CN1580022A - Method for preparing chiral binaphthalene diol - Google Patents
Method for preparing chiral binaphthalene diol Download PDFInfo
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- CN1580022A CN1580022A CN 03127433 CN03127433A CN1580022A CN 1580022 A CN1580022 A CN 1580022A CN 03127433 CN03127433 CN 03127433 CN 03127433 A CN03127433 A CN 03127433A CN 1580022 A CN1580022 A CN 1580022A
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Abstract
The invention refers to a kind of manufacturing method of chiral binaphthyl diphenol. It chooses the L-(-)- chloro carbonic acid menthol ester as the resolving agent to produce diastereomer ramification and is separated by recrystallization. The ramification is hydrolyzed by alkali (NaOH, KOH) in the condition of water-alcohol or ketone. We get the organic solvent out of it, extract it with ligroin, neutralize the layer of water, extract it with aether, dry it, get rid of the solvent and get the corresponding chiral binaphthyl diphenol.
Description
Technical field
The present invention relates to the optically active organic compound preparation method of a class, in detail, relate to a kind of preparation method of chiral binaphthyl diphenol.
Background technology
Optically pure 1,1 '-naphthyl naphthalene and analogue thereof are auxiliary agents important in the asymmetric catalysis synthesis, and catalyst ligand is widely used in the important organic synthesis such as asymmetric cycloaddition, aldol condensation, reduction.The preparation of this compounds and to use be very active research field of one of Synthetic Organic Chemistry always.
1 of present resolution of racemic, the means of 1 '-binaphthol [602-09-5] and derivative thereof comprise:
1) utilize the characteristics of functional groups of BINOL, by becoming ester, become ether or with the Chiral Amine effect, form diastereomer, reach the purpose of fractionation by the crystalline means.
2) utilize optically pure host compound and its enantioselectivity ground to generate the inclusion crystal, according to the difference of solubleness, reach isolating purpose equally.
3) utilize its ester derivative of enzymatic hydrolysis, obtain optically active BINOL.
In the aforesaid method, method 1 is carried out under absolute anhydrous condition, and chiral source and organic bases cost an arm and a leg, and also need use LiAlH
4, complex operation, cost height.
Aforesaid method 2 is considered to practical means the most, but still has two drawbacks: the resolution reagent usage quantity is big, the cost height, and the kind that splits compound is less.
The enzyme kinetics of aforesaid method 3 splits and has above complex operation equally, and cost height and reaction times need a few hours to problems such as a couple of days.
Ottorino De Lucchi etc. use L-(-)-Menthyl chloroformate under the anaerobic anhydrous condition, making solvent with benzene splits, derivative normal hexane recrystallization, solid with Lithium Aluminium Hydride reduce (R)-binaphthol, yield 86.6% (pure), mother liquid evaporation, Lithium Aluminium Hydride reduce (S)-isomer, yield 91.6% (90%ee).This method advantage is that yield is high and purity is good, and shortcoming is derivatize and goes derivatize all to carry out under the anhydrous and oxygen-free condition of strictness, and used resolving agent purity is very high, costs an arm and a leg.
Summary of the invention
The object of the present invention is to provide the preparation method of the chiral binaphthyl diphenol of a kind of convenience and practicality.
The present invention is to racemic 1, and the fractionation of 1 '-binaphthol is the method by phase transition, with the agent that splits of L-(-)-Menthyl chloroformate, generate non-enantiomer derivative, separate by the method for recrystallization, derivative is respectively under water-alcohol or ketone condition, (NaOH, KOH) hydrolysis steam organic solvent with highly basic, petroleum ether extraction, in and water layer, extracted with diethyl ether, drying, desolventizing obtains corresponding chirality binaphthol; Its reaction scheme is shown below:
Above-mentioned by in the method for Menthyl chloroformate resolution of racemic binaphthol, its key step is:
A) racemize dinaphthalene diphenol is dissolved in the sodium hydroxide or potassium hydroxide solution of 1-15%, wherein, the add-on of alkaline solution is the 1.5-2.0 equivalent of dinaphthalene diphenol, is cooled to room temperature;
B) add phase-transfer catalyst and organic solvent, wherein, the add-on of phase-transfer catalyst is the 10-50% equivalent of dinaphthalene diphenol, and the organic solvent add-on is 5-10 milliliter/every gram dinaphthalene diphenol, stirs;
C) add the resolving agent Menthyl chloroformate, the add-on of this resolving agent is the 1.2-2.0 equivalent of dinaphthalene diphenol, reacted 3-15 minute, and static layering, water merges organic phase with organic solvent extraction for several times;
D) remove organic solvent, generate non-enantiomer derivative, with hexane or sherwood oil substep recrystallization this derivative is split, wherein, the add-on of hexane or sherwood oil is 20-60 milliliter/every gram dinaphthalene diphenol;
E) get the steps d product, under the argon gas atmosphere, add water-soluble alcohol solution and sodium hydroxide or potassium hydroxide, wherein Chun add-on is 25-50 milliliter/every gram dinaphthalene diphenol, and the add-on of alkali is the 5-10 equivalent of steps d product, backflow 1-3 hour, with ether or Petroleum ether extraction, aqueous phase as acidified is to pH=5-7, and recrystallizing methanol gets the chiral binaphthyl diphenol;
Above-mentioned phase-transfer catalyst is: quaternary ammonium salts such as Tetrabutyl amonium bromide, distearyl dimethyl ammonium chloride or palmityl trimethyl ammonium chloride;
Above-mentioned organic solvent is: one or more mixed solvents in methylene dichloride, chloroform, toluene, dimethylbenzene and the methylene dichloride.
The sherwood oil that described recrystallization is used is 60-90 ℃.
Used alcoholic solution can be the solution that water-soluble alcohol and water is formed among the step e, and wherein the volume ratio of alcohol and water is 2: 0-1.
The invention has the advantages that with the method for phase transition and avoided traditional anhydrous and oxygen-free operation, reagent and easy-operating method with cheapness, reached the purpose of resolution of racemic binaphthol easily, the close R-as a result of anhydrous and oxygen-free operational condition isomer 83.1% when purity and yield reach and split agent with L-(-)-Menthyl chloroformate,＞99%ee[document 86.6%, 100%ee], S-isomer yield 83.2%, 91%ee[document 91.6%, 90%ee].
The present invention is simple to operate, and method economy and chiral source are easy to get, and resolution reagent prepares easily, and low price has been realized the binaphthol high-level efficiency optical resolution to racemic modification.
The present invention has realized fractionation to the racemize binaphthol with the method for phase transition first; Substituted the process that expensive Lithium Aluminium Hydride reduction removes menthol ester with common alkali (NaOH, KOH) hydrolysis, yield and purity are close with literature method 1.Compare the advantage that the present invention has with technical literature:
1) derivatize of technical literature and reduction reaction are all carried out under the anhydrous and oxygen-free condition, and the present invention carries out in the presence of the water having, easily operation.
2) the present invention has replaced the Lithium Aluminium Hydride and the organic bases of costliness in the technical literature with cheap mineral alkali (NaOH, KOH).
3) speed of response of the present invention is fast, only needs the several minutes reaction to finish.
4) the present invention needn't adopt pure L-(-)-Menthyl chloroformate resolving agent, is a very difficult thing and prepare pure L-(-)-Menthyl chloroformate.
Embodiment
Embodiment one
Under agitation, with racemize 1,1 '-dinaphthalene-2,2 '-diphenol 1.00 gram is dissolved in 10 milliliter 6% the sodium hydroxide solution, be cooled to room temperature,, stir fast toward wherein adding 0.20 gram Tetrabutyl amonium bromide and 10.0 milliliters of methylene dichloride, add 1.04 milliliter (80.9% of Menthyl chloroformate, 1.39 equivalent), kept room temperature reaction 8 minutes, leave standstill, tell organic layer, the water layer dichloromethane extraction merges organic layer, 3 * 10 milliliters of washings, anhydrous sodium sulfate drying, rotary evaporation is sloughed solvent, gets thick liquid, with a small amount of methylene dichloride dissolving, cross a short column, silica gel is stationary phase, long 5 centimetres, and 10% ether/sherwood oil drip washing, slough solvent, with 30 milliliters of hexane recrystallizations.Get compound 1.03 grams (90.5% yield), fusing point 195-198 ℃ of [a] 25D=-134.9, infrared [KBr, cm-1] 2958 (w), 2935 (m), 1756 (s), 1223 (s), 1251 (s), 962 (s).The mother liquor evaporate to dryness gets compound b 0.98 gram, yield 86.3%, fusing point 60-65 ℃, [a] 25D=-12.5, infrared [KBr, cm-1] 2958 (w), 2935 (m), 1756 (s), 1223 (s), 1251 (s), 962 (s).
Get the compound 1.00g that derivatize obtains, under argon shield, add 70 ml waters; 100 milliliters of ethanol, 20.0 gram sodium hydroxide refluxed 1 hour 30 minutes; cooling slightly, rotary evaporation takes off ethanol, water layer 2 * 70 milliliters of extractions of sherwood oil (60-90 ℃); be neutralized to slightly acidic with hydrochloric acid then; there are a large amount of white precipitates to generate 2 * 50 milliliters of ether extraction, anhydrous sodium sulfate drying; filter; slough ether, sherwood oil and methylene dichloride recrystallization (9: 1) get clear crystal R isomer 0.42 gram; yield 95.4%; fusing point 210-211 ℃, and [a] 25D=+34.6 (c=1.0, THF);＞99%ee, and pure menthol 0.45 gram (yield 98%).Get another S isomer with quadrat method, yield 96.4%, fusing point 209-210 ℃, [a] 25D=-30.2,91%ee, pure menthol 0.40g, the rate of recovery 97.6%.
Embodiment two
Under agitation, with racemize 1,1 '-dinaphthalene-2,2 '-diphenol 2.00 gram is dissolved in 15 milliliter 10% the potassium hydroxide solution, is cooled to room temperature, toward wherein adding 0.30 gram Tetrabutyl amonium bromide and 15.0 milliliters of toluene, stir fast, add 2.1 milliliters of Menthyl chloroformates (80.9%, 1.4 equivalent), keep room temperature reaction 16 minutes, and left standstill, tell organic layer, water layer merges organic layer, 3 * 10 milliliters of washings with 3 * 10 milliliters of extractions of methylene dichloride, anhydrous sodium sulfate drying filters, and rotary evaporation is sloughed solvent, get thick liquid, 30 milliliters of 60-90 ℃ of sherwood oil recrystallizations, mother liquor concentrates, cross a short column, silica gel is stationary phase, long 5 centimetres, 10% ether/sherwood oil drip washing is sloughed solvent, with 30 milliliters of sherwood oil recrystallizations, merge crystal, 60 milliliters of 60-90 ℃ of sherwood oil recrystallizations get clear crystal, (2.1g 92.2% yield), fusing point 196-198 ℃ of [a] D=-134.9, infrared [KBr, cm-1] 2958 (w), 2935 (m), 1756 (s), 1223 (s), 1251 (s), 962 (s).The mother liquor evaporate to dryness gets compound 1.96 grams, yield 86.3%, fusing point 60-65 ℃, [a] 25D=-12.5, infrared [KBr, cm-1] 2958 (w), 2935 (m), 1756 (s), 1223 (s), 1251 (s), 962 (s).
Compound 0.98 gram of obtaining, under argon shield, 100 milliliters of ethanol, 20.0 gram sodium hydroxide refluxed 2 hours, slightly cooling, rotary evaporation takes off ethanol, add 60 ml waters,, be neutralized to PH=5-7 with hydrochloric acid then with 2 * 70 milliliters of extractions of sherwood oil, there are a large amount of white precipitates to generate, 50 milliliters of ethyl acetate extraction, anhydrous sodium sulfate drying filters, slough ethyl acetate, get S configuration binaphthol 0.364 gram, fusing point 209-210 ℃, [a] 25D=-30.2,91%ee, yield 96.4%, pure menthol 0.40 gram, the rate of recovery 97.6%; Get R isomer yield 95.4% with quadrat method, fusing point 210-211 ℃, [a] 25D=+34.6 (c=1.0, THF),＞99%ee, and pure menthol 0.45g (yield 98%).
Resolving agent chloro-formic ester menthol ester of the present invention can be an existing products, also can be prepared as follows and assay:
Preparation: 500 milliliters of round-bottomed flasks, machine stir under the also argon shield, add solid phosgene 22.0 grams; 200 milliliters of dry toluenes and menthol 32.0 grams are cooled to-5～10 ℃, drip 32.0 milliliters of dry triethylamine; 0 ℃ was reacted 18 hours, filtered, and washed twice; anhydrous magnesium sulfate drying filters, and sloughs solvent; 70-72 ℃/2mmHg product is collected in underpressure distillation, weighs; get product Menthyl chloroformate 40.0 grams, yield 89.3%
Measure: take by weighing two parts of above-mentioned each 0.3563g of Menthyl chloroformate crude product, portion is done blank, and another part adds 20 ml waters, 0.3 milliliter of pyridine, under the room temperature, stirring reaction 10 minutes adds 20 milliliters of 6M nitric acid respectively, 3.0 milliliters of ferriammonium sulfate indicator, 20.0 the silver nitrate solution of the about 0.1M of milliliter, to light red, 30 seconds are constant, are terminal point with ammonium thiocyanate 0.1022M titration; 18.05 milliliters of ammonium thiocyanates of blank consumption, the sample that adds the pyridine reaction consumes 5.15 milliliters.
Claims (3)
1, a kind of preparation method of chiral binaphthyl diphenol, its key step is:
A) racemize dinaphthalene diphenol is dissolved in the sodium hydroxide or potassium hydroxide solution of 1-15%, wherein, the add-on of alkaline solution is the 1.5-2.0 equivalent of dinaphthalene diphenol, is cooled to room temperature;
B) add phase-transfer catalyst and organic solvent, wherein, the add-on of phase-transfer catalyst is the 0.1-0.5 equivalent of dinaphthalene diphenol, and the organic solvent add-on is 5-10 milliliter/every gram dinaphthalene diphenol, stirs;
C) add the resolving agent Menthyl chloroformate, the add-on of this resolving agent is the 1.2-2.0 equivalent of dinaphthalene diphenol, reacted 3-15 minute, and static layering, water merges organic phase with organic solvent extraction for several times;
D) remove organic solvent, generate non-enantiomer derivative, with hexane or sherwood oil substep recrystallization this derivative is split, wherein, the add-on of hexane or sherwood oil is 20-60 milliliter/every gram dinaphthalene diphenol;
E) get the steps d product, under the argon gas atmosphere, add water-soluble alcohol solution and sodium hydroxide or potassium hydroxide, wherein Chun add-on is 25-50 milliliter/every gram dinaphthalene diphenol, and the add-on of alkali is the 5-10 equivalent of steps d product, backflow 1-3 hour, with ether or Petroleum ether extraction, aqueous phase as acidified is to pH=5-7, and recrystallizing methanol gets the chiral binaphthyl diphenol;
Above-mentioned phase-transfer catalyst is: quaternary ammonium salts such as Tetrabutyl amonium bromide, distearyl dimethyl ammonium chloride or palmityl trimethyl ammonium chloride;
Above-mentioned organic solvent is: one or more mixed solvents in methylene dichloride, chloroform, toluene, dimethylbenzene and the methylene dichloride.
2, preparation method as claimed in claim 1 is characterized in that, the sherwood oil that described recrystallization is used is 60-90 ℃.
3, preparation method as claimed in claim 1 is characterized in that, used alcoholic solution is the solution that water-soluble alcohol and water is formed among the step e, and wherein the volume ratio of alcohol and water is 2: 0-1.
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| CN 03127433 CN1256312C (en) | 2003-08-06 | 2003-08-06 | Method for preparing chiral binaphthalene diol |
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| CN 03127433 CN1256312C (en) | 2003-08-06 | 2003-08-06 | Method for preparing chiral binaphthalene diol |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101992076A (en) * | 2010-10-29 | 2011-03-30 | 华东理工大学 | Chiral binaphthyl chromatogram immobile phase, and preparation method and application thereof |
| CN111253215A (en) * | 2018-11-30 | 2020-06-09 | 上海科胜药物研发有限公司 | L-menthol recovery process method |
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2003
- 2003-08-06 CN CN 03127433 patent/CN1256312C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101992076A (en) * | 2010-10-29 | 2011-03-30 | 华东理工大学 | Chiral binaphthyl chromatogram immobile phase, and preparation method and application thereof |
| CN101992076B (en) * | 2010-10-29 | 2012-05-30 | 华东理工大学 | Chiral binaphthyl chromatogram immobile phase, and preparation method and application thereof |
| CN111253215A (en) * | 2018-11-30 | 2020-06-09 | 上海科胜药物研发有限公司 | L-menthol recovery process method |
| CN111253215B (en) * | 2018-11-30 | 2023-04-11 | 上海科胜药物研发有限公司 | L-menthol recovery process method |
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| CN1256312C (en) | 2006-05-17 |
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