CN101531670A - 7-methyl-3a-(trifluoromethyl)-3, 3a-dihydrobenzo (d) pyrrole (2, 1-b)-oxazole-1(2H)-ketone and synthetic method thereof - Google Patents
7-methyl-3a-(trifluoromethyl)-3, 3a-dihydrobenzo (d) pyrrole (2, 1-b)-oxazole-1(2H)-ketone and synthetic method thereof Download PDFInfo
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- CN101531670A CN101531670A CN200910048357A CN200910048357A CN101531670A CN 101531670 A CN101531670 A CN 101531670A CN 200910048357 A CN200910048357 A CN 200910048357A CN 200910048357 A CN200910048357 A CN 200910048357A CN 101531670 A CN101531670 A CN 101531670A
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- trifluoromethyl
- dihydrobenzo
- oxazole
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Abstract
The invention relates to a 7-methyl-3a-(trifluoromethyl)-3, 3a-dihydrobenzo (d) pyrrole (2, 1-b)-oxazole-1(2H)-ketone and a synthetic method thereof. The structural formula of the compound is shown as the right formula; the method comprises the following steps: trifluoro-gama-methyl ketonic acid and p-toluene sulfonic acid with the amount of a catalyst are dissolved in methylbenzene, anhydrous magnesium sulfate with the amount of the catalyst is added, reflux is carried out for 20 to 60 minutes under stirring and then 2-amino-4-methylphenol is added; the obtained mixture continuously reacts for 10 to 15 hours, and then p-toluene sulfonic acid with the amount of the catalyst is added and reflux reaction is carried out for 10 to 15 hours and then reaction is ended; and pale-yellow solid is obtained by separation and purification, namely 7-methyl-3a-(trifluoromethyl)-3, 3a-dihydrobenzo (d) pyrrole (2, 1-b)-oxazole-1(2H)-ketone. The 7-methyl-3a-(trifluoromethyl)-3, 3a-dihydrobenzo (d) pyrrole (2, 1-b)-oxazole-1(2H)-ketone has stronger activity and is more beneficial to being absorbed. The invention has easily obtained raw materials and very simple operation, adopts one-pot synthesis, has productivity up to 78 percent and is applicable to production on large scale.
Description
Technical field:
The present invention relates to a kind of is 3 '-Trifluoromethyl-1-toluene Bing oxazole pyrrolidinone derivatives and synthetic method thereof, particularly a kind of 7-methyl-3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone and synthetic method thereof.
Background technology:
Up to now, in thousands of organic compound of synthetic, have only the organic compound of minority to have physiologically active, and have in the organic compound of physiologically active at these, great majority contain heterocycle.Therefore, design has caused the attention of synthetic chemistry man with synthetic heterogeneous ring compound with physiologically active.Heterocyclic chemistry and life science, Materials science has confidential relation.Some components of life entity have heterocycle structure, as amino acid, nucleic acid etc.
Contain nitrogen oxygen heterocyclic diazoles compound, especially benzoxazole ring architecture compound has a wide range of applications especially.The benzoxazole compounds 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.In addition, the NNRTI that contains the benzoxazole structure has the activity of anti-HIV.2-pyrrolidinone derivative is the important penta azacyclo compound of a class.Pyrrolidone has a lot of purposes in medicine, food, household chemicals, coating, high molecular polymerization field.。
Document (Thomas, L. were arranged in 2007; Peter, A.; Hans, G.; Silvia H.Bioorganic ﹠amp; Medicinal ChemistryLetters, 17,2007,4708-4714) report is similar to our this nitrogenous oxygen heteroatom dicyclic compound of synthetic, 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 7-methyl-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 7-methyl-3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone is characterized in that, the structure of this compound is:
7-methyl-3a-(trifluoromethyl)-3, and 3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone
The physical parameter of this compound:
Molecular formula: C
12H
10F
3NO
2
Structural formula:
Chinese named: 7-methyl-3a-(trifluoromethyl)-3, and 3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone
English name:
7-methyl-3a-(trifluoromethyl)-3，3a-dihydrobenzo[d]pyrrolo[2，1-b]oxazol-1(2H)-one
Molecular weight: 257.21
Outward appearance: faint yellow solid
Fusing point: 64.9～68.4 degrees centigrade
Infrared spectra (adopting the Perkin-Elmer983G infrared spectrometer, liquid-film method):
v?max(cm
-1)：3011，2942，1954，1876，1743，1601，1506，1454，1391，1187，1167，1072，1054，973，879，839，824
Proton nmr spectra (500MHz, CDCl
3): 7.327,7.325, (d, J=1Hz, 1H, ArH); 6.901,6.900,6.885,6.884 (dd, J
1=8Hz, J
2=0.5Hz, 1H, ArH); 6.805,6.789 (d, J=8Hz, 1H, ArH); 2.958～2.881 (m, 2H, CH
2); 2.668～2.512 (m, 2H, CH
2); 2.333 (s, 1H, CH
3)
Nucleus magnetic resonance fluorine spectrum (470MHz, CDCl
3, interior mark: C
6F
6): δ=-86.26 (s)
Carbon-13 nmr spectra (125MHz, CDCl
3): 175.98; 149.97; 132.42; 128.36; 126.15; 126.13,123.85,121.57,119.29 (J=285Hz); 116.52; 108.97; 101.15,100.88,100.61,100.34 (J=33.75Hz); 32.40; 29.3; 20.98
A kind of synthetic above-mentioned 7-methyl-3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone, the concrete steps that it is characterized in that this method are as follows: 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 is 20～60 minutes under stirring, add 2-amino-4-methylphenol, continue reaction after 10～15 hours, add catalytic dosage of paratoluenesulfonic acid again, back flow reaction 10～15 hours, reaction finishes, and through separation and purification, gets faint yellow solid and is 7-methyl 3a-(trifluoromethyl)-3,3a dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-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 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.The fluoro-containing group trifluoromethyl that the handle of the invention has an electrophilic function is incorporated into the 3a position of benzoxazole pyrrolones derivative, make 7-methyl-3a-of the present invention (trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H) 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 2-amino-4-methylphenol 0.246 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 6: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets faint yellow solid 0.40 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 2-amino-4-methylphenol 6.2 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 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 6: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets faint yellow solid 9.76 grams, and productive rate is 76%.
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 2-amino-4-methylphenol 62 and restrains 2. reactant reaction solution yellowing gradually under refluxing after half an hour.React and add 4.75 gram p-methyl benzenesulfonic acids 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 6: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets faint yellow solid 94.7 grams, and productive rate is 74%.
Claims (2)
1. a 7-methyl-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 7-methyl-3a-according to claim 1 (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, back flow reaction is 20～60 minutes under stirring, add 2-amino-4-methylphenol, continue reaction after 10～15 hours, add catalytic dosage of paratoluenesulfonic acid again, back flow reaction 10～15 hours, reaction finishes, and through separation and purification, gets faint yellow solid and is 7-methyl-3a-(trifluoromethyl)-3,3a-dihydrobenzo [d] pyrroles [2,1-b] oxazole-1 (2H)-ketone.
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| CN200910048357A CN101531670A (en) | 2009-03-26 | 2009-03-26 | 7-methyl-3a-(trifluoromethyl)-3, 3a-dihydrobenzo (d) pyrrole (2, 1-b)-oxazole-1(2H)-ketone and synthetic method thereof |
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| CN200910048357A CN101531670A (en) | 2009-03-26 | 2009-03-26 | 7-methyl-3a-(trifluoromethyl)-3, 3a-dihydrobenzo (d) pyrrole (2, 1-b)-oxazole-1(2H)-ketone and synthetic method thereof |
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