CN1328252C - Novel optical pure water soluble diamine and derivative, preparation method and use thereof - Google Patents
Novel optical pure water soluble diamine and derivative, preparation method and use thereof Download PDFInfo
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- CN1328252C CN1328252C CNB031351816A CN03135181A CN1328252C CN 1328252 C CN1328252 C CN 1328252C CN B031351816 A CNB031351816 A CN B031351816A CN 03135181 A CN03135181 A CN 03135181A CN 1328252 C CN1328252 C CN 1328252C
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Abstract
The present invention relates to novel water soluble chiral diamine, a derivative, a preparation method of the diamine and the derivative and an application of the diamine and the derivative, particularly a preparation method of 1, 2-diphenylethylenediamine substituted by an optical pure 2, 2'-disulfonic acid radix and N-monosulfonic acylation 1, 2-diphenylethylenediamine substituted by the optical pure 2, 2'-disulfonic acid radix and an application of the 1, 2-diphenylethylenediamine and the N-monosulfonic acylation 1, 2-diphenylethylenediamine in asymmetric catalysis. When the N-monosulfonic acylation 1, 2-diphenylethylenediamine substituted by the optical pure 2, 2'-disulfonic acid radix and the complex compounds of the transition metal in an eighth family, such as ruthenium, rhodium, iridium, etc., are used for the asymmetric catalysis transfer hydrogenation of ketonic water phase and ketonic water-organism two phases, much fragrance alkyl ketone obtains results similar to the results of homogeneous catalysis, and enantioselectivity is as high as 98% ee. Particularly, when an omega-bromo fragrance alkyl ketonic compound reacts in the medium of the water phase and the medium of the water-organism two phases, a prospective chiral omega-bromo fragrance alkyl ketonic compound or epoxide can be obtained. A catalyst still has very high conversion rate after a plurality of times of use, the enantioselectivity remains unchanged, and a surface active agent can well promote a reaction.
Description
The invention belongs to the organic chemistry asymmetric catalysis field, specifically is optical purity 2,1 of 2 '-disulfonic acid root replacement, the single sulfonylation derivative of 2-diphenyl ethylene diamine and N-and preparation and the application in asymmetry catalysis.
Green Chemistry research is directly connected to the Sustainable development of human society.In order to realize the greenization of chemical engineering, need aspect a lot of, carry out effort.The water catalyzed reaction is important content [the OrganicReactions on Aqueous Media John Wiley ﹠amp of Green Chemistry research always; Sons:New York, 1997; Organic Synthesis inWater Blacky Academic and Professional:London, England, 1998; Aqueous PhaseOrganometallic Catalysis Wiley-Vch:Weinheim, Germany, 1998].The organic reaction of metal catalytic will be carried out in water medium, and except reaction reagent will be stablized water medium, the synthesizing water-solubility part was a key point.Chiral diamine and derivative thereof are class chiral molecules highly significant, in the last few years, this quasi-molecule is used increasing in organic synthesis, especially in the asymmetric catalysis research field, in series reaction, show very high three-dimensional controllability [Angew.Chem.Int.Ed.Engl.1998,37,2580].Therefore, water-soluble chiral two amine ligands and the application in the water asymmetric catalysis thereof cause our great interest.
One of purpose of the present invention is to provide a class optically pure water-soluble diamines, and the metal complex of the water-soluble diamines of such optical activity is catalysis water and water-organic biphase asymmetric reaction effectively.Optical purity 2; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; the complex compound of 2-diphenyl ethylene diamine and ruthenium, rhodium, iridium grade in an imperial examination eight group 4 transition metals is in the water and water-organic two-phase asymmetry catalysis hydrogen transference research of aromatic alkyl ketone; majority is obtained the result suitable with homogeneous catalysis, and enantioselectivity is up to 98%ee.Reaction solution use with the immiscible organic solvent extraction product of water after, catalyzer still has very high transformation efficiency through repeatedly using, enantioselectivity remains unchanged.
Chirality ω-bromo aromatic alkyl alcohol compound is the medicine intermediate of crucial synthetic beta-adrenoceptor antagonists class medicine, till now, the effective way that can realize this ω-bromo aromatic alkyl ketone compounds chiral reduction is to utilize the asymmetric hydroboration [Angew.Chem.Int.Ed.Engl.1998 of Shou oxazole borane reagent, 37,1986].
Two of purpose of the present invention is to provide new approach for chirality ω-bromo aromatic alkyl alcohol compound and chiral epoxy thing synthetic.Optical purity 2 under water and water-organic two-phase condition; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; the hydrogen transfer reduction of the complex catalysis of 2-diphenyl ethylene diamine and ruthenium, rhodium, iridium grade in an imperial examination eight group 4 transition metals; by controlled temperature, can optionally obtain chirality ω-bromo aromatic alkyl alcohol compound or chiral epoxy thing.This method is compared with Shou oxazole borane reagent, operate easier, the condition milder; Because water cooked solvent, cleaning, more cheap more.
As most water asymmetric catalysis [Adv.Synth.Catal.2002,344,221], tensio-active agent and phase-transfer catalyst all have good promoter action to this reaction.Particularly when tensio-active agent is cationic surfactant, reactive activity increases greatly and enantioselectivity also is significantly improved (as methyl phenyl ketone up to 96%ee).
The objective of the invention is to realize by following technical proposals:
Optical purity 2; 1 of 2 '-disulfonic acid root replacement; 2-diphenyl ethylene diamine and optical purity 2, the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces, the preparation method of 2-diphenyl ethylene diamine and the application in asymmetry catalysis thereof; it is characterized in that its structure is 2; 1 of 2 '-disulfonic acid root replacement, 2-diphenyl ethylene diamine and 2, the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; the 2-diphenyl ethylene diamine, its chemical structural formula is as follows:
Optical purity 2,2 '-optical purity 2,2 that the disulfonic acid root replaces '-the disulfonic acid root replaces
1, the single sulfonylation 1 of 2-diphenyl ethylene diamine N-, 2-diphenyl ethylene diamine
Wherein, R is following I-III group
And straight chained alkyl (C
1-C
18), cycloalkyl (C
3-C
10), adamantyl and other alkyl and amido (NR
2R
3), R
1Be following group :-NO
2,-OR
2, straight chained alkyl (C
1-C
18), cycloalkyl (C
3-C
10), adamantyl and other alkyl, R
2And R
3Be following group: straight chained alkyl (C
1-C
18), cycloalkyl (C
3-C
10), adamantyl and other alkyl, M
2+Be Ba
2+, Mg
2+, Ca
2+With other positive divalent ions, M
+Be Na
+, K
+, Li
+With other positive monovalent ions.
In the such scheme, optical purity 2,1 of 2 '-disulfonic acid root replacement, the preparation method of 2-diphenyl ethylene diamine, it is characterized in that optical purity 2,1 of 2 '-disulfonic acid root replacement, the 2-diphenyl ethylene diamine is by optical purity 1,2-diphenyl ethylene diamine and oleum with the dissolving of 1: 10～100 mass ratio after, obtain optical purity 2 in reaction under 0 ℃～35 ℃ the temperature after 1 day, 2 '-disulfonic acid root replace 1, the 2-diphenyl ethylene diamine, through mineral alkali neutralization, with water: the bulk specific gravity crystallization of ethanol=1: 10～100, purifying final vacuum drying obtains white solid.
In the such scheme; optical purity 2; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; the preparation method of 2-diphenyl ethylene diamine; it is characterized in that optical purity 2; 1 of 2 ' disulfonic acid root replacement; 2-diphenyl ethylene diamine and water are alkalescence with 1: 10～50 the back inorganic adjusting PH with base that adds 1.0～1.5 times of mol ratios of mass ratio dissolving; the tensio-active agent or the phase-transfer catalyst that add 0.1～0.2 times of mol ratio; drip the SULPHURYL CHLORIDE of 1.0～1.5 times of mol ratios; obtained optical purity 2 in 8～45 hours 0 ℃～35 ℃ reactions; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; 2-diphenyl ethylene diamine, this water-soluble chiral diamines are with water: the bulk specific gravity crystallization final vacuum of ethanol=1: 10～100 dry white solid.
In the such scheme, the mineral alkali of use is: sodium hydroxide, lithium hydroxide, potassium hydroxide, hydrated barta, magnesium hydroxide, calcium hydroxide, yellow soda ash, Quilonum Retard, salt of wormwood, barium carbonate, magnesiumcarbonate, lime carbonate, sodium bicarbonate, saleratus.
In the such scheme, optical purity 2, the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces, the application of 2-diphenyl ethylene diamine in asymmetry catalysis, it is characterized in that optical purity 2, the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces, 2-diphenyl ethylene diamine and ruthenium, rhodium, the complex compound of iridium grade in an imperial examination eight group 4 transition metals, in the presence of tensio-active agent or phase-transfer catalyst, the asymmetry catalysis hydrogen transference research of aromatic alkyl ketone in water and water-organic two-phase, majority has been obtained the result suitable with homogeneous catalysis, enantioselectivity is up to 98%ee, and especially ω-bromo aromatic alkyl ketone compounds reacts in water and water-organic two-phase medium and can optionally obtain the chirality ω-bromo aromatic alkyl alcohol compound or the epoxide of expecting;
---will react the distilled water that uses and handle through the degassing, when carrying out under inert atmosphere, catalyzer still has very high transformation efficiency through repeatedly using, and enantioselectivity remains unchanged.
In the such scheme, aromatic alkyl ketone is IV-XIV formula compound
Wherein, R
1Be following group :-NO
2,-OR
2,-Cl ,-F ,-Br ,-I, straight chained alkyl (C
1-C
18), cycloalkyl (C
3-C
10), adamantyl and other alkyl, R
2Be following group: straight chained alkyl (C
1-C
18), cycloalkyl (C
3-C
10), adamantyl, alpha-brominated alkyl, n=1-3, X=O, S, N.
In the such scheme, organic phase is the mixed solvent of ester class (manthanoate, acetic ester, propionic ester, butyric ester etc.), ethers (ether, glycol dimethyl ether, methyl tert butyl ether, tetrahydrofuran (THF) etc.), alkanes (sherwood oil, normal hexane, hexanaphthene etc.), haloalkane hydro carbons (methylene dichloride, trichloromethane, tetracol phenixin, 1,2-ethylene dichloride etc.), aromatics (benzene,toluene,xylene, trimethylbenzene etc.) and wherein two or more (comprising two kinds).
In the such scheme, tensio-active agent or phase-transfer catalyst are: aniorfic surfactant (Sodium palmityl sulfate, sodium cetanesulfonate, tetradecyl sodium sulfonate etc.), cationic surfactant (hexadecyl trialkyl brometo de amonio, tetradecyl trialkyl brometo de amonio etc.), double ion type tensio-active agent (the hexadecyl trialkyl brometo de amonio that sulfonic acid replaces, the tetradecyl trialkyl brometo de amonio that sulfonic acid replaces etc.), nonionic surface active agent (polyoxyethylene glycol-100, polyoxyethylene glycol-400, polyoxyethylene glycol-2000, polyoxyethylene glycol-10000, cyclodextrin etc.), crown ether-like phase transfer catalysts (15-hat-5,18-hat-6 etc.), quaternary ammonium salt-type phase transfer catalyst (tetra-alkyl ammonium chloride, the tetraalkyl brometo de amonio, tetraalkyl ammonium iodide etc.), wherein the described tensio-active agent of claim 5 is a cationic surfactant (hexadecyl trialkyl brometo de amonio, tetradecyl trialkyl brometo de amonio etc.), quaternary ammonium salt-type phase transfer catalyst (tetra-alkyl ammonium chloride, the tetraalkyl brometo de amonio, tetraalkyl ammonium iodides etc.) time, reactive activity increases greatly and enantioselectivity also is significantly improved (as methyl phenyl ketone up to 96%ee).
The present invention prepares optical purity 2 first, 1 of 2 '-disulfonic acid root replacement, and the single sulfonylation derivative of 2-diphenyl ethylene diamine and N-thereof comprises following reactions steps:
Step 1: with optical purity 1, the 2-diphenyl ethylene diamine is the sulfonated optical purity 2 for preparing directly, 1 of 2 '-disulfonic acid root replacement, 2-diphenyl ethylene diamine.
Optical purity 1,2-diphenyl ethylene diamine optical purity 2,2 '-replacement of disulfonic acid root
1, the 2-diphenyl ethylene diamine
Step 2: under the alkaline condition, optical purity 2,1 of 2 '-disulfonic acid root replacement, 2-diphenyl ethylene diamine and SULPHURYL CHLORIDE reaction, purified drying obtains optical purity 2, the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces, 2-diphenyl ethylene diamine.
The optical purity 2,2 that optical purity 2,2 '-disulfonic acid root replace '-the single sulfonylation of N-that the disulfonic acid root replaces
1,2-diphenyl ethylene diamine 1,2-diphenyl ethylene diamine
Utilize optical purity 2 among the present invention first; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; the complex compound of 2-diphenyl ethylene diamine and ruthenium, rhodium, iridium grade in an imperial examination eight group 4 transition metals is in the presence of tensio-active agent or phase-transfer catalyst; water and water-organic two-phase asymmetry catalysis hydrogen transference to aromatic alkyl ketone are studied; majority has been obtained the result suitable with homogeneous catalysis, and enantioselectivity is up to 98%ee.The distilled water that reaction is used is handled through the degassing, and when carrying out under inert atmosphere, catalyzer still has very high transformation efficiency through repeatedly using, and enantioselectivity remains unchanged.When tensio-active agent is a cationic surfactant, during as CTAB (cetyl trimethylammonium bromide), reactive activity increases greatly, and enantioselectivity also be significantly improved (as methyl phenyl ketone up to 96%ee).
The present invention provides new approach for chirality ω-bromo aromatic alkyl alcohol compound and chiral epoxy thing synthetic.Optical purity 2 under water and water-organic two-phase condition; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; the hydrogen transfer reduction of the complex catalysis of 2-diphenyl ethylene diamine and ruthenium, rhodium, iridium grade in an imperial examination eight group 4 transition metals; by controlled temperature, can optionally obtain chirality ω-bromo aromatic alkyl alcohol compound or chiral epoxy thing.This method is compared with Shou oxazole borane reagent, operate easier, the condition milder; Because water cooked solvent, cleaning, more cheap more.
Be embodiments of the invention below.
Embodiment one
Optical purity 2,1 of 2 '-disulfonic acid root replacement, the preparation of 2-diphenyl ethylene diamine
With 1.000 gram (4.717mmol) [optical purity-1,2-diphenyl ethylene diamines (DPEN)], join under 0 ℃ in the 10 gram oleums, mixed solution vigorous stirring 24 hours, reaction solution becomes thick red liquid.Stir down, pour in the 50 gram trash ices, add excessive BaCO
3Solid is until pH=7-8.Filter, after filtrate concentrates, add the 10mL ethyl alcohol recrystallization and get white solid, the reversed phase chromatography column purification gets 1.765 gram white solid (R, R)-2 (yields 68%).
Embodiment two
Optical purity 2, the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces, the preparation of 2-diphenyl ethylene diamine
With 1.715 gram (3.096mmol) optical purityes 2,1 of 2 '-disulfonic acid root replacement, the 2-diphenyl ethylene diamine, 176 milligrams of (4.391mmol) sodium hydroxide are dissolved in 15mL water, add 184 milligrams of (0.676mmol) SDS (sodium lauryl sulfate).Vigorous stirring under the room temperature slowly is added drop-wise to 769 milligrams of Tosyl chlorides (3.715mmol) (being dissolved in the 30mL methylene dichloride) in the reaction system, reacts after 24 hours, filters out SDS (sodium lauryl sulfate), and the methylene dichloride separatory is removed.Aqueous phase adds 433 milligrams of (3.406mmol) anhydrous Na
2SO
4, with Ba
2+Quantitative precipitation and be converted into sodium salt.Filter out insoluble white solid (BaSO
4), after filtrate concentrates, adding the 10mL ethyl alcohol recrystallization and get white solid, the reversed phase chromatography column purification gets 1.353 gram white solid optical purityes 2, and the N-that 2 '-disulfonic acid root replaces is single to methyl benzene sulfonyl chloride 1,2-diphenyl ethylene diamine (yield 72%).
Embodiment three
The asymmetric transfer hydrogenation reaction of aqueous phase methyl phenyl ketone
With 3.1 milligrams of (0.005mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1.0mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5.0mmol) HCO then
2Na2H
2O adds 0.120mL (1.0mmol) substrate methyl phenyl ketone as hydrogen source, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying, going up the mensuration transformation efficiency by gas-chromatography at chiral column (CP-cyclodex B-236 M column) is 34.4%, enantioselectivity is 88.9%ee.
Embodiment four
The asymmetric transfer hydrogenation reaction of aqueous phase methyl phenyl ketone
With 1.5 milligrams of (0.0025mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 3.3 milligrams of (0.0055mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 0.5mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 260 milligrams of (2.5mmol) HCO then
2Na2H
2O is as hydrogen source, and 5.4 milligrams of (0.020mmol) SDS (sodium lauryl sulfate) add 0.060mL (0.5mmol) substrate methyl phenyl ketone as tensio-active agent, and vigorous stirring in 40 ℃ of oil baths was directly reacted 5 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying, (transformation efficiency is 5.3% with chirality gas Chromatographic Determination transformation efficiency and ee value to get supernatant liquor; 94%ee).
Embodiment five
The asymmetric transfer hydrogenation reaction of aqueous phase methyl phenyl ketone
With 1.5 milligrams of (0.0025mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 3.3 milligrams of (0.0055mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 0.5mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 260 milligrams of (2.5mmol) HCO then
2Na2H
2O is as hydrogen source, and 6.4 milligrams of (0.020mmol) CTAB (cetyl trimethylammonium bromide) add 0.060mL (0.5mmol) substrate methyl phenyl ketone as tensio-active agent, and vigorous stirring in 40 ℃ of oil baths was directly reacted 5 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying, (transformation efficiency is 98% with chirality gas Chromatographic Determination transformation efficiency and ee value to get supernatant liquor; 94%ee).
Embodiment six
The asymmetric transfer hydrogenation reaction of aqueous phase methyl phenyl ketone
With 1.5 milligrams of (0.0025mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 3.3 milligrams of (0.0055mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 0.5mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 260 milligrams of (2.5mmol) HCO then
2Na2H
2O is as hydrogen source, and 5.4 milligrams of (0.020mmol) SDS (sodium lauryl sulfate) add 0.060mL (0.5mmol) substrate methyl phenyl ketone as tensio-active agent, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying, going up the mensuration transformation efficiency by gas-chromatography at chiral column (CP-cyclodex B-236 M column) is 99.2%, enantioselectivity is 92.%ee.Merging concentrates then, and crude product is purified, gets 0.039 gram chiral alcohol, yield 64.1%.
Embodiment seven
The asymmetric transfer hydrogenation reaction of aqueous phase methyl phenyl ketone
With 3.1 milligrams of (0.005mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1.0mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5.0mmol) HCO then
2Na2H
2O is as hydrogen source, and 0.008mL (0.040mmol) 15-hat-5 adds 0.120mL (1.0mmol) substrate methyl phenyl ketone as the epiphase transfer catalyst, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying, going up the mensuration transformation efficiency by gas-chromatography at chiral column (CP-cyclodex B-236 M column) is 99.7%, enantioselectivity is 93.0%ee.
Embodiment eight
The asymmetric transfer hydrogenation reaction of aqueous phase methyl phenyl ketone
With 2.5 milligrams of (0.005mmol) ruthenium complex precursor [RuCl
2(benzene)]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1.0mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5.0mmol) HCO then
2Na2H
2O adds 0.120mL (1.0mmol) substrate methyl phenyl ketone as hydrogen source, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying, going up the mensuration transformation efficiency by gas-chromatography at chiral column (CP-cyclodex B-236 M column) is 66.3%, enantioselectivity is 70.9%ee.
Embodiment nine
The asymmetric transfer hydrogenation reaction of aqueous phase methyl phenyl ketone
With 3.1 milligrams of (0.005mmol) rhodium complex precursor [Cp
*RhCl
2]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1.0mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5.0mmol) HCO then
2Na2H
2O adds 0.120mL (1.0mmol) substrate methyl phenyl ketone as hydrogen source, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying, going up the mensuration transformation efficiency by gas-chromatography at chiral column (CP-cyclodex B-236 M column) is 92.3%, enantioselectivity is 83.7%ee.
Embodiment ten
The asymmetric transfer hydrogenation reaction of aqueous phase methyl phenyl ketone
With 4.0 milligrams of (0.005mmol) iridium complex precursor [Cp
*IrCl
2]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1.0mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5.0mmol) HCO then
2Na2H
2O adds 0.120mL (1.0mmol) substrate methyl phenyl ketone as hydrogen source, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying, going up the mensuration transformation efficiency by gas-chromatography at chiral column (CP-cyclodex B-236 M column) is 10.2%, enantioselectivity is 57.8%ee.
Embodiment 11
The general operation that aqueous phase methyl phenyl ketone asymmetric transfer hydrogenation recycles
With 1.5 milligrams of (0.0025mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 3.3 milligrams of (0.0055mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1mL de aerated water to methyl benzene sulfonyl chloride 1, and stir-activating is 1 hour under 40 ℃ of controlled atmospheres.Add 260 milligrams of (2.5mmol) HCO then
2Na2H
2O is as hydrogen source, and 5.5 milligrams of (0.020mmol) SDS (sodium lauryl sulfate) add 0.060mL (0.5mmol) substrate methyl phenyl ketone as tensio-active agent, vigorous stirring under the controlled atmosphere, and 40 ℃ were reacted 24 hours.Use then ether/normal hexane (v/v, 1: 1) extract fast (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Dry.Add 0.020mL (0.5mmol) 99% formic acid in the reaction system and recover system, have a large amount of bubbles to emerge, add 0.060mL (0.5mmol) substrate methyl phenyl ketone, displaced air, vigorous stirring under the controlled atmosphere, 40 ℃ were reacted 24 hours.Use then ether/normal hexane (v/v, 1: 1) extract fast (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Dry.As above use repeatedly,, still have transformation efficiency, enantioselectivity remain unchanged (95%ee) up to 93.2% to the 6th time.
Embodiment 12
The asymmetric transfer hydrogenation reaction of aqueous phase p-methyl aceto phenone
With 3.1 milligrams of (0.005mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5mmol) HCO then
2Na2H
2O is as hydrogen source, and 11 milligrams of (0.040mmol) SDS (sodium lauryl sulfate) add 0.134mL (1mmol) substrate p-methyl aceto phenone as tensio-active agent, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying concentrates, and crude product is purified, gets 0.128 gram chiral alcohol, yield 93.6%.
Embodiment 13
Aqueous phase is to the asymmetric transfer hydrogenation reaction of fluoro acetophenone
With 3.1 milligrams of (0.005mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5mmol) HCO then
2Na2H
2O is as hydrogen source, and 11 milligrams of (0.040mmol) SDS (sodium lauryl sulfate) add 0.122mL (1mmol) substrate to fluoro acetophenone as tensio-active agent, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying concentrates, and crude product is purified)], get 0.124 gram chiral alcohol, receive emerald green 88.3%.
Embodiment 14
The asymmetric transfer hydrogenation reaction of aqueous phase o-fluoro acetophenone
With 3.1 milligrams of (0.005mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5mmol) HCO then
2Na2H
2O is as hydrogen source, and 11 milligrams of (0.040mmol) SDS (sodium lauryl sulfate) add 0.123mL (1mmol) substrate o-fluoro acetophenone as tensio-active agent, and vigorous stirring in 40 ℃ of oil baths was directly reacted 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying concentrates, and crude product is purified)], get 0.137 gram chiral alcohol, yield 97.6%.
Embodiment 15
The asymmetric transfer hydrogenation of p-nitroacetophenone reaction in water/methylene dichloride two-phase system
With 3.1 milligrams of (0.005mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 6.6 milligrams of (0.011mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 1mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 520 milligrams of (5mmol) HCO then
2Na2H
2O is as hydrogen source, 11 milligrams of (0.040mmol) SDS (sodium lauryl sulfate) are as tensio-active agent, add 0.165g (1mmol) substrate p-nitroacetophenone, add behind the 1mL methylene dichloride vigorous stirring in 40 ℃ of oil baths, directly reaction 24 hours under air atmosphere.Use then ether/normal hexane (v/v, 1: 1) extract (3 * 3mL), the extraction liquid anhydrous Na
2SO
4Drying concentrates, and crude product is purified)], get 0.278 gram chiral alcohol, yield 85.8%.
The water of other ketone and water-organic two-phase asymmetric transfer hydrogenation reaction result See Figure:
88％(83％)
a，88％ee 99％(83％)
a，83％ee 19％，80％ee
100％，
b88％ee 100％，
b81％ee
66％，83％ee 21％，98％ee 13％，92％ee 72％(43％)
a，95％ee
69％，
b94％ee
The asymmetric hydrogen transfer reduction of other ketone in water and water-organic two-phase (
aData are separation yield in the bracket.
bMethylene dichloride/water two-phase system reaction result)
Embodiment 16
The asymmetric transfer hydrogenation of ω-bromoacetophenone reaction in water/methylene dichloride two-phase system
With 1.5 milligrams of (0.0025mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 3.3 milligrams of (0.0055mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 0.5mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 260 milligrams of (2.5mmol) HCO then
2Na2H
2O is as hydrogen source, 5.5 milligram (0.020mmol) SDS (sodium lauryl sulfate) is as tensio-active agent, add 99.5 milligrams of (0.5mmol) substrate ω-bromoacetophenones, add the 0.5mL methylene dichloride at last, vigorous stirring, 28 ℃ of oil baths were directly reacted 24 hours under air atmosphere, thin plate and gas chromatographic detection reaction.Extract with methylene dichloride then that (3 * 3mL), extraction liquid is through anhydrous Na
2SO
4Drying filters out Na
2SO
4, concentrate methylene dichloride, purifying get ω-pure product of bromobenzene ethanol (yield 87%, 94%ee).
Embodiment 17
The asymmetric transfer hydrogenation of ω-bromoacetophenone reaction in water/tetrahydrofuran (THF) system
With 1.5 milligrams of (0.0025mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 3.3 milligrams of (0.0055mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 0.5mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 260 milligrams of (2.5mmol) HCO then
2Na2H
2O is as hydrogen source, 5.5 milligram (0.020mmol) SDS (sodium lauryl sulfate) is as tensio-active agent, add 99.5 milligrams of (0.5mmol) substrate ω-bromoacetophenones, add the 0.5mL tetrahydrofuran (THF) at last, vigorous stirring, 60 ℃ of oil baths were directly reacted 20 hours under air atmosphere, thin plate and gas chromatographic detection reaction.Decompression extracts behind the tetrahydrofuran (THF) and to extract with methylene dichloride that (3 * 3mL), extraction liquid is through anhydrous Na
2SO
4Drying filters out Na
2SO
4, concentrate methylene dichloride, purifying get the pure product of chirality phenyl ethylene oxide (yield 63%, 94%ee).
Embodiment 18
The asymmetric transfer hydrogenation reaction of ω in water/methylene dichloride two-phase system-bromo p-nitroacetophenone
With 1.5 milligrams of (0.0025mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 3.3 milligrams of (0.0055mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 0.5mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 260 milligrams of (2.5mmol) HCO then
2Na2H
2O is as hydrogen source, 5.5 milligram (0.020mmol) SDS (sodium lauryl sulfate) is as tensio-active agent, add 123 milligrams of (0.5mmol) substrate ω-bromo p-nitroacetophenones, add the 0.5mL methylene dichloride at last, vigorous stirring, 28 ℃ of oil baths were directly reacted 24 hours under air atmosphere, thin plate and gas chromatographic detection reaction.Extract with methylene dichloride then that (3 * 3mL), extraction liquid is through anhydrous Na
2SO
4Drying filters out Na
2SO
4, concentrate methylene dichloride, purifying get ω-pure product of bromo p-nitrophenyl ethanol (yield 58%, 84%ee).
Embodiment 19
ω-bromo is to the asymmetric transfer hydrogenation reaction of benzyloxy methyl phenyl ketone in water/methylene dichloride two-phase system
With 1.5 milligrams of (0.0025mmol) ruthenium complex precursor [RuCl
2(p-cymene)]
2With 3.3 milligrams of (0.0055mmol) optical purityes 2, the N-that 2 '-disulfonic acid root replaces is single, and the 2-diphenyl ethylene diamine is dissolved in the 0.5 mL water to methyl benzene sulfonyl chloride 1,40 ℃ of following stir-activatings 1 hour.Add 260 milligrams of (2.5mmol) HCO then
2Na2H
2O is as hydrogen source, 5.5 milligram (0.020mmol) SDS (sodium lauryl sulfate) is as tensio-active agent, add 153 milligrams of (0.5mmol) substrate ω-bromos to the benzyloxy methyl phenyl ketone, add the 0.5mL methylene dichloride at last, vigorous stirring, 28 ℃ of oil baths were directly reacted 48 hours under air atmosphere, thin plate and gas chromatographic detection reaction.Extract with methylene dichloride then that (3 * 3mL), extraction liquid is through anhydrous Na
2SO
4Drying filters out Na
2SO
4, concentrate methylene dichloride, purifying get ω-bromo to the pure product of benzyloxy phenylethyl alcohol (yield 47%, 92%ee).
Claims (10)
1. soluble chiral diamino is characterized in that this compounds is optically pure 2,2 '-disulfonic acid root replace 1; 2-diphenyl ethylene diamine and 2; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces, 2-diphenyl ethylene diamine or its salt, its structure is shown in general formula:
Optical purity 2,2 '-optical purity 2,2 that the disulfonic acid root replaces '-the disulfonic acid root replaces
1, the single sulfonylation 1 of 2-diphenyl ethylene diamine N-, 2-diphenyl ethylene diamine
R is following group:
C
1-C
18Straight chained alkyl, C
3-C
10Cycloalkyl or-NR
2R
3Amido,
R
1Be selected from following group :-NO
2,-OR
2,-Cl ,-F ,-Br ,-I, C
1-C
18Straight chained alkyl or C
3-C
10Cycloalkyl,
R
2And R
3Be selected from following group: C
1-C
18Straight chained alkyl or C
3-C
10Cycloalkyl,
M
2+Be selected from positive divalent ion Ba
2+, Mg
2+Or Ca
2+,
M
+Be selected from positive monovalent ion: Na
+, K
+Or Li
+
2. water-soluble chiral diamines according to claim 1, described compound are optically pure 2,2 '-disulfonic acid root replace 1,2-diphenyl ethylene diamine or optically pure 2, the N-that 2 '-disulfonic acid root replaces is single to methyl benzene sulfonyl chloride 1, the 2-diphenyl ethylene diamine.
3. the synthetic method of water-soluble chiral diamines according to claim 1 and 2 is characterized in that
Step 1: by optical purity 1,2-diphenyl ethylene diamine and oleum with the dissolving of 1: 10～100 mass ratio after, obtain optical purity 2 in reaction under 0 ℃～35 ℃ the temperature after 1 day, 1 of 2 '-disulfonic acid root replacement, the 2-diphenyl ethylene diamine, through mineral alkali neutralization, with water: the bulk specific gravity crystallization of ethanol=1: 10～100
Purifying final vacuum drying obtains optical purity 2,1 of 2 '-disulfonic acid root replacement, 2-diphenyl ethylene diamine;
Step 2: optical purity 2; 1 of 2 '-disulfonic acid root replacement; 2-diphenyl ethylene diamine and water are alkalescence with 1: 10～50 the back inorganic adjusting PH with base that adds 1.0～1.5 times of mol ratios of mass ratio dissolving; the tensio-active agent or the phase-transfer catalyst that add 0.1～0.2 times of mol ratio; drip the SULPHURYL CHLORIDE of 1.0～1.5 times of mol ratios; obtained optical purity 2 in 8～45 hours 0 ℃～35 ℃ reactions; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; the 2-diphenyl ethylene diamine; this water-soluble chiral diamines is with water: the bulk specific gravity crystallization final vacuum of ethanol=1: 10～100 dry optical purity 2; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces, the 2-diphenyl ethylene diamine.
4. the synthetic method of water-soluble chiral diamines according to claim 3, described tensio-active agent is a Sodium palmityl sulfate, sodium cetanesulfonate, the tetradecyl sodium sulfonate, hexadecyl trialkyl brometo de amonio, tetradecyl trialkyl brometo de amonio, the hexadecyl trialkyl brometo de amonio that sulfonic acid replaces, the tetradecyl trialkyl brometo de amonio that sulfonic acid replaces, polyoxyethylene glycol-100, polyoxyethylene glycol-400, polyoxyethylene glycol-2000, polyoxyethylene glycol-10000 or cyclodextrin, described phase-transfer catalyst are 15-hat-5,18-is preced with-6 crown ethers, tetra-alkyl ammonium chloride, tetraalkyl brometo de amonio or tetraalkyl ammonium iodide quaternary ammonium salt.
5. the synthetic method of water-soluble chiral diamines according to claim 3, described mineral alkali are sodium hydroxide, lithium hydroxide, potassium hydroxide, hydrated barta, magnesium hydroxide, calcium hydroxide, yellow soda ash, Quilonum Retard, salt of wormwood, barium carbonate, magnesiumcarbonate, lime carbonate, sodium bicarbonate or saleratus.
6. the application of water-soluble chiral diamines according to claim 1 and 2 in asymmetry catalysis; it is characterized in that optical purity 2; the single sulfonylation 1 of the N-that 2 '-disulfonic acid root replaces; the complex compound of 2-diphenyl ethylene diamine and ruthenium, rhodium, iridium the 8th group 4 transition metal; in the presence of tensio-active agent or phase-transfer catalyst, the asymmetry catalysis hydrogen transfer reactions of aromatic alkyl ketone takes place in water or water-organic two-phase.
7. the application of water-soluble chiral diamines according to claim 6 in asymmetry catalysis, aromatic alkyl ketone are I-XI formula compound
Wherein, R
1Be selected from following group :-NO
2,-Cl ,-F ,-Br ,-I, C
1-C
18Straight chained alkyl, C
3-C
10Cycloalkyl, R
2Be selected from following group: C
1-C
18Straight chained alkyl, C
3-C
10Cycloalkyl, alpha-brominated alkyl, n=1-3, X=O, S, N.
8. according to claim 6 or 7 application of described water-soluble chiral diamines in asymmetry catalysis, described aromatic alkyl ketone is ω-bromo aromatic alkyl ketone compound, the asymmetry catalysis hydrogen transfer reactions takes place optionally obtain chirality ω-bromo aromatic alkyl alcohol compound or epoxide.
9. according to claim 6 or 7 application of described water-soluble chiral diamines in asymmetry catalysis, described organic phase is manthanoate, acetic ester, propionic ester, butyric ester, ether, glycol dimethyl ether, methyl tert butyl ether, tetrahydrofuran (THF), sherwood oil, normal hexane, hexanaphthene, methylene dichloride, trichloromethane, tetracol phenixin, 1,2-ethylene dichloride, benzene,toluene,xylene or trimethylbenzene aromatic hydrocarbon, or two or more mixed solvent wherein.
10. according in claim 6 or 7 application of described water-soluble chiral diamines in asymmetry catalysis, described tensio-active agent is a Sodium palmityl sulfate, sodium cetanesulfonate, the tetradecyl sodium sulfonate, hexadecyl trialkyl brometo de amonio, tetradecyl trialkyl brometo de amonio, the hexadecyl trialkyl brometo de amonio that sulfonic acid replaces, the tetradecyl trialkyl brometo de amonio that sulfonic acid replaces, polyoxyethylene glycol-100, polyoxyethylene glycol-400, polyoxyethylene glycol-2000, polyoxyethylene glycol-10000, cyclodextrin, described phase-transfer catalysis are 15-hat-5,18-is preced with-6 crown ethers, tetra-alkyl ammonium chloride, tetraalkyl brometo de amonio or tetraalkyl ammonium iodide quaternary ammonium salt.
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| ORGANIC LETTERS YAPING MA,2103.2106,ASYMMETRIC TRANSFER HYDROGENATION OFPROCHIRAL KETONES IN AQUEOUS MEDIA WITH NEWWATER.SOLUBLE CHIRAL VICINAL DIAMINE AS LIGAND 2003;高等学校化学学报 董春娥，1070.1072，新型磺酰胺类含氮手性配体的合成，晶体结构，以及对话苯乙酮的不对陈催化反应 2000 * |
| 高等学校化学学报 董春娥，1070.1072，新型磺酰胺类含氮手性配体的合成，晶体结构，以及对话苯乙酮的不对陈催化反应 2000 * |
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