JPS63264574A - Production of 1,3,5-substituted-5-(4-methylphenacyloxy) pyrazole - Google Patents

Abstract

PURPOSE:To obtain, simply in high selectivity, the title compound by using a specific solvent and a specific catalyst in the reaction of 1,3-dimethyl-4-(2,4- dichloro-3-methylbenzoyl)-5-hydroxypyra-zole with 4-methylphenacyl halide. CONSTITUTION:The reaction of 1,3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5- hydroxypyrazole with 4-methylphenacyl halide is carried out in the presence of a phase-transfer catalyst in an inert organic solvent which is sparingly soluble in water and dissolves the objective compound selectively in a reduced amount (dissolving less than 1g per 100g of the solvent) such as diethyl ether, n-hexane to give the objective compound: 1,3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5-(4- methylphenacyloxy)pyrazole.

Description

Detailed Description of the Invention Technical Field The present invention relates to 1,3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5-(4-methylphenacyloxy)pyrazole (compound *C) This relates to a manufacturing method.

Compound C is known as a compound having herbicidal activity, and is useful as a herbicide.

The prior art method for producing compound C is disclosed in JP-A-57-72903.
As disclosed in the publication, 1,3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl) is prepared using a solvent such as methyl ethyl ketone or acetonitrile in the presence of a deoxidizing agent such as potassium carbonate. A method is known in which -5-hydroxypyrazole (compound '@A) and 4-methylphenacyl halide (compound @mB) are reacted under conditions such as heating under reflux.

However, in this method, in addition to the presence of inorganic salts, there are byproducts of the decomposition reaction of the compound B due to the high temperature conditions. It has the disadvantage that distillation and recrystallization are complicated.

On the other hand, a similar compound of compound C 1,3-dimethyl-4-(
2,4-dichlorobenzoyl) -5-1u conversion power yv
As a manufacturing method for
Publication No. 167971 discloses that a similar compound 1.3 of Compound A is prepared using an inert hydrocarbon that is sparingly soluble in water and/or water as a solvent in the presence of a phase transfer catalyst of a quaternary ammonium salt and a deoxidizing agent. -dimethyl-4-(2,4-dichlorobenzoyl)-5-hydroxypyrazole and formula X-CH,C
0-RCX is Cl%Br or 0-RCX, and R represents a phenyl group that may be substituted with a methyl group or a tertiary-butyl group that may be substituted with a halogen atom. is proposed.

In this method, hydrocarbons such as toluene, dichloroethane, etc. and/or water are used as solvents, so the inorganic salts are dissolved and removed in water. Even if operations such as drying and distillation of the solvent are performed, organic impurities are not removed, so the desired product is obtained only in the form of crude crystals.

Furthermore, JP-A-61-103872 discloses that in the presence of a phase transfer catalyst of a cyclic imine quaternary salt and a deoxidizing agent, an inert hydrocarbon that is sparingly soluble in water, such as toluene or 1,2-dichloroethane, is used as a solvent. A method of reacting compound A and compound B to cleave compound C using water and water is proposed.

However, in this method, since a highly active phase transfer catalyst exists in the hydrocarbon layer, the aqueous layer is first separated and removed after the reaction, and then the organic layer is washed with acid and water to transfer the phase transfer. A series of steps are required in which the entire aqueous layer containing the catalyst is separated and removed, and finally the organic solvent is distilled off under reduced pressure.

After all, in order to produce the target compound Ct-m according to the known technology, it is essential to separate and remove inorganic salts, catalyst, solvent, by-products, etc. from the reaction mixture, and in terms of equipment for industrialization,
As long as the target substance is dissolved in the solvent, it is necessary to install an evaporation drying device, a recrystallization device, etc.

Therefore, how to synthesize the target compound with high selectivity and simplify the process is an important point in industrialization.

Summary of the Invention The present invention provides 1,3-dimethyl-4-(2,4-dichloro-
3-methylbenzoyl)-5-hydroxypyrazole (
Compound A) and 4-methylphenacyl halide (Compound B
) in the presence of a deoxidizing agent to produce 1,3-dimethyl-4
-(2,4-dichloro-3-methylbenzoyl)-5-
(4-methylphenacyloxy)pyrazole (compound C
)'t- In the agricultural method, water and an inert organic solvent that is sparingly soluble in water and selectively showing low solubility for the compound C are used as the solvent, and the reaction is carried out in the presence of a phase transfer catalyst. 1, 3.4-Replacement-
A method for producing 5-(4-methylphenacyloxy)pyrazole is provided.

Effects of the Invention According to the method of the present invention, the target compound C can be obtained with high selectivity and high yield, and the purification operation can be simplified to just filtering out the crystallized target compound C.

Furthermore, the organic solvent layer of the reaction solution after separation and removal of the target compound C4 can be separated from the aqueous layer and reused as it is as a reaction solvent, and the loss of the target compound C can be significantly reduced. or,
The amount of catalyst used can also be significantly reduced.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a combination of 1,3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5-hydroxypyrazole (compound A) and 4-methylphenacyl halide (compound B). in the presence of a deoxidizing agent, using water and an inert organic solvent that is sparingly soluble in water and selectively exhibits low solubility for the compound C, and in the presence of a chiral phase transfer medium. This is a method of reacting to produce 1,3-dimethyl-4-(2,4-dichloro-3-methylbenzoyl)-5-(4-methylphenacyloxy)pyrazole (compound *C) kff.

In the reaction of the method of the present invention, Compound A, its salts, and the deoxidizing agent are easily soluble in water, and Compound B1 is a decomposition reaction by-product of Compound B, other organic by-products, etc., and a phase transfer catalyst. is easily soluble in the inert organic solvent, and since compound C is a bath in water and a slight bath in the inert organic solvent, only the target compound C crystallizes as the reaction progresses. It's coming.

The inert organic solvent that is sparingly soluble in water and selectively shows low solubility for compound C used in the method of the present invention is:
Examples include ethers such as diethyl ether and diisopropyl ether, and aliphatic or hydrocarbons such as n-hexane, n-hebutane and cyclohexane. Here, the solubility of compound C in the inert organic solvent is about 3f7100
F solvent or less, preferably 11//100 f solvent or less.

These organic solvents may be used alone or in combination.

The proportion of the mixed solvent consisting of an inert organic solvent and water used in the present invention can be changed as appropriate.

For example, inert organic 1 volume: water (response ratio) = 1: about 0
．． A mixing ratio of 3 to about 5, preferably 1:0.8 to about 1.5 can be exemplified. The amount of the mixed solvent to be used may be within a range that can achieve selectively low solubility of Compound C, for example, about 5 to about 50 times the weight of compound mA, preferably about 10 to about 30 times by weight. An example of a usage amount such as a quantity can be given.

The phase transfer 'kJJ' flux used in the present invention has the following formula, [wherein R1, R2, R3, and R4 are an alkyl group, a hydroxyalkyl group, a haloalkyl group, an alkoxyalkyl group, an aralkyl group, an alkenyl group, or an alkynyl group. groups, which may be the same or different, and R,,
A cyclic base may be formed from R and a nitrogen atom, or from R1, R,, R, and a nitrogen atom. Y is a hydroxyl group, a halogen atom, an organic acid residue or an inorganic acid residue.

] Examples of the quaternary ammonium salts include the following.

(Left below) Promidochloridetate ``J'''') = ``C:NC,,H-1?4''' PY
LC Muchloride, Yuu. , , , H3C4N C, □) I2.
Of' 4PCLC Benzyl Picolinium Chloride (Ko'c Mountain Beni) α”
MPCBC Quaternary ammonium salts such as those exemplified above can be used alone or in combination. The amount used can be selected appropriately, but for example, for 1 mole of compound A,
All examples of usage amounts such as from about 0.01 to about 0.5 moles, preferably from about 0.02 to about 0.1 moles, may be given.

Furthermore, when carrying out the method of the present invention, compound B, 4-
When using 4-methylphenacyl chloride in which the halide is 0 as the methylphenacyl halide, in addition to using a compound as described above as a phase transfer catalyst, for example, potassium iodide, iodide (IJ) It is better to add, for example, about 0.01 to about 1 mole per mole of compound %, ff1A, using cocatalysts such as aluminum, cuprous iodide, cuprous bromide, potassium bromide, and sodium bromide. The target product can be obtained at a high production rate.

Preferred examples of the deoxidizing agent used in the present invention include basic inorganic compounds such as sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide. The amount used can be selected as appropriate, but for example, the amount used is about 0.5 to about 6 mol, preferably about 0.55 to about 1 mol, per 1 mol of compound A. Can be done.

In the method of the invention 1,3-dimethyl-4-(2,4
-dichloro-3-methylbenzoyl)-5-hydroxypyrazole (compound A) can also be subjected to the reaction in the form of its alkali metal salt or alkaline earth metal salt. Therefore, in the present invention, the term "reacting a compound with compound B" includes the embodiment in which compound A in the form of a salt and compound 'l>2JB are reacted.

Examples of such salts of compound A include alkali metal salts such as sodium salts and potassium salts, and alkaline earth metal salts such as calcium salts and magnesium salts. When these salts are subjected to the reaction, the above-mentioned deoxidizing agent is not necessarily required.

In the method of the present invention, compound ? The reaction molar ratio of 7A and Compound B can be selected and changed as appropriate, but it is preferable to use approximately equimolar amounts, for example, about 0.8 to about 1.2 mol of Compound B to 1 mol of Compound A. Examples of reaction molar ratios include: Since the reaction proceeds almost stoichiometrically, if compound A is provided in excess of compound B,
After the reaction, unreacted Compound A remains in the aqueous layer in the form of a salt, but if this aqueous solution is extracted with acid in the presence of a solvent such as 1,2-dichloroethane, and then subjected to controlled alkaline extraction, it can be quantitatively extracted. Compound A can be recovered and reused.

On the other hand, even if compound B is provided in excess of compound A, unreacted compound Bt can be easily reused after the reaction as described below.

In the reaction of the present invention, compound A and compound B are brought into contact with each other in the presence of the above-mentioned inert organic solvent and water in the presence of the above-mentioned quaternary ammonium salt as a phase transfer catalyst and a deoxidizing agent. This can be easily done by doing the following.

This contact between compound A and compound B can be carried out in any manner, for example, compound A1 and compound B1 are present in the solvent.
The reaction can be carried out by adding the above-mentioned quaternary ammonium salt and deoxidizing agent in any order or even simultaneously. At this time, these reaction components, phase transfer catalyst, and deoxidizing agent may be added in the form of an appropriate solution. For example, to an aqueous solution of the compound A in the form of a salt, compound B, It is also possible to add the ammonium salt and the organic solvent in any order or simultaneously.

The reaction temperature and time can be changed as appropriate, for example, about 0.
Reaction temperatures and times such as 0°C to reflux and about 1 to about 48 hours may be exemplified. Since the reaction proceeds even at room temperature, there is no particular need for heating, but it is preferable to use a temperature between room temperature and about 60°C.

The target compound C selectively crystallizes as the reaction progresses, so after the reaction is completed, the solution part is removed by filtration and the filtered crystals are dried to obtain the target compound Ct in high purity. .

In addition, in the organic solvent layer of the mother liquor after separating and removing compound C, the target compound C1 phase transfer catalyst and/or unreacted raw material compound B are dissolved in the organic solvent layer. The obtained organic solvent layer can be reused as it is as a solvent containing a phase transfer catalyst. Therefore, the second
The subsequent reactions can be carried out, for example, by adding the recovered organic solvent and compound Bt to an aqueous solution of compound A in salt form. Further, the target compound C crystallized in the second and subsequent reactions can be obtained in high yield because the organic solvent is a saturated solution of the target compound.

Examples Example 1 First reaction: Compound A 5.98 t (20.0 mmol), sodium carbonate 1.71 F (16.1 mmol), potassium iodide 0.10 Of (0,603 mmol) and TOMAC as a phase transfer catalyst in a 90°72 solution of water.
o, 255 f (0,630 mmol), 55.6 f of diimpropyl ether and 3.37 f (20,0 mmol) of (J4-methyl 7-enacyl chloride) were added;
The reaction was carried out at 50°C for 29 hours. After the reaction was completed, the precipitate was collected by filtration and dried to obtain 7.93 F crystals of the target compound C (purity 97.8%, 18.0 mmol, yield 89.9%). The filtered mother liquor was separated and the organic layer was quantified by total liquid chromatography.
, 3 mmol) (reaction yield 96.2%)
.

Second reaction: Using the entire amount of the organic layer after the first reaction, add Compound A1 sodium carbonate, potassium iodide, water and Compound B in the same amount as in the first reaction, and carry out the reaction in the same way. , and post-processed in the same way. The crystals of the target compound C obtained were 8.3
4 t (purity 97.9%, 18.9 mmol, yield 9
4.6), and the organic layer contains 0.64 t (1,5
The reaction yield calculated by subtracting all the contents in the reused organic layer was 95.7%.

@3rd to 5th reactions: Table 1 shows the results of repeating the 3rd to 5th reactions in the same manner.

Table 1 1st 96.2 89.9 97.8 2nd 95.7 94.6 97.
9 3rd 95.6 94.5 9
8.2 4th 95.0 96.7 97
．． 2 5th 94.7 94.0
96.9 Example 2 Cyclohexane 76.3fi was used as the organic solvent, 3
The reaction was carried out in the same manner as the first reaction in Example 1, except that the reaction was carried out for 1 hour, and 7.65 F crystals of the target compound C (purity: 98.1, 17.4 mmol, yield: 87.0) were obtained. Obtained. Also, in the organic layer, 0.789 (1°8 mmol)
(reaction yield 96.0%).

Example 3 The reaction was carried out in the same manner as the first reaction in Example 1, except that 52.79 f of n-hexane was used as the organic solvent, 6.16 f (20.6 mmol) of Compound A was used, and the reaction was carried out for 14 hours. 8.34 tons of crystals of the target compound C (purity 95.6%, 18.5 mmol, yield 92.4) were obtained. Further, the organic layer contained 0.189 (0.42 mmol) (reaction yield 94.5%).

Example 4 Toluene 1.02 and n-heptane 50.
The reaction was carried out in the same manner as the first reaction in Example 1, except that a mixed solvent with 7f was used and the reaction was carried out for 24 hours. (Purity 98°5%, 17.
8 mmol, yield 89.2).

Further, the organic layer contained 0.69 F (1.6 mmol) (reaction yield 97.2%).

Example 5 The same procedure as in the first reaction of Example 1 was carried out except that 1'LMACO, 344t (0°600 mm IJ mol) was used as a phase transfer catalyst and the reaction was carried out for 12 hours. .99 F (purity 97.3, 18.
0.17 mol, yield 90.1%). Further, the organic layer contained II'i0.53 F (1.2 mmol) (reaction yield 96.3%).

Example 6 LHHCO, 466f (0,60
Example 1 except that 0 mmol) was used and the reaction was carried out for 18 hours.
The reaction was carried out in the same manner as the first reaction, and crystals of the target compound C were obtained at 7.80 ? (Purity 97.2 excellent, 17-6 mi')
mol, yield 8f, 9%). Also, in the organic layer, 0.5
8 F (1.3 mmol) was contained (reaction yield: 94.6).

Example 7 Compound A 5.98 F (20,0 mmol), sodium carbonate L70 F (16,0 mmol) and water 9
TOMACO, as a phase transfer catalyst, was added to the solution at 0°4f.
Same as Example 1 except that 242f (0,600 mmol), diisopropyl ether 54.9 F and 4-methylphenacylbromide 4.269 (20,0 mmol) were added and limed at 30°C for 7 hours. After post-treatment, the target compound C8,11f (purity 98°4, 18.
5 mmol, yield 92.5 h) was obtained.

The organic layer contained 0.55 f (1.3 mmol) (reaction yield: 98.9).

Claims (2)

[Claims] (1) 1,3-dimethyl-4-(2,4-dichloro-3
-methylbenzoyl)-5-hydroxypyrazole (compound A) and 4-methylphenacyl halide (compound B)
1,3-dimethyl-4-
(2,4-dichloro-3-methylbenzoyl)-5-(
4-Methylphenacyloxy)pyrazole (compound C)
In the method for producing, the reaction is carried out in the presence of a phase transfer catalyst, using water and an inert organic solvent that is sparingly soluble in water and selectively showing low solubility for the compound C as a solvent. 1,3,4-substituted-5-(
Method for producing 4-methylphenacyloxy)pyrazole. (2) The production method according to claim 1, characterized in that the organic solvent layer of the solution obtained by separating and removing compound C precipitated from the reaction product is reused as the reaction solvent.