JPH0121137B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to the production of fluorophenols. More specifically, the present invention relates to a method for first converting bromofluorobenzenes into fluoroanisoles and then producing fluorophenols. Fluorophenols are useful substances as intermediate raw materials for medicines and agrochemicals. Conventional methods for producing fluorophenols include (1) a method of melting bromofluorobenzenes in the presence of calcium hydroxide and water (J.Org.Chem., 26 4641 (1961));
(2) Method of thermally decomposing aminophenols after converting them into diazonium salts (J.Amer.Chem.Soc., 71
1863 (1949)), (3) A method of hydrolyzing fluorophenetols obtained by converting phenetidines into diazonium salts and then heating or photolyzing them (J.Amer.
Chem.Soc., 61 165 (1939)) and (4) Method for fluorinating phenols with fluorine (J.Fluorine
Chem., 21 191 (1982)). However, in these methods, method (1) requires high temperature and high pressure, has low selectivity, and the physical properties of the by-product phenols are very similar to those of the target fluorophenols, so high purity fluorinated phenols cannot be obtained. Phenols are difficult to isolate. Methods (2) and (3) have low yields and low selectivities, so they cannot be called industrial production methods. In method (4), a mixture of fluorophenol isomers is obtained,
Since the physical properties of these isomers are very similar, it is extremely difficult to isolate the desired fluorophenol. The present inventors aimed to provide an industrially advantageous method for producing fluorophenols under mild conditions, and as a result of intensive study on a method for producing fluorophenols that does not produce by-products of isomers or phenols. By reacting bromofluorobenzenes with alkali metal methylates in the presence of copper and/or cobalt compound catalysts to form fluoroanisoles, and then hydrolyzing them, fluorophenols with a purity of at least 99% can be obtained in good yields. The present invention has been achieved by discovering what can be obtained. According to the invention, the general formula

[Formula] Fluoroanisoles can be produced in good yield by heating bromofluorobenzenes represented by (where n = 1 to 5) with an alkali metal methylate in the presence of a catalyst without a solvent or in an organic solvent, and then by a conventional method. The desired product can be easily produced by hydrolysis according to the following. Moreover, according to this method, no isomers or phenols are produced as by-products, so the target product can be easily isolated by distillation or recrystallization, making it extremely industrially possible. It's advantageous. The bromofluorobenzenes represented by the general formula used in the method of the present invention include, for example, o-bromofluorobenzene, m-bromofluorobenzene,
p-bromofluorobenzene, 3,4-difluorobromobenzene, 3,5-difluorobromobenzene, 2,5-difluorobromobenzene,
2,6-difluorobrombenzene, and 2,
Examples include 3,4,5-tetrafluorobrombenzene. As the alkali metal methylate, sodium methylate, potassium methylate, lithium methylate, etc. are used, but sodium methylate is economically preferred. The amount of alkali metal methylate to be used is theoretically equivalent to the equivalent mole of bromofluorobenzenes, and it is usually sufficient to use a small excess of the theoretical amount; there is no particular limitation and it should be determined in consideration of economic efficiency. It is usually in the range of equimole to 7 moles. As a catalyst, a copper compound and/or a cobalt compound can be used, such as cuprous chloride, cupric chloride, cuprous bromide, cupric bromide, cuprous iodide, cuprous oxide, cupric oxide, etc. Examples include copper, copper naphthenate, cobalt chloride, cobalt iodide, cobalt bromide, and cobalt naphthenate, but especially for the purpose of shortening the reaction time, cuprous bromide and cuprous iodide are used. preferable. The amount of these catalysts used is required to be 1% or more based on the bromofluorobenzene, but is not particularly limited, although it is preferably 5 to 30% in order to shorten the reaction time. Also, as organic solvents, methanol, ethanol,
Common aprotic polar solvents can be used, such as alcohols such as propyl alcohol, dimethylformamide, diethylformamide, dimethylacetamide, ethylenediamine, acetonitrile, dimethylsulfoxide, sulfolane, and dimethylsulfone. The heating temperature is generally 60 to 250°C, the progress of the reaction is monitored by gas chromatography, and the reaction time is determined when most of the bromofluorobenzenes have disappeared. Hydrolysis can be carried out by heating under reflux with a hydrohalic acid such as hydrogen bromide or hydriodic acid, or in an inert solvent such as benzene or carbon tetrachloride.
A known method of hydrolysis using a Lewis acid such as aluminum chloride, iron chloride, or zinc bromide can be used. The present invention will be described below in detail with reference to Examples, but the present invention is not limited to these specific Examples. Example 1 100 g of p-bromofluorobenzene, 231 g (2.1 times the mole) of a methanol solution of 28% sodium methoxide, and 15.2 g of copper iodide were added to a 500 ml glass reactor under nitrogen atmosphere, and the mixture was heated under reflux (80°C) for 9 hours. did. The reaction proceeded quantitatively, with a conversion rate of p-bromofluorobenzene of 99.9% and a selectivity of p-fluoroanisole of 100%. After cooling, 300 ml of water was added and filtered through Celite to isolate p-fluoroanisole, which was separated into a lower layer.The aqueous layer was further extracted with n-hexane to recover p-fluoroanisole. Yield 60.0
(Yield: 83%) Next, 246 g of 47% hydrobromic acid was added to 60 g of this p-fluoroanisole, and the mixture was heated under reflux (110° C.) for 10 hours. After cooling, the upper organic layer was separated and distilled to obtain 49 g of p-fluorophenol with a purity of 99.9% or higher. Yield 92%, boiling point 74℃/
11mmHg. Note that no other by-products were observed. Example 2 2 g of p-bromofluorobenzene, 2.2 g (3.5 times the mole) of sodium methoxide, 0.2 g of copper iodide, and 10 g of dimethylformamide were added, and the mixture was heated under reflux (150° C.) for 3 hours. The p-fluoroanisole obtained by post-treatment in the same manner as in Example 1 was hydrolyzed with hydrobromic acid to obtain 1.16 g of p-fluorophenol with a purity of 99.9% or more. Yield 91%. Example 3 10 g of p-bromofluorobenzene, 4.8 g (1.2 times the mole) of potassium methoxide, and 1.1 g of cobalt naphthenate were added and reacted at 150° C. for 1.5 hours with stirring.
After cooling, 5 ml of water was added and the same post-treatment as in Example 1 was carried out to obtain p-fluoroanisole. 16 g of aluminum chloride was added to this p-fluoroanisole, refluxed in a benzene solvent for 5 hours, and then water was added. The extract was extracted with methylene chloride, and the concentrated solution was recrystallized from n-hexane to obtain 4.16 g of p-fluorophenol with a purity of 99.9% or higher. Yield 65%. Melting point 47℃. Example 4 0.96 g of o-fluorophenol was obtained in the same manner as in Example 1 using 2 g of o-bromofluorobenzene, 8 g of a methanol solution of 28% sodium methoxide (3.6 times the mole), and 0.2 g of copper bromide. Ta. Yield 75%. Boiling point 172℃. Example 5 2,4-difluorobrombenzene 3.0g, 28
% sodium methoxide in methanol 8g
(2.5 times the mole) and 0.5 g of copper iodide were added under nitrogen atmosphere and refluxed (80°C) for 9 hours. After cooling, 10 ml of water was added and filtered through Celite. The 2,4-difluoroanisole separated in the lower layer was separated. The liquid was drained, 10 g of 47% hydrobromic acid was added, and the mixture was heated under reflux (110°C) for 20 hours. After cooling, the upper organic layer was separated and distilled to obtain 1.8 g of 2,4-difluorophenol with a purity of 99.9% or higher.
Yield 85%. Boiling point 150℃.

Claims (1)

[Claims] 1 Bromofluorobenzenes represented by the general formula, [Formula] (where n = 1 to 5) are reacted with alkali metal methylates in the presence of a catalyst of copper and/or cobalt compounds to form fluoroanisoles. A method for producing fluorophenols, which is characterized in that the fluorophenols are then hydrolyzed.