CN101143862B - Ionic compound containing chiral amine-thiourea (urea) and its preparation method and application - Google Patents
Ionic compound containing chiral amine-thiourea (urea) and its preparation method and application Download PDFInfo
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- CN101143862B CN101143862B CN2007101563865A CN200710156386A CN101143862B CN 101143862 B CN101143862 B CN 101143862B CN 2007101563865 A CN2007101563865 A CN 2007101563865A CN 200710156386 A CN200710156386 A CN 200710156386A CN 101143862 B CN101143862 B CN 101143862B
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- thiocarbamide
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- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 150000008040 ionic compounds Chemical class 0.000 title claims description 58
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title abstract description 28
- 239000004202 carbamide Substances 0.000 title description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 239000000126 substance Substances 0.000 claims abstract description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000003579 shift reagent Substances 0.000 claims abstract description 5
- 159000000000 sodium salts Chemical class 0.000 claims abstract description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 239000002904 solvent Substances 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 239000000706 filtrate Substances 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 22
- 239000007787 solid Substances 0.000 claims description 21
- -1 3,5-diisopropyl phenyl Chemical group 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 229960001701 chloroform Drugs 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 238000006957 Michael reaction Methods 0.000 claims description 7
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000005557 chiral recognition Methods 0.000 claims description 6
- 238000005712 Baylis-Hillman reaction Methods 0.000 claims description 5
- 238000005575 aldol reaction Methods 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 5
- 238000010523 cascade reaction Methods 0.000 claims description 4
- 229960004756 ethanol Drugs 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- 238000006683 Mannich reaction Methods 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 235000021050 feed intake Nutrition 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000006493 trifluoromethyl benzyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 24
- 239000000463 material Substances 0.000 abstract description 5
- 239000012069 chiral reagent Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 20
- 230000006837 decompression Effects 0.000 description 19
- 238000004821 distillation Methods 0.000 description 19
- 238000001556 precipitation Methods 0.000 description 19
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 16
- 239000004324 sodium propionate Substances 0.000 description 16
- 229960003212 sodium propionate Drugs 0.000 description 16
- 235000010334 sodium propionate Nutrition 0.000 description 16
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000006555 catalytic reaction Methods 0.000 description 8
- 229940125782 compound 2 Drugs 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- GIEFFCXIJRRYFW-UHFFFAOYSA-N Br[BrH]Br.c1ccncc1 Chemical compound Br[BrH]Br.c1ccncc1 GIEFFCXIJRRYFW-UHFFFAOYSA-N 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- 238000011914 asymmetric synthesis Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 235000013877 carbamide Nutrition 0.000 description 3
- 229940125810 compound 20 Drugs 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003512 tertiary amines Chemical group 0.000 description 2
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 1
- IEJPPSMHUUQABK-UHFFFAOYSA-N 2,4-diphenyl-4h-1,3-oxazol-5-one Chemical compound O=C1OC(C=2C=CC=CC=2)=NC1C1=CC=CC=C1 IEJPPSMHUUQABK-UHFFFAOYSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 238000007247 aza-Henry reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 239000011982 enantioselective catalyst Substances 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- PIAOLBVUVDXHHL-VOTSOKGWSA-N β-nitrostyrene Chemical compound [O-][N+](=O)\C=C\C1=CC=CC=C1 PIAOLBVUVDXHHL-VOTSOKGWSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to an ion type compound containing a chiral amine-thiourea (urea) structure, the general formula is <A> <plus> <B> <minus>, wherein, the structure of < A > <plus> is shown as the formular (I), and the structure of <B> <minus> is shown as the formular (V). In a preparation method, the bromine salt of <A> <plus>and the sodium salt of <B> <minus> are resolved in organic solvent, under the room temperature, stiring continues untile the reaction is sufficient, and therefore the ion type compound containing a chiral amine-thiourea (urea) structure is produced. The substance ofthe invention can be used as not only a catalyst in an organic asymmetric reaction but also a chiral shift reagent in the chiral identification. The substance of the invention has a good chiral inducement property and can be used as a chiral reagent, a catalyst and a chiral material in the fields of organic synthesis, materials, etc.
Description
(1) technical field
The present invention relates to a kind of novel ionic compound that contains Chiral Amine-thiocarbamide (urea) structure, the invention still further relates to the preparation method of this ionic compound that contains Chiral Amine-thiocarbamide (urea) structure and, be meant that especially organic asymmetric reaction is the application in Michael reaction, Aldol reaction, Baylis-Hillman reaction or the Michael-Aldol cascade reaction in the application of asymmetry catalysis aspect synthetic.The ionic compound that also relates to Chiral Amine-thiocarbamide (urea) structure in addition in chiral recognition as the application of chiral shift reagent.
(2) background technology
Chirality is one of natural essential attribute, also is the basis of all life.Chirality synthetic (asymmetric synthesis) reaction then is the requisite ways and means of synthesis of chiral material.The catalysis asymmetric synthesis is optimal method of asymmetric synthesis, it only uses a spot of chiral catalyst just can obtain a large amount of chiral product, therefore for asymmetric catalysis, selection of catalysts is most important, its activity and efficient are to need one of key issue that solves in the asymmetric catalyst research from now on, and realize that high-level efficiency, the highly selective of catalyzer are to realize the practicality and the industrialized key of asymmetric catalysis.
In recent years, hydrogen bond in the reaction of asymmetric organic catalysis as the activation substrate effect huge advantage by people cognition.A lot of organic catalysts has all proved effective hydrogen bond donor.Wherein thiocarbamide (urea) catalyzer improves its reactive behavior owing to contain two N-H parts that can constitute the bidentate hydrogen bond in its structure thereby can effectively form hydrogen bond with substrate.Recently, people such as Takemoto develop a kind of difunctional thiourea catalyst 1 that has the tertiary amine part, and use it for catalysis asymmetric Michael Reaction (J.Am.Chem.Soc.2005,127,119) and aza-Henry reaction (Org.Lett.2004,6,625), product has all obtained very high ee value (93%, 75%).Berkessel group is same reacts with having tertiary amine part difunctional thiourea catalyst catalysis vinyl carbinol and racemize azlactone that to have obtained the ee value be the alpha-amino acid derivatives (J.Am.Chem.Soc.2003,125,12672) of 78-95%.Tsogoeva group has then synthesized a kind of difunctional thiourea catalyst 2 that has the primary amine part, and in asymmetric Michael addition reaction, verified the catalytic performance of catalyzer, the Michael product has obtained 86% ee value (Chem.Pharm.Bull.2004 in the short period of time, 52,477).
The thiocarbamide micromolecule catalyst has been widely used in the asymmetric synthesis, functionalization ionic compound (as the Chiral Amine ionic compound) then has catalytic activity efficiently, it can be dissolved in green solvent (as water, polyoxyethylene glycol), and can be repeatedly used, simultaneously can also provide ionic environment, therefore in conjunction with the advantage of the two, we design the synthetic a series of ionic compound that contains Chiral Amine-thiocarbamide (urea) structure, are not seen in report both at home and abroad as yet.
(3) summary of the invention
The object of the present invention is to provide a kind of ionic compound that contains Chiral Amine-thiocarbamide (urea) structure.
Another object of the present invention is to provide the preparation method of the ionic compound that contains Chiral Amine-thiocarbamide (urea) structure.
A further object of the present invention be to provide contain Chiral Amine-thiocarbamide (urea) structure ionic compound in organic asymmetric catalysis as Application of Catalyst and in chiral recognition as the application of chiral reagent.
For reaching goal of the invention the technical solution used in the present invention be:
A kind of ionic compound that contains Chiral Amine-thiocarbamide (urea) structure, its general formula is A
+B
-Described A
+Structure is suc as formula shown in (I):
Wherein, Y is one of following:
R in its Chinese style (II)
1, R in (III)
2Be saturated alkyl, phenyl or the benzyl of 1～10 carbon atom independently of one another; R in the formula (IV)
3Saturated alkyl for hydrogen or 1～5 carbon atom;
B
-Structure is shown in formula V:
Wherein, X is oxygen or sulphur; R
4Be saturated alkyl, phenyl, benzyl, diphenyl-methyl, trityl, (the S)-1-styroyl, 3 that contains 1～10 carbon atom, 5-two trifluoromethyls, (R)-1-styroyl, 3,5-two trifluoromethyl benzyls, 3,5-diisopropyl phenyl or 3,5-di-isopropyl benzyl; R
5Saturated alkyl, phenyl or benzyl for hydrogen, 1～5 carbon atom.
R in the formula of the present invention (II)
1Be preferably methyl.
R in the formula of the present invention (III)
2Be preferably methyl.
R in the formula of the present invention (IV)
3Be preferably hydrogen or methyl.
R in the formula V of the present invention
4Elect phenyl or (S)-1-styroyl as, R
5Elect as and be hydrogen or benzyl.
The preparation method of the ionic compound of Chiral Amine-thiocarbamide of the present invention (urea) structure is: with A
+Bromine salt and B
-Sodium salt be dissolved in solvent, room temperature, stirring reaction is complete, remove solvent, solid reaction product filters with anhydrous methanol, dehydrated alcohol, methylene dichloride or trichloromethane dissolving, gets filtrate and removes solvent and promptly obtain the described ionic compound that contains Chiral Amine-thiocarbamide (urea) structure; Described A
+Bromine salt and B
-The sodium salt amount of substance ratio that feeds intake be 0.5～2: 1, A
+Bromine salt and B
-Sodium salt feed intake amount of substance than preferred 1: 1; Described solvent is tetrahydrofuran (THF) (THF), acetone, ethanol, methyl alcohol, water or wherein any two kinds mixed solution, the volume of described solvent and B
-The sodium salt amount of substance ratio that feeds intake be 10～100: 1L/mol is preferably 20～50: 1L/mol.
Solvent is the mixed solution of acetone and water among the preparation method of the ionic compound that contains Chiral Amine-thiocarbamide (urea) structure of the present invention, and described acetone and water volume ratio are 1～10: 1 mixed solution, and preferred acetone and water volume ratio are 2: 1.
The reaction times is generally 1～3 day in the method for the ionic compound that contains Chiral Amine-thiocarbamide (urea) structure of the present invention.
The ionic compound that contains Chiral Amine-thiocarbamide (urea) structure of the present invention can be used as catalyzer and is applied to obtain having the product of optical selective in organic asymmetric reaction.
The application that contains the ionic compound of Chiral Amine-thiocarbamide (urea) structure of the present invention is characterized in that described organic asymmetric reaction is Michael reaction, Aldol reaction, Baylis-Hillman reaction or Michael-Aldol cascade reaction.
The ionic compound of Chiral Amine-thiocarbamide (urea) structure that contains of the present invention is as the application of chiral recognition as chiral shift reagent.
The present invention compared with prior art, its beneficial effect is: a kind of novel ionic compound that contains Chiral Amine-thiocarbamide (urea) structure is provided, contain pyrrolidyl in this chipal compounds, thioether group, imidazole ring, pyridine and thiocarbamide functional groups such as (ureas), zwitterion all has chirality, each functional group's synergy shows good chiral induction character, as Application of Catalyst, organic asymmetric reaction is the Michael reaction to the ionic compound that contains Chiral Amine-thiocarbamide (urea) structure provided by the invention in organic asymmetric reaction, the Aldol reaction, Baylis-Hillman reaction or Michael-Aldol cascade reaction.Its advantage is that catalyst levels is few, reactive behavior is high, wide application.Especially the product that obtains in Michael reaction has higher yield and ee value in than document.The ionic compound of described in addition Chiral Amine-thiocarbamide (urea) structure also can be used as chiral shift reagent in chiral recognition.
The ionic compound that benzene is invented described Chiral Amine-thiocarbamide (urea) structure can be used as chiral reagent, catalyzer, chiral material etc. and is applied to fields such as organic synthesis, material.
(4) embodiment
The part particular compound structure that the present invention relates to is as follows:
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this.
Embodiment 1: the preparation of chirality ionic compound 1
Add 3-methyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (1mmol), (3-phenyl-thioureido) sodium acetate (1mmol), THF (60mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with trichloromethane 20mL then, remove by filter inorganic salt, obtain target compound (yield 94%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+45 °.
Embodiment 2: the preparation of chirality ionic compound 2
Add 3-methyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (1mmol), (S)-3-phenyl-2-(3-phenyl-thioureido) Sodium Propionate (1mmol), ethanol (10mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, solid dissolves with trichloromethane 20mL then, remove by filter inorganic salt, obtain target compound (yield 93%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+28.4 °.
Embodiment 3: the preparation of chirality ionic compound 3
Add 3-methyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (1mmol), (R)-3-phenyl-2-(3-phenyl-thioureido) Sodium Propionate (1mmol), methyl alcohol (60mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with trichloromethane 20mL then, remove by filter inorganic salt, obtain target compound (95%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+28.4 °.
Embodiment 4: the preparation of chirality ionic compound 4
Add 3-methyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (1mmol), (S)-3-phenyl-2-(the 3-tertiary butyl-thioureido) Sodium Propionate (1mmol), acetone (50mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with methylene dichloride 20mL then, remove by filter inorganic salt, obtain target compound (yield 90%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+32 °.
Embodiment 5: the preparation of chirality ionic compound 5
Add 3-normal-butyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (0.5mmol), (S)-3-phenyl-2-(3-benzyl-thioureido) Sodium Propionate (1mmol), acetone (50mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 2 days, after reacting completely, the decompression precipitation, solid dissolves with methylene dichloride 20mL then, remove by filter inorganic salt, obtain target compound (yield 90%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+26 °.
Embodiment 6: the preparation of chirality ionic compound 6
Add 3-sec.-propyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (2mmol), (S)-3-phenyl-2-(3-diphenyl-methyl-thioureido) Sodium Propionate (1mmol), acetone (50mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 3 days, after reacting completely, the decompression precipitation, solid dissolves with methylene dichloride 20mL then, remove by filter inorganic salt, obtain target compound (yield 95%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+30 °.
Embodiment 7: the preparation of chirality ionic compound 7
Add 3-methyl isophthalic acid-((S)-pyrrolidyl-2-methyl)-3H-imidazoles bromine salt (1mmol), (3-phenyl-thioureido) sodium acetate (1mmol), water (70mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with methylene dichloride 20mL then, remove by filter inorganic salt, obtain target compound (yield 93%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+40 °.
Embodiment 8: the preparation of chirality ionic compound 8
Add 3-methyl isophthalic acid-((S)-pyrrolidyl-2-methyl)-3H-imidazoles bromine salt (1mmol), (S)-3-phenyl-2-(3-phenyl-thioureido) Sodium Propionate (1mmol), acetone (30mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with dehydrated alcohol 20mL then, remove by filter inorganic salt, obtain target compound (yield 94%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+23 °.
Embodiment 9: the preparation of chirality ionic compound 9
Add 3-methyl isophthalic acid-((S)-pyrrolidyl-2-methyl)-3H-imidazoles bromine salt (1mmol), (R)-3-phenyl-2-(3-phenyl-thioureido) Sodium Propionate (1mmol), acetone (60mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with dehydrated alcohol 20mL then, remove by filter inorganic salt, obtain target compound (yield 90%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+25 °.
Embodiment 10: the preparation of chirality ionic compound 10
Add 3-methyl isophthalic acid-((S)-pyrrolidyl-2-methyl)-3H-imidazoles bromine salt (1mmol), (S)-3-phenyl-2-(the 3-tertiary butyl-thioureido) Sodium Propionate (1mmol), acetone (10mL) and water (10mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with dehydrated alcohol 20mL then, remove by filter inorganic salt, obtain target compound (yield 92%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+28 °.
Embodiment 11: the preparation of chirality ionic compound 11
Add 3-normal-butyl-1-((S)-pyrrolidyl-2-methyl)-3H-imidazoles bromine salt (1mmol), (S)-3-phenyl-2-(3-benzyl-thioureido) Sodium Propionate (1mmol), acetone (50mL) and water (10mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with dehydrated alcohol 20mL then, remove by filter inorganic salt, obtain target compound (yield 94%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+29 °.
Embodiment 12: the preparation of chirality ionic compound 12
Add 3-sec.-propyl-1-((S)-pyrrolidyl-2-methyl) imidazoles bromine salt (1mmol), (S)-3-phenyl-2-(3-diphenyl-methyl-thioureido) Sodium Propionate (1mmol), methyl alcohol (50mL) and water (5mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with dehydrated alcohol 20mL then, remove by filter inorganic salt, obtain target compound (yield 95%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+30 °.
Embodiment 13: the preparation of chirality ionic compound 13
Add 1-((S)-pyrrolidyl-2-methyl) pyridinium tribromide salt (1mmol), (3-phenyl-thioureido) sodium acetate (1mmol), ethanol (40mL) and water (20mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with anhydrous methanol 20mL then, remove by filter inorganic salt, obtain target compound (yield 93%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+19 °.
Embodiment 14: the preparation of chirality ionic compound 14
Add 1-((S)-pyrrolidyl-2-methyl) pyridinium tribromide salt (1mmol), (S)-3-phenyl-2-(3-phenyl-thioureido) Sodium Propionate (1mmol), methyl alcohol (40mL) and water (20mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with anhydrous methanol 20mL then, remove by filter inorganic salt, obtain target compound (yield 92%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+18 °.
Embodiment 15: the preparation of chirality ionic compound 15
Add 2-methyl isophthalic acid-((S)-pyrrolidyl-2-methyl) pyridinium tribromide salt (1mmol), (R)-3-phenyl-2-(3-phenyl-thioureido) Sodium Propionate (1mmol), acetone (40mL) and water (20mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with anhydrous methanol 20mL then, remove by filter inorganic salt, obtain target compound (yield 92%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+20 °.
Embodiment 16: the preparation of chirality ionic compound 16
Add 1-((S)-tetramethyleneimine-2-methyl) pyridinium tribromide salt (1mmol), (S)-3-phenyl-2-(3-diphenyl-methyl-thioureido) Sodium Propionate (1mmol), acetone (60mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, with anhydrous methanol 20mL dissolving, remove by filter inorganic salt then, repeat 2 times, filtrate is merged, and redistillation obtains target compound (yield 93%) after taking off most solvent.Its specific rotatory power [α]
D 20=+15 °.
Embodiment 17: the preparation of chirality ionic compound 17
Add 1-((S)-tetramethyleneimine-2-methyl) pyridinium tribromide salt (1mmol), (S)-3-phenyl-2-(the 3-tertiary butyl-thioureido) Sodium Propionate (1mmol), acetone (60mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with anhydrous methanol 20mL then, remove by filter inorganic salt, obtain target compound (yield 92%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+20 °.
Embodiment 18: the preparation of chirality ionic compound 18
Add 3-methyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (1mmol), (3-benzene-urea groups) sodium acetate (1mmol), acetone (60mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with trichloromethane 20mL then, remove by filter inorganic salt, obtain target compound (yield 95%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+44 °.
Embodiment 19: the preparation of chirality ionic compound 19
Add 3-normal-butyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (1mmol), (S)-3-phenyl-2-(3-benzyl-urea groups) Sodium Propionate (1mmol), acetone (70mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with trichloromethane 20mL then, remove by filter inorganic salt, obtain target compound (yield 90%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+27 °.
Embodiment 20: the preparation of chirality ionic compound 20
Add 3-methyl-2-((S)-pyrrolidyl-2-methylthio group)-3H-imidazoles bromine salt (1mmol), (S)-3-phenyl-2-(3-phenyl-urea groups) Sodium Propionate (1mmol), acetone (60mL) and water (30mL) in the 100mL Erlenmeyer flask, stirring at room 24h, after reacting completely, the decompression precipitation, solid dissolves with trichloromethane 20mL then, remove by filter inorganic salt, obtain target compound (yield 95%) after more most solvent being taken off in filtrate distillation.Its specific rotatory power [α]
D 20=+25 °.
Embodiment 21: the application of chirality ionic compound 2 in asymmetric Michael Reaction
Add in two mouthfuls of flasks of 20mL chirality thiocarbamide ionic compound 2 (0.025g, 0.05mmol), beta-nitrostyrene (0.0752g, 99%, 0.5mmol), pimelinketone (0.0600g, 98%, 1mmol), hexanaphthene (4mL) and propyl carbinol (1mL), at room temperature reaction 15h, ethyl acetate extraction (3 * 20mL), remove solvent, obtain target product (0.1210g, yield 97%, d/r is 97: 3, ee value 98%).
Embodiment 22: the application of chirality ionic compound 6 in asymmetric Mannich reaction
Add chirality thiocarbamide ionic compound 6 (0.053g in two mouthfuls of flasks of 20mL, 0.1mmol), formaldehyde (0.040g, 40%, 0.5mmol), pimelinketone (0.098g, 99%, 1.0mmol), P-nethoxyaniline (0.068g 1mmol) and hexanaphthene (4mL) and propyl carbinol (1mL), at room temperature reaction 18h, extracted with diethyl ether (3 * 20mL), remove solvent, obtain target product (0.108g, yield 93%, ee value 54%).
Embodiment 23: the application of chirality ionic compound 20 in asymmetric Baylis-Hillman reaction
Add in two mouthfuls of flasks of 20mL chirality thiocarbamide ionic compound 20 (0.049g, 0.0001mol), hexanaphthene formaldehyde (0.056g, 99%, 0.5mmol), cyclonene (0.096g, 99%, 0.1mmol), DABCO (0.106g, 99%, 0.5mmol), toluene (4mL) and methyl alcohol (1mL), at room temperature reaction 120h, extracted with diethyl ether (3 * 20mL), remove solvent, obtain target product (0.088g, yield 85%, ee value 60%).
Embodiment 24: add chirality thiocarbamide ionic compound 2 (0.025g in chirality ionic compound 2 two mouthfuls of flasks of application 20mL in asymmetric Michael-Aldol reaction, 0.05mmol), phenylacrolein (0.033g, 0.25mmol), salicylic aldehyde (0.031g, 0.25mmol), 4AMS (1mg), hexanaphthene (4mL) and propyl carbinol (1mL), room temperature reaction 3 days, extracted with diethyl ether (3 * 20mL), remove solvent, obtain target product (0.05g, yield 85%, ee value 50%).
Embodiment 25: the application of chirality ionic compound 2 in chiral recognition
In the nuclear-magnetism pipe, add chirality thiocarbamide ionic compound 2 (0.015g, 0.03mmol), α-methoxyl group-α-trifluoromethyl phenylacetic acid (0.007g, 0.03mmol) and CDCl
3, in Varian 400 nuclear magnetic resonance analyser, obtain
1Branch takes place obviously to split and moves to low field in H NMR collection of illustrative plates, the methyl peak of α-methoxyl group, and Δ δ reaches 0.016ppm.
Claims (10)
1. ionic compound that contains Chiral Amine-thiocarbamide or Chiral Amine-urea structure, its general formula is A
+B
-Described A
+Structure is suc as formula shown in (I):
Wherein, Y is one of following:
R in its Chinese style (II)
1, R in (III)
2Be saturated alkyl, phenyl or the benzyl of 1～10 carbon atom independently of one another; R in the formula (IV)
3Saturated alkyl for hydrogen or 1～5 carbon atom;
B
-Structure is shown in formula V:
Wherein, X is oxygen or sulphur; R
4Be saturated alkyl, phenyl, benzyl, diphenyl-methyl, trityl, (the S)-1-styroyl, 3 that contains 1～10 carbon atom, 5-two trifluoromethyls, (R)-1-styroyl,, 3,5-two trifluoromethyl benzyls, 3,5-diisopropyl phenyl or 3,5-di-isopropyl benzyl; R
5Saturated alkyl, phenyl or benzyl for hydrogen, 1～5 carbon atom.
2. the ionic compound that contains Chiral Amine-thiocarbamide or Chiral Amine-urea structure as claimed in claim 1 is characterized in that the R in the described formula (II)
1Be methyl.
3. the ionic compound that contains Chiral Amine-thiocarbamide or Chiral Amine-urea structure as claimed in claim 1 is characterized in that the R in the described formula (III)
2Be methyl.
4. the ionic compound that contains Chiral Amine-thiocarbamide or Chiral Amine-urea structure as claimed in claim 1 is characterized in that R in the described formula (IV)
3Be hydrogen or methyl.
5. the ionic compound that contains Chiral Amine-thiocarbamide or Chiral Amine-urea structure as claimed in claim 1 is characterized in that R in the described formula V
4For phenyl or (S)-and the 1-styroyl, R
5Be hydrogen or benzyl.
6. a method for preparing the ionic compound of Chiral Amine-thiocarbamide as claimed in claim 1 or Chiral Amine-urea structure is characterized in that: with A
+Bromine salt and B
-Sodium salt be dissolved in solvent, room temperature, stirring reaction is complete, remove solvent, solid reaction product filters with anhydrous methanol, dehydrated alcohol, methylene dichloride or trichloromethane dissolving, gets filtrate and removes solvent and promptly obtain the described chirality ionic compound that contains Chiral Amine-thiocarbamide or Chiral Amine-urea structure; Described A
+Bromine salt and B
-The sodium salt amount of substance ratio that feeds intake be 0.5～2: 1, described solvent is THF, acetone, ethanol, methyl alcohol, water or wherein any two kinds mixed solution, the feed intake ratio of amount of substance of the volume of described solvent and the sodium salt of B-is 10～100: 1L/mol.
7. the preparation method who contains the ionic compound of Chiral Amine-thiocarbamide or Chiral Amine-urea structure as claimed in claim 6 is characterized in that described solvent is the mixed solution of acetone and water, and described acetone and water volume ratio are 1～10: 1.
8. the ionic compound that contains Chiral Amine-thiocarbamide or Chiral Amine-urea structure as claimed in claim 1 in organic asymmetric reaction as Application of Catalyst; Described organic asymmetric reaction is Michael reaction, Aldol reaction, Baylis-Hillman reaction or Michael-Aldol cascade reaction.
The ionic compound of structure shown in 2 in the chiral recognition of α-methoxyl group-α-trifluoromethyl phenylacetic acid as the application of chiral shift reagent;
The ionic compound of structure shown in 6 in Mannich reaction as Application of Catalyst;
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