JP3534810B2 - Method for producing phenethyl alcohol derivative (2) - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a phenethyl alcohol derivative which improves the storage stability of a color image on a heat sensitive recording material.

[0002]

2. Description of the Related Art Conventionally, when a compound having an ether bond is produced by reacting a phenol (alcohol) with a compound having an epoxy group, a tertiary amine or quaternary ammonium salt is used as a catalyst in an organic solvent. A method of carrying out an addition reaction in a medium grade is generally known. However, in this reaction, it is known that there are α-cleavage and β-cleavage in the cleavage direction of the epoxy ring (Makromol.
m. , 183.587 (1982)), which makes it difficult to obtain only one of the desired products in high yield.

Further, to a compound having two or more phenolic hydroxyl groups such as a dihydroxydiphenyl sulfone compound, a reaction of selectively adding a compound having an epoxy group to only one hydroxyl group without using a protecting group is carried out. It was very difficult to do. Furthermore, it is known that a compound having an epoxy group is generally unstable in the presence of an acidic or alkaline compound and easily makes a polymer, and the addition reaction of the compound having an epoxy group under such conditions is easy. There wasn't.

[0004]

DISCLOSURE OF THE INVENTION According to the present invention, first, a styrene oxide compound and a hydrogen halide are reacted to selectively obtain 2-halogeno-2-phenylethanol, and then this and a dihydroxydiphenyl sulfone compound are obtained. The present invention proposes a method for producing a desired phenethyl alcohol derivative with a high selectivity by selectively reacting a halogen atom with a hydroxyl group by reacting with.

[0005]

That is, the present invention relates to a halohydrin compound represented by the general formula (II) obtained by the reaction of a styrene oxide compound and hydrogen halide,
A method for producing a phenethyl alcohol derivative represented by the general formula (I), which comprises reacting the dihydroxydiphenyl sulfone compound represented by the general formula (III) in the presence of an alkaline substance.

[0006]

Embedded image General formula (I) General formula (II) General formula (III) (In the formula, R ¹ , R ² and R ³ each independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkenyl group, R ⁴ represents a hydrogen atom, a lower alkyl group or a phenyl group, and n, m And p each represent an integer of 1 to 4, and X represents a halogen atom.)

The manufacturing method of the present invention will be described in detail below. In the production method of the present invention, first, 1 mol of a styrene oxide compound is reacted with 1 mol or more of a hydrohalic acid such as hydrobromic acid in a water-insoluble organic solvent to give a compound represented by the general formula (II) 2 -Halogeno-2-phenylethanol is obtained.

As the solvent used in the production method of the present invention, either a water-insoluble organic solvent alone or a water-organic solvent bilayer solvent can be used, but preferably,
In a two-layer system solvent of water and a water-insoluble organic solvent.

In the present invention, the mixing ratio of water to the water-insoluble organic solvent is 0.1-1.
It is 5 volumes, more preferably about the same volume, and an alkaline substance and the 4,4′-dihydroxydiphenyl sulfone compound represented by the general formula (III) are added to this two-layer system solvent, and the above-mentioned 2- Add halogeno-2-phenylethanol and react.

In the production method of the present invention, the reaction temperature is 5
0 to 90 ° C is preferable, and more preferably 60 to 70 ° C.
React for several hours to several tens of hours. When the temperature is 50 ° C. or lower, the yield tends to decrease, and when the temperature is 90 ° C. or higher, the yield tends to decrease due to the lower selectivity, and the di-substituted product tends to increase.

In the production method of the present invention, the amount of each used is 0.5 to 2 mol, preferably 0.8 to 2 mol per 1 mol of the diphenyl sulfone compound in the case of an alkaline substance.
1.2 mol, in the case of 2-halogeno-2-phenylethanol, 0.2 to 1 mol, preferably 0.4 to
It is 0.5 mol.

The general formula (II) used in the present invention is
As the dihydrocyphenyl sulfone represented by I),
4,4'-dihydroxydiphenyl sulfone, 4,4 '
-Dihydroxy-3,3'-dichlorodiphenyl sulfone, 4,4'-dihydroxy-3,3'-dibromodiphenyl sulfone, 4,4'-dihydroxy-3,3 ',
5,5'-tetrachlorodiphenyl sulfone, 4,4 '
-Dihydroxy-3,3 ', 5,5'-tetrabromodiphenyl sulfone, 4,4'-dihydroxy-3,3'
-Dimethyldiphenylsulfone, 4,4'-dihydroxy-3,3 ', 5,5'-tetramethyldiphenylsulfone, 4,4'-dihydroxy-3,3'-diallyldiphenylsulfone, 4,4'-dihydroxy- Three
3 ', 5,5'-tetraallyl diphenyl sulfone,
4,4'-dihydroxy-3,3'-dichloro-5,
5'-dimethyldiphenyl sulfone, 4,4'-dihydroxy-3,3'-dibromo-5,5'-dimethyldiphenyl sulfone, 4,4'-dihydroxy-3,3'-
Examples thereof include dimethyl-5,5'-diallyldiphenyl sulfone.

The general formula (II) used in the present invention
As the halohydrin compound represented by 1-chloro-2
-Phenylethanol, 1-bromo-2-phenylethanol, 1-chloro-1-methyl-2-phenylethanol, 1-bromo-1-methyl-2-phenylethanol, 1-chloro-1,2-diphenylethanol, 1-
Bromo-1,2-diphenylethanol, 1-chloro-
2- (2-chlorophenyl) ethanol, 1-bromo-
2- (2-chlorophenyl) ethanol, 1-chloro-
2- (3-chlorophenyl) ethanol, 1-bromo-
2- (3-chlorophenyl) ethanol, 1-chloro-
2- (4-chlorophenyl) ethanol, 1-bromo-
2- (4-chlorophenyl) ethanol, 1-chloro-
2- (2-methylphenyl) ethanol, 1-bromo-
2- (2-methylphenyl) ethanol, 1-chloro-
2- (3-methylphenyl) ethanol, 1-bromo-
2- (3-methylphenyl) ethanol, 1-chloro-
2- (4-methylphenyl) ethanol, 1-bromo-
2- (4-methylphenyl) ethanol, 1-chloro-
2- (2-bromophenyl) ethanol, 1-bromo-
2- (2-bromophenyl) ethanol, 1-chloro-
2- (3-bromophenyl) ethanol, 1-bromo-
2- (3-Bromophenyl) ethanol, 1-chloro-
2- (4-bromophenyl) ethanol, 1-bromo-
2- (4-bromophenyl) ethanol, 1-chloro-
1-methyl-2- (2-chlorophenyl) ethanol,
1-Bromo-1-methyl-2- (2-chlorophenyl)
Ethanol, 1-chloro-1-methyl-2- (3-chlorophenyl) ethanol, 1-bromo-1-methyl-2
-(3-chlorophenyl) ethanol, 1-chloro-1
-Methyl-2- (4-chlorophenyl) ethanol, 1
-Bromo-1-methyl-2- (4-chlorophenyl) ethanol, 1-chloro-1- (2-chlorophenyl)-
2-phenylethanol, 1-bromo-1- (2-chlorophenyl) -2-phenylethanol, 1-chloro-
1- (3-chlorophenyl) -2-phenylethanol, 1-bromo-1- (3-chlorophenyl) -2-phenylethanol, 1-chloro-1- (4-chlorophenyl) -2-phenylethanol, 1-bromo -1-
(4-chlorophenyl) -2-phenylethanol, 1
-Chloro-1- (2-methylphenyl) -2-phenylethanol, 1-bromo-1- (2-methylphenyl)
2-phenylethanol, 1-chloro-1- (3-methylphenyl) -2-phenylethanol, 1-bromo-1- (3-methylphenyl) -2-phenylethanol, 1-chloro-1- (4 Examples include -methylphenyl) -2-phenylethanol and 1-bromo-1- (4-methylphenyl) -2-phenylethanol.

Examples of the water-insoluble organic solvent used in the present invention include aromatic organic solvents such as benzene, toluene, chlorobenzene and dichlorobenzene, methyl isobutyl ketone, diethyl ketone and ethyl butyl ketone. Examples thereof include ketone organic solvents, ester organic solvents such as ethyl acetate, and aliphatic halogenated solvents such as chloroform and carbon tetrachloride.

In the present invention, the alkaline substance may be an organic or inorganic alkaline substance.
However, it is economically preferable to use an inorganic alkaline substance, for example, a hydroxide or carbonate of an alkali metal or an alkaline earth metal, specifically sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate. , Potassium carbonate, lithium carbonate and the like.

In the production method of the present invention, various treatment methods after completion of the reaction are possible. For example, an acidic compound such as sulfuric acid is added to the reaction solution to adjust the pH to be weakly alkaline, and the aqueous layer is separated. Then, there is a method in which a hot alkaline substance aqueous solution is added to the organic solvent layer to extract the target compound in the aqueous layer, and the target compound is obtained by precipitating crystals by cooling or acidifying.

In this way, α containing a small amount of by-products
Cleavage of the target compound is obtained, but if necessary, using an organic solvent such as acetic acid esters, dialkyl ketones or an aqueous solution of a heated alkaline compound, and further performing recrystallization by using both in combination, a higher purity target compound can be obtained. The compound can be prepared.

[0017]

EXAMPLES The present invention will be described in more detail with reference to Reference Examples and Examples below, but the present invention is not necessarily limited to these. Reference Example (Synthesis of Halohydrin Compound) 20 ml of chloroform and 6 g (0.05 mol) of styrene oxide were placed in a 100 ml four-diameter flask, and then,
47% hydrobromic acid 8.6 g (0.05 mol) 10-1
After adding at 5 ° C., the mixture was stirred for 15 minutes. Liquid separation is performed to obtain an organic solvent layer, and the organic solvent is distilled off to give a light yellow transparent oily substance 1
0.0 g was obtained. This was confirmed to be 2-bromo-2-phenylethanol by NMR spectrum ( ¹ H-NMR: 7.35 (m, 5H); 5.0
2 (t, J = 5.8 Hz, 1 H); 3.98 (m, 2
H); 2.79 ppm (bs, 1H, OH). ). Yield: 99%.

(Example 1) 50 ml of water and 4 g (0.1 mol) of sodium hydroxide were added to a 300 ml four-diameter flask.
4'-dihydrosidiphenyl sulfone (hereinafter referred to as "BP
25 g (0.1 mole) of S) and 30 ml of methyl isobutyl ketone were added. Then, 2-bromo-2-phenylethanol produced by the method shown in Reference Example 10.
36 g of a methyl isobutyl ketone solution containing 0 g (0.05 mol) was added dropwise over 30 minutes, and the mixture was further stirred at 60 to 65 ° C for 5 hours. After the reaction was completed, dilute sulfuric acid was added to acidify the aqueous layer and the layers were separated. When the organic layer was analyzed by high performance liquid chromatography, it contained 7.0 g of the desired product, 4- (4- (2-hydroxy-1-phenylethyloxy) phenylsulfonyl) phenol. The selectivity was 93%, and the yield from styrene oxide was 38%.

(Example 2) 47% as in the reference example
35% hydrochloric acid was used in place of hydrobromic acid to give 2-chloro-2-phenylethanol as a colorless and transparent oily substance. 7.
8 g was obtained. Using this 7.8 g (0.05 mol),
In the same manner as in Example 1, using 50 ml of water, 4 g (0.1 mol) of sodium hydroxide, 25 g (0.1 mol) of BPS, and 50 ml of methyl isobutyl ketone at 60 to 65 ° C.
And reacted for 5 hours. Then, after performing the same treatment, the organic solvent layer was analyzed by high performance liquid chromatography. As a result, 5- (4- (2-hydroxy-1-phenylethyloxy) phenylsulfonyl) phenol, which was the target substance, was found to be 5 The content of the target compound was 94%, and the yield from styrene oxide was 28%.

(Example 3) 47% as in the reference example
57% hydroiodic acid was used in place of hydrobromic acid,
12.4 g of a pale orange transparent oily substance of iodo-2-phenylethanol was obtained. Using 12.4 g (0.05 mol) of this, in the same manner as in Example 1, 50 ml of water, 4 g of sodium hydroxide (0.1 mol), and 25 g of BPS.
(0.1 mol) and 50 ml of methyl isobutyl ketone were used and reacted at 60 to 65 ° C for 5 hours. After performing the same treatment below, the organic solvent layer was analyzed by high performance liquid chromatography to find that it was 4- (4- (2-
Contains 9.6 g of hydroxy-1-phenylethyloxy) phenylsulfonyl) phenol, the selectivity of the target product is 93%, and the yield from styrene oxide is 52%.
Met.

[0021]

When the dihydroxydiphenyl sulfone compound and the styrene oxide compound are directly reacted, an extremely large amount of by-products are generated due to the di-substituted product, the polymer and the cleavage direction of the epoxy group. However, according to the production method of the present invention, one hydroxyl group reacts with a halogen group, and a phenethyl alcohol derivative having an α-cleavage ether bond can be obtained with high selectivity.

─────────────────────────────────────────────────── --- Continuation of the front page (56) References JP-A-5-246924 (JP, A) JP-A-5-255234 (JP, A) JP-A-6-166649 (JP, A) JP-A-6- 166648 (JP, A) International publication 94/07832 (WO, A1) (58) Fields investigated (Int.Cl. ⁷ , DB name) C07C 315/04 C07C 317/22 C07C 41/03 C07C 43/23 CA ( STN) CAOLD (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. A halohydrin compound represented by the general formula (II) and a dihydroxydiphenyl sulfone compound represented by the general formula (III) in the presence of an alkaline substance.
A method for producing a phenethyl alcohol derivative represented by the general formula (I), which comprises reacting. Embedded image General formula (I) General formula (II) General formula (III) (In the formula, R ¹ , R ² and R ³ each independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkenyl group, R ⁴ represents a hydrogen atom, a lower alkyl group or a phenyl group, and n, m And p each represent an integer of 1 to 4, and X represents a halogen atom.) 2. The method for producing a phenethyl alcohol derivative according to claim 1, wherein the reaction is carried out in a water-organic solvent bilayer solvent.