December 2012 (2012-12-31) * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106187772A (en) * | 2015-04-30 | 2016-12-07 | 苗怡文 | A kind of prepare antipyretic, analgesia, the method for anti-inflammatory drug aspirin crystal compound |
| CN106220505A (en) * | 2015-04-30 | 2016-12-14 | 苗怡文 | A kind of prepare antipyretic, analgesia, the method for anti-inflammatory drug compound |
| CN106220506A (en) * | 2015-04-30 | 2016-12-14 | 苗怡文 | A kind of prepare antipyretic, analgesia, the method for anti-inflammatory drug compound |
| CN106966899A (en) * | 2017-03-01 | 2017-07-21 | 山东裕欣药业有限公司 | A kind of preparation method of guacetisal |
| CN107868001A (en) * | 2017-11-03 | 2018-04-03 | 山东泰和水处理科技股份有限公司 | A kind of novel processing step of acetylsalicylic acid |
| CN111620915A (en) * | 2020-07-07 | 2020-09-04 | 华中科技大学 | Stannous chloride catalyzed hydroxyl high-selectivity acylation protection method |
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| PB01 | Publication | ||
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
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Application publication date: 20141008 |