WO2006024783A1

WO2006024783A1 - Method for acylating nucleophilic compounds in particular anilines

Info

Publication number: WO2006024783A1
Application number: PCT/FR2005/002024
Authority: WO
Inventors: Joseph Lopez; Alice Rolland
Original assignee: Rhodia Chimie
Priority date: 2004-08-04
Filing date: 2005-08-03
Publication date: 2006-03-09
Also published as: FR2874010A1; FR2874010B1

Abstract

The invention concerns a method for acylating a nucleophilic compound by reacting said compound with 2-trifluoromethylbenzoyl fluoride or a derivative thereof comprising on the benzene ring at least another substituent non interfering with the acylation reaction. The nucleophilic compound is in particular a primary or secondary amine, an alcohol or a thiol. In accordance with a preferred embodiment, said nucleophilic compound is an aniline.

Description

PROCESS FOR ACYLATION OF NUCLEOPHILIC COMPOUNDS, IN PARTICULAR

ANILINES

The present invention relates to a process for acylation of nucleophilic compounds.

There are many important compounds used in the agrochemical and pharmaceutical fields, for example, aniline derivatives, which result from the acylation of a nucleophilic compound, eg aniline, by a suitable reagent comprising one or more electrons.

The object of the present invention is to provide an alternative method for the acylation of nucleophilic compounds.

Another object of the invention is to provide such a method which has a certain selectivity.

The subject of the invention is therefore a process for the acylation of a nucleophilic compound by reaction of this compound with 2-trifluoromethylbenzoyl fluoride or a derivative thereof comprising on the benzene ring at least one other non-interfering substituent. with the acylation reaction. Such a substituent may be selected from: CF _3, Cl and NO _2, alkyl -C ₄ alkoxy, C ₁ -C ₄ alkyl, halogen, preferably Cl, CF ₃ and NO _2.

Particularly targeted nucleophilic compounds are primary or secondary amines, alcohols and thiols. In a particular embodiment, the nucleophilic compounds are aromatic amines, in particular anilines.

These nucleophilic compounds include an electron donating group, while the -CF ₃ group carried by the fluoride is electron withdrawing. In this description, the terms "aromatic""electrondonor" and "electron withdrawing" are heard as defined by HC BROWN in the work by Jerry March - Advanced Organic Chemistry, ^4th edition, John Wiley and Sons, 1992, Chapter 9, pp. 273 - 292. As examples of electro-donating groups that may be present in the starting nucleophilic compound, mention may be made in particular of:

a linear or branched alkyl group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl,

a linear or branched alkenyl group having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, such as vinyl, allyl,

a linear or branched alkoxy group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, such as the methoxy, ethoxy, propoxy, isopropoxy or butoxy groups, a 2-oxypropionic group,

a cycloalkyl group having from 3 to 8 carbon atoms, preferably a cyclohexyl group,

a benzyl group, a phenyl group,

a group of formula:

-R ₁ -OCOR ₂ -R ₁ -N (R ₂ ) ₂ -R ₁ -CO-N (Ra) ₂ in said formulas,

. R ₁ represents a valency bond or a linear or branched, saturated or unsaturated, divalent hydrocarbon group having from 1 to 6 carbon atoms such as, preferably, methylene, ethylene, propylene, isopropylene, isopropylidene; . the groups R ₂ , which may be identical or different, represent a hydrogen atom, an alkyl, alkenyl, cycloalkyl, aryl or aralkyl group.

The term "alkyl" means a linear or branched hydrocarbon chain having, unless otherwise indicated, from 1 to 6 carbon atoms and preferably from 1 to 4 carbon atoms. Examples of preferred alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl and t-butyl.

By "alkenyl" is meant a linear or branched hydrocarbon group having from 2 to 6 carbon atoms, preferably from 2 to 4 carbon atoms, comprising a double bond, such as vinyl or allyl By "cycloalkyl" is meant a cyclic hydrocarbon group comprising from 3 to 8 carbon atoms, preferably from 5 to 6 carbon atoms, for example cyclohexyl.

By "aryl" is meant an aromatic mono- or polycyclic group, preferably mono- or bicyclic comprising from 6 to 20 carbon atoms, preferably phenyl or naphthyl. When the group is polycyclic, that is to say that it comprises more than one ring nucleus, the ring nuclei can be condensed two by two or attached in pairs by bonds σ.

Preferred examples of (C ₆ -C 16) aryl groups include phenyl, naphthyl.

It can also be phenyl groups substituted with alkyl groups, alkoxy groups or hydrogen atoms or a trifluoromethyl group.

By "arylalkyl" is meant a linear or branched hydrocarbon group bearing a monocyclic aromatic ring and comprising from 7 to 12 carbon atoms, preferably benzyl.

According to one aspect of the invention, the nucleophilic compounds that can be used in the process of the invention are

Δ either primary or secondary amine compounds of formula (I)

Rs-NHR'a, with R'3 representing hydrogen or a second group R ₃ , identical or different,

Δ is compounds of alcohol or thiol type of formula (H) R ₃ -Z, with Z a group of OMi or SMi type in which Mi represents a hydrogen atom or a metal cation, preferably an alkali metal cation, and R ₃ being a hydrocarbon group preferably having 1 to 20 carbon atoms.

The preferred compounds have the formula (I) or (II) wherein R ₃ represents a hydrocarbon group having from 1 to 20 carbon atoms which may be a saturated or unsaturated, linear or branched acyclic aliphatic group; a saturated, unsaturated or aromatic, monocyclic or polycyclic carbocyclic or heterocyclic group; a sequence of the aforementioned groups. In a first aspect, R ₃ represents a linear or branched saturated acyclic aliphatic group preferably having from 1 to 12 carbon atoms, and even more preferably from 1 to 4 carbon atoms. The invention does not exclude the presence of unsaturation on the hydrocarbon chain such as one or more double bonds which may or may not be conjugated, or a triple bond. The hydrocarbon chain may optionally be interrupted by a heteroatom, a functional group or bearing one or more substituents.

According to a second aspect, R 3 represents a saturated or unsaturated carbocyclic group preferably having 5 or 6 carbon atoms in the ring; a heterocyclic group, saturated or unsaturated, in particular containing 5 or 6 atoms in the ring, including 1 or 2 heteroatoms such as nitrogen, sulfur, oxygen or phosphorus atoms; an aromatic or monocyclic aromatic carbocyclic or heterocyclic group, preferably phenyl, pyridyl, furyl, pyranyl, thiofenyl, thienyl, phospholyl, pyrazolyl, imidazolyl, pyrolyl or polycyclic fused or unsubstituted, preferably naphthyl.

Since R ₃ comprises a cycle, it can also be substituted. The nature of the substituent can be any as long as it does not interfere with the main reaction. The number of substituents is generally at most 4 per cycle but most often equal to 1 or 2.

The invention also relates to the case where R ₃ comprises a chain of aliphatic and / or cyclic, carbocyclic and / or heterocyclic groups.

An acyclic aliphatic group may be linked to a ring by a valency bond, heteroatom, or functional group such as oxy, carbonyl, carboxy, sulfonyl, and the like.

More particularly, cycloalkylalkyl groups, for example cyclohexylalkyl or aralkyl groups having 7 to 12 carbon atoms, in particular benzyl or phenylethyl, are more particularly targeted.

The invention also contemplates a chain of carbocyclic and / or heterocyclic groups and more particularly a sequence of phenyl groups separated by a valency bond or an atom or functional group such as: oxygen, sulfur, sulfo, sulphonyl, carbonyl, carbonyloxy, imino, carbonylimino, hydrazo, alkylene (C 1 -C ₁₀ , preferably C 1) -diimino.

The acyclic aliphatic group, saturated or unsaturated, linear or branched may optionally carry a cyclic substituent. By ring is meant a carbocyclic or heterocyclic ring, saturated, unsaturated or aromatic.

Preferred compounds of formula (I) more particularly correspond to general formula (h):

in which :

- B represents the residue of an aromatic, monocyclic or polycyclic carbocyclic group or a divalent group consisting of a chain of two or more monocyclic aromatic carbocyclic groups, - R ₄ represents one or more substituents, which may be identical or different,

n 'is a number less than or equal to 5, preferably 1, 2 or 3,

- R ₅ represents a group R ₃ as defined above including a group

B, R ₄ and n 'having the meanings indicated above.

The preferred compounds of formula (II) more particularly correspond to the general formula (II-i):

in which : B represents the remainder of an aromatic, monocyclic or polycyclic carbocyclic group or a divalent group consisting of a chain of two or more monocyclic aromatic carbocyclic groups,

R ₄ represents one or more substituents, which may be identical or different, Z represents a group of OMi or SMi type as described above,

n 'is a number less than or equal to 5, preferably 1, 2 or 3,

The substituents R ₄ are advantageously in the ortho or para position.

Examples of substituents R ₄ in formulas (li) and (II-i) include: a linear or branched, linear or branched, C 1 to C ₁₂ , for example C ₁ to C ₆ or C ₁ to C ₄ , linear or branched alkyl group, such as, for example, methyl, ethyl, propyl or isopropyl; , butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, neohexyl,

. a linear or branched C ₂ to C ₆ alkenyl or alkynyl group, preferably from C ₂ to CA, such as vinyl, allyl,

. a linear or branched C ₁ to C ₆ , preferably C ₁ to C ₄ alkoxy or thioether group such as methoxy, ethoxy, propoxy, isopropoxy or butoxy, an alkenyloxy group, preferably an allyloxy group or a phenoxy group,. a cyclohexyl, phenyl or benzyl group,

. a group or function such as: hydroxyl, thiol (these two groups are preferably protected for example in ester or thioester form), carboxylic acid, ester, amide, formyl, acyl, aroyl, amide, urea, isocyanate, thioisocyanate, nitrile, azide , nitro, sulfone, sulfonic, halogen, pseudohalogen, trifluoromethyl.

According to a preferred aspect of the invention, the nucleophilic compound is an aniline of formula (II):

formula in which X signifies that the phenyl ring may comprise one or more substituents, in particular 1 or 2, preferably 1. The substituent (s), which may be identical or different, are chosen from R ₄ groups, for example OCH ₃ , C 1 alkyl -C ₈ , for example C ₁ -C e, C ₁ -C ₄ alkoxy, halogen, preferably Cl, CF ₃ and NO ₂ .

By way of non-limiting example, there may be mentioned aniline or phenylamine C ₆ H ₅ -NH ₂ , p-chloroaniline, p-anisidine and o-anisidine.

A particular object of the invention is therefore a process for acylating aniline by reaction with 2-trifluoromethylbenzoyl fluoride or a derivative thereof as defined above.

As compounds carrying alcohol or thiol functions, there may be mentioned by way of example:

hydroquinone, pyrocatechol, resorcinol, alkylphenols, alkylthiophenols, alkoxyphenols, salicylic aldehyde, p-hydroxybenzaldehyde, methyl salicylate, methyl ester of p-hydroxybenzoic acid, chlorophenols, nitrophenols, p-acetamidophenol,

dialkylphenols, vanillin, isovanillin, 2-hydroxy-5-acetamido-benzaldehyde, 2-hydroxypropionamido-5-benzaldehyde, 4-allyloxybenzaldehyde, dichlorophenols, methylhydroquinone, chlorohydroquinone, bromo -4 vanillin, 4-hydroxy vanillin, trialkylphenols, trinitro-

2,4,6-phenol, 2,6-dichloro-4-nitrophenol, trichlorophenols, dichlorohydroquinones, 3,5-dimethoxy-4-hydroxybenzaldehyde,

dihydroxynaphthalene, 4-methoxy-1-naphthol, 6-bromo-2-naphthol,

- 2-phenoxy phenol, phenoxy phenol-3, phenylhydroquinone, dihydroxy biphenyl-4,4 ^1, 4,4-isopropylidene diphenol ¹ (bis-phenol A), bis (4-hydroxyphenyl) methane , bis (4-hydroxyphenyl) sulfone, bis (4-hydroxyphenyl) sulfoxide, tetrabromobisphenol A.

According to one characteristic of the invention, the acylation reaction is conducted in the presence of a base whose function is to trap the leaving group HF. Among the bases that may be used, mention may be made, inter alia, of mineral bases such as carbonates, hydrogen carbonates, phosphates or hydroxides of alkali metals, preferably of sodium, of potassium, of cesium or of alkaline earth metals, preferably of calcium, barium or magnesium.

It is also possible to use alkali metal hydrides, preferably sodium hydride or alkali metal alcoholates, preferably sodium or potassium, and more preferably sodium methoxide, ethylate or tert-butoxide.

Also suitable tertiary amines and more particularly include triethylamine, diisopropylethylamine, tri-i-propylamine, tri-n-butylamine, methyldibutylamine, methyldicyclohexylamine, ethyldiisopropylamine, N, N-diethylcyclohexylamine pyridine, 4-dimethylaminopyridine, N-methylpiperidine, N-ethylpiperidine, N-β-butylpiperidine, 1,2-dimethylpiperidine, N-methylpyrrolidine, 1,2-dimethylpyrrolidine.

The amount of base used is such that the ratio between the number of moles of base and the number of moles of fluoride varies preferably between 1 and 4, preferably between 1 and 2.

According to another characteristic of the invention, the process employs a suitable solvent. In this respect, mention may be made of: aliphatic hydrocarbons and more particularly paraffins such as in particular pentane, hexane, heptane, octane, isooctane, nonane, decane, undecane, tetradecane, petroleum ether and cyclohexane; aromatic hydrocarbons such as, in particular, benzene, toluene, xylenes, ethylbenzene, diethylbenzenes, trimethylbenzenes, cumene, pseudocumene, petroleum fractions consisting of a mixture of alkylbenzenes, especially Solvesso® type cuts,

aliphatic or aromatic halogenated hydrocarbons, and there may be mentioned: perchlorinated hydrocarbons such as in particular trichloromethane, tetrachlorethylene; partially chlorinated hydrocarbons such as dichloromethane, dichloroethane, tetrachloroethane, trichlorethylene, 1-chlorobutane, 1,2- dichlorobutane; monochlorobenzene, 1,2-dichiorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene or mixtures of different chlorobenzenes,

aliphatic, cycloaliphatic or aromatic ether-oxides and, more particularly, deiethylether, methyl-tert-butyl ether, dipentyl ether, diisopentyl ether, ethylene glycol dimethyl ether (or 1,2-dimethoxyethane) ), dimethyl ether of diethylene glycol (or 1,5-dimethoxy-3-oxapentane) or cyclic ethers, for example, dioxane, tetrahydrofuran, aliphatic or aromatic nitriles such as acetonitrile, propionitrile, butanenitrile, isobutanenitrile, benzonitrile, benzyl cyanide,

linear or cyclic carboxamides such as Λ, Λ-dimethylacetamide (DMAC), N, N-diethylacetamide, dimethylformamide (DMF) or diethylformamide,

N-methylpyrrolidone.

The respective amounts of fluoride and nucleophilic compound are not critical. Typically, stoichiometric or quasi-stoichiometric amounts are used.

The reaction may be carried out at a temperature ranging from 0 to 120 ^° C., preferably from 20 ^° C. to 100 ° C. and more preferably from 20 ° C. to 80 ^° C.

Pressure is not a critical parameter and one generally works at atmospheric pressure.

According to one characteristic of the invention, the reaction is carried out under an inert atmosphere, preferably a nitrogen atmosphere.

The reaction time may vary widely and may depend on the amount of nucleophilic compounds present, with the reaction proceeding more rapidly for a larger amount of nucleophilic compounds. According to one characteristic of the invention, stirring of the medium is carried out during the reaction.

It is possible to influence the selectivity (in particular regioselectivity or chemioselectivity) of the reaction by adjusting certain parameters such as the reaction temperature and the concentration of the medium in reagents. The selectivity is increased by working in the lower temperature ranges, for example between 0 and 40 ⁰ C, especially at room temperature, and / or operating in diluted medium.

The reagents can be introduced in any order.

At the end of the reaction, the salts formed by washing with water can be removed and the product recovered in a conventional manner, in particular by extraction with the aid of an organic solvent, for example a chlorinated aliphatic hydrocarbon (dichloromethane, chloroform). or chlorinated aromatic (monochlorobenzene).

The aqueous and organic phases can be separated and the product can be obtained after evaporation of the solvent.

The reaction is conducted in an apparatus preferably in a fllor resistant material or coated with a fluorine resistant material: e.g. Teflon® or stainless steel, preferably Hastelloy®.

Examples of embodiments of the invention are given below. These examples are given for information only, and are not limiting in nature.

1. Obtaining 2-trifluoromethylbenzoyl fluoride

1.1 Typical test for Step 1: Chlorination of 2-methylbenzoic acid (o-toluic acid).

After purging the glass reactor with nitrogen, 410 g of 98% 2-methylbenzoic acid (mass) is added.

The reactor is heated to 120 ° C and stirred. When the acid is fully melted, 1.1 equivalent of 99.5% thionyl chloride (mass) are added using a syringe pump, the temperature of the reaction medium being maintained at 12O ⁰ C. After After 2 hours of addition, the mixture is refluxed at 120 ^° C. for 1.5 hours.

An analysis of the reaction medium by gas chromatography makes it possible to verify that the degree of conversion of 2-methylbenzoic acid is complete.

Then, the reaction medium is distilled, firstly at 90 ° C. under 50 mmHg to eliminate the residual SOCI ₂ , then under 20 mmHg with a column top temperature of 86-87 ^° C. The performances of this step are excellent: TT of o-toluic acid = 100%, selectivity to o-toluyl chloride = 96%.

1.2. Typical test for Step 2: Chlorination of o-toluyl chloride.

138 g of o-toluyl chloride at 98 mol% are charged at room temperature into a glass reactor. The reaction medium is brought to 115 ° C. under a slight stream of nitrogen. When this temperature is reached, a solution of AIBN (azobisisobutyronitrile) at 4% by weight in chlorobenzene is added with a flow rate of 5.5 g / h. After 5 minutes of addition of the radical initiator, the nitrogen sweep is stopped and the chlorine feed starts with a flow rate of 20 g / h. The molar ratio AIBN / C! ₂ is 0.55%.

After 86 hours of chlorination, the reaction medium is distilled to remove chlorobenzene (90 ^° C. under 40 mmHg). The reaction medium then contains a mixture of 2-monochloromethylbenzoyl chloride, 2-dichloromethylbenzoyl chloride and 2-trichloromethylbenzoyl chloride.

TT o-toluyl chloride = 100%, selectivity to 2-trichloromethylbenzoyl chloride = 42% (% area, approximate)

1.3. Typical test for step 3: Fluorination of trichloromethyl benzoyl chloride.

The reaction mass obtained during step 2 is loaded into the Hastelloy fluorination reactor and then heated to 105 ^° C. A first charge of 10.2 equivalents of HF relative to the chlorinated products is added to the medium, in 2 hrs 50 under 12 bars at 105 ^° C. After 1 h of finishing at 105 ° C under 12 bar, a second load of HF (1.2 equivalent) is added in 15 min, followed by 2.5 h finishing at 105 ⁰ C under 12 bars.

The reaction medium is then degassed at 70 ^° C. by nitrogen sweeping for 17 h to remove the excess of HF.

The reaction mass is then withdrawn and the reactor washed with fluorobenzene. The washing phases are added to the reaction medium, from NaF is added and a precipitate is formed. After filtration the cake is washed with fluorobenzene.

In order to isolate the trifluoromethyl benzoyl fluoride, the reaction medium is distilled, firstly at 45 ^° C. under 50 mmHg, then under 20 mmHg at 65 ° C. at the top of the column.

TT = 100%, selectivity to trifluoromethyl benzoyl fluoride = 96% (% areas).

2. Reactivity of 2-trifluoromethylbenzoyl fluoride

2.1. General procedure followed:

All tests were performed in closed Schott tubes of 30 mL stirred by magnetic bar. Acyl chlorides and fluorides were loaded into the Schott tubes in a glove box to avoid hydrolysis of these products. The solvent (toluene), aniline (or substituted aniline), and optionally an additional base, are added to the syringe through a septum.

At the end of the test, the reaction medium is analyzed by GC. In cases where a precipitate is formed, the medium is taken up in dichloromethane and is then washed with a basic aqueous solution to remove the salts. The organic phase is then concentrated for analysis.

The formed products were identified by GC-MS and quantified by NMR.

Reagents used:

Toluene with 40 ppm water

99% Triethylamine

Distilled aniline Benzoyl fluoride, benzoyl chloride, 2-trifluoromethyl benzoyl fluoride and 2-trifluoromethyl benzoyl chloride stored and loaded into schott tubes in glove box

2.2. Reactivity of 2-trifluoromethylbenzoyl fluoride The 2-trifluoromethylbenzoyl fluoride obtained according to the procedure described above was used in tests carried out at 20 ° C. in the presence of triethylamine. After 1 night under these conditions, the conversion is complete for the tests using aniline or p-methoxyaniline.

A weak hydrolysis of the fluoride in acid is demonstrated, it represents less than 8% after 20 hours in the tube.

These tests show that 2-trifluoromethylbenzoyl fluoride can react with anilines to give the corresponding amides quantitatively.

It should be understood that the invention defined by the appended claims is not limited to the particular embodiments indicated in the description above, but encompasses variants that do not depart from the scope or spirit of the present invention. present invention.

Claims

1 - Process for acylating a nucleophilic compound by reacting this compound with 2-trifluoromethylbenzoyl fluoride or a derivative thereof comprising on the benzene ring at least one other substituent not interfering with the acylation reaction .

2 - Process according to claim 1, wherein the nucleophilic compound is a primary or secondary amine, an alcohol or a thiol.

3 - Process according to claim 1 or 2, wherein the nucleophilic compound comprises an electron-donor group chosen from: a linear or branched alkyl group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, carbon, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl,

a benzyl group,

a phenyl group,

a group of formula:

-R ₁ -OCOR ₂ -R ₁ -N (Rz) ₂

-R ₁ -CO-N (Rz) ₂ in said formulas,

4 - Process according to claim 1, wherein the nucleophilic compound is a primary or secondary amine compound of formula (I)

Rs-NHR's, with R ' ₃ representing hydrogen or a second group R ₃ , identical or different, R ₃ being a hydrocarbon group preferably having from 1 to 20 carbon atoms.

5 - Process according to claim 1, wherein the nucleophilic compound is an alcohol or thiol compound of formula (II) R ₃ -Z, with Z representing a group of OMi or SMi type in which Mi represents a hydrogen atom or a metal cation, preferably an alkali metal cation,

R ₃ being a hydrocarbon group preferably having 1 to 20 carbon atoms.

6 - Process according to claim 4 or 5, wherein R ₃ represents a hydrocarbon group having 1 to 20 carbon atoms which may be a saturated or unsaturated, linear or branched acyclic aliphatic group; a saturated, unsaturated or aromatic, monocyclic or polycyclic carbocyclic or heterocyclic group; a sequence of the aforementioned groups.

7 - Process according to claim 6, in which the nucleophilic compound corresponds to the general formula (I ₁ ):

in which :

B represents the remainder of an aromatic, monocyclic or polycyclic carbocyclic group or a divalent group consisting of a chain of two or more monocyclic aromatic carbocyclic groups,

- R ₄ represents one or more substituents, identical or different, n 'is a number less than or equal to 5, preferably 1, 2 or 3,

- R ₅ represents a group R ₃ including a group

B, R ₄ and n 'having the meanings indicated above. ^j

8 - Process according to claim 6, in which the nucleophilic compound corresponds to the general formula (II-i):

in which :

- R ₄ represents one or more substituents, identical or different,

Z represents a group of OMi or SM _{1 type} as described above,

n 'is a number less than or equal to 5, preferably 1, 2 or 3,

9 - Process according to claim 7 or 8, wherein R ₄ is chosen from:

. a linear or branched C ₁ to C- ₁₂ alkyl group, linear or branched, preferably C ₁ to C ₅ , such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, neohexyl,

. a linear or branched C ₂ to C ₆ , preferably C ₂ to C ₄ , alkenyl or alkynyl group, such as vinyl, allyl,

. a linear or branched C ₁ to C ₆ , preferably C ₁ to C ₄ alkoxy or thioether group such as methoxy, ethoxy, propoxy, isopropoxy or butoxy, an alkenyloxy group, preferably an allyloxy group or a phenoxy group, . a cyclohexyl, phenyl or benzyl group,

. a group or function such as: hydroxyl, thiol, carboxylic, ester, amide, formyl, acyl, aroyl, amide, urea, isocyanate, thioisocyanate, nitrile, azide, nitro, sulfone, sulfonic, halogen, pseudohalogen, trifluoromethyl.

10 - Process according to claim 1, in which the nucleophilic compound is an aniline of formula (II):

wherein X means that the phenyl ring may comprise one or more substituents, especially 1 or 2, preferably 1.

11 - Process according to claim 10, wherein the nucleophilic compound is aniline or phenylamine C ₆ H ₅ -NH ₂ , p-chloroaniline, p-anisidine or o-anisidine.

12 - Process according to any one of the preceding claims, wherein the acylation reaction is conducted in the presence of a base whose function is to trap the leaving group HF, preferably a mineral base, an alkali metal hydride, or a tertiary amine.

13 - Process according to any one of the preceding claims, wherein the process uses a solvent chosen from:

aliphatic hydrocarbons and more particularly paraffins such as, in particular, pentane, hexane, heptane, octane, isooctane, nonane, decane, undecane, tetradecane, petroleum ether; and cyclohexane; aromatic hydrocarbons such as, in particular, benzene, toluene, xylenes, ethylbenzene, diethylbenzenes, trimethylbenzenes, cumene, pseudocumene, petroleum fractions consisting of a mixture of alkylbenzenes, especially Solvesso® type cuts, aliphatic or aromatic halogenated hydrocarbons, and there may be mentioned: perchlorinated hydrocarbons such as in particular trichloromethane, tetrachlorethylene; partially chlorinated hydrocarbons such as dichloromethane, dichloroethane, tetrachloroethane, trichlorethylene, 1-chlorobutane, 1,2-dichlorobutane; monochlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene or mixtures of different chlorobenzenes,

linear or cyclic carboxamides, for example dimethylacetamide (DMAC), diethylformamide, diethylformamide, diethylformamide, dimethylformamide (DMF),

N-methylpyrrolidone.

14 - Process according to any one of the preceding claims, in which the reaction is carried out at a temperature ranging from 0 to 120 ^° C., preferably from 20 ^° C. to 100 ^° C. and more preferably from 20 ^° C. to 80 ^° C. .

15 - Process according to any of the preceding claims, wherein 2-trifluoromethylbenzoyl fluoride is used as reagent.