JPH02182198A - Method for producing optically active 1,1'-binaphthol - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing optically active 1,1'-binaphthol, which is an important compound as an asymmetric source for asymmetric synthesis and optical resolution.

[Conventional technology]

l,1' which has a hydroxyl group as a substituent at the 2,2'-position is an important compound as a chiral source for asymmetric synthesis and optical resolution.
- Since binaphthol has axial asymmetry, the rotation of the two sets of naphthalene rings with respect to the binaphthyl bond axis is extremely inhibited, and the optical isomers Is and IR derived from the axial asymmetry exist stably and mutually interact with each other. Forms a stable optically active substance that has an enantiomeric relationship.

Conventionally, methods for obtaining such optically active l,1'-binaphthol include (1) a method using a chromatographic separation method (J, Amer, Chem, 103, 3964.
1981) (2) Asymmetric synthesis method using binaphthol copper(n)-amine complex (Tetrahedron, 41, 3
313.1985) (3) Inclusion method using optically active sulfoxide (Chem, Lett, 2085.19
84) (4) Asymmetric hydrolysis method of diacetate of binaphthol using specific microorganisms (J, Chem, Soc.
, ,Chem,Commun,, 1333.1985
) (5) Enzymatic asymmetric hydrolysis method of diacetate of binaphthol (JP-A-63-148996) (6) Cyclic phosphate ester is diastereomerized with natural alkaloids (quinine, quinidine) and recrystallized. A method of optical separation by chromatography (Tetrahedron, Lett,
, 4617.1971), etc. are known.

However, the chromatographic separation method (1) not only requires complicated operations but also has low purity of the obtained optically active substance, and methods (2) and (3) have complicated steps and optical The yield and purity of the active substance are not very high, and this method cannot be called a practical method.

In addition, methods (4) and (5) in which the acetate diester of binaphthol is hydrolyzed using microorganisms or enzymes can yield a highly pure optically active substance, but method (4) has a very high reaction concentration. It is not an efficient method because it requires a reaction time of 10 days or more, and method (5) has the disadvantage that it cannot be recovered and reused unless the enzyme is made insolubilized by a method such as immobilization.

Furthermore, the method (6) of optically resolving a phosphoric acid ester with a natural alkaloid requires complicated operations, and furthermore, in the case of large plate production, the influence of the natural alkaloid on the human body becomes a problem.

[Problems to be Solved by the Invention] The present invention has been made in view of the actual state of the prior art, and its purpose is to improve the optical activity of 1,1'
- It is an object of the present invention to provide a method for producing optically active 1,1'-binaphthol, which can obtain binaphthol with high selectivity in a short time, is simple to operate, and is industrially extremely advantageous.

[Means to solve the problem]

The present inventors have intensively investigated the industrially advantageous method for producing optically active 1,1'-binane I-ol that meets the above objectives. It has been found that optically active 1°1'-binaphthol can be obtained with high selectivity by alcoholysis in a solvent in the presence of lipase. The present invention has been made based on this knowledge.

That is, according to the present invention, optically active 1,1'-binane (.- Provided is a method for manufacturing a bottle.

Optically active 1,1'-binaphthol as used in the present invention has the structural formula shown below, with (S)-1,1'-binaphthol represented by IS and (S)-1,1'-binaphthol represented by IR.
R) 1.1'-Binaphthol alone or a mixture containing both in unequal proportions.

(15) (IR) The raw material used in the present invention is a racemic lower fatty acid half ester of 1,1'-binaphthol. In this case, as the lower fatty acid, in addition to a linear type having 2 to 8 carbon atoms, lower fatty acids containing an electron-withdrawing group such as a halogen, such as chloroacetic acid and fluoroacetic acid, can also be used.

This lower fatty acid half ester of 1,1'-binaphthol can be easily synthesized by reacting racemic 1,1'-binaphthol with a lower fatty acid in an organic solvent.

The lipase used in the present invention exhibits a catalytic effect in the alcoholysis reaction.

Specific examples of lipases preferably used in the present invention include lipoprotein lipase derived from Pseudomonas aeruginosa, porcine pancreatic lipase, yeast lipase derived from the genus Candida, and bacterial lipase derived from the genus Aspergillus, Mucor, and Pseudomonas. Examples include lipases. Among these, lipoprotein lipase derived from Pseudomonas aeruginosa is preferred from the viewpoint of reaction selectivity, rate stability, and the like. These lipases may be purified products or crude products, and either powdered or granular forms can be used.

Furthermore, immobilization carriers such as polymers such as polystyrene, polypropylene, starch, and gluten, and inorganic materials such as activated carbon, porous glass, celite, zeolite, kaolinite, bentonite, alumina, silica gel, hydroxyapatite, calcium phosphate, and metal oxides can be used. It is also possible to use dried immobilized lipase, etc., which is obtained by supporting and immobilizing the above-mentioned lipase on a material etc. by a physical adsorption method. Further, after the reaction is completed, the lipase collected by filtration from the reaction solution retains sufficient activity and stereoselectivity of the reaction, and therefore can be repeatedly reused. Furthermore, it can also be used for continuous reactions.

The amount of lipase to be used is preferably 0.5 to 5 times the amount of the half ester of 1,1'-binaphthol (as a weight ratio, the same applies hereinafter), and particularly 1 to 2 times the amount is most suitable.

Further, the alcohol used in the alcoholysis reaction of the present invention preferably has 1 to 6 carbon atoms, such as methanol, ethanol, propatool, butanol, pentanal, hexanal, etc., and the amount used is 1.1 to 6.
0.5 to half ester of '-binaphthol
10 equivalents is suitable.

The organic solvent used in the alcoholysis reaction is not particularly limited, but the above-mentioned alcohols and other aprotic organic solvents are preferably used. Specific examples of aprotic organic solvents include linear hydrocarbons such as n-hebutane, n-hexane, and n-hebutane, isobutane, isopentane, and
- Branched chain hydrocarbons such as methylpentane, alicyclic hydrocarbons such as cyclopentane and cyclohexane, halogen-containing hydrocarbons such as methylene dichloride, chloroform, carbon tetrachloride, dichloroethane and trichloroethane, benzene, 1-
Examples include aromatic hydrocarbons such as toluene, xylene, cumene, cymene, mesitylene, diisopropylbenzene, aliphatic ethers such as diethyl ether, diisopropyl ether, n-dibutyl ether, and alicyclic 1-methyl such as tetrahydrofuran and tetrahydropyran. However, among these, isopropyl ether and carbon tetrachloride are more suitable. Moreover, in the present invention, there is no problem even if the alcohol used for alcoholysis is used alone as an organic solvent without using these aprotic organic solvents.

The reaction temperature is preferably set at 20 to 50°C from the viewpoint of stability of the lipase, but more preferably set at around 25 to 40°C from the viewpoint of reaction rate and suppression of side reactions. The reaction time varies depending on the raw materials and solvent used, as well as the type of parser, but is generally 5 to 30 hours.

To specifically explain the method of the present invention, the above-mentioned 1, 1'
- Place the binaphthol half ester in an Erlenmeyer flask and dissolve it in an aprotic organic solvent such as isopropyl ether, carbon tetrachloride, benzene, or toluene. A predetermined amount of lipase and alcohol are added to the resulting solution to carry out a reaction. After the reaction, lipase can be easily removed by filtration and used repeatedly. When the filtrate is concentrated, a reaction product is obtained as shown in the following reaction formula.

(D (n)
(m) (R; substituted or unsubstituted alkyl group) In the present invention, the reaction product is then converted into an optically active substance,
That is, optically active half ester or optically active 1
, 1'-binaphthol alcohol. In this case, as a specific separation method, for example, an extraction operation using a two-phase system of a poorly water-soluble or water-insoluble organic solvent and water, a separation operation using a column, separation by distillation, etc. are employed.

〔effect〕

Since the present invention has the above-mentioned configuration, it exhibits extremely significant impact effects as described below.

■The present invention can optically resolve optically active 1,1'-binaphthol from racemic 1,1'-binaphthol half ester with high selectivity. It is possible to manufacture efficiently.

■Since the present invention is carried out in an organic solvent, the enzyme in the reaction system does not dissolve, so the enzyme and the product can be separated and recovered by simple operations such as filtration, and the recovered enzyme remains intact. It is possible to reuse.

Therefore, the method of the present invention is extremely useful as a method for producing photoactive 1,1'-binaphthol derivatives useful as catalysts in the production process of optically active substances such as prostaglandin and Q-menthol.

〔Example〕

Next, the present invention will be explained with reference to reference examples and examples.

Reference Example 1 Synthesis of 2-acetoxy-2'-hydroxy-1,1'-binaphthyl (half ester) (in formula (■), R
is a methyl group) 1 g (3,49 mmo'J-) of binaphthol is dissolved in a mixed solvent of 15-year-old alcohol and 10-year-old dichloromethane. To this at room temperature, add 3 pieces of pyridine to give 17.1 mg (0,175 mmol) of dimethylaminopyridine as a catalyst.
was added, and 0.39 g (3.84 mmol) of acetic anhydride was added dropwise, followed by stirring at room temperature for 6 hours. After that, the pressure was reduced and the solvent was distilled off, then dissolved in dimethyl ether and IN-H (
, Q, saturated Na2CO, aqueous solution, and saturated NaCQ water, and then dried and the solvent was distilled off. Thereafter, after purification and separation using a silica gel column (hexane/acetone = 5/1), the desired product was obtained with a yield of 90%.

Reference Example 2 Synthesis of 2-butyloxy-2'-hydroxy-1,1'-binaphthyl (half ester) (in formula (1), R
(propyl group) 1. Dissolve 1'-binaphthol Ig (3.49 mmol 1.) in a mixed solvent of 15 1-toluene or 10 dichloromethane + nll.

To this, 3d of pyridine is added at room temperature, 17.1 mg (0.175 mmol) of dimethylaminopyridine is added as a catalyst, 0.61 g (3.84 mmol) of butyric anhydride is added dropwise, and the mixture is stirred at room temperature for 6 hours. After that, the solvent was distilled off under reduced pressure, and then dissolved in ether, IN-HC (1, saturated N
After washing with a2Co3 aqueous solution and saturated NaCQ water,
Perform dry solvent evaporation. Thereafter, the target product was obtained with a yield of 91% after purification using a column (hexane/acetone = 5/l).

Example 1 Alcoholysis of 2-acetoxy-2'-hydroxy-1,1'-binaphthyl Racemic 2-acetoxy-2' was added to 20 Erlenmeyer flasks.
-Hydroxy-1,1'-binaphthyl 5g (15mmo
1), add 500 mfl of isopropyl ether and dissolve.

To this, 4.8 g (150 mmol) of methanol,
Add 10 g of lipase (manufactured by Toyobo) and stir at 150 rpm per minute while maintaining the temperature at 40°C. After 96 hours, the enzyme was filtered off from the reaction solution, and the solvent was distilled off from the filtrate under reduced pressure.
An oily substance was obtained. This was fractionated using silica gel column chromatography using chloroform as a developing solvent to obtain a half ester of S and 1,1'-binaphthol of R. When the optical purity of each was measured, the S half ester was 99% ([α-32.1, c 1.30
, THF), 96% 1,1'-binaphthol of R ([
αko. +28.8, c 1.00, THF).

Example 2 Alcoholysis of 2-acetoxy-2'-hydroxy-1,1'-binaphthyl Racemic 2-acetoxy-2' was placed in an Erlenmeyer flask.
~Hydroxy-1,1'-binaphthyl 5g (15mmo
1), add 50 ml of carbon tetrachloride and dissolve. Add 6.9 g (150 mmol) of ethanol and Lipase (manufactured by Toyobo) to this, and add 1.
Stir at 50 rpm.

After 60 hours, the enzyme was removed by filtration from the reaction solution, and the solvent was distilled off from the filtrate under reduced pressure to obtain an oily substance. This was fractionated using silica gel column chromatography using chloroform as a developing solvent to obtain a half ester of S and 1,1'-binaphthol of R.

When the optical purity of each was measured, the half ester of S was 95% ([αco;)-31,2, c 1.00, THF
), 96% of 1.1′-binaphthol in R ([α]D5
÷27,2, c 1.10, T) IF).

Example 3 Alcoholysis of 2-acetoxy-2'-hydroxy-1,1'-binaphthyl Racemic 2-acetoxy 2' was added to a 20 ml Erlenmeyer flask.
-Hydroxy-1,1'-binaphthyl 5g (15,2m
mol) and add 500% of isopropyl ether to dissolve. To this, 1 g of n-butanol (150 mmo
l) and lipase (manufactured by Toyobo) Log, and stirred at 150 rpm per minute while maintaining the temperature at 40°C. After 96 hours,
After removing the enzyme from the reaction solution by filtration, the solvent was distilled off from the filtrate under reduced pressure to obtain an oily substance. This was then subjected to silica gel column chromatography using chloroform as the developing solvent.
Fractionation was carried out to obtain S half ester and R 1,1'-binaphthol. When the optical purity of each was measured, S
96% half ester ([a]o'-31,6,
C1,00,THF), H binaphthol is 96 Da ([
α Komi +29.9, c 1.10. THF).

Example 4 Alcoholysis of 2-acetoxy-2'-hydroxy-1,1'-binaphthyl Racemic 2-acetoxy 2 was added to a 20 m Erlenmeyer flask.
'-Hydroxy-1,1'-binaphthyl 5g (15,2
mmol), add 500 mmol of isopropyl ether and dissolve. Add to this 15g of n-hexanol (150
mmol) and 10 g of lipase (manufactured by Toyobo),
Stir at 150 rpm per minute while maintaining at 0°C. After 96 hours, the enzyme was removed by filtration from the reaction solution, and the solvent was distilled off from the filtrate under reduced pressure to obtain an oily substance. This was fractionated using silica gel column chromatography using chloroform as a developing solvent, and the half ester of S and the 1,1
'Binaphthol was obtained. When the optical purity of each was measured, the half ester of S was 95 μ([α]mi'-30,4
, c 1.00, THF), ■ 96% dog 1,1'-binaphthol ([a:bl+''+29.9, c 1.
00. THF).

Example 5 Alcoholysis of 2-butyroxy-25-hydroxy-1,1'-binaphthyl Racemic 2-butyroxy-2' was added to a 20-mL Erlenmeyer flask.
-Hydroxy-1,1'-binaphthyl 5.3g (15m
mol) and add 500 mQ of isopropyl ether to dissolve. To this, 4.8 g of methanol (150 mmo
l) and 10g of lipase (manufactured by Toyobo) and heated at 40°C.
Stir at 150 rpm per minute while maintaining After 50 hours, the enzyme was removed by filtration from the reaction solution, and the solvent was distilled off from the filtrate under reduced pressure to obtain an oily substance. This was fractionated using silica gel column chromatography using chloroform as a developing solvent, and the half ester of S and the 1,1'
- Binaphthol was obtained. When the optical purity of each was measured, the S half ester was 96% ([αcoD-44.0,
C1,37, THF), 98% 1,1'-binaphthol of R ([α]D+31.4, c 1.01, T)IF
)Met.

Example 6 Alcoholysis of 2-hexyloxy-2'-hydroxy-1,1'-binaphthyl Racemic 2-hexyloxy-
2'-hydroxy-1,1'-binaphthyl 6.3g (1
Take 5.2 mmol) and add 500 mmol of isopropyl ether.
Add +++R and dissolve. Add to this 6.9g of ethanol (
150 mmol) and lipase (manufactured by Toyobo) Log were added, and the mixture was stirred at 150 rpm per minute while maintaining the temperature at 40°C.

After 72 hours, the enzyme was removed by filtration from the reaction solution, and the solvent was distilled off from the filtrate under reduced pressure to obtain an oily substance. This was fractionated using silica gel column chromatography using chloroform as a developing solvent to obtain the half ester of S and the 1,1' binaph 1--ol of R. The optical purity of each was measured, and the half ester of S was 95% ([αcoD-4
8.2, c 1.440, THF), R monobinaphthol 98% ([α]D+28.7, c O,97, TH
F).

Example 7 2-chloroacetoxy-2'-hydroxy-1,1'-
Alcoholysis of Binaphthyl 5 g of racemic 2-chloroacetoxy-2'-hydroxy-1,1'-binaphthyl (1
Take 5 mmol) and add 500 mQ of isopropyl ether.
Add and dissolve. Add to this 4.8 g of methanol (150 m
mol) and 10 g of lipase (manufactured by Toyobo), and
Stir at 150 rpm per minute while maintaining temperature. After 96 hours, the enzyme was removed by filtration from the reaction solution, and the solvent was distilled off from the filtrate under reduced pressure to obtain an oily substance. This was separated using silica gel column chromatography using chloroform as a developing solvent to obtain a half ester of S and a 1,1' binaphthol of R. When the optical purity of each was measured, S
99% half ester ([α]D-17.1, C0
092, THF), 1,1'-binaphthol of R is 62
%([α]D+19.1, c 1.01, TI(F).

Claims (1)

[Claims] (1) A method for producing optically active 1,1'-binaphthol, which comprises subjecting a lower fatty acid half ester of 1,1'-binaphthol to asymmetric alcoholysis in an organic solvent in the presence of lipase.