JPH0678264B2 - Process for producing 4- (parafluorobenzoyl) phenols - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing 4- (parafluorobenzoyl) phenols, which are important as monomers for heat-resistant polymers or intermediates for agricultural chemicals, pharmaceuticals and the like.

(Prior Art and Problems) As a method for producing 4- (parafluorobenzoyl) phenol, a method of reacting a large amount of parafluorobenzoic acid and phenol in polyphosphoric acid (Japanese Patent Publication No. 50-4653), a large amount In anhydrous hydrogen fluoride (JP-A-53-9735), in a large amount of methanesulfonic acid (JP-A-57-154140), in a large amount of trifluoromethanesulfonic acid. Method of reacting (JP-A-58)
-62132) is proposed, but these methods are expensive due to the expensiveness of parafluorobenzoic acid, the use of a large amount of strong acid, and the water produced by the dehydration reaction. The acid is diluted and must be concentrated in order to maintain the required acid concentration, but it has drawbacks such as the large affinity of these acids with water and the difficulty in separating them. There is. Further, a method of carrying out a Fluder-Crafts reaction between parafluorobenzoic acid chloride and phenol (JP-A-53-9735 and JP-A-58-15936).
However, parafluorobenzoic acid chloride is more expensive.

Furthermore, a method of reacting fluorinated benzene and parahydroxybenzoic acid in anhydrous hydrogen fluoride-boron trifluoride (JP-A-58-15936), a method of reacting in a large amount of trifluoromethanesulfonic acid ( JP-A-58-62132
However, para-hydroxybenzoic acid is a relatively expensive raw material, and it is difficult to separate water generated by the dehydration reaction from these strong acids as described above. It has drawbacks such as

(Means for Solving the Problems) Therefore, the present inventors inexpensively produced 4- (parafluorobenzoyl) phenols from simple compounds such as fluorinated benzene, carbon monoxide, and alkali metal salts of phenols. As a result of extensive studies on the method of manufacturing, the present invention has been completed.

That is, the present invention includes: a) an iodination step of reacting iodine and / or hydrogen iodide with fluorinated benzene in the presence of an oxidizing agent to obtain paraiodofluorobenzene; and b) carbonylation of the paraiodofluorobenzene. An esterification step in which carbon monoxide and an alkali metal salt of a phenol having no substituent at the para position are reacted in the presence of a catalyst to obtain parafluorobenzoic acid phenyl esters; and c) the parafluorobenzoic acid A method for producing 4- (parafluorobenzoyl) phenols, which comprises a rearrangement reaction step of rearranging acid phenyl esters into 4- (parafluorobenzoyl) phenols in the presence of an acid catalyst.

The method of the present invention is represented by the following reaction formula.

a) Iodination process Or / and b Esterification process c) Rearrangement reaction process (In the formula, R ¹ , R ² , R ³ , and R ⁴ each represent hydrogen, or a substituent selected from a lower alkyl group, a lower alkoxy group, a fluorine atom, a nitro group, and a cyano group, and these are respectively And M'represents an alkali metal atom.) In the iodination step of the present invention, an iodinating agent comprising iodine and / or hydrogen iodide and an oxidizing agent is a fluorinated benzene. The iodination reaction is carried out by reacting with, but it is preferable to carry out so as to maximize the selectivity and yield of paraiodofluorobenzene, and iodine containing at least 80 mol% paraiodofluorobenzene. It is necessary to do so in order to obtain a fluorinated fluorobenzene mixture. For that purpose, it is preferable to use 2 mol or more of fluorinated benzene per 1 mol of iodine,
More preferably, it is carried out using 2.5 to 10 mol of fluorinated benzene. If the amount of fluorinated benzene used is less than 2 mol per 1 mol of iodine, the amount of polyiodofluorobenzene such as diiodofluorobenzene is increased as a by-product, and unreacted iodine remains, resulting in paraiodofluoro. The yield and selectivity of benzene decrease. Further, more than 10-fold mole of fluorinated benzene may be used, but this is not so preferable method because the reactor becomes large and the amount of unreacted fluorinated benzene to be separated increases.

As the oxidizing agent which is combined with iodine and / or hydrogen iodide to serve as an iodination agent, various oxidizing agents can be used. For example, oxidative inorganic acids such as nitric acid, nitrous acid, and sulfuric acid; oxidative nitrogen oxides such as NO ₂ and N ₂ O ₃ ; halogen oxyacids such as iodic acid and periodic acid; peracetic acid, Peroxides such as hydrogen peroxide are preferably used. Particularly preferred are nitric acid and / or nitrogen oxides having oxidizing power, which are inexpensive and have good reactivity.

The amount of the oxidizing agent used is preferably 2 moles or more in the case of a one-electron oxidizing agent and 1 mole or more in the case of a two-electron oxidizing agent per 1 mole of iodine.

The iodination reaction is preferably carried out at a temperature as low as possible in order to maximize the selectivity of paraiodofluorobenzene in the iodinated fluorobenzene mixture,
If the reaction temperature is too low, the reaction rate becomes slow, which is not a preferable method. Paraiodofluorobenzene selectivity is 80% or more, in order to react at an appropriate reaction rate, the range of 10 ~ 150 ℃ is preferable, more preferably 3
It is in the range of 0 to 100 ° C.

In the iodination reaction, it is not necessary to use a catalyst, but an iron-based catalyst such as iron powder, iron chloride, iron bromide or iron iodide, or an aluminum-based catalyst such as aluminum chloride or aluminum iodide can also be used.

Further, it is also a preferable method to carry out the iodination step without using a solvent other than fluorinated benzene, but a solvent can be used if necessary. As such a solvent, any solvent can be used as long as it does not adversely affect the reaction, for example, lower aliphatic carboxylic acids such as acetic acid and propionic acid; carbon tetrachloride, chloroform, methylene chloride, trichloroethane, etc. Lower aliphatic halogenated hydrocarbons; ethers such as ether and dioxane; carbon disulfide; water and the like.

Depending on the type of iodizing agent used and, in some cases, the type of solvent used, the iodination reaction may be carried out in a heterogeneous liquid phase. , The reaction can proceed smoothly.

The iodination step can be carried out in either a batch system or a flow system,
In the reaction system, it is important to react with the iodination agent in a state in which the fluorinated benzene is present in excess of the equivalent amount, and also to make the reaction rate of iodine and / or hydrogen iodide as high as possible. Reacting is also important.

A separation / purification step is carried out in order to separate and obtain paraiodofluorobenzene from the iodinated fluorobenzene mixture obtained in the iodination step. The reaction mixture that has undergone the iodination step usually contains unreacted fluorinated benzene and para-iodofluorobenzene, which are present in excess during the reaction, orthoiodofluorobenzene and, in some cases, metaiodofluorobenzene and diiodofluorobenzene. Water containing the iodinated product of polyiodofluorobenzene and the reduced product of the oxidant, or possibly unreacted oxidant left by the use of excess amounts. It is made up of divisions.

If the amount of water or the amount of residual oxidant is smaller than that of the organic part, the organic part can be separated directly by a method such as distillation.
Although it can be recovered, it is usually preferable to separate the organic part by two-layer separation and the like, then wash with water, and then carry out the separation / purification step of the organic part.

Separation / purification of the iodinated fluorobenzene mixture is carried out by distillation or / and crystallization operation to obtain highly pure paraiodofluorobenzene.

In the esterification step of the present invention, the paraiodofluorobenzene obtained in the iodination step is reacted with carbon monoxide and an alkali metal salt of a phenol having no substituent at the para position in the presence of a carbonylation catalyst. Then, parafluorobenzoic acid phenyl esters are obtained.

As the carbonylation catalyst, a catalyst containing a white metal element such as palladium, rhodium, ruthenium, platinum or iridium, or a catalyst containing a metal element such as iron, cobalt or nickel is preferably used. Particularly preferred is a palladium catalyst or a nickel catalyst. The palladium catalyst is not particularly limited as long as it contains a palladium element as a component, and palladium may be in a metallic state or may be a component forming a compound. Also,
This palladium component is, for example, activated carbon, graphite,
Carriers of silica, alumina, silica-alumina, silica-titania, titania, zirconia, barium sulfate, calcium carbonate, asbestos, bentonite, diatomaceous earth, polymers, ion exchange resins, zeolites, molecular sieves, magnesium silicate, magnesia, etc. It may be supported on the.

Examples of the palladium in the metallic state include palladium metal, palladium black, and a compound containing palladium ions supported on the carrier as described above, followed by reduction treatment with hydrogen, formaldehyde, hydrazine, or the like, and an alloy containing palladium or an intermetallic compound. Are used. Examples of alloys or intermetallic compounds include selenium, tellurium,
Sulfur, antimony, bismuth, copper, silver, gold, zinc, tin, vanadium, iron, cobalt, nickel, mercury, lead,
Examples thereof include those containing thallium, chromium, molybdenum, tungsten and the like. Of course, these alloys or intermetallic compounds may be supported on the carrier as described above.

On the other hand, as the compound containing palladium, PdCl ₂ , PdBr ₂ ,
Inorganic salts such as PdI ₂ , Pd (NO ₃ ) ₂ and PdSO ₄ ; Pd (OCOCH ₃ ) ₂ ,
Organic acid salts such as barium oxalate; Pd (CN) ₂ ; PdO; P
dS; M ₂ [PdX ₄ ], M ₂ [PdX ₆ ] Palladates (M represents an alkali metal or an ammonium ion, X is a nitro group, a cyano group, a halogen, NO ₃ , Ammine complexes of palladium such as [Pd (NH ₃ ) ₄ X ₄ and [Pd (en) ₂ ] X ₂ (X has the same meaning as above, and en represents ethylenediamine); PdCl ₂ (PhCN ) ₂ ,
PdCl ₂ (PR ₃ ) ₂ , Pd (CO) (PR ₃ ) ₃ , Pd (PPh ₃ ) ₄ ,, PdCl
(R) (PPh ₃ ) ₂ , Pd (C ₂ H ₄ ) (PPh ₃ ) ₂ , Pd (C ₂ H ₅ ) ₂ and other complexing compounds or organometallic compounds (R is an organic group such as alkylaryl) Complex compounds in which a chelate ligand such as Pd (acac) ₂ is coordinated (acac represents acetylacetone) and the like are used.

The nickel catalyst used in the present invention is not particularly limited as long as it contains a nickel element as a component, and nickel may be in a metallic state or may be a component forming a compound. Further, the nickel component may be supported on the carrier as described above.

On the other hand, compounds containing nickel include NiCl ₂ , NiBr ₂ and Ni.
Halogenated nickels such as I ₂ ; NiSO ₄ , Ni (NO ₃ ) ₂ , NiCO
Nickel salts of inorganic acids such as ₃ , Ni (SCN) ₂ and Ni (ClO ₄ ) ₂ ; Nickel salts of organic acids such as Ni (OCOCH ₃ ) ₂ and oxalic acid nickel; Nickel oxide; Nickel hydroxide; Nickel sulfide; Nickel phosphide; nickel salts represented by M ₂ [NiX ₄ ], M ₄ [NiX ₆ ] (M represents an alkali metal or ammonium ion, X represents a nitro group, a cyano group, a halogen, NO ₃ , 1 / 2SO ₄ ); [Ni (NH ₃ ) ₄ ] X ₂ , [Ni
Nickel ammine complexes such as (Y) ₃ ] X ₂ , [Ni (Y) ₂ ] X ₂ , [Ni (py) ₄ ] X ₄ (X has the same meaning as above, Y is ethylenediamine, diethylenetriamine, Represents chelating ligands such as bipyridine and phenanthroline, py represents pyridine); Complex compounds in which chelating ligands such as Ni (acac) ₂ are coordinated (acac represents acetylacetone); Ni (CO ) ₄ , Ni (CO) ₃ (PR ₃ ), Ni (C
O) ₂ (PR ₃ ) ₂ , NiX ₂ (PR ₃ ) ₂ , NiX (PR ₃ ) ₃ , Ni (PR ₃ ) ₄ ,
NiXPh (PR ₃ ) ₂ , Ni (RNC) ₂ , [NiX (allyl)] ₂ Ni (C
_{5 H 5) 2, Ni (} CO) 2 (C 5 H 5), NiX (C 5 H 5) (PR 3), Ni (C
Complex compounds such as OD) ₂ , Ni (COD) (PR ₃ ) or organic nickel compounds (R and X are as described above and COD represents cyclooctadiene) and the like are used. In addition,
Some of these compounds may be used in the form of hydrates.

These palladium catalysts and nickel catalysts may be used alone or in combination of two or more.

Further, other compounds can be added for the purpose of improving the yield and selectivity, increasing the reaction rate, and decreasing the reaction temperature. Examples of such a compound include a phosphine compound represented by the general formula (1).

RP ′ ₁ R ′ ₂ R ′ ₃ (I) (In the formula, R ′ ₁ , R ₂ ′ and R ′ ₃ are hydrogen, halogen, an aliphatic group, an alicyclic group, an aromatic group and an araliphatic group. Which may be the same or may be elements constituting a ring containing phosphorus.) Of course, such a polyphosphine compound containing two or more phosphorus in one molecule may be used. Good.

Examples of such phosphine compounds include n-octylphosphine, di-n-butylphosphine, diethylbutylphosphine, tri-n-propylphosphine,
Alkylphosphines such as tri-n-butylphosphine, dialkylphosphines and trialkylphosphines; cycloaliphatic phosphines such as cyclohexylphosphine and dicyclohexylphosphine; benzylphosphines, dibenzylphosphines, dibenzylethyl Aroaliphatic phosphines such as phosphine and tribenzylphosphine; methylphenylphosphine, ethylphenylphosphine, dimethylphenylphosphine, methyldiphenylphosphine, methylbenzylphenylphosphine, ethyldiphenylphosphine And mixed cyclophosphines such as dicyclohexylphenylphosphine; phenylphosphine, tolylphosphine, diphenylphosphine, triphenylphosphine, tristrilphosphine, diphenyltolylphosphine Which arylphosphines, diarylphosphines and triarylphosphines; bis (biphenylphosphino) methane, bis (diphenylphosphino) ethane, orthophenylenebis (diethylphosphine), 2,2'-bis (diphine) Enylphosphine)-
Diphosphines such as 1,1′-binaphthyl are used.

Such phosphine compounds may be of one type or of two types.
You may use it in mixture of 2 or more types. Among such phosphine compounds, triarylphosphine is particularly preferably used. Among the triaryl phosphines, triphenyl phosphine is particularly preferably used because of its easy availability.

The alkali metal salt of a phenol having no substituent at the para position used in the present invention has the general formula The compound represented by the formula (1) is a compound in which a hydrogen atom of a hydroxyl group of a phenol is substituted with an alkali metal atom. (However, R ¹ , R ² , R ³ , R ⁴ , and M ′ are as described above.) Such a compound may be obtained by any method, for example, an alkali metal It can be easily obtained from a basic substance containing an atom and phenols having no substituent at the para position. As the basic substance containing an alkali metal atom, for example, an alkali metal, an alkali metal oxide,
Examples thereof include alkali metal hydroxides, alkali metal carbonates and alkali metal bicarbonates. In particular, the method by the reaction of a phenol with an alkali metal hydroxide such as lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide or cesium hydroxide is the easiest.

Examples of such phenols as a raw material of alkali metal salts of phenols having no substituent at the para-position include phenol, cresol, dimethylphenol, trimethylphenol, tetramethylphenol, ethylphenol, diethylphenol, triethylphenol,
Ethyl cresol, methoxyphenol, ethoxyphenol, dimethoxyphenol, methoxycresol,
Fluorophenol, difluorophenol, fluorocresol, nitrophenol, dinitrophenol,
Nitrocresol, cyanophenol, dicyanophenol, cyanocresol, fluoronitrophenol,
Fluoronitrocresol, fluorocyanophenol, nitrocyanophenol, cyclohexylphenol, cyclohexylcresol, cyclohexylfluorophenol and the like are used (however, in the case of substituted phenols, those in which the para position is substituted with respect to the hydroxyl group are excluded).

Of these alkali metal salts of phenols, sodium salt or potassium salt of phenol or 2,6-dimethylphenol is particularly preferably used.

The carbon monoxide may be pure carbon monoxide, or may be diluted with another gas such as nitrogen, argon, helium, or lower hydrocarbon that does not adversely affect the reaction. Carbon monoxide has a partial pressure of 0.1 to 300 kg / cm ² , preferably 1 to 200 kg /
Used in the cm ² range.

In carrying out the esterification step, the carbonylation catalyst is preferably used in an amount of usually 0.0001 to 1,000 times the molar amount of the metal atom contained therein with respect to paraiodofluorobenzene.

When an additive such as a phosphine compound is used, it is usually added in an amount of 0.01 to about 100 to the metal atom in the carbonylation catalyst.
It is preferably used in an amount of 1,000 times the molar amount.

Alkali metal salts of phenols having no substituents at the para position are preferred for para iodofluorobenzene.
It is used in the range of 0.5 to 2.0 equivalents, more preferably 0.8 to 1.5 equivalents.

In the esterification step of the present invention, a reaction solvent may not be used, but a solvent which does not adversely influence the reaction can be used if necessary.

Examples of such a solvent include aliphatic hydrocarbons such as hexane, heptane, octane, decane, and pentadecane; alicyclic hydrocarbons such as cyclohexane and methylcyclohexane; aromatics such as benzene, toluene, xylene, and mesitylene. Hydrocarbons; Nitriles such as acetonitrile and benzenenitrile; Sulfones such as sulfolane, methylsulfolane and dimethylsulfolane; Ethers such as toterahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane; Acetone, methyl ethyl ketone, etc. Ketones; esters such as ethyl acetate and ethyl benzoate; amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone and hexamethylphosphoramide.

Esterification reaction is usually 50 ~ 350 ℃, preferably 100 ~ 300
In the range of ℃, the reaction pressure is usually 1 ~ 500kg / cm ² ,
It is preferably carried out in the range of 5 to 300 kg / cm ² .

By carrying out such a carbonylation reaction, the fluorine atom of paraiodofluorobenzene is not replaced,
Parafluorobenzoic acid phenyl esters in which only the iodine atom is substituted with an aryloxycarbonyl group,
It has been found that a high yield of 90% or more and a high selectivity can be obtained.

Further, the alkali metal iodide produced as a by-product in the esterification step is easily separated from the parafluorobenzoic acid phenyl ester by a method such as washing the esterification reaction mixture with water. And from this salt of hydrogen iodide and a base, it can be easily recovered as a hydrogen iodide and a base, or as an iodine and a base, respectively, by a known method. It can be recycled and reused in the esterification step.

In the rearrangement reaction step of the present invention, the parafluorobenzoic acid phenyl ester obtained in the esterification step is subjected to a rearrangement reaction in the presence of an acid catalyst to give the desired 4- (parafluorobenzoyl) phenols. obtain.

As the acid catalyst that can be used in the rearrangement reaction step, it is possible to use an acid catalyst that does not substantially contain water, but in order to maximize yield and selectivity, Lewis acid, and It is preferable to use a strong acidic protonic acid. Such Lewis acids include boron, aluminum, gallium, indium, thallium,
Group III element halides such as scandium and yttrium; Group IV element halides such as silicon, germanium, tin, titanium, and zirconium; V such as antimony, bismuth, vanadium, niobium, and tantalum.
Halides of elements belonging to the genus, halides of metals such as iron, copper and zinc are used. Further, as strongly acidic protonic acids, hydrogen fluoride anhydride; fluorocarboxylic acids such as trifluoroacetic acid and perfluoropropionic acid; sulfonic acids such as methanesulfonic acid, ethanesulfonic acid and benzenesulfonic acid; fluorosulfonic acid, chlorosulfonic acid , Halogenated sulfonic acids such as trifluoromethanesulfonic acid, trichloromethanesulfonic acid and perfluoroethanesulfonic acid, and halogenated alkanesulfonic acids. Further, a high-silica-containing zeolite which is a solid acid, a strongly acidic cation exchange resin, and an acid called a solid superacid can be used in the rearrangement reaction of the present invention. A solid super strong acid is a solid strong acid having a stronger acid strength than 100% sulfuric acid.
For example, SbF ₅ , TaF ₅ , BF ₃ , CF ₃ SO ₃ H, SbF ₅ --HF, SbF ₅ --FSO ₃ H or a mixture thereof may be used as SiO ₂ --Al ₂ O ₃ , SiO ₂ --TiO ₂ , SiO _{2.
-ZrO 2, TiO 2 -ZrO 2,} Al 2 O 3 -B 2 O 3, SiO 2 -WO 3, HF- _{zeolite, Al 2 O 3, SiO 2} , graphite, cation exchange resin,
Examples include activated carbon, those supported on fluorine graphite, and fluorine-containing sulfonic acid resins. Here, the fluorinated sulfonic acid resin is a -CF ₂ SO ₃ H group and / or
Alternatively, it is a resin having a CFSO ₃ H group.

These acids can be used alone or in combination of two or more.

Further, this rearrangement reaction may be carried out without a solvent, but a solvent which does not adversely influence the reaction can also be used. Such solvents include carbon disulfide; halogenated hydrocarbons such as chloroform, methylene chloride, carbon tetrachloride, dichloroethane, trichloroethane, and tetrachloroethane; halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, bromobenzene, and chloronaphthalene. Aromatic hydrocarbons; nitro compounds such as nitrobenzene, nitrotoluene and nitromethane are used.

This rearrangement reaction is preferably performed under substantially anhydrous conditions. When water is present in the reaction system, hydrolysis of the phenyl ester of p-fluorobenzoic acid occurs, and the desired 4
This is because the yield of-(parafluorobenzoyl) phenol decreases. Therefore, not to mention the water content in the acid catalyst, when using a solvent, it is preferable to keep the water content in the solvent as low as possible.

The temperature and reaction time for carrying out this rearrangement reaction vary depending on other reaction conditions such as the type of catalyst and solvent used, but are usually in the temperature range of -30 to 250 ° C, preferably -20 to 200 ° C.
It ranges from a few minutes to a few tens of hours.

By carrying out such a rearrangement reaction, 4- (parafluorobenzoyl) phenols can be obtained from parafluorobenzoic acid phenyl esters with high yield and high selectivity.

(Effect of the Invention) According to the method of the present invention, 4- (parafluorobenzoyl) is obtained from an alkali metal salt of fluorinated benzene, carbon monoxide and phenols having no substituent at the para position in high yield and high selectivity. It has become clear that phenols can be produced.

(Examples) Hereinafter, the present invention will be further described with reference to Examples, but the present invention is not limited to these Examples.

Example 1 288 g of fluorinated benzene and iodine were placed in a flask equipped with a reflux condenser.
254 g was added, the mixture was heated to 65 to 70 ° C., and then 840 g of 61% nitric acid was gradually added dropwise with stirring. After completion of dropping, stirring was continued for further 3 hours to complete the reaction. Iodine was completely consumed. The reaction mixture was made into two layers, and the organic layer was washed with water, an aqueous solution of sodium carbonate and water in this order, and then distilled. The composition after distilling off excess fluorinated benzene and a small amount of water was 91.9% paraiodofluorobenzene, 7.6% orthoiodofluorobenzene, and 0.5% metaiodofluorobenzene, and weighed 442 g.
(99.5% yield as monoiodofluorobenzene).

The following esterification step was carried out using paraiodofluorobenzene obtained by rectifying this monoiodofluorobenzene using a packed column rectification apparatus equipped with a reflux device.

22.2 g of paraiodofluorobenzene, phenol and an equivalent amount of sodium hydroxide were reacted in an aqueous solution and then dehydrated,
12.8 g of sodium phenoxide obtained by drying, 0.1 g of palladium chloride, 0.3 g of triphenylphosphine, and 50 ml of toluene were placed in an autoclave, and after replacing the inside of the autoclave with carbon monoxide, 50 kg of carbon monoxide / Pressed into cm ² . After reacting at 180 ° C. for 2 hours under stirring, the mixture was cooled, filtered, and the filtrate was analyzed. As a result, the reaction rate of paraiodofluorobenzene was 100%, and parafluorobenzoic acid phenyl ester was The yield was 99% and the selectivity was 99%. The slag was sodium iodide containing unreacted sodium phenoxide that was present in excess. Iodine was quantitatively recovered as sodium iodide.

Using parafluorobenzoic acid phenyl ester obtained by vacuum distillation of the esterification reaction mixture,
The next rearrangement reaction step was performed.

Add 10.8 g of phenyl parafluorobenzoate and 22 g of trifluoromethanesulfonic acid to the flask and stir at 45-50 ° C under stirring.
And reacted for 2 hours. After that, most of trifluoromethanesulfonic acid was distilled off under reduced pressure, and then the reaction mixture was put into cold water. The white crystals thus formed were separated by filtration, dried under reduced pressure and analyzed. As a result, it was found that 4- (parafluorobenzoyl) phenol was obtained in a yield of 96% and a selectivity of 96%.

Since the unreacted fluorinated benzene can be recovered and reused in the iodination step by circulation, in this example, 4- (parafluorobenzoyl) phenol was obtained in a yield of 87% and a selectivity of 87 with respect to the reacted fluorinated benzene. It shows that it was obtained in%.

Example 2 844 g of fluorinated benzene, 687 g of finely ground iodine and 145 g of 61% nitric acid were placed in a flask equipped with a reflux condenser,
Heat to 54 ° C. Then, 1 kg of 61% nitric acid was gradually added dropwise with stirring. After completion of dropping, stirring was continued for further 5 hours to complete the reaction. Iodine was completely consumed. The same treatment as in Example 1 was carried out to give paraiodofluorobenzene.
Monoiodofluorobenzene consisting of 92.2%, orthoiodofluorobenzene 7.4%, and metaiodofluorobenzene 0.4% was obtained with a yield of 99.6%.

By cooling this iodofluorobenzene mixture to −30 to −40 ° C., para-iodofluorobenzene crystallized was obtained. The following esterification step was performed using this paraiodofluorobenzene.

Paraiodofluorobenzene 22.2g, sodium-2,6-
Example 1 except that dimethylphenoxide (15,8 g), nickel acetylacetonate Ni (acac) ₂ (0.8 g) and toluene (50 ml) were placed in an autoclave and reacted at 200 ° C. for 2 hours.
As a result of carrying out the reaction in the same manner as in the esterification step, 2,6-dimethylphenyl ester of parafluorobenzoic acid was obtained with a yield of 97% and a selectivity of 97%.

In addition, sodium-2,6-dimethylphenoxide is 2,6
-Dimethylphenol was reacted with an equivalent amount of sodium hydroxide in an aqueous solution, dehydrated and dried, and then used.

19.5 g of this parafluorobenzoic acid-2,6-dimethylphenyl ester and 76 g of methanesulfonic acid were placed in a flask and reacted under stirring at 150 ° C for 1.5 hours, and then most of the methanesulfonic acid was distilled off under reduced pressure. did. Then, the reaction mixture was put into cold water to separate white crystals that had formed, and the crystals were dried under reduced pressure. The white crystals are 4- (parafluorobenzoyl)
It was -2,6-dimethylphenol with a yield of 97% and a selectivity of 99%.

Since the unreacted fluorinated benzene is recovered and can be reused in the iodination process by circulation, in this example, 4- (parafluorobenzoyl) -2,6 is used as a reference based on the reacted fluorinated benzene.
-Indicates that dimethylphenol was obtained with a yield of 86% and a selectivity of 88%.

Example 3 192 g of fluorinated benzene, 63.5 g of iodine, 28.4 g of periodic acid dihydrate, 500 ml of acetic acid, 1 g of sulfuric acid were put in a flask, and 45-
The reaction was carried out at 50 ° C. for 5 hours with stirring. After the completion of the reaction, fluorinated benzene and acetic acid were distilled off, and the mixture was washed with an aqueous sodium carbonate solution and water and then dried.

The reaction product consisted of paraiodofluorobenzene 93.0%, orthoiodofluorobenzene 6.7%, and metaiodofluorobenzene 0.3%, and the yield as monoiodofluorobenzene was 98.8%.

This monoiodofluorobenzene mixture was crystallized in the same manner as in Example 2 to obtain 22.2 g of para-iodofluorobenzene and 12.8 of sodium phenoxide.
g, nickel chloride NiCl ₂ 0.2 g, triphenylphosphine 0.
As a result of carrying out the same reaction and operation as in the esterification step of Example 1 except that 4 g and 50 g of toluene were reacted at 230 ° C. for 2 hours, the yield of parafluorobenzoic acid phenyl ester was increased.
It was obtained with 95% and a selectivity of 95%.

Using the perfluorobenzoic acid phenyl ester obtained by distilling the esterification reaction mixture under reduced pressure,
The next rearrangement reaction step was performed.

15 g of parafluorobenzoic acid phenyl ester and 150 g of liquid anhydrous hydrogen fluoride were placed in a polyethylene flask equipped with a reflux condenser, and reacted at 0-10 ° C. for 10 hours with stirring. After the reaction
The system was raised to 20-40 ° C and anhydrous hydrogen fluoride was recovered by distillation. The obtained residue was washed with a small amount of diluted alkaline water and distilled water, and then dried under reduced pressure. As a result of analysis of the product, the reaction rate of paraphenyl fluorobenzoic acid phenyl ester was 85%, and 4- (parafluorobenzoyl) phenol was produced in a yield of 84% and a selectivity of 99%. The isomer 2- (parafluorobenzoyl) phenol was only detected at 1%.

Unreacted paraiodofluorobenzene and parafluorobenzoic acid phenyl ester can be recovered and reused in the iodination step and the rearrangement reaction step, respectively. −
(This indicates that parafluorobenzoylphenol was obtained with a yield of 86.4% and a selectivity of 86.4%.

Example 4 The following esterification step was performed using the paraiodofluorobenzene obtained in Example 2.

Paraiodofluorobenzene 22.2g, sodium-2,6-
Dimethylphenoxide (16.0 g), palladium acetate (50 mg) and xylene (50 ml) were placed in an autoclave, the inside of the autoclave was replaced with carbon monoxide, and then heated to 190 ° C. At this temperature, while continuously introducing carbon monoxide so as to keep the reaction pressure at 50 kg / cm ² , the mixture was reacted for 2 hours under stirring, cooled, filtered, filtered, and analyzed. As a result, parafluorobenzoic acid-2,6-dimethylphenyl ester was obtained with a yield of 98% and a selectivity of 98%. Iodine was quantitatively recovered as sodium iodide.

Next, 12.2 g of this parafluorobenzoic acid-2,6-dimethylphenyl ester, 7.3 g of anhydrous aluminum chloride, and 70 ml of dry orthodichlorobenzene were placed in a flask,
The reaction was carried out for 4 hours under stirring at ℃. After the reaction, orthodichlorobenzene was distilled off under reduced pressure, and a hydrochloric acid aqueous solution was added to the residue and the mixture was stirred. Then, extraction with ethyl acetate was performed, and ethyl acetate was distilled off from the extract to give 4- (parafluorobenzoyl) -2,6-dimethylphenol in a yield of 94%.
Got with. The standard yield of reacted fluorinated benzene is 84.6%.
It was.

Example 5 The following esterification step was carried out using the paraiodofluorobenzene obtained in Example 2.

Paraiodofluorobenzene 22.2 g, potassium phenoxide 13.5 g, 5% palladium on activated carbon supporting 5% Pd /
C1g, 50 ml of toluene, and 0.5 g of triphenylphosphine were placed in an autoclave, the inside of the autoclave was replaced with carbon monoxide, and then carbon monoxide was injected up to 50 kg / cm ² .
After reacting at 170 ° C. for 2 hours under stirring, the mixture was cooled, the reaction mixture was filtered, and Pd / C and potassium iodide were separated by filtration. As a result of analyzing this liquid component, parafluorobenzoic acid phenyl ester was produced in a yield of 99% and a selectivity of 99%.

After distilling toluene off from the esterification reaction mixture,
Vacuum distillation was carried out to obtain highly pure parafluorobenzoic acid phenyl ester.

It was also quantitatively recovered as potassium iodide.

This parafluorobenzoic acid phenyl ester 17.3g, methanesulfonic acid 50g, trifluoromethanesulfonic acid 1g
Was placed in a flask and reacted at 100 ° C. for 30 minutes under stirring, and then most of methanesulfonic acid and trifluoromethanesulfonic acid were distilled off under reduced pressure. Then, the reaction mixture was put into cold water to separate white crystals that had formed, and the crystals were dried under reduced pressure. 4- (parafluorobenzoyl) phenol was obtained with a yield of 96% and a selectivity of 96%. The yield based on the reacted fluorinated benzene was 87.3%.

Incidentally, the ortho- and meta-iodofluorobenzene produced as a by-product in the iodination step of these Examples are subjected to a hydrogenolysis reaction in the presence of a catalyst and a base,
It can be quantitatively converted into a fluorinated benzene and a salt of hydrogen iodide and the base, and if the fluorinated benzene recovered by performing this operation is recycled and reused, the fluorinated benzene in these examples is used. It goes without saying that the yields of 4- (parafluorobenzoyl) phenols based on benzene rise to even higher values around 95%, respectively.

Preferred embodiments of the present invention are as follows.

(1) The method according to claim 1, wherein the oxidizing agent is nitric acid and / or a nitrogen oxide having an oxidizing power. (2) The alkali metal salt of phenols having no substituent at the para position is phenol or A method according to the claims, which is a sodium salt or a potassium salt of 2,6-dimethylphenol (3) A method according to the claims, wherein the carbonylation catalyst is a palladium catalyst or a nickel catalyst (4) The acid catalyst is Lewis An acid and / or a strongly acidic protic acid.

Claims (1)

[Claims] 1. A) iodination step of reacting iodine and / or hydrogen iodide with fluorinated benzene in the presence of an oxidizing agent to obtain para-iodofluorobenzene, and b) carbonylation of the para-iodofluorobenzene. An esterification step of reacting with carbon monoxide and an alkali metal salt of a phenol having no substituent in the para position in the presence of a catalyst to obtain parafluorobenzoic acid phenyl ester; and c) the parafluorobenzoic acid A process for producing 4- (parafluorobenzoyl) phenols, which comprises a rearrangement reaction step of rearranging acid phenyl esters into 4- (parafluorobenzoyl) phenols in the presence of an acid catalyst.