CN102603706A - One-step synthesis of thiopheneethanol by using Lewis acid to catalyze - Google Patents
One-step synthesis of thiopheneethanol by using Lewis acid to catalyze Download PDFInfo
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- CN102603706A CN102603706A CN2011100271334A CN201110027133A CN102603706A CN 102603706 A CN102603706 A CN 102603706A CN 2011100271334 A CN2011100271334 A CN 2011100271334A CN 201110027133 A CN201110027133 A CN 201110027133A CN 102603706 A CN102603706 A CN 102603706A
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- CN
- China
- Prior art keywords
- reaction
- thiopheneethanol
- step synthesis
- catalyze
- lewis acid
- 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.)
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- VMJOFTHFJMLIKL-UHFFFAOYSA-N 2-thiophen-2-ylethanol Chemical compound OCCC1=CC=CS1 VMJOFTHFJMLIKL-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 230000015572 biosynthetic process Effects 0.000 title abstract description 6
- 238000003786 synthesis reaction Methods 0.000 title abstract description 6
- 239000002841 Lewis acid Substances 0.000 title abstract 2
- 150000007517 lewis acids Chemical class 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 12
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims description 9
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 abstract description 10
- 229930192474 thiophene Natural products 0.000 abstract description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract 2
- 239000003054 catalyst Substances 0.000 abstract 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 5
- 229940063656 aluminum chloride Drugs 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 238000007171 acid catalysis Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229940055858 aluminum chloride anhydrous Drugs 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000004795 grignard reagents Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical class C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses a novel synthetic method of thiopheneethanol, and the novel synthetic method is characterized in that the reaction equation of one-step synthesis of the thiopheneethanol by utilizing Lewis acid to catalyze is as shown in the specification, and the reaction conditions are as follows: the reaction temperature of a catalyst, an aluminium trichloride solvent and ether or tetrahydrofuran is minus 15 DEG C (ice salt bath), the reaction time is 2-3h, and the molar ratio of thiophene to epoxy ethane to aluminium trichloride to solvent is of 1: 1.1: 1.2: 10.
Description
Technical field
The present invention relates to a kind of novel method for synthesizing of medicine intermediate thiophene ethanol.
Background technology
Thiophene ethanol can be used for the synthetic of multiple medicine, and it is the precursor raw material of new drugs such as multiple cardiovascular disease relevant with thrombocyte and thrombus and anti-inflammatory analgesic.For example, can be used for synthesizing thiofuran and pyridine, and two kinds of thienopyridine derivative clopidogrels and Ticlopidine just are being used for the treatment and the prevention of coronary heart disease at present as antiplatelet drug.It is Grignard reagent technology that the compound method of thiophene ethanol commonly used is gone up in industry at present.This method is to be raw material with the thiophene, and the first step makes the 2-bromothiophene through bromination; Second step was grignard reaction; The 3rd step directly fed oxyethane with the product behind the grignard reaction; In the 4th step, hydrolysis under acidic conditions finally obtains title product.Technological process is comparatively complicated, constantly change temperature of reaction, under different reaction environments, carries out.
Summary of the invention
The object of the invention is exactly in order to solve the problems of the technologies described above, and through the novel method of the one-step synthesis thiophene ethanol under the research Louis acid catalysis, reduces the time of this reaction, reduces reaction cost, simplifies reaction conditions.Its reaction equation is:
To achieve these goals, at present will be through repeatedly experiment, the final Louis acid catalysis one-step synthesis thiophene ethanol of confirming is characterized in that:
Catalyzer: aluminum chloride
Solvent: ether or THF
Temperature of reaction :-15 ℃ (cryosel bath)
Reaction times: 2-3h
Mol ratio: thiophene: oxyethane: aluminum chloride: solvent=1: 1.1: 1.2: 10
Description of drawings
Fig. 1 is the process synoptic diagram of reaction.
Embodiment
Preparing experiment: in refrigerator, operate, guarantee that oxyethane can not volatilize, oxyethane is dissolved in the dry normal hexane of crossing, the ethylene oxide solution mass percent is: 9.6%.The solvent that need use in the experiment is carried out drying with sodium, promptly in normal hexane, ether, THF, add sodium, backflow 2h distills under corresponding temperature again.Handle remaining useless sodium in the experiment with absolute ethyl alcohol.The chlorination of hydrochloric acid ammonium buffered soln of preparation 1mol/l is as the solution of washing separated product.
Main body experiment: in 100ml twoport flask, add raw material 1:1ml thiophene, 4ml ethylene oxide solution, solvent 2:10ml ether or THF, catalyzer 2:1.6g Aluminum chloride anhydrous, aluminum chloride is dissolved gradually with magnetic stirrer.In temperature of reaction 3:-15 ℃ (cryosel bath) reaction down.Each amount of substance is about 0.0125mol in the reaction system.Stirring reaction 2-3h, reaction product 4: thiophene ethanol gets product with the chlorination of hydrochloric acid ammonium buffered soln washing of 1mol/l after the separation.
The present invention is not limited to above-mentioned concrete embodiment, as long as adopted the catalyzer of aluminum chloride as one-step synthesis, has adopted ether or THF all to belong among protection scope of the present invention as dissolvant of reaction system.
Claims (3)
1. the novel method for synthesizing of a thiophene ethanol is characterized in that, uses aluminum chloride as catalyzer.
2. the novel method for synthesizing of thiophene ethanol according to claim 1 is characterized in that, uses ether or THF as solvent.
3. the novel method for synthesizing of thiophene ethanol according to claim 1 is characterized in that, reaction environment is that cryosel is bathed (about 15 ℃).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100271334A CN102603706A (en) | 2011-01-18 | 2011-01-18 | One-step synthesis of thiopheneethanol by using Lewis acid to catalyze |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100271334A CN102603706A (en) | 2011-01-18 | 2011-01-18 | One-step synthesis of thiopheneethanol by using Lewis acid to catalyze |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102603706A true CN102603706A (en) | 2012-07-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100271334A Pending CN102603706A (en) | 2011-01-18 | 2011-01-18 | One-step synthesis of thiopheneethanol by using Lewis acid to catalyze |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110894195A (en) * | 2019-12-09 | 2020-03-20 | 门希国 | Novel preparation method of 2-thiopheneacetic acid |
| CN112442007A (en) * | 2020-12-17 | 2021-03-05 | 安达市海纳贝尔化工有限公司 | 2-thiophene ethanol rectification process |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4127580A (en) * | 1975-02-07 | 1978-11-28 | Parcor | Process for the preparation of thieno-pyridine derivatives |
| US6639083B1 (en) * | 1999-10-22 | 2003-10-28 | Sanofi-Synthelabo | Method for preparing a thiopene derivative |
| CN101885720A (en) * | 2010-07-19 | 2010-11-17 | 连云港宏业化工有限公司 | Method for synthesizing 2-thiophene ethylamine |
-
2011
- 2011-01-18 CN CN2011100271334A patent/CN102603706A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4127580A (en) * | 1975-02-07 | 1978-11-28 | Parcor | Process for the preparation of thieno-pyridine derivatives |
| US6639083B1 (en) * | 1999-10-22 | 2003-10-28 | Sanofi-Synthelabo | Method for preparing a thiopene derivative |
| CN101885720A (en) * | 2010-07-19 | 2010-11-17 | 连云港宏业化工有限公司 | Method for synthesizing 2-thiophene ethylamine |
Non-Patent Citations (2)
| Title |
|---|
| 季永新: "噻吩乙醇的合成研究", 《化工时刊》 * |
| 邢其毅，等，: "《基础有机化学》", 31 May 2009, 高等教育出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110894195A (en) * | 2019-12-09 | 2020-03-20 | 门希国 | Novel preparation method of 2-thiopheneacetic acid |
| CN112442007A (en) * | 2020-12-17 | 2021-03-05 | 安达市海纳贝尔化工有限公司 | 2-thiophene ethanol rectification process |
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Application publication date: 20120725 |