CN108752312A - A method of new preparation 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides - Google Patents
A method of new preparation 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides Download PDFInfo
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- CN108752312A CN108752312A CN201810991663.2A CN201810991663A CN108752312A CN 108752312 A CN108752312 A CN 108752312A CN 201810991663 A CN201810991663 A CN 201810991663A CN 108752312 A CN108752312 A CN 108752312A
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- Prior art keywords
- methyl
- thiophene
- methoxycarbonyl group
- sulfonic acid
- acid chlorides
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- 0 C*c(nccc1C(F)(F)F)c1Cl Chemical compound C*c(nccc1C(F)(F)F)c1Cl 0.000 description 2
- OMVSGCJXABXZMH-UHFFFAOYSA-N Cc(c(C(F)(F)F)ccn1)c1OC Chemical compound Cc(c(C(F)(F)F)ccn1)c1OC OMVSGCJXABXZMH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Abstract
The present invention provides one kind, the invention belongs to technical field of organic synthesis, and in particular to a method of new preparation 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides.This method reacts 2- methyl -4- methoxycarbonyl group thiophene, sulphur, anhydrous tetrahydro furan with lithium diisopropylamine tetrahydrofuran solution, then instills the dichloromethane solution dissolved with chlorine.The method provided by the invention for synthesizing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides by chlorine, has industrial wastewater few, the high outstanding advantages of reaction yield.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of new preparation 2- methyl -3- thiophene -5- methoxy carbonyls
The method of base sulfonic acid chloride.
Background technology
Thiophene ketone sulphur is grand, English common name：Thiencarbazone-methyl, CAS accession number：317815-83-1, chemistry
Title：4- [(4,5- dihydro -3- methoxyl group -4- methyl -5- oxo -1H-1,2,4- triazol-1-yls) carbonylamino sulfonyl] -
5- methylthiophene -3- carboxylate methyl esters are the sulfonyl-amino-carbnyl triazolinone class herbicides of Bayer exploitation.Grand thiophene ketone sulphur is acetyl
Lactic acid synzyme (ALS) inhibitor makes cessation of cell division, weeds by inhibiting the biosynthesis of plant essential amino acid
Plant stops growing.There is soil activation and cauline leaf spraying activity simultaneously, absorbed by weeds root system and blade, and conduct upwards,
With tagging and remain herbicidal effect.
2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides are the grand key intermediates of synthetic herbicide thiophene ketone sulphur, are reported at present
The synthetic route in road is mainly the following：
(1) United States Patent (USP) US6964939A1 passes through nitrous using 2- methyl -3- amino -4- methoxycarbonyl groups thiophene as raw material
Sour sodium (0-5 DEG C) diazotising at low temperature is added drop-wise in the dichloromethane solution dissolved with sulfur dioxide at 0-5 DEG C, 20 DEG C of reactions
12 hours, yield 81%, but diazo-reaction, it is dangerous big, a large amount of acid waste water is generated, sulfur dioxide gas is air master
One of pollutant is wanted, it is big to environmental hazard.
(2)《Zhejiang chemical industry》Fourth phase nineteen ninety-five volume 26, P6~9, entitled 2- methoxycarbonyl groups -3- thiophenesulfonyl chlorides close
At method commentary, three kinds of synthetic routes are described respectively：
1. acrylic acid ester process
2. acrylonitrile method
3. 3- sulfydryl -2- thiophenic acid methods
Above method reaction step is longer, and shortest route is required for four-step reaction.
Invention content
It is an object of the invention to overcome the deficiencies of existing technologies, provide that a kind of industrial wastewater is few, the high conjunction of reaction yield
At the method for 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides.
Realizing the technical solution of above-mentioned purpose of the present invention is：A kind of new preparation 2- methyl -3- thiophene -5- methoxycarbonyl group sulphurs
The method of acyl chlorides, it is characterised in that include the following steps：
(1) 2- methyl -4- methoxycarbonyl groups thiophene, sulphur and anhydrous tetrahydro furan are added in the reaction vessel, subzero 70
Lithium diisopropylamine tetrahydrofuran solution is added dropwise at ± 5 DEG C, drips off rear room temperature and is stirred to react；
(2) it is 5~7 with hydrochloric acid acidizing reaction liquid to pH under ice bath, stirs 1~6h；
(3) dichloromethane solution dissolved with chlorine is instilled in the reaction solution obtained to step (2), is dripped off and is stirred at room temperature, point
Layer, water layer are extracted with organic solvent, and organic solvent layer decompression precipitation obtains 2- methyl -3- thiophene -5- methoxycarbonyl group sulphonyl after extraction
Chlorine；
Preferably, the molar ratio of lithium diisopropylamine and 2- methyl -4- methoxycarbonyl group thiophene is in the step (1)
1.1~2.0：1.
Preferably, in the step (1) lithium diisopropylamine tetrahydrofuran solution a concentration of 1~4mol/L；Into one
Step, a concentration of 2~4mol/L of lithium diisopropylamine tetrahydrofuran solution in the step (1).
Preferably, the molar ratio of sulphur and 2- methyl -4- methoxycarbonyl group thiophene is 1.1~1.5 in the step (1)：1；
Further, the molar ratio of sulphur and 2- methyl -4- methoxycarbonyl group thiophene is 1.2~1.5 in the step (1)：1.
Preferably, the weight of anhydrous tetrahydro furan is the 2~5 of 2- methyl -4- methoxycarbonyl group thiophene in the step (1)
Times；Further, the weight of anhydrous tetrahydro furan is 3~4 times of 2- methyl -4- methoxycarbonyl group thiophene in the step (1).
Preferably, the mass concentration of hydrochloric acid is 18%~36% in the step (2).
Preferably, the temperature range that hydrochloric acid is acidified in the step (2) is that temperature is -10 DEG C~-15 DEG C.
Preferably, the mole of chlorine is 6~10 times of 2- methyl -4- methoxycarbonyl group thiophene in the step (3).
Preferably, the organic solvent used when extraction in the step (3) is tetrahydrofuran, dichloromethane, dichloroethanes
Or chloroform.
Preferably, the organic solvent weight used when extraction in the step (3) is 2- methyl -4- methoxycarbonyl group thiophene
10~20 times.
The advantageous effect that the present invention obtains：It is provided by the invention that 2- methyl -3- thiophene -5- methoxycarbonyl groups are synthesized by chlorine
The method of sulfonic acid chloride has industrial wastewater few, the high outstanding advantages of reaction yield.
Specific implementation mode
The present invention is further described specifically with reference to embodiments, but not limited to this.
Embodiment 1
2- methyl -4- methoxycarbonyl group thiophene 15.6g (0.1mol), sulphur 3.8g are added in tri- mouthfuls of reaction bulb A of 500ml
(0.12mol), anhydrous tetrahydro furan 46.8g are cooled to subzero 70 ± 5 DEG C, the lithium diisopropylamine of 2mol/L are slowly added dropwise
Tetrahydrofuran solution 55ml (0.11mol) drips off rear room temperature and is stirred to react 6 hours, with 18% hydrochloric acid acidizing reaction under ice bath
Liquid stirs 2h to pH=7, and dichloromethane 200g is added in another reaction bulb, is passed through chlorine 42.6g (0.6mol), instills anti-
It answers in bottle A, drips off and be stirred at room temperature, be layered, water layer is extracted with dichloromethane 100g, and dichloromethane layer decompression precipitation obtains 2- methyl-
3- thiophene -5- methoxycarbonyl group sulfonic acid chloride 23.4g, yield 91.9%, product content 99.3%.
Embodiment 2
2- methyl -4- methoxycarbonyl group thiophene 15.6g (0.1mol), sulphur 3.8g are added in tri- mouthfuls of reaction bulbs of 500ml
(0.12mol), anhydrous tetrahydro furan 62.4g are cooled to subzero 70 ± 5 DEG C, the lithium diisopropylamine of 4mol/L are slowly added dropwise
Tetrahydrofuran solution 30ml (0.12mol) drips off rear room temperature and is stirred to react 6 hours, with 36% hydrochloric acid acidizing reaction under ice bath
Liquid pH=6 stirs 3h, then instills the dichloromethane solution 150g dissolved with chlorine 49.7g (0.7mol), drip off and be stirred at room temperature,
Layering, water layer are extracted with dichloromethane 50g, and dichloromethane layer decompression precipitation obtains 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides
24.1g, yield 94.7%, product content 98.5%.
Embodiment 3
2- methyl -4- methoxycarbonyl group thiophene 15.6g (0.1mol), sulphur 4.8g are added in tri- mouthfuls of reaction bulbs of 500ml
(0.15mol), anhydrous tetrahydro furan 46.8g are cooled to subzero 70 ± 5 DEG C, 2mol/L lithium diisopropylamines four are slowly added dropwise
Hydrogen tetrahydrofuran solution 70ml (0.14mol) drips off rear room temperature and is stirred to react 6 hours, with 18% hydrochloric acid acidizing reaction liquid under ice bath
PH=5 stirs 4h, then instills the dichloromethane solution 200g dissolved with chlorine 42.6g (0.6mol), drip off and be stirred at room temperature, point
Layer, water layer are extracted with dichloromethane 50g, and dichloromethane layer decompression precipitation obtains 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides
23.8g, yield 93.5%, product content 98.8%.
The product of above-described embodiment confirms through nuclear-magnetism and mass spectrum.
All documents that the present invention refers to are incorporated herein by reference, and are individually drawn just as each document
It is used as with reference to such.
Claims (10)
1. a kind of new method for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides, it is characterised in that including following step
Suddenly：
(1) sodium hydroxide, sulphur and NaHS are added in organic solvent, and back flow reaction to system dissolved clarification is stopped at after homogeneous
It only reacts, cools down；The chloro- 4- trifluoromethyl pyridines of 2- methoxyl groups -3- are added in reaction solution, back flow reaction, reaction knot are continued
Shu Hou, removing solvent, acidification purify to obtain 2- methoxyl group -3- sulfydryl -4- trifluoromethyl pyridines；
(2) 2- methoxyl group -3- sulfydryl -4- trifluoromethyl pyridines are formed into suspension in organic solvent and water, be passed through chlorine into
Row reaction is layered after reaction, and 2- methoxyl group -4- trifluoromethyl pyridine -3- sulfonic acid chlorides are distilled to obtain in washing；
Its reaction route is as follows：
2. the new method for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides according to claim 1, feature
It is, the molar ratio of lithium diisopropylamine and 2- methyl -4- methoxycarbonyl group thiophene is 1.1~2.0 in the step (1):1.
3. the new method for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides according to claim 1, feature
It is, a concentration of 1~4mol/L of lithium diisopropylamine tetrahydrofuran solution in the step (1).
4. the new method for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides according to claim 1, feature
It is, the molar ratio of sulphur and 2- methyl -4- methoxycarbonyl group thiophene is 1.1~1.5 in the step (1)：1.
5. the new method for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides according to claim 1, feature
It is, the weight of anhydrous tetrahydro furan is 2~5 times of 2- methyl -4- methoxycarbonyl group thiophene in the step (1).
6. the new method for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides according to claim 1, feature
It is, the mass concentration of hydrochloric acid is 18%~36% in the step (2).
7. the new method for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides according to claim 1, feature
It is, the temperature range that hydrochloric acid is acidified in the step (2) is that temperature is -10 DEG C~-15 DEG C.
8. according to the new side for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides of claim 1~7 any one of them
Method, which is characterized in that the mole of chlorine is 6~10 times of 2- methyl -4- methoxycarbonyl group thiophene in step (3).
9. according to the new side for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides of claim 1~7 any one of them
Method, which is characterized in that the organic solvent used when extraction in the step (3) be tetrahydrofuran, dichloromethane, dichloroethanes or
Chloroform.
10. according to the new side for preparing 2- methyl -3- thiophene -5- methoxycarbonyl group sulfonic acid chlorides of claim 1~7 any one of them
Method, which is characterized in that the organic solvent weight used when extraction in the step (3) is 2- methyl -4- methoxycarbonyl group thiophene
10~20 times.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111732568A (en) * | 2020-06-23 | 2020-10-02 | 北京怡力生物科技有限公司 | Synthesis method of 4-methoxycarbonyl-2-methylthiophene-3-sulfonyl chloride |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1137119C (en) * | 1999-08-06 | 2004-02-04 | 拜尔公司 | Substituted thineyl (amino) sulfonylureas |
| CN103189380A (en) * | 2010-10-12 | 2013-07-03 | 新日铁住金化学株式会社 | Chalcogen-containing aromatic compound, organic semiconductor material, and organic electronic device |
| CN104395297A (en) * | 2012-04-24 | 2015-03-04 | 味之素株式会社 | Sulfonamide derivative and medicinal use thereof |
-
2018
- 2018-08-29 CN CN201810991663.2A patent/CN108752312A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1137119C (en) * | 1999-08-06 | 2004-02-04 | 拜尔公司 | Substituted thineyl (amino) sulfonylureas |
| CN103189380A (en) * | 2010-10-12 | 2013-07-03 | 新日铁住金化学株式会社 | Chalcogen-containing aromatic compound, organic semiconductor material, and organic electronic device |
| CN104395297A (en) * | 2012-04-24 | 2015-03-04 | 味之素株式会社 | Sulfonamide derivative and medicinal use thereof |
Non-Patent Citations (1)
| Title |
|---|
| JASON A. WILES ET AL.: "Selenophene-Containing Inhibitors of Type IIA Bacterial Topoisomerases", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111732568A (en) * | 2020-06-23 | 2020-10-02 | 北京怡力生物科技有限公司 | Synthesis method of 4-methoxycarbonyl-2-methylthiophene-3-sulfonyl chloride |
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