CN106831508B - A method of catalysis asymmetric oxidation thioether - Google Patents
A method of catalysis asymmetric oxidation thioether Download PDFInfo
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- CN106831508B CN106831508B CN201510881333.4A CN201510881333A CN106831508B CN 106831508 B CN106831508 B CN 106831508B CN 201510881333 A CN201510881333 A CN 201510881333A CN 106831508 B CN106831508 B CN 106831508B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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Abstract
The present invention provides a kind of asymmetric oxidation method of thioether.The chiral complex for using four tooth nitrogen organic ligands and metal scadium compound to be formed is catalyst, using hydrogen peroxide as oxidant, asymmetry catalysis oxidation reaction is carried out to such thioether, obtains corresponding chiral sulfoxides, yield enantioselectivity is all larger than 90%.The reaction has cleaning, and reaction condition is mild, high conversion and corresponding selection.With industrial prospect.
Description
Technical field
The present invention relates to the methods that the asymmetric oxidation to thioether prepares chiral sulfoxide.
Background technique
Chiral sulfoxide is a kind of important organic synthesis intermediate, in fine chemicals such as drug, fragrance, food additives
Synthesis in have extremely be widely applied.Therefore, the preparation of chiral sulfoxide has important theory and realistic meaning.Text at present
It mainly includes that chiral diol (phenol)-titanium is catalyzed that the transition metal-catalyzed thioether asymmetric oxidation system of report, which is offered, by chiral ligand classification
System, chiral three hydramine-titanium, chirality porphyrin metal complex catalyst system, chiral Salen metal complex catalyst system and hand
Property Schiff base metal complex catalyst system (Arkivoc, 2011, (i), 1-110；Journal of Sulfur
Chemistry,2013,34(3),301-341)。
Although above-mentioned system can realize the asymmetric oxidation reaction of thioether, it is big that there are still catalyst amounts, substrate
The problems such as narrow application range, not environment friendly and long reaction time.These problems all limit thioether asymmetric oxidation reaction
Industrial production.
Summary of the invention
The purpose of the present invention is to provide one kind efficiently, and highly-solid selectively, quickly, environmental-friendly catalysis thioether be not right
Claim the new method of oxidation reaction synthesis of chiral sulfoxide.
In order to achieve the above objectives, the technical solution adopted by the present invention:
A method of chiral sulfoxides being prepared for asymmetry catalysis sulfide oxidation, it is in organic solvent, used
Hydrogen oxide is oxidant, and the complex compound formed using chiral four tooth nitrogen organic ligands and metal scadium compound is catalyst, by thioether
It is oxidized to chiral sulfoxide.Wherein, the molar ratio of chiral ligand and scadium compound is 1:1, and the molar ratio of chiral ligand and substrate is
1:5000~1:50, preferably 1:1000~1:100.The molar ratio of hydrogen peroxide and substrate is 1:1~10:1, preferably 1.5:1
~2.5:1.
The thioether is R4-S-R5, and wherein R4, R5 are respectively selected from the aryl of C6-12, the aryl methyl (C6-12 of C6-12
The aryl methyl of aryl and C6-12 can be no substituent group or has halogen, C1-4 alkyl, C1-4 alkoxy, C2-5
Alkoxy carbonyl, nitro or-CN substituent group), C1-6 alkyl (C1-6 alkyl can be no substituent group or contain halogen,
Nitro, hydroxyl or-CN substituent group.
The sulfoxide compound of corresponding chirality isWherein R4, R5It is respectively selected from C6-12Aryl, C6-12Aryl first
Base (C6-12Aryl and C6-12Aryl methyl can be no substituent group or have halogen, a C1-4Alkyl, C1-4Alkoxy,
C2-5Alkoxy carbonyl, nitro or-CN substituent group), C1-6Alkyl (C1-6Alkyl can be no substituent group or contain halogen,
Nitro, hydroxyl or-CN substituent group.
Manganese compound of the present invention is trifluoromethanesulfonic acid manganese [Sc (OTf)3]。
Chiral four teeth nitrogen ligand of the present invention is the compound having the following structure, and wherein R1, R2, R3 are respectively
Hydrogen, alkyl (molecular formula CnH2n+1, n=1-5), aryl, aryl alkyl (molecular formula C6H5CnH2n+1, n=1-5) or alkane
Oxygroup (molecular formula OCnH2n+1, n=1-5), R1, R2, R3 are identical or different；X is O, S or N.
Organic solvent organic solvent of the present invention be acetonitrile, methanol, one of tetrahydrofuran or methylene chloride, preferably
Tetrahydrofuran.The mass concentration of hydrogen peroxide is 15wt%~70wt%, preferably 30wt%~50wt%.Reaction temperature be-
70 DEG C~20 DEG C, preferably -30 DEG C~0 DEG C.Reaction time 5-30min.
Yield enantioselectivity of the present invention is all larger than 90%.The reaction have cleaning, reaction condition is mild, high conversion and
Enantioselectivity.With industrial prospect.
Due to the utilization of above-mentioned technology, compared with the prior art, the invention has the following advantages:
1. metallic compound is cheap and easy to get；
2. reaction speed is fast；
3. additive-free
4. ligand is recyclable after reaction, reuse；
Specific embodiment
Embodiment 1
The investigation of reaction condition
Under the conditions of 25 DEG C, be added in 1.0mL THF Sc (OTf) 3 (1.0mg, 0.0021mmol) and L2 (1.0mg,
0.0021mmol) stir 4h.Reaction mixture is cooled to 0 DEG C, 0.42mmol thioether and 45% hydrogen peroxide is then added
(0.42mmol) is maintained and is stirred 1h at 0 DEG C.Ethyl acetate extraction, 10% hypo solution washing, merges organic phase,
Dry, efficient liquid phase chromatographic analysis obtains ee value, and column chromatographs to obtain product, and yield is calculated.
Reaction condition is optimized using phenyl methyl sulfide as model substrates.As a result such as following table.
A separation yield.The detection of b chiral high performance liquid chromatography.
By table as it can be seen that solvent is tetrahydrofuran, the molar ratio of hydrogen peroxide and substrate thioether is 1.5:1, reaction temperature is-
Result is best at 20 DEG C, and the reaction result of the four tooth nitrogen ligand of chirality of different structure is different, and the result of L2 is better than other ligands.
8.3),6.40(1H,d,J 9.8),5.66(1H,d,J 9.8),1.48(3H,s)；13C NMR(100MHz,CDCl3)δ153.17
(s),141.47(s),134.46(s),131.68(s),129.29(s),127.24(s),125.58(s),122.93(s),
122.01(s),117.20(s),77.50(dd,J 62.4,30.4),28.71(s)；Ee value measures (color by Chiral HPLC
Column: DAICEL OD-H is composed, mobile phase: n-hexane/isopropanol=90:10 (volume ratio), flow velocity: 0.5mL/min, wavelength:
254nm。).
Claims (9)
1. a kind of method for being catalyzed asymmetric oxidation thioether, it is characterised in that:
In organic solvent, it is oxidant with hydrogen peroxide, is formed with chiral four tooth nitrogen organic ligands and metal scadium compound
Complex compound is catalyst, and substrate pro-chiral sulphide is oxidized to chiral sulfoxide compound；Wherein, chiral four tooth nitrogen organic ligands with
The molar ratio of scadium compound is 1:1, and the molar ratio of chiral four tooth nitrogen organic ligands and substrate thioether is 1:5000~1:50；Peroxide
The molar ratio for changing hydrogen and substrate thioether is 1:1~10:1；
The four tooth nitrogen ligand of chirality is the compound having the following structure, wherein R1、R2、R3Respectively hydrogen, alkyl, aryl,
Aryl alkyl or alkoxy, the molecular formula of alkyl are CnH2n+1, and n=1-5, aryl alkyl molecular formula is C6H5CnH2n, n=1-
5, alkoxy molecular formula is OCnH2n+1, n=1-5, R1、R2、R3It is identical or different；X is O, S or N；
2. according to the method for claim 1, it is characterised in that:
The molar ratio of chiral four tooth nitrogen organic ligands and substrate thioether is 1:1000~1:100；Hydrogen peroxide and substrate thioether
Molar ratio is 1.5:1~2.5:1.
3. according to the method for claim 1, it is characterised in that: the oxidant is using aqueous hydrogen peroxide solution, mistake
The mass concentration of hydrogen oxide is 15wt%~70wt%.
4. according to the method for claim 1, it is characterised in that: reaction temperature is -70 DEG C~20 DEG C.
5. according to the method for claim 1, it is characterised in that: scadium compound is trifluoromethayl sulfonic acid scandium [Sc (OTf)3]。
6. according to the method for claim 1, it is characterised in that: chiral four tooth nitrogen organic ligand recoverables.
7. according to the method for claim 1, it is characterised in that:
The thioether is R4-S-R5, wherein R4, and R5 is respectively selected from the aryl or C6-12 aryl of C6-12 with halogen, C1-4
One or two or more kinds of substituted aryl in alkyl, C1-4 alkoxy, the alkoxy carbonyl of C2-5, nitro or-CN substituent group, virtue
It is taken on base alkyl or aryl alkyl with halogen, C1-4 alkyl, C1-4 alkoxy, the alkoxy carbonyl of C2-5, nitro or-CN
On the substituted aryl alkyl of Dai Jizhong one or two or more kinds, C1-6 alkyl or C1-6 alkyl containing halogen, nitro, hydroxyl or-
One or two or more kinds of substitution alkyl in CN substituent group；The aryl alkyl molecular formula is C6H5CnH2n, n=1-5.
8. according to method described in claim 1 or 7, it is characterised in that:
The sulfoxide compound of corresponding chirality isWherein R4For phenyl, R5For methyl.
9. according to method described in claim 1 or 7, it is characterised in that:
Organic solvent is acetonitrile, methanol, one of tetrahydrofuran or methylene chloride.
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