CN101514203A - 7-nitryl-3a-(trifluoromethyl)-2,3,3a,4-tetrahydrogen-1H-benzo(d) pyrrole (1,2-a) imidazole-1-ketone and synthesis method thereof - Google Patents
7-nitryl-3a-(trifluoromethyl)-2,3,3a,4-tetrahydrogen-1H-benzo(d) pyrrole (1,2-a) imidazole-1-ketone and synthesis method thereof Download PDFInfo
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- CN101514203A CN101514203A CNA2009100483398A CN200910048339A CN101514203A CN 101514203 A CN101514203 A CN 101514203A CN A2009100483398 A CNA2009100483398 A CN A2009100483398A CN 200910048339 A CN200910048339 A CN 200910048339A CN 101514203 A CN101514203 A CN 101514203A
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Abstract
The invention relates to a 7-nitryl-3a-(trifluoromethyl)-2,3,3a,4-tetrahydrogen-1H-benzo(d) pyrrole (1,2-a) imidazole-1-ketone and a synthesis method thereof. The compound has the following chemical formula: FORMULA (see the figure). The method comprises the following steps of: dissolving trifluoro Gamma-keto acid methyl ester and p-toluene sulfonic acid with catalyst dosage in toluene; adding in anhydrous magnesium sulfate with catalyst dosage; adding in 1,4-diaminobutane dihydrochloride after reflux reacting for 20-60 minutes under the condition of stirring; and adding in the p-toluene sulfonic acid with catalyst dosage after reacting for 10-15 h so as to finish the reaction; and separating and purifying to obtain yellow solid: 7-nitryl-3a-(trifluoromethyl)-2,3,3a,4-tetrahydrogen-1H-benzo(d) pyrrole (1,2-a) imidazole-1-ketone. The 7-nitryl-3a-(trifluoromethyl)-2,3,3a,4-tetrahydrogen-1H-benzo(d) pyrrole (1,2-a) imidazole-1-ketone has stronger activity and is more beneficial to being absorbed. The invention has the advantages of easy obtaining of raw materials, very simple operation, one-pot synthesis and productivity of 26% and is suitable for large-scale production.
Description
Technical field:
The present invention relates to a kind of is 3 '-Trifluoromethyl-1-nitrobenzimidazole 2-pyrrolidinone derivative and synthetic method thereof, particularly a kind of 7-nitro-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone and synthetic method thereof.
Background technology:
Heterogeneous ring compound extensively is present in nature, is classes maximum in the organic compound.All contain heterocyclic system in a lot of natural compoundss, and these compounds often has very strong physiologically active.Some artificial synthetic heterogeneous ring compounds have been widely used in subjects such as pharmacy, materialogy in recent years, and some heterogeneous ring compound has been applied to produce as medicine, have obtained good economic benefits and social benefit.
Pyrrolidone compound is the very high compound of a class using value, is important medicine intermediate, in order to produce piracetam, Myelosan etc., also is the raw material of producing Polyvinylpyrolidone (PVP).The benzoglyoxaline member ring systems has the physiologically active of height, as agricultural chemicals, medicine, dyestuff etc. application is comparatively widely being arranged in industrial and agricultural production.For example, the benzimidazoles insect repellent is a kind of insect repellent commonly used in edible animal (pig, ox, sheep, horse, poultry etc.) aquaculture.The polymkeric substance of benzoglyoxaline pyrrolidone compound is widely used as heat-resisting gas separation membrane material (as: poly-pyrrole throat) usually.
Document (Chimirri, A. were arranged in 1989; Sarro, A.D.; Sarro, G.D.; Grasso, S.; Trimarchi, G.R.J.Med.Chem.1989,32,93-95.) reported that benzoglyoxaline pyrrolones derivative has anti-epileptic, anticonvulsant biological activity, 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 7-nitro-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 has adopted is:
According to above-mentioned reaction mechanism, the present invention adopts following technical scheme:
A kind of 7-nitro-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:
7-nitro-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone
The physical parameter of this compound:
Molecular formula: C
11H
8F
3N
3O
3
Structural formula:
Chinese named: 7-nitro-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone
English name:
7-nitro-3a-(trifluoromethyl)-2，3，3a，4-tetrahydro-1H-benzo[d]pyrrolo[1，2-a]imidazol-1-one
Molecular weight: 287.19
Outward appearance: yellow solid
Fusing point: 208.6～208.9
Infrared spectra (adopting the Perkin-Elmer983G infrared spectrometer, liquid-film method):
v?max(cm
-1)：3353，2931，1931，1874，1715，1610，1497，1458，1326，1196，1176，1156，1072，1055，972，881，841，825
Proton nmr spectra (500MHz, Acetone): 8.115,8.110 (d, J=2.5Hz, 1H, ArH); 8.037,8.033,8.020,8.015 (dd, J
1=8.5Hz, J
2=2.5Hz, 1H, ArH); 7.889 (s, 1H, NH); 6.859,6.842 (d, J=8.5Hz, 1H, ArH); 2.997～2.919 (m, 2H, CH
2); 2.860～2.801 (m, 1H, CH
2); 2.684～2.619 (m, 1H, CH
2)
Nucleus magnetic resonance fluorine spectrum (470MHz, Acetone, interior mark: C
6F
6): δ=-87.39 (s)
Carbon-13 nmr spectra (125MHz, Acetone): 177.76; 149.43; 114.98; 131.17; 128.93,126.64,124.36,122.07 (J=286.25Hz); 124.81; 110.92; 108.05; 87.58,87.31,87.06,86.80 (J=33.75Hz); 32.92; 31.80
A kind of synthetic above-mentioned 7-nitro-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, back flow reaction adds after 20～60 minutes the nitro O-Phenylene Diamine under stirring, and continues reaction after 10～15 hours, adds catalytic dosage of paratoluenesulfonic acid again, back flow reaction 10～15 hours, reaction finishes, and through separation and purification, gets yellow solid and is 7-nitro-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 7-nitro-3a-of the present invention (trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone has 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 43% 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 nitro O-Phenylene Diamine 0.306 gram; 2. reactant reaction solution under refluxing becomes scarlet gradually.React and add 0.019 gram p-methyl benzenesulfonic acid after 12 hours again.Continue reaction 24 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 2: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets yellow solid 0.25 gram, and productive rate is 43%.
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 nitro O-Phenylene Diamine 7.65 grams; 2. reactant reaction solution under refluxing becomes scarlet gradually.React and add 0.475 gram p-methyl benzenesulfonic acid after 16 hours again.Continue reaction 32 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 2: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets yellow solid 5.87 grams, and productive rate is 41%.
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 and 2. nitro O-Phenylene Diamine 76.5 is restrained reactant reaction solution under refluxing becomes scarlet gradually.React and add 4.75 gram p-methyl benzenesulfonic acids after 18 hours again.Continue reaction 48 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 2: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets yellow solid 56.1 grams, and productive rate is 39%.
Claims (2)
1. a 7-nitro-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 7-nitro-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, back flow reaction adds after 20～60 minutes the nitro O-Phenylene Diamine under stirring, and continues reaction after 10～15 hours, adds catalytic dosage of paratoluenesulfonic acid again, back flow reaction 10～15 hours, reaction finishes, and through separation and purification, gets yellow solid and is 7-nitro-3a-(trifluoromethyl)-2,3,3a, 4-tetrahydrochysene-1H-benzo [d] pyrroles [1,2-a] imidazoles-1-ketone.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2009100483398A CN101514203A (en) | 2009-03-26 | 2009-03-26 | 7-nitryl-3a-(trifluoromethyl)-2,3,3a,4-tetrahydrogen-1H-benzo(d) pyrrole (1,2-a) imidazole-1-ketone and synthesis method thereof |
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| CNA2009100483398A CN101514203A (en) | 2009-03-26 | 2009-03-26 | 7-nitryl-3a-(trifluoromethyl)-2,3,3a,4-tetrahydrogen-1H-benzo(d) pyrrole (1,2-a) imidazole-1-ketone and synthesis method thereof |
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| CN101514203A true CN101514203A (en) | 2009-08-26 |
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| CNA2009100483398A Pending CN101514203A (en) | 2009-03-26 | 2009-03-26 | 7-nitryl-3a-(trifluoromethyl)-2,3,3a,4-tetrahydrogen-1H-benzo(d) pyrrole (1,2-a) imidazole-1-ketone and synthesis method thereof |
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