JPS62238241A - Production of fluorine-substituted aromatic carboxylic acid aryl ester - Google Patents

Abstract

PURPOSE:To obtain the titled compound important as an intermediate for pharmaceuticals and agricultural chemicals, in high yield and selectivity, by reacting a fluorine-substituted aromatic halide with CO and an alkali metal salt of an aromatic hydroxy compound in the presence of Pd and/or Ni catalyst. CONSTITUTION:The objective compound can be produced by reacting (A) a fluorine-substituted aromatic halide compound (e.g. p-fluorobromobenzene) wherein both of fluorine atom and halogen atom other than fluorine atom are directly bonded to the aromatic ring with (B) CO and (C) an alkali metal salt of an aromatic hydroxy compound (e.g. phenol, 2,6-dimethylphenol, etc.) in the presence of Pd catalyst and/or Ni catalyst at 50-350 deg.C, preferably 100-300 deg.C under a pressure of 1-500kg/cm<2>, preferably 5-300kg/cm<2>. USE:Intermediate for monomer of heat-resistant polymer.

Description

DETAILED DESCRIPTION OF THE INVENTION (Fields of Application on Chestnuts) The present invention is directed to the use of unsubstituted fluorinated aromatic fluorinated compounds as monomer intermediates for heat-resistant polymers or as intermediates for agricultural products, pharmaceuticals, etc. The present invention relates to a method for producing an aromatic carboxylic acid aryl ester.

(Conventional technology) 7 pieces! Substituted aromatic carboxylic acid aryl esters are produced by a method in which a fluorine-substituted aromatic carboxylic acid and an aromatic hydroxy compound are reacted with a dehydration condensation agent such as phosphorus oxychloride (Pharmaceutical Journal Vol. 78, p. 546, 1958)
7t is left behind by the reaction of fluorine #L-substituted aromatic carbon-position chloride with an aromatic hydroxy compound, etc.
6 However, the fluorine-substituted aromatic carboxylic acids and fluorine-substituted aromatic carboxylic acid chlorides used as raw materials for these are linear, and the dehydration condensation agent such as phosphorus oxychloride is a must for chemistry IT theory. The disposal of waste leaves is also troublesome and has been difficult to implement industrially.

On the other hand, it is also known that non-fluorinated derivatives of bromobenzene or iodobenzene react with carbon monoxide and phenol in the presence of a palladium catalyst and a base to give benzoic acid phenyl ester gold (JP-A-5
9-2964).

However, regarding the reaction of fluorine-substituted aromatic halides, which are compounds in which fluorine and a compound different from fluorine are both directly bonded to an aromatic ring, with carbon oxides and aromatic hydroxy compounds.

This is not known, and nothing is known about the substituents f) such as fluorine. Therefore, the present inventors continued to investigate and develop a method capable of producing fluorinated aromatic carboxylic acid arylco, sterk + Wb from fluorinated aromatic halogen compounds, and as a result, palladium or A fluorine-substituted aromatic halide in which both fluorine and a halogen different from fluorine are directly bonded to an aromatic ring in the presence of an anal medium system consisting of a palladium compound and a phosphine compound and a base, carbon monoxide, and an aromatic hydroxy compound. and anti-i5 by 8
The objective was to obtain fluorine-substituted aromatic carboxylic acid briyl ester BSM in high yield and high selectivity, and a patent application was previously filed for this invention (Japanese Patent Application No. 26596/1982).

(Means and Effects of the Invention) The present inventors have further investigated this reaction and found that by using one alkaline earth metal salt of an aromatic didrooxy compound as a reagent, two separate It has been found that the desired fluorine-substituted aromatic carboxylic acid aryl ester can be obtained in high yield and high selectivity without using a base and an aromatic hydroxy compound as anti-16 reagents.

That is, the present invention provides an aromatic halide in which fluorine and a fluorine different from fluorine are both directly bonded to an aromatic ring and exchange fluorine + in the presence of a palladium catalyst and a nickel catalyst. This is a method for producing a fluorine-substituted aromatic carboxylic acid aryl ester, which is characterized by reacting with carbon oxide and an alkali metal salt of an aromatic hydroxy compound.

The method of the present invention has a different power than previously filed.

A feature of this method is that no aromatic hydroxy compound is present in the carbonylation reaction system.

The palladium catalyst used in the present invention includes:

There is no particular restriction as long as it contains the palladium element as a component, and palladium may be in a metallic state or may be a component that forms a whole compound.

In addition, this palladium component is, for example, activated carbon, graphite, silica, alumina, silica-alumina, silica-alumina, etc.
Titania, titania, zirconia.

When supported on carriers such as barium sulfate, calcium carbonate, asbestos, bentonite, diatomaceous polymers, ion-containing resins, zeolites, molecular sieves, silica magnesium, and magnesia, even palladium in a 0-total state can be obtained. After supporting palladium metal, palladium black, or a compound containing palladium ions on a carrier such as the above, reduction treatment is performed with hydrogen, formaldehyde, hydrazine, etc. to produce IC products, alloys containing palladium, or intermetallic compounds containing palladium. is used. Examples of alloys or intermetallic compounds include selenium, tellurium, and sulfur.

antimony, bismuth, steel, silver, gold, zinc, tin.

Examples include those containing vanadium, iron, cobalt, nickel, mercury, lead, thallium, chromium, molybdenum, and tungsten. Of course, these alloys or intermetallic compounds may be supported on the above-mentioned support.

On the other hand, as a compound containing 6-bafdium gold, PdC4゜P
dBr, , Pdl! , Pd(NO,), , P
sim salts such as dSO4; Pd (OCOCH,),
, organic acids such as radium oxalate km M ;
Pd(CN)1; PdO; Pds; M, [P
[IPd(NH,). ]For.

Ammine complexes of palladium such as (: Pd (en)!)
), , PdCum (P too),.

Pd(CO)(PRm)s, Pd(PPb,),
, PdC4(R)(PPhs)x -Pd(CtL
) (pph, ), , PdCC5Hs)t and other complex compounds or organic parallel compounds (R represents an organic group 2)
; pd(aeae), a complex compound jA coordinated with a chelate ligand such as (aeac represents acetylacetone gold)
etc. are used.

95. What is the nickel catalyst used in the present invention?

There is no particular restriction as long as it contains nickel as a component, and nickel may be in a metallic state or may be a component that undergoes chemical conversion. Furthermore, the nickel salts may be supported on the carrier as described above.

On the other hand, nickel? The compound containing 1.1 and NiC.

NiBr1 , Ni 11 fx and other IJ nickel halides; N15O,.

Nr (NOs)t, N凰COB,,Ni
(SCN)2, Ni (C106)z fi: Nickel salt of any inorganic acid; Ni (OCOCH3), ,
Nickel salts of organic acids such as nickel oxalate; fermented nickel; nickel hydroxide; nickel sulfide; In the complete representation, X is nido oi, cyano group, halogen.

NO8,±SO4') p (N1(N
Hs)4)X2.

CN1(Y)s)Xt, [N1(Y)t)Xt,
ammine complexes of nickel such as (Ni(py)a:] N1(Co); Friend complex compounds coordinated with chelate ligands such as N1(aeac) (represents acacld acetylacetone); N1(Co)4. N1(Co);
)1(PR,18N1(Co)1(PRI)1°N1X
t(PR,),, N1X(PR,),, N
1(PR,),, N1XPh(PR,),.

N1 (RNC)1. [N1X(ally&＞”11
Ni(CsHs)t, Ni(Co)t(CsHs)m.

N1X (CsHs) (PR3), N1 (COD),
Column compounds such as N1 (COD) (PR, )↓1 or catalytic nickel compounds (R represents an organic group such as alkyl or aryl, COD represents cycloofmediene)
etc. are used. Note that the compounds made of these compounds may be used in the form of water-based compounds.

These haladium catalysts and nickel catalysts may be used in an amount of 1 or more gold.

Furthermore, the purpose is to improve the yield and selectivity, increase the reaction rate, and lower the reaction temperature.

The entire pond compound can also be added. Examples of such compounds include phosphine compounds represented by general formula (I).

P R'+ R'tR's (1) (wherein,'
B + 'E'pr r R'3 represents all hydrogen, halogen, aliphatic group, alicyclic group, aromatic group, and araliphatic group.

These may be the same thing, or they may be elements that form a cylindrical groove. ) Of course, a polyphosphine compound containing two or more phosphorus molecules in one molecule may also be used.

Examples of such phosphine compounds include 5.

n-octylphosphine, di-n-butylphosphine,
Alicyclic phosphines such as diethylbutylphosphine, tri-n-j lobylphosphine, tri-n-butylphosphine, alkylphosphine, dialkylphosphine, and trialkylphosphine; dichlorohexylphosphine, dicyclohexylphosphine; benzylphosphine;

dibenzylphosphine, dibenzylethylphosphine,
Aroaliphatic phosphines such as tribenzylphosphine; mixed phosphines such as methylphenylphosphine, ethylphenylphosphine, dimethylphenylphosphine, methyldiphenylphosphine, methylbenzylphenylphosphine, ethyldiphenylphosphine, dicyclohexylphene; and rufospine; phenyl Phosphine, tosylphosphine. Arylphosphine, diarylphosphine and triarylphosphine such as diphenylphosphine, triphenylphosphine, tristrylphosphine, diphenyltolylphosphine; bis(
Diphenylphosphino) meta/l Bis(diphenylphosphino)ethane, orthophenylenebis(diethylphosphine, 12,2'-bis(diphenylphosphine)
-t, t'-Binaphthyl and other diphosphines are used.

Such phosphine compounds may be monofamily or S
You may use a mixture of two or more. Among such phosphine compounds, triarylphosphines are particularly preferably used. Among triarylphosphines, triphenylphosphine is particularly preferably used because of its ease of availability.

The fluorine-substituted aromatic halide used as a raw material in the present invention may be any aromatic compound in which both fluorine and a halogen different from fluorine as substituents are directly bonded to an aromatic ring. Examples of such fluorine-substituted aromatic halides include benzene, toluene, xylene, ethylbenzene, diethylbenzene, propylbenzene, cumene, and trimethylbenzene.

Compounds vIJ in which hydrogen in the aromatic ring of an aromatic hydrocarbon such as tetramethylbenzene, naphthalene, anthracene, etc. is substituted with one or more fluorine and 11 [1 or more other) rogens; pyridine, quinoline, bipyridine, etc. The hydrogen in the aromatic ring of the heteroaromatic compound is 1111! Compounds with the above fluorine and one or more other 7-rogens converted to tt: formula [where A is a simple bond, '4 is -o+, -8+
.

-80,+, -co-, -CHtomi-, -C(R)t
- (4 represents a divalent group such as a lower alkyl group)] Hydrogen in the aromatic ring of an aromatic hydrocarbon is substituted with 11 or more fluorine and one or more other fluorine, resulting in a cultural compound. Examples include the following. A particularly preferred halogen is bromine or iodine.

1t, other substituents in these fluorine-substituted aromatic halides that do not adversely affect R# in one reaction.

For example, it may be substituted with a substituent such as a lower alkyl group, a lower alkoxy group, an ester group, a nitro group, or a cyan group.

Among such fluorine If-substituted aromatic halides, benzene derivatives are particularly preferably used, such as fluorochlorobenzene (all isomers) and fluorobromobenzene (all isomers).

Monofluoromonohalogenated benzenes such as fluoroiodobenzene (each isomer); fluorodichlorobenzene (each isomer), S fluorodibromobenzene (=21 isomer), fluoroshortbenzene (each isomer), mono Monofluoropolyhalogenated benzenes such as fluorotribromobenzene (octamers), monofluorotriiodobenzene (isomers), and monofluorotribromobenzene (tetramers) difluorochlorobenzene (isomers) , difluorobromobenzene (each isomer).

Polyfluoromonohalogenated benzenes such as difluoroiodobenzene (each isomer), trifluorobromobenzene (each isomer), and pentafluorobromobenzene (each isomer); difluorodichlorobenzene (each isomer), difluorobromobenzene Examples include polyfluoroborino and rogonated benzenes such as bromobenzene (each isomer), difluoroshortbenzene (each isomer), difluorotribromobenzene (each isomer), and trifluorobromobenzene (each isomer). It will be done.

Among these benzene derivatives, parafluorobromobenzene and parafluoroiodobenzene are particularly preferably used.

The alkali metal salt of an aromatic hydroxy compound used in the present invention is a compound in which the hydrogen atom of the hydroxyl group of the aromatic hydroxy compound is substituted with an alkali metal atom. Such a compound can be obtained by any method, but for example, it can be easily obtained from an alkali (a basic substance containing a group 6 atom) and an aromatic hydroxy compound. Examples of the basic substances include (6) alkali metal oxides, alkali metal oxides, alkaline carbonates, alkali metal bicarbonates, and the like.

Among others, aromatic hydroxy compounds and lithium hydroxide,
The easiest method is to use alkali-related hydroxides such as thorium hydroxide, potassium hydroxide, rhodium hydroxide, and water (hycesium).

H as such an aromatic hydroxy compound.

Any compound having a hydroxyl group bonded directly to an aromatic group may be used, such as phenol; cresol (all isomers), xylenol (all isomers), trimethylphenol ( Each alkylphenol such as tetramethylphenol (each isomer), ethylphenol (each isomer), propyl 7jC/-l (each isomer); anisole (each isomer), = each cypress alkoxyphenol such as t-diphenol (each isomer); formula (however, 6A is as in Ai, the aromatic ring is a lower alkyl group, aN alkoxy group, ester group, di-1-ro group, cyano group) Keyaki-substituted phenols (which may be substituted with substituents such as groups); naphthol (each isomer) and various substituted naphthols; Hydroxyquinoline (each isomer) natonoheteroaromatic hydroxyl compound; aromatic dihydropal compounds such as hydroquinone, resorcinol, catechol, su7toquinone, anthraquinone, and their alkyl-substituted dihydroxy compounds; is as described above, and the aromatic JA4 may be substituted with a substituent such as a lower alkyl a, a ta alkoxy group, an ester group, a diF/ro group, a cyan group, etc.) I can open something like that.

Particularly preferred alkali metal salts of aromatic hydroxy compounds are alkali metal salts of phenol and 2,6-dimethylphenol, and examples of the alkali metal salts include 1. Particularly preferred are sodium and potassium.

In the case of the reaction gold of the present invention, an alkali metal salt of banfluorohalogenobenzentophenol, for example, the reaction is expressed by the following linear reaction formula.

(X represents C6, Br, Ii, and 1M represents an alkali metal atom.) As described above, one of the features of the method of the present invention is that only halogens different from fluorine can be substituted with 7-aryloxycarbonyl groups; By leaving it on without swelling. Does fluorine have an adverse effect on this esterification reaction?S
In fact, it has been found that in some cases, it has a positive effect on yield, selectivity, and reaction rate.

In carrying out the present invention, a palladium catalyst of 1.7?

/ and nickel catalysts, as these metal atoms,
For fluorine rt-substituted aromatic halides.

It is usually used in an amount of 0.0001 to 1,000 times the mole.

Alkali metal salts of aromatic hydroxy compounds.

Although it is not necessary to use a particularly limited range for fluorine-substituted aromatic halides, it is preferably 0.5 to 2.0.
equivalent, more preferably in the range of 0.8=1.5 equivalent.

The carbon monoxide may be pure carbon monoxide, or it may be diluted with other gases that do not adversely affect the reaction, such as nitrogen, 5 argon, helium, or carbon-grade hydrocarbons. Q, 1,300 yu/d, preferably 1-2
It is used in the range of 00 Yu/d.

Although the method of the present invention can be carried out without using a reaction bath medium. It is a convenient method to use a bath medium that does not adversely affect metals in the reaction. Such bath media include, for example, 1lir rib hydrocarbons such as hexane, heptane, octane, decane, and pentadecane; alicyclic hydrocarbons such as dichlorohexane and methylcyclohexane; benzene, toluene, xylene, mesitylene, etc. Aromatic carbon hydrocarbons such as; nitriles such as a7tonitrile 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; ethyl acetate.

Esters such as ethyl benzoate; N,N-dimethylformamide, N,N-dimethylacetamide.

Examples include amides such as N-methylpyrrolidone and hexamethylphosphoramide.

The reaction of the present invention is carried out at 1 usually 50 to 350C, preferably 10
In the range of 0 to 500C, the reaction pressure is usually 1 to 1.
500kg/7. Preferably 5 to 300 kg/(,7
It is carried out within the range of d.

The time required for one incubation and six hours varies depending on the catalyst system used, the type I of the raw H7, and other reaction conditions such as temperature and pressure, but it is usually several minutes to several tens of hours.

The anti-16 method, 5-dose method, continuous method, and combinations thereof may all be adopted.

(Effects of the Invention) By the method of the present invention, a fluorine-It-substituted carboxylic acid aryl ester is produced from a fluorine-It-substituted aromatic halide, carbon monoxide, and an alkali salt of an aromatic hydroxy compound in high yield and high selectivity. Natsuko is happy to be able to manufacture it.

This fluorine-substituted aromatic carbonate aryl ester is
It is not only used as an intermediate for agricultural chemicals and medicines, but also
Some of its compounds, such as rose fluorobenzoic acid phenyl ester, rose fluorobenzoic acid '111-2+ 6
-7 Methyl phenyl ester and the like are important as precursors of 7-mers for aromatic polyether ketones that are heat resistant and hot water resistant.

That is, these esters are rearranged by rearrangement reaction '6.

4-(barafluorobenzoyl)phenol and HI-(barafluorobenzoyl)-2゜6-dimethylphenol Vcd can be easily substituted, respectively, and these phenol conductors can be substituted with 5 on their own or with 1 on the chassis. As a component, 1) h et al. can be used as a component of aromatic polyetherketone.

(Example) The following is an actual hm example of the present invention? I'll explain further.

The present invention is not limited to these examples.

Example 1 After fertilizing anti-F6 in a total aqueous solution of sodium hydroxide equivalent to phenol, 0 mmot of fluorofluorobromobenzene, 0 mmot of nickel acetylacetone (aeac
)! 2.5 mmot, ) Luxun S 5 ff was placed in an autoclave, and the interior of the autoclave was replaced with aroused carbon. Press inject carbon monoxide to 5Okl/cm. After reacting at 250C for 1 hour with stirring, it was cooled to 5
As a result of analysis of the six liquids, halafluoroammonium, t-fragrance phenyl ester was obtained with a yield of 82% and a selectivity of 87%, with a reaction rate of q94% for halafluorobromobenzene.

Example 2 Using rose fluoroiodobenzene 50 mmot'4-in place of rose fluorobromobenzene, 2 at 200C
The reaction rate of rose fluoroiodobenzene was 95%.
So, the yield of rosefluorobenzoic acid phenyl ester was 9!
1%, obtained with transparent selection*98ch.7.

Example 3 Nickel chloride (Ni) instead of nickel acetylacetone
/! , 2.5 mmol and triphenylphosphine 5 mr11otf, except for incubation at 220C.

As a result of carrying out the reaction in the same manner as in Example 2, rosefluoroben b dil phenyl ester was obtained with a yield of 86% and a selectivity of 86%.

Fruit Mukuri 4 Thorium-2,6- in place of sodium phenoxide
The entire reaction was carried out in the same manner as in Example 2 except that 60 mmol'jl of dimegol phenoxide was used. As a result, rosefluorobenzoic acid 2,6-tmethylphenyl ester was obtained in a yield of 94% and an is selectivity of 97. Obtained in a whisper.

In addition, sodium-2,6-dimethylphenoxide is
The product obtained by reacting 2.6-trimethylphenol and an equivalent amount of sodium hydroxide in an aqueous solution, followed by dehydration and drying, was used.

Implementation $1 J 5 Parafluorobromobenzene 50 mmol, Sodium phenoxide 50 mmot, Halacium chloride 0.5 mmot, To'J phenylphosphine 1 r
The mixture was placed in an autoclave, and the inside of the autoclave was replaced with carbon monoxide, and then carbon monoxide gold was press-fitted at 50 yu/d. Under stirring 1c220G
After stirring for 2 hours, the reaction liquid was cooled and the reaction liquid gold was analyzed.
%"l?, halafluorobenzoic acid fugonyl ester, yield 97%, selectivity 99%.

Example 6 4-fluoro-- instead of parafluorobrombenzene
Il Jd for 4'-iodobiphenyl 50 xxl f
The outside is the result of performing all reactions in the same manner as the actual mfIj5.

4-(barafluorophenyl) Benzoic acid phenyl ester yield? 7fi with a selectivity of 98%.

Example 7 2-fluoro-4 instead of parafluorobromobenzene
The reaction was carried out in the same manner as in Example 5, except that chlorotoluene was used in a 50 mmot tray and 70 ky/c++t of carbon monoxide was used. Benzoic acid phenyl ester was obtained with a yield of 60% and a selectivity of 75%.

Example 8 Sodium-2,6- instead of sodium phenoxide
Except for using dimethyl phenoxide 60 mmotf.
The entire reaction was carried out in the same manner as in Example 5.
7 A/olobenzoic acid 2,6-methylphenyl ester was obtained in a yield of 97 and 1 selection, 99.

Example 9 As a result of conducting 16 incubations in the same manner as in Example 2 using sodium-1-naphthoxide 0 mmotf instead of sodium phenoxide, rosefluorobenzoic acid naphthyl ester was obtained with a yield of 96 mm and a selectivity of 98 mm. I was beaten.

Example 10 2-fluoro-6 instead of parafluorobromobenzene
-The reaction was carried out in the same manner as in Example 2 except that 50 ir+mot'g of iodonaphthalene was used.9 results.

2-Fluoronaphthalene-6-carboxylic acid phenyl ester was obtained with a yield of 96% and a selectivity of 97%.

Example 11 Potassium phenoxide 0 mmot obtained by mixing, dehydrating, and drying an equivalent amount of potassium hydroxide to phenol in an aqueous solution instead of sodium phenoxide.

The reaction was carried out in the same manner as in Example 2, except that phenyl fluorobenzoate was obtained in a yield of 95% and a selectivity of 913%.

Example 12 Reaction 16 was carried out in the same manner as in Example 5, except that 0 mmot'ft of potassium phenoxide was used instead of sodium phenoxide. As a result, rosefluorobenzoic acid phenyl ester was obtained in a yield of 97% and a selectivity of 98%. Obtained with.

Example 15 2 instead of sodium-2,6-dimethylphenoxide
．． Nine-potassium-2.6-trimethylphenol was mixed with an equivalent amount of potassium hydroxide in a gold water bath, dehydrated, and dried.
The reaction was carried out in the same manner as in Example 4 except for using 60 mrnol of 6-dimethylphenoxide. As a result, rosefluorobenzoic acid 2,6-trimethylphenyl ester was obtained, [9596, selectivity Example 14 Lithium phenoxide obtained by mixing, dehydrating, and drying phenol and lithium hydroxide in an aqueous solution instead of sodium phenoxide 0 mmot 'z As a result of carrying out reaction [6] in the same manner as in Example 2, phenyl fluorobenzoate was obtained with a yield of 95% and a selectivity of 97%.

Claims (7)

[Claims] (1) In the presence of a palladium catalyst or/and a nickel catalyst, a fluorine-substituted aromatic halide in which fluorine and a halogen different from fluorine are both directly bonded to the aromatic ring,
A method for producing a fluorine-substituted aromatic carboxylic acid aryl ester, which comprises reacting with carbon monoxide and an alkali metal salt of an aromatic hydroxy compound. (2) The method according to claim 1, wherein the halogen different from fluorine is bromine or iodine. (3) The method according to claim 1, wherein the fluorine-substituted aromatic halide in which fluorine and a halogen different from fluorine are both directly bonded to an aromatic ring is a benzene derivative having fluorine and a halogen different from fluorine as substituents. . (4) The method according to claim 3, wherein the benzene derivative is parafluorobromobenzene or parafluoroiodobenzene. (5) The method according to any one of claims 1 to 4, wherein the aromatic hydroxy compound is an aromatic monohydroxy compound. (6) The method according to claim 5, wherein the aromatic hydroxy compound is phenol and/or 2,6-dimethylphenol. (7) The method according to any one of claims 1 to 6, in which a phosphine compound is used as an additional promoter.