WO2004067490A2

WO2004067490A2 - Use of indium benzoates as acylation catalysts

Info

Publication number: WO2004067490A2
Application number: PCT/FR2004/000129
Authority: WO
Inventors: Christophe Duquenne; Jean-Philippe Gillet; Jacques Kervennal; Christophe Ruppin; Michel Vaultier
Original assignee: Arkema
Priority date: 2003-01-22
Filing date: 2004-01-22
Publication date: 2004-08-12
Also published as: WO2004067490A3; FR2850104A1

Abstract

The invention relates to the use of indium benzoates in processes involving the acylation of aromatic compounds, said indium benzoates having formula I, wherein: X represents a chlorine atom or a bromine atom, R represents a linear or branched alkyl radical having between 1 and 10 carbon atoms, a fluorine, chlorine or bromine atom, y is equal to 0, 1, 2, 3, 4 or 5 and x is the integer 1, 2 or 3.

Description

I

USE OF INDIUM BENZOATES AS CATALYSTS OF ACYLATION REACTIONS OF AROMATIC COfAPOSES

TECHNICAL FIELD The present invention relates to the use of indium benzoates in acylation reactions of aromatic compounds as catalysts of the Friedel and Craf ts type.

In the present invention, the term “aromatic compound” should be understood to mean any activated or non-activated aromatic compound, ie an aromatic compound in which a hydrogen atom directly linked to the aromatic nucleus is replaced either by an activating substituent or by a substituent deactivating the aromatic nucleus. An unactivated or deactivated aromatic compound can be, for example, benzene or a benzene comprising one or more substituents deactivating the benzene nucleus, such as, for example, chlorine in chlorobenzene. An activated aromatic compound can for example be a benzene comprising one or more activating substituents such as CH ₃ O-, CH ₃ -. By “aromatic”, we currently designate the classic notion of aromaticity as defined in the literature, in particular by Jerry March “Advanced Organic Chemistry” - 2 ^nd edition - Me βraw-Hill, Inc. 1977, pp 41 et seq. PRIOR ART

In general, the methods of acylation of aromatic compounds commonly used are homogeneous liquid phase methods which consist in reacting an aromatic compound and an acylating agent in the presence of a soluble catalyst which is generally chloride d 'aluminum. However, the use of aluminum chloride has many disadvantages. It is necessary to use a large amount of aluminum chloride, an amount at least equal to stoechio etrie, as a result of the co plexation of the aromatic ketone formed by said aluminum chloride. AlCI ₃ cannot therefore be considered as a catalyst. Also, the use of large amounts of A \ C \ ₃ complicates the process.

Indeed, at the end of the reaction, it is necessary to destroy the complex formed and therefore to recover the aromatic ketone formed, to carry out a generally basic hydrolysis.

This involves the addition of water to the reaction medium, which results in the formation of polyoxo and / or polyhydroxo aluminum complexes which are difficult to separate. This leads to long and costly treatments of the hydrolysis reaction medium, treatments which consist in extracting the phase organic, separation of the aqueous and organic phases, or even drying of the latter.

Industrially, the separation of the aluminum chloride is a long and costly operation which generates ef f luent aqueous difficult valoπ ^'sands. In addition, AICI ₃ cannot be recycled as such due to its hydrolysis.

Add that aluminum chloride is a corrosive and irritant product, unstable in the open air.

To avoid the drawbacks linked to the use of aluminum chloride in stoichiometric quantity, Michel Desbois et Coll. in FR 2,534,905, propose to use as catalyst acylation reactions of non-activated or deactivated benzenic compounds such as benzene or chlorobenzene, a Lewis acid in a molar amount of less than 10% relative to the agent acylation, operating at a temperature above the boiling point of the reagent having the lowest boiling point. In general, these authors operate to obtain said reaction temperature with a molar ratio of the reagent having the highest boiling point to the reagent having the lowest boiling point greater than 1 and, in that, in addition, the pressure is greater than 1 bar.

The Lewis acid used is an halide of iron, zinc, aluminum, tin, antimony, titanium or gallium. In particular the Lewis acid is FeCI ₃ , ZnCI ₂ , AlCI ₃ , SnCI ₄ , SbCI ₅ , TiCI ₃ , TiCI or βaCl ₃ . Preferably, the Lewis acid is FeCl ₃ .

This way of operating has the advantage of using smaller amounts of catalyst. Thus, for example, 4-chlorobenzophenone is obtained with a yield of crystallized product of 51% by heating for 4 hours at 200 ° C. a mixture of chlorobenzene and benzoyl chloride used according to a chlorobenzene / benzoyl chloride molar ratio equal to 5 in the presence of FeCl ₃ used in a molar amount equal to 8% relative to the benzoyl chloride. However, the fact remains that in order to isolate the aromatic ketone, it is necessary to carry out hydrolysis of the reaction medium. Consequently, this alternative solution is not fully satisfactory since there are partly the drawbacks mentioned above. In addition, it only applies to the acylation of compounds which are not activated or deactivated. STATEMENT OF THE INVENTION

The problem which arises is therefore to find a catalyst which can overcome the above-mentioned drawbacks, that is to say in particular be used in small quantities and make it possible to avoid the hydrolysis treatment of the reaction medium. The Applicant has found a catalyst which meets the abovementioned requirements and which, used in a process for the acylation of deactivated or non-activated aromatic compounds, made it possible to overcome the drawbacks mentioned above.

A first subject of the invention relates to the use of the compounds of formula D

wherein X represents a chlorine atom or a bromine atom, R represents an alkyl radical, linear or branched, having a number of carbon atoms ranging from 1 to 10; a fluorine, chlorine, or bromine atom; y is 0, 1, 2, 3, 4 or 5; x is an integer equal to 1, 2 or 3, in a process for acylating an aromatic compound which consists in reacting said aromatic compound with an acylating agent in the presence of said compound of formula

(I). The subject of the invention is therefore also a process for the acylation of benzene, aromatic hydrocarbons with condensed rings, optionally substituted, such as naphthalene or an aromatic compound of formula (II):

in which R ² represents an alkyl radical, linear or branched, having a number of carbon atoms ranging from 1 to 10 an alkoxy radical R ³ O- in which R ³ represents an alkyl radical, linear or branched having a number of carbon atoms ranging from 1 to 10; a radical R ³ C (O) O-; a halogen atom; a perhaloalkyl radical having a number of carbon atoms ranging from 1 to 3; a phenyl radical optionally substituted by 1 or more halogen atoms; a nitro radical; a cyano radical, an R ³ OC (O) - radical; n is 1, 2 or 3; which consists in reacting said aromatic compound (II) with an acylating agent of formula of formula: R ⁴ - C (O) X, in which R ⁴ represents a phenyl radical optionally substituted by one or more atom (s) of chlorine, bromine or fluorine, by a linear or branched alkyl radical having a number of carbon atoms ranging from 1 to 10; X represents a chlorine or bromine atom or a residue R ⁴ C (O) O-; in the presence of a catalyst according to reaction (1) '.

II III IV

and recovering the ketone (IV) formed, said process being characterized in that the acylation reaction is carried out in the presence of an effective amount of indium benzoate (I) as catalyst; and that, the product (IV) isolated, the catalyst is optionally reused for one or more subsequent acylation reactions. By way of illustration of indium benzoates which can be used according to the present invention, mention will be made of indium dichlorobenzoate, indium tribenzoate and indium dichloro (2-fluorobenzoate). Preferably, indium dichlorobenzoate will be used. According to the present invention, indium benzoate is used in molar amounts relative to the acylating agent, ranging from 0.01% to 10% and preferably ranging from 0.1% to 5%.

The molar ratio of aromatic compound (II) / acylating agent (III) is at most equal to 2.5 and, preferably between 1.5 and 2. According to the present invention, the reaction temperature is the reflux temperature of the reaction medium.

It is preferably carried out at atmospheric pressure but higher pressures may also be suitable. The acylation reaction is preferably carried out under a stream of inert gas such as nitrogen or argon and in an anhydrous medium. According to the present invention, a preferred procedure consists in loading the catalyst into a reactor which will be dried and then put under a current of inert gas, in pouring the aromatic compound (II) onto the catalyst then in stirring the reaction medium which is gradually brought to reflux and slowly add the acylating agent (III) while maintaining effective agitation. When the addition of the acylating agent is complete, the reaction is continued, until the latter is completely converted, still at reflux of the reaction medium and with stirring.

The progress of the reaction is determined by gas chromatography analysis (GC) of samples taken from the reaction medium. Once the reaction is complete, the acylated product formed (IV) is isolated by means known to a person skilled in the art, such as in particular by distillation, after prior removal of the unprocessed reagent (s). The residue, consisting essentially of the catalyst used, can, according to the present invention, be reused without special treatment for one or more subsequent acylation reactions.

The process according to the present invention applies very particularly to the benzoylation of benzene, naphthalene and aromatic compounds (II) in which R represents either an activating substituent (electron donor group) such as

CH ₃ -, CH ₃ O-; either a deactivating substituent (electron-withdrawing group) such as Cl-,

Br-, F-.

The compounds (II) to which the process of the invention particularly applies are benzene, toluene, fluorobenzene, bromobenzene, chlorobenzene, 1,3-dichlorobenzene, anisole.

The preferred acylating agents (III) are those in which X represents a chlorine atom, or else an R ⁴ C (O) O- residue in which R ⁴ is a phenyl radical optionally substituted by a chlorine or bromine atom or fluorine. By way of illustration of acylating agents which can be used according to the present invention, mention will be made of benzoyl chloride, 3-chlorobenzoyl chloride, 2-fluorobenzoyl chloride, 2-bromobenzoyl chloride, benzoic anhydride.

In accordance with the process of the invention, an aromatic ketone of formula (IV) is obtained:

in which R ² , R ⁴ and n have the meaning given above.

The process according to the present invention has the advantage of acylating activated, non-activated or deactivated aromatic compounds with high yields using small amounts of indium benzoate as catalyst. In addition, this catalyst can optionally be reused as it is one or more times while retaining a high activity.

We operate without third-party solvent, with aromatic compound molar ratios

(II) / weak acylating agent (III), suitable for industrial exploitation.

In addition, the hydrohalic acid formed can be advantageously recovered in the form of marketable aqueous solutions.

Another subject of the invention relates, as new products, to the compounds of formula:

X _3-x In [OC (0) - (Q] _x (D

where X represents a chlorine atom or a bromine atom, R represents an alkyl radical, linear or branched, having a number of carbon atoms ranging from 1 to 10; a atom of fluorine, chlorine, or bromine; y is 0, 1, 2, 3, 4 or 5; x is an integer equal to 1 or 2.

According to the present invention, the compounds in the formula of which are preferred

X represents a chlorine atom, x is equal to 1, y = 0 or 1 and, when y = 1, R represents a fluorine atom. Particular preference is given to indium dichlorobenzoate.

One mode of preparation of the compounds of formula (I) in which x = 1, consists in reacting an excess of acid chloride of formula:

on indium oxide, in a solvent medium, at the boiling point of said solvent. By way of illustration of solvents which can be used according to the invention, mention will be made of benzene, toluene, xylenes

To obtain the compounds of formula (I) in which x = 3 which can be used as catalysts in acylation reactions, an alkylindium IR ^ can be reacted, in which R ^ Hs-, C2H ₅ -, or C ₃ H ₇ - on a benzoic acid of formula:

in a solvent medium, depending on the reaction:

Mention may be made, as solvents which can be used according to the present invention, of chloroalkanes such as methylene chloride.

The following examples illustrate the invention. EXAMPLES:

The compounds obtained are identified by * H and ¹³ C NMR as well as by mass spectrometry coupled with gas chromatography and by elemental analysis.

The proportions of the different isomers, if present, are determined by gas chromatography.

The aromatic compounds used are dried beforehand. EXAMPLE 1:

Obtaining indium dichlorobenzoate CI ₂ InOC (0) ₆ Hs:

2.22 g of indium oxide (8 mmol) are introduced into a reactor. The assembly is dried and then placed under an argon atmosphere. The reactor is then equipped with a refrigerant connected to a bubbler. Anhydrous toluene (15 ml) is added to the medium. The reactor is placed in an oil bath brought to 150 ° C. When the reflux is reached, benzoyl chloride (28.1 g - 0.2 mol) diluted in 20 ml of anhydrous toluene is introduced over 20 mm. Heating is maintained 2 hours after the end of the addition. The toluene and optionally the acylation products are eliminated under reduced pressure. The distillation bottom is washed with 100 ml of anhydrous dichloromethane and filtered. The precipitate is washed again with 40 ml of anhydrous pentane and dried under reduced pressure. 3.31 g of indium dichlorobenzoate are obtained which is in the form of a gray white solid (yield: 67.5% relative to the indium oxide used).

The analytical results are given below:

- molecular mass determined by mass spectrometry: 305.87 g.mol ^"1 (for C ₇ H ₅ O ₂ CI ₂ In),

- elementary analysis (raw formula: ₇ H ₅ θ ₂ l ₂ ln): calculated percentage: C = 27.4; H = 1.64; Cl = 23, 11; In = 37.42 percent found: C = 26.07; H = 2.41; Cl = 22.56; In = 35.94.

EXAMPLE 2:

Obtaining indium dichloro (2-fluorobenzoate): CI ₂ InOC (0) C ₆ H ₄ F.

0.83 g of indium oxide (3 mmol) is introduced into a reactor. The assembly is dried and then placed under an argon atmosphere. The reactor is then equipped with a coolant connected to a bubbler. Anhydrous toluene (15 ml) is added to the medium. The reactor is placed in an oil bath at 150 ° C. When reflux is reached, 2-fluorobenzoyie chloride (9.51 g - 0.06 mol) is introduced over 20 minutes. Heating is maintained 3 hours after the end of the addition. The toluene and optionally the acylation products are eliminated under reduced pressure. The distillation bottom is washed with 100 ml of anhydrous dichloromethane and then filtered. 0.615 g of indium dichloro (2-f lurobenzoate) is obtained, which is in the form of a yellow solid (yield: 31% in isolated product). The analytical results are given below: - molecular mass determined by mass spectrometry:

M ⁺ theoretical: 323.8611 for C ₇ H ₄ O ₂ FCI ₂ In

M ⁺ found: 323.8608.

EXAMPLE 3:

Obtaining indium tribenzoate: [C ₆ H ₅ C (O) O] ₃ In In a 50 ml Schlenk flask equipped with a magnetic bar, is introduced using a 1 ml glass syringe, 0 , 5 ml of triethylindium, diethylether (1.77.

10 ^"3 mol) then 2 ml of anhydrous CH ₂ CI ₂ . 0.725 benzoic acid (5.94.10 × ^{3 −3} mol) dissolved in 10 ml of CH ₂ CI2 is introduced slowly and with stirring onto the triethylindium cooled by means of an ice bath. From the start of the addition, gas evolution is observed.

At the end of the addition of the benzoic acid, the reaction medium is in the form of a clear colorless solution.

It is left overnight at room temperature and with stirring. A white precipitate is obtained. The methylene chloride is slowly removed.

The solid obtained is ground and washed 3 times with 10 ml of anhydrous pentane.

Then the suspension is filtered and the cake is dried. 0.95 g of a white solid are obtained (yield: 94.5% relative to InEt ₃ ,

And ₂ O implemented).

Elementary analysis: (raw formula: ₂ ιHi5θ ₆ In)

Percentage calculated: C = 52.75 and H = 3.16;

Percentage found: C = 51.61 and H = 3.11. EXAMPLE 4:

Use of indium dichlorobenzoate for the preparation of chlorobenzophenones:

0.152 g of indium dichlorobenzoate prepared in Example 1 (0.0005 mol or 2 mol% relative to benzoyl chloride) is introduced into a 20 ml reactor equipped with mechanical stirring, a thermometric sheath and a sampling rod. The assembly is dried and then inert under an argon atmosphere. The reactor is then equipped with a refrigerant connected to a bubbler, the gas line ending in a washing bottle containing distilled water. 5.1 ml of chlorobenzene (0.05 mol) are poured onto the indium dichlorobenzoate via a septum, which is then replaced by a non-isobaric dropping funnel containing 3.63 g of benzoyl chloride (0.025 mol). reactor is placed in an oil bath brought to 160 ° C. When the reflux is reached, the temperature is then close to 130 ° C., benzoyl chloride is introduced over one hour. Stirring is maintained for the whole period Heating of the reaction medium is maintained for 22 hours at this temperature and with stirring After cooling to room temperature, the chlorobenzene is removed under reduced pressure and the chlorobenzophenones are then isolated by distillation under a reduced pressure of 1.333 Pa (0 , 01 torr) at a temperature of 200-210 ° C in a ball oven.

4.17 g of a white solid are obtained, which is a mixture of non-separated isomers containing 94% (by weight) of 4-chlorobenzophenone.

Yield: 77% relative to the benzoyl chloride used. EXAMPLE 5: Use of indium dichlorobenzoate for the benzoylation of toluene with benzoic anhydride as an acylating agent:

0.608 g of indium dichlorobenzoate prepared according to Example 1 (0.002 mol or 5 mol% relative to benzoic anhydride) is introduced into a 100 ml reactor equipped with mechanical stirring, a thermometric sheath and d '' a sampling rod. The assembly is dried and then inert under an argon atmosphere. The reactor is then equipped with a refrigerant connected to a bubbler, the gas line ending in a washing bottle containing distilled water. 8.50 ml of toluene (0.08 mol) are poured onto the indium dichlorobenzoate, which is then replaced by a dropping funnel heated to 60 ° C., containing 9.04 g of benzoic anhydride (0.040 mol). The reactor is placed in an oil bath brought to 160 ° C. When the reflux is reached, the temperature is then close to 110 ° C., the benzoic anhydride is introduced in one hour. The agitation is maintained throughout the reflux period. The temperature of the reaction medium gradually increases to reach 130 ° C. at the end of the addition. The heating of the reaction medium is maintained for 24 hours at this temperature and with stirring.

After cooling to room temperature, the toluene is removed under reduced pressure and the reaction crude is subjected to distillation. After purification of the distillate, 6.75 g of a white solid are obtained, which is a mixture of isomers not separated from methylbenzophenones.

The methylbenzophenone yield is 86% relative to the benzoic anhydride used. EXAMPLE 6 Use of indium tribenzoate for the benzoylation of toluene with benzoyl chloride.

0.0735 g of indium tribenzoate prepared according to Example 3 (0.00013 mol or 0.5 mol% relative to the benzoyl chloride) are introduced into a 20 ml reactor fitted with mechanical stirring, a thermometric sheath and a sampling rod. The assembly is dried and then inert under an argon atmosphere. The reactor is then equipped with a refrigerant connected to a bubbler, the gas line ending in a washing bottle containing distilled water. 4.6 ml of toluene are poured onto the indium tribenzoate via a septum, which is then replaced by a non-isobaric dropping funnel containing 2.9 ml of benzoyl chloride (0.025 mole). The reactor is placed in an oil bath brought to 160 ° C. When the reflux is reached, the temperature is close to 110 ° C., the benzoyl chloride is introduced over one hour, with stirring. The temperature of the reaction medium gradually increases to reach approximately 130 ° C. at the end of the addition. The heating of the reaction medium is maintained for 7 hours at this temperature and with stirring.

Samples of the reaction medium are carried out throughout this period, which are analyzed by mass spectrometry coupled to gas phase chromatography. It is found that after 2 hours, 80% of the benzoyl chloride are transformed and that after 6:30, about 98% of the benzoyl chloride are transformed.

Claims

CLAIMS ONS

1. Process for the acylation of aromatic compounds using one or more of the compounds of formula (I):

wherein X represents a chlorine atom or a bromine atom, R represents an alkyl radical, linear or branched, having a number of carbon atoms ranging from 1 to 10; a fluorine, chlorine or bromine atom; y is 0, 1,

2

3

4 or 5; x is an integer equal to 1, 2 or 3. 2. Process for the acylation of benzene, aromatic hydrocarbons with condensed rings, optionally substituted or of a compound of formula (II):

in which R ² represents an alkyl radical, linear or branched, having a number of carbon atoms ranging from 1 to 10 an alkoxy radical R ³ O- in which R ³ represents an alkyl radical, linear or branched having a number of carbon atoms ranging from 1 to 10; a radical R ³ C (O) O-; a halogen atom; a perhaloalkyl radical having a number of carbon atoms ranging from 1 to 3; a phenyl radical optionally substituted by 1 or more halogen atoms; a nitro radical; a cyano radical; a radical R ³ OC (O) -; n is 1, 2 or 3; which consists in reacting said aromatic compound (II) with an acylating agent of formula (III): R ⁴ - C (O) X, in which R ⁴ represents a phenyl radical optionally substituted by one or more atom (s) chlorine, bromine or fluorine, by a linear or branched alkyl radical having a number of carbon atoms ranging from 1 to 10; X represents a chlorine or bromine atom or a residue R ⁴ C (O) O-; in the presence of a catalyst according to reaction (1):

and recovering the ketone (IV) formed, said process being characterized in that the acylation reaction is carried out in the presence of an effective amount at least one indium benzoate as defined in claim 1 as catalyst. 3. Method according to claim 2, characterized in that the indium benzoate (I) is indium dichlorobenzoate. - 4. Method according to claim 2, characterized in that the indium benzoate is indium tribenzoate.

5. Method according to any one of claims 1 to 4, characterized in that indium benzoate is used in molar amounts relative to the acylating agent (III) ranging from 0.01 to 10 % and preferably ranging from 0.1% to 5%.

6. Method according to any one of claims 1 to 5, characterized in that the molar ratio aromatic compound (II) / acylating agent (III) is at most equal to 2.5 and, preferably, between 1 , 5 and 2.

7. Method according to any one of claims 1 to 6, characterized in that the reaction temperature is the reflux temperature of the reaction medium.

8. Method according to any one of claims 1 to 7, characterized in that the catalyst is loaded into a reactor which is dried and then put under a stream of inert gas, which is poured aromatic compound (II) on the catalyst, the reaction medium is stirred, which is gradually brought to reflux, then the acylating agent (III) is added slowly while maintaining effective stirring, then the addition of the acylating agent completed, the reaction is continued until complete conversion of said acylating agent and the product (IV) is isolated.

9. Method according to any one of claims 1 to 8, characterized in that, the product (IV) isolated, the catalyst is reused at least once in a subsequent acylation reaction.

10. Method according to any one of claims 1 to 9, characterized in that the aromatic compound (II) is benzene.

11. Method according to any one of claims 1 to 10, characterized in that, in the formula of the aromatic compound (II), R ² represents an activating substituent.

12. Method according to claim 11, characterized in that the activating substituent is CH ₃ - or CH ₃ O-.

13. Method according to any one of claims 1 to 9, characterized in that, in the formula of the aromatic compound (II), R ² represents a deactivating substituent.

14. Method according to claim 13, characterized in that the deactivating substituent is Cl-, Br- or F-.

15. Method according to any one of claims 1 to 9, characterized in that, in the formula of the acylating agent (III), R ⁴ is a phenyl radical or else a phenyl radical substituted by an atom of chlorine, bromine or fluorine and X represents a chlorine atom or else a residue R ⁴ C (O) O- in which R ⁴ is a phenyl radical.

16. The method of claim 15, characterized in that the acylating agent (III) is benzoyl chloride, 3-chlorobenzoyl chloride, 2-fluorobenzoyl chloride, 2-bromobenzoyl chloride, l benzoic anhydride.

17. Compound of formula (I):

wherein X represents a chlorine atom or a bromine atom, R represents an alkyl radical, linear or branched, having a number of carbon atoms ranging from 1 to 10; a fluorine, chlorine or bromine atom; y is 0, 1, 2, 3, 4 or 5; x is an integer equal to 1 or 2.

18. Indium dichlorobenzoate: CI ₂ InOC (O) C ₆ H ₅ .

19. Dichloro (indium 2-fluorobenzoate):