JPH0420416B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing optically active 1-halogeno-2-alkanols that are used as intermediates for producing medicines, agricultural chemicals, or ferroelectric liquid crystals. .

Prior Art Conventionally, optically active 1-halogeno-2-alkanols have been synthesized using a method using an optically active natural substance or an optically active substance obtained by optical resolution as a starting material [e.g. PALevene, HL
Haller, Journal of Biological Chemistry (J.Biol.Chem.,) 74 , 343 (1927).
has been adopted.

However, the above method requires many steps,
Moreover, since complicated optical resolution must be carried out, there has been a demand for the development of a method capable of synthesizing optically active 1-halogeno-2-alkanol by a relatively simple method.

Problems to be Solved by the Invention In view of the above circumstances, the present invention provides optically active 1-halogeno-2-alkanols by a simple process using optically active 1,2-epoxyalkanes as a starting material. The objective is to provide a method that can be synthesized.

The present invention will be explained in detail below.

Structure of the Invention A feature of the present invention is that an optically active 1,2-epoxyalkane is synthesized with the formula Li ₂ MX ₄ (where M is Cu
or Ni and X represents a halogen).

Means for Solving the Problems The optically active 1,2-epoxy alkanes used as starting materials in the present invention include (+)-
1,2-epoxyhexane, (+)-1,2-epoxyheptane, (+)-1,2-epoxyoctane, (+)-1,2-epoxynonane, (+)-1,
2-epoxydecane, (+)-1,2-epoxyundecane, (+)-1,2-epoxydodecane,
(+)-1,2-epoxytridecane, (+)-1,
2-epoxytetradecane, (+)-1,2-epoxypentadecane, (+)-1,2-epoxyhexadecane, (+)-1,2-epoxyheptadecane, (+)-1,2-epoxyoctadecane, etc. ,
Also, the above-mentioned epoxides (-) can be exemplified.

These epoxides are produced using microorganisms.
- Can be prepared by oxidizing olefins (see Japanese Patent Publication No. 1983-40).

The present invention provides these 1,2-epoxy alkanes with Li ₂ CuCl ₄ , Li ₂ NiCl ₄ , Li ₂ CuBr ₄ or
By reacting with Li ₂ NiBr ₄ or the like, corresponding 1-halogeno-2-alkanols can be obtained. The above reaction is preferably carried out in an organic solvent such as tetrahydrofuran.
- an epoxyalkane dissolved in an organic solvent, such as Li ₂ CuCl ₄ , Li ₂ NiCl ₄ , Li ₂ CuBr ₄ or
This may be carried out by dropping a solution of an organic solvent such as Li ₂ NiBr ₄ .

The reaction temperature is carried out over a wide range of -78°C to 66°C, but a temperature in the range of -10°C to 30°C is preferable, and it actually depends on the type of 1,2-epoxyalkane used as the starting material for the reaction. You should decide accordingly.

Moreover, the reaction time is preferably determined in the range of 3 to 48 hours depending on the reaction temperature.

The final concentration of 1,2-epoxyalkane as starting material ranges from 0.1 to 1 mmol/ml of solvent, but preferably from 1.2 to 0.6 mmol/ml of solvent.

Compounds represented by the formula Li ₂ MX ₄ used in the reaction in the present invention include Li ₂ CuCl ₄ , Li ₂ NiCl ₄ ,
Li ₂ NiBr ₄ , Li ₂ CuBr ₄ and the like can be exemplified, and the preparation thereof can be carried out as follows.

For example, Li ₂ CuCl ₄ and Li ₂ NiCl ₄ are dissolved in organic solvents.
Suspend LiCl, add 1/2 molar ratio of CuCl ₂ and
It can be prepared by adding _NiCl2 and
Li ₂ CuBr ₄ and Li ₂ NiBr ₄ can be prepared by adding CuBr ₂ and NiBr ₂ at a molar ratio of 1/2 to LiBr to an organic solvent.

The appropriate amount of Li ₂ MX ₄ to be used is 1 to 3 times the molar ratio of 1,2-epoxyalkane.

After carrying out the reaction as described above, the optically active 1-
Separate and purify the halogeno-2-alkanol.

As described above, according to the present invention, optically active 1-halogeno-2-alkanols can be advantageously produced by a simple method using an optically active 1,2-epoxyalkane as a starting material. The present invention is useful in the production of important optically active 1-halogeno-2-alkanols as intermediates for various useful substances as mentioned above.

The present invention will be specifically explained below using Examples.

Example 1 51.3 g (0.4 mol) of (R)-(+)-1,2-epoxyoctane ([α] ²⁵ _D +14.3° (neat)) was dissolved in 200 ml of tetrahydrofuran, and added to this under a nitrogen stream. Then, 54.3g (1.2mol) of LiCl was added to tetrahydrofuran.
After dispersing in 640 ml, a tetrahydrofuran solution of Li ₂ CuCl ₄ prepared by adding 86.1 g (0.6 mol) of CuCl ₂ was added dropwise, and the mixture was stirred at room temperature for 24 hours to carry out the reaction.

Next, after the reaction was completed, 800 ml of phosphate buffer was added to the reaction mixture and the tetrahydrofuran layer was separated.
The aqueous layer was extracted three times with ether 0.5, the ether layer,
Combine the tetrahydrofuran layer with anhydrous _MgSO4
It was dried. After removing the solvent under reduced pressure, distillation is performed under reduced pressure,
1-chloro-2-octanol 54.8g (yield 83%,
2-chloro-1-octanol as an impurity
This was then purified by silica gel column chromatography using benzene as a solvent to obtain 46.9 g of 1-chloro-2-octanol with a purity of 99%. Yield 71%, bq70℃/3mmHg,
[α] ²⁵ _D +9.0° (neat).

The purity was determined using a gas chromatograph equipped with a 2 m column carrying 15% diethylene glycol succinate on Unport B and an ionization flame detector. In addition, the optical purity was determined by the method of Mosher et al. (JADale, DLDull, HSMosher, J.Org.
Chem., 34, 2543 (1969) 1-chloro-2
-octanol as an ester of (+)-α-methoxy-α-trifluoromethyl-phenylacetic acid, determined on a gas chromatograph with a 60 m capillary column and ionization flame detector with OV-225 as the liquid phase. As a result, 1-chloro-2-
The optical purity of octanol was 90%ee.

Example 2 3.8 g (30 mmol) of (R)-(+)-1,2-epoxyoctane ([α] ²⁵ _D +14.3° (neat)) was dissolved in 30 ml of tetrahydrofuran, and added to this under a nitrogen stream. , anhydrous LiCl4.07g (96mmol) and anhydrous
6.23 g (48 mmol) of NiCl ₂ in 96 g of tetrahydrofuran
ml, the mixture was stirred at room temperature for 30 hours, and a tetrahydrofuran solution of Li ₂ NiCl ₄ prepared by filtering insoluble matters was added dropwise, followed by stirring at room temperature for 24 hours to carry out the reaction.

Next, after the reaction was completed, 200 ml of phosphate buffer was added to the reaction mixture to separate the tetrahydrofuran layer.
Extract the aqueous layer three times with 150 ml of ether,
Combine the tetrahydrofuran layer with anhydrous _MgSO4
It was dried. The solvent is distilled off under reduced pressure, and then distilled under reduced pressure.
1-chloro-2-octanol 0.82g (yield 18.5
%, containing 16% 2-chloro-1-octanol as an impurity). Next, this was purified by silica gel column chromatography using benzene as a solvent, and the optical purity was measured by the method described in Example 1, and the result was 92% ee.

Example 3 3.84 g (30 mmol) of (R)-(+)-1,2-epoxyoctane ([α] ²⁵ _D +14.3° (neat)) was dissolved in 90 ml of tetrahydrofuran and cooled on ice. to this,
LiBr8.34g (96mmol) and _NiBr2 10.49g (48mmol)
A tetrahydrofuran solution of Li _{2 NiBr 4 prepared by dissolving Li 2} NiBr ₄ (mol) in 115 ml of tetrahydrofuran was added dropwise, and the mixture was stirred for 5.5 hours to carry out the reaction.

Then, after the reaction was completed, 150 ml of phosphate buffer was added to the reaction mixture, and the tetrahydrofuran layer was separated.
Extract the aqueous layer twice with 100 ml of ether,
Combine the tetrahydrofuran layer and add anhydrous Na ₂ SO ₄
It was dried. After the solvent was distilled off under reduced pressure, 1.07 g of 1-bromo-2-octanol (purity 93
%) was obtained. The yield was 17%, the optical purity was 78%ee, and the optical purity was measured in the same manner as in Example 1.

Example 4 3.84 g (30 mmol) of (R)-(+)-1,2-epoxyoctane ([α] ²⁵ _D +14.3° (neat)) was dissolved in 30 ml of tetrahydrofuran and cooled on ice. to this,
Anhydrous LiBr8.33g (96 mmol) and anhydrous
10.72g (48mmol) of CuBr ₂ in 96g of tetrahydrofuran
A solution of Li _{2 CuBr 4 in tetrahydrofuran prepared by dissolving Li 2} CuBr ₄ in ml was added dropwise thereto, and the mixture was stirred for 4 hours to carry out the reaction.

After the reaction is complete, 200 ml of phosphate buffer is added to the reaction mixture, the tetrahydrofuran layer is separated, the aqueous layer is extracted three times with 150 ml of ether, and the ether and tetrahydrofuran layers are combined and extracted with anhydrous
Dried _{with Na2SO4} . After removing the solvent under reduced pressure, distillation was performed under reduced pressure to obtain 2.84 g of 1-bromo-2-octanol.
(purity 88%) was obtained. Yield 57%, optical purity 78%e.
e. Purity and optical purity were measured in the same manner as in Example 1.

Claims (1)

[Claims] 1. Reacting an optically active 1,2-epoxyalkane with a compound represented by the formula Li ₂ MX ₄ (wherein M represents Cu or Ni and X represents a halogen). An expression () characterized by A method for producing 1-halogeno-2-alkanols having optical activity represented by the formula (wherein X represents a halogen and R represents an alkyl group having 1 to 20 carbon atoms).