CN101544657A - 3a-(trifluoromethyl)-3,3a-dihydrobenzene[d]pyrrole[2,1-b]oxazole-1(2H)-ketone and synthesis method thereof - Google Patents
3a-(trifluoromethyl)-3,3a-dihydrobenzene[d]pyrrole[2,1-b]oxazole-1(2H)-ketone and synthesis method thereof Download PDFInfo
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- CN101544657A CN101544657A CN200910048352A CN200910048352A CN101544657A CN 101544657 A CN101544657 A CN 101544657A CN 200910048352 A CN200910048352 A CN 200910048352A CN 200910048352 A CN200910048352 A CN 200910048352A CN 101544657 A CN101544657 A CN 101544657A
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Abstract
The invention relates to 3a-(trifluoromethyl)-3,3a-dihydrobenzene[d]pyrrole[2,1-b]oxazole-1(2H)-ketone and a synthesis method thereof. The structural formula of the compound is shown as right. The method comprises the following steps: dissolving trifluoro gamma-methyl keto ester and catalytic dosage of paratoluenesulfonic acid into toluene, adding catalytic dosage of anhydrous magnesium sulfate, carrying out reflux reaction on the mixture for 20 to 60 minutes with stirring, and then adding ortho-aminophenol; adding the catalytic dosage of paratoluenesulfonic acid after reacting for 10 to 15 hours, performing reflux reaction for 10 to 15 hours, and ending the reaction; and performing separation and purification to obtain a white solid, namely 3'-trifluoromethyl-1-benzopyrrole ketopyrrolidine derivative. The 3a-(trifluoromethyl)-3,3a-dihydrobenzene[d]pyrrole[2,1-b]oxazole-1(2H)-ketone creatively introduces a fluoridebearing group of trifluoromethyl with electron absorbing function to 3a position of benzopyrrole ketopyrrolidine so as to enhance the activity and be favorable for absorbing. In the invention, raw materials are easy to obtain, the operation is simple, the product is synthesized by a one-pot method, the productivity is up to 71 percent, and the product is suitable to be produced on a large scale.
Description
Technical field:
The present invention relates to a kind of is 3 '-Trifluoromethyl-1 ,-benzoxazole pyrrolidinone derivatives and synthetic methods thereof, particularly a kind of 3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone and synthetic method thereof.
Background technology:
Heterogeneous ring compound is a most active fields in the organic chemistry, heterogeneous ring compound and life science, some confidential relation of Materials science.The amino acid that plays an important role in the human life activity, VITAMIN, nucleic acid base and alkaloid all contain heterocycle structure.Heterogeneous ring compound piece act very as medicine.In addition, in some Insecticides (tech) ﹠ Herbicides (tech)s, dyestuff, plastics etc., all contain heterocycle structure.
The benzoxazole member ring systems has certain property of medicine, is present in the minority medicine.Still be the important intermediate of dyestuff, agricultural chemicals, medicine in addition, this type of organic compound is widely used in the preparation of medicine, dyestuff, agricultural chemicals.There is a kind of white dyes OB just to contain two benzoxazole structures at present, this whitening agent can be widely used in plastics such as PVC, PS, ABS, PE, PP, because it has superior fluorescent brightening effect, good thermostability, addition characteristics seldom are as one of domestic white dyes that generally adopts.This whitening agent has fluorescence property preferably, and heat-resisting, fast light, anti-chlorine floats, and every index is all better, is specially adapted to brightening of polyster fibre and brightening of terylene and cotton and other fiber mixed fabrics.Also can be used for brightening of plastics, polyester stoste.White dyes OB can with the special luminance brightness of the shared generation of dyestuff, this act in the coloured formulations effective especially.In addition, the NNRTI that contains the benzoxazole structure has the activity of anti-HIV.
Document (Thomas, L. were arranged in 2007; Peter, A.; Hans, G.; Silvia H.Bioorganic ﹠amp; Medicinal ChemistryLetters, 17,2007,4708-4714) reported that nitrogenous oxygen heteroatom dicyclic compound has the effect of resisting gram-positive bacterium, can be used as a kind of novel antibiotic clinically.
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 3a-(trifluoromethyl)-3, and 3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-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 3 '-Trifluoromethyl-1 ,-benzoxazole pyrrolidinone derivatives is characterized in that the structure of this compound is:
3a-(trifluoromethyl)-3, and 3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone
The physical parameter of this compound:
Molecular formula: C
11H
8F
3NO
2
Structural formula:
Chinese named: 3a-(trifluoromethyl)-3, and 3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone
English name: 3a-(trifluoromethyl)-3,3a-dihydrobenzo[d] pyrrolo[2,1-b] oxazol-1 (2H)-one
Molecular weight: 243.18
Outward appearance: white solid
Fusing point: 100.3～101.5 degrees centigrade
Infrared spectra (adopting the Perkin-Elmer983G infrared spectrometer, liquid-film method):
νmax(cm
-1)：3030，2937，1749，1601，1503，1448，1359，1334，1217，1165，1143，1051，1021，978，769，747
Proton nmr spectra (500MHz, CDCl
3): 7.508,7.506,7.493,7.491 (dd, J
1=7.5Hz, J
2=1Hz, 1H, ArH); 7.130,7.127,7.114,7.111,7.098,7.096 (td, 1H, J
1=8Hz, J
2=1.5Hz, ArH); 7.031,7.029,7.016,7.014,7.001,6.999 (td, J
1=7.5Hz, J
2=1Hz, 1H, ArH); 6.940,6.924 (d, J=8Hz, 1H, ArH); 2.976～2.882 (m, 2H, CH
2); 2.682～2.524 (m, 2H, CH
2)
Nucleus magnetic resonance fluorine spectrum (470MHz, CDCl
3, interior mark: C
6F
6): δ=-86.31 (s)
Carbon-13 nmr spectra (125MHz, CDCl
3): 176.13; 152.06; 128.56; 126.39; 126.16,123.87,121.59,119.3 (J=286.25Hz); 122.58; 115.94; 109.58; 101.10,100.83,100.56,100.29 (J=33.75Hz); 32.37; 29.35
A kind of synthetic above-mentioned 3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2, the method of 1-b] oxazole-1 (2H)-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 added Ortho-Aminophenol after 20～60 minutes; React and add catalytic dosage of paratoluenesulfonic acid again after 10～15 hours; The mol ratio of described trifluoro γ-ketone acid methyl esters and Ortho-Aminophenol is: (1～1.2): 1; Back flow reaction 10～15 hours, reaction finishes; Get white solid through separation and purification and be 3 '-Trifluoromethyl-1 ,-benzoxazole pyrrolidinone derivatives.
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 key 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.3a-of the present invention (trifluoromethyl)-3, [2, the fluoro-containing group trifluoromethyl that 1-b] oxazole-1 (2H)-ketone, creationary handle have an electrophilic function is incorporated into the 3a position of benzoxazole pyrrolidone to 3a-dihydrobenzo [d] pyrroles, to strengthen its activity, is more conducive to absorb.
The present invention has following conspicuous high-lighting characteristics and significance advantage: raw material of the present invention is easy to get, and operates very simply, and one kettle way is synthetic, and productive rate 71% is fit to scale operation.
Embodiment:
Embodiment 1: preparation 3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone adopts following steps: 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 Ortho-Aminophenol 0.218 gram after half an hour; 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 the sherwood oil of 6:1 and the mixed solvent of ethyl acetate, gets white solid 0.35 gram, and productive rate is 71%.
Embodiment 2: preparation 3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone adopts following steps: 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 8 grams.Said mixture stirring and refluxing in oil bath adds Ortho-Aminophenol 5.45 grams after half an hour; 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 the sherwood oil of 6:1 and the mixed solvent of ethyl acetate, gets white solid 8.4 grams, and productive rate is 69%.
Embodiment 3: preparation 3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone adopts following steps: 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 Ortho-Aminophenol 54.5 grams after half an hour; 2. reactant reaction solution yellowing gradually under refluxing.React and add 4.75 gram p-methyl benzenesulfonic acids after 12 hours again.Continue reaction 20 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 the sherwood oil of 6:1 and the mixed solvent of ethyl acetate, gets white solid 81.4 grams, and productive rate is 67%.
Claims (2)
1. a 3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazoles-1 (2H)-ketone is characterized in that the structure of this compound is:
2. one kind is synthesized 3a-according to claim 1 (trifluoromethyl) 3,3a-dihydrobenzo [d] pyrroles [2, the method of 1-b] oxazole-1 (2H)-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 added Ortho-Aminophenol after 20～60 minutes; React and add catalytic dosage of paratoluenesulfonic acid again after 10～15 hours; The mol ratio of described trifluoro γ-ketone acid methyl esters and Ortho-Aminophenol is: (1～1.2): 1; Back flow reaction 10～15 hours, reaction finishes; Get white solid through separation and purification and be 3 '-Trifluoromethyl-1 ,-benzoxazole pyrrolidinone derivatives.
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| CN200910048352A CN101544657A (en) | 2009-03-26 | 2009-03-26 | 3a-(trifluoromethyl)-3,3a-dihydrobenzene[d]pyrrole[2,1-b]oxazole-1(2H)-ketone and synthesis method thereof |
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| CN200910048352A CN101544657A (en) | 2009-03-26 | 2009-03-26 | 3a-(trifluoromethyl)-3,3a-dihydrobenzene[d]pyrrole[2,1-b]oxazole-1(2H)-ketone and synthesis method thereof |
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