CN104610263B - Chiral imidazolidinone-phenol - Google Patents
Chiral imidazolidinone-phenol Download PDFInfo
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- CN104610263B CN104610263B CN201410472460.4A CN201410472460A CN104610263B CN 104610263 B CN104610263 B CN 104610263B CN 201410472460 A CN201410472460 A CN 201410472460A CN 104610263 B CN104610263 B CN 104610263B
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Abstract
The invention discloses a kind of from L-prolineamide and 3,5-di-tert-butyl salicylaldehyde synthesis of chiral imidazolone-phenol (systematic naming method: (7aS)-3-(3,5-di-t-butyl-2-hydroxy phenyl)-hexahydropyrrolo also [1,2-e] imidazoles-1-ketone), it is used for the sulfide oxidation of vanadyl acetylacetonate catalysis for chiral sulfoxide using this compound as chiral ligand.This chiral ligand structure is special, and easily, with low cost, enantioselectivity is good, has important application prospect in synthesis.
Description
Technical field
The present invention relates to the application as catalyst of asymmetry catalysis, organic synthesis and vanadic salts, be exactly specifically with chiral imidazolidinone-phenolic compounds be part, with vanadyl acetylacetonate for catalyst, phenylethyl thioether is chiral sulfoxide by catalytic oxidation.
Background technology
Chiral sulfoxide is present among multi-medicament, for instance, Esso omeprazole, rabeprazole, lansoprazole.Chiral sulfoxide can also as chiral ligand and catalyst.Chiral sulfoxide is also used to the synthesis of natural product.
The sulfoxide of racemization can be synthesized by general chemical oxidation thioether, for instance, make solvent hydrogen peroxide oxidation thioether at acetic acid, aoxidize with m-chloro-benzoic acid peroxide or other peroxide.The multiple methods such as oxidation, chiral separation, chiral reagent and other reagent reacting that chiral sulfoxide generally can be aoxidized by asymmetry catalysis, enzyme or microorganism promote synthesizes.
The method synthesis of chiral sulfoxide of asymmetry catalysis oxidation, is method both economical in chemical method, cheap, effective.The asymmetry catalysis oxidizing sulfur ether of synthesis of chiral sulfoxide mainly has titanium as catalyst and vanadium as catalyst two kinds.
Titanium catalyst is through frequently with tetraisopropyl titanate and suitable chiral ligand.Shortcoming is that the especially easy moisture absorption of tetraisopropyl titanate is rotten, meet water is hydrolyzed inefficacy at once, and, the catalytic amount generally used is relatively larger, general more than 10mol%.
Vanadium catalyst mainly adopts vanadyl acetylacetonate and chiral ligand to constitute.This catalyst amount is smaller, general 1mol%, and to water, air-stable, directly with aqueous hydrogen peroxide solution as oxidant, relatively green, environmental protection.And, China's v-ti magnetite mineral deposit is widely distributed, rich reserves, carries out utilizing of vanadium significant.
Asymmetry catalysis sulfide oxidation has had many reports with vanadium for catalyst.What put forward here is a kind of new chiral ligand imidazolone-phenol, for asymmetry catalysis sulfide oxidation.Chiral imidazolidinone-phenol is directly obtained by amino acid amide and substituted salicylic aldehydes one step condensation.The advantage of this chiral ligand be prepare simple, with low cost, enantioselectivity is high.
Summary of the invention
It is an object of the invention to provide a kind of novel chiral ligands imidazolone-phenol (systematic naming method: (7aS)-3-(3 for the oxidation of vanadium catalysis unsymmetrical sulfides, 5-di-t-butyl-2-hydroxy phenyl)-hexahydropyrrolo also [1,2-e] imidazoles-1-ketone).
The present invention is with (7aS)-3-(3,5-di-t-butyl-2-hydroxy phenyl)-hexahydropyrrolo also [1,2-e] imidazoles-1-ketone is chiral ligand, under the catalysis of vanadyl acetylacetonate, phenylethyl thioether is by phenylethyl sulfoxide that 30% hydrogen peroxide oxidation is 100%ee.
The laboratory operating procedures of this chiral ligand synthesis: taking 3,5-di-tert-butyl salicylaldehydes of equimolar amounts and L-prolineamide adds in band magnetic stir bar flask, solvent made by toluene, being placed in oil bath pan agitating heating reacts a period of time.After cooling, reactant mixture, through separating purification, obtains the target product of white powdery solids.Product passes through1The furanones such as HNMR.
Vanadium catalysis phenylethyl thioether asymmetric oxidation is the operating procedure of chiral sulfoxide: phenylethyl thioether, 0.5 ~ 2mol% vanadyl acetylacetonate, 1 ~ 5mol% (7aS)-3-(3, 5-di-t-butyl-2-hydroxy phenyl)-hexahydropyrrolo also [1, 2-e] imidazoles-1-ketone and dichloroethanes join in the reaction vessel being furnished with magnetic stir bar, then test tube is placed in ice-water bath stirring at low speed, then 30% hydrogen peroxide of excessive 10 ~ 100mol% it is slowly added into, after stirring at low speed 24 hours, with dichloromethane extraction, dichloromethane layer saturated common salt is washed, anhydrous magnesium sulfate dries, filter.Filtrate obtains crude product through concentrating under reduced pressure, through with petroleum ether and ethyl acetate be eluant, silica gel column chromatography separating purification obtain the phenylethyl sulfoxide of enantiomer enrichment.
Detailed description of the invention
The present invention is expanded on further by the examples below, does not therefore limit the present invention among described scope of embodiments.
Embodiment 1
Synthesis (7aS)-3-(3,5-di-t-butyl-2-hydroxy phenyl)-hexahydropyrrolo also [1,2-e] experimental procedures of imidazoles-1-ketone: take the clean round-bottomed flask of 100mL, weigh 3,5-di-tert-butyl salicylaldehyde (2.34g, 0.01mol), weigh (1.14g again, 0.01mol), the two is poured in flask, add magnetic stir bar, make solvent (50mL) with toluene, vibration shakes up, and is placed in 60 DEG C of oil bath pans agitating heating and reacts 24 hours.After cooling, reactant mixture 10mL water washing 2 times, add anhydrous magnesium sulfate and dry, be filtered to remove desiccant, spin concentration filtrate of reducing pressure.Using the mixed liquor of petroleum ether and ethyl acetate as eluant, the target product 2.59g obtaining white powdery solids with silica gel column chromatography separating purification reacting coarse product, productivity 79%.1HNMR(300MHz,CD3COCD3)δ12.47(s,1H),7.90(s,1H),7.24(d,J=2.3Hz,1H),7.02(d,J=2.2Hz,1H),5.43(s,1H),3.79(dd,J=9.0,4.4Hz,1H),3.35–3.13(m,1H),3.11–2.92(m,1H),2.82(d,J=10.0Hz,4H),2.27–1.79(m,6H),1.41(d,J=9.4Hz,9H),1.27(d,J=13.1Hz,9H)。
Embodiment 2
Vanadium catalysis phenylethyl thioether asymmetric oxidation is the operating procedure of chiral sulfoxide: 1mmol phenylethyl thioether, 0.01mmol vanadyl acetylacetonate, 0.011mmol (7aS)-3-(3, 5-di-t-butyl-2-hydroxy phenyl)-hexahydropyrrolo also [1, 2-e] imidazoles-1-ketone and 2 milliliters of dichloroethanes join in the test tube being furnished with magnetic stir bar, then test tube is placed in ice-water bath stirring at low speed, then 1.2mmol30% hydrogen peroxide it is slowly added into, after stirring at low speed 24 hours, with dichloromethane extraction, dichloromethane layer saturated common salt is washed, anhydrous magnesium sulfate dries, filter.Filtrate obtains crude product through concentrating under reduced pressure.Crude product through with petroleum ether and ethyl acetate mixtures be eluant, silica gel column chromatography separating purification obtain phenylethyl sulfoxide, productivity 75%.Phenylethyl sulfoxide liquid chromatograph after purification is analyzed.Chiral chromatographic column used by liquid chromatograph is Japan's Daicel ChiralcelOD-H chiral column, normal hexane/isopropanol=90:10, and flow velocity is 0.8mL/min, and detector adopts UV-detector, wavelength 254nm.Phenylethyl sulfoxide raceme appearance time is 12.8 minutes (sulfoxides corresponding to R configuration) and 16.0 minutes (corresponding to S configuration sulfoxide), the product phenylethyl sulfoxide of vanadium catalysis asymmetric oxidation only goes out a peak when same analysis, appearance time is at about 16.0min, therefore, the enantioselectivity of the product phenylethyl sulfoxide of asymmetry catalysis oxidation is 100%ee, is configured as S configuration.
Claims (3)
1. chiral imidazolidinone-phenol, it is characterised in that it is the compound of following chemical formula (I):
In formula, R is the tert-butyl group.
2. the synthetic method of the compound described in claim 1, it is characterised in that: 3,5-di-tert-butyl salicylaldehydes of equimolar amounts and L-prolineamide 60 DEG C of heated and stirred in toluene are reacted 24 hours.
3. the application in synthesis of phenyl ethyl-sulfoxide of the compound described in claim 1, it is characterised in that the catalyst that this compound and vanadyl acetylacetonate are formed is for phenylethyl thioether oxidative synthesis phenylethyl sulfoxide.
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| CN201410472460.4A CN104610263B (en) | 2014-09-17 | 2014-09-17 | Chiral imidazolidinone-phenol |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1681590A (en) * | 2002-09-17 | 2005-10-12 | 罗迪亚药业公司 | Active catalysts for stereoselective ring-opening reactions |
| CN101323582A (en) * | 2008-07-30 | 2008-12-17 | 大连理工大学 | Chiral schiff base ligand and use thereof in sulfide unsymmetrical oxidation reaction |
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| WO2003002582A1 (en) * | 2001-06-27 | 2003-01-09 | Rs Tech Corp. | New chiral salen catalyst and methods for the preparation of chiral compounds from racemic epoxides by using new catalyst |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1681590A (en) * | 2002-09-17 | 2005-10-12 | 罗迪亚药业公司 | Active catalysts for stereoselective ring-opening reactions |
| CN101323582A (en) * | 2008-07-30 | 2008-12-17 | 大连理工大学 | Chiral schiff base ligand and use thereof in sulfide unsymmetrical oxidation reaction |
Non-Patent Citations (4)
| Title |
|---|
| "Highly Enantioselective Insertion of Carbenoids into N-H Bonds Catalyzed by Copper(I) Complexes of Binol Derivatives";Zongrui Hou et al.;《Angew. Chem. Int. Ed.》;20100608(第49期);第4763-4766页 * |
| "手性噁唑啉配体的研究进展";张颂 等;《化学工程与装备》;20100131(第1期);第137-138页 * |
| "金属络合物不对称催化硫醚氧化研究现状";杨治仁 等;《广东化工》;20111231;第38卷(第6期);第284-285页 * |
| "钛催化不对称硫醚氧化合成手性药物";高珊 等;《化学进展》;20100930;第22卷(第9期);第1760-1766页 * |
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