WO2000061573A1 - Novel benzodioxinones and method for obtaining same - Google Patents

Abstract

The invention concerns novel benzodioxinones and a method for obtaining them. The inventive benzodioxinones correspond to the general formula (I) wherein: R1 to R6 are as described in Claim 1. The invention also concerns a method for obtaining derivatives resulting from benzodioxinones.

Description

 NOVEL BENZODIOXINONES AND PROCESS FOR OBTAINING SAME.

The present invention relates to new benzodioxinones and their process for obtaining. The invention also aims to obtain the derivatives obtained from benzodioxinones.

In many fields of application, in particular in the pharmaceutical field, we are looking for new molecules. New chemicals have now been found which in their preferred embodiment are precursors of acetylsalicylic acid, commonly known as "aspirin".

More specifically, the subject of the invention is new benzodioxinones corresponding to the general formula (I):

dans ladite formule (I) :

in said formula (I):

- R-, to R ₆ , identical or different, represent a hydrogen atom, a halogen atom, a functional group or an optionally substituted hydrocarbon residue R having from 1 to 24 carbon atoms which may be a saturated aliphatic radical or unsaturated, linear or branched; a saturated, unsaturated or aromatic monocyclic or polycyclic carbocyclic radical; a chain of the aforementioned radicals separated by a valential bond, a divalent hydrocarbon radical, a heteroatom or a functional group,

- R <\ and R2 can form a divalent radical thus forming a ring which can contain from 4 to 7 atoms.

More specifically, in formula (I), R ₁ to R ₆ represent a halogen atom, preferably a chlorine atom; a functional group preferably a hydroxyl, amino, substituted amino, amido, substituted amido, sulfonic group or a hydrocarbon residue. The groups R to R ₆ represent a hydrocarbon residue R which may be an aliphatic, saturated or unsaturated radical which may be of a linear or branched alkyl or alkenyl radical having from 1 to 12 carbon atoms, preferably from 1 to 6 atoms carbon: the hydrocarbon chain can possibly be interrupted by a heteroatom (for example, oxygen), by a functional group (for example -CO-, -O-CO-, -CO-O-) and / or carrier d 'a substituent (for example, a halogen, an ester function, preferably methyl or ethyl).

The groups R ₁ to R ₆ also represent a carbocyclic radical saturated or comprising 1 or 2 unsaturations in the ring, generally having from 3 to 8 carbon atoms, preferably, 6 carbon atoms in the ring; a monocyclic aromatic carbocyclic radical preferably having 6 carbon atoms in the ring; a polycyclic aromatic radical with rings which can form between them ortho-condensed, ortho- and peri-condensed systems, preferably having 12 carbon atoms in the rings.

The groups R ^ to R ₆ represent a polycyclic aromatic carbocyclic radical with several ring systems condensed or not linked together by a valential bond; an alkylene or alkylidene radical having from 1 to 4 carbon atoms, preferably a methylene, isopropylidene radical; a heteroatom, preferably oxygen; a functional group, preferably one of the following groups: -O-CO-, -CO-O-, - CO -, - SO -, -SO ₂ -.

As soon as one of the groups R 1 to R ₆ comprises a ring, it is possible for the ring to be substituted and as examples of substituents, it is possible to envisage, inter alia, the substituents such as alkyl or alkoxy radicals having generally from 1 to 4 carbon atoms, halogen atom, trifluoromethyl group, acetoxy group, acetamido group, etc.

The preferred compounds of the invention correspond to formula (I) in which: - the R- groups. to R ₆ , identical or different, represent:

- a hydrogen atom,

- a hydroxyl group,

- a group S0 ₃ H,

a group -N- (R ₈ ) ₂ in which the identical or different radicals R ₈ represent a hydrogen atom, a linear or branched alkyl radical having from 1 to 6 carbon atoms and even more preferably from 1 to 4 atoms carbon or a phenyl radical, a group -NH-CO-R ₈ in which the radical R ₈ has the meaning given above,

- a halogen atom, preferably a fluorine atom,

- a group CF ₃ , - the groups R 1 to R ₆ , which are identical or different, represent a hydrocarbon residue R, namely:

- a linear or branched alkyl radical preferably having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms, - a linear or branched alkenyl radical preferably having from 2 to 6 carbon atoms and even more preferably from 2 to 4 carbon atoms,

- a cyclohexyl radical,

- a phenyl radical, - tolyl, xylyl radicals,

- a benzyl radical,

- a 2-acetoxyphenyl radical,

- a 2- (3-benzoylphenyl) ethyl radical,

- an alkoxy radical R ₇ -O- or thioether R ₇ -S- in which R ₇ represents a linear or branched alkyl radical having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms, an alkenyloxy radical , preferably, an allyloxy radical. - Ri and R2 can form a divalent radical thus forming a saturated or unsaturated ring which may contain from 4 to 7 atoms.

The compounds of choice of the invention more particularly correspond to formula (I) in which:

- R-, represents a hydrogen atom, an alkyl radical having from 1 to 4 carbon atoms, an alkenyl radical having from 2 to 4 carbon atoms, an alkoxy radical having from 1 to 4 carbon atoms, a cyclohexyl radical , a phenyl radical, an o- m- or p-tolyl radical,

- R ₂ to R ₆ represent a hydrogen atom,

- R ₁ and R ₂ form an alkylene radical having 3 to 6 carbon atoms.

Another subject of the invention resides in one of the access routes of the benzodioxinones of the invention. More specifically, the process for obtaining benzodioxinones of formula (I) is characterized in that it consists in carrying out thermal cyclization, in the presence of a base, of a compound of formula (II):

dans ladite formule (II) :

in said formula (II):

- R _T to R ₆ have the meaning given above,

- X represents a halogen atom, preferably a chlorine atom. One of the characteristics of the compound of formula (II) is to have on the side chain carrying the ester functional group, a carbon atom carrying at least one hydrogen atom on the carbon atom located in position α of the group carbonyl.

As compounds of formula (II) preferably used in the process of the invention, there may be mentioned, among others:

- o-acetyloxybenzoyl chloride, - o-ethylcarbonyloxybenzoyl chloride,

- o-allylcarbonyloxybenzoyl chloride,

- o-methoxymethylenecarbonyloxybenzoyl chloride,

- o- (m-tolylmethylenecarbonyloxy) benzoyl chloride,

- O-cyclohexylcarbonyloxybenzoyl chloride. In accordance with the process of the invention, the compounds of formula (I) are prepared by cyclization of compounds of formula (II).

According to the invention, the cyclization is carried out in the presence of a base strong enough to trap the hydracid released during the cyclization.

A preferred variant of the invention consists in using, as a base, a tertiary amine.

Among the bases which can be used, mention should be made of tertiary amines and more particularly those corresponding to the general formula (III)

N - (R ₉ ) ₃ (III) in said formula (III): - The radicals Rg, identical or different, represent hydrocarbon residues having from 1 to 20 carbon atoms, such as alkyl, cycloalkyl, aryl or heterocyclic radicals;

- 2 radicals Rg together form and with the nitrogen atom a heterocycle having 4 to 6 atoms.

More particularly, the preferred amines correspond to formula (III) in which:

the symbols R ₉ represent an alkyl radical having 1 to 10 carbon atoms and preferably 1 to 4 carbon atoms or a cyclopentyl or cyclohexyl radical or a pyridinyl radical;

- 2 Rg radicals form together and with the nitrogen atom a piperidine or pyrrolidine cycle. As examples of such amines, mention may be made of triethylamine, tri-n-propylamine, tri-n-butylamine, methyldibutylamine, hexamine, methyldicyclohexylamine, ethyldiisopropylamine, N, N-diethylcyclohexylamine, dimethylamino-4 pyridine, N-methylpiperidine, N-ethylpiperidine, Nn-butylpiperidine, 1,2-dimethylpiperidine, N-methylpyrrolidine, 1,2-dimethylpyrrolidine.

The amount of tertiary amine used must be sufficient to neutralize the hydracid released by the reaction.

There is no critical upper limit on the quantity of tertiary amine, which can therefore be used in large excess relative to the quantity theoretically necessary for the neutralization of the hydracid formed. Generally, at least the stoichiometric amount is used up to an excess of 20% relative to the stoichiometry.

The cyclization reaction is generally carried out in the presence of an organic solvent.

Any organic solvent which is inert under the reaction conditions may also be used. Thus, one can use aliphatic or cycloaliphatic hydrocarbons, halogenated or not such as for example, hexane, cyclohexane, dichloromethane, dichloroethane or aromatic, halogenated or not such as benzene, toluene, xylenes, chlorobenzenes ; aliphatic, linear or cyclic ethers such as ethyl ether, isopropyl ether, isopropyl ether, tetrahydrofuran or dioxane.

The concentration of the compound of formula (II) used in the solvent can vary within very wide limits. Generally, it represents from 5 to 30% of the weight of the reaction mixture. As regards the cyclization operation proper, it is carried out by heating the reaction medium. The cyclization temperature is between 90 ° C and 200 ° C, and even more preferably between 95 ° C and 180 ° C. The duration of the heating must be sufficient for the reaction to be sufficiently complete. It most often varies, between 5 and 24 hours.

Generally, the reaction is carried out at atmospheric pressure but lower or higher pressures may also be suitable.

It is preferred to carry out the reaction under a controlled atmosphere of inert gases such as nitrogen or rare gases, for example argon.

From a practical point of view, the compound of formula (II), the solvent and the base are preferably used.

After bringing the reactants into contact, the reaction mixture is brought to the desired temperature. At the end of the reaction, the halohydrate of the tertiary amine is generally recovered in the precipitated form.

The latter is separated according to conventional solid / liquid separation techniques, preferably by filtration.

The liquid phase obtained comprises the cyclized compound which can be purified in a conventional manner, in particular by distillation or by chromatography on a silica column.

The starting compounds corresponding to formula (II) which are O-esterified acid halides, are known products. It will be specified, by way of indication, that they can be obtained in particular according to an O-esterification reaction between: - an acid of salicylic type corresponding to formula (IV):

(IV) dans ladite formule (IV) : - R₃ à R₆ ont la signification donnée précédemment,

(IV) in said formula (IV): - R ₃ to R ₆ have the meaning given above,

dans ladite formule (V) :- and a carboxylic acid corresponding to formula (V):

in said formula (V):

- R and R ₂ have the meaning given above.

It is also possible to use the compound of formula (V) in the halide form, preferably chloride or its anhydride form.

The O-esterification reaction is carried out in a conventional manner, generally in the presence of a base as mentioned above and in particular triethylamine or pyridine. (Brenner M. and Zimmermann J.P., Helv. Chim. Acta, 1957, p. 40)

According to another subject of the invention, the compounds of formula (I) release by hydrolysis products which may be particularly advantageous and which correspond to the general formula (VI):

R,

(VI) in said formula (VI):

- R ₁ to R ₆ have the meaning given above.

In a preferred embodiment of the invention which consists of a compound of formula (I) in which R-- to R _Q represent a hydrogen atom, the compound of formula (VI) corresponding to viz. acetylsalicylic acid or aspirin.

The compounds of formula (VI) are obtained by hydrolysis of the compounds of formula (I).

A preferred implementation consists in carrying out an acid hydrolysis. To this end, a mineral acid is used.

As examples of mineral acids, use is preferably made of the following mineral acids: hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid. We particularly choose hydrochloric acid. The commercial forms of said acids are generally used, for example hydrochloric acid at 36% by weight and sulfuric acid at 95% by weight.

The quantity of mineral acid used is such that the pH obtained is acid, preferably less than 5 and more preferably between 1 and 4.

The concentration of the compound of formula (I) used is of the order of 0.1 to 0.5 mol / l.

As for the temperature of the hydrolysis reaction, it is advantageously between 15 and 45 ° C, preferably between 20 and 40 ° C.

At the end of the reaction, the compound of formula (VI) is obtained.

Another object of the invention lies in obtaining, from compounds of formula (I), compounds which more particularly correspond to formula (VII):

dans ladite formule (VII) :

in said formula (VII):

- R _T to R ₆ have the meaning given above.

The compound of formula (VII) is obtained by hydrolysis at neutral pH (pH preferably between 6 and 8) of the compound of formula (I), by simple suspension in water.

The compound of formula (VII) is extracted using an appropriate organic solvent, for example ethyl acetate.

dans ladite formule (VIII) :Another object of the invention lies in obtaining from the compounds of formula (I), compounds which correspond to formula (VIII):

in said formula (VIII):

- Ri to R ₆ have the meaning given above,

- R _has the meaning given for R ^ to R ₆ in formula (I) with regard to the hydrocarbon residue R.

The compound of formula (VIII) is obtained by addition to the compound of formula (I) of a carboxylic acid corresponding to formula (IX):

_R - COOH (IX) in said formula (IX): - R _a has the meanings given above.

A carboxylic acid corresponding to formula (IX) is used more particularly in which R _a represents:

a linear or branched alkyl radical preferably having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms,

a linear or branched alkenyl radical preferably having from 2 to 6 carbon atoms and even more preferably from 2 to 4 carbon atoms,

- an acetoxymethylene radical, - a cyclohexyl radical,

- a phenyl radical,

- tolyl, xylyl radicals,

- a benzyl radical,

- a 2-acetoxyphenyl radical, - a 2-acetamidophenyl radical,

- a 2- (3-benzoylphenyl) ethyl radical,

- an alkoxy radical R ₇ -O- or thioether R ₇ -S- in which R ₇ represents a linear or branched alkyl radical having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms, an alkenyloxy radical , preferably, an allyloxy radical.

As examples of carboxylic acids which are very suitable for the invention, mention may be made in particular of salicylic acid, acetylsalicylic acid and a preferred class of carboxylic acids, namely arylpropionic acids. More specifically, said acids can be represented by the formula (IXa):

H, C - CH - COOH

I

(IXa) in said formula (IXa):

- R _b represents an optionally substituted phenyl radical; a chain of one or more of said phenyl radicals separated by a valential bond, a divalent hydrocarbon radical, a heteroatom or a functional group; or an optionally substituted naphthyl radical. In the formula (IXa), the radical R _b represents a phenyl or naphthyl radical which may carry a substituent or more substituents representing one of the following groups: - a linear or branched alkyl or alkenyl radical having from 1 to 12 carbon atoms, preferably a linear or branched alkyl radical having from 1 to 4 carbon atoms,

a linear or branched alkoxy radical having from 1 to 12 carbon atoms, preferably a linear or branched alkoxy radical having from 1 to 4 carbon atoms,

a linear or branched acyl radical having from 2 to 8 carbon atoms, preferably an acetyl radical or a benzoyl radical,

a linear or branched acyloxy group having from 2 to 8 carbon atoms, preferably an acetoxy group, a linear or branched alkylamido group having from 1 to 8 carbon atoms, preferably an acetamido group.

The nature of the substituents is given by way of illustration but without limitation. The number of substituents on the cycle is easily determined by a person skilled in the art. It is generally from 1 to 3. In the formula (IXa), reference is made to the preceding description for the definition of the group separating the (preferably two) phenyl radicals.

As specific examples, mention may be made of 2- (3-benzoylphenyl) propionic acid (Ketoprofen®), 2- (4-isobutylphenyl) propionic acid (Ibuprofen®), 2- (6-methoxynaphthyl) propionic acid (Naproxene®).

In accordance with the process of the invention, a compound of formula (VIII) is obtained by reacting a benzodioxinone corresponding to formula (I) with a carboxylic acid of formula (IX) and more preferably of formula (IXa).

The amount of benzodioxinone used is such that the benzodioxinone molar ratio of formula (I) / carboxylic acid of formula (IX) or (IXa) varies between 0.9 and 1.1.

The addition reaction is generally carried out in the presence of an organic solvent.

Any organic solvent which is inert under the reaction conditions may also be used. Thus, one can use aliphatic or cycloaliphatic hydrocarbons, halogenated or not such as for example, hexane, cyclohexane, dichloromethane, dichloroethane or aromatic, halogenated or not such as benzene, toluene, xylenes, chlorobenzenes ; aliphatic esters, preferably ethyl acetate.

As for the temperature of the addition reaction, it is advantageously between 15 and 45 ° C, preferably between 20 and 40 ° C.

The duration of the heating must be sufficient for the reaction to be sufficiently complete. It most often varies, between 5 and 24 hours.

Generally, the reaction is carried out at atmospheric pressure but lower or higher pressures may also be suitable.

It is preferred to carry out the reaction under a controlled atmosphere of inert gases such as nitrogen or rare gases, for example argon.

From a practical point of view, the reagents and the organic solvent are used in any order.

At the end of the reaction, the compound of formula (VIII) is obtained!

The present invention also relates to new molecules which result from the implementation of the process of the invention and which more particularly correspond to the general formula (Villa):

(Villa)

in said formula (Villa):

- Ri to R ₆ , have the meaning given above, - R _b represents an optionally substituted phenyl radical; a chain of one or more of said phenyl radicals separated by a valential bond, a divalent hydrocarbon radical, a heteroatom or a functional group; or an optionally substituted naphthyl radical. The preferred compounds correspond to the formula (Villa) in which R to

R ₆ represent a hydrogen atom.

In the formula (Villa), the radical R represents a phenyl or naphthyl radical which can carry a substituent or several substituents representing inter alia one of the following groups: - a linear or branched alkyl or alkenyl radical having from 1 to 12 carbon atoms, preferably a linear or branched alkyl radical having from 1 to

4 carbon atoms,

a linear or branched alkoxy radical having from 1 to 12 carbon atoms, preferably a linear or branched alkoxy radical having from 1 to 4 carbon atoms,

a linear or branched acyl group having from 2 to 8 carbon atoms, preferably an acetyl group or a benzoyl group,

a linear or branched acyloxy group having from 2 to 8 carbon atoms, preferably an acetoxy group, a linear or branched alkylamido group having from 1 to 8 carbon atoms, preferably an acetamido group. The preferred compounds of the invention correspond to the formula (Villa) in which:

- Ri to R ₆ , represent a hydrogen atom, - R represents an optionally substituted phenyl or naphthyl radical or a chain of phenyl radicals separated by a carbonyl group.

The invention is particularly interesting because it provides access to new molecules, the benzodioxinones of formula (I) as well as their hydrolysis products of formula (VI) or (VII) and their addition products (VIII ).

Examples of the invention are given below.

These examples are given by way of illustration and without limitation. Example 1:

1 - In this example, we pre ule (the):

To a solution of o-acetyloxybenzoyl chloride (19.2 g, 0.1 mol) in toluene (100 ml) while scanning with argon, triethylamine (12 g, 0.12 mol) is added at temperature ambient with magnetic stirring.

The reaction medium is then heated at 110 ° C for 15 hours. After cooling, the ammonium hydrochloride formed is removed by filtration and the light products are evaporated in vacuo on a rotary evaporator. The cyclized product (la) is then purified by distillation under reduced pressure of 0.1 mm of mercury (Yield = 60%, Eb _0, ι = 71 ° C, F = 46 ° C). 2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250 MHz, CDCI ₃ solvent _, internal ref.): 3.98 (s, 2H), 6.95 (dd, 1H,

³ J = 7.8 Hz, ⁴ J = 0.9 Hz), 7.10 (ddd, 1 H, ³ J = 7.8 Hz, ³ J = 7.8 Hz, ⁴ J = 0.9 Hz) , 7.55 (ddd, 1 H, ³ J = 7.8 Hz, ³ J = 7.8 Hz, ⁴ J = 1.6 Hz), 7.82 (dd, 1 H, ³ J = 7.8 Hz, ⁴ J

= 1.6 Hz). In benzene d ₆ , the singlet-like peak at 3.98 ppm gives 4 fine lines.

¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 73.1 (CH ₂ ), 110.8 (Cq), 115.3-123.4-129.0-136.9 (4CH ), 154.3-154.8-156.2 (3Cq). IR (film, absorption bands): 3071, 1770, 1682, 1615, 1468, 1310, 1260,

1241, 1067, 752.

Example 2:

1 - In this example, the compound of formula (1b) is prepared:

It is obtained according to the procedure of Example 1 from o-ethylcarbonyloxybenzoyl chloride.

The reaction medium is then heated at 110 ° C for 15 hours.

The final product is purified by distillation (Yield = 67%, Eb ₀ ,. = 99 ° C). 2 - The respective physico-chemical characterizations are given below: ¹ H NMR (250 MHz, CDCI ₃ solvent _, internal ref.): 1.64 and 1.67 (2d, 3H, Z and E, ³ J = 7.1 Hz), 4.48 (q, 1 H, ³ J = 7.1 Hz), 6.98 and 7.07 (2d, 1H, Z and E, ³ J = 8.4 Hz), 7.17 (m, 1 H), 7.60 (m, 1H), 7.9 (dd, 1H, ³ J = 7.8 Hz, ⁴ J = 1.6 Hz).

¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 8.11 and 8.24 (CH ₃ ), 84.9 and 85.0 (CH), 111, 5 and 11, 7 (Cq ), 115.1 and 115.6 (CH), 123.3 and 123.5 (CH), 129.6 (CH), 137.0 and 137.1 (CH), 149.1 (Cq), 155 , 6 and 155.9 (Cq), 157.4 and 157.5 (Cq). Some peaks are split due to the presence of the Z and E isomers

IR (film, absorption bands): 1770, 1709, 1613, 1594.

Example 3:

1 - In this example, the compound of formula (Ia) is prepared:

Il est obtenu selon le mode opératoire de l'exemple 1 à partir de chlorure d'o-allylcarbonyloxybenzoyle. Le milieu réactionnel est ensuite chauffé à 110°C pendant 15 heures.

It is obtained according to the procedure of Example 1 from o-allylcarbonyloxybenzoyl chloride. The reaction medium is then heated at 110 ° C for 15 hours.

The final product is purified by distillation (yield = 33%, Eb _0.5 . = 100 ° C). 2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250 MHz, CDCI ₃ solvent _, internal ref.): 5.0 (m, 1 H), 5.1-5.2 (m, 2H), 6.55 (m, 1 H), 7 , 05 (m, 1 H), 7.18 (m, 1 H), 7.61 (m, 1 H), 7.91 (m, 1 H). ¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 91, 9 and 92.2 (CH), 112.2

(Cq), 115.0 and 115.2 (CH ₂ ), 118.7 and 118.8 (CH), 123.9 and 124.1 (CH), 127.7 and 127.8 (CH), 129 , 7 (CH), 137.4 (CH), 150.1 and 150.2 (Cq), 156.7 and 156.8 (Cq), 157.5 and 157.6 (Cq). Some peaks are split because of the presence of the Z and E isomers. IR (film, absorption bands): 1774, 1681, 1617, 1606.

Example 4:

1 - In this example, the compound of formula (Id) is prepared:

O

O

⁰ dd) It is obtained according to the procedure of Example 1 from o-methoxymethylenecarbonyloxybenzoyl chloride.

The reaction medium is then heated at 110 ° C for 15 hours. The final product is purified by distillation (yield = 46%, Eb _0.5 . = 108 ° C). 2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250 MHz, CDCI ₃ solvent _, internal ref.): 3.51 and 3.53 (2s, 3H), 5.7 and 5.72 (2s, 1 H), 6.86-7.08 (m, 2H), 7.46 (m, 1H), 7.77 (dd, 1H „ ³ J = 7.8 Hz, ⁴ J = 1.7 Hz),

¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 60.8 and 60.9 (CH ₃ ), 115.8 and 115.9 (Cq), 119.0 and 119.1 (CH) , 123.7 and 124.2 (CH), 128.8 (CH), 130.0 and 130.1 (CH), 136.9 and 137.6 (CH), 142.6 and 142.8 (Cq ), 156.1 (Cq), 157.4 (Cq). Some peaks are split due to the presence of the Z and E isomers

IR (film, absorption bands): 1771, 1731, 1614, 1591.

Example 5:

1 - In this example, the)

II est obtenu selon le mode opératoire de l'exemple 1 à partir de chlorure d'o-(m-tolylméthylènecarbonyloxy)benzoyle.

It is obtained according to the procedure of Example 1 from o- (m-tolylmethylenecarbonyloxy) benzoyl chloride.

The reaction medium is then heated at 100 ° C for 2 hours. In order to purify it, the reaction mixture is chromatographed on a silica column, eluting with a pentane / methylene chloride mixture (1/1). Two pure products are obtained, one of which has a melting point of 93 ° C and the other of 102 ° C (overall yield 27%). 2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250 MHz, CDCI solvent _3ι internal ref.): 2.46 (s, 3H), 5.57 (s, 1H), 7.08-7.38 (m, 4H), 7.44 ( s, 1 H), 7.55 (d, 1 H, ³ J = 7.8 Hz), 7.77 (ddd, 1H, ³ J = 7.6 Hz, ³ J = 7.8 Hz, ⁴ J = 1.7 Hz), 8.04 (dd, 1 H, ³ J = 7.8 Hz, J = 1.6 Hz).

¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 21, 2 (CH ₃ ), 91, 3 (CH), 111, 2 (Cq), 115.8 (CH), 123.8 (CH), 125.2 (CH), 127.4 (CH), 128.5 (CH), 128.9 (CH), 129.8 (CH), 132.3 (Cq), 135.5 ( CH), 138.1 (Cq), 149.4 (Cq), 155.9 (Cq), 156.4 (Cq), IR (KBr pellets, absorption bands): 1771, 1681, 1609, 1593.

¹ H NMR (250 MHz, CDCI ₃ solvent _, internal ref.): 2.41 (s, 3H), 5.49 (s, 1H), 7.08 (d, 1 H, ³ J = 8.0 Hz ), 7.14-7.38 (m, 4H), 7.47 (d, 1H, ³ J = 7.9 Hz), 7.67 (ddd,

1 H, "J = 7.6 Hz, 3 ^J J. - = 7.8 Hz, \ J = 1.7 Hz), 8.01 (dd, 1 H, ° 3J. = - 7.8 Hz, \ J = 1.6Hz), ¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 21.5 (CH ₃ ), 91.7 (CH),

112.6 (Cq), 115.9 (CH), 124.2 (CH), 125.0 (CH), 127.3 (CH), 128.4 (CH), 128.9 (CH), 129.9 (CH), 133.1 (Cq), 137.3 (CH), 138.3 (Cq), 149.9 (Cq), 156.2 (Cq),

156.7 (Cq).

IR (KBr tablets, absorption bands): 1758, 1677, 1613, 1593.

Example 6:

1 - In this example, we have (If)

II est obtenu selon le mode opératoire de l'exemple 1 à partir de chlorure d'o-cyclohexylcarbonyloxybenzoyle .

It is obtained according to the procedure of Example 1 from o-cyclohexylcarbonyloxybenzoyl chloride.

The reaction medium is then heated at 110 ° C for 15 hours. The final product is purified by distillation (Yield = 58%, Eb _0.5 = 130 ° C, F = 30 ° C). 2 - The respective physicochemical characterizations are given below: ¹ H NMR (250 MHz, CDCI ₃ solvent _, internal ref.): 1.50 (widened s, 6H), 2.22 (widened s, 4H), 7.01 (dd, 1 H, ³ J = 8.3 Hz, ⁴ J = 0.6 Hz), 7.10 (ddd, 1 H, ³ J = 7.7 Hz, ³ J = 7.8 Hz , ⁴ J = 0.6 Hz), 7.54 (ddd, 1 H, ³ J = 8.3 Hz, ³ J = 7.7 Hz, ⁴ J = 1.7 Hz), 7.88 (dd, 1H, ³ J = 7.8 Hz, ⁴ J = 1.7 Hz), ¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 25.3 (CH ₂ ), 25.6 (CH ₂ ),

28.3 (CH ₂ ), 28.7 (CH ₂ ), 28.8 (CH ₂ ), 102.5 (Cq), 102.3 (Cq), 115.6 (CH), 123.2 (CH ), 129.8 (CH), 136.8 (CH), 141, 7 (Cq), 156.7 (Cq), 158.8 (Cq). IR (film, absorption bands): 1769, 1710, 1612, 1591.

Example 7:

1 g of the compound of formula (la), obtained according to Example 1, is suspended in an aqueous solution (20 ml) of hydrochloric acid of pH = 1 or pH = 4.

The product hydrolyzes quickly (30 to 60 min) to give essentially aspirin. Example 8:

1 - In this example, the compound of formula (VI la) is prepared from the compound of formula (la):

At neutral pH, 1 g of the compound of formula (la) obtained according to example 1 is suspended in water (20 ml).

After one hour of stirring at room temperature, ethyl acetate (5 ml) is added.

After decantation, the organic phase is dried over magnesium sulphate then the solvent is evaporated by simple abandonment in air.

Before complete drying, white crystals are collected by filtration and then dried (0.6 g, M = 120 ° C). 2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250 MHz, CDCI ₃ solvent _, internal ref.): 2.35 (s, 3H), 2.37 (s, 3H), 6.98-7.22 (m, 4H), 7.42 -7.63 (m, 2H), 7.7, (dd, 1H, 3M | - = 7.8 Hz, 4 \ J | - = 1.6 Hz), 7.98

(dd, 1 H, ³ J = 7.8 Hz, ⁴ J = 1.6 Hz),

¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 20.9-24.0 (2CH ₃ ), 113.0-

116.8 (2Cq), 117.0 (CH), 122.1 (Cq), 123.9-124.1-126.0-129.4-131, 7-134.7-

137.0 (7CH), 150.8-153.5-158.3-160.5-169.5 (5Cq). IR (KBr pellet, absorption bands): 1770, 1744, 1617, 1604.

Example 9:

1 - In this example, the compound of formula (VI Mb) is prepared

A solution of the compound of formula (la) obtained according to Example 1 (1 g, 6.1 mmol) and acetylsalicylic acid (1.11 g, 6.1 mmol) in ethyl acetate (5 ml) is stirred for 24 hours at room temperature and under an inert atmosphere. The solvent is evaporated by simple abandonment in air; before complete drying, the compound of formula (VIIIb) is recovered in the form of white crystals. (Yield = 57%, F = 120 ° C). 2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250MHz, CDCI ₃ solvent _, internal ref.): 2.35 (s, 3H), 2.37 (s, 3H), 6.98-7.22 (m, 4H), 7.42- 7.63 (m, 2H), 7.7, (dd, 1 H, ³ J = 7.8 Hz, ⁴ J = 1.6 Hz), 7.98 (dd, 1 H, ³ J = 7, 8 Hz, ⁴ J = 1.6 Hz).

¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 20.9-24.0 (2CH ₃ ), 113.0- 116.8 (2Cq), 117.0 (CH), 122.1 (Cq), 123.9-124.1-126.0-129.4-131, 7-134.7- 137.0 (7CH), 150.8-153.5-158.3-160.5 -169.5 (5Cq).

IR (KBr pellet, absorption bands): 1770, 1744, 1617, 1604.

Example 10:

1 - In this example, we prepare the compound of formula (City):

(City)

A solution of the compound of formula (la) obtained according to Example 1 (1 g, 6.1 mmol) and phenylacetic acid (0.83 g, 6.1 mmol) in ethyl acetate (5 ml) is stirred for 24 hours at room temperature and under an inert atmosphere.

The solvent is then removed under reduced pressure (0.05 mm of mercury) and the compound (Ville) is recovered in the form of an oil (1.7 g, 85%) and stored under an inert atmosphere.

By NMR, the presence of traces of phenylacetic acid is noted. 2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250MHz, CDCI ₃ solvent _, internal ref.): 2.17 (s, 3H), 3.39 (s, 2H), 6.89-6.93 (m, 2H), 7.08- 7.12 (m, 5H), 7.48, (ddd, 1 H, ³ J = 7.8 Hz, ³ J = 7.7 Hz, ⁴ J = 1, 3 Hz), 7.84 (dd, 1 H, ³ J = 7.8 Hz, ⁴ J = 1.5 Hz).

¹³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 23.9 (1CH ₃ ), 41, 7 (1CH ₂ ), 113.2-116.3 (2Cq), 116.8-123, 9-127.2-128.5-128.8-129.4 (8CH), 132.7 (1Cq), 136.7 (1CH), 153.5-158.3-167.6 (3Cq).

IR (film, absorption bands): 1760, 1616. Example 11:

1 - In this example, the compound of formula (VIIll) is prepared:

(Vllld)

A solution of the compound of formula (la) obtained according to Example 1 (1 g, 6.1 mmol) and 2- (3-benzoylphenyl) propionic acid (1.54 g, 6.1 mmol) in l ethyl acetate (5 ml) is stirred for 24 hours at room temperature and under an inert atmosphere.

The solvent is then removed under reduced pressure (0.05 mm of mercury) and the compound of formula (IIIll) is recovered in the form of an oil (2.3 g, 90%) and stored under an inert atmosphere.

By NMR, the presence of traces of 2- (3-benzoylphenyl) propionic acid is noted. 2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250MHz, CDCI ₃ solvent _, internal ref.): 1, 27-1, 31 (2d 3H, ³ J = 6.1 Hz), 2.13-2.16 (2s, 3H), 3, 57 (m, 1H), 6.79-7.75 (m, 13H).

³ C NMR (50.3 MHz, CDCI ₃ solvent, internal ref.): 17.4-23.6 (2CH ₃ ), 45.5 (1CH), 113.1-116.3 (2Cq), 116.7 -123.9-128.3-128.4-128.7-129.0-129.2-130.0- 131, 1-132.6-136.6 (13CH), 137.3-137, 7-139.4-153.4-158.5-170.0-196.0 (7Cq).

IR (film, absorption bands): 1758, 1659.

Example 12:

1 - In this example, we prepare the compound of formula (City):

(Ville) Une solution du composé de formule (la) obtenu selon l'exemple 1 (9 g, 55,5 mmol) et d'acide acétique glacial (3,4 g, 56,6 mmol) dans de l'acétate d'éthyle (40 ml) est agitée à température ambiante, sous atmosphère inerte d'azote pendant 18 heures. Le mélange réactionnel est concentré sous pression réduite (0,05 mm de mercure) jusqu'à l'obtention d'un précipité blanc.

(City) A solution of the compound of formula (la) obtained according to Example 1 (9 g, 55.5 mmol) and glacial acetic acid (3.4 g, 56.6 mmol) in ethyl acetate ( 40 ml) is stirred at room temperature, under an inert nitrogen atmosphere for 18 hours. The reaction mixture is concentrated under reduced pressure (0.05 mm of mercury) until a white precipitate is obtained.

After filtration, 9.2 g of crude product are obtained in the form of a white powder.

The product (Ville) is crystallized from ethyl acetate (Yield = 41%, M = 90 ° C).

2 - The respective physico-chemical characterizations are given below:

¹ H NMR (250 MHz, CDCI ₃ , internal reference): 1.84 (s, 3H); 2.14 (s, 3H); 6.99 (d, 1H, ³ J = 8.2 Hz); 7.16 (dd, 1 H, ³ J = 7.6 Hz); 7.55 (dd, 1 H, ³ J = 8.2 Hz, ³ J = 7.6 Hz); 7.91 (d, 1H, ³ J = 7.6 Hz). ¹³ C NMR (63 MHz, CDCI ₃ , internal reference): 21.3; 23 9 (2CH ₃ ); 113; 1;

116.0 (2C _q ); 116.9; 123.9; 129.3; 136.8 (4CH); 153.6; 158.4; 167.1 (3C _q ).

IR (KBr pellet, absorption bands): 1768, 1745.

Example 13: 1 - In this example, the compound of formula (Vlllf) is prepared:

(Vlllf)

(Vlllf)

A solution of the compound of formula (la) obtained according to the example (2 g, 12.3 mmol) and acetoxyaeetic acid (1.45 g, 12.3 mmol) in ethyl acetate (20 ml ) is stirred at room temperature for 18 hours.

The reaction mixture is concentrated under reduced pressure (0.05 mm of mercury) until a white precipitate is obtained.

After filtration, 3 g of crude product are obtained in the form of a white powder. The product (Vlllf) is crystallized from ethyl acetate (Yield = 26%,

Mp 90 ° C). 2 - The respective physicochemical characterizations are given below: ¹ H NMR (250 MHz, CDCI ₃ , internal reference): 2.03 (s, 3H); 2.24 (s, 3H);

4.31 (d, 1 H, ² J = 16.2 Hz); 4.43 (d, 1H, ² J = 16.2 Hz); 7.07 (dd, 1H, ³ J = 8.2 Hz,

⁴ J = 0.6 Hz); 7.25 (ddd, 1H, ³ J = 7.6 Hz, ⁴ J = 0.6 Hz); 7.64 (ddd, 1H, ³ J = 8.2 Hz, ³ J = 7.6 Hz, ⁴ J = 1.8 Hz); 7.99 (dd, 1 H, ³ J = 7.6 Hz, ⁴ J = 1.8 Hz).

¹³ C NMR (63 MHz, CDCI ₃ , internal reference): 20.2; 24.1 (2CH ₃ ); 60.3

(CH ₂ ); 113.9; 116.8 (C _q ); 117.1; 124.2; 129.5; 137.0 (4CH); 153.9; 164.8;

170.1 (3C _q ).

IR (KBr tablet, absorption bands): 1769, 1750.

Example 14:

1 - In this example, the compound of formula (Vlllg) is prepared:

(Vlllg)

(Vlllg)

A solution of the compound of formula (la) obtained according to the example (2 g,

12.3 mmol) and N-acetylanthranilic acid (2.21 g, 12.3 mmol) in ethyl acetate (20 ml) is stirred at room temperature for 48 hours. The reaction mixture is concentrated under reduced pressure (0.05 mm of mercury) until a white precipitate is obtained. After filtration, the product (Vlllg) is crystallized from ethyl acetate (Yield =

59%, M = 146 ° C).

2 - The respective physicochemical characterizations are given below: ¹ H NMR (250 MHz, CDCI ₃ , internal reference): 2.22 (s, CH ₃ ), 2.35 (s, CH ₃ ),

6.89-6.95 (m, 1H); 7.09-7.13 (m, 1H); 7.16-7.24 (m, 1H); 7.43-7.52 (m, 1H); 7.58-7.67 (m, 2H), 7.99 (d, 1H, ³ J = 7.8 Hz); 8.63 (d, 1 H, ³ J = 8.7 Hz); 10.30 (broad s, NH).

¹³ C NMR (63 MHz, CDCI ₃ , internal reference): 24.2 (CH ₃ ); 25.5 (CH ₃ );

112.9; 113.4 (2C _q ); 116.9 (CH); 117.1 (C _q ); 120.4; 122.5; 124.2; 129.5;

130.8; 135.6; 137.1 (7CH); 142.2; 153.6; 158.1; 164.7; 169.1 (5C _q ) IR (KBr pellet, absorption bands): 3327, 1750, 1709, 1697.

Claims

1 - Benzodioxinones corresponding to the general formula (I):

in said formula (I): - Ri to R ₆ , identical or different, represent a hydrogen atom, a halogen atom, a functional group or an optionally substituted hydrocarbon residue R having from 1 to 24 carbon atoms which may be a saturated or unsaturated aliphatic radical , linear or branched; a saturated, unsaturated or aromatic monocyclic or polycyclic carbocyclic radical; a chain of the aforementioned radicals separated by a valential bond, a divalent hydrocarbon radical, a heteroatom or a functional group, - R ₁ and R2 can form a divalent radical thus forming a ring which may contain from 4 to 7 atoms. 2 - Benzodioxinones according to claim 1, characterized in that they correspond to formula (I), in which R 1 to R ₆ represent a chlorine atom; a hydroxyl, amino, substituted amino, amido, substituted amido, sulfonic group or a hydrocarbon group. 3 - Benzodioxinones according to either of Claims 1 and 2, characterized in that they correspond to formula (I) in which Ri to R ₆ represent a hydrocarbon residue R which may be an aliphatic, saturated or unsaturated radical which may be a linear or branched alkyl or alkenyl radical having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms: the hydrocarbon chain can possibly be interrupted by a heteroatom, by a functional group and or carrying a substituting; a carbocyclic radical saturated or comprising 1 or 2 unsaturations in the ring, generally having from 3 to 8 carbon atoms, preferably 6 carbon atoms in the ring; a monocyclic aromatic carbocyclic radical preferably having 6 carbon atoms in the ring; a polycyclic aromatic radical with rings which can form ortho- condensed, ortho- and peri-condensed, preferably having 12 carbon atoms in the rings; a polycyclic aromatic carbocyclic radical with several ring systems condensed or not linked to each other by a valential bond, an alkylene or alkydene radical having from 1 to 4 carbon atoms, preferably a methylene, isopropylidene radical, a heteroatom, preferably the oxygen, a functional group, preferably one of the following groups: -O-CO-, -CO-O-, - CO -, - SO -, -SO ₂ ~. 4 - Benzodioxinones according to one of Claims 1 to 3, characterized in that they correspond to formula (I) in which: - groups Ri to R ₆ , identical or different, represent: - a hydrogen atom, - a hydroxyl group, - a group S0 ₃ H, - a radical -N- (R ₈ ) ₂ in which the radicals R ₈ identical or different represent a hydrogen atom, a linear or branched alkyl radical having from 1 to 6 carbon atoms and also more preferably from 1 to 4 carbon atoms or a phenyl radical, a group -NH-CO-R ₈ in which the radical R ₈ has the meaning given above, - a halogen atom, preferably a fluorine atom, - a CF ₃ group, the groups R 1 to R ₆ , which are identical or different, represent a hydrocarbon residue R, namely: a linear or branched alkyl radical preferably having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms, a linear or branched alkenyl radical preferably having from 2 to 6 carbon atoms and even more preferably from 2 to 4 carbon atoms, - a cyclohexyl radical, - a phenyl radical, - tolyl, xylyl radicals, - a benzyl radical, - a 2-acetoxyphenyl radical, - a 2- (3-benzoylphenyl) ethyl radical, an alkoxy radical R ₇ -O- or thioether R ₇ -S- in which R ₇ represents a linear or branched alkyl radical having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms, an alkenyloxy radical, preferably an allyloxy radical. - Ri and R ₂ can form a divalent radical thus forming a saturated or unsaturated ring which may contain from 4 to 7 atoms. 5 - Benzodioxinones according to one of Claims 1 to 4, characterized in that they correspond to formula (I) in which: Ri represents a hydrogen atom, an alkyl radical having from 1 to 4 carbon atoms, an alkenyl radical having from 2 to 4 carbon atoms, an alkoxy radical having from 1 to 4 carbon atoms, a cyclohexyl radical, a phenyl radical, an o- m- or p-tolyl radical, - R ₂ to R ₆ represent a hydrogen atom, - Ri and R ₂ form an alkylene radical having 3 to 6 carbon atoms. 6 - Process for obtaining the benzodioxinones of formula (I) described in one of claims 1 to 5 characterized by the fact that it consists in carrying out thermal cyclization, in the pose of formula (II):

in said formula (II): - Ri to R ₆ have the meaning given previously in one of claims 1 to 5, - X represents a halogen atom, preferably a chlorine atom. 7 - Process according to claim 6 characterized in that the compound of formula (II) is chosen from: - o-acetyloxybenzoyl chloride, - o-ethylcarbonyloxybenzoyl chloride, - o-allylcarbonyloxybenzoyl chloride, - o-methoxymethylenecarbonyloxybenzoyl chloride, - o- (m-tolylmethylenecarbonyloxy) benzoyl chloride, - O-cyclohexylcarbonyloxybenzoyl chloride. 8 - Method according to one of claims 6 and 7 characterized in that the cyclization is carried out in the presence of a base 9 - Process according to claim 8 characterized in that the base is a tertiary amine. 10 - Process according to claim 9 characterized in that the tertiary amine corresponds to the general formula (III) N - (R ₉ ) ₃ (III) in said formula (III): - the radicals R ₉ , identical or different, represent hydrocarbon residues having from 1 to 20 carbon atoms, such as alkyl, cycloalkyl, aryl or heterocyclic radicals; - 2 radicals Rg together form and with the nitrogen atom a heterocycle having 4 to 6 atoms. 11 - Process according to claim 9 characterized in that the tertiary amine is chosen from: triethylamine, tri-n-propylamine, tri-n-butylamine, methyldibutylamine, hexamine, methyldicyclohexylamine, ethyldiisopropylamine , N, N-diethylcyclohexylamine, 4-dimethylamino pyridine, N-methylpiperidine, N-ethylpiperidine, Nn-butylpiperidine, 1, 2-dimethylpiperidine, N-methylpyrrolidine, 1, 2-dimethylpyrrolidine. 12 - Process according to claim 6 characterized in that the cyclization reaction is generally carried out in the presence of an organic solvent. 13 - Process according to claim 12 characterized in that the organic solvent is chosen from aliphatic, cycloaliphatic or aromatic hydrocarbons, halogenated or not; aliphatic, linear or cyclic ethers. 14 - Method according to one of claims 6 to 13 characterized in that the cyclization temperature is between 90 ° C and 200 ° C, and preferably between 95 ° C and 180 ° C 15 - Method according to one of claims 6 to 14 characterized in that the product of formula (I) is recovered from the liquid phase. 16 - Method according to one of claims 6 to 15 characterized in that the compound of formula (II) is obtained according to an O-esterification reaction between: - a salicylic type acid corresponding to formula (IV):

in said formula (IV): - R ₃ to R ₆ have the meaning given previously in one of claims 1 to 5, - and a carboxylic acid corresponding to formula (V):

in said formula (V): - Ri and R ₂ have the meaning given previously in one of claims 1 to 5. 17 - Use of the compounds of formula (I) described in one of claims 1 to 5, to liberate by hydrolysis of the compounds corresponding to the general formula (VI):

in said formula (VI): - Ri to R ₆ have the meaning given previously in one of claims 1 to 5. 18 - Use of the compound of formula (I) described in one of claims 1 to 5, in which R- | to R ₆ represent a hydrogen atom, to obtain acetylsalicylic acid by acid hydrolysis. 19 - Use according to one of claims 17 and 18 characterized in that the hydrolysis is carried out at an acidic pH, preferably less than 5 and more preferably between 1 and 4. 20 - Use of the compounds of formula (I) described in one of claims 1 to 5, for the preparation of compounds corresponding to the general formula (VII):

in said formula (VII): - Ri to R ₆ have the meaning given previously in one of claims 1 to 5. 21 - Use according to claim 20 characterized in that the hydrolysis is carried out at a neutral pH. 22 - Use of the compounds of formula (I) described in one of claims 1 to 5, for the preparation of compounds corresponding to the general formula (VIII):

in said formula (VIII): - Ri to R ₆ have the meaning given previously in one of claims 1 to 5, - R _has the meaning given in one of claims 1, 3 to 5, for Ri to R ₆ in formula (I) with regard to the hydrocarbon residue R. 23 - Use according to claim 22 characterized in that the compound of formula (VIII) is obtained by addition to the compound (I) of a carboxylic acid corresponding to the formula (IX): R _a - COOH (IX) in said formula (IX), R _a has the meaning given in claim 22. 24 - Use according to claim 23 characterized in that the carboxylic acid corresponds to formula (IX) in which R _a represents: - a linear or branched alkyl radical preferably having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms, a linear or branched alkenyl radical preferably having from 2 to 6 carbon atoms and even more preferably from 2 to 4 carbon atoms, - an acetoxymethylene radical, - a cyclohexyl radical, - a phenyl radical, - tolyl, xylyl radicals, - a benzyl radical, - a 2-acetoxyphenyl radical, - a 2-acetamidophenyl radical, - a 2- (3-benzoylphenyl) ethyl radical, - an alkoxy radical R ₇ -O- or thioether R ₇ -S- in which R ₇ represents a linear or branched alkyl radical having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms, an alkenyloxy radical , preferably, an allyloxy radical, 25 - Use according to one of claims 22 and 23 characterized in that the carboxylic acid corresponds to the formula (IXa): H_C - CH - COOH ³ I R b (IXa) in said formula (IXa): - R _b represents an optionally substituted phenyl radical; a chain of one or more of said phenyl radicals separated by a valential bond, a divalent hydrocarbon radical, a heteroatom or a functional group; or an optionally substituted naphthyl radical. 26 - Use according to claim 25 characterized in that the carboxylic acid corresponds to the formula (IXa) in which the radical R _b represents a phenyl or naphthyl radical which can carry a substituent or several substituents representing one of the following radicals: a linear or branched alkyl or alkenyl radical having from 1 to 12 carbon atoms, preferably a linear or branched alkyl radical having from 1 to 4 carbon atoms, a linear or branched alkoxy radical having from 1 to 12 carbon atoms, preferably a linear or branched alkoxy radical having from 1 to 4 carbon atoms, a linear or branched acyl group having from 2 to 8 carbon atoms, preferably an acetyl group or a benzoyl group, a linear or branched acyloxy group having 2 to 8 carbon atoms, preferably an acetoxy group, a linear or branched alkylamido group having from 1 to 8 carbon atoms, preferably an acetamido group. 27 - Use according to one of claims 23 to 26 characterized in that the carboxylic acid corresponding to formula (IX) is chosen from: salicylic acid, acetylsalicylic acid, 2- (3- benzoylphenyl) propionic, 2- (4-isobutylphenyl) propionic acid, 2- (6-methoxynaphtyl) propionic acid. 28 - Benzodioxinone derivatives corresponding to the formula (Villa):

(Villa) in the said formula (Villa): - Ri to R ₆ , have the meaning given previously in one of claims 1 to 5, - R _b represents an optionally substituted phenyl radical; a chain of one or more of said phenyl radicals separated by a valential bond, a divalent hydrocarbon radical, a heteroatom or a functional group; or an optionally substituted naphthyl radical. 29 - Derivatives according to claim 28 characterized in that they correspond to the formula (Villa) in which the radicals Ri to R ₆ represent a hydrogen atom 30 - Derivatives according to Claim 28, characterized in that they correspond to the formula (Villa) in which the radical R _b represents a phenyl or naphthyl radical which can carry a substituent or several substituents representing one of the groups following: a linear or branched alkyl or alkenyl radical having from 1 to 12 carbon atoms, preferably a linear or branched alkyl radical having from 1 to 4 carbon atoms, a linear or branched alkoxy radical having from 1 to 12 carbon atoms, preferably a linear or branched alkoxy radical having from 1 to 4 carbon atoms, a linear or branched acyl group having from 2 to 8 carbon atoms, preferably an acetyl group or a benzoyl group, a linear or branched acyloxy group having 2 to 8 carbon atoms, preferably an acetoxy group, a linear or branched alkylamido group having from 1 to 8 carbon atoms, preferably an acetamido group. 31 - Derivatives according to claim 28 characterized in that they correspond to the formula (Villa) in which: - Ri to R ₆ , represent a hydrogen atom, - R _b represents a phenyl or naphthyl radical optionally substituted or a chain of phenyl radicals separated by a carbonyl group.