CN101768118A - Bi-imidazoline diphenylamine compound and preparation method thereof - Google Patents
Bi-imidazoline diphenylamine compound and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a bi-imidazoline diphenylamine compound and a preparation method thereof. The structure of the bi-imidazoline diphenylamine compound is shown in graph 1; the preparation thereof includes that: 2,2'-dicarboxylate diphenylamine reacts with thionyl chloride to obtain acyl chloride; the acyl chloride is compounded with ethylenediamine derivant amide to obtain bi-amino amide derivant; the bi-amino amide derivant reacts with the mixture of triphenyl phosphate and oxygen anhydride trifluoromethane sulfonate as cyclization reagent to obtain the bi-imidazoline diphenylamine compound. The bi-imidazoline diphenylamine compound preparation method is simple and requires mild reaction conditions; the chirality bi-imidazoline diphenylamine compound can be used as ligand to react with transition metal ions to obtain chirality catalyst through complexation for catalyzing asymmetric reactions.
Description
Technical field
The invention belongs to the synthetic and chirality synthesis technical field of organic compound, be specifically related to a kind of novel bi-imidazoline ligand compound and preparation method.
Background technology
Chipal compounds has important use in fields such as medicine, agricultural chemicals, spices and liquid crystal materials.The key of catalysis asymmetric synthesis chipal compounds is the chiral catalyst technology.Design synthesizes to have the chiral ligand of good catalytic compound and chiral catalyst, and the asymmetry catalysis method that develops new high enantioselectivity has crucial meaning for asymmetric synthesis research and industrial application.In the chiral ligand of ligating atoms such as numerous nitrogenous, sulphur, phosphorus, chirality bisoxazoline part is to be considered to a class " advantage or franchise " part, this part is easy to preparation, chirality derives from optically active amino acids or the chiral amino alcohol that is very easy to obtain, and the structure regulating ratio is easier to.The complexing of bisoxazoline part and each metal ion species can obtain chirality bisoxazoline metal complex catalysts, they cause scientist's very big interest (Chem.Rev.2006 because of have good catalytic activity in a series of asymmetric reactions, 106,3561; Chem.Rev.2009,109,2505).
The analogue of Zuo Wei oxazoline, tetrahydroglyoxaline and derivative thereof are the very important biological activity heterogeneous ring compounds of a class, have sterilization, weeding, desinsection and medicinal activity as the imidazolone type heterocycle, have broad application prospects.In recent years, optically active tetrahydroglyoxaline also successfully is used for a series of asymmetric catalysis such as asymmetric hydrogenation, asymmetric Epoxidation, asymmetric Heck reaction, asymmetric Henry and asymmetric rearrangement of alkene as the catalyzer of chiral ligand and metal-complexing formation.Studies show that, reactive behavior is not only relevant with the space structure of chiral imidazole quinoline part with stereoselectivity, also relevant with electronic effect, and can come by the substituting group on the nitrogen in the change tetrahydroglyoxaline part electronic effect is regulated to improve catalytic activity and selectivity.Compare Yu the development of bisoxazoline, the kind and the quantity of synthetic tetrahydroglyoxaline part are also very limited at present, can be applicable to that the part in the multiple asymmetric catalysis is rare especially.Therefore, the chiral imidazole quinoline part of design and composite structure novelty is with the preparation chiral catalyst, and it is significant to study their catalytic asymmetric reactions.
Summary of the invention
In order to increase the kind of bi-imidazoline compounds, expand them in chirality synthetic technology and other Application for Field, the purpose of this invention is to provide a kind of novel bi-imidazoline diphenylamine compound and preparation method thereof, described method can prepare chirality and achiral bi-imidazoline diphenylamine compound.
The objective of the invention is to be achieved through the following technical solutions.
A kind of bi-imidazoline diphenylamine compound, its structural formula be as shown in Equation 1:
Wherein, R
1Alkyl, phenyl or benzyl for C1～C6; R
2Alkyl or phenyl for hydrogen, C1～C6; R
1And R
2Separate or connect into ring; R
3Alkyl, benzyl, benzoyl, methylsulfonyl, benzenesulfonyl or p-toluenesulfonyl for hydrogen, C1～C6.
R
1Preferentially be selected from phenyl, benzyl, sec.-propyl, isobutyl-, the tertiary butyl; R
2Be preferably hydrogen, phenyl; R
1And R
2Can also connect into ring-type by four carbon atom, be butylidene; R
3Be preferably benzenesulfonyl or p-toluenesulfonyl.
Bi-imidazoline part of the present invention has chiral centre, has optically active isomer, and the equal amount of mixture of two enantiomers then becomes racemic modification.Bi-imidazoline part of the present invention comprises racemic modification, (R)-isomer and (S)-isomer, and racemic modification, (R)-isomer and (S)-isomer have identical chemical structural formula, have different three-dimensional arrangements and rotary light performance.
The preparation method of bi-imidazoline diphenylamine compound of the present invention is: with 2,2 '-dicarboxyl pentanoic and thionyl chloride reaction obtain corresponding two chloride compounds, this pair chloride compounds synthesizes two aminoamide derivatives with the ethylene diamine derivative amidation again, the mixture stirring reaction of two then aminoamide derivatives and triphenylphosphinc oxide and Trifluoromethanesulfonic anhydride, the reaction cancellation separates obtaining bi-imidazoline diphenylamine compound.Its concrete preparation process can be as follows:
1) with 2,2 '-dicarboxyl pentanoic mixes post-heating to back flow reaction by a certain percentage with thionyl chloride, obtains two acyl chlorides (as shown in the formula 3 compounds), and reaction formula is as follows;
Wherein, 2,2 '-dicarboxyl pentanoic and thionyl chloride are preferably pressed the mixed of 1mmol: 2～10mL, are heated to back flow reaction 2～10 hours, and excessive thionyl chloride is removed in decompression then, obtains two acyl chlorides.
2) in the presence of triethylamine, the synthetic two aminoamide derivatives (as shown in the formula 2 compounds) of the above-mentioned pair of acyl chlorides and ethylene diamine derivative (as shown in the formula 4 compounds) reaction, reaction formula is as follows:
Step 2) detailed process is: at first above-mentioned pair of acyl chlorides is dissolved in the organic solvent; In another container, ethylene diamine derivative and triethylamine also are dissolved in the organic solvent simultaneously, and are cooled to 0 ℃; Then the organic solution of two acyl chlorides is added drop-wise in the organic solution of the ethylene diamine derivative of precooling and triethylamine, dropwised under the mixture room temperature of back stirring reaction 10～48 hours; The cancellation reaction, organic phase washes after drying with water, concentrates, and column chromatography for separation obtains two aminoamide derivatives.
Above-mentioned organic solvent is an inert organic solvents with respect to reactant, is preferably methylene dichloride, and the amount ratio that two acyl chlorides is dissolved in methylene dichloride is two acyl chlorides: methylene dichloride is 1mmol: 10～30mL; And the amount ratio of ethylene diamine derivative, triethylamine and methylene dichloride is an ethylene diamine derivative: triethylamine: methylene dichloride=1mmol: 2～5mmol: 2～10mL.
Under the room temperature behind the stirring reaction certain hour, preferably with saturated aqueous ammonium chloride cancellation reaction, organic phase washes with water, separatory after the washing, with the organic phase anhydrous sodium sulfate drying, concentrated solution separates through silica gel column chromatography then, and developping agent is the mixture of sherwood oil and ethyl acetate, sherwood oil: the volume ratio of ethyl acetate is 2: 1 to 1: 1, obtains two aminoamide derivatives.
3) the two aminoamide derivatives triphenylphosphinc oxide (Ph that step 2) obtains
3PO) and Trifluoromethanesulfonic anhydride (Tf
2O) mixture reacts bi-imidazoline diphenylamine compound shown in the acquisition formula 1 as closing cyclization reagent, and is as follows:
Be preferably 1mmol as the triphenylphosphinc oxide that closes cyclization reagent and the amount ratio of Trifluoromethanesulfonic anhydride: 0.5～1mmol, and the solvent of above-mentioned reaction is preferably methylene dichloride.
The detailed process of reaction is preferably: add earlier triphenylphosphinc oxide and methylene dichloride in the exsiccant reaction vessel, reaction solution is cooled to-10～10 ℃, add Trifluoromethanesulfonic anhydride again, wherein the amount ratio of triphenylphosphinc oxide, Trifluoromethanesulfonic anhydride and methylene dichloride is a triphenylphosphinc oxide: Trifluoromethanesulfonic anhydride: methylene dichloride=1mmol: 0.5～1mmol: 1～10mL, and reaction mixture was-10～10 ℃ of stirring reactions 0.5～2 hour; Slowly add above-mentioned steps 2 then) dichloromethane solution of two aminoamide derivatives of preparation, finish, reaction mixture was-10～20 ℃ of stirrings 1～5 hour; Reaction saturated sodium bicarbonate aqueous solution cancellation; Separate organic phase, the water dichloromethane extraction, and merge organic phase; The organic phase anhydrous sodium sulfate drying, removal of solvent under reduced pressure; Crude product separates with silica gel column chromatography, makees eluent with methylene dichloride, obtains bi-imidazoline diphenylamine compound.
Positively effect of the present invention:
The invention provides the novel bi-imidazoline diphenylamine compound of a class, the preparation method of this compounds is simple, the reaction conditions gentleness, and can prepare chirality and achiral bi-imidazoline diphenylamine compound.Bi-imidazoline diphenylamine compound of the present invention can be used as part, forms complex compound with metal ion.For example, the chirality bi-imidazoline diphenylamine compound is made the chiral ligand compound can form the complex compound chiral catalyst with transition metal, have good catalytic performance, study the catalytic activity of these new chiral catalysts, can develop the asymmetry catalysis synthetic method efficient, that selectivity is good.One of chirality bi-imidazoline ligand compound purposes of the present invention is made this compound zinc metal complex chiral catalyst exactly, is used for the asymmetric Friedel-Crafts alkylated reaction of catalysis.The complex compound of bi-imidazoline diphenylamine compound and zinc has catalytic activity and stereoselectivity preferably in the Friedel-Crafts of indoles and nitroolefin alkylated reaction, enantioselectivity can reach 98%ee.
Embodiment
Further describe the present invention below in conjunction with specific embodiment, but the invention is not restricted to following embodiment.
Embodiment one: 2,2 '-two [(S)-and 1-(4-Methyl benzenesulfonyl base)-4-benzylimidazoline-2-yl]-1,1 '-pentanoic (1a) preparation
1) add 2 in round-bottomed flask, (514mg, 2.0mmol) and thionyl chloride (5mL), reflux 4 hours removes excessive thionyl chloride under reduced pressure and obtains two acyl chlorides, and is dissolved in methylene dichloride (30mL) 2 '-dicarboxyl pentanoic then.
2) in another round-bottomed flask, add N-[(2S)-2-amino-2-phenylethyl]-4-methyl benzenesulfonamide (1.160g, 4mmol), triethylamine (1.4mL, 10mmol) and methylene dichloride (20mL), mixture is chilled to 0 ℃, dropwise drips two solution of acid chloride of step 1) preparation.Finish, mixture was stirring at room 24 hours.The saturated aqueous ammonium chloride cancellation is used in reaction, and organic phase washes with water.Separatory after the washing, then with the organic phase anhydrous sodium sulfate drying, concentrate after silica gel column chromatography separates, developping agent is the mixture of sherwood oil and ethyl acetate, sherwood oil: the volume ratio of ethyl acetate is 2: 1 to 1: 1, obtain 2,2 '-two [N-[(S)-2-(4-Methyl benzenesulfonyl amino)-1-phenylethyl] amido]-1,1 '-pentanoic (2a) 426mg, productive rate is 71%, white solid, fusing point: 128-130 ℃.
3) in the exsiccant reaction tubes, add triphenylphosphinc oxide (1.596g, 5.74mmol) and methylene dichloride (10mL).Reaction solution is cooled to 0 ℃, and the adding Trifluoromethanesulfonic anhydride (0.472mL, 2.87mmol).Reaction mixture stirred 0.5 hour at 0 ℃, slowly add above-mentioned steps 2 then) preparation 2,2 '-two [N-[(S)-2-(4-Methyl benzenesulfonyl amino)-1-phenylethyl] amido]-1,1 '-pentanoic (2a) (766mg, methylene dichloride 0.956mmol) (10mL) solution.Finish, reaction mixture stirred 2 hours at 0 ℃.Reaction saturated sodium bicarbonate aqueous solution cancellation.Separate organic phase, water dichloromethane extraction (2 * 10mL).Merge organic phase, use anhydrous sodium sulfate drying, removal of solvent under reduced pressure.Crude product separates with silica gel column chromatography, makees eluent with methylene dichloride, obtain 2,2 '-two [(S)-and 1-(4-Methyl benzenesulfonyl base)-4-benzylimidazoline-2-yl]-1,1 '-pentanoic (1a) 570mg, productive rate 78%, white solid, fusing point 164-166 ℃, [α]
D 20=+121.5 (c 0.54, CH
2Cl
2).
Embodiment two: 2,2 '-two [(S)-and 4-benzyl-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1, the preparation of 1 '-pentanoic (1b)
1) with embodiment one step 1).
2) with embodiment one step 2), the difference is that N-[(2S)-2-amino-2-phenylethyl]-4-methyl benzenesulfonamide (1.160g, 4mmol) change N-[(2S into)-2-amino-3-phenyl propyl]-(1.216g 4mmol), obtains 2 to the 4-methyl benzenesulfonamide, 2 '-two [N-[(S)-1-benzyl-2-(4-Methyl benzenesulfonyl amino) ethyl] amido]-1,1 '-pentanoic (2b) 1.003g, productive rate is 60%, white solid, fusing point 110-112 ℃, [α]
D 20=-59.9 (c 0.68, CH
2Cl
2).
3) with embodiment one step 3); the difference is that 2; 2 '-two [N-[(S)-2-(4-Methyl benzenesulfonyl amino)-1-phenylethyl] amido]-1; 1 '-pentanoic (2a) (766mg; 0.956mmol) change 2 into; 2-pair [N-[(S)-1-benzyl-2-(4-Methyl benzenesulfonyl amino) ethyl] amido]-1; (990mg 1.194mmol), obtains 2 to 1 '-pentanoic (2b); 2 '-two [(S)-and 4-benzyl-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1; 1 '-pentanoic (1b) 826mg, productive rate 87%, white solid; fusing point 215-217 ℃, [α]
D 20=+34.4 (c 0.62, CH
2Cl
2).
Embodiment three: 2,2 '-two [(S)-and 4-sec.-propyl-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1, the preparation of 1 '-pentanoic (1c)
1) with embodiment one step 1).
2) with embodiment one step 2), the difference is that N-[(2S)-2-amino-2-phenylethyl]-4-methyl benzenesulfonamide (1.160g, 4mmol) change N-[(2S into)-2-amino-3-methyl butyl]-(1.024g 4mmol), obtains 2 to the 4-methyl benzenesulfonamide, 2 '-two [N-[(S)-2-methyl isophthalic acid-[(4-Methyl benzenesulfonyl amino) methyl] propyl group] amido]-1,1 '-pentanoic (2c) 943mg, productive rate is 64%, white solid, fusing point 111-113 ℃, [α]
D 20=-61.6 (c 0.79, CH
2Cl
2).
3) with embodiment one step 3); the difference is that 2; 2 '-two [N-[(S)-2-(4-Methyl benzenesulfonyl amino)-1-phenylethyl] amido]-1; 1 '-pentanoic (2a) (766mg; 0.956mmol) change 2 into; 2 '-two [N-[(S)-2-methyl isophthalic acid-[(4-Methyl benzenesulfonyl amino) methyl] propyl group] amido]-1; (586mg 0.8mmol), obtains 2 to 1 '-pentanoic (2c); 2 '-two [(S)-and 4-sec.-propyl-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1; 1 '-pentanoic (1c) 496mg, productive rate 89%, white solid; fusing point 200-201 ℃, [α]
D 20=+96.6 (c 0.75, CH
2Cl
2).
Embodiment four: 2,2 '-two [(S)-and the 4-tertiary butyl-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1, the preparation of 1 '-pentanoic (1d)
1) with embodiment one step 1).
2) with embodiment one step 2), the difference is that 2,2 '-dicarboxyl pentanoic consumption is 386mg (1.5mmol), with N-[(2S)-2-amino-2-phenylethyl]-4-methyl benzenesulfonamide (1.160g, 4mmol) change N-[(2S into)-2-amino-3, the 3-dimethylbutyl]-4-methyl benzenesulfonamide (810mg, 3mmol), obtain 2,2 '-two [N-[(S)-2,2-dimethyl-1-[(4-Methyl benzenesulfonyl amino) methyl] propyl group] amido]-1,1 '-pentanoic (2d) 786mg, productive rate is 69%, white solid, fusing point 121-123 ℃, [α]
D 20=-47.9 (c 0.79, CH
2Cl
2).
3) with embodiment one step 3); the difference is that 2; 2 '-two [N-[(S)-2-(4-Methyl benzenesulfonyl amino)-1-phenylethyl] amido]-1; 1 '-pentanoic (2a) (766mg; 0.956mmol) change 2 into; 2 '-two [N-[(S)-2,2-dimethyl-1-[(4-Methyl benzenesulfonyl amino) methyl] propyl group] amido]-1,1 '-pentanoic (2d) (381mg; 0.5mmol); obtain 2,2 '-two [(S)-and the 4-tertiary butyl-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1,1 '-pentanoic (1d) 341mg; productive rate 94%; white solid, fusing point 249-250 ℃, [α]
D 20=+87.4 (c 0.51, CH
2Cl
2).
Embodiment five: 2,2 '-two [(4S, 5S)-4,5-butylidene-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1, the preparation of 1 '-pentanoic (1e)
1) with embodiment one step 1).
2) with embodiment one step 2), the difference is that 2,2 '-dicarboxyl pentanoic consumption is 257mg (1mmol), with N-[(2S)-2-amino-2-phenylethyl]-4-methyl benzenesulfonamide (1.160g, 4mmol) change N-[(1S into, 2S)-2-aminocyclohexane-1-yl]-4-methyl benzenesulfonamide (536mg, 2mmol), obtain 2,2 '-two [N-[(1S, 2S)-and 2-[(4-Methyl benzenesulfonyl amino) hexanaphthene-1-yl] amido]-1,1 '-pentanoic (2e) 524mg, productive rate is 69%, white solid, fusing point 143-145 ℃, [α]
D 20=-75.3 (c 0.64, CH
2Cl
2).
3) with embodiment one step 3); the difference is that 2; 2 '-two [N-[(S)-2-(4-Methyl benzenesulfonyl amino)-1-phenylethyl] amido]-1; (766mg 0.956mmol) changes 2,2 '-two [N-[(1S into to 1 '-pentanoic (2a); 2S)-and 2-[(4-Methyl benzenesulfonyl amino) hexanaphthene-1-yl] amido]-1; (524mg 0.692mmol), obtains 2 to 1 '-pentanoic (2e); 2 '-two [(4S; 5S)-4,5-butylidene-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1,1 '-pentanoic (1e) 291mg; productive rate 58%; white solid, fusing point 190-191 ℃, [α]
D 20=-45.3 (c 0.51, CH
2Cl
2).
Embodiment six: 2,2 '-two [(4S, 5S)-4,5-phenylbenzene-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1, the preparation of 1 '-pentanoic (1f)
1) with embodiment one step 1).
2) with embodiment one step 2), the difference is that N-[(2S)-2-amino-2-phenylethyl]-(1.160g 4mmol) changes N-[(1S into to the 4-methyl benzenesulfonamide, 2S)-and 2-amino-1, the 2-diphenyl-ethyl]-the 4-methyl benzenesulfonamide (1.464g, 4mmol), obtain 2,2 '-two [N-[(1S, 2S)-1,2-phenylbenzene-2-[(4-Methyl benzenesulfonyl amino)] ethyl] amido]-1,1 '-pentanoic (2f) 1.348g, productive rate is 71%, white solid, fusing point 149-151 ℃, [α]
D 20=+39.8 (c 1.5, CH
2Cl
2).
3) with embodiment one step 3); the difference is that 2; 2 '-two [N-[(S)-2-(4-Methyl benzenesulfonyl amino)-1-phenylethyl] amido]-1; (766mg 0.956mmol) changes 2,2 '-two [N-[(1S into to 1 '-pentanoic (2a); 2S)-and 2-[(4-Methyl benzenesulfonyl amino) hexanaphthene-1-yl] amido]-1; (1.348g 1.41mmol), obtains 2 to 1 '-pentanoic (2f); 2 '-two [(4S; 5S)-4,5-phenylbenzene-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1,1 '-pentanoic (1f) 1.097g; productive rate 85%; white solid, fusing point 250-252 ℃, [α]
D 20=+151.0 (c 0.63, CH
2Cl
2).
Embodiment seven: asymmetry catalysis Friedel-Crafts reaction
Under nitrogen protection, in the exsiccant reaction tubes, add Zn (OTf)
2(9.3mg; 0.025mmol), 2; 2 '-two [(4S; 5S)-4; 5-phenylbenzene-1-(4-Methyl benzenesulfonyl base) tetrahydroglyoxaline-2-yl]-1,1 '-pentanoic (1f) (25.2mg, 0.028mmol) and toluene (3mL); mixture adds beta-nitrostyrene (0.5mmol) stirring at room 2 hours.Stir after 10 minutes, be cooled to-20 ℃.(58.5mg, 0.5mmol) ,-20 ℃ were stirred 24 hours down to add indoles again.Mixture separates with the alkali alumina column chromatography, is that 5: 1 to 1: 1 sherwood oil and ethyl acetate is developping agent with volume ratio, obtains colorless oil product 3-(1-phenyl-2-nitro-ethyl) indoles 119mg, productive rate 89%, [α]
D 20=-25.7 (c 0.84, CH
2Cl
2), recording enantioselectivity by HPLC is 98%ee.
Claims (10)
1. bi-imidazoline diphenylamine compound, its structure be as shown in Equation 1:
Wherein: R
1Alkyl, phenyl or benzyl for C1～C6; R
2Alkyl or phenyl for hydrogen, C1～C6; R
1And R
2Separate or connect into ring; R
3Alkyl, benzyl, benzoyl, methylsulfonyl, benzenesulfonyl or p-toluenesulfonyl for hydrogen, C1～C6.
2. bi-imidazoline diphenylamine compound as claimed in claim 1 is characterized in that, described R
1Be phenyl, benzyl, sec.-propyl, isobutyl-or the tertiary butyl.
3. bi-imidazoline diphenylamine compound as claimed in claim 1 is characterized in that, described R
2Be hydrogen or phenyl.
4. bi-imidazoline diphenylamine compound as claimed in claim 1 is characterized in that, described R
1And R
2Connect into ring-type, be butylidene.
5. bi-imidazoline diphenylamine compound as claimed in claim 1 is characterized in that, described R
3Be benzenesulfonyl or p-toluenesulfonyl.
6. the preparation method of a bi-imidazoline diphenylamine compound comprises the steps:
1) 2,2 '-dicarboxyl pentanoic and thionyl chloride reaction obtain as shown in the formula the two chloride compounds shown in 3;
2) the two aminoamide derivatives shown in the ethylene diamine derivative amide compound accepted way of doing sth 2 shown in two chloride compounds and the formula 4 shown in the formula 3;
3) mixture with triphenylphosphinc oxide and Trifluoromethanesulfonic anhydride serves as to close cyclization reagent, and two aminoamide derivatives close ring and obtain bi-imidazoline diphenylamine compound shown in the formula 1 shown in the formula 2;
Wherein the structural formula of each compound is as follows:
Above-mentioned various in: R
1Alkyl, phenyl or benzyl for C1～C6; R
2Alkyl or phenyl for hydrogen, C1～C6; R
1And R
2Separate or connect into ring; R
3Alkyl, benzyl, benzoyl, methylsulfonyl, benzenesulfonyl or p-toluenesulfonyl for hydrogen, C1～C6.
7. preparation method as claimed in claim 6, it is characterized in that, described step 1) 2,2 '-dicarboxyl pentanoic and thionyl chloride are pressed 1mmol: the mixed of 2～10mL, be heated to back flow reaction 2～10 hours, excessive thionyl chloride is removed in decompression then, obtains two chloride compounds shown in the formula 3.
8. preparation method as claimed in claim 6 is characterized in that, described step 2) at first two chloride compounds shown in the formula 3 are dissolved in and obtain organic solution A in the organic solvent; In another container, ethylene diamine derivative shown in the formula 4 and triethylamine also be dissolved in simultaneously and obtain organic solution B in the organic solvent, and be cooled to 0 ℃; Described organic solution A is added drop-wise among the described organic solution B of precooling then, dropwised under the mixture room temperature of back stirring reaction 10～48 hours; Then cancellation reaction, organic phase washes after drying with water, concentrates, and column chromatography for separation obtains two aminoamide derivatives shown in the formula 2.
9. preparation method as claimed in claim 8 is characterized in that step 2) described in organic solvent be methylene dichloride, the amount ratio that two chloride compounds shown in the formula 3 is dissolved in methylene dichloride is two acyl chlorides: methylene dichloride is 1mmol: 10～30mL; The amount ratio that ethylene diamine derivative shown in the formula 4 and triethylamine is dissolved in methylene dichloride is an ethylene diamine derivative: triethylamine: methylene dichloride=1mmol: 2～5mmol: 2～10mL; React with the saturated aqueous ammonium chloride cancellation reaction back; Organic phase is used the silica gel column chromatography separated product through washing, drying and after concentrating.
10. preparation method as claimed in claim 6, it is characterized in that, the solvent of described step 3) reaction is a methylene dichloride, earlier triphenylphosphinc oxide is added in the methylene dichloride, be cooled to-10～10 ℃, add Trifluoromethanesulfonic anhydride again, wherein triphenylphosphinc oxide: Trifluoromethanesulfonic anhydride: the amount ratio of methylene dichloride is 1mmol: 0.5～1mmol: 1～10mL, and mixture stirred 0.5～2 hour at-10～10 ℃; Slowly add shown in the formula 2 dichloromethane solution of two aminoamide derivatives then, finish, reaction mixture was-10～20 ℃ of stirring reactions 1～5 hour; Then with saturated sodium bicarbonate aqueous solution cancellation reaction; Separate organic phase, the water dichloromethane extraction merges organic phase and carries out drying, and removal of solvent under reduced pressure obtains crude product then; Crude product separates with silica gel column chromatography, makees eluent with methylene dichloride, obtains bi-imidazoline diphenylamine compound shown in the formula 1.
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| CN101962366A (en) * | 2010-09-15 | 2011-02-02 | 北京理工大学 | Diphenyl thioether linked bis-imidazoline ligand compound and preparation method thereof |
| CN102924380A (en) * | 2012-11-13 | 2013-02-13 | 齐鲁动物保健品有限公司 | Preparation method of imidocarb |
| CN108424391A (en) * | 2018-05-16 | 2018-08-21 | 江苏师范大学 | The double imidazoles chiral ligands of double benzenesulfonyls and its synthetic method |
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| CN100478333C (en) * | 2007-01-29 | 2009-04-15 | 郑州大学 | Chiral and non-chiral diimidazolinylbenzene compounds and synthesis method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101962366A (en) * | 2010-09-15 | 2011-02-02 | 北京理工大学 | Diphenyl thioether linked bis-imidazoline ligand compound and preparation method thereof |
| CN102924380A (en) * | 2012-11-13 | 2013-02-13 | 齐鲁动物保健品有限公司 | Preparation method of imidocarb |
| CN102924380B (en) * | 2012-11-13 | 2014-12-31 | 齐鲁动物保健品有限公司 | Preparation method of imidocarb |
| CN108424391A (en) * | 2018-05-16 | 2018-08-21 | 江苏师范大学 | The double imidazoles chiral ligands of double benzenesulfonyls and its synthetic method |
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