JPS62114939A - Production of fluorobenzene derivative - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for medicines, agricultural chemicals, etc., in good yield, by fluorinating a benzene derivative with a specific fluorinating agent without using a reaction solvent to substitute 1-2Cl or Br atoms in the benzene nucleus with 1-2 F atoms. CONSTITUTION:A benzene derivative expressed by formula I [X is nitro or cyano; Y is Cl or Br; n is 1 or 2; m is 1-(6-n)], e.g. 1,3-dinitro-4,6- dichlorobenzene, is reacted with a fluorinating agent, e.g. alkali metal fluoride such as KF, etc., or alkaline earth metal fluoride such as CaF2, etc, without a solvent at room temperature <= 300 deg.C, preferably 100-250 deg.C for 5-20hr under ordinary pressure to afford the aimed fluorobenzene derivative expressed by formula II [p is n; q is 0-(6-n-p)], e.g. 1,3-dinitro-4,6-difluorobenzene, etc. EFFECT:The aimed compound can be industrially and advantageously produced without problems of recovering the reaction solvent, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for producing fluorobenzene derivatives useful as intermediates for medicines and agrochemicals.

<Prior art> The method of fluorinating a chlorine or bromine atom on a benzene ring activated with a nitro group or a cyano group by halogen exchange with an alkali metal fluoride has been studied for a long time, and many methods have been used. Literature has been published.

For example, a method for producing fluoronitrobenzene using sulfolane, a polar high-boiling solvent, was published in JP-A-58-1
It is described in the specification of No. 70735.

<Problems to be solved by the invention> However, in the conventionally known fluorination reactions using polar high-boiling solvents, it is necessary to recover the solvent, dry or purify the solvent, and this is not necessarily advantageous as an industrial production method. It cannot be called a method.

<Means to Solve the Problem> The present inventors have investigated a method for conducting a fluorine reaction of a benzene derivative activated with a nitro group or a cyano group without a solvent and under as mild conditions as possible. When either an alkali metal fluoride or an alkaline earth metal is used as a fluorinating agent, the reaction is extremely slow, but when both are used together, fluorination proceeds in the absence of a solvent, resulting in a high yield. It was discovered that the desired product could be obtained with high efficiency, leading to the present invention.

That is, the present invention provides general formula (I) [However, X represents a nitro group or a cyano group.

Y represents a chlorine atom or a bromine atom. n is 1 or 2,
m represents an integer of 1 to (6-n). [However, X represents a nitro group or a cyano group] [wherein X represents a nitro group or a cyano group] .

Y represents a chlorine atom or a bromine atom. n is 1 or 2,
P represents 1 or 2, and q represents an integer of 1 to (6-n-p).

In the present invention, the benzene derivative as a raw material is as follows:
Examples include o-chloronitrobenzene, p-chloronitrobenzene, 1,3-dinitro-4°6-dichlorobenzene, 3,4-dichloronitrobenzene, and 2,6-cyclopenzonitrile.

Examples of the alkali metal fluoride used in the present invention include sodium fluoride, potassium fluoride, and cesium fluoride, with potassium fluoride and cesium fluoride being preferred. Examples of alkaline earth metal fluorides include magnesium fluoride, calcium fluoride, strontium fluoride, barium fluoride, etc.
Preferable examples include calcium fluoride.

The amount of alkaline earth metal fluoride used relative to the alkali metal fluoride is usually 5 times the catalytic amount by mole, but preferably 0.5 to 3 times the mole amount.

The amount of alkali metal fluoride used is usually 0.2 molar equivalent to a large excess, preferably 0.63 molar equivalent to 3 molar equivalent, relative to the benzene derivative as the starting material.

The reaction is usually carried out under normal pressure, and the reaction temperature ranges from room temperature to 300℃.
℃, preferably 100 to 250℃.

The reaction time is generally 5 to 20 hours.

<Effects of the Invention> Thus, according to the method of the present invention, one or two of the chlorine atoms or bromine atoms bonded to the benzene nucleus in the raw benzene derivative are replaced with fluorine atoms, and the desired general The fluorobenzene derivative represented by formula (I) can be obtained in good yield, and since the method of the present invention does not use a reaction solvent, there are no problems such as recovery of the reaction solvent, making it very advantageous as an industrial production method. Become.

<Example> The present invention will be explained below with reference to Examples.

Example 1 1,3-dinitro-4,6-cyclobenzene 10
g (42.2 mmole), potassium fluoride 7.4 g
(127,4 mmole), and calcium fluoride 6
．． Mix 6g (84,5mmole), 140-15
The mixture was stirred at 0t: for 9 hours. Pour into reaction condensate and add toluene.
Extract with ethyl acetate (2:1 weight ratio), filter, and concentrate.
1.3-'; 7.9 g of nitro-4,6-difluorobenzene crystals (melting point 71.5-73°C, yield 91.7%)
I got it.

For comparison, a reaction similar to the above was attempted except that 18 g (230 mmole) of calcium fluoride alone was used as the fluorinating agent, but the reaction hardly proceeded.

Similarly, 12.8g of potassium fluoride (
220.4 mmole), the reaction did not complete completely and the yield of 1,3-dinitro-4,6-cyfluoronitrobenzene was 60%.

Example 2 150 g of 0-chloronitrobenzene (0.95 mole
), potassium fluoride 18.4 g (0.32 mol
e) and calcium fluoride 49.5 g (0,63
mole) and stirred at 240-245°C for 6 hours.

After the reaction, pour into water, extract with toluene, filter, and concentrate.
4 g of oil was obtained. 144 g of oil obtained
! 23.5 g of 0-fluoronitrobenzene (
bpl 1 g, 5-119 °C/30 mmHg, ) was obtained, and o-chloronitrobenzene 107.8 g (bp 13
6-137°C/30 mmHg) was collected.

The reaction rate of 0-chloronitrobenzene at this time was 28.
1%, and the yield of 0-fluoronitrobenzene based on the consumed 0-chloronitrobenzene was 62.2%.

For comparison, 55.2 g of potassium fluoride (0.95 mo
le) and calcium fluoride 74.2 g (0.95 m
ole) was used alone and reacted in the same manner as above, but almost no 0-fluoronitrobenzene was obtained, which is a raw material. -More than 99% of chloronitrobenzene was recovered.

Example 3 2.6-dichlorobenzonitrile 17.2g (0,1
mole), potassium fluoride 14 g (0.24 m
ole) and calcium fluoride 9.4 g (0,1
2 mole) and stirred at 225-240°C for 7 hours. After the reaction, the mixture was poured into water, extracted with toluene, and filtered. The toluene layer was washed with water, concentrated, and further cleaned to give a
-cyfluorobenzonitrile 0.9g (bp53℃15
mmHg) and 2-chloro-6-fluorobenzonitrile (7.0 g (bp 63-65°C, 15 mm/1 g)), and from the clean residue, 2,6-cyclopenzonitrile 6.
3g was recovered.

The reaction rate of 2,6-dichlorobenzonitrile at this time was 63.3%, and the yield based on the consumed 2,6-dichlorobenzonitrile was 10.2% of 2,6-difluorobenzonitrile, 2- The content of chloro-6-fluorobenzonitrile was 71.0%.

For comparison, 20.9 g of potassium fluoride (0.36 mo
le) and calcium fluoride 28.1 g (0.36 m
ole) was used alone and reacted in the same manner as above, but the reaction hardly proceeded.

Example 4 3.4-dichloronitrobenzene 10 g (52 mmo
le), potassium fluoride 6.1 g (0.1 mole
) and calcium fluoride 4.1 g (52 mmol
e) was mixed and stirred at 235-240°C for 6 hours. After the reaction, pour into water, extract with toluene, filter, and concentrate.9.
8 g of oil was obtained. 3-chloro-4 by making a thin groove
- 0.8 g of fluoronitrobenzene (bp 95-96°C
15 mml1g) was obtained, and 8.2g of 3,4-dichloronitrobenzene (bp 110-112℃15 mml1g) was obtained.
) were collected.

The reaction rate of 3,4-dichloronitrobenzene at this time was 18%, and the yield based on the consumed 3,4-dichloronitrobenzene was 48.6%.

For comparison, 8.9 g (153 mmol) of potassium fluoride
e) and calcium fluoride 11.9 g (152 mmo
le) was used alone and reacted in the same manner as above, but the reaction hardly proceeded.

Claims (2)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [However, X represents a nitro group or a cyano group. Y represents a chlorine atom or a bromine atom. n is 1 or 2,
m represents an integer of 1 to (6-n). General formula (II), which is characterized by reacting a benzene derivative represented by ] with an alkali metal fluoride and an alkaline earth metal fluoride in the absence of a solvent ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I
I) [However, X represents a nitro group or a cyano group. Y represents a chlorine atom or a bromine atom. n is 1 or 2,
P represents 1 or 2, and q represents an integer of 0 to (6-n-p). ] A method for producing a fluorobenzene derivative represented by (2) The method for producing a fluorobenzene derivative according to claim 1, characterized in that potassium fluoride and calcium fluoride are used as the alkali metal fluoride and alkaline earth metal fluoride.