JPS58109443A - Preparation of 3-(2'-chloro-4'-trifluoromethylphenoxy) acetophenone - Google Patents

Abstract

PURPOSE:To prepare the titled substance useful as an intermediate raw material of agricultural chemicals, pharmaceuticals, etc., easily, in short steps, by using 3-bromoacetophenone which is available at a relatively low cost, as a raw material, and reacting the compound with 2-chloro-4-trichloromethylphenol in the presence of copper. CONSTITUTION:The objective compound is prepared by reacting 3-bromoacetophenone with 2-chloro-4-trifluoromethylphenol or its alkali metal salt in an inert solvent, preferably pyridine or N,N-dimethyl-4-amino-pyridine, in the presence of copper and/or a copper compound at 60-170 deg.C, preferably 80-140 deg.C. The amount of 2-chloro-4-trifluoromethylphenol or its alkali metal salt is preferably 0.65-1.25mol per 1mol of 3-bromoacetophenone.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 3-(2'-chloro-4'-1-lifluoromethylphenoxy)acetophenone. More specifically, the present invention involves reacting 3-bromoacetophenone and 2-chloro-4-trichloromethylphenol or an alkali metal salt thereof in an inactive solvent in the presence of copper and/or a copper compound. 3-(2'~chloro=4'-1
-Relating to a method for producing lifluoromethylphenoxy)acetophenone.

3-(2'-chloro-4'-1 produced by the method of the present invention)
-Lifluoromethylphenoxy)acetophenone is represented by the structural formula [I] shown below. (Hereinafter abbreviated as compound [■]).

Compound (1) is further nitrilized to form compound (n) having the following structure. It is an extremely important substance that is used as an intermediate raw material for agricultural chemicals, medicines, etc.

(2) As a conventionally known method for producing compound (1), as shown below, 3-hydroxyacetophenone and 3.4
A common method is the condensation of -dichlorobenztrifluoride, such as the condensation reaction of 3-hydroxyacetophenone and promhenzene (US Pat. No. 3.6).
00,437)), it can be analogized to a container.

However, in this method, the raw material compound 3-hydroxyacetophenone is difficult to synthesize industrially at a low cost and must be produced through an extremely complicated multi-step reaction, making it an expensive substance. I can't say it's an advantageous method.

Furthermore, as a method for directly producing compound (n), 2-
di-o-5-fluoroacetophenone and 2-chloro-4-
There is a method of reacting trifluoromethylphenol as follows.

(3) However, this method also has a high content of 2-2I-5-fluoroacetophenone as a raw material compound, and cannot be said to be an industrially advantageous method.

The present inventors have discovered that the target compound (1) or compound (I
As a result of various studies on methods for producing I), the condensation of 3-bromoacetophenone and 2-chloro-4-trifluoromethylphenol or an alkali metal salt thereof,
The present invention was completed by discovering a method for producing compound [1] and confirming that this is an industrially advantageous method.

As a method for directly producing compound (r) or compound (II), in the reaction investigated by the present inventors, one of the raw materials, 3
-Haloacetophenone and the resulting compounds are listed below. Note that the other raw material, 2-chloro-4-
Trifluoromethylphenol (4) was omitted since it is commonly used in all reactions.

Below is the blank space (5) Classification 3-haloacetophenone To the product compound
CJl B 'C11 D CH E C1l! (6) The reactivities of the 3-position halokene atoms of the raw material compounds shown above are arranged in order from A to F in a direction from high to low. Among these, the target compound (1) or (
C and D are raw materials that can produce n) in good yield. That is, even if the reactivity is too high, the reaction rate is high but the yield of the target compound is low, in other words, the selectivity is low. Furthermore, if the reactivity is too low, the reaction rate will be low and the yield will be low. Therefore, raw materials C and D are the only substances with the most balanced reaction rates, but raw material C is unfortunately difficult to synthesize and is extremely expensive as an industrial raw material. In this way, it was confirmed that the most important and only ideal raw material for the present invention is D, 3-bromoacetophenone.

According to the method of the present invention, 3-bromoacetophenone and 2
-Chloro-4-trifluoromethylphenol or its alkali metal salt is reacted with 3-(2'
-Chloro-4'-trifluoromethylphenoxy)acetophenone can be produced (7). As an inert solvent, pyridine,
Pyridine derivatives, dimethylformamide, N-methylpyrrolidone, quinoline, toluene, xylene, dimethyl sulfoxide, diglyme, collidine, tertiary amine compounds, etc. are used, but the most preferred are pyridine and N-methylpyrrolidone.
, N-dimethyl-4-aminopyridine.

Copper compounds used in the method of the present invention include cuprous chloride, cupric chloride, cuprous bromide, cupric bromide, cuprous iodide, cuprous oxide, cupric oxide, etc. can be given. In the method of the present invention, copper and copper compounds are used in an amount of 0.025 mol or more, preferably 0.05 to 1 mol, per 1 mol of 3-bromoacetophenone. If the amount of copper and copper compound is less than 0.025 mol per 1 mol of 3-bromoacetophenone, a large amount of oily high-boiling substance will be produced and the yield of the target compound (1) will decrease, which is not preferable.

Even if the amount of copper and copper compound exceeds 1 mol, no improvement effect is observed and it is not economical.

The reaction temperature in the method of the present invention is not particularly limited, but (8) it is generally carried out at a temperature of 60°C to 170°C, preferably 80°C to 140°C. When the reaction temperature is lower than this temperature range, the reaction rate decreases and it takes a long time to complete the reaction.

Further, in order to shorten the reaction time, the reaction may be carried out at a high temperature under pressure within the system, but if the temperature exceeds 170°C, by-products tend to increase, which is not a good idea.

The appropriate amount of 2-chloro-4-trifluoromethylphenol or its alkali metal salt to be used is 0.65 to 1.25 times, preferably 0.75 to 1.0 times by mole, relative to 3-bromoacetophenone. use When this molar ratio is lower than the above range, the raw material 3-bromoacetophenone remains unreacted, and when it is higher than the above range, another important raw material 2-chloro-4-trifluoromethylphenol or its alkali metal A large amount of salt remains, complicating the purification process.

The manufacturing method of the present invention will be explained in more detail with reference to Examples below.

(9) Example 1 10.9 g (50 mmol) of the sodium salt of 2-chloro-4-trifluoromethylphenol synthesized by a conventional method
), 0.5 g (5 mmol) of cuprous chloride, and 2oIllIl of pyridine were placed in a fourth flask and heated to 90° C. under a nitrogen stream. Next, 10.5 g (55 mmol) of 3-bromoacetophenone was added dropwise over 20 minutes, and the mixture was reacted for 4 hours with stirring under reflux.

After cooling the reaction product to room temperature, it was diluted with 100 mJ of water,
Concentrated hydrochloric acid was added dropwise to adjust pn to 1, followed by extraction with ethyl ether. The ether layer was washed three times with water, dried over anhydrous magnesium sulfate, and the ether was distilled off to yield a crude product 15.
0 g was obtained. This product was analyzed by high performance liquid chromatography using diphenyl ether as an internal standard, and the purity was calculated to be 13.8 g. 2-
The yield based on chloro-4-trifluoromethylphenol sodium salt was 92.6%.

Examples 2 to 6 (lO) The reaction was carried out in the same manner as in Example 1, changing the reaction temperature, reaction solvent, type and amount of catalyst, and type of alkali metal in the raw material phenol salt as shown in Table 1. carried out.

The results are shown in Table-1.

Margin table below-1 Example 23 4 56 Reaction 120°C90°C loo”c 85°C13
5°C temperature reaction Quinopyri N,N-jin Jin N,N-jin solvent Lin Jin Chil-4-lythyl-4-aminobim Aminopyridine Lysine catalyst Chloride Steel Bromide Oxidation Chloride g Cuprous powder Cuprous Cupric cupric cupric (mmol) 0
．． 5・0.64 0.72 0.80 2.02(5
) (10) (5) (10) −(15
) Raw material phenol salt alkali KNaNa K, Na metal compound (1) 87L3%80.5%93.7% 64.1
% 83.4% 1 Yield Procedural Amendment (Voluntary) January 28, 1980 Commissioner of the Japan Patent Office Shima 1) Haruki-dono ■, Indication of the Case 1988 Patent Application No. 208061 2, Title of the Invention 3- (2'-Chloro-4'-trifluoromethylphenoxy) Production method of acetophenone 3, relationship to the amended person's case Patent applicant name (003) Asahi Kasei Corporation 4, agent address Toranomon, Minato-ku, Tokyo - Shizuko Toranomon Building, No. 8-10 Chome (1) 5. Subject of amendment") Column 6 of "Detailed Description of the Invention" of the specification, Contents of amendment ■) The formula on page 3, line 5 of the specification is as follows: Correct as shown.

2) Correct the formula in the first line of page 4 as follows.

3) The table on page 6 of the same page is amended as follows.

Margin below (2)? Classification 3-Haloacetophenone Product compound (3) 4) In the reaction solvent column of Example 5 in Table 1 on page 12, "diglyme" is replaced with "diglyme".

that's all (4)

Claims (2)

[Claims] 1.3- Bromoacetophenone is reacted with 2-chloro-4-trifluoromethylphenol or an alkali metal salt thereof in an inert solvent in the presence of copper and/or a copper compound. A method for producing (2'-chloro-4'-trifluoromethylphenoxy)acetophenone. 2. The manufacturing method according to claim 1, wherein 0.025 mol or more of copper and/or a copper compound is used per 1 mol of 3-bromoacetophenone.