CN101585839A - 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone and synthetic method thereof - Google Patents
6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone and synthetic method thereof Download PDFInfo
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- CN101585839A CN101585839A CNA200910048342XA CN200910048342A CN101585839A CN 101585839 A CN101585839 A CN 101585839A CN A200910048342X A CNA200910048342X A CN A200910048342XA CN 200910048342 A CN200910048342 A CN 200910048342A CN 101585839 A CN101585839 A CN 101585839A
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Abstract
The present invention relates to a kind of 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone and synthetic method thereof, the structural formula of this compound is: this method has following steps: trifluoro γ-ketone acid methyl esters and catalytic dosage of paratoluenesulfonic acid are dissolved in the toluene, the anhydrous magnesium sulfate that adds catalyst levels again, stirring down, back flow reaction adds after 20～60 minutes the methoxyl group O-Phenylene Diamine, continue reaction and add catalytic dosage of paratoluenesulfonic acid again after 10～15 hours, back flow reaction 10～15 hours, reaction finishes, through separation and purification, get white solid and be 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone.6-methoxyl group-3a-of the present invention (trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone should have stronger activity, more helps absorbing.Raw material of the present invention is easy to get, and operates very simply, and one kettle way is synthetic, and productive rate is fit to scale operation up to 78%.
Description
Technical field:
The present invention relates to a kind of is 3 '-Trifluoromethyl-1-methoxyl group benzo imidazoles 2-pyrrolidinone derivative and synthetic method thereof, particularly a kind of 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone and synthetic method thereof.
Background technology:
Nitrogen-containing heterocycle compound is a part important in the organic compound, and it has almost accounted for the overwhelming majority of heterogeneous ring compound.Nitrogen-containing heterocycle compound has a wide range of applications in field of fine chemical such as agricultural chemicals, medicine, dyestuff, is the focus that people study all the time.
Benzoglyoxaline lopps compound has certain property of medicine as a kind of important nitrogen-containing heterocycle compound, is present in the minority medicine.They are widely used in the control of agricultural disease worm, control and other industrial circles of human body diseases.And the benzimidazoles medicine is to the mammal low toxicity, is a kind of antiparasitic of efficient, wide spectrum.Pyrrolidone compound also is the very high compound of a class using value, is important medicine intermediate, is the raw material of producing piracetam, Myelosan etc., also is the raw material of producing Polyvinylpyrolidone (PVP) (burn medicine).The benzoglyoxaline pyrrolidone compound is the bis-heterocyclic compounds that contains two nitrogen heteroatoms, and structure is special, and their polymkeric substance is widely used as heat-resisting gas separation membrane material usually.
As far back as eighties of last century document (Chimirri, A. were just arranged in the eighties; Sarro, A.D.; Sarro, G.D.; Grasso, S.; Trimarchi, G.R.J.Med.Chem.1989,32, reported that 93-95.) the benzoglyoxaline 2-pyrrolidinone derivative has anti-epileptic, antitetanic physiologically active, can be applicable in the medicine.There is phenyl ring the benzoglyoxaline pyrrolones derivative 3a position of being reported in this piece article, and on the phenyl ring electron-withdrawing group is arranged.
The synthetic method of this compound does not have report at present as yet.
Summary of the invention:
One of purpose of the present invention is to provide a kind of new compound 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone.
Two of purpose of the present invention is to provide the synthetic method of this compound.
For achieving the above object, the reaction mechanism that the inventive method adopts is:
According to above-mentioned reaction mechanism, the present invention adopts following technical scheme:
A kind of 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone is characterized in that the structure of this compound is:
6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, the physical parameter of 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-this compound of 1-ketone:
Molecular formula: C
12H
11F
3N
2O
2
Structural formula:
Chinese named: 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, the English name of 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone: 6-methoxy-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydro-1H-benzo[d] pyrrolo[1,2-a] imidazol-1-one
Molecular weight: 272.08
Outward appearance: white solid
Fusing point: 113.5～115.4
Infrared spectra (adopting the Perkin-Elmer983G infrared spectrometer, liquid-film method):
v?max(cm
-1)：3342，3004，2931，1921，1868，1716，1610，1499，1454，1390，1194，1171，1069，1060，979，884，847，820
Proton nmr spectra (500MHz, CDCl
3): 7.346,7.329 (d, J=8.5Hz, 1H, ArH); 6.355,6.338,6.324 (t, J=7.75Hz, 2H, ArH); 4.847 (s, 1H, NH); 3.736 (s, 3H, Ar-OCH
3); 2.929～2.855 (m, 1H, CH
2); 2.809,2.783,2.765 (t, J=11Hz, 1H, CH
2); 2.572,2.5455,2.519 (t, J=13.25Hz, 1H, CH
2); 2.439,2.417,2.394,2.372 (q, J=11.2Hz, 1H, CH
2)
Nucleus magnetic resonance fluorine spectrum (470MHz, CDCl
3, interior mark: C
6F
6): δ=-86.27 (s)
Carbon-13 nmr spectra (125MHz, CDCl
3): 177.74; 158.40; 142.70; 127.91; 125.61,123.32,121.02 (J=287.5Hz); 123.60; 115.40; 103.94; 98.12; 85.92,85.67,85.41,85.16 (J=31.25Hz); 55.65; 32.68; 31.14
A kind of synthetic above-mentioned 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] method of imidazoles-1-ketone, the concrete steps that it is characterized in that this method are: trifluoro γ-ketone acid methyl esters and catalytic dosage of paratoluenesulfonic acid are dissolved in the toluene, the anhydrous magnesium sulfate that adds catalyst levels again, stirring down, back flow reaction adds after 20～60 minutes the methoxyl group O-Phenylene Diamine, continue reaction and add catalytic dosage of paratoluenesulfonic acid again after 10～15 hours, back flow reaction 10～15 hours, reaction finishes, through separation and purification, get white solid and be 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone.
In the pharmaceutical chemistry field, fluorine atom or one contain fluoroalkyl and are incorporated into and are considered to one of most effectual way that host compound is modified in the host molecule.Because the fluorine atom radius is little, has bigger electronegativity again, its formed C-F key bond energy is than big many of c h bond bond energy, the stability and the physiologically active of organofluorine compound have been increased significantly, fluorinated organic compound also has higher fat-soluble and hydrophobicity in addition, promote it to absorb in vivo and transmission speed, physiological action is changed.Have characteristics such as consumption is few, toxicity is low, drug effect is high, metabolic capacity is strong so a lot of fluorine-containing medicines and agricultural chemicals are relative on performance, this makes its proportion in the new pharmaceutical pesticide species more and more higher.The fluoro-containing group trifluoromethyl that the handle of the invention has an electrophilic function is incorporated into the 3a position of benzoglyoxaline pyrrolones derivative, replace the phenyl ring that has the electrophilic function originally, make 6-methoxyl group-3a-of the present invention (trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone should have stronger activity, more helps absorbing.The inventive method raw material is easy to get, and operates very simply, and one kettle way is synthetic, and productive rate 78% is fit to scale operation.
Embodiment:
Embodiment 1: 1. add trifluoro γ-ketone acid methyl esters 0.44 gram in 50 milliliters the round-bottomed flask that reflux condensing tube is housed, p-methyl benzenesulfonic acid 0.019 gram, 25 milliliters of toluene, anhydrous magnesium sulfate 0.2 gram.Said mixture stirring and refluxing in oil bath adds after half an hour methoxyl group O-Phenylene Diamine 0.276 gram; 2. reactant reaction solution yellowing gradually under refluxing.React and add 0.019 gram p-methyl benzenesulfonic acid after 12 hours again.Continue reaction 12 hours, then stopped reaction.Suction filtration was removed anhydrous magnesium sulfate, concentrated filtrate after reaction finished.3. the concentrated solution that obtains is separated with silica gel column chromatography, developping agent is that volume ratio is 8: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets white solid 0.42 gram, and productive rate is 78%.
Embodiment 2: 1. add trifluoro γ-ketone acid methyl esters 11 grams in 250 milliliters the round-bottomed flask that reflux condensing tube is housed, p-methyl benzenesulfonic acid 0.475 gram, 150 milliliters of toluene, anhydrous magnesium sulfate 5 grams.Said mixture stirring and refluxing in oil bath adds after half an hour methoxyl group O-Phenylene Diamine 6.9 grams; 2. reactant reaction solution yellowing gradually under refluxing.React and add 0.475 gram p-methyl benzenesulfonic acid after 12 hours again.Continue reaction 16 hours, then stopped reaction.Suction filtration was removed anhydrous magnesium sulfate, concentrated filtrate after reaction finished.3. the concentrated solution that obtains is separated with silica gel column chromatography, developping agent is that volume ratio is 8: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets white solid 10.2 grams, and productive rate is 75%.
Embodiment 3: 1. add trifluoro γ-ketone acid methyl esters 110 grams in 2 liters the round-bottomed flask that reflux condensing tube is housed, p-methyl benzenesulfonic acid 4.75 grams, 1000 milliliters of toluene, anhydrous magnesium sulfate 25 grams.Said mixture stirring and refluxing in oil bath adds after half an hour 2. methoxyl group O-Phenylene Diamine 69 is restrained reactant reaction solution yellowing gradually under refluxing.React and add 4.75 gram p-methyl benzenesulfonic acids after 12 hours again.Continue reaction 23 hours, then stopped reaction.Suction filtration was removed anhydrous magnesium sulfate, concentrated filtrate after reaction finished.3. the concentrated solution that obtains is separated with silica gel column chromatography, developping agent is that volume ratio is 6: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets white solid 99.3 grams, and productive rate is 73%.
Claims (2)
1. a 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone is characterized in that the structure of this compound is:
2. one kind is synthesized 6-methoxyl group-3a-according to claim 1 (trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] method of imidazoles-1-ketone, it is characterized in that this method has following steps: trifluoro γ-ketone acid methyl esters and catalytic dosage of paratoluenesulfonic acid are dissolved in the toluene, the anhydrous magnesium sulfate that adds catalyst levels again, stirring down, back flow reaction adds after 20～60 minutes the methoxyl group O-Phenylene Diamine, continue reaction and add catalytic dosage of paratoluenesulfonic acid again after 10～15 hours, back flow reaction 10～15 hours, reaction finishes, through separation and purification, get white solid and be 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone.
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| CNA200910048342XA CN101585839A (en) | 2009-03-26 | 2009-03-26 | 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone and synthetic method thereof |
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| CNA200910048342XA CN101585839A (en) | 2009-03-26 | 2009-03-26 | 6-methoxyl group-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone and synthetic method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10053817B2 (en) | 2010-04-27 | 2018-08-21 | Fiberlean Technologies Limited | Process for the manufacture of structured materials using nano-fibrillar cellulose gels |
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2009
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10053817B2 (en) | 2010-04-27 | 2018-08-21 | Fiberlean Technologies Limited | Process for the manufacture of structured materials using nano-fibrillar cellulose gels |
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