CN1300117C - Microwave radiation synthesis of 1,3-substituted imidazole-2-thioketone - Google Patents
Microwave radiation synthesis of 1,3-substituted imidazole-2-thioketone Download PDFInfo
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- CN1300117C CN1300117C CNB2005100492011A CN200510049201A CN1300117C CN 1300117 C CN1300117 C CN 1300117C CN B2005100492011 A CNB2005100492011 A CN B2005100492011A CN 200510049201 A CN200510049201 A CN 200510049201A CN 1300117 C CN1300117 C CN 1300117C
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- CN
- China
- Prior art keywords
- microwave radiation
- reaction
- thioketones
- thioketone
- benzyl
- Prior art date
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- 230000005855 radiation Effects 0.000 title claims abstract description 22
- 230000015572 biosynthetic process Effects 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 10
- -1 1, 3-disubstituted imidazolium Chemical class 0.000 claims abstract description 7
- 230000035484 reaction time Effects 0.000 claims abstract description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 3
- SDJHDRMYZQFJJO-UHFFFAOYSA-N ethanethioic s-acid;potassium Chemical compound [K].CC(S)=O SDJHDRMYZQFJJO-UHFFFAOYSA-N 0.000 claims description 3
- 150000002460 imidazoles Chemical class 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 abstract description 7
- 238000000605 extraction Methods 0.000 abstract description 2
- 238000001914 filtration Methods 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 abstract 2
- 238000004090 dissolution Methods 0.000 abstract 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 abstract 1
- 229940116357 potassium thiocyanate Drugs 0.000 abstract 1
- 230000036632 reaction speed Effects 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 1
- 239000000047 product Substances 0.000 description 9
- 239000002994 raw material Substances 0.000 description 8
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 230000031709 bromination Effects 0.000 description 5
- 238000005893 bromination reaction Methods 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 235000007686 potassium Nutrition 0.000 description 2
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 2
- MNYOKDIIUJDYBM-UHFFFAOYSA-N 1-benzyl-3-methyl-2h-imidazole Chemical compound C1=CN(C)CN1CC1=CC=CC=C1 MNYOKDIIUJDYBM-UHFFFAOYSA-N 0.000 description 1
- KAIPKTYOBMEXRR-UHFFFAOYSA-N 1-butyl-3-methyl-2h-imidazole Chemical compound CCCCN1CN(C)C=C1 KAIPKTYOBMEXRR-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 101000643890 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 5 Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 102100021017 Ubiquitin carboxyl-terminal hydrolase 5 Human genes 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
- NBGMRMDAEWWFIR-UHFFFAOYSA-N imidazole-2-thione Chemical compound S=C1N=CC=N1 NBGMRMDAEWWFIR-UHFFFAOYSA-N 0.000 description 1
- YDTFRJLNMPSCFM-YDALLXLXSA-M levothyroxine sodium anhydrous Chemical compound [Na+].IC1=CC(C[C@H](N)C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 YDTFRJLNMPSCFM-YDALLXLXSA-M 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229960002178 thiamazole Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses a method for synthesizing 1, 3-disubstitutedimidazole-2-thioketone by microwave radiation. 1, 3-disubstitutedimidazole-2-thioketone is synthesized from 1, 3-disubstituted imidazolium and potassium thiocyanate in the equivalent ratio of 1:1 to 3 under the condition of microwave radiation; the power of the microwave radiation is from 50 to 300W; the reaction time of the microwave radiation is from 2 to 20 minutes. A reaction formula is disclosed in the specification, wherein R1 is equal to alkyl (C1 to 4) and benzyl; R2 is equal to alkyl (C1 to 4), benzyl, allyl, ethoxyl and acetoxy ethyl; X is equal to Cl, BR, BF4 and PF6. Compared with the existing method, the present invention has following advantages that the reaction speed is greatly improved by the microwave radiation, and the usual reaction time is from 2 to 20 minutes; reaction is simply and conveniently operated without the need of water removal; the post treatment of the reaction is simple and only needs dissolution, extraction, filtration, wash and concentration, and the purity of a coarse product is more than 80%; the reaction has no need of organic solvent and no pollution.
Description
Technical field
The present invention relates to a kind of microwave radiation and synthesize 1, the method for 3-disubstituted imidazole-2-thioketones.
Background technology
Imidazoles-2-thioketones is a class important compound that is widely used in medicine and chemical field, as 1-Methylimidazole-2-thioketones (Methimazole
) can be used for treating the Tiroidina parasecretion; Some imidazoles-2-thioketones class medicine also can be used for treatment of arthritis.In addition, imidazole thione has anti-oxidant and anti-flaming function, can be used as rubber antioxidants as the benzoglyoxaline thioketones; 1,3-dialkylimidazolium-2-thioketones can be used as the catalyzer of synthetic epoxy resin and can significantly improve the performance of resin.Arduengo has applied for synthetic 1 in 1992, patent (the USP5 of 3-dialkylimidazolium-2-thioketones, 104,993), this synthetic method is in the presence of salt of wormwood, with 1,3-alkyl imidazole salt and sulphur are raw material synthetic 1,3-dialkylimidazolium-2-thioketones, long reaction time (24～48 hours) also requires anhydrously, and methyl alcohol has bigger murder by poisoning again.
Summary of the invention
The purpose of this invention is to provide a kind of microwave radiation and synthesized 1, the method for 3-disubstituted imidazole-2-thioketones
Equivalence ratio be 1: 1～3 1,3-disubstituted imidazole salt and thioacetic acid potassium, synthetic 1 under the microwave radiation condition, 3-disubstituted imidazole-2-thioketones, the power of microwave radiation are 50～300W, the microwave radiation reaction times is 2～20 minutes, reaction formula is:
R wherein
1=C
1-4Alkyl, benzyl, R
2=C
1～4Alkyl, benzyl, allyl group, acetyl oxygen ethyl, X=Cl, Br, BF
4, PF
6
The present invention compares with existent method, has the following advantages:
1. improve speed of response greatly with microwave radiation, the reaction times is 2～20 minutes usually;
2. operation is easy, need not to dewater;
3. post-reaction treatment is simple, only needs dissolving extraction, filtration, washing, concentrates, and the purity of crude product is greater than 80%;
4. reaction need not organic solvent, and is pollution-free.
Embodiment
Following examples will help to understand the present invention, but be not limited to content of the present invention:
Embodiment 11,3 methylimidazoles-2-thioketones synthetic
In 20 milliliters of single port bottles with 10 mmole chlorinations 1,3-methylimidazole and 11 mmole thioacetic acid potassiums mix, load onto reflux condensing tube, reaction is 5 minutes under 150W power microwave radiation, naturally cool to room temperature, after reaction mixture dissolves with 50 milliliters of ethyl acetate-water (volume ratio 1: 1), insert in the separating funnel, tell organic phase, after dry 2 hours, concentrate with anhydrous potassium sulfate, (eluent is a normal hexane: ethyl acetate=2: 1) with silica gel column chromatography, 1,998 milligrams of 3-methylimidazoles-2-thioketones, yield is 75%.
1HNMR(500MHz，CDCl
3)：δ＝3.60(s，6H)，6.71(s，2H)；
13CNMR(500MHz，CDCl
3)：δ＝34.56，117.55，162.12；
IR(cm
-1)2957，1445，1230，1045；
MS([M+H]
+)：128.8；
Embodiment 21,3-methylimidazole-2-thioketones synthetic
Reactions steps is with embodiment 1, and different is with bromination 1, and the 3-methylimidazole is a raw material, obtains product, and yield is 78%.
Embodiment 31,3-methylimidazole-2-thioketones synthetic
Reactions steps is with embodiment 1, and different is with 1, and 3-methylimidazole a tetrafluoro borate is a raw material, obtains product, and yield is 79%.
Embodiment 41,3-methylimidazole-2-thioketones synthetic
Reactions steps is with embodiment 1, and different is to react 8 minutes under 100W power microwave radiation, obtains product, and yield is 82%.
Synthesizing of embodiment 5 1-butyl-3-Methylimidazole-2-thioketones
Reactions steps is with embodiment 1, and different is with bromination 1-butyl-3-Methylimidazole is raw material, obtains product, and yield is 78%.
1HNMR(500MHz，CDCl
3)：δ＝0.96(t，3H)，1.38(m，2H)，1.75(m，2H)，3.61(s，3H)，4.03(t，2H)，6.71(dd，2H)；
13CNMR(500MHz，CDCl
3)：13.74，19.82，31.02，35.10，47.83，116.63，117.74，161.72
IR(cm
-1)2958，2933，1568，1462，1414；
MS([M+H]
+)：170.8；
Synthesizing of embodiment 6 1-butyl-3-Methylimidazole-2-thioketones
Reactions steps is with embodiment 5, and different is with 1-butyl-3-Methylimidazole hexafluorophosphate is raw material, and reaction is 6 minutes under 120W power microwave radiation, obtains product, and yield is 82%.
Synthesizing of embodiment 7 1-butyl-3-Methylimidazole-2-thioketones
Reactions steps is with embodiment 6, and different is to use 15 mmole thioacetic acid potassiums, and reaction is 6 minutes under 120W power microwave radiation, obtains product, and yield is 85%.
Synthesizing of embodiment 8 1-allyl group-3-Methylimidazole-2-thioketones
Reactions steps is with embodiment 1, and different is with bromination 1-allyl group-3-Methylimidazole is raw material, obtains product, and yield is 72%.
1HNMR(500MHz，CDCl
3)：δ＝3.62(s，3H)，4.68(d，2H)，5.25(m，2H)，5.93(m，1H)，6.70(dd，2H)；
13CNMR(500MHz，CDCl
3)：35.30，50.36，116.39，117.99，119.23，132.06，162.62；
IR(cm
-1)：2925，1568，1459，1398；
MS([M+H]
+)：154.7；
Synthesizing of embodiment 9 1-benzyl-3-Methylimidazole-2-thioketones
Reactions steps is with embodiment 1, and different is with bromination 1-benzyl-3-Methylimidazole is raw material, obtains product, and yield is 82%.
1HNMR(500MHz，CDCl
3)：δ＝3.63(s，3H)，5.24(s，2H)，6.60(dd，2H)；
13CNMR(500MHz，CDCl
3)：35.39，51.50，116.49，118.14，128.28，128.44，129.00，136.02，162.50；
IR(cm
-1)：3137，1455，1409，1393；
MS([M+H]
+)：204.8；
Synthesizing of embodiment 10 1-acetyl oxygen ethyl-3-Methylimidazole-2-thioketones
Reactions steps is with embodiment 1, and different is that ethyl-the 3-Methylimidazole is a raw material, obtains product with bromination 1-acetyl oxygen, and yield is 81%.
1HNMR(500MHz，CDCl
3)：δ＝1.30(t，3H)，3.62(s，3H)，4.25(m，2H)，4.87(s，2H)，6.74(dd，2H)；
13CNMR(500MHz，CDCl
3)：14.22，35.42，48.78，61.97，117.43，118.08，163.83，167.57；
IR(cm
-1)：2987，1732，1570，1425，1403，1389；
MS([M+H]
+)：200.8
Claims (4)
1. one kind synthetic 1, the method of 3-disubstituted imidazole-2-thioketones, it is characterized in that equivalence ratio be 1: 1～3 1,3-disubstituted imidazole salt and thioacetic acid potassium, synthesize 1 under the microwave radiation condition, 3-disubstituted imidazole-2-thioketones, the power of microwave radiation are 50～300W, the microwave radiation reaction times is 2～20 minutes, and reaction formula is:
R wherein
1=C
1～4Alkyl, benzyl, R
2=C
1～4Alkyl, benzyl, allyl group, acetyl oxygen ethyl, X=Cl, Br, BF
4, PF
6
2. according to claim 1 a kind of synthetic 1, the method for 3-disubstituted imidazole-2-thioketones, the power that it is characterized in that said microwave radiation is 50～200W.
3. according to claim 1 a kind of synthetic 1, the method for 3-disubstituted imidazole-2-thioketones is characterized in that the said microwave radiation reaction times is 2～10 minutes.
4. according to claim 1 a kind of synthetic 1, the method for 3-disubstituted imidazole-2-thioketones is characterized in that 1, and the equivalence ratio of 3-disubstituted imidazole salt and thioacetic acid potassium is 1: 1～2.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100492011A CN1300117C (en) | 2005-01-24 | 2005-01-24 | Microwave radiation synthesis of 1,3-substituted imidazole-2-thioketone |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100492011A CN1300117C (en) | 2005-01-24 | 2005-01-24 | Microwave radiation synthesis of 1,3-substituted imidazole-2-thioketone |
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| Publication Number | Publication Date |
|---|---|
| CN1680337A CN1680337A (en) | 2005-10-12 |
| CN1300117C true CN1300117C (en) | 2007-02-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100492011A Expired - Fee Related CN1300117C (en) | 2005-01-24 | 2005-01-24 | Microwave radiation synthesis of 1,3-substituted imidazole-2-thioketone |
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|---|---|---|---|---|
| CN107964590A (en) * | 2017-11-29 | 2018-04-27 | 山东省医学科学院药物研究所 | A kind of technique of solvent extraction efficiently concentrating recycling noble silver |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0411927A1 (en) * | 1989-08-04 | 1991-02-06 | E.I. Du Pont De Nemours And Company | Coating compositions containing 1,3-dialkylimidazole-2-thione catalysts |
| US5104993A (en) * | 1989-08-04 | 1992-04-14 | E. I. Du Pont De Nemours And Company | 1,3-dialkylimidazole-2-thione catalysts and method of making same |
-
2005
- 2005-01-24 CN CNB2005100492011A patent/CN1300117C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0411927A1 (en) * | 1989-08-04 | 1991-02-06 | E.I. Du Pont De Nemours And Company | Coating compositions containing 1,3-dialkylimidazole-2-thione catalysts |
| US5104993A (en) * | 1989-08-04 | 1992-04-14 | E. I. Du Pont De Nemours And Company | 1,3-dialkylimidazole-2-thione catalysts and method of making same |
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| CN1680337A (en) | 2005-10-12 |
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