CN101544608B - 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglioxaline) methyl valerate and synthesis method thereof - Google Patents
5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglioxaline) methyl valerate and synthesis method thereof Download PDFInfo
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- dihydro
- trifluoromethyl
- methyl
- methyl valerate
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Abstract
The invention relates to 5-(2-(trifluoromethyl)-2,3-dihydro-1H- benzoglioxaline) methyl valerate and a synthesis method thereof. The structural formula of the compound is shown as above. 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, stirring the mixture to reflux for 20 to 60 minutes, and then adding o-phenylenediamine, wherein the mol ratio of the trifluoro gamma-methyl keto ester to the o-phenylenediamine is (1-1.2):1; 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 suction filtration, filtrate condensation, separation and purification to obtain a white solid, namely the 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglioxaline) methyl valerate. The 5-(2-(trifluoromethyl)-2,3-dihydro-1H- benzoglioxaline) methyl valerate and the synthesis method thereof have prominent characteristics and marked advantages that: raw materials are easy to obtain, the operation is simple, the product is synthesized by a one-pot method, the productivity is high up to 87 percent, and the product is suitable to be produced on a large scale.
Description
Technical field:
The present invention relates to a kind of 5-of being (2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate and synthetic method thereof.
Background technology:
Organic fluorine chemistry is from finding just extremely people's concern of beginning.Because a lot of products in the fluorine chemical can be made medicine, pesticide intermediate, fluorochemicals has wide prospect.Fluorine medicine is because fluorinated organic compound has special biological activity and organism adaptability, and the curative effect of fluorine-containing medicine is than all strong several times of general medicines, and its exploitation is the most active.At present commercialization and the fluorine-containing medicines developed have nearly hundred kinds in the world.The fluorine agricultural chemicals since the seventies China begun the research of fluoro-containing pesticide, sterilants such as weedicide such as fluometuron, trifluralin, oxyfluorfen and fluorine aphid locust, diflubenzuron, fluorine-containing pyrethroid have successively been developed, wherein trifluralin has been realized suitability for industrialized production, if so, tiger fear, diflubenzuron etc. also have batch process.
Heterogeneous ring compound is very wide in distributed in nature, and its quantity almost accounts for 1/3rd of known organic compound, and purposes is also a lot.Some of many important materials such as chlorophyll and clinical application have the natural drug of significant curative effect and synthetic drugs etc., all contain the structure of heterogeneous ring compound.Benzimidazoles compound has excellent structure and performance characteristics and uses very extensive.It has good biological activity such as anticancer, antimycotic, anti-inflammatory, treatment hypoglycemia and physiologic derangement etc.; Also have multiple medical active such as proton pump inhibition, parasiticide, antiviral property, atherogenic activity etc.
Fluorine-containing heterocycles has very high research and using value at medicine, agricultural chemicals and special material etc.Fluorine atom or one are contained fluoroalkyl to be incorporated into and to be 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.
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 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate.
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 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate is characterized in that the structure of this compound is:
5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate
The physical parameter of this compound:
Molecular formula: C
14H
17F
3N
2O
2
Structural formula:
Chinese named: 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate
English name: methyl 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzo[d] imidazol-2-yl) pentanoate
Molecular weight: 302.12
Outward appearance: white solid
Fusing point: 89.7～89.9
Infrared spectra (adopting the Perkin-Elmer983G infrared spectrometer, liquid-film method):
νmax(cm
-1)：3367，3048，2958，2932，2863，1972，1910，1859，1729，1609，1496，1433，1248，1192，1145，1006，969，744
Proton nmr spectra (500MHz, CDCl
3): 6.690～6.656 (m, 2H, ArH); 6.593～6.560 (m, 2H, ArH); 3.985 (s, 2H, NH); 3.653 (s, 3H, OCH
3), 2.341,2.326,2.312 (t, J=7Hz, 2H, CH
2); 1.895,1.879,1.862 (t, J=8.5Hz, 2H, CH
2); 1.718～1.658 (m, 2H, CH
2); 1.539～1.475 (m, 2H, CH
2)
Nucleus magnetic resonance fluorine spectrum (470MHz, CDCl
3, interior mark: C
6F
6): δ=-85.54 (s)
Carbon-13 nmr spectra (125MHz, CDCl
3): 173.98; 138.65; 128.20,125.92,123.63,121.34 (q, J=285Hz); 120.39; 108.82; 82.13,81.90,81.66,81.43 (q, J=27.5Hz); 51.68; 33.52; 30.98; 24.76; 21.43
A kind of above-mentioned 5-(2-(trifluoromethyl)-2 for preparing, 3-dihydro-1H-benzoglyoxaline) method of methyl valerate, it is characterized in that this method has following steps: trifluoro ε-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, backflow added O-Phenylene Diamine after 20～60 minutes; Wherein the mol ratio of trifluoro ε-ketone acid methyl esters and O-Phenylene Diamine is: (1～1.2): 1; React and add catalytic dosage of paratoluenesulfonic acid again after 10～15 hours; Back flow reaction 10～15 hours, reaction finishes; Suction filtration, concentrated filtrate, separation and purification obtain white solid and are 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate.
The present invention introduces fluorine atom in the benzimidazoles compound structure, make 5-of the present invention (2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate should have lower toxicity, more helps absorbing.And this invention product structure is stable, and good heat stability is easy to preserve, and is fit to scale operation.
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 is up to 87%.
Embodiment:
Embodiment one: preparation 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate adopts following steps: 1. add trifluoro ε-ketone acid methyl esters 0.51 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 O-Phenylene Diamine 0.216 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 1: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets white solid 0.51 gram, and productive rate is 89%.
Embodiment two: preparation 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate adopts following steps: 1. add trifluoro ε-ketone acid methyl esters 12.75 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 O-Phenylene Diamine 5.4 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 1: 1 the sherwood oil and the mixed solvent of ethyl acetate, gets white solid 12.5 grams, and productive rate is 87%.
Embodiment three: preparation 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate adopts following steps: 1. add trifluoro ε-ketone acid methyl esters 127.5 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 20 grams.Said mixture stirring and refluxing in oil bath adds O-Phenylene Diamine 54 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 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 white solid 120.9 grams, and productive rate is 84%.
Claims (2)
1. a 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate is characterized in that the structure of this compound is:
2. one kind is synthesized 5-according to claim 1 (2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) method of methyl valerate, it is characterized in that this method has following steps: trifluoro ε-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, backflow added O-Phenylene Diamine after 20～60 minutes; Wherein the mol ratio of trifluoro ε-ketone acid methyl esters and O-Phenylene Diamine is: (1～1.2): 1; React and add catalytic dosage of paratoluenesulfonic acid again after 10～15 hours; Back flow reaction 10～15 hours, reaction finishes; Suction filtration, concentrated filtrate, separation and purification obtain white solid and are 5-(2-(trifluoromethyl)-2,3-dihydro-1H-benzoglyoxaline) methyl valerate.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1775760A (en) * | 2005-12-09 | 2006-05-24 | 上海大学 | Method for preparing 2-trifluoro methyl benzimidazole |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1775760A (en) * | 2005-12-09 | 2006-05-24 | 上海大学 | Method for preparing 2-trifluoro methyl benzimidazole |
Non-Patent Citations (3)
| Title |
|---|
| Abid M et al.Synthesis of trifluoromethyl-imines by solid acid/superacid catalyzed microwave assisted approach.《Journal of Fluorine Chemistry》.2007,第128卷587-594. * |
| Prakash G.K.S.et al.Efficient One-Pot Synthesis of Fluorinated Benzimidazolines,Benzothiazolines, Benzoxazolines, and Dihydrobenzoxazinones Using Gallium(III) Triflate as a Catalyst.《Organic Letters》.2006,第9卷(第2期),179-182. * |
| Takahashi M et al.3,3,3-Trifluoro-2,2-dihydroxypropanesulfonamides as building blocks for trifluoromethyl-containing pyrazoles and benzimidazoles.《Journal of Heterocyclic Chemistry》.1997,第34卷1395-1398. * |
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