JPH0369903B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the formula () A triazolyl styryl ketone derivative represented by
That is, 1-(2,4-dichlorophenyl)-4,
The present invention relates to a method for separating geometric isomers of 4-dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-one from a mixture of geometric isomers. The triazolyl styryl ketone derivative represented by the formula () is itself advantageous as a bactericide (Japanese Unexamined Patent Publication No. 130661/1983), but the triazolyl styryl ketone derivative represented by the formula () obtained by reducing it is A triazolylstyryl carbinol derivative represented by, i.e. 1-(2,4-dichlorophenyl)
-2-(1,2,4-triazol-1-yl)-
4,4-Dimethyl-1-penten-3-ol is useful as a fungicide, herbicide, and plant growth regulator, and it is known that its E form is particularly more effective than its Z form. (Unexamined Japanese Patent Publication No. 54-41875)
No. 55-124771, Publication No. 56-25105). By the way, the triazolyl styryl ketone derivative of formula () (hereinafter, unless otherwise specified, E of the triazolyl styryl ketone derivative of formula ())
E body, Z body, and E, Z mixture are respectively E body and Z body.
(referred to as the body and the E/Z body),
For example, there are the following methods. (1) Isomerizing the E/Z form or the Z form to the E form using light (Japanese Patent Application Laid-open No. 147265/1983). (2) Separate the E/Z form by chromatography (Japanese Patent Application Laid-open No. 147265/1983). (3) Only the Z form is precipitated as crystals from the E/Z form, and a mixture rich in the E form is obtained from the mother liquor. If necessary, the Z form is isomerized into the E/Z form (Japanese Patent Application Laid-open No. 1983
−140978, etc.). However, method (1) above requires a special device such as a photoreaction device. Method (2) has many difficulties as an industrial method. Method (3) involves recovering the E form from the mother liquor, and has disadvantages such as not being able to increase the content of the E form too much, and impurities in the raw material E/Z form being unable to be removed. In order to overcome these drawbacks, the present inventors conducted intensive research and found that it was possible to selectively crystallize only the sulfate of the E form from the E/Z form, and after separating and obtaining it, It was discovered that highly pure E-isomer can be obtained by decomposition, and after further various studies, the present invention was arrived at. That is, in the present invention, the E/Z form of the triazolyl styryl ketone derivative represented by the formula () is reacted with sulfuric acid in a solvent, precipitated as a sulfate salt of the E form of the derivative, and then separated and obtained. This is a method for separating geometric isomers of triazolyl styryl ketone derivatives, which is characterized by separating the sulfate to obtain the E form. If the concentration of sulfuric acid used in the method of the present invention is too dilute, the amount of sulfate precipitated will decrease, or in some cases will not precipitate at all. More preferably it is 90-98%. In addition, the amount of sulfuric acid used is usually in the range of 0.5 to 3 times the mole of the E form of the E/Z form in pure terms, but if the amount of sulfuric acid, especially the amount of highly concentrated sulfuric acid, is too large, The amount is more preferably in the range of 0.95 to 1.2 times the mole since the Z-form sulfate is likely to be accompanied by precipitation. The solvent used in the method of the present invention is
Although not particularly limited as long as it is an inert solvent, preferred examples include aprotic organic solvents, such as aromatic hydrocarbons such as benzene, toluene, and xylene, methylene chloride, chloroform, carbon tetrachloride, and dichloroethane. , halogenated hydrocarbons such as trichrene, perchrene, monochlorobenzene, dichlorobenzene, ethyl acetate,
Ester solvents such as ethyl formate, ether solvents such as diethyl ether and tetrahydrofuran, aliphatic or alicyclic hydrocarbons such as hexane, heptane, octane, petroleum ether, ligroin, cyclohexane, and methylcyclohexane, acetone,
Methyl ethyl ketone, methyl isobutyl ketone,
Examples include ketone solvents such as cyclohexanone, nitrile solvents such as acetonitrile and propionitrile, and mixed solvents thereof. Aromatic hydrocarbons and halogenated hydrocarbons are particularly preferably used. The amount of solvent to be used cannot be determined unconditionally as it varies depending on the type and crystallization temperature, but it is usually in the range of 0.5 times to 20 times the weight of the E/Z form of the raw material. In the method of the present invention, the precipitation of E-form sulfate is as follows:
Inoculation of seed crystals is not essential since it usually starts naturally, but may be done to ensure greater certainty. This seed crystal may be added after mixing the sulfuric acid and the raw material E/Z form, or may be added to the E/Z form solution before mixing. The reaction temperature or crystallization temperature is below the boiling point of the solvent and is carried out at a temperature that does not involve side reactions such as isomerization, preferably at 0°C to 80°C. The E-form sulfate can be separated from the reaction solution by using conventional methods such as filtration, centrifugation, and decantation. From the sulfate of E form obtained as above, E
To recover the body, it is usually immiscible with water and E
By mixing the sulfate with a large excess of water in the presence of a solvent that dissolves the sulfate, such as toluene, chlorobenzene, ethyl acetate, ether, carbon tetrachloride, etc., the sulfate is decomposed and a highly purified product is extracted from the oil layer. Body E is recovered. At this time, a base such as sodium carbonate, sodium bicarbonate, sodium hydroxide, or ammonia may be present in excess of sulfuric acid in the aqueous layer. In addition to water, the sulfate can be decomposed using an excessive amount of water-containing protic solvents such as methanol or acetic acid, or bases such as amines. Note that the mother liquor after removing E-form sulfate by the method of the present invention contains a large amount of Z-form, but after removing sulfuric acid by washing with water etc. After isomerizing to the E/Z form by the method shown in the above publication, it can be used again in the method of the present invention, or an excess molar amount of sulfuric acid, more preferably, a Z form sulfate is further added to the mother liquor. Z-form sulfate can also be precipitated by adding seed crystals. Hereinafter, the present invention will be explained using specific examples, but it goes without saying that the present invention is not limited to these examples. Note that E/Z body represents the ratio of E body and Z body. Reference Example 1 1 g of Form E was dissolved in 10 g of toluene, kept at 20°C, and 0.165 cc of concentrated sulfuric acid was added while stirring. The mixture was stirred for 2 hours and then filtered. After washing the crystals with a small amount of toluene, the crystals were vacuum dried. Crystal yield 1.27g Melting point 205.5-207℃ Elemental analysis amount C(%) H(%) N(%) 42.8 4.1 9.8 Elemental analysis amount S(%) Cl(%) 7.5 16.9 Reference example 2 1g of Z-isomer was mixed with 10g of toluene 0.083 cc of concentrated sulfuric acid was added dropwise while stirring while keeping the mixture at 20°C. then 12
The crystals were collected after 6 hours, washed with a small amount of toluene, and then dried in vacuum. Crystal yield 0.62g Melting point 117.5-118℃ Elemental analysis amount C(%) H(%) N(%) 43.0 4.2 9.9 Elemental analysis amount S(%) Cl(%) 7.4 17.1 Example 1 E/Z form (purity 96.8%, E/Z43.0/57.0) 8.11
Dissolve g in 80 g of toluene and add 1.22 g of concentrated sulfuric acid at 20℃.
was dripped. After stirring and keeping warm at 20℃ for 4.5 hours, take it out.
After washing the crystals with 10 c.c. of hexane, the crystals were vacuum dried. Crystal yield: 4.23 g Melting point: 197-205°C Next, 4 c.c. of a 10% aqueous sodium bicarbonate solution, 20 c.c. of toluene and 20 c.c. of water were added to 1 g of this crystal, and at room temperature (20-5°C), After stirring until the crystals disappeared, the aqueous layer was separated, and the oil layer was washed twice with water and concentrated. The obtained crystals were 0.76 g (40% in total based on the E/Z form of the raw material), and the E/Z was 96.0/4.0. Examples 2 to 6 Using the same amount of the E/Z form used in Example 1, the E form was separated in the same manner as in Example 1, except that the solvent, temperature, and time were changed.

【table】

[Table] Example 7 8.11 g of the E/Z substance used in Example 1 was dissolved in 20 g of monochlorobenzene. After keeping the temperature at 30°C, 1.22 g of concentrated sulfuric acid was added dropwise, and the mixture was stirred at the same temperature for 5 hours and then filtered. The crystals were washed with 20 c.c. of monochlorobenzene and then dried in vacuum. The yield was 4.29g. 1 g of this crystal was dissolved in 2 c.c. of dimethylformamide, 20 c.c. of toluene and 20 c.c. of water were added and mixed well, and the aqueous layer was separated. After washing the oil layer twice with water, it was concentrated to obtain E form (E/Z, 97.3/2.7).
0.77g was obtained. Example 8 80% sulfuric acid 3.07 g instead of 1.22 g of concentrated sulfuric acid in Example 7
The same procedure as in Example 7 was carried out except that g was used. The obtained crystal was 4.58 g, and the yield of E form obtained by decomposing 1 g of this crystal was 0.71 g, and E/Z was 96.7/3.3.
It was hot. Note that this salt had a water content of 3.5% and a melting point of 188-193°C. Example 9 The same procedure as in Example 7 was repeated except that 2.45 g of 50% sulfuric acid was used instead of concentrated sulfuric acid. The obtained salt is
3.35g, the E form obtained by decomposing 1g of this crystal is 0.62
g (E/Z100.0/0.0). Additionally, this salt contained 8.4% water and had a melting point of 158-165°C. Example 10 Crude E/Z form (purity 84.4%, E/Z30.6/69.4)
Dissolve 2g in 5g of monochlorobenzene,
0.072 cc of concentrated sulfuric acid was added. After inoculating a small amount of E-form sulfate crystals (obtained in the same manner as in Example 1), the mixture was stirred at 27 to 32°C for 4 hours. The obtained crystal is 0.504g, and the E form obtained by decomposing it is
It weighed 0.384 g, and its purity was 97.6%, E/Z 99.1/0.9. On the other hand, 1.566 g of triazolyl styryl ketone derivative recovered from this mother liquor had a purity of 82.4%.
It was E/Z9.5/90.5. Take 1g of this, dissolve it in 3.2g of monochlorobenzene, and add 0.136cc of concentrated sulfuric acid.
was added at 30°C, stirred for 4 hours, and washed with filtrate and a small amount of monochlorobenzene to obtain 0.915 g of crystals. The entire amount of this crystal was decomposed and 0.7g (purity
95.2%, E/Z9.9/90.1) was recovered. Example 11 5 c.c. of toluene and 10 c.c. of water were added to 2 g of the sulfate obtained in Example 7, and the mixture was stirred at 40°C for 30 minutes.
The crystals almost disappeared, and after further stirring for 30 minutes, the aqueous layer was separated, washed twice with 10 c.c. of water, and then the oil layer was concentrated. 1.481 g of E form was obtained. Example 12 The same procedure as in Example 7 was carried out except that 2.45 g of concentrated sulfuric acid was used instead of 1.22 g of concentrated sulfuric acid. The obtained salt was 4.68g, and 1g of this crystal was decomposed to give E/Z.
An E-body with a ratio of 97.7/2.3 was obtained. Comparative Example 1 In Example 12, after finishing dropping concentrated sulfuric acid, the E-form sulfate obtained in Reference Example 1 and Reference Example 2 were added.
The same procedure was followed except that about 1 mg of each of the Z-isomer sulfates obtained in (1) was added. The obtained crystal was 7.60 g, and when 1 g of this crystal was decomposed, it was found to be an E/Z form with E/Z of 60.8/39.2.

Claims (1)

[Claims] 1 formula A mixture of geometric isomers of a triazolyl styryl ketone derivative represented by is reacted with sulfuric acid in a solvent to precipitate the sulfate of the E form of the derivative as crystals, and after separating and obtaining it, it is decomposed. A method for separating the E form of the triazolyl styryl ketone derivative. 2. The method according to claim 1, wherein the sulfuric acid is 40% or more sulfuric acid. 3. The method according to claim 1 or 2, wherein the sulfuric acid is 90% or more sulfuric acid. 4. The method according to claim 1, 2 or 3, in which sulfuric acid is used in an amount of 0.5 to 3 times the mole of the E-form of the triazolyl styryl ketone derivative. 5. The method according to claim 1, 2, 3, or 4, in which sulfuric acid is used in an amount of 0.95 to 1.2 times the mole of E-form of the triazolyl styryl ketone derivative. 6. The method according to claim 1, 2, 3, 4 or 5, wherein the solvent is an aprotic inert solvent. 7. The method according to claim 6, wherein the solvent is an aromatic hydrocarbon or a halogenated hydrocarbon.