JPH0334937A - Production of m-fluoro aromatic compound - Google Patents

Abstract

PURPOSE:To obtain the subject substance at a low temperature in good yield by reacting an aromatic sulfonyl fluoride with an alkali metal fluoride in the presence of a quaternary phosphonium salt as a catalyst or further carrying out the reaction while taking out the resultant product to the outside of the system by distillation. CONSTITUTION:A compound (e.g. 3-nitrobenzenesulfonyl fluoride) expressed by formula I (R is electron attractive group, such as SO2Cl, SO2F, COCl, NO2, CF3, CN or CHO; X is halogen, alkyl or H; n is an integer of 0-4) is reacted with an alkali metal fluoride (e.g. NaF) in the presence of a quaternary phoshonium salt (e.g. tetraphenylphosphonium chloride) at 100-250 deg.C to provide a compound expressed by formula II. Side reaction can be suppressed and the above-mentioned reaction can be smoothly advanced by distilling the compound expressed by formula II under ordinary or reduced pressure and taking out the aforementioned compound to the outside of the system. The compound expressed by formula II is useful as a synthetic intermediate for medicines, agricultural chemicals, electronic materials, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION (Objects of the Invention) The present invention relates to an improved method for producing aromatic fluorine compounds.

(Industrial Application Field) The aromatic fluorine compound obtained by the present invention can be used for agricultural chemicals, pharmaceuticals,
It is a compound useful as a synthetic intermediate for electronic materials, etc.

(Prior art and problems) In producing aromatic fluorine compounds, the halogen exchange fluorination method, in which the corresponding chlorine derivative is reacted with an alkali metal fluoride, mainly potassium fluoride, is a low-risk, industrial process. Often used. [Organic Chemical Association Journal, Volume 47, P258 (198
[9] However, this process usually requires the presence of a strong electron-withdrawing group in the ortho or para position of the chlorine atom being exchanged, and the chlorine atom located in the meta position of the electron-withdrawing group is There is a restriction that it is difficult to exchange with fluorine atoms. An example has been reported in which a chlorine atom at the meta position of an electron-withdrawing group is exchanged with a fluorine atom only under special conditions of high temperature and high pressure [JP-A-61-14831.63-20
3636, Journal of the Organic Synthesis and Decomposition Chemistry Society, Volume 47, P2O (19
1989)]. On the other hand, groups substituted with fluorine atoms are not limited to halogen atoms; for example, there are reports of producing aromatic fluorine compounds by reacting aromatic compounds with nitro groups or halogenated sulfonyl groups with alkali metal fluorides. . In the former case, the produced aromatic fluorine compound is decomposed due to a side reaction caused by the released nitrite ions, so it is necessary to use an equivalent amount or more of an expensive nitrite ion trapping agent for the reaction. Therefore, the reaction system becomes complicated.
2. The raw material nitro compound has the danger of explosion, and it is difficult to carry out this reaction industrially (Japanese Patent Application Laid-Open No. 60-130537
．． 60-158141. ). As an example of the latter reaction, there is a report that a small amount of aromatic fluorine compound was produced by reacting an aromatic sulfonyl chloride derivative with potassium fluoride in an autoclave at 290°C for 40 hours [Chem.
,Abstr,, 66. 94741 (↓967
) :]. Furthermore, a method for obtaining a fluorobenzenesulfonyl fluoride conductor by reacting a benzene disulfonyl fluoride derivative with potassium fluoride and converting the fluorosulfonyl group into a fluorine atom is also disclosed [J
', Org, Ct+em, 534398 (19
88)]. Although there is a slight improvement in yield according to this method, the yield is still around 50% except for one example of ○-benzenedisulfonyl fluoride. It is limited and can only be applied in low yields to the production of fluorine compounds with other substituents.

(Problems to be Solved by the Invention) In view of the current situation, the present inventors have developed aromatic fluorine compounds, especially m-
After intensive research into ways to efficiently remove fluorobenzene derivatives, we found that it is possible to use a fluorosulfonyl group as a leaving group to substitute fluorine with an alkali metal fluoride, by adding a catalyst, or by further combining a reactive distillation operation. We have developed a method that can synthesize aromatic and fluorine compounds with much higher yield than conventional methods.

That is, the present invention provides a method for converting a quaternary phosphonium salt into a catalyst (in the formula:
RLllSO2C1,5o2F, Cock.

It represents an electron-withdrawing group such as NO, CF3, CN, CHO, etc., X represents a halogen atom, an alkyl group, or a hydrogen atom, and n represents an integer of 0 to 4.

) is reacted with an alkali metal fluoride to provide a method for producing an aromatic fluorine compound represented by the general formula (R, X, and n are the same) in good yield.

In the present invention, a quaternary phosphonium salt is used as a catalyst. Examples of the quaternary phosphonium salt include tetraphenylphosphonium chloride, tetraphenylphosphonium bromide, triphenyltolylphosphonium bromide, tritolylphenylphosphonium bromide,
Examples include tri-p-anisylphenylphosphonium bromide and triphenylmethylphosphonium iodide.

The above catalyst is S, Affandi et, at, 5y
ntt+, l1eact, In.

rg, Met, Org, Chem, 17. 307
(1987).

It can be easily made into synthetic leather by the method described in .

Further, the amount of the catalyst is 05 mol% or more, preferably 5 to 10% by mole, based on the benzenesulfonyl fluoride derivative [general formula <■>].
Mol% is used.

Examples of the pensene sulfonyl fluoride [general formula (■)] used as a raw material in the present invention include 3-nitrobenzenesulfonyl fluoride, 2-fluoro-5-nitrobenzenesulfonyl fluoride, and 2-chloro-5-nitrobenzenesulfonyl fluoride. fluoride, 4fluoro-5-nitrobenzenesulfonyl fluoride, 2-fluoro-4-nitrobenzenesulfonyl fluoride, 2,6-dichloro-3-nitrobenzenesulfonyl fluoride, 2,6-difluoro3 -nonitrobenzene sulfonyl fluoride such as nitrobenzene sulfonyl fluoride, 13-penzene disulfonyl fluoride, 1,3.5-penzene trisulfonyl fluoride, 1
．． Pencenesulfonyl fluoride such as 2-benzenedisulfonyl fluoride, 4-fluoro-1,3-benzenedisulfonyl fluoride, 3-fluorosulfonylbenzoyl fluoride, 3-fluorosulfonyl-4fluorobenzoyl fluoride, 3 - Halogenobenzoyl fluorides such as chloro-4-fluorosulfonylbenzoyl fluoride, 2-fluoro-4-fluorosulfonylbenzoyl fluoride, 3,5-dichloro-4-fluorosulfonylbenzoyl fluoride, 2-fluoro-5- Fluorosulfonylbenzonitrile such as fluorosulfonylbenzonitrile, 3-fluoro-4-fluorosulfonylbenzonitrile, 3-fluorosulfonyl-4-fluorobenzonitrile, 3-1-lifluoromethyl-4-fluorobenzenesulfonyl fluoride, Examples include trifluoromethylbenzenesulfonyl fluorides such as 2-fluoro-4-trifluoromethylbenzenesulfonyl fluoride, and alkylbenzenesulfonyl fluorides such as 4-methyl-13-benzenedisulfonyl fluoride.

These can be easily synthesized by chlorosulfonation using chlorosulfuric acid or fuming sulfuric acid in a conventional manner, followed by reaction with potassium fluoride.

In addition, the alkali metal fluoride used is sodium fluoride, potassium fluoride, cesium fluoride, or a mixture thereof, and any particulate alkali metal fluoride may be used. For example, spray-dried, freeze-dried, pulverized, or other industrially manufacturable fine particles may be used. The amount used is 0.000% relative to the halogen atom to be replaced.
5 to 10 equivalents, preferably 1 to 3 equivalents are used. There is no problem in using a solvent in this reaction.

When used, for example, aprotic polar solvents such as dimethyl sulfoxide, sulfolane, and N-methylpyrrolidone, and aromatic solvents such as dichlorotoluene, trichlorobenzene, chloronaphthalene, and methylnaphthalene are used. The reaction proceeds smoothly at room temperature or above, preferably at 100 to 250°C. Further, the above reaction proceeds smoothly while suppressing side reactions by reactively distilling the aromatic fluorine compound [general formula (■)] produced under normal pressure or reduced pressure and removing it from the reaction system.

(Effect of the invention) The halogen exchange fluorination method can be used in a high yield by carrying out the reaction between aromatic sulfonyl fluoride and alkali metal fluoride using a quaternary phosphonium salt as a catalyst or by further performing reactive distillation. The aromatic fluorine compound represented by the general formula (II) in which the meta-position that has not been substituted with fluoro can be produced in high yield at a temperature much lower than that of the conventional method.

(Example) The present invention will be specifically explained below using Examples.

Example 1 Into a 100 flask equipped with a condenser, a mechanical stirrer, and a thermometer, 6.5 g (0.11 mol) of spray-dried potassium fluoride (manufactured by Riedel) and tetraphenylphosphonium bromide (manufactured by Saishin Kagaku) were added. 1
g (0,005 moJL,), l (water sulborane 8
．． After azeotropic dehydration with toluene, the condenser was replaced with a fractionating head and 1.1.15 g of 2-fluoro-5-nitrobenzenesulfonyl fluoride (0
, 05 mol) was added, and 300 mml (g of 21
．． The mixture was stirred for 5 hours while performing reactive distillation at 0 t. The distillate has a boiling point of 160°C/300mmHg and 34-
It was a compound (3.88 g) of difluoronitrobenzene and 2,5-difluorobenzenesulfonyl fluoride.

When this mixture was analyzed by gas chromatography, 3
, 4-difluoronitrobenzene and 25-difluorobenzenesulfonyl fluoride was 7:1 (yield 49%).

3.4-difluoronitrobenzene, GC, MSl,
59 (Ma 2.5-difluorobenzenesulfonyl fluoride.

GC-MS: 1.96 (M”) Comparative Example 1 Into a 100-flask equipped with a condenser, mechanical stirrer and thermometer, 6.5 g (0.11 mol) of spray-dried potassium fluoride (manufactured by Riedel), anhydrous After adding 8.5 m of sulfolane!! and performing azeotropic dehydration with toluene, 11.15 g (0.05 mol) of 2-fluoro-5-nitrobenzenesulfonyl fluoride was added, and the mixture was heated at 220°C under a nitrogen atmosphere. After cooling, the reaction mixture was diluted with 100% dichloromethane and the inorganic salts were filtered off.

The residue obtained by concentrating the filtrate was distilled under reduced pressure to obtain a compound (1.0 g) of 3,4-difluoronitrobenzene and 2,5-difluorobenzenesulfonyl fluoride. Analysis of this mixture by gas chromatography revealed that 3.4-difluoronitrobenzene and 2. The ratio of 5-difluorobenzenesulfonyl fluoride was 7:1 (yield 1
3%). Moreover, the boiling point was 87° C./20 mmf (g).

Example 2 A reaction was carried out in the same manner as in Example 1 using 1,3-benzenedisulfonyl fluoride instead of 2-fluoro-5-nitropencenesulfonyl fluoride.

Into a 100 flask equipped with a condenser, mechanical stirrer, and thermometer, 6.5 g (0.11 mol) of spray-dried potassium fluoride (manufactured by Riedel) and 2.1 g (0.1 mol) of tetraphenylphosphonium bromide (manufactured by Saishin Kagaku) were added.
,005 mol) and 8.5 mol of anhydrous sulfolane were added, and after azeotropic dehydration with toluene, the mixture was replaced with 2.1 g of 13 (stirred under reduced pressure of 0° for 21 hours).

The yield of 3 hydride with a boiling point is 6°.Take the condenser into the fractionation head, add 105 mol of benzenedisulfonyl fluoride, and while performing reactive distillation at 270 mmHg O ℃, the 5 distillate is fluorobenzene at 170 ℃/270 mmHg. 56 g (yield 74%) of sulfonylfuro was obtained.

Comparative examples 2, 3, 4. and Example 3 Comparative Examples 2 and 3 in the same manner as Example 2 unless otherwise specified
,4. And Example 3 was carried out. The comparison results are shown below in a table.

Table 1 Comparative Example 2 240 5 - Yes 57
3 240 5 - None 44
Example 3 220 2 0.1eq None 3
8 Comparative Example 4 220 2 - None 20T
PPB:) lb Phosphonium Bromide Example 4 In a 100-flask equipped with a condenser, mechanical stirrer, and thermometer, spray-dried potassium fluoride (Riedel) 6.5 g (0.11 mol), tetraphenylphosphonium Promid (sacramental chemistry) 2.1g (
After adding 8.5 g of anhydrous sulfolane and performing azeotropic dehydration with toluene, the condenser was replaced with a fractionating head and 11.2 g of 3-fluorosulfonyl-4-fluorobenzoyl fluoride was added (0,005 mol). 05 mol) was added thereto, and the mixture was stirred for 4 hours while performing reactive distillation at 210° C. under a reduced pressure of 270 mmHg. Distillate is 140℃/27
3,4-difluorobenzoyl fluoride (3,21 g) with a boiling point of 0 mm) Ig was obtained.

The conversion rate was 92% and the selectivity was 49%. G(, M3:
160 (M+) [: High resolution mass spectrum:
Calculated value (160,0136), analyzed value (160,013
5). ] This 3°4-difluorobenzoyl fluoride was hydrolyzed to 3,4-difluorobenzoic acid, and the compound was identified. The melting point was 120°C.

[Literature value: 119.2-120.1°C; J, Or
g, Cham,, 17. 1.429 (195
2):] Example 5 Example 1 except that 2-fluoro-5-nitrobenzenesulfonyl fluoride was modified and 10.3 g (0.05 mol) of 3-sulfonyl fluoride benzoyl fluoride was added. I did the same. The reaction was carried out under a reduced pressure of 300 mmHg for 2
The mixture was stirred for 6 hours while performing reactive distillation at 10°C. The distillate was 3-fluorobenzenesulfonyl fluoride (1,56 g) with a boiling point of 120° C./300 mm Hg;
The conversion rate was 31% and the selectivity was 71%.

Example 6 11.6 g (0.2 mol) of spray-dried potassium fluoride, 2.08 g (0.2 mol) of tetraphosphonium bromide were spray-dried in a 50-flask equipped with a water separator, stirrer and thermometer.
005 mol), 25 g 1 of anhydrous sulfolane, and 40 g of toluene were added, and 15 mol of toluene was distilled off under heating for azeotropic dehydration. Furthermore, the pressure inside the reaction vessel was reduced using a vacuum pump, and the temperature was raised to 150° C. at 30 mmHg, and toluene was distilled off. After cooling the inside of the reaction vessel to 100°C, the inside of the reaction vessel was replaced with nitrogen gas, and 34-dichloro-5-
Chlorosulfonylbenzoyl chloride 15.4g (0
.

When the reaction solution was analyzed by gas chromatography, 3
-Chloro-4,5-difluorobenzoyl fluoride is 5
It was 3% viable.

Claims (2)

[Claims] (1) Using a quaternary phosphonium salt as a catalyst, there are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (I) (wherein, R is SO_2Cl, SO_2F, COCl, N
It represents an electron-withdrawing group such as O_2, CF_3, CN, CHO, etc., X represents a halogen atom, an alkyl group, or a hydrogen atom, and n represents an integer of 0 to 4. ) is characterized by reacting an aromatic sulfonyl fluoride with an alkali metal fluoride, and is represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) (R, X, and n are the same) A method for producing an aromatic fluorine compound. (2) In the method for producing an aromatic fluorine compound according to claim 1, the aromatic fluorine compound represented by the general formula (II) is distilled out of the reaction system under normal pressure or reduced pressure during the reaction. A method for producing an aromatic fluorine compound, which is characterized in that the process is carried out while taking out the aromatic fluorine compound.