WO1999042424A1

WO1999042424A1 - Method for preparing aromatic ketone compounds

Info

Publication number: WO1999042424A1
Application number: PCT/FR1999/000381
Authority: WO
Inventors: Jean-Roger Desmurs
Original assignee: Rhodia Chimie
Priority date: 1998-02-20
Filing date: 1999-02-19
Publication date: 1999-08-26
Also published as: FR2775284B1; FR2775284A1; AU2525399A

Abstract

The invention concerns a method for making aromatic ketone compounds and more particularly for preparing 1-[2'-methoxynaphth-6'-yl]but-2en-3-one which is an intermediate product useful for preparing 1-[2'-methoxynaphth-6'-yl]butan-3-one. The method for preparing an aromatic ketone compound from an aromatic compound bearing two halogen atoms and a donor group located in ortho position of one of the halogen atoms is characterised in that it consists in reacting said compound with an α-ketoolefin, in the presence of hydrogen and in the presence of a base and a catalyst comprising at least an element of group VIII of the periodic table of the elements, said element being complexed with at least an agent of co-ordination or a ligand.

Description

1

PROCESS FOR THE PREPARATION OF CETONIC COMPOUNDS

AROMATIC,

The present invention relates to a process for the preparation of aromatic ketone compounds.

The invention relates more particularly to the preparation of 1- [2'-methoxynapht-6'-yl] -but-2-en-3-one which is an intermediate product which can be used for the preparation of 1- [2'-methoxynapht- 6'-yl] -butan-3-one.

The 1- [2'-methoxynapht-6'-yl] -butan-3-one represented by the following formula:

is described in FR-A-2 407 907, as an anti-inflammatory and / or analgesic agent used for example for the treatment of rheumatism and arthritic affections.

There are many access routes to 1- [2'-methoxynapht-6'-yl] -butan-

3-one from 2-formyl-6-methoxynaphthalene and in particular a certain number involve a haloaromatic compound. 2-bromo-6-methoxynaphthalene or bromoneroline is a product which can be used as the raw material of choice in the synthesis of 2-formyl-6-methoxynaphthalene.

Thus, it was mentioned obtaining an 80% yield of 2-formyl-6-methoxynaphthalene, by reaction of ethyl orthoformate on the magnesium of bromoneroline [H. Rabbit, Chimia. Abstr JJ 141-3 (1964)].

Although the yield is quite good, this process suffers from several drawbacks. It comprises several stages, preparation of the magnesium, formylation and hydrolysis which complicates its implementation and it is difficult to transpose to the industrial scale. Another access route to aldehyde according to EP-A-415524 consists in reacting N-bromosuccinimide with 2-methyl-6-methoxynaphthalene, in the presence of a radical initiator (aza / sσbutyronitrile) leading to dibromation of the methyl group. The dibromed intermediate is subjected to hydrolysis which makes it possible to obtain on the order of 12% aldehyde. 2

This radical bromination method is not very industrial and does not give satisfactory reaction yields.

It is also described in IL-A-93474, a process for obtaining 2-formyl-

6-methoxynaphthalene, from 2-bromo-6-methoxynaphthalene, by hydroformylation catalyzed by a catalyst comprising a salt of formic acid, a palladium compound and a cation exchange resin

(Amberlyst® A26).

The yield obtained is 63% but the reaction time is long (20 h) and there is formation of a by-product, 2-methoxynapht-6-oic acid which must be eliminated.

The various processes described are not compatible with industrial operation.

Furthermore, all the known methods passing through 2-formyl-6-methoxynaphthalene remain long and costly. The object of the present invention is precisely to propose a method enabling these drawbacks to be overcome.

It has now been found, and this is what constitutes the object of the present invention, a process for the preparation of an aromatic ketone compound from an aromatic compound carrying two halogen atoms and an electro group. donor located in the ortho position of one of the halogen atoms, characterized in that it consists in reacting said compound with an α-ketoolefin, in the presence of hydrogen and in the presence of a base and of a catalyst comprising at least one element from group VIII of the periodic table, said element being complexed with at least one coordinating agent or ligand.

In accordance with the process of the invention, a process has been found which makes it possible to transform a 1,6-dihalo-2-methoxynaphthalene and more particularly 1, 6-dibromo-2-methoxynaphthalene, into 1 - [2'-methoxynapht-6 '- yl] -but-2-en-3-one and in 1- [2'-methoxynapht-6'-yl] -butan-3-one.

More precisely, one starts from an aromatic substrate carrying two halogen atoms and from an electron donor group located in the ortho position of one of the halogen atoms. It will be designated subsequently by haloaromatic compound. By halogen atom is meant more particularly a chlorine, bromine or fluorine atom.

In the following description of the present invention, the term "aromatic compound" means the classic notion of aromaticity as defined in the literature, in particular by Jerry MARCH, Advanced Organic Chemistry, 4 ^th edition, John Wiley and Sons, 1992, pp. 40 and following.

In the present text, the term “electro-donor group” is understood to mean a group as defined by H.C. BROWN in the work of Jerry MARCH - Advanced Organic Chemistry, chapter 9, pages 243 and 244 (1985).

The starting haloaromatic compound can be symbolized by the general formula (I):

^(R) n

(I) in which:

- A symbolizes the remainder of a cycle forming all or part of a carbocyclic or heterocyclic, aromatic, monocyclic or polycyclic system carrying at least one electron donor group R,

- X represents a halogen atom, - n represents the number of electron donor groups and is at least equal to 1,

- m represents the total number of halogen atoms and is at least equal to 2.

The invention applies in particular to aromatic compounds corresponding to formula (I) in which A is the residue of a cyclic compound, preferably having at least 4 atoms in the ring, preferably 5 or 6, optionally substituted , and representing at least one of the following cycles:. an aromatic, monocyclic or polycyclic carbocycle,. an aromatic, monocyclic or polycyclic heterocycle comprising at least one of the heteroatoms O, N and S,

It will be specified, without however limiting the scope of the invention, that the optionally substituted residue A represents, the rest:

- a monocyclic, carbocyclic, aromatic compound, such as, for example, benzene or toluene,

- a polycyclic, condensed, aromatic compound, such as, for example, naphthalene, - a polycyclic, non-condensed, carbocyclic, aromatic compound, such as, for example, \ 'o-, p- or tπ- phenoxybenzene,

- a polycyclic, condensed, carbocyclic, partially aromatic compound, such as, for example, tetralin,

- a polycyclic, non-condensed, carbocyclic, partially aromatic compound, such as, for example, o-, p- or m-cyclohexylbenzene, 4

a monocyclic, heterocyclic, aromatic compound, such as, for example, pyridine, furan, thiophene,

- a polycyclic, condensed, aromatic, partially heterocyclic compound, such as, for example, quinoline or indole, - a polycyclic, non-condensed, aromatic, partially heterocyclic compound, such as, for example, phenylpyridines , naphthylpyridines,

- a polycyclic, condensed, partially aromatic, partially heterocyclic compound, such as, for example, tetrahydroquinoline,

- A polycylic compound, non-condensed, partially aromatic, partially heterocyclic, such as, for example, \ 'o-, m- and p- cyclohexylpyridine.

In the process of the invention, an aromatic compound of formula (I) is preferably used in which A represents a benzene or naphthalene ring. The aromatic compound of formula (I) can carry one or more substituents.

The number of substituents present on the cycle depends on the carbon condensation of the cycle and on the presence or not of unsaturations on the cycle.

The maximum number of substituents likely to be carried by a cycle, is easily determined by a person skilled in the art.

In the present text, the term "several" is generally understood to mean less than 4 substituents on an aromatic ring.

The aromatic nucleus carries at least one electron donor group, but the invention does not exclude other substituents. Examples of substituents are given below, but this list is not limiting.

The remainder A can optionally carry one or more electron-donor groups which are represented in formula (I), by the symbol R and whose preferred meanings are defined below:

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

- the phenyl radical,

- the hydroxyl group,

- the alkoxy radicals R-j-O- in which R- | represents a linear or branched alkyl radical having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms or the phenyl radical,

- -N- (R2) 2 groups in which the identical or different R2 radicals represent a hydrogen atom, a linear or branched alkyl radical having 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms or a phenyl radical,

- -NH-CO-R2 groups in which the radical R2 has the meaning given above,

- the fluorine atom.

When n is greater than or equal to 2, two radicals R and the 2 successive atoms of the aromatic ring can be linked together by an alkylene, alkenylene or alkenylidene radical having from 2 to 4 carbon atoms to form a saturated, unsaturated or aromatic heterocycle having 5 to 7 carbon atoms. One or more carbon atoms can be replaced by another heteroatom, preferably oxygen. Thus, the radicals R can represent a methylenedioxy or ethylenedioxy radical.

Even more preferably, the compounds of formula (I) are chosen in which the radical (s) R represent a hydrogen atom, a hydroxyl group, an alkyl radical having from 1 to 4 carbon atoms, a methoxy radical, a methylene radical dioxy or ethylene dioxy.

The present invention applies very particularly to monocyclic or polycyclic haloaromatic compounds with rings which can form between them an orthocondensed system corresponding to the formula fl '):

P (r) in said formula (D, the symbols R, X, identical or different, have the meaning given above; p represents a number equal to 0 or 1; m 'and n', identical or different, are equal to 0 , 1 or 2.

When the haloaromatic compound is monocyclic (p = 0), the two halogen atoms are in position 2.4 relative to an electron donor group in position 1.

When the haloaromatic compound is bicyclic (p = 1), the two halogen atoms are in position 1, 6 and an electron donor group is in position 2.

Among the polycyclic haloaromatic compounds, the invention applies very particularly to the compounds of formula (a):

(R) 'n'

(X) m (X) m '(a) 6 in which:

- X represents a halogen atom, preferably bromine or chlorine,

- R represents an electro-donor group,

- n 'represents the number of electron-donor groups in the naphthalene system and is at least equal to 1,

- m 'represents the number of halogen atoms per cycle and is at least equal to 1.

The preferred compounds correspond to formula (a) in which at least one of the benzene rings of the naphthalene system carries at least one electron-donor group. Thus, n 'is equal to 1 or 2, preferably equal to 1.

The preferred compounds correspond to formula (a) in which m ′ is equal to 1 or 2, preferably equal to 1.

The haloaromatic compounds preferably used in the process of the invention are 2,4-dibromogaiacol, 2,4-dibromoan isolate, 2,4-dibromomethylenedioxybenzene, 1,6-dibromo-2-methoxynaphthalene.

In accordance with the process of the invention, the haloaromatic compound reacting preferably corresponding to formula (I) or (D or (a)) is reacted with an α-ketoolefin which can be symbolized by the general formula (II):

O

^R o (II) in which:

- R ₀ represents a hydrogen atom, a benzyloxycarbonyl group or an alkyloxycarbonyl group.

In formula (II), R ₀ can represent an alkyloxycarbonyl group, the alkyl part comprising from 1 to 12 carbon atoms, preferably from 1 to 4. The compound corresponding to formula (II) preferably used in the method of the invention is methylvinyl ketone or 3- [benzyloxycarbonyl] -but-3-en-2-one.

Intervened in the process of the invention is a catalyst which is preferably in the form of a complex.

As catalysts, one can use for the implementation of the process according to the invention, a finely divided noble metal, from group VIII of the periodic table of elements such as palladium, rhodium and iridium, or their salts. mineral or organic acids. The preferred metal is palladium. However, the other metals, although less active, may be of significant interest due to the high price of palladium.

Palladium derivatives are particularly suitable for the process of the invention.

As specific examples of palladium derivatives, mention may be made of carboxylates such as in particular acetates, propionates, butyrates or benzoates of palladium (II), palladous chloride.

It is also possible to use complexes of mineral or organic salts of palladium with phosphine.

In the latter case, this complex is generally produced in situ between the palladium derivative and the phosphine present. However, the said complex can also be prepared extemporaneously and introduced into the reaction medium. It is then possible to add or not an additional quantity of free phosphine. Said coordinating agents are advantageously hydrocarbon derivatives of the elements of column V.

Said hydrocarbon derivatives of the elements of column V derive from the valence III state of nitrogen such as amines, phosphorus such as phosphines, arsenic such as arsines and antimony such as stibines. They are advantageously chosen from the hydrocarbon derivatives of the elements of column VB preferably of period greater than the 2nd, phosphorus such as phosphines.

Advantageously, aliphatic, cycloaliphatic or arylaliphatic phosphines or mixed, aliphatic and / or cycloaliphatic and / or arylaliphatic and / or aromatic phosphines are used.

These phosphines are in particular those which correspond to the general formula (III):

R ₄

IR _j - P— R ₅ (III) in which the symbols R3, R ₄ and R5, identical or different, represent:

- an alkyl radical having from 1 to 12 carbon atoms,

- a cycloalkyl radical having 5 or 6 carbon atoms,

a cycloalkyl radical having 5 or 6 carbon atoms, substituted by one or more alkyl radicals having 1 to 4 carbon atoms, alkoxy having 1 or 4 carbon atoms,

- a phenylalkyl radical, the aliphatic part of which contains from 1 to 6 carbon atoms, 8

- one or two of the radicals R3, R4 and R5 represent a phenyl radical or a phenyl radical substituted by one or more alkyl radicals having 1 to 4 carbon atoms or alkoxy radicals having 1 to 4 carbon atoms. As examples of such phosphines, there may be mentioned, without limitation: tricyclohexylphosphine, trimethylphosphine, triethylphosphine, tri-π- butylphosphine, triisobutylphosphine, tri-tetf-butylphosphine, triphenylphosphine, tribenzylphosphine, dicycloosphine, dicyclophine dimethylphenylphosphine, diethylphenylphosphine, di-tet - butylphenylphosphine. Among the bases which can be used, mention should be made of tertiary amines and more particularly those corresponding to the general formula (IV)

N - (R6) ₃ (IV) in which:

- The radicals R ^, identical or different, represent hydrocarbon residues having from 1 to 20 carbon atoms, such as alkyl, cycloalkyl, aryl or heterocyclic radicals;

- 2 radicals R ₀ together form and with the nitrogen atom a heterocycle having 4 to 6 atoms.

More particularly: the symbols R 1 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 radicals R ₀ together form and with the nitrogen atom a piperidine or pyrrolidine cycle. Examples of such amines include triethylamine, tri-n-propylamine, tri-tr-butylamine, methyldibutylamine, methyldicyclohexylamine, ethyldiisopropylamine, N, N-diethylcyclohexylamine, dimethylamino-4 pyridine, N-methylpiperidine, N-ethylpiperidine, Nt> butylpiperidine, 1,2-dimethylpiperidine, N-methylpyrrolidine, 1,2-dimethylpyrrolidine.

However, the base can also be a strong mineral base or a relatively weak acid salt or a mixture of the above.

Carbonates, bicarbonates, phosphates and hydrogenophosphates, especially the latter, give good results. The HP0 ₄ ^" ion is particularly favorable. Mention may also be made, as anions which give good results, of the sulphate anions, the acetate anions and the trifluoroacetate anions. As for the various reagents and substrates, they are used in the quantities specified below.

The amount of keto-olefin used, expressed by the α-keto-olefin / haloaromatic compound molar ratio advantageously varies between 1 and 3 and is preferably chosen between 1, 2 and 1, 5.

The amount of catalyst expressed in moles of metal atoms or in moles of metal derivative per mole of haloaromatic compound of formula (I) or (D or (a)) can vary within wide limits.

Thus, it can be between 10 "5 and 10 ^* 1 mole / mole and preferably between 10 ^{" 4} and 10 ' ² mole / mole.

The amount of free phosphine and / or in the form of a complex with the catalyst is such that the phosphine / noble metal molar ratio of the catalyst is at least equal to 1.

The phosphine / noble metal ratio can reach values as high as 10,000.

A phosphine / noble metal ratio of between 1 and 1,000 is generally very suitable. It is preferably chosen between 1 and 100.

With regard to the base, the quantity used is specified in the case of a tertiary amine, but these values can be transposed by a person skilled in the art to any other base.

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

In addition, the concentration of tertiary amine in the medium must be at least 2 moles per liter for the duration of the reaction. There is no critical upper limit on the quantity of tertiary amine, which can therefore be used in a large excess relative to the quantity theoretically necessary for the neutralization of the hydracid formed.

To maintain the tertiary amine concentration, at least equal to the limit values indicated above, throughout the duration of the reaction, the quantity of amine engaged must be calculated so that at the end of the reaction, the concentration is at least equal to these values. It is also possible to add an additional amount of tertiary amine as the reaction proceeds, in order to compensate for the amount of amine consumed by the neutralization of the hydracid. The reaction temperature is advantageously between 50 and

250 ° C, and preferably between 100 and 200 ° C.

The reaction takes place under hydrogen pressure ranging from a pressure slightly higher than atmospheric pressure to a pressure of 10 several hundred bar. Advantageously, the hydrogen pressure varies from 0.1 to 10 MPa (1 to 100 bar) and preferably from 1 to 5 MPa (10 to 50 bar).

Olefin / H2 mixtures having different molar ratios of the two gases can be used. Generally, the olefin / H2 molar ratio varies between 0.1 and 10.

The process according to the invention is carried out in the liquid phase. An inert solvent can be used under the conditions of the reaction of the invention. Thus, it is possible to use saturated aliphatic or cycloaliphatic hydrocarbons such as hexane or cyclohexane, or aromatic hydrocarbons such as benzene, toluene, xylenes; esters such as methyl benzoate, methyl terephthalate, methyl adipate, dibutyl phthalate; polyol esters or ethers such as tetraethylene glycol diacetate; cyclic ethers such as tetrahydrofuran or dioxane.

The concentration of the haloaromatic compound of formula (I) or d ') or (a) used in the solvent can vary within very wide limits, until saturation under the operating conditions. Generally, it is not economically advantageous to use less than 5% by weight of haloaromatic compound per volume of solvent.

Generally, the concentration by weight of haloaromatic compound per volume of solvent is between 5% and 50% and preferably between 10% and 40%.

In practice, the process according to the invention can be implemented by introducing into an inert autoclave the haloaromatic compound of formula (I) or d ') or (a), the tertiary amine, the catalyst, the phosphine, the α-ketoolefin of formula (II) and the solvent, then, after the usual purges, by feeding the autoclave with an adequate pressure of hydrogen; the contents of the autoclave are then brought under stirring to the appropriate temperature until absorption ceases. The pressure in the autoclave can be kept constant for the duration of the reaction by virtue of a reserve of gaseous mixture, which supplies it at the selected pressure.

At the end of the reaction, the autoclave is cooled and degassed. The reaction mixture is recovered.

A simple washing of the organic phase with a dilute acid solution, preferably an aqueous solution of dilute hydrochloric acid (for example from 5 to 20% by weight), makes it possible to remove the traces of amine.

The ketone obtained can be purified, in particular by recrystallization from an aliphatic hydrocarbon, preferably hexane or heptane. 11

The process can be carried out batchwise or continuously as indicated above by recycling the catalyst, the phosphine and the tertiary amine.

In accordance with the process of the invention, essentially 1- [2'-methoxynapht-6'-yl] -but-2-en-3-one is obtained, which is an intermediate product which can be used for the preparation of 1 - [2 ' -methoxynapht-6'-yl] -butan-3-one.

The latter can be obtained in a conventional manner, such as for example by catalytic hydrogenation carried out in the presence of a palladium catalyst. One can refer for more details in particular to EP-A-0003643.

The examples which follow illustrate the invention without however limiting it. In the examples, the conversion rate and the yield obtained are defined. The conversion rate (TT) corresponds to the ratio between the number of substrates transformed and the number of moles of substrate engaged.

The yield (RR) corresponds to the ratio between the number of moles of product formed and the number of moles of substrate used.

Example 1 In this example, 1- [2'-methoxynapht-6'-yl] -but-2-en-3-one is prepared from 1, 6-dibromo-2-methoxynaphthalene.

The following are successively introduced into a 125 ml HB autoclave:

- 1, 6-dibromo-2-methoxynaphthalene (3.16 g - 10 mmol),

- triphenylphosphine (655.0 mg - 2.5 mmol), - methylvinyl ketone (1.05 g - 15 mmol),

- palladium diacetate (112.0 mg - 0.5 mmol),

- anhydrous toluene (20 ml)

- then triethylamine (2.02 g - 20 mmol) previously distilled and degassed.

The reactor is purged three times with 10 bar of hydrogen and then pressurized to 25 bar at 25 ° C.

The temperature is adjusted to 150 ° C and the back pressure to 40 bar; the progress of the reaction is followed by consumption of the gaseous mixture. After four hours of stirring, consumption has stabilized. The heating is stopped and the autoclave is cooled. The reaction mixture is filtered on a frit (porosity = 4), the triethylamine hydrobromide (3.62 g) is washed twice with 15 ml of toluene, dried under reduced pressure (15 mm of mercury) allowing 3 to be obtained, 23 g of a gray white solid. 12

The filtrate concentrated on a rotary evaporator, leads to a yellow liquid which solidifies slowly at room temperature.

The mass obtained is 2.35 g after drying under reduced pressure in a heated desiccator (10 mm of mercury, 50 ° C). The solid (crude reaction) is analyzed by high performance gradient liquid chromatography. The results obtained are as follows:

- ^π 1, 6-dibromo-2-methoxynaphthalene = 100%

- measured yields:

^RR 2-methoxynaphthalene = 3ι8% RRi - [2'-methoxynapht-6'-yl] -but-2-en-3-one = 55%

Example 2

The following are successively introduced into a 125 ml HB2 autoclave:

- 1, 6-dibromo-2-methoxynaphthalene (3.16 g - 10 mmol), - triphenylphosphine (131 mg - 0.5 mmol),

- methylvinylketone (1.05 g - 15 mmol),

- palladium diacetate (24 mg - 0.1 mmol),

- anhydrous toluene (20 ml)

- then triethylamine (2.22 g - 22 mmol) previously distilled and degassed. The reactor is purged three times with 10 bar of hydrogen and then pressurized to 25 bar at 25 ° C.

The temperature is adjusted to 150 ° C and the back pressure to 40 bar; the progress of the reaction is followed by consumption of the gaseous mixture.

After four hours of stirring, consumption has stabilized. The heating is stopped and the autoclave is cooled.

The reaction mixture is filtered on a frit (porosity = 4), the triethylamine hydrobromide (3.65 g) is washed twice with 15 ml of toluene, dried under reduced pressure (15 mm of mercury) allowing 3 to be obtained, 51 g of a gray white solid.

The filtrate concentrated on a rotary evaporator leaves a yellow liquid which solidifies slowly at room temperature.

The mass obtained is dried under reduced pressure in a heated desiccator (10 mm of mercury, 50 ° C).

The solid (crude reaction) is analyzed by high performance gradient liquid chromatography. The results obtained are as follows: " ^π 1, 6-dibromo-2-methoxynaphthalene = 100%

- measured yields:

^RR 1- [2'-methoxynapht-6'-yl] -but-2-en-3-one = 58% ^RR 1- [2'-methoxynapht-6'-yl] -butan-3-one = 5%

Claims

13

1 - Process for the preparation of an aromatic ketone compound from an aromatic compound carrying two halogen atoms and an electron donor group located in the ortho position of one of the halogen atoms characterized in that it consists in reacting said compound with an α-ketoolefin, in the presence of hydrogen and in the presence of a base and of a catalyst comprising at least one element from group VIII of the periodic table of elements, said element being complexed with at least one coordinating agent or ligand.

2 - Method according to claim 1 characterized in that the haloaromatic compound corresponds to the general formula (I):

(X) m (R) _r

(I) in which:

- m represents the total number of halogen atoms and is at least equal to 2.

3 - Method according to one of claims 1 and 2 characterized in that the haloaromatic compound corresponds to formula (I) in which A is the remainder of a cyclic compound, preferably having at least 4 atoms in the ring , preferably 5 or 6, optionally substituted.

4 - Method according to one of claims 1 to 3 characterized in that the haloaromatic compound corresponds to the general formula (I) in which A optionally substituted represents, the rest:

- a polycyclic, condensed, aromatic compound, such as, for example, naphthalene, - a polycyclic, non-condensed, carbocyclic, aromatic compound, such as, for example, o, p- or phenoxybenzene , 14

- a polycyclic, non-condensed, carbocyclic, partially aromatic compound, such as, for example, \ 'o-, p- or m-cyclohexylbenzene, - a monocyclic, heterocyclic, aromatic compound, such as, for example, pyridine, furan, thiophene,

- a polycyclic, condensed, aromatic, partially heterocyclic compound, such as, for example, quinoline or indole,

- a polycyclic, non-condensed, aromatic, partially heterocyclic compound, such as, for example, phenylpyridines, naphthyipyridines,

5 - Method according to one of claims 1 to 4 characterized in that the haloaromatic compound corresponds to the general formula (I) in which A optionally substituted represents a benzene or naphthalene ring.

6 - Method according to one of claims 1 to 5 characterized in that the haloaromatic compound corresponds to the general formula (I) in which the remainder A carries one or more electron-donor groups such as:

- the phenyl radical,

- the hydroxyl group,

- -N- (R2) 2 groups in which the identical or different R2 radicals 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 carbon atoms or a phenyl radical, the groups -NH-CO-R2 in which the radical R2 has the meaning given above,

- the fluorine atom. 15

7 - Process according to claim 6 characterized in that the haloaromatic compound corresponds to the general formula (I) in which, when n is greater than or equal to 2, two radicals R and the 2 successive atoms of the aromatic ring can be linked between them by an alkylene, alkenylene or alkenylidene radical having from 2 to 4 carbon atoms to form a saturated, unsaturated or aromatic heterocycle having from 5 to 7 carbon atoms: one or more carbon atoms which can be replaced by another heteroatom, preferably oxygen.

8 - Method according to one of claims 1 to 7 characterized in that the haloaromatic compound corresponds to the general formula (I) in which, the radical or radicals R represent a hydrogen atom, a hydroxyl group, an alkyl radical having from 1 to 4 carbon atoms, a methoxy radical, a methylene dioxy or ethylene dioxy radical.

9 - Method according to one of claims 1 to 8 characterized in that the haloaromatic compound corresponds to the general formula of):

d ') in said formula d'), the symbols R, X, identical or different, have the meaning given above; p represents a number equal to 0 or 1; m 'and n', identical or different, are equal to 0, 1 or 2.

10 - Process according to claim 1 characterized in that the haloaromatic compound is 1, 6-dibromo-2-methoxynaphthalene.

11 - Process according to claim 1 characterized in that the α-ketoolefin corresponds to the general formula (II):

O

^R o (II) in which:

- R ₀ represents a hydrogen atom, a benzyloxycarbonyl group or an alkyloxycarbonyl group. 16

12 - Process according to claim 11 characterized in that the α-ketoolefin corresponds to the general formula (II) is methylvinylketone or 3- [benzyloxycarbonyl] -but-3-en-2-one.

13 - Process according to claim 1 characterized in that the catalyst used is a finely divided noble metal, from group VIII of the periodic table of elements such as palladium, rhodium and iridium, or their mineral acid salts or organic.

14 - Process according to claim 13 characterized in that the catalyst used is chosen from palladium derivatives such as carboxylates, in particular acetates, propionates, butyrates or benzoates of palladium (II) and palladous chloride.

15 - Method according to one of claims 1 to 12 characterized in that the amount of α-ketoolefin used expressed by the molar ratio α- ketoolefin / haloaromatic compound advantageously varies between 1 and 3 and is preferably chosen between 1 , 2 and 1, 5.

16 - Method according to one of claims 13 and 14 characterized in that the amount of catalyst expressed in moles of metal atoms or in moles of metal derivative per mole of haloaromatic compound of formula (I) or (D or ( a) is between 10 ^" 5 and 10 ^~ 1 mole / mole and preferably between 10" ⁴ and 10 " ² mole / mole.

17 - Process according to claim 1 characterized in that the ligand is an aliphatic, cycloaliphatic or arylaliphatic phosphine or a mixed, aliphatic and / or cycloaliphatic and / or arylaliphatic and / or aromatic phosphine.

18 - Process according to claim 17 characterized in that the phosphine used corresponds to the general formula (III):

R ₄

I

R3- P— R ₅ (III) in which the symbols R3, R4 and R5, identical or different, represent:

- an alkyl radical having from 1 to 12 carbon atoms,

- a cycloalkyl radical having 5 or 6 carbon atoms, 17

- a phenylalkyl radical, the aliphatic part of which contains from 1 to 6 carbon atoms,

one or two of the radicals R3, R ₄ and R ₅ represent a phenyl radical or a phenyl radical substituted by one or more alkyl radicals having 1 to 4 carbon atoms or alkoxy radical having from 1 to 4 carbon atoms.

19 - Method according to one of claims 17 and 18 characterized in that the phosphine used is chosen from tricyclohexylphosphine, trimethylphosphine, triethylphosphine, tri-n-butylphosphine, triisobutylphosphine, tri-tet -butylphosphine, triphenylphosphine, tribenzylphosphine, dicyclohexylphenylphosphine, dimethylphenylphosphine, diethylphenylphosphine, di-tet - butylphenylphosphine.

20 - Method according to one of claims 17 to 19 characterized in that the amount of free phosphine and / or in the form of complex with the catalyst is such that the phosphine / noble metal molar ratio of the catalyst is between 1 and 10,000 and preferably between 1 and 1,000 and even more preferably between 1 and 100.

21 - Process according to claim 1 characterized in that the base used is a tertiary amine.

22 - Process according to claim 21 characterized in that the tertiary amine used is an amine of general formula (IV):

N - (R6) ₃ (IV) in which:

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

23 - Process according to claim 22 characterized in that the tertiary amine used is an amine of general formula (IV) in which: 18

the radicals R ₆ 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 radicals R ₆ together form and with the nitrogen atom a piperidine or pyrrolidine cycle.

24 - Method according to one of claims 22 and 23 characterized in that the tertiary amine used is triethylamine, tri-t7-propylamine, tri-n-butylamine, methyldibutylamine, methyldicyclohexylamine, ethyldiisopropylamine, N, N-diethylcyclohexylamine, 4-dimethylamino pyridine, N-methylpiperidine, N-ethylpiperidine, Nn-butylpiperidine, 1, 2-dimethylpiperidine, N-methylpyrrolidine, 1, 2-dimethylpyrrolidine.

25 - Method according to one of claims 22 to 24 characterized in that the amount of tertiary amine is sufficient to neutralize the hydracid released by the reaction, preferably, at least 2 moles per liter for the duration of the reaction.

26 - Method according to one of claims 1 to 25 characterized in that the reaction temperature is between 50 and 250 ° C, and preferably between

100 and 200 ° C.

27 - Method according to one of claims 1 to 26 characterized in that the hydrogen pressure varies from 0.1 to 10 MPa (1 to 100 bar) and preferably from 1 to 5 MPa (10 to 50 bar) .

28 - Method according to one of claims 1 to 27 characterized in that it is carried out in an inert solvent under the conditions of the hydrocarbonylation reaction chosen from saturated aliphatic or cycloaliphatic hydrocarbons such as hexane or cyclohexane , or aromatics such as benzene, toluene, xylenes; esters such as methyl benzoate, methyl terephthalate, methyl adipate, dibutyl phthalate; polyol esters or ethers such as tetraethylene glycol diacetate; cyclic ethers such as tetrahydrofuran or dioxane.

29 - Method according to one of claims 1 to 28 characterized in that the concentration of the haloaromatic compound used expressed by weight 19 of said compound per volume of solvent, is between 5% and 50%, preferably between 10% and 40%.

30 - Use of 1- [2'-methoxynapht-6'-yl] -but-2-en-3-one obtained according to the process described in one of claims 1 to 29 as an intermediate for manufacturing 1- [2'-methoxynapht-6'-yl] -butan-3-one.