JPH0676344B2 - Method for producing chlorofluorobenzenes - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing chlorofluorobenzenes.

[Problems to be Solved by Prior Art and Invention] The following methods are known as methods for producing chlorofluorobenzenes. (1) Reduction and Balz and Schiemann
Method by combination of methods (Rec.trav.chim., 51 , 98-113 (19
32); Acta Chim, Acad.Sci.Hung., 10 , 227-32 (195
6)). (2) Method by a combination of reduction and Sandmeyer method.
(3) Method for denitrochlorinating 2,4-dinitrofluorobenzene (Khim. Nauka i Prom., 3 , 404-5 (1958); Z
h.Obshch.Khim., 31 , 1222-6 (1961)).

Besides, (4) a method of fluorinating 1,2,4-trichlorobenzene with potassium fluoride (J. Fluorine Chem., 2 (1), 1
9-26 (1972)) or (5) Method of fluorinating paradichlorobenzene with silver fluoride (J.Org. Chem., 45 (1
8), 3597-603 (1980).

The method (1) has a drawback in that a large amount of dangerous hydrofluoric acid is used and the volume efficiency is low. The method (2) not only requires a two-step reaction as described below, but also a large amount of hydrochloric acid waste liquid is by-produced in the second step Sandmeyer method, resulting in high processing cost and low volumetric efficiency, which is expensive. Manufacturing method.

In the method (3), unreacted chlorofluoronitrobenzene is easily produced as a by-product and the yield is low. The methods (4) and (5) have lower yields and cannot be industrial methods.

[Means for Solving the Problems] The inventors of the present invention have conducted intensive studies to find a method of industrially advantageously obtaining chlorofluorobenzenes from fluorinated nitrobenzenes, and as a result, the number of steps is shown here. We have completed and proposed an excellent method that can shorten and achieve high productivity.

That is, the present invention is characterized by reacting a fluorine-containing nitrobenzene represented by the following general formula (1) with chlorine gas to obtain a chlorofluorobenzene represented by the following general formula (2). The present invention relates to a method for producing benzenes.

In the above formula, n and m are integers satisfying 1 ≦ n ≦ 3, 0 ≦ m ≦ 2, 1 ≦ n + m ≦ 3, and at least one fluorine-containing nitrobenzene represented by the general formula (1) is used. Fluorine is bound to the benzene nucleus. The chlorofluorobenzenes represented by the general formula (2) are those in which at least one fluorine and at least one chlorine are bonded to the benzene nucleus because the nitro group of the fluorine-containing nitrobenzene is converted to chlorine. Is.

The reaction temperature in the method of the present invention may vary depending on the starting materials and the reaction pressure, but a gas phase reaction which is typically carried out in the range of about 300 to 600 ° C. is preferred. Preferably the starting material is 3,
In 4-difluoronitrobenzene, etc., 380-450
℃. The reaction can be carried out at normal pressure, but reduced pressure or increased pressure may be used.

The amount of chlorine gas used may vary depending on the desired reaction rate, but it is also possible to use an excess of chlorine gas. For example, 0.1 to 20 times mol, preferably 1 to 5 times mol, is suitable for 1 mol of fluorine-containing nitrobenzene as a starting material. For gas phase reactions, the residence time required for the reaction is 0.1-100.
Seconds, preferably 5 to 20 seconds, and the starting material is vaporized prior to being fed to the reactor, but at this time, a reaction-inert gas such as nitrogen, argon, or helium is used to facilitate vaporization. You may dilute. Alternatively, the starting material may be previously dissolved in a reaction-inert solvent and then supplied to the vaporizer.

Although the type of reactor is arbitrary, an empty reactor is generally used.

As a method for producing chlorofluorobenzenes of the present invention, a method of reacting a fluorine-containing nitrobenzene represented by the following general formula (3) with chlorine gas to obtain a chlorofluorobenzene represented by the following general formula (4) is particularly preferable. It is advantageous.

(In the formula, n and m are integers satisfying 1 ≤ n ≤ 3, 0 ≤ m ≤ 2, 1 ≤ n + m ≤ 3.) Conventionally, chlorination of a nitro group of nitrobenzene has been performed at a para position with respect to the nitro group. Occurs when there is a substituent with a large electron-withdrawing force such as NO ₂ , CN, CF ₃ (see US Pat. No. 4,470,930, etc.), and it is less likely to occur when there is a substituent with a small electron-withdrawing force such as chlorine. It is said that. For example, it is said that dichlorobenzene is not produced in the following reaction. [Be
richte der deutschen chemischen Geselshaft 24 , 3749
(1891)] However, even if fluorine having a substituent constant δp (a larger value is larger in electron withdrawing force), which is one index of electron withdrawing force, is smaller than chlorine in the para position to the nitro group, chlorination of this nitro group It has been found for the first time in the present invention that the phenomenon occurs easily. As a result, the reaction of introducing chlorine at the para position with respect to the fluorine directly bonded to the benzene ring can be extremely advantageously performed.

The chlorofluorobenzenes in the present invention are represented by the following general formula (6) obtained by a fluorination reaction of an aromatic nitro compound represented by the following general formula (5) as a starting material with this and a fluorinating agent. It can also be obtained by chlorinating this through fluorinated nitrobenzene.

In the formula, X ¹ and X ² are each H, Cl or F, and Y ¹ and Y ² are each H, Cl or F. However, when X ¹ and X ² are H or F, X ¹ = Y ¹ and X ² = Y ² , and when X ¹ and X ² are Cl, Y ¹ and Y ²
Are Cl or F, respectively. Usually, in the case of fluorination with only a fluorinating agent, Cl of X ¹ and X ² is not replaced by F, but it can be replaced by F by using a fluorination catalyst.

The reaction temperature of the fluorination reaction may vary depending on the starting materials and the like, but a temperature range of typically about 100 to 300 ° C, preferably 150 to 250 ° C is suitable.

Alkali metal fluorides are preferable as the fluorinating agent, particularly KF, RbF, CsF and the like are preferable, and the amount thereof is a reaction theoretical amount necessary for fluorinating chlorine to be fluorine-substituted in the aromatic nitro compound. 1-3 times, preferably 1-
Twice is appropriate.

A reaction solvent is not always necessary in this reaction,
An aprotic polar solvent can also be used. Examples of the aprotic polar solvent include acetonitrile, dimethylformamide, dimethylsulfoxide, sulfolane, N-methyl-2-pyrrolidone, N-cyclohexyl-2.
-Pyrrolidone, hexamethylphosphortriamide, 1,3-
Examples thereof include dimethyl-2-imidazolidinone, and sulfolane and 1,3-dimethyl-2-imidazolidinone are particularly preferable. The amount of the solvent to be used is not particularly limited, but 0.2 to 10 times by weight, preferably 1 to 5 times by weight, is suitable for the aromatic nitro compound as a starting material.

Moreover, you may add a phase transfer catalyst as needed. Examples of the phase transfer catalyst include, for example, tetrabutylammonium bromide, quaternary ammonium salts such as tetramethylammonium chloride, or quaternary phosphonium salts such as tetrabutylphosphonium bromide, or N-
Examples include viridinium salts such as (2-ethyl-hexylamino) -4- (N ', N'-dimethyl) -virdinium chloride.

On the other hand, for the reaction from the fluorine-containing nitrobenzene represented by the general formula (6) to the chlorofluorobenzenes represented by the general formula (7), the above-mentioned chlorination reaction of the present invention can be adopted.

[Example] Example 1 3,4-Difluoronitrobenzene was continuously supplied to a vaporizer made of glass to be vaporized, and a small amount of nitrogen was entrained in the vaporizer and supplied to a reactor. The molar ratio of 3,4-difluoronitrobenzene to nitrogen was 130: 1. 400 by salt bath furnace
The above-mentioned gas and chlorine gas were continuously circulated in a nickel reactor having an inner diameter of 27 mm and a length of 1000 mm, which was kept at ℃. At this time, the residence time was 10 seconds, and the molar ratio of chlorine to 3,4-difluoronitrobenzene was 1.2. When the liquid condensed by cooling at the outlet was analyzed by gas chromatography, the reaction rate of 3,4-difluoronitrobenzene was 100% and the selectivity of 3,4-difluorochlorobenzene was 100%.
It was 82%.

Comparative Example 1 (Synthesis method using reduction method and diazo chlorination method) 10 g of 3,4-difluoronitrobenzene was dissolved in 20 g of methanol, 10 g of concentrated hydrochloric acid and 2 g of iron powder were added, and the mixture was mixed at 60 ° C. for 2 hours.
Stir for hours and distill it to give 3,4-difluoroaniline. The reduction yield was 86%. To this, add 70g of 36% hydrochloric acid to form the hydrochloride salt, and add 18g at 0 ℃ with stirring.
25% NaNO ₂ aqueous solution was added to obtain a diazonium salt. This was dropped into a hydrochloric acid solution of cupric chloride heated to 120 ° C,
Pyrolysis was performed. The diazotization yield was 84%. The overall yield was 72% and 3,4-difluorochlorobenzene was obtained.

Example 2 The reaction was performed in the same manner as in Example 1 except that 3-chloro-4-fluoronitrobenzene was used as the starting material, and the reaction rate of 3-chloro-4-fluoronitrobenzene was 95%, 1,3. The selectivity of -dichloro-4-fluorobenzene was 90%.

Example 3 3,4-in a 200 ml glass reactor equipped with a reflux condenser.
Charge 50 g of dichloronitrobenzene, 20 g of spray-dried KF, and 100 g of sulfolane, and stir vigorously at 225 ° C.
And reacted for 4.5 hours.

When the reaction solution was analyzed by gas chromatography, the reaction rate of the raw materials was 10
The selectivity to 0% and 3-chloro-4-fluoronitrobenzene was 93%.

3-Chloro-4-fluoronitrobenzene obtained by distilling and purifying this reaction solution was continuously supplied to a vaporizer made of glass for vaporization, and a small amount of nitrogen was entrained in the vaporizer and supplied to the reactor. The molar ratio of 3-chloro-4-fluoronitrobenzene to nitrogen was 130: 1. The above gas and chlorine gas were continuously circulated in a nickel reactor having an inner diameter of 27 mm and a length of 10,000 mm, which was kept at 400 ° C. by a salt bath furnace. At this time, the residence time was 10 seconds, and the molar ratio of chlorine to 3-chloro-4-fluoronitrobenzene was 1.2.
When the liquid cooled and condensed at the outlet was analyzed by gas chromatography, the reaction rate of 3-chloro-4-fluoronitrobenzene was 95% and the selectivity of 1,3-dichloro-4-fluorobenzene was 90%. .

Example 4 3,4-in a 200 ml glass reactor equipped with a reflux condenser.
Dichloronitrobenzene 50g, spray dried KF30g, N-
(2-Ethyl-hexylamino) -4- (N ', N'-dimethyl) -pyrudinium chloride (2.5 g) and sulfolane (100 g) were charged, and the reaction was carried out at 190 ° C for 15 hours with vigorous stirring.

When the reaction solution was analyzed by gas chromatography, the reaction rate of the raw materials was 10
0%, 51% selectivity to 3,4-difluoronitrobenzene
Met.

A chlorination reaction was performed in the same manner as in Example 3 except that 3,4-difluoronitrobenzene obtained by distilling and purifying this reaction solution was used as a starting material, and the reaction rate of 3,4-difluoronitrobenzene was 100. %, The selectivity of 3,4-difluorochlorobenzene was 82%.

Example 5 3,4,5 in a 200 ml glass reactor equipped with a reflux condenser.
-Trichloronitrobenzene 50g, spray dried KF 20g,
Charge 100g of sulfolane and stir vigorously 22
The reaction was carried out at 0 ° C for 4.5 hours.

When the reaction solution was analyzed by gas chromatography, the reaction rate of the raw materials was 95.
%, The selectivity to 3,5-dichloro-4-fluoronitrobenzene was 83%.

In addition to using 3,5-dichloro-4-fluoronitrobenzene obtained by distilling and purifying this reaction solution as a starting material,
When the chlorination reaction was carried out in the same manner as in Example 3, it was found to be 3,5
-The reaction rate of dichloro-4-fluoronitrobenzene is 94
%, The selectivity of 1,3,5-trichloro-2-fluorobenzene was 92%.

Example 6 3,4,5 in a 200 ml glass reactor equipped with a reflux condenser.
-Trichloronitrobenzene 50g, spray dried KF40g,
Charge tetra (n-butyl) phosphonium bromide 5g and sulfolane 100g and stir vigorously at 200 ℃
And reacted for 15 hours.

When the reaction solution was analyzed by gas chromatography, the reaction rate of the raw materials was 81.
%, The selectivity to 3-chloro-4,5-difluoronitrobenzene was 65%.

3-chloro-4,5-difluoronitrobenzene obtained by distilling and purifying this reaction solution was used as a starting material,
When the chlorination reaction was carried out in the same manner as in Example 3, 3-
The reaction rate of chloro-4,5-difluoronitroben is 96%,
The selectivity of 1,3-difluorobenzene was 90%.

[Effects of the Invention] According to the present invention, 1,3-dichloro-4-fluorobenzene, 3,4-difluorochlorobenzene, and the like, which are useful as raw materials for intermediates for medical and agricultural chemicals, particularly for antibacterial agents, can be industrially produced. Can be obtained in an advantageous manner.

Claims (10)

[Claims] 1. A chlorofluorobenzene represented by the following general formula (1) is obtained by reacting a fluorine-containing nitrobenzene represented by the following general formula (1) with chlorine gas to obtain a chlorofluorobenzene represented by the following general formula (2). Production method. (In the formula, n and m are integers satisfying 1 ≦ n ≦ 3, 0 ≦ m ≦ 2, 1 ≦ n + m ≦ 3.) 2. The method according to claim 1, wherein the reaction between the fluorine-containing nitrobenzene and chlorine gas is carried out by a gas phase reaction at a reaction temperature selected from 300 to 600 ° C. 3. The production method according to claim 1, wherein the amount of chlorine gas used is 0.1 to 20 times mol per mol of fluorine-containing nitrobenzene. 4. The production method according to claim 1, wherein the fluorinated nitrobenzenes are represented by the following general formula (3) and the chlorofluorobenzenes are represented by the following general formula (4). (In the formula, n and m are integers satisfying 1 ≦ n ≦ 3, 0 ≦ m ≦ 2, 1 ≦ n + m ≦ 3.) 5. An aromatic nitro compound represented by the following general formula (5) is reacted with a fluorinating agent to give the following general formula (6):
The method for producing chlorofluorobenzenes is characterized in that the fluorinated nitrobenzenes represented by the formula (1) are obtained, and then this is reacted with chlorine gas to obtain the chlorofluorobenzenes represented by the following general formula (7). (In the formula, X ¹ and X ² are H, Cl or F, and Y ¹ and Y ² are H, Cl or F, respectively, provided that when X ¹ and X ² are H and F, X ¹ = Y ¹ , X ²
= Y ² , and when X ¹ and X ² are Cl, Y ¹ and Y ² are Cl or F, respectively. ) 6. The reaction between the aromatic nitro compound and the fluorinating agent is carried out at a reaction temperature selected from 100 to 300 ° C.
The manufacturing method described in. 7. The process according to claim 5, wherein the amount of the fluorinating agent used is 1 to 3 times the stoichiometric amount necessary for fluorinating the chlorine to be fluorine-substituted in the aromatic nitro compound. Method. 8. The method according to claim 5, wherein the fluorinating agent is an alkali metal fluoride. 9. The production method according to claim 5, wherein the reaction between the fluorine-containing nitrobenzene and chlorine gas is carried out by a gas phase reaction at a reaction temperature selected from 300 to 600 ° C. 10. The production method according to claim 5, wherein the amount of chlorine gas used is 0.1 to 20 times mol per mol of fluorine-containing nitrobenzene.