CN1065857A - Photolytic activity 1,1 '-dinaphthalene-2,2 '-synthetic method of diphenol - Google Patents
Photolytic activity 1,1 '-dinaphthalene-2,2 '-synthetic method of diphenol Download PDFInfo
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- CN1065857A CN1065857A CN 91102332 CN91102332A CN1065857A CN 1065857 A CN1065857 A CN 1065857A CN 91102332 CN91102332 CN 91102332 CN 91102332 A CN91102332 A CN 91102332A CN 1065857 A CN1065857 A CN 1065857A
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Abstract
The present invention relates to photolytic activity 1,1 '-dinaphthalene-2,2 '-synthetic method of diphenol (hereinafter to be referred as photolytic activity I).Photolytic activity I is a kind of chiral reagent of excellence, all has been widely used in asymmetric synthesis and host-guest chemistry.The present invention adopts photolytic activity α-rubigan isobutylamine and derivative thereof to replace S-amphetamine as chiral source, both can avoid toxicity, can reduce cost again, and also having a pair of optical isomer simultaneously can utilize; With post layer method purified product, can obtain optically pure product; The yield height---can obtain 57% chemical yield and nearly 100% chemical yield; Cost significantly is lower than existing the whole bag of tricks.
Description
The present invention relates to photolytic activity 1,1 '-dinaphthalene-2,2 '-method of asymmetric synthesis of diphenol (hereinafter to be referred as the photolytic activity I).1,1 '-dinaphthalene-2,2 '-molecular structure of diphenol (hereinafter to be referred as I) is as follows:
The photolytic activity I is a kind of chiral reagent of excellence, is widely used in asymmetric synthesis.The asymmetric reduction that can be used for ketone as its lithium aluminum hydride complex compound; Its zinc complex can be used for replacing the stereoselectivity polyreaction of thiirane; It also is widely used in the main-guest chemistry, as the synthesis of chiral crown ether, generates inclusion compound to split the material (as: sulfoxide, selenoxide etc.) that some are difficult to split with general chemistry, physical method.
The existing synthetic method of photolytic activity I has two kinds:
Method one:
Traditional method is at first synthetic I, gets (Tetrahedron lett, 1971,48 through splitting its phosphoric acid ester; 4617), totally five step reactions, total recovery is less than 20%, and uses high cinchonine, the cinchonine of price to reach lithium aluminum hydride surely, thereby its cost high (existing market price 60-70 dollar/gram).
Method two:
Reported first such as Ben Feringa in 1978 use up the oxygenant of active copper-amine complex as β-dinaphthol oxidative coupling, made photolytic activity I (Bioorg chem, 1978,7 of enantiomeric excess by 2-Naphthol; 397), but chemical yield and optical yield not high (being respectively 60% and 2.8%).
Nineteen eighty-three Brussee etc. use the asymmetric oxidation coupled reaction of S-amphetamine as the 2-Naphthol of chiral source, can obtain the optical yield of 80% chemical yield and 95% the photolytic activity I (Tetrahedron hrtt, 1983,24(31); 3261), Brussee in 1985 etc. reported again with oxidation even summation reacting phase with condition under, I, S-amphetamine-copper complex are stirred the photolytic activity I that obtains 91% optical yield in methyl alcohol under 25 ℃, be referred to as chiral induction fractionation-racemization reaction (Tetrahedron, 1985,41(16); 3313).
The step of method one is overcharged rate low (＜20%), and uses lithium aluminum hydride in the reaction, is not suitable for producing in enormous quantities.
Though the method two single step reaction has obtained the photolytic activity I of high optical yield, because S-amphetamine is difficult to obtain and is narcotics, this is restricted with regard to the application that makes it.
The objective of the invention is to select cheap and easy to get and efficiently Chiral Amine be used for the chiral induction fractionation-racemization reaction of the asymmetric oxidation coupled reaction and the I of 2-Naphthol, be used for the synthetic of photolytic activity I to replace S-amohetamine and to reduce cost.
Select a kind of being suitable for to produce in enormous quantities, optical yield height, cost are low, the simple synthetic method of technology is a purpose of the present invention.
Foregoing invention mainly by selecting the inexpensive α of photolytic activity efficiently-rubigan isobutylamine and derivative II a_d(Chinese patent application thereof numbers 89108639.4 for use) replace S-amphetamine, be used for the asymmetric oxidation coupled reaction of 2-Naphthol.
Synthesizing of photolytic activity I
With a certain amount of II, methyl alcohol and mantoquita mix, and drip the methanol solution of 2-Naphthol or I then under nitrogen protection; after dropwising, continue to stir 20 hours the solid that directly adds acid treatment or processing and leached again; with the solid of gained through column chromatography purification, the photolytic activity I.
Embodiment 1:
Respectively with 1.6g(+) II a, the 20ml methanol solution of 20ml methyl alcohol and 1.45g nitric hydrate copper places 100ml there-necked flask (nitrogen protecting system, thermometer and dropping funnel are housed).Stir 30 minutes (20 ℃), get deep green suspension, slowly drip the 10ml methanol solution of 0.43g 2-Naphthol, dropwised in about 30 minutes, and continued to stir 20 hours, have a large amount of deep green solids to produce, Dropwise 5 0ml2N hydrochloric acid, solids disappeared is poured in the 400ml beaker, adds the 100ml deionized water, produce white precipitate, with extracted with diethyl ether (50ml * 2) anhydrous magnesium sulfate drying, steaming desolventizes, and gets 0.32g light brown solid, M.P.202-206 ℃, [α]=30 are through column chromatography (silica gel 200-300 order, CH
2Cl
2Be eluent), get the 0.26g white solid, MP204-206 ℃, [α]=+ 35.4(C=1, THF).
Embodiment 2 to embodiment 7 recently carries out this reaction for different optically active amines with different moles, and operation is with embodiment 1, and table 1 is the gained result:
The asymmetric oxidation coupled reaction result of table 1: β one naphthols
| Numbering | Part | The various mol ratios that feed intake | Yield % | Optical purity % | ||
| 2-Naphthol | Cupric nitrate | Part | ||||
| 2 | （＋）Ⅱa | 1 | 2 | 8.9 | 80.1 | 66.0 |
| 3 | （＋）Ⅱa | 1 | 1 | 4 | 66.7 | 20.1 |
| 4 | （－）Ⅱa | 1 | 1 | 6 | 69.0 | 38.9 |
| 5 | （＋）Ⅱb | 1 | 1 | 4 | 65.4 | 9.9 |
| 6 | （＋）Ⅱc | 1 | 1 | 4 | 67.4 | 12.7 |
| 7 | （＋）Ⅱd | 1 | 1 | 2 | 62.6 | 7.0 |
Embodiment 8
In being housed, the 25ml there-necked flask of nitrogen protection device, dropping funnel and thermometer adds 3.4g hydration cupric chloride respectively; 14.7g(-) II a, 120ml methyl alcohol stirs 20 minutes (20 ℃); get mazarine suspension; drip the 25ml methanol solution of 2.86g I, added the gained dark brown solid in 10 minutes; (100ml) leaches the solid of separating out with 10% hcl acidifying; the dry 2.2g Dark grey solid that gets, column chromatography for separation gets the 1.5g faint yellow solid.M.P206-207℃，〔α〕
20 D＝35.0（C＝1，THF）
Add sodium sulphite in the mother liquor, make the Cu(II) precipitate fully, filter, filtrate is removed methyl alcohol, add NaoH and make solution show alkalescence (PH=12), dichloromethane extraction, the Anhydrous potassium carbonate drying is removed solvent, distill 11.8g(-) II.
Embodiment 9:
Get the 0.012mol cupric nitrate, 0.08mol(+) II a, 120ml methyl alcohol; drip the 25ml methanol solution (operation is with embodiment 8) of 0.008molI; get the 1.8g crude product, add 0.0055mol cupric nitrate, 0.023mol(+) II a in the filtrate; drip the 20ml methanol solution of 0.0056mol I; nitrogen protection was stirred 20 hours down, and filtration treatment gets the 2.7g dark red solid, continues cyclical operation similarly twice; thick product is handled through column chromatography, and the gained result is as shown in table 2:
Table 2: the cyclical operation result of synthetic photolytic activity I
| Numbering | Various reactant ratios (mol ratio) | ［α］ | Optical purity (OP%) | Yield (%) | ||
| Ⅰ | Ⅱa | Cupric nitrate | ||||
| 1 | 1 | 10 | 1.2 | 35.2 | 99.2 | 42 |
| 2 | 1 | 4 | 1 | 35.1 | 98.9 | 79 |
| 3 | 1 | 4 | 1 | 34.6 | 97.5 | 60 |
| 4 | 1 | 4 | 1 | 34.5 | 97.2 | 50 |
Total recovery 57.8%, optical yield are 98.2%.
The present invention's following characteristics of having compared with the method for Brussee:
1, the present invention has used photolytic activity II cheap and easy to get to replace s-amphetamine in the Brussee method as chiral source, has both had the low characteristics of cost, has avoided again toxicity, and also having simultaneously one pair of optical isomer can utilize.
2, the present invention has used the column chromatography purification product to obtain optically pure I, and the Brussee method has just obtained the I of 95% optical purity.
3, the present invention uses the method (embodiment 9) of recycling reaction mother liquor, makes the consumption of optically active amine be reduced to 5.5 times by 10.7 times in the Brussee method, calculates by the rate of recovery 80%, and every production 1mol photolytic activity I reduces consuming nearly 2mol optically active amine.
With the photolytic activity I that the method is produced, can obtain 57% chemical yield and nearly 100% optical yield, method is simple, and raw material is cheap and easy to get, by reagent market price calculating (raw material is all in the reagent market price). About 20 yuans of the required cost of every gram photolytic activity I. Significantly be lower than the existing market price.
Claims (2)
1, a kind of synthetic photolytic activity 1,1 '-dinaphthalene-2,2 '-method of diphenol, it is characterized in that:
(1) the asymmetric oxidation coupled reaction that is used for 2-Naphthol as chiral source with a series of new Chiral Amine α-rubigan isobutylamines and N-alkyl substituent (a_d) thereof.
(2) column chromatography purification product uses silica gel (200-300 order) to be that filler, methylene dichloride are eluent, monitor with the silica GF254 thin plate.
2,, when it is characterized in that using photolytic activity II a,, can reuse mother liquor and carry out cyclical operation with preferential crystallization-racemization reaction as chiral source according to the method for the described synthetic photolytic activity I of claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 91102332 CN1065857A (en) | 1991-04-16 | 1991-04-16 | Photolytic activity 1,1 '-dinaphthalene-2,2 '-synthetic method of diphenol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 91102332 CN1065857A (en) | 1991-04-16 | 1991-04-16 | Photolytic activity 1,1 '-dinaphthalene-2,2 '-synthetic method of diphenol |
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| CN1065857A true CN1065857A (en) | 1992-11-04 |
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| CN 91102332 Pending CN1065857A (en) | 1991-04-16 | 1991-04-16 | Photolytic activity 1,1 '-dinaphthalene-2,2 '-synthetic method of diphenol |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5981599A (en) * | 1996-05-01 | 1999-11-09 | Nps Pharmaceuticals, Inc. | Inorganic ion receptor active compounds |
| US6001884A (en) * | 1991-08-23 | 1999-12-14 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US6011068A (en) * | 1991-08-23 | 2000-01-04 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US6031003A (en) * | 1991-08-23 | 2000-02-29 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
-
1991
- 1991-04-16 CN CN 91102332 patent/CN1065857A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6001884A (en) * | 1991-08-23 | 1999-12-14 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US6011068A (en) * | 1991-08-23 | 2000-01-04 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US6031003A (en) * | 1991-08-23 | 2000-02-29 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US5981599A (en) * | 1996-05-01 | 1999-11-09 | Nps Pharmaceuticals, Inc. | Inorganic ion receptor active compounds |
| US6342532B1 (en) | 1996-05-01 | 2002-01-29 | Nps Pharmaceuticals, Inc. | Inorganic ion receptor active compounds |
| US6710088B2 (en) | 1996-05-01 | 2004-03-23 | Nps Pharmaceuticals, Inc. | Inorganic ion receptor-active compounds |
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