JPH0678263B2 - 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 parafluorobenzoic acid and phenol in a large amount of polyphosphoric acid (Japanese Patent Publication No. 50-4653), a large amount of Reaction in anhydrous hydrogen fluoride (JP-A-53-9735), reaction in a large amount of methanesulfonic acid (JP-A-57-154140), reaction in a large amount of trifluoromethanesulfonic acid Method (JP-A-58)
However, in these methods, due to the high cost of parafluorobenzoic acid, the use of a large amount of strong acid, and the water generated by the dehydration reaction, Acid has been diluted and must be concentrated to maintain the required acid concentration,
These acids have the disadvantages that they have a high affinity for water and their separation is difficult. Further, a method of carrying out the Friedel-Crafts reaction between parafluorobenzoic acid chloride and phenol (Japanese Patent Laid-Open No. 9735/53, Japanese Patent Laid-Open No.
No. 15936), but 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 that.

(Means for Solving Problems) Therefore, the present inventors have proposed a method for inexpensively producing 4- (parafluorobenzoyl) phenols from simple compounds such as fluorinated benzene, carbon monoxide, and phenols. As a result of repeated intensive studies, the present invention has been completed.

That is, in the present invention, in producing 4- (parafluorobenzoyl) phenols from fluorinated benzene, carbon monoxide and phenols, (a) bromine and / or molecular oxygen and hydrogen bromide are used. A bromination step of reacting an agent with fluorinated benzene to obtain para-bromofluorobenzene, and (b) the para-bromofluorobenzene in the presence of a carbonylation catalyst and a base at the carbon monoxide and para-substituents An esterification step for obtaining parafluorobenzoic acid phenyl esters by reacting with phenols having no
And (c) a rearrangement reaction step of rearranging the parafluorobenzoic acid phenyl esters into 4- (parafluorobenzoyl) phenols in the presence of an acid catalyst. It is to provide a manufacturing method of a class.

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

(A) Bromination process And / or (B) Esterification step (C) Rearrangement reaction step (In the formula, R ¹ , R ² , R ³ , and R ⁴ each represent a substituent selected from hydrogen or a lower alkyl group, a lower alkoxy group, a fluorine atom, a nitro group, and a cyano group, and these are respectively May be the same, and Base represents a base.) In the brominating step of the present invention, bromine as a brominating agent, or molecular oxygen and hydrogen bromide are each independently,
Alternatively, they can be used in combination.

The bromination reaction of fluorinated benzene using bromine is carried out in the gas phase,
Although either liquid phase can be used, in order to obtain para-bromofluorobenzene with high selectivity and high yield, the reaction in liquid phase is more preferable. When carrying out the liquid phase bromination reaction, 1.1 to 10 mol of fluorinated benzene is preferably used, and more preferably 1.3 to 5 mol of fluorinated benzene is used per mol of bromine. If the amount of fluorobenzene used is less than 1.1 mol per mol of bromine, the amount of polybrominated fluorobenzene such as dibromofluorobenzene and tribromofluorobenzene will increase, and unreacted bromine will remain. The yield and selectivity of para-bromofluorobenzene decrease. Further, it is preferable to use more than 10 times mol of fluorinated benzene because the bromination reaction itself has no problem, but the reactor becomes large and the amount of unreacted fluorinated benzene to be separated increases. Not the way.

Further, in order to increase the selectivity of para-bromofluorobenzene and reduce the amount of by-products such as isomers ortho-bromofluorobenzene, meta-bromofluorobenzene, or polybrominated fluorobenzene, the liquid-phase bromination reaction should be performed as much as possible. It is preferable to carry out at a low temperature. In this sense, the reaction is preferably carried out at a temperature of 100 ° C or lower,
The range is −20 to 100 ° C., more preferably −10 to 8 ° C.
It is in the range of 0 ° C.

This liquid phase bromination reaction can be carried out without a catalyst, but it is also possible to use a catalyst because it is possible to lower the reaction temperature to improve the selectivity of para-bromofluorobenzene and to increase the reaction rate. is there.

As such a catalyst, iron powder, iron chloride, iron bromide, iron hydroxide and other iron catalysts; aluminum chloride, aluminum bromide and other aluminum catalysts; iodine and the like can be used. Particularly preferred is an iron catalyst.

Further, it is also a preferable method to carry out the liquid phase bromination reaction 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, and for example, lower aliphatic carboxylic acids such as acetic acid and propionic acid; carbon tetrachloride, chloroform, methylene chloride, Lower aliphatic halogenated hydrocarbons such as trichloroethane; ethers,
Ethers such as dioxane; carbon disulfide and the like.

This liquid phase bromination reaction can be carried out by either a batch system or a flow system, but it is important to carry out the reaction in the reaction system in a state where fluorinated benzene is present in excess of the equivalent amount with respect to bromine.

By such liquid phase bromination reaction using bromine as a brominating agent, para-bromofluorobenzene was converted to
% Yields and selectivities, and in the usual cases, even higher yields and selectivities of 90% or higher or 95% or higher can be achieved.

In addition, the oxybromination reaction of fluorinated benzene using molecular oxygen and hydrogen bromide as brominating agents can be carried out in either the gas phase or the liquid phase, but the high productivity and explosion limit In consideration, the reaction in the gas phase is more preferable.

This gas phase oxybromination reaction can be carried out without a catalyst, but a catalyst is used for the purpose of further improving the yield and selectivity of parabromofluorobenzene, lowering the reaction temperature, and improving the reaction rate. Is a more preferable method. As such a catalyst, a copper-based catalyst, an iron-based catalyst, a catalyst obtained by mixing these, or the like is preferably used, but a solid catalyst containing copper is particularly preferable. As such a copper-based catalyst, copper metal such as copper powder;
Halides such as copper chloride, copper bromide and copper iodide; salts such as copper nitrate, copper sulfate and copper acetate; oxides and sulfides such as cuprous oxide, cupric oxide and copper sulfide Various copper compounds are used.

These metallic coppers or copper compounds can be used alone or, for example, activated carbon, graphite, silica, alumina, silica-alumina, silica-titania,
It may be supported on a carrier such as titania, zirconia, barium sulfate, calcium carbonate, asbestos, bentonite, diatomaceous earth, polymer, ion exchange resin, zeolite, molecular sieve, magnesium silicate or magnesia.

Further, as the solid catalyst containing copper, zeolite ion-exchanged with copper ions is also preferably used. Such copper ion-exchanged zeolite, by immersing the zeolite in an aqueous solution containing copper ions, after exchanging sodium cations in the zeolite with a predetermined amount of copper cations,
It is a dried product and can be easily obtained. The exchange amount of copper ions is 5% or more of the ion exchange capacity,
It is more preferably 10% or more. Incidentally, AlO ₄ The ion exchange capacity here is an anion of the zeolite ^-
It is the total amount of the cation portion paired with.

As such a zeolite, Y-type zeolite, mordenite, ZSM-5 and the like are preferably used, but Y-type zeolite is particularly preferable.

The molar ratio of fluorinated benzene to hydrogen bromide in the raw material for this gas phase oxybromination reaction is in the range of 1.0 to 10 and more preferably in the range of 1.2 to 8. If this ratio is less than 1.0, unreacted Of hydrogen bromide and the amount of by-produced polybrominated fluorobenzene increase, which is not preferable. Further, if this ratio is carried out at 10 or more, there is no adverse effect on the reaction, but the space-time yield of para-bromofluorobenzene is reduced, and the amount of unreacted fluorinated benzene to be separated is increased. is not.

The molar ratio of molecular oxygen to hydrogen bromide in the feed gas is in the range of 0.5 to 10, more preferably 0.6 to 5. If this ratio is less than 0.5, unreacted hydrogen bromide remains, which is not preferable. On the other hand, if it is more than 10, the space-time yield of the product is lowered, which is not preferable.

This molecular oxygen may be pure oxygen or oxygen-containing oxygen, and may be air, or other gas that does not interfere with the reaction with air or pure oxygen, such as nitrogen, argon, helium, carbon dioxide, or the like. It may be diluted with active gas.

The reaction temperature of the gas phase oxybromination reaction is not particularly limited as long as it is a temperature that can maintain the reaction system in the gas phase, but if the temperature is too high, the selectivity or yield of para-bromofluorobenzene decreases, so it is usually 60 ~ 400 ° C, preferably 100-300
C., more preferably 150 to 250.degree.

The gas phase oxybromination reaction can be carried out under any of reduced pressure, normal pressure and increased pressure, but is usually carried out in the range of 0.5 to 10 atm, preferably 0.8 to 5 atm.

By such a gas-phase oxybromination reaction, para-bromofluorobenzene can be obtained in a yield and selectivity of 80% or more with respect to hydrogen bromide, which is usually higher than 90%.
The above yield and selectivity can be achieved.

It is of course possible to use not only hydrogen bromide but also a mixture of hydrogen bromide and bromine as the bromine source in the gas phase oxybromination reaction.

In the case of the bromination reaction using bromine, hydrogen bromide is usually produced as a by-product, and it is also a preferable method to use this by-produced hydrogen bromide in the oxybromination reaction. In this case, the by-product hydrogen bromide can be taken out of the system and reacted in another oxybromination reaction device, or molecular oxygen or nitric acid, which is an oxidant, can be added to the bromination reaction system using bromine. By adding it, it is also possible to carry out the oxybromination reaction concurrently.

Of course, it is also possible to take out by-product hydrogen bromide or its form in the form of a salt out of the bromination reaction system and recover it as bromine by a known method.

The brominated fluorobenzene mixture obtained by such a bromination reaction contains para-bromofluorobenzene as a main component, but usually contains a small amount of ortho-bromofluorobenzene, and In some cases, trace amounts of metabromofluorobenzene and dibromofluorobenzene may be contained, but these by-products should be removed by operations such as distillation and / or crystallization, if necessary. You can

In the esterification step of the present invention, the parabromofluorobenzene obtained in the bromination step is reacted with carbon monoxide and phenols in the presence of a carbonylation catalyst and a base to give parafluorobenzoic acid phenyl esters. To get

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. Further, this palladium component is, for example, activated carbon, graphite, silica, alumina, silica-alumina, silica-titania, titania, zirconia, barium sulfate, calcium carbonate, asbestos, bentonite, diatomaceous earth, polymer, ion exchange resin, zeolite, It may be supported on a carrier such as molecular sieve, magnesium silicate or magnesia.

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 palladium 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 , 1/2 SO _Four
Amnesium 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 (PhC
N) ₂ , PdCl ₂ (PR ₃ ) ₂ ,, Pd (CO) (PR ₃ ) ₃ ,, Pd (PPh ₃ ) ₄ ,, Pd
_{Cl (R) (PPh 3)} 2, Pd (C 2 H 4) (PPh 3) 2, Pd (C 3 H 5) 2
Complex compounds or organometallic compounds (R represents an organic group such as alkyl or aryl); complex compounds in which a chelate ligand such as Pd (acac) ₂ is coordinated (acac represents acetylacetone), etc. 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, the compounds containing nickel include NiCl ₂ , NiBr ₂ ,
Halogenated nickels such as NiI ₂ ; NiSO ₄ , Ni (N
Nickel salts of inorganic acids such as O ₃ ) ₂ , NiCO ₃ , Ni (SCN) ₂ and Ni (ClO ₄ ) ₂ ; Nickel salts of organic acids such as Ni (OCOCH ₃ ) ₂ and oxalic acid; Nickel oxide; Water Nickel oxide; Nickel sulfide; Nickel phosphide; M ₂ [NiX ₄ ], M
₄ Nickel salts represented by [NiX ₆ ] (M represents an alkali metal or ammonium ion, X is a nitro group,
Cyano group, halogen, NO ₃ , Represents;); [Ni (NH ₃ ) ₄ ] X ₂ , [Ni (Y) ₃ ] X ₂ ,
Nickel ammine complexes such as [Ni (Y) ₂ ] X ₂ and [Ni (py) ₄ ] X ₂ (X has the same meaning as above, Y is a chelate such as ethylenediamine, diethylenetriamine, bipyridine, and phenanthroline. Represents a ligand, py represents pyridine); complex compounds in which a chelate ligand such as Ni (acac) ₂ is coordinated (acac represents acetylacetone); Ni (CO) ₄ , Ni (CO) ₃ (PR ₃ ), Ni (CO) ₂ (PR
₃ ) ₂ , NiX ₂ (PR ₃ ) ₂ , NiX (PR ₃ ) ₃ , Ni (PR ₃ ) ₄ , N
iXPh (PR ₃ ) ₂ , Ni (RNC) ₂ , [NiX (allyl)] ₂ Ni (C
_{5 H 5) 2, Ni (} CO) 2 (C 5 H 5) 2, NiX (C 5 H 5) (P
R ₃ ), Ni (COD) ₂ , Ni (COD) (PR ₃ ) and other complex compounds or organic nickel compounds (R represents an organic group such as alkyl and aryl, COD represents cyclooctadiene), etc. Is used. Note that 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 (I).

PR ′ ₁ R ′ ₂ R ′ ₃ (I) (wherein 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 (diphenylphosphino) methane, bis (diphenylphosphino) ethane, orthophenylenebis (diethylphosphine, 2,2'-bis (diphine) Enylphosphine) -1,
Diphosphines such as 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 triarylphosphines, triphenylphosphine is particularly preferably used because it is easily available.

The base used in the present invention may be either inorganic or organic. Examples of such a base include lithium oxide, lithium peroxide, sodium oxide, sodium peroxide, sodium superoxide, potassium oxide, potassium peroxide, dipotassium trioxide, potassium superoxide, rubidium oxide, rubidium peroxide, Alkali metal oxides such as rubidium trioxide, rubidium superoxide, rubidium ozonide, cesium oxide, cesium peroxide, cesium trioxide, cesium superoxide, and cesium ozonide; beryllium oxide, magnesium oxide,
Alkaline earth metal oxides such as calcium oxide, calcium peroxide, strontium oxide, strontium peroxide, barium oxide and barium peroxide; lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide , Beryllium hydroxide, magnesium hydroxide, calcium hydroxide, strontium hydroxide,
Alkali metal and alkaline earth metal hydroxides such as barium hydroxide; sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, barium carbonate,
Salts of strong bases and weak acids such as sodium silicate, magnesium silicate, potassium aluminate, calcium aluminate, sodium borate, and barium borate; carbides such as calcium carbide and cesium carbide; aluminum hydroxide,
Potassium hydroxide, indium hydroxide, thallium hydroxide,
Aluminum group metal hydroxides and oxides such as thallium oxide; rare earth element oxides and hydroxides such as lanthanum oxide, cerium oxide and cerium hydroxide; lithium hydride, sodium hydride, sodium borohydride , Hydrides such as calcium hydride and lithium aluminum hydride; alkali metal or alkaline earth metal sulfides and sulfides such as sodium sulfide, sodium hydrogen sulfide, potassium sulfide and calcium sulfide; tetraethylammonium hydroxide; Quaternary ammonium hydroxide compounds such as tetrapropylammonium hydroxide; Quaternary phosphonium hydroxide compounds such as methyltriphenylphosphonium hydroxide and tetramethylphosphonium hydroxide; triethylsulfonium hydroxide, triphenylsulfonium hydroxide Hydroxy Tertiary sulfonium compounds; sodium acetate, potassium benzoate, oxalate rubidium,
Salts of strong bases such as barium propionate with weak organic acids;
Alcohols of alkali metals and alkaline earth metals such as sodium methylate, sodium ethylate, calcium ethylate; alkali metal and alkaline earth metal phenolates such as sodium phenolate, potassium phenolate, magnesium phenolate and the like Alkali metal salts or alkaline earth metals of aromatic hydroxy compounds; alkali metal and alkaline earth metal amides such as lithium amide, sodium amide, calcium amide, lithium dimethylamide; trimethylamine, triethylamine, tri-n-butylamine, Triphenylamine, diethylmethylamine, N, N
-Diethylaniline, N-methylpiperidine, N, N'-
Diethylpiperazine, N-methylmorpholine, triethylenediamine, hexamethylenetetramine, N, N, N, N '
-Tetramethylethylenediamine, dicyclohexylethylamine, 1,2,2,6,6-pentamethylpiperidine, pyridine, quinoline, phenanthroline, indole, N
-Methylimidazole, 1,8-diazabicyclo- [5,4,
0] -undecene-7 (DBU), 1,5-diazobicyclo-
Tertiary amines such as [4,3,0] -nonene-5 (DBU) and cyclic nitrogen-containing compounds (however, those having no NH group); crown ethers, azacrown ethers, thiacrowns Crown compounds such as ether and azacrown, and complexes of these crown compounds with alkali metal or alkaline earth metal ions are used.

Further, two or more of these basic groups may be present in the molecule, and they may form a part of a polymer such as an anion exchange resin having a quaternary ammonium hydroxide group. May be. Further, these basic substances or groups having basicity may be supported on a solid or chemically bound. These bases may be used alone or in combination of two or more.

The phenols having no substituent at the para position used in the present invention have the general formula (R ¹ , R ² , R ³ , and R ⁴ are as described above).

Examples of such phenols include phenol, cresol, dimethylphenol, trimethylphenol, tetramethylphenol, ethylphenol,
Diethylphenol, triethylphenol, ethylcresol, methoxyphenol, ethoxyphenol,
Dimethoxyphenol, methoxycresol, fluorophenol, difluorophenol, fluorocresol, nitrophenol, dinitrophenol, nitrocresol, cyanophenol, dicyanophenol, cyanocresol, fluoronitrophenol, fluoronitrocresol, fluorocyanophenol, nitrocyanophenol, cyclohexyl Used are phenol, cyclohexylcresol, cyclohexylfluorophenol, etc. (However, in the case of substituted phenol,
Excluding those in which the para position is substituted with respect to the hydroxyl group).

Among such phenols, 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 as a metal atom contained therein usually in an amount of 0.001 to 1,000 times mol based on parabromofluorobenzene.

The base is preferably used in an amount necessary to neutralize the hydrogen bromide formed, but of course, it may be less or more than this.

When an additive such as a phosphine compound is used, the amount of the metal atom in the carbonylation catalyst is usually 0.
It is preferably used in an amount of 01 to 1,000 times the molar amount.

It is preferable to use at least an equivalent amount of phenols with respect to para-bromofluorobenzene. It is also possible to use a solvent by using an excess amount of phenols.

Thus, the esterification reaction can be carried out without using a reaction solvent, 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; aliphatic hydrocarbons such as cyclohexane and methylcyclohexane; aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene. Hydrogen; Nitriles such as acetonitrile and benzonitrile; Sulfolane, Methylsulfolane,
Sulfones such as dimethylsulfolane; ethers such as tetrahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane; ketones such as acetone and methyl ethyl ketone; esters such as ethyl acetate and ethyl benzoate;
Examples thereof include amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone and hexamethylphosphoramide.

Esterification reaction is usually 50 ~ 350 ℃, preferably 100 ~ 30
In the range of 0 ℃, 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 performing such a carbonylation reaction, the fluorine atom of para-bromofluorobenzene is not replaced,
Parafluorobenzoic acid phenyl esters in which only the bromine atom is replaced by an aryloxycarbonyl group are
It was found that a high yield of not less than% and a high selectivity can be obtained.

Further, the salt of hydrogen bromide and a base 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. Then, from this salt of hydrogen bromide and a base, as a hydrogen bromide and a base by a known method, or as bromine and a base, respectively, they can be easily recovered, respectively. It can be recycled and reused in the esterification step.

In the rearrangement reaction step of the present invention, the rearrangement reaction of the parafluorobenzoic acid phenyl esters obtained in the etherification step is carried out in the presence of an acid catalyst to obtain the desired 4- (parafluorobenzoyl) phenols. To get

As the acid catalyst that can be used in the rearrangement reaction step, it is possible to use an acid catalyst that contains substantially no water, but in order to maximize yield and selectivity, a Lewis acid and / or a strong acid can be used. It is preferable to use a protic acid.

Such Lewis acids include boron, aluminum,
Halides of Group III elements such as gallium, indium, thallium, scandium, yttrium; silicon, germanium, tin, titanium, zirconium, etc.
Group IV element halides; antimony, bismuth,
Halides of Group V elements such as vanadium, niobium, and tantalum, and metal halides such as iron, copper, and zinc are used.

The strongly acidic protonic acids include 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 and chlorosulfone. Acids, halogenated sulfonic acids such as trifluoromethanesulfonic acid, trichloromethanesulfonic acid, perfluoroethanesulfonic acid, and halogenated alkanesulfonic acids are used.
In addition, a high-silica-containing zeolite that is a solid acid, a strongly acidic cation exchange resin, or an acid called a solid superacid can also be used in the rearrangement reaction of the present invention.

A solid super strong acid is a solid strong acid having an acid strength stronger than 100% sulfuric acid, and examples thereof include Sb.
_{F 5, TaF 5, BF 3} , CF 3 SO 3 H, SbF 5 -HF, SbF 5 -FSO 3 H or mixtures thereof and the like _{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-
Examples thereof include zeolite, Al ₂ O ₃ , SiO ₂ , grafitite, cation exchange resin, activated carbon, supported fluorinated grafitite, and fluorinated sulfonic acid resin. Here, the fluorinated sulfonic acid resin is -CF ₂ SO ₃
It is a resin having an H group and / or 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, the parafluorobenzoic acid phenyl esters are hydrolyzed, and the yield of the desired 4- (parafluorobenzoyl) phenols is decreased. 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 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, it is possible to obtain 4
-(Parafluorobenzoyl) phenols are obtained.

(Effect of the Invention) It was revealed that the method of the present invention can produce 4- (parafluorobenzoyl) phenols from fluorinated benzene, carbon monoxide and phenols in high yield and high selectivity.

(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 Liquid phase bromination reaction using a four-necked flask equipped with a stirrer, a thermometer, a nitrogen inlet extending into the liquid, a cooling pipe and a gas outlet, and a dropping funnel having the inlet extending into the liquid. Was carried out. Fluorinated benzene 40g, iron powder 0.2g in the flask
, While slowly flowing dry nitrogen, the system 5 ~ 10 ℃
Cooled to. Under stirring, 25 g of bromine was gradually added dropwise from the dropping funnel. Bromine was added so that the amount of hydrogen bromide gas generated was almost constant, and the reaction was carried out at 10 to 15 ° C. It took about 30 minutes. Then, as a result of continuing the reaction at 40 ° C. for about 30 minutes, bromine was completely consumed.

By distilling off unreacted fluorinated benzene from the liquid phase, 27.3 g of a brominated fluorobenzene mixture was obtained. The composition of the brominated fluorobenzene mixture was 98.5% para-bromofluorobenzene, 1.0% ortho-bromofluorobenzene and 0.5% meta-fluorobromobenzene. The following esterification step was performed using para-bromofluorobenzene separated from this brominated fluorobenzene mixture by a crystallization operation.

Para-bromofluorobenzene 17.5g, phenol 11.3g,
22.2 g of tri-n-butylamine, 40 mg of palladium chloride,
Add 0.4 g of triphenylphosphine to the autoclave,
After substituting the inside of the autoclave with carbon monoxide, carbon monoxide was injected under pressure of 30 kg / cm ² . After reacting at 200 ° C for 2 hours with stirring, the mixture was cooled, and the reaction mixture was analyzed. As a result, the reaction rate of parabromofluorobenzene was 99%, and the yield of parafluorobenzoic acid phenyl ester was 98%. Obtained in 99%.

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. Then, most of the trifluoromethanesulfonic acid was distilled off under reduced pressure, and the reaction mixture was put into cold water. The white crystals formed were separated and 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 unreacted fluorinated benzene and para-bromofluorobenzene can be recovered and reused in the bromination step and the esterification step, respectively, the present example is based on the reacted fluorinated benzene as 4- (parafluorobenzoyl). ) It shows that phenol was obtained with a yield of 93.6% and a selectivity of 93.6%.

Example 2 About 65% of sodium ions of Y-type zeolite was exchanged with divalent copper ions, and prepared by exchanging copper-Y-type zeolite as a catalyst. The gas phase oxybromination reaction of fluorinated benzene was carried out by introducing hydrogen gas, molecular oxygen, fluorinated benzene, and nitrogen as a diluent.

The feed composition is fluorinated benzene / HBr / O ₂ / N ₂ =
On 2/1/1/3, WHSV based on fluorinated benzene was subjected to reaction at a temperature of 190 to 200 ° C under atmospheric pressure for 10 hr ^-1 , and after reaching a steady state, the reaction product was analyzed and Reaction rate of hydrogen fluoride is 10
At 0%, the reaction rate of fluorinated benzene is 49%, the composition in the brominated fluorobenzene mixture is 93.1% para-bromofluorobenzene, 2.7% ortho-bromofluorobenzene 2.7%, meta-bromofluorobenzene 3.0%, in mol%. It was dibromofluorobenzene 1.2%.

The following esterification reaction was carried out using para-bromofluorobenzene obtained from this brominated fluorobenzene mixture by distillation and crystallization.

Parabromofluorobenzene (17.5 g), 2,6-dimethylphenol (14.6 g), tri-n-butylamine (22.2 g), palladium black (25 mg) and triphenylphosphine (0.4 g) were used. As a result of reacting for 2 hours at ℃, the reaction rate of parafluorobromobenzene is 9
At 8.2%, parafluorobenzoic acid 2,6-dimethylphenyl ester was obtained with a yield of 97.0% and a selectivity of 98.8%.

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, then most of the methanesulfonic acid was distilled off under reduced pressure. did. Then, the reaction mixture was put in cold water, the white crystals that had formed were separated, and dried under reduced pressure. The white crystals were 4- (parafluorobenzoyl) -2,6-dimethylphenol, and the yield was 97.
%, The selectivity was 99%.

Unreacted fluorinated benzene and para-bromofluorobenzene can be respectively recovered and recycled for the bromination step and the esterification step. Therefore, in this example, 4- (parafluorofluorobenzene was used as a reference based on the reacted fluorinated benzene. Benzoyl) -2,6-dimethylphenol yield 89.2%,
It shows that the selectivity was obtained at 91.1%.

Example 3 Using a continuous reaction apparatus as shown in FIG. 1 in the bromination process, a liquid phase bromination reaction with bromine and a gas phase oxybromination reaction with hydrogen bromide produced as a by-product at that time are continuously performed. Carried out.

Liquid phase bromination reactor The first tank (1) is kept at 5 to 10 ° C, the second layer (2) is kept at 20 to 25 ° C, and the third tank (3) is kept at 40 to 45 ° C. For each 40 minutes, fluorinated benzene and bromine were introduced into the first tank (1) in a molar ratio of 3: 1. The catalyst was added such that FeBr ₃ was 0.1 mol% with respect to the fluorobenzene.

The liquid-phase reaction mixture flowing out of the third tank (3) due to overflow was led to a distillation apparatus (4), and fluorinated benzene was recovered from the top of the column and monobromofluorobenzene was recovered from the middle stage of the column, and was collected from the bottom of the column. The brominated fluorobenzene and catalyst were separated.

Part of the fluorinated benzene recovered from the top of the column and hydrogen bromide gas produced in the liquid phase bromination reaction are introduced together with oxygen and nitrogen from the upper part of the gas phase oxybromination reactor (5). The molar ratio is fluorinated benzene / HBr / O ₂ / N ₂ =
It is adjusted to 1.2 / 1 / 0.8 / 3, and the reaction mixture is introduced into the distillation apparatus (6) and separated. The gas phase oxybromination reactor had the same Cu ²⁺ as used in Example 1.
It is packed with ion-exchange Y zeolite and has a reaction temperature of 19
The reaction was carried out at 0-200 ° C and WHSV of 7 hr ^-1 .

The selectivity of monobromofluorobenzene in the brominated fluorobenzene obtained by the liquid phase bromination reaction was 99%, and the para form in the monobromofluorobenzene was 97%, the ortho form was 2%, and the meta form was 1%. Atsuta The selectivity of monobromofluorobenzene in the brominated fluorobenzene obtained by the gas phase oxybromination reaction is 97%, the para body in the monobromofluorobenzene is 94%, and the ortho body 2
%, And the meta form was 4%.

The following esterification step was carried out using para-bromofluorobenzene obtained from this brominated fluorobenzene mixture by distillation and crystallization.

Parafluorobromobenzene 17.5g, phenol 11.3g,
Tri-n-butylamine 22.2 g, nickel acetylacetonate Ni (acac) ₂ 1.2 g, triphenylphosphine 2.6
g was placed in an autoclave, the inside of the autoclave was replaced with carbon monoxide, and then carbon monoxide was injected under pressure of 50 kg / cm ² . After reacting at 210 to 230 ° C. for 2 hours under stirring, the mixture was cooled, and the reaction solution was analyzed. As a result, the reaction rate of parafluorobromobenzene was 95%, and the yield of parafluorobenzoic acid phenyl ester was 88.4%. The selectivity was 93%.

Using parafluorobenzoic acid phenyl ester obtained by vacuum distillation of the esterification reaction mixture,
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 to 10 ° C. for 6 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 analyzing the product, the reaction rate of parafluorobenzoic acid phenyl ester was 67%, and 4- (parafluorobenzoyl) phenol was produced in a yield of 66.3% and a selectivity of 99%. The isomer 2- (parafluorobenzoyl) phenol was only detected at 1%.

Unreacted fluorinated benzene, para-bromofluorobenzene and para-fluorobenzoic acid phenyl ester can be recovered and reused in the bromination step, the esterification step and the rearrangement reaction step, respectively. Based on the fluorinated benzene, 4- (parafluorobenzoyl) phenol yield 87.2%, selectivity 87.2%
It has been obtained in.

The recovery rate of anhydrous hydrogen fluoride was 98%.

Example 4 The following esterification step was carried out using para-bromofluorobenzene obtained by the liquid phase bromination reaction of bromine and fluorobenzene in the same manner as in the bromination reaction step of Example 1. Ivy.

Parafluorobromobenzene 17.5 g, 2,6-dimethylphenol 14.6 g, pyridine 10 g, palladium acetate 60 mg, tris (4-methylphenyl) phosphine 0.3 g were placed in an autoclave, and the reaction was carried out by the same method as in Example 1. , Parafluorobenzoic acid-2,6-dimethylphenyl ester was obtained with a yield of 96% and a selectivity of 98%.

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 stirred. Then, extraction was performed with ethyl acetate, and ethyl acetate was distilled off from the extract to give 4- (parafluorobenzoyl) -2,6-dimethylphenol in a yield of 94%.
Got with. The yield based on the reacted fluorinated benzene was 90.7%.

Example 5 The following esterification step was carried out using the parabromofluorobenzene obtained by the method of Example 3. Parabromofluorobenzene 17.5g, phenol 11.3g, triethylamine 12.2g, 5% P supporting 5w% palladium on carbon
d / C (1.06 g) and triphenylphosphine (0.67 g) were placed in an autoclave, the inside of the autoclave was replaced with carbon monoxide, and then carbon monoxide was injected under a pressure of 50 kg / cm ² . 170 with stirring
After reacting for 2 hours at ℃, cooled, benzene was added to the reaction mixture, Pd / C and hydrobromide of triethylamine were separated, and the liquid components were analyzed. As a result, the yield of phenyl parafluorobenzoate was 99%. , Was generated with a selectivity of 99%.

Benzene was distilled off from the liquid containing the esterification reaction mixture, and then vacuum distillation was performed to obtain 20.6 g of parafluorobenzoic acid phenyl ester.

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, and white crystals that had formed were separated and 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 90%.

Preferred embodiments of the present invention are as follows.

(1) The method according to the claims, wherein the bromination step is carried out by a liquid phase bromination reaction with bromine.

(2) The method according to the claims, wherein the brominating step is carried out by a gas phase oxybromination reaction using molecular oxygen and hydrogen bromide.

(3) The method according to the claims, wherein the bromination step is carried out by using a liquid phase bromination reaction with bromine and a gas phase oxybromination reaction using molecular oxygen and hydrogen bromide in combination.

(4) The method according to the claims, wherein the phenols are phenol or 2,6-dimethylphenol.

(5) The method according to the claims, wherein the carbonylation catalyst is a palladium catalyst or a nickel catalyst.

(6) The method according to the claims, wherein the acid catalyst is a Lewis acid and / or a strongly acidic protic acid.

[Brief description of drawings]

FIG. 1 is a schematic diagram showing an example of a continuous flow reactor in the bromination process of the present invention.

Claims (1)

[Claims] 1. When producing 4- (parafluorobenzoyl) phenols from fluorinated benzene, carbon monoxide and phenols, (a) bromination comprising bromine and / or molecular oxygen and hydrogen bromide. A brominating step of reacting an agent with fluorinated benzene to obtain para-bromofluorobenzene, (b) adding a substituent at carbon monoxide and a para-position to the para-bromofluorobenzene in the presence of a carbonylation catalyst and a base. An esterification step for obtaining parafluorobenzoic acid phenyl esters by reacting with phenols that do not have,
And (c) a 4- (parafluorobenzoyl) phenol, which comprises a rearrangement reaction step of rearranging the parafluorobenzoic acid phenyl esters into 4- (parafluorobenzoyl) phenols in the presence of an acid catalyst. Manufacturing method.