JP2000239225A - Production of optically active hydroxyester compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new process for the production of an optically active hydroxyester compound useful as an intermediate for pharmaceuticals and agrochemicals on an industrial scale at a low cost. SOLUTION: The objective optically active hydroxyester compound such as (S)-2-benzoyloxy-1-phenyl-1-ethanol can be produced by reacting a racemic 1,2-diol compound such as 1-phenyl-1,2-ethanediol with a carboxylic acid halide compound such as benzoyl chloride in the presence of an inorganic base such as sodium carbonate, water and an optically active 4,4-dibromo-4,5-dihydro-3H- dinaphtho[2,1-c:1',2'-e]stannepine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to racemic 1,2
The present invention relates to a method for producing an optically active hydroxyester compound in which only a primary hydroxyl group of one of the isomers of a diol compound is selectively protected by a carboxylic acid halide compound.

[0002]

2. Description of the Related Art Hydroxyester compounds in which only the primary hydroxyl group of a 1,2-diol compound is protected are known as pharmaceuticals,
It is an important compound indispensable for the synthesis of pesticides.

In recent years, in the production of pharmaceuticals and agricultural chemicals, when an asymmetric carbon is present in the molecule, the absolute configuration of only one isomer of R or S is considered due to problems such as pharmacological activity and toxicity. There is an increasing tendency to use. Therefore, it is important to selectively obtain only one of the isomers in the hydroxy ester compound as a raw material.

[0004] For this reason, the technology for obtaining optically active hydroxyester compounds from racemic 1,2-diol compounds as raw materials has become increasingly important.

Hitherto, as a method for producing an optically active 1,2-diol derivative from a racemic 1,2-diol compound, only an enzymatic method is known, and a chemical synthesis method is completely unknown. Absent.

As a method for producing an optically active 1,2-diol derivative by an enzymatic method, a method of selectively acylating a primary hydroxyl group using an enzyme such as lipase {Journal of Organic Chemistry, 59 Volume 3,
88-393, 1994 (J. Org. Chem.
1994, 59, 388-393)} and the like.

[0007]

However, in general, in the enzymatic method, the reaction proceeds further after the reaction for producing the desired optical enantiomer is completed, and the reaction for producing an undesired optical enantiomer occurs. In many cases, the conversion of the reaction must be stopped at 50% or less in order to keep the optical purity high.

[0008] For this reason, in this method, it is necessary to always observe changes over time, and complicated operations are required from the viewpoint of an industrial production method. Furthermore, since vinyl acetate used as a hydroxyl-protecting agent (that is, an acylating agent) is used in an amount equivalent to 7 times the amount of the substrate, it is not economically advantageous.

For this reason, the amount of the reaction reagent to be used as a protecting agent for the hydroxyl group is theoretically required, and a method for producing an optically active 1,2-diol derivative by chemical synthesis which does not require frequent observation of changes over time is required. Was strongly desired.

[0010]

Means for Solving the Problems In view of such circumstances, the present inventors have made intensive studies, and have found that optically active 4,4-dibromo-4,5-dihydro-3H-dinaphtho [2,1-c:
By reacting a 1,2-diol compound with a carboxylic acid halide compound serving as a protective agent for the hydroxyl group thereof in the presence of a catalyst comprising 1 ', 2'-e] stanepine, an inorganic base and water, an optically active compound is obtained. They have found that a hydroxyester compound can be produced, and have completed the present invention.

That is, the present invention relates to an optically active 4,4-dibromo-4,5-dihydro-3H-dinaphtho [2,1-c:
An optically active hydroxyester compound characterized by reacting a 1,2-diol compound with a carboxylic acid halide compound in the presence of a catalyst comprising 1 ', 2'-e] stanepine, an inorganic base, and water. It is a manufacturing method of.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION 1,2 used in the present invention
-As a diol compound, a hydroxyl group is bonded to each adjacent carbon atom, and one of the adjacent carbon atoms is located at the terminal of the alkyl group, and the other carbon atom is asymmetric. If the compound is carbon,
Can be used without any restrictions. Among these carbon atoms, the following general formula (I)

[0013]

Embedded image

(Where R is an aryl group having 1 to 11 carbon atoms or a halogen-substituted aryl group, an aryloxyalkyl group having 1 to 11 carbon atoms or a halogen-substituted aryloxyalkyl group, or an alkyl group having 1 to 10 carbon atoms) 1, 2-diol compound represented by the following formula:

In the above formula (I), R represents a phenyl group, a methylphenyl group, an ethylphenyl group, a naphthyl group, a methylnaphthyl group or the like having 1 to 11 carbon atoms.
And halogen-substituted aryl groups having 1 to 11 carbon atoms in which halogen atoms such as chlorine and bromine are bonded to these groups; phenoxymethyl, methylphenoxymethyl, ethylphenoxymethyl, naphthyloxymethyl, etc. And a halogen-substituted aryloxymethyl group having 1 to 11 carbon atoms in which a halogen atom such as a chlorine atom or a bromine atom is bonded to these groups; and a methyl group, an ethyl group, or a propyl group And a butyl group and other alkyl groups having 1 to 10 carbon atoms.

Specific examples of the 1,2-diol compound represented by the above general formula (I) having these groups include:
1-phenyl-1,2-ethanediol, 1- (4-methylphenyl) -1,2-ethanediol, 1- (3-
Methylphenyl) -1,2-ethanediol, 1- (4
-Ethylphenyl) -1,2-ethanediol, 1-
(2-naphthyl) -1,2-ethanediol, 1- (6
-Methyl-2-naphthyl) -1,2-ethanediol,
1- (4-chlorophenyl) -1,2-ethanediol, 1- (4-bromophenyl) -1,2-ethanediol, 1- (6-chloro-2-naphthyl) -1,2-ethanediol, 1-phenoxymethyl-1,2-ethanediol, 1- (4-methylphenoxymethyl) -1,2
-Ethanediol, 1- (3-methylphenoxymethyl) -1,2-ethanediol, 1- (4-ethylphenoxymethyl) -1,2-ethanediol, 1- (2-
Naphthoxymethyl) -1,2-ethanediol, 1-
(4-chlorophenoxymethyl) -1,2-ethanediol, 1- (4-bromophenoxymethyl) -1,2-
Ethanediol, 1- (3-chlorophenoxymethyl)
-1,2-ethanediol, 1- (6-chloro-2-naphthoxymethyl) -1,2-ethanediol, 1,2-
Propanediol, 1,2-butanediol, 1,2-
Pentanediol, 1,2-hexanediol, 1,2
-Heptanediol, 1,2-octanediol, 1,
2-nonanediol, 1,2-decanediol, 1,2
-Undecanediol, 1,2-dodecanediol and the like.

Among these 1,2-diol compounds, 1-phenyl-1,2-ethanediol, 1-phenyldiol,
(4-methylphenyl) -1,2-ethanediol, 1-
(3-methylphenyl) -1,2-ethanediol, 1
-(2-naphthyl) -1,2-ethanediol, 1-
(4-chlorophenyl) -1,2-ethanediol, 1
-(4-bromophenyl) -1,2-ethanediol,
1-phenoxymethyl-1,2-ethanediol, 1-
(4-methylphenoxymethyl) -1,2-ethanediol, 1- (3-methylphenoxymethyl) -1,2-ethanediol, 1- (4-ethylphenoxymethyl)-
1,2-ethanediol, 1- (2-naphthoxymethyl) -1,2-ethanediol, 1- (4-chlorophenoxymethyl) -1,2-ethanediol, 1,2-heptanediol, 2-octanediol, 1,2-
1, such as nonanediol, 1,2-decanediol, 1,2-undecanediol, and 1,2-dodecanediol;
The 2-diol compound is effective in the present invention because it exhibits high selectivity when reacting with a carboxylic acid halide compound.

As the carboxylic acid halide compound used in the present invention, a carboxylic acid halide compound which is usually available as a reagent can be used without any limitation.

Specific examples of these carboxylic acid halide compounds include aliphatic carboxylic acid halide compounds such as acetyl chloride, propionyl chloride, butyryl chloride, valeryl chloride, benzoyl chloride, benzoyl bromide, 2-methylbenzoyl chloride, Aromatic carboxylic acid halide compounds such as 3-methylbenzoyl chloride and 4-methylbenzoyl chloride can be mentioned. Among them, particularly, since they exhibit high selectivity, aliphatic carboxylic acid halide compounds such as acetyl chloride and propionyl chloride, and aromatic carboxylic acid halide compounds such as benzoyl chloride and 4-methylbenzoyl chloride are preferably used. You.

The amount of the carboxylic acid halide compound to be used is not particularly limited. However, since 0.5 mol is a theoretical equivalent to 1 mol of the 1,2-diol compound, the reaction efficiency and the excessive use of the carboxylic acid halide compound are reduced. From an avoiding point of view, this amount is usually used.

The inorganic bases used in the present invention are expected to act not only as a supplement for hydrogen chloride generated in the reaction but also as a promoter. As the inorganic bases, inorganic bases which are usually available as reagents can be used without any limitation.

Specific examples of these inorganic bases include carbonates such as sodium carbonate, potassium carbonate, magnesium carbonate, calcium carbonate, lithium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate and lithium hydrogencarbonate;
Sodium hydroxide, potassium hydroxide, lithium hydroxide,
Hydroxides such as magnesium hydroxide and calcium hydroxide can be mentioned. Among them, particularly, carbonates such as sodium carbonate, potassium carbonate, magnesium carbonate, calcium carbonate, lithium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, and lithium hydrogencarbonate are preferably used because they exhibit high selectivity and yield. .

Further, when an inorganic base having a large specific surface area is used as the inorganic base used in the present invention, the selectivity is further improved. Usually, the size of the specific surface area of the inorganic base used is preferably in the range of 0.8 to ³ m ² / g. The method for preparing the inorganic bases having such a specific surface area is not particularly limited, provided that the specific surface area of the inorganic bases that are industrially manufactured or available as a reagent is within the above range. The specific surface area may be employed as it is, or if the specific surface area is smaller than the above range, it may be pulverized by a pulverizer or the like to adjust the specific surface area corresponding to the above range.

The amount of the inorganic base used in the present invention is
Although there is no particular limitation, if the amount is too large, the post-treatment step becomes complicated, and the possibility of contributing to the decomposition reaction of the product increases.If the amount is too small, the conversion of the reaction becomes low, so that 0.1 to 1 mol of 1,2-diol compound.
It is good to select from the range of 5 to 5 mol, preferably 0.5 to 4 mol.

The optically active 4,4- used in the present invention
Dibromo-4,5-dihydro-3H-dinaphtho [2,1
-C: 1 ', 2'-e] stanepine is disclosed in
No. 03, the optically active 2,
After refluxing 2'-bis (bromomethyl) -1,1'-binaphthalene and tin in a toluene solution in the presence of water,
It can be easily prepared by crystallization. Also, optically active 2,2′-bis (bromomethyl) -1,
The method for producing 1′-binaphthalene includes synthesis,
317-320 (1985) (Synthesi)
s, 317-320, 1985), and (S) -2,2'-bis (bromomethyl) -1,
As for 1′-biphenyl, 2,2′-bis (bromomethyl) -1,1′-biphenyl is reacted with an excess of 1-ephedrine to form a salt, which is then crystallized from ethanol to obtain (S ) -2,2'-Bis (bromomethyl)-
After fractionating the salt of 1,1′-biphenyl and 1-ephedrine, the salt is reduced with lithium aluminum hydride in tetrahydrofuran to obtain
After conversion into (S) -2,2'-dimethyl-1,1'-biphenyl, it can be produced by bromination with N-bromosuccinimide. Also, (R)
Regarding -2,2'-bis (bromomethyl) -1,1'-biphenyl, (S) -2,2 'obtained by the above method.
-Bis (bromomethyl) -1,1'-biphenyl and l-
After unreacted l-ephedrine was removed from the mother liquor after fractionation of the salt with ephedrine, crystallization from acetone gave (R) -2,2'-bis (bromomethyl) -1,1'-. After obtaining a salt of biphenyl and 1-ephedrine, it can be produced by performing reduction and bromination by the same operation as the above method.

In the present invention, the absolute configuration of the objective optically active hydroxyester compound is determined by the optically active 4,4-dibromo-4,5-dihydro-3H-dinaphtho [2,1-c: 1 ′]. , 2'-e] stanepin. That is, when S-form hydroxyesters are desired, S-form 4,4-dibromo-4,5-
Dihydro-3H-dinaphtho [2,1-c: 1 ′, 2′-
e] Stannepine may be used, and if an R-form hydroxyester is desired, the R-form 4,4-dibromo-
4,5-dihydro-3H-dinaphtho [2,1-c:
1 ', 2'-e] stanepin may be used.

The compound acts as a catalyst. When the amount of the compound is too large, the post-treatment step becomes complicated, and when the amount is too small, the reaction rate decreases and the selectivity decreases. Usually, it may be selected from the range of 0.01 to 10 mol%, preferably 0.05 to 5 mol%, based on 1 mol of the 1,2-diol compound as a raw material.

The amount of water used in the present invention is not particularly limited, but if the amount is too large or too small, the selectivity will be reduced. On the other hand, 10 to 1000 ml, preferably 20 to
Preferably, it is selected from the range of 800 ml.

Although the present invention can be carried out without a solvent,
It is usually performed in an organic solvent. As the organic solvent used in the present invention, any solvent that does not react with the 1,2-diol compound, carboxylic acid halide compound and the like can be used without any limitation. Specific examples of these organic solvents include ethers such as tetrahydrofuran, 1,4-dioxane, diethyl ether and tert-butyl methyl ale; halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride; and acetonitrile. , Nitriles such as propionitrile, benzene, toluene, aromatic hydrocarbons such as xylene, acetone, ketones such as methyl ethyl ketone, carbonates such as dimethyl carbonate, ethyl acetate, acetates such as propyl acetate, hexane, Examples thereof include aliphatic hydrocarbons such as heptane.

Among these organic solvents, particularly, tetrahydrofuran, 1,
Ethers such as 4-dioxane, esters such as ethyl acetate, halogenated aliphatic hydrocarbons such as dichloromethane and chloroform, and aromatic hydrocarbons such as benzene and toluene are preferably used.

The amount of the organic solvent used in the present invention is not particularly limited. However, if the amount is too large, the yield per batch is reduced, which is not economical. If the amount is too small, stirring and the like are hindered. For this reason, it is usually preferable to use an organic solvent so that the concentration of the 1,2-diol compound in the reaction solvent is 0.1 to 70% by weight, more preferably 1 to 60% by weight.

Although the reaction method in the present invention is not particularly limited, a 1,2 diol compound, water, inorganic salts,
Optically active 4,4-dibromo-4,5-dihydro-3H
-Dinaphtho [2,1-c: 1 ′, 2′-e] stanepine,
The reaction can be suitably performed by charging a solvent as needed and adding a carboxylic acid halide compound with stirring.

At this time, the reaction temperature used was 1,
Since it depends on the type of the 2-diol compound, the inorganic base and the carboxylic acid halide compound, it cannot be said unconditionally, but if the temperature is too low, the reaction rate becomes extremely low,
If the temperature is too high, a side reaction is promoted.
It is good to carry out in the range of 0 to 20 ° C, preferably -40 to 0 ° C.

The reaction time is not particularly limited, but 0.1 to 40 hours is sufficient.

The above reaction in the present invention is carried out under normal pressure, reduced pressure,
It can be implemented in any state of pressurization. The reaction may be carried out in air or under an atmosphere of an inert gas such as nitrogen, helium or argon.

The thus obtained optically active hydroxyester compound is isolated and purified by a known method. For example, after separating the precipitated base, the solvent is distilled off, and the obtained residue is separated and purified by silica gel chromatography or the like.

[0037]

EXAMPLES The present invention will now be described specifically with reference to examples, but the present invention is not limited to these examples. Incidentally, the yields in the Examples are 1, 2 of the starting materials.
-Calculated based on a diol compound.

Example 1 1-Phenyl-1,2-
Ethanediol 0.14 g (1 mmol), (S)-
4,4-dibromo-4,5-dihydro-3H-dinaphtho
[2,1-c: 1 ', 2'-e] stanepine 1.4mg
(2.5 × 10 −3 mmol), specific surface area 2.6 m ² /
g of sodium carbonate (0.16 g, 1.5 mmol), tetrahydrofuran (5 ml) and water (100 μl) were added.
Cool to 0 ° C.

To this mixed solution, 0.070 g (0.5 mmol) of benzoyl chloride is added dropwise and reacted at -20 ° C. for 14 hours. After completion of the reaction, the precipitated inorganic base is filtered off, and the solvent in the filtrate is distilled off. When the obtained residue was separated and purified by silica gel chromatography, (S) -2-benzoyloxy-1-phenyl-1 was obtained.
0.099 g of ethanol (yield 41%, optical purity 8
4% ee).

Examples 2 to 5 The same operation as in Example 1 was performed except that the reaction temperature was changed to the temperature shown in Table 1. The results are shown in Table 1.

[0041]

[Table 1]

Examples 6 to 9 The same operation as in Example 1 was performed except that the 1,2-diol compounds shown in Table 2 were used. The results are shown in Table 2.

[0043]

[Table 2]

Example 10 The same operation as in Example 1 was performed except that acetyl chloride was used instead of benzoyl chloride. As a result, 0.034 g of (S) -2-acetoxy-1-phenyl-1-ethanol (yield 38%, optical purity 78% e)
e).

Example 11 (S) -4,4-dibromo-4,5-dihydro-3H-
Instead of dinaphtho [2,1-c: 1 ′, 2′-e] stanepine, (R) -4,4-dibromo-4,5-dihydro-3H-dinaphtho [2,1-c: 1 ′, The same operation as in Example 1 was performed except that 2'-e] stanepine was used. As a result, 0.096 g of (R) -2-benzoyloxy-1-phenyl-1-ethanol could be obtained in a yield of 40% and an optical purity of 84% ee.

Examples 12 to 15 0.16 g of sodium carbonate having a specific surface area of 2.6 m ² / g
The same operation as in Example 1 was performed using the inorganic bases shown in Table 3 instead of (1.5 mmol). Table 3 shows the results.

[0047]

[Table 3]

Examples 16 to 17 The same operation as in Example 1 was carried out except that the amount of water added was as shown in Table 4. Table 4 shows the results.

[0049]

[Table 4]

Comparative Example 1 (S) -4,4-dibromo-4,5-dihydro-3H-
The same operation as in Example 1 was performed without using dinaphtho [2,1-c: 1 ′, 2′-e] stanepine. as a result,
Only 0.024 g (yield 10%) of 2-benzoyloxy-1-phenyl-1-ethanol was obtained, and it was a complete racemate.

Comparative Example 2 The same operation as in Example 1 was performed except that no water was used. As a result, 0.075 g of (S) -2-benzoyloxy-1-phenyl-1-ethanol was obtained (yield 31%).
However, the optical purity was only 29% ee.

Comparative Example 3 The same operation as in Example 1 was performed, except that triethylamine was used instead of sodium carbonate. As a result, the amount of 2-benzoyloxy-1-phenyl-1-ethanol was 0.1%.
Although 104 g (yield 43%) was obtained, the optical purity was only 10% ee.

[0053]

According to the present invention, an optically active hydroxyester compound which is a very important compound as a raw material for medicines and agricultural chemicals can be obtained efficiently and easily. That is, it can be said that the production method of the present invention is extremely useful as an industrial production method of an optically active hydroxyester compound.

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Claims (1)

[Claims] 1. An optically active 4,4-dibromo-4,5-dihydro-3H-dinaphtho [2,1-c: 1 ′, 2′-e].
A method for producing an optically active hydroxyester compound, comprising reacting a 1,2-diol compound with a carboxylic acid halide compound in the presence of a catalyst comprising stanepin, an inorganic base, and water.