JPH0461858B2 - - Google Patents

Description

[Detailed description of the invention]

[Object of the invention] (Industrial field of application) This invention relates to the production of ω-haloacetophenones. ω-Haloacetophenones, such as ω-bromo-P-chloroacetophenone, are useful substances as intermediate raw materials for pharmaceuticals, agricultural chemicals, and the like. (Prior art) As a method for producing ω-haloacetophenones, a conventional method generally involves halogenating acetophenones in acetic acid (ORGANIC SYNTHESES).
Collective Volume 1, pp. 127-128, published in 1967) and a method of halogenation using a catalyst such as aluminum chloride in an inert solvent, such as an ether (ORGANIC SYNTHESES).
Collective Volume 2, pp. 480-481, published in 1966). (Problems to be Solved by the Invention) The above-mentioned reaction in the conventional method has (1) severe reaction conditions. (2) The yield is low because a considerable amount of ω,ω-dihaloacetophenones are produced as by-products. (3) Separation of by-products is difficult. It has the following drawbacks and cannot be said to be an industrially advantageous method. The present invention provides a method for industrially producing ω-haloacetophenones in high yield by eliminating the drawbacks of the conventional methods described above and halogenating acetophenones using an inexpensive lower alcohol as a solvent. It is. [Structure of the invention] (Means for solving the problems) The gist of the present invention is the general formula ()

[Formula] (where R ₁ and R ₂ do not depend on each other and are H, Cl, Br, I, a C ₁ to C ₅ alkyl group, a hydroxyl group, a C ₁ to C ₅ alkoxy group, a nitro group, a cyano group) group, sulfonamide group) is halogenated in a lower alcohol to form the general formula ().

[Formula] (Here, R ₁ and R ₂ are R ₁ and R ₂ shown in the general formula ().
This is a method for producing ω-haloacetophenones represented by the same formula (X represents a halogen atom). Here, the halogen atom represented by X is chlorine,
Bromine, iodine, etc. General formula () used as a raw material of the present invention

[Formula] (where R ₁ and R ₂ are independent of each other, H, Cl, Br,
I, _C1 - _C5 alkyl group, hydroxyl group, _C1
- _C5 alkoxy group, nitro group, cyano group, sulfonamide group)) Many acetophenones are easily available. Examples include acetonephenone, P-chloroacetophenone, P-methylacetophenone, O-hydroxyacetophenone, m-nitroacetophenone, P-methoxyacetophenone, P-cyanoacetophenone. , 3,4-dimethylacetophenone, 2-hydroxy-3-methylacetophenone, 4-chloro-2-methylacetophenone,
Examples include 2,4-dichloroacetophenone, 2,4-dimethoxyacetophenone and 2,4-dihydroxyacetophenone. The lower alcohol used in halogenation can be any alcohol as long as it dissolves the raw material acetophenones, and usually C ₁ to C ₄ alcohols are used. Examples include methanol, ethanol, isopropanol, n- Examples include butanol. Among them, methanol is generally used from the viewpoint of handling and economy. In the halogenation, chlorine, bromine, iodine, etc. are used as the halogen, and the amount used is preferably equimolar to the acetophenone, and there is no need to add an excessive amount. In addition, the reaction temperature during halogenation is 20~
Good results are obtained when the temperature is 90°C, preferably in the range of 30 to 60°C. If the temperature is too low, the raw materials will not dissolve and the reaction rate will be slow; if the temperature is too high, a disproportionation reaction will occur and by-products will be produced, resulting in a decrease in yield. (Function) Although the reaction mechanism of the present invention is not fully detailed, it is presumed as follows. That is, the general formula produced by halogenating acetophenones in a lower alcohol (where R ₁ and R ₂ are R ₁ shown in the general formula (),
Same as R ₂ , R ₃ is a C ₁ to C ₄ alkyl group, and X is a halogen atom). It is thought that phenones can be obtained. In the hydrolysis, the appropriate amount of water to be added is 1 to 100 times the molar amount of the raw material acetophenones. If the amount is less than 1 mole, the hydrolysis will not be completed, and if it is added more than 100 times the mole, no commensurate effect will be obtained and the volumetric efficiency will deteriorate, which is not preferred. (Example) The following will be described in detail with reference to Examples. Example 1 P-chloroacetophenone 15.4g (0.1mol)
was dissolved in 180 g of methanol, and then 16.0 g (0.1 mol) of bromine was added dropwise over 1 hour at a temperature of 30 to 40°C. After stirring for an additional 10 minutes, 80 g of water was added, and the mixture was stirred at room temperature for 30 minutes. Thereafter, the temperature was kept at 50°C or lower to distill off some methanol and water, and the precipitated results were separated, washed with water, and dried to produce 22.4 g of white ω-bromo-P-chloroacetophenone (melting point 96~
97℃) was obtained. The yield was 95.9%. Examples 2 to 35 The same procedure as in Example 1 was performed except that the starting materials and halogenating agents shown in Table 1 were used to obtain the results shown in Table 1.

【table】

【table】

[Table] Example 36 P-chloroacetophenone 15.4g (0.1mol)
After dissolving in 180g of isopropanol, 30~
16.0 g (0.1 mol) of bromine was added dropwise over 1 hour at 40°C. After stirring for another 10 minutes, add 180 g of water.
was added and stirred at room temperature for 30 minutes. Thereafter, a portion of isopropanol and water were distilled off at 50°C or below, and the precipitated crystals were separated, washed with water, and dried to produce 21.8 g of white ω-bromo-P-chloroacetophenone (melting point 96
~97°C) was obtained. The yield was 93.6%. (Effects) If ω-haloacetophenones are produced by the method of the present invention, the target product can be obtained in high yield with less generation of ω,ω-dihaloacetophenones as by-products. .

Claims (1)

[Claims] 1 General formula () (Here, R ₁ and R ₂ are independent of each other, H, Cl, Br,
I, _C1 - _C5 alkyl group, hydroxyl group, _C1
General formula () characterized by halogenating acetophenones represented by ~ _C5 alkoxy group, nitro group, cyano group, sulfonamide group) in a lower alcohol (Here, R ₁ and R ₂ are R ₁ and R ₂ shown in the general formula ().
, where X represents a halogen atom) A method for producing ω-haloacetophenones. 2. The method according to claim 1, wherein the lower alcohol is methanol. 3. The method according to claim 1, wherein water is added after halogenation.