FR2669924A1 - Process for the preparation of polyalkoxylated aromatic compounds - Google Patents

Abstract

The subject of the present invention is a process for the preparation of polyalkoxylated aromatic compounds from aromatic compounds carrying at least one halogen atom and at least one hydroxyl group. More precisely, the invention is a process for the preparation of polyalkoxylated aromatic compounds, characterised in that the following stages are carried out: 1 - An aromatic compound carrying at least one halogen atom and at least one hydroxyl group is reacted with an alkali metal or alkaline-earth metal alkoxide in the presence of a catalyst which is copper and/or a copper compound and of a cocatalyst chosen from organic carbonates, organometallic mixed carbonates, carbon dioxide or compounds capable of forming carbon dioxide. 2 - The hydroxyl group(s) of the product obtained above after alkoxylation is or are O-alkylated by directly adding, to the organic reaction mixture, an alkylating agent chosen from lower alkyl halides, dialkyl sulphates or dialkyl carbonates. The invention thus makes it possible to successively carry out the alkoxylation reaction and the O-alkylation reaction.

Description

PROCESS FOR THE PREPARATION OF POLYALKOXYLATED AROMATIC COMPOUNDS
The subject of the present invention is a process for the preparation of polyalkoxylated aromatic compounds from aromatic compounds carrying at least one halogen atom and at least one hydroxyl group and, more particularly, 3,4-dialkoxy benzaldehyde. and 3,4,5-trialkoxy benzaldehydes.

 The invention relates more particularly to the preparation of 3,4,5,5-trimethoxy benzaldehyde from 5-bromo-4-hydroxy-3-methoxy benzaldehyde commonly called "5-bromo-vanillin" and 3,4-dimethoxy benzaldehyde called "veratraldehyde" .

 A conventional route for preparing 3,4,5,5-trimethoxy benzaldehyde from 5-bromo-vanillin consists in hydrolyzing the bromine atom using an aqueous sodium hydroxide solution and in the presence of copper.

 After isolation of 4,5-dihydroxy-3-methoxy-benzaldehyde (or 5-hydroxy-vanillin), this leads to 3,4,5-trimethoxy-benzaldehyde after methylation using dimethyl sulphate or methyl chloride.

 Thus, patent FR-A 2 177 693 describes the methylation of hydroxy-5 vanillin by dimethyl sulfate, in the presence of an alkali metal carbonate.

 Hydroxy-5 vanillin is itself obtained by hydrolysis of bromo-5 vanillin and is then extracted, in particular, with toluene for 47 hours, recrystallized, washed and dried.

The isolation phase of 5-hydroxy vanillin is therefore long and costly.

In addition, the catalyst cannot be recovered and recycled.

 Before avoiding the intermediate separation of 5-hydroxy vanillin, there has been proposed according to patent FR-A 2 609 984, a process for the preparation of 4,5-dialkoxy-3-methoxy-benzaldehyde from 5-bromo vanillin which consists in carrying out successively, the hydrolysis of 5-bromo vanillin to 5-hydroxy vanillin, with an alkali metal hydroxide, in water and in the presence of a copper catalyst, then the etherification of 5-hydroxy vanillin using a lower alkyl halide, in an aqueous medium and maintaining the pH between 6 and 12, optionally in the presence of a catalyst.

 A major drawback of this process is that there is a formation, on hydrolysis of the bromo-5 vanillin, of a relatively large amount of vanillin approximately 10 to 15% which, after the etherification reaction, leads to the veratric aldehyde (3,4-dimethoxy benzaldehyde).

 Veratric aldehyde can be separated from 3,4,5 trimethoxy benzaldehyde by distillation. However, the recovery of 3,4,5,5-trimethoxy benzaldehyde from the reaction medium is made more complicated due to the presence of veratric aldehyde.

 The present invention provides a general process for the preparation of polyalkoxylated aromatic compounds which is suitable, inter alia, quite well in the case of the preparation of 3,4,5-trimethoxy, benzaldehyde, a process which makes it possible to avoid the abovementioned drawbacks.

The subject of the invention is therefore a process for the preparation of polyalkoxylated aromatic compounds of general formula (I)
(R1-O) rrT Ro OR) n (I) in which
- m and n are whole numbers greater than or equal to I with, of
preferably, m + n between 2 and 6,
- Ro represents an aromatic cyclic radical having at least 5 atoms
in the cycle, possibly substituted, and representing at least
one of the following radicals
. an aromatic, monocyclic or polycyclic carbocyclic radical,
an aromatic, monocyclic or polycyclic heterocyclic radical
comprising at least one of the heteroatoms O, N and S,
- R represents a hydrocarbon radical having from 1 to 12 atoms of
carbon, which can be an acyclic, saturated or aliphatic radical
unsaturated, linear or branched; a saturated cycloaliphatic radical
or unsaturated, monocyclic or polycyclic; a radical
cycloaliphatic- or arylaliphatic, saturated or unsaturated, linear
or branched,
~ R1 is a linear or branched alkyl radical having from 1 to 6 atoms
carbon, process characterized in that the following steps are carried out successively 1 - An aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponding to the general formula (II) is reacted ) ::
(HO + m- Ro - + X) n (II) in which
- m and n are whole numbers greater than or equal to 1 with, of
preferably, m + n between 2 and 6,
- X represents an iodine, bromine or chlorine atom,
- Ro represents an aromatic cyclic radical having at least 5 atoms
in the cycles, possibly substituted, and representing at least
one of the following radicals
. an aromatic, monocyclic or polycyclic carbocyclic radical,
. an aromatic, monocyclic or polycyclic heterocyclic radical
comprising at least one of the heteroatoms O, N and S, - and an alkali or alkaline earth metal alcoholate of general formula (III)
MW + [O - R] w ~ (III) in which
- M represents an alkali or alkaline earth metal,
- w represents the valence of the alkali or alkaline-earth metal,
- R represents a hydrocarbon radical having from 1 to 12 atoms of
carbon, which can be an acyclic, saturated aliphatic radical
or unsaturated, linear or branched; a cycloaliphatic radical,
saturated or unsaturated, monocyclic or polycyclic; a radical
cycioaliphatic- or arylaliphatic, saturated or unsaturated, linear
area or branched, in the presence of a copper catalyst which is copper and / or a copper compound and an effective amount of a co-catalyst chosen from organic carbonates, mixed organometallic carbonates, dioxide of carbon or the compounds capable of forming carbon dioxide, 20 - O-alkylation of the hydroxyl group (s) of the product obtained above is carried out after alkoxylation, by directly adding an alkylating agent chosen from among the organic reaction medium lower alkyl halides, dialkylsulfates, dialkylcarbonates.

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, 3rd edition, John Wiley and Sons, 1985 P. 37 and following.

 The term "polyalkoxylated aromatic compound" means an aromatic compound carrying at least two alkoxy radicals.

 In the present text, alkoxy radicals denote, in a simplified manner, radicals of the RO- type in which R represents both a saturated or unsaturated aliphatic radical as well as a saturated or unsaturated cycloaliphatic radical and an aliphatic radical carrying a saturated, unsaturated or aromatic carbocycle.

 In all cases, the substitution of the halogen atom by the radical R-O- is hereinafter referred to as "alkoxylation reaction", whatever the nature of the radical R.

 The term "alcoholate" is used in this text generically and also denotes metallic aralkoxides.

 The invention applies more particularly to aromatic compounds carrying at least one halogen atom and at least one hydroxyl group of formula (II) in which the radical Ro symbolizes 10 - an aromatic, monocyclic or polycyclic carbocyclic radical .

By "polycyclic carbocyclic radical" is meant
a radical consisting of at least 2 aromatic carbocycles and
forming between them ortho or ortho and pericondensed systems,
a radical consisting of at least 2 carbocycles of which only one
of them is aromatic and forming between them ortho systems
or ortho and pericondensed.

- an aromatic, monocyclic or polycyclic heterocyclic radical.

By "polycyclic heterocyclic radical", we define
a radical consisting of at least 2 heterocyclics containing at
at least one heteroatom in each cycle, at least one of which
cycles is aromatic and forming between them ortho systems or
ortho and pericondensed,
a radical consisting of at least one hydrocarbon ring and at
at least one heterocycle of which at least one of the cycles is aromatic
and forming between them ortho or ortho and pericondensed systems.

30 - a divalent radical constituted by a chain of groups, as defined in paragraphs 1 and / or 2 linked together
by a valential link,
by an alkylene or alkylidene radical having from 1 to 4 atoms of
carbon, preferably a methylene or isopropylidene radical,
by one of the following groups
+, CO
-S-, -SO-, -SO2-

in these formulas, R2 representing a hydrogen atom or a radical
alkyl having from 1 to 4 carbon atoms, a cyclohexyl or phenyl radical
Examples of radicals listed under 10 to 30 include 10 - phenylene, tolylene, xylylene, naphthylene, 20 - pyrrolidinediyl, imidazolidinediyl, piperidinediyl, furannediyl, pyrrolediyl, thiofenediyl, isoxazolediyl, furazannediyl, isidiazol , pyridinediyle, pyridazinediyle, pyrimidinediyle; naphthyridine-1,8 diyl, quinolinediyl, indolediyl, benzofuranediyl radicals.

- the biphenylene, methylene-1,1 'biphenylene, isopropylidene-1,1' biphenylene, oxy-1, 1 'biphenylene, imino-1, 1' biphenylene radicals.

 The preferred compounds are those corresponding to formula (II) in which the radical Ro represents a benzene nucleus.

 As mentioned previously, the radical Ro which is an aromatic radical carrying at least one hydroxyl group and at least one halogen atom, may also be carrying one or more other substituents which may be another hydroxyl group or another halogen atom or of any other nature as long as they do not interfere with the reaction. Generally, by several substituents, less than four substituents are defined on an aromatic ring.

As examples of substituents given by way of illustration and without limitation, one can mention one of the following groups or functions
. a radical of formula -R3-OH in which the radical R3 represents
a valential bond or a divalent, linear or
branched, saturated or unsaturated having from 1 to 4 carbon atoms, such as
for example, methylene, ethylene, propylene, isopropylene,
isopropylidene,
. an alkyl radical, linear or branched, having from I to 6 atoms of
carbon, preferably from 1 to 4 carbon atoms, such as methyl,
ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,
tert-butyl,
a linear or branched alkenyl radical having from 2 to 6 carbon atoms
bone, preferably from 2 to 4 carbon atoms, such as vinyl,
allyle,
. a linear or branched alkoxy radical having from 1 to 6 atoms of
carbon, preferably from 1 to 4 carbon atoms such as the radicals
methoxy, ethoxy, propoxy, isopropoxy, butoxy,
. a -CHO group,
. an acyl group having from 2 to 6 carbon atoms,
. a radical of formula -R3-COOH, R3 having the given meaning
previously,
. a radical of formula -R3-COOR4 in which R3 has the meaning
given above and R4 represents an alkyl radical, linear or
branched, having from 1 to 6 carbon atoms,
. a radical of formula -R3-NH2 with an N-protected NH2 group, R3 having
the meaning given above,
. a radical of formula -R3-N (R'4) in which R3 has the meaning
given previously and the identical or different radicals R'4 represent
feel a hydrogen atom or an alkyl radical, linear or branched,
having from 1 to 6 carbon atoms,
. a radical of formula -R3-CO-N (R'4), R3 and R'4 having the meaning
previously given,
. a radical of formula -R3-Z in which R3 has the meaning
given above and Z symbolizes a halogen atom X, such that
previously defined, a fluorine atom or a CF3 group.

 If there are substituents on the aromatic cycle, care should be taken to ensure that the latter does not interfere with the desired product.

 Likewise, during the presence of a primary amine function, it may be necessary to N-protect it with a protective group, for example acyl, and more especially acetyl.

 If the ring carries a group of the type -R3-COOR4, the group R4 will be exchanged by the group R coming from the alkali metal alkoxide or alkaline-earth metal, if R4 and R are alkyl groups of different nature.

 If the cycle carries an acid function of the type -R3-COOH, the group will be salified and will therefore cause additional consumption of the alcoholate used.

 When the aromatic ring carries a side aliphatic chain with the presence of a halogen atom X, this can also be substituted by the group RO- originating from the alkali metal alkali or alkaline earth metal alcoholate and there will therefore have to be taken into account when determining the quantities of reagents to be used.

As examples of substituents cited by way of preference and without limitation, there may be mentioned
- one or more alkyl radicals having from 1 to 4 carbon atoms,
- one or more alkoxy radicals having from 1 to 4 carbon atoms,
- one or more hydroxyl radicals.

As examples of aromatic compounds carrying at least one halogen atom and at least one hydroxyl group corresponding to the general formula (II), there may be mentioned more particularly
- 2-bromo phenol
- 3-bromo phenol
- 4-bromo phenol
- bromo-1 naphthol-2
- bromo-6 naphthol-2
- 2-bromo-4-methylphenol
- 4-bromo-2,6-dimethylphenol
- 4-bromo-3,5 dimethyl phenol
- 2,6-dibromo-4-methylphenol
- bromo-2-p-cresol
- 2-bromo-4 chloro-phenol
- 4-bromo-2 chloro-phenol
- 4-bromo-chloro-6-o-cresol
- bromofluorophenols
- bromo bis-phenols
- isopropylidene-4,4 'bis-phenols bromo
The alkali or alkaline earth metal alcoholate which is involved in the process of the invention corresponds to formula (III) in which R represents 10 - an alkyl, alkenyl, alkadienyl, linear or branched alkynyl radical having, preferably, less of 6 carbon atoms, 20 - a cycloalkyl or cycloalkenyl radical preferably having from 5 to 7 carbon atoms and mention may in particular be made of the cyclohexyl radical, 30 - an acyclic, saturated or unsaturated, linear or acyclic aliphatic radical branched as specified under 10, carrying a cyclic substituent. By cycle is meant a saturated, unsaturated or aromatic carbocyclic cycle.

As an example, mention may be made of the benzyl radical.

 Among the above-mentioned alcoholates, preferably used in the process of the invention, the alkali metal alcoholates and more particularly the sodium or potassium alcoholates of the primary or secondary alkanols having 1 to 4 carbon atoms are particularly suitable.

 The most frequently used are sodium methylate and sodium ethylate.

dans laquelle
- R', R'1, R6 identiques ou différents représentent un radical alkyle,
linéaire ou ramifié, ayant de 1 à 4 atomes de carbone,
- R6 pouvant représenter également un atome d'hydrogène, un radical
alkoxy, linéaire ou ramifié ayant de 1 à 4 atomes de carbone.A preferred embodiment of the invention resides in a process for the preparation of a polyalkoxylated aromatic compound falling within the definition of formula (I) and more particularly corresponding to the general formula (Ia)

in which
- R ', R'1, R6, identical or different, represent an alkyl radical,
linear or branched, having from 1 to 4 carbon atoms,
- R6 can also represent a hydrogen atom, a radical
alkoxy, linear or branched having from 1 to 4 carbon atoms.

dans laquelle
- X représente un atome d'iode, de brome ou de chlore,
- R7 représente un atome d'hydrogène, un atome d'iode, de brome, un
atome de chlore, un radical alkyle ayant de 1 à 4 atomes de carbone,
un radical alkoxy ayant de 1 à 4 atomes de carbone, un radical
hydroxyle,
dans ladite formule (IIa), le radical hydroxyle pouvant être en
position ortho-, méta- ou para- de la fonction aldéhyde, avec un alcoolate de métal alcalin ou alcalino-terreux ayant de 1 à 4 atomes de carbone, en présence d'un catalyseur au cuivre qui est le cuivre et/ou un composé du cuivre et d'une quantité efficace d'un co-catalyseur choisi parmi les carbonates organiques, les carbonates mixtes organo-métalliques, le dioxyde de carbone ou les composés susceptibles de former du dioxyde de carbone, 20 - On réalise la O-alkylation du ou des groupes hydroxyle du produit obtenu précédemment après alkoxylation, par addition directement dans le milieu réactionnel organique d'un agent d'alkylation apportant le reste alkyle R'1 ayant de 1 à 4 atomes de carbone.The process according to the invention, for the preparation of a polyalkoxylated aromatic compound corresponding to the general formula (Ia) comprises the following steps 10 - An aromatic compound falling within the general definition of the formula (II) is reacted which is a halogeno hydroxy benzaldehyde corresponding to the general formula (IIa):

in which
- X represents an iodine, bromine or chlorine atom,
- R7 represents a hydrogen atom, an iodine, bromine atom, a
chlorine atom, an alkyl radical having from 1 to 4 carbon atoms,
an alkoxy radical having from 1 to 4 carbon atoms, a radical
hydroxyl,
in said formula (IIa), the hydroxyl radical possibly being
ortho-, meta- or para- position of the aldehyde function, with an alkali or alkaline earth metal alcoholate having from 1 to 4 carbon atoms, in the presence of a copper catalyst which is copper and / or a compound copper and an effective amount of a co-catalyst chosen from organic carbonates, mixed organometallic carbonates, carbon dioxide or compounds capable of forming carbon dioxide, 20 - O-alkylation is carried out of the hydroxyl group (s) of the product obtained previously after alkoxylation, by adding directly to the organic reaction medium an alkylating agent providing the alkyl residue R'1 having from 1 to 4 carbon atoms.

As examples of substrates preferably used, there may be mentioned more particularly the compounds corresponding to the general formula (IIa) in which. GROUP I
the OH radical is in the para position with respect to the CHO function,
~ the halogen atom X is in the ortho position relative to the radical
OH,
- the radical R7 is in the ortho position relative to the radical OH.

. GROUP IT
the OH radical is in the ortho position with respect to the CHO function,
- the halogen atom X is in the para position relative to the OH radical,
- the radical R7 is in the ortho position relative to the radical OH.

. GROUP III
the OH radical is in the ortho position with respect to the CHO function,
- the halogen atom X is in the ortho position relative to the radical
OH,
- the radical R7 is in the para position relative to the radical OH,. GROUP IV
the OH radical is in the meta position with respect to the CHO function,
- the halogen atom X is in the ortho position relative to the radical
OH,
- the radical R7 is in the para position relative to the radical OH.

. GROUP V
the OH radical is in the meta position with respect to the CHO function,
- the halogen atom X is in the para position relative to the OH radical,
- the radical R7 is in the ortho position relative to the radical OH.

The compounds of formula (IIa) preferably used correspond more precisely to the following formulas

dans lesquelles
- X et R7 ont les significations données précédemment.

in which
- X and R7 have the meanings given above.

 In the process of the invention, very preferably, a halo hydroxy benzaldehyde corresponding to the general formula (rIal) in which X is a bromine atom and R7 symbolizes a methoxy or ethoxy radical.

As examples of halo hydroxy benzaldehydes corresponding to formula (IIa) which serve as starting substrates in the present process, there may be mentioned more precisely
- 3-bromo-4-hydroxy benzaldehyde,
- iodo-3 hydroxy-4 benzaldehyde
- 3,5-dibromo-4-hydroxy benzaldehyde
- 3,5-diiodo-4-hydroxy benzaldehyde
- 5-bromo-3-methoxy-4-hydroxy benzaldehyde
- 5-iodo-3-methoxy-4-hydroxy-benzaldehyde
- 5-bromo-3-ethoxy-4-hydroxy benzaldehyde
- iodo-5 ethoxy-3 hydroxy-4 benzaldehyde
- 3-bromo-4,5 dihydroxy benzaldehyde
- iodo-3 dihydroxy-4,5 benzaldehyde
- 2,5-bromo-2,5-dihydroxy benzaldehyde
- iodo-3 dihydroxy-2,5 benzaldehyde
- 2-bromo-4-hydroxy benzaldehyde
- 2-hydroxy-4-iodo benzaldehyde
- 4-bromo-3-hydroxy benzaldehyde
- iodo-4 hydroxy-3 benzaldehyde
- 3-bromo-2-hydroxy benzaldehyde
- iodo-3 hydroxy-2 benzaldehyde
- 5-bromo-2-hydroxy benzaldehyde
- 5-iodo-2-hydroxy benzaldehyde
In a preferred embodiment of the process of the invention for the preparation of polyalkoxylated aromatic compounds of formula (Ia), the alkali or alkaline earth metal alcoholate of formula (III) is preferably a sodium alcoholate or potassium of a primary or secondary alkanol having from 1 to 4 carbon atoms and, preferably, sodium methylate or ethylate.

 In accordance with the process of the invention, the aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponding to formula (II) is reacted with an alkali or alkaline earth metal alcoholate of formula (III), in the presence of a copper catalyst and of a co-catalyst chosen from organic carbonates, mixed organo-metallic carbonates, carbon dioxide or the compounds capable of forming carbon dioxide.

 The copper compounds serving as catalysts are known. These are generally all the organic or inorganic compounds of copper I or copper II.

 Copper metal can be used, but its action is slower because it must first transform into copper I or copper II.

 As non-limiting examples, copper compounds, cuprous chloride, cupric chloride, basic copper carbonate II, cuprous nitrate, cupric nitrate, cupric sulfate, cupric acetate, cupric trifluoromethylsulfonate, etc. cupric hydroxide, copper picolinate II, copper methylate I, copper methylate II, copper chelate II of 8-quinoline, copper compounds of formula ClCuOCH3, Cu2 (OCH3) 2 (acac) 2 .

The organic carbonates and the organometallic mixed carbonates used in the invention are more particularly the carbonates of general formula (IV):
[R8 - O - CO - O -) p - Rg (IV) in which - R8 represents
. an alkyl radical, linear or branched, having 1 to 6 atoms of
carbon,
. a cycloalkyl radical having 5 to 6 carbon atoms,
. a cycloalkyl radical, having 5 or 6 carbon atoms substituted by
one or two alkyl radicals having 1 to 12 carbon atoms,
. an aryl radical having from 6 to 12 carbon atoms,
. an aryl radical substituted by 1 or 2 alkyl radicals having 1 to 12
carbon atoms;
. a radical R10 - O - CO - in which R10 represents a radical
alkyl, linear or branched having 1 to 6 carbon atoms, one
aryl radical having from 6 to 12 carbon atoms, a radical
cycloalkyl having 5 or 6 carbon atoms - Rg represents
. an alkyl radical, linear or branched, having 1 to 6 atoms of
carbon,
. a cycloalkyl radical having 5 or 6 carbon atoms,
. a cycloalkyl radical having 5 or 6 carbon atoms substituted by
one or two alkyl radicals having 1 to 12 carbon atoms,
. an aryl radical having 6 to 12 carbon atoms,
. an aryl radical substituted by 1 or 2 alkyl radicals having 1 to
12 carbon atoms,
an alkali or alkaline earth metal, preferably sodium or potassium - p = 1 or p = 2 when Rg represents an alkaline earth metal; - R8 and Rg can together form an alkylene radical having 2 to 6
carbon atoms.

Preferably, the organic carbonates and the mixed organo-metallic carbonates are the carbonates of general formula (IVa)
R8 - O - CO - O - Rg (IVa) in which - R8 represents
. an alkyl radical, linear or branched, having 1 to 6 atoms of
carbon,
. a cycloalkyl radical having 5 to 6 carbon atoms,
. a cycloalkyl radical, having 5 or 6 carbon atoms substituted by
one or two alkyl radicals having 1 to 4 carbon atoms,
. a phenyl radical,
. a phenyl radical substituted by 1 or 2 alkyl radicals having 1 to 4
carbon atoms,
. a radical R10 - O - CO - in which R10 represents a radical
alkyl, linear or branched having 1 to 6 carbon atoms, one
phenyl radical, a cycloalkyl radical having 5 or 6 atoms of
carbon - Rg represents
an alkyl radical, linear or branched, having 1 to 6 atoms of
carbon,
. a cycloalkyl radical having 5 or 6 carbon atoms,
. a cycloalkyl radical having 5 or 6 carbon atoms substituted by
one or two alkyl radicals having 1 to 4 carbon atoms,
. a phenyl radical,
. a phenyl radical substituted by one or two alkyl radicals having 1 to
4 carbon atoms,
. a sodium or potassium atom, - R8 and Rg can together form an alkylene radical having 2 to 6 atoms
of carbon.

 As examples of organic or organometallic carbonates, mention may be made of: ditertiobutyl carbonate, diethyl carbonate, dimethyl carbonate, ethylene carbonate, propylene carbonate, phenyl and tertiobutyl carbonate, carbonate tert-butyl and sodium, ditertiobutyl dicarbonate.

 As regards carbon dioxide, it can be used in solution in the reaction medium, by circulation therein.

As examples of compounds capable of forming carbon dioxide in the reaction medium, there may be mentioned - the a (or ss) ketoesters and the a (or ss) ketoacids - amine carbonates, ureas and carbodiimides; - dicarboxylic acids such as malonic acid, α-cyano acids
or a-nitro-carboxylic; - pyunsaturated carboxylic acids.

 In accordance with the process of the invention, the aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponding to formula (II) is subjected to an alkoxylation reaction by reacting said compound with the alkali or alkaline earth metal alcoholate, in the presence of a copper catalyst and a co-catalyst of the CO2 or carbonate type, then subjecting the aromatic compound thus obtained carrying at least one alkoxy group and at least one hydroxyl group, to an O-alkylation reaction by reacting it with an alkylating agent.

According to the present invention, for example, a 3,4-dialkoxy and a 3,4,5-trialkoxy-benzaldehyde are prepared from a 3-hydroxy-4-benzaldehyde and a 4-hydroxy-4-halo respectively 3-alkoxy benzaldehyde of formula (IIa) by subjecting the starting substrates, first to an alkoxylation reaction and then to a reaction of
O-alkylation
In the case where the compound of formula (II) has one or more of a halogen atom and one or more of a hydroxyl group, a mono- or poly-alkoxylation will be carried out respectively in the first step or a mono- or poly-O-alkylation in the second step, the only condition being only to adapt the amounts of reactants according to the number of groups to be substituted.

 The first step of the process of the invention therefore resides in the alkoxylation of the aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponding to the formula (II).

 In the case where said compound corresponds more particularly to the general formula (IIa), that is to say when it also carries an aldehyde function, it is reacted according to the invention with an alkali metal alcoholate or alkaline earth, in the presence of a copper catalyst and a co-catalyst as mentioned above, which thus makes it possible to conduct the alkoxylation reaction without it being necessary to protect the aldehyde function, in the form of acetal . Such a process is the subject of patent applications FR 89/13370 and EP 90402786.9 in the name of the applicant.

 According to the process of the invention, the alkoxylation of the aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponding to formula (II) is carried out in an organic medium consisting, most often, by the alkanol corresponding to the alkali or alkaline earth metal alcoholate used.

 Methanol or ethanol is preferably chosen as solvent.

 When the alkali or alkaline earth metal alcoholate has a carbon condensation greater than 4 carbon atoms, it is desirable to use a solvent inert with respect to the reaction and to choose, preferably, a solvent polar aprotic.

 As examples of polar aprotic solvents suitable for carrying out the process of the invention, there may be mentioned, more particularly ethers and, more precisely, dimethyl ethers derived from ethylene oxide or propylene oxide such as ethylene glycol dimethyl ether (or 1,2-dimethoxy ethane), diethylene glycol dimethyl ether (or 1,5-dimethoxy-3-oxa-pentane), 1,8-dimethoxy-3,6-dioxa-octane, dimethoxy -1.11 trioxa-3,6,9 undecane, dimethoxy-1,2 methyl-1 ethane, dimethoxy-1,5 dimethyl-1,4 oxa-3 pentane, dimethoxy-1,7 dimethyl-1, 4 dioxa-3,6 octane.

 Several solvents can also be used.

 Among all the aforementioned solvents, ethylene glycol dimethyl ether and diethylene glycol dimethyl ether are preferred.

 The concentration of the compound of formula (II) expressed by weight of said compound (II) relative to the total weight of compound (II) + solvent is generally from 3 to 40% and, preferably, from 10 to 30%.

 The amount of alkali or alkaline earth metal alcoholate used is equal to or greater than the stoichiometric amount necessary, on the one hand to transform the halogen atom (s) into alkoxy groups and on the other hand to transform the compound of formula (II) as an alkali or alkaline earth metal phenate in the case where said compound has one or more hydroxyl radicals. The salification of the OH group or groups is therefore carried out.

 Generally, the alkali or alkaline earth metal alcoholate is used in an amount corresponding to the stoichiometric amount necessary to salify the hydroxyl groups plus an equal amount from 1 to 5 times, and preferably from 1 to 3 times, the stoichiometric quantity necessary to transform the halogen atom (s) into alkoxy groups.

 The concentration of alkali or alkaline earth metal alcoholate is advantageously greater than 1 mole / liter and, preferably between 1 and 5 moles / liter.

It should be noted that the upper bound has no critical character.

 Conveniently, the alkali or alkaline earth metal alcoholate is formed in situ, by reacting an excess of alkanol with the chosen alkali or alkaline earth metal.

 The amount of copper catalyst used in the process of the invention can vary widely.

 Usually, the catalyst to copper / compound of formula (II) molar ratio is from 1 to 50% and preferably from 2% to 20%.

 The quantity of cocatalyst used in the process of the invention is such that there is a cocatalyst / catalyst to copper molar ratio of 1 to 10 and, preferably, from 1 to 5.

 The temperature of the alkoxylation or aralkoxylation reaction is generally between 600C and 2200C, and preferably between 1000C and 1800C.

 The pressure is not a critical parameter in itself, but to reach the temperatures indicated above and not to lose solvent, the process is usually carried out under autogenous pressure.

 Generally, this autogenous pressure of the reaction mixture is less than or equal to 5 MPa (50 bars).

 The duration of the alkoxylation reaction can vary widely between 1 and 10 hours, preferably between 2 and 5 hours.

 In the second step of the process of the invention, the reaction of O-alkylation of the aromatic compound previously obtained which carries at least one alkoxy group and at least one hydroxyl group is carried out.

 To this end, it is brought into contact with an alkylating agent. Use may be made of alkyl sulphates of formula R1-O-S02-O-R1 or of alkylcarbonates of formula R? -O-CO-O-R1, in said formulas, R1 represents an alkyl radical, linear or branched, having 1 to 6 carbon atoms.

 Among the abovementioned alkylating agents, dimethylsulfate or dimethylcarbonate are preferred.

 However, it is preferred according to the invention to choose, as alkylating agent, a lower alkyl halide corresponding to the general formula (V) Rî-X (V) in said formula, X represents a bromine atom, of chlorine or iodine and R1 represents a linear or branched alkyl radical having from 1 to 6 carbon atoms.

Among the halides of formula (V), it is preferred to use those corresponding to formula (V) in which X is a chlorine atom and
R'1 a linear or branched alkyl radical having from 1 to 4 carbon atoms.

 Most often, a methyl halide or an ethyl halide is used.

 Among the halides, the chlorides, bromides and iodides are generally used and more specifically still methyl chloride, chloroethane, methyl bromide and bromoethane.

 Due to their lower cost, it is preferred to use methyl chloride and chloroethane.

 An alternative embodiment of the invention consists in adding to the reaction medium, preferably before the addition of the alkylating agent, a salt in the form of iodide, in order to have higher kinetics. As salts, there may be mentioned iodides of alkali metal, in particular of sodium, potassium or lithium.

 Generally, the O-alkylation reaction is carried out directly after the alkoxylation reaction, by introducing the alkylating agent at the required temperature. However, in some cases it may be more advantageous to maintain the pH at a pH between 6 and 12 for the duration of the reaction.

 When operating at a pH below 6, a decrease in the O-alkylation reaction is observed as well as a slowing down of this reaction.

 Preferably, the pH of the medium is maintained between 9 and 11.

 Regulation of the pH can be ensured if necessary by continuous addition of a base, preferably an aqueous solution of an alkali metal hydroxide. All alkali metal hydroxides can be used.

However for economic considerations, soda is preferred.

 According to a preferred variant of the process of the invention, the reaction is carried out in the presence of a catalyst, in order to have higher kinetics and milder conditions, in particular of pressure.

The catalyst is chosen from amines and quaternary ammonium salts
All primary, secondary or tertiary amines can be used.

 It is thus possible to use primary and secondary aliphatic, aromatic, arylaliphatic, cycloaliphatic or heterocyclic amines.

 By way of nonlimiting examples of such amines, mention may be made of ethylamine, propylamine, butylamine, hexylamine, octylamine, decylamine, laurylamine, dimethylamine, dipropylamine, diisopropylamine, dibutylamine, diisobutylamine, dihexylamine, aniline, piperidine, benzylamine, methylaniline, ethylaniline, pyrrolidine, limidazole.

 The tertiary amines which can be used are also very diverse; these are, for example, trialkylamines in which the alkyl radicals can be identical or different and have 1 to 24 carbon atoms; cycloalkylalkylamines; benzylalkylamines; phenylalkylamines cyclic amines: these amines can have other functions such as ether or hydroxyl functions.

There may be mentioned, without limitation, trimethylamine, triethylamine, tripropylamine, tributylamine, ethyldimethylamine, lauryldimethylamine, octadecyldimethylamine, propyldimethylamine, pentyldimethylamine, benzyldimethylamine, trioctylamine, triethanolamine, N, N -dimethylaniline, butyldimethylamine,
N, N-diethylaniline, N-methylpiperidine, N-ethylpiperidine,
N-methylpyrrolidine, N-methylimidazole, pyridine, 3-methyl pyridine, 2-methyl pyridine, 4-methyl pyridine, 2,4-dimethyl pyridine, 2,6-dimethyl pyridine, triethylenediamine.

 It is, of course, possible to use industrial mixtures (industrial cuts) available of different amines.

 In general, it is preferred to use the amines which are most easily quaternizable under the reaction conditions.

 The quaternary ammonium salts can also be used as catalyst. These are, for example, halides, hydroxides, alkyl, cycloalkyl or benzyl sulfates derived from the preceding amines.

 Generally preferred are quaternary ammonium chlorides or bromides.

 As regards the quantity of reagents to be used in the second step of the process of the invention, the preferred quantities are defined below.

 The amount of alkylating agent used depends on the number of hydroxyl groups present on the aromatic nucleus of the product obtained above, after alkoxylation. It is preferably at least equal to a stoichiometric amount up to an excess of up to 200%. It is preferably equal to the stoichiometric amount.

 By way of examples, it will be specified that the molar ratio of alkyl halide / alkoxy hydroxy benzaldehyde varies from 1.0 to 3.0 and preferably close to 1.0 and that the molar ratio of alkyl halide / alkoxy dihydroxy benzaldehyde ranges from 2.0 to 6.0 and preferably around 2.0.

 The amount of base is determined so that the pH is maintained within the above range.

 The amount of catalyst used in the preferred variant of the invention can vary within wide limits. Generally, from 0 to 30 mol% of catalyst are used relative to the product obtained after alkoxylation, preferably from 0 to 20%.

 The amount of salt in the form of iodide used according to another preferred variant of the invention can also vary widely.

Usually, the molar ratio between the salt in the form of iodide and the alkylating agent varies between 0.05 and 0.20 and is preferably around 0.10.

With regard to the reaction conditions, the temperature of the O-alkylation reaction is not critical; it has an influence on the kinetics of the reaction. Generally, the reaction of
O-alkylation between 800C and 2000C. Preferably, one operates at a temperature between 1000C and 1600C.

 The pressure is not critical. It affects the kinetics of the reaction. It usually varies between atmospheric pressure and 50 bars.

 The choice to operate under a higher or lower pressure will be conditioned in particular by the presence or absence of catalyst. In the presence of catalyst, the higher the amount of said catalyst, the lower the pressure may be, that is to say for example be between atmospheric pressure and 20 bars.

 The pressure is usually created by the reaction solvent and the alkylating agent used for O-alkylation when they are gaseous under the reaction conditions.

 The duration of the O-alkylation reaction depends in particular on the reaction temperature. It most often varies between 1 hour and 8 hours. Generally, a duration of 1 to 4 hours is sufficient.

 According to a practical embodiment of the invention, it is possible to mix all the reactants of the first step, namely the aromatic compound of formula (II), the copper catalyst and the co-catalyst of the CO2 or carbonate type and after heating for the time necessary for the alkoxylation reaction, add to the reaction medium, the alkylating agent optionally a base and the amine-type catalyst.

 A preferred mode of practicing the invention consists first of all in preparing a solution of the alkali metal alcoholate in the corresponding alkanol in an amount of, for example, 20 to 50% by weight.

 In the apparatus, nitrogen gas, the aromatic compound of formula (II), the copper catalyst and then the co-catalyst of the CO2 or carbonate type are preferably loaded under an inert gas atmosphere, alkali metal alcoholate solution. In the case of carbon dioxide, a gas stream is therefore sent into the reaction medium.

 The reaction medium is then brought to the temperature chosen between 600C and 2200C, preferably between 1000C and 1800C, for the pre-defined period.

 The alkylating agent is then introduced, preferably the alkyl halide which may be liquid or gaseous, and the alkali metal hydroxide solution is injected or poured in parallel, if this is necessary to adjust the pH in the aforementioned area.

 Heating is maintained between 80 ° C. and 2000 ° C., preferably between 1000 ° C. and 1600 ° C., for the time necessary for the O-alkylation reaction.

 At the end of the reaction, the polyalkoxylated aromatic compound of formula (I) obtained is separated, according to conventional separation techniques, either by distillation or by extraction with an appropriate solvent, for example toluene in the case of trimethoxy-3, 4.5 benzaldehyde.

 It is possible to remove the copper catalyst from the reaction medium according to conventional treatments, in particular by acid treatment.

 One of the advantages of the process of the invention is that it makes it possible to carry out, in a row and in the same reactor, the reaction of alkoxylation and O-alkylation.

 In the case of the preparation of 3,4,5,5-trimethoxy benzaldehyde, its preparation is carried out from 5-bromo-4-hydroxy-3-methoxy-benzaldehyde, in essentially homogeneous organic medium, without separation of the alkoxylated intermediate product, which is very advantageous from an industrial point of view.

 Compared to the process described in FR-A 2 609 984, the separation of 3,4,5-trimethoxybenzaldehyde is simpler, since there is no formation of veratric aldehyde which must then be separated.

The process of the invention is therefore particularly well suited to the preparation of the following alkoxybenzaldehydes
- 3,4,5-trimethoxy benzaldehyde
- 3,4-dimethoxy benzaldehyde.

- 3,4-diethoxy benzaldehyde
- 3-ethoxy-4-methoxy benzaldehyde
The 3,4,5-trimethoxybenzaldehyde which can be prepared according to the process of the invention is used in particular for the preparation of pharmaceutical products.

 The examples which follow illustrate the invention without however limiting it.

In the examples, the following abbreviations mean
BHB: 5-bromo-2-hydroxy benzaldehyde
DMBA: 2,5-dimethoxy benzaldehyde
Number of moles of BHB transformed
TTBHB =
Number of moles of BHB introduced
Number of moles of DMBA formed
RTDMBA =
Number of moles of BHB transformed
EXAMPLE 1
Nitrogen atmosphere is charged to a 3.9-liter stainless steel reactor with a heating system and a stirrer
- 150 g (0.750 mole) of 5-bromo-2-hydroxy benzaldehyde (BHMB)
- 162 g of sodium methylate
- 1785 cm3 (1428 g) of methanol
- 8.3 g of basic copper II carbonate of formula CuCO3, Cu (OH) 2
- 16 g of carbon dioxide
Carbon dioxide is supplied in gaseous form, by bubbling into the reaction mixture.

 The mixture is heated with stirring for 5 hours at 1250C under autogenous pressure in order to carry out the methoxylation reaction.

 The reaction mixture is cooled to 1200C and then charged with 150 g of methyl chloride.

 The reaction mixture is kept at 1200C for 3 hours.

 Cool to room temperature.

 The insoluble part is filtered off.

 Dosing is carried out by high performance liquid chromatography, the unreacted BHB and the 2,5-dimethoxy-benzaldehyde obtained.

The results obtained are as follows
- BHB transformation rate (TTBHB%) = 75%
- DMBA yield (RTDMBA%) = 81%

Claims (28)

CLAIMS 1 - Process for the preparation of polyalkoxylated aromatic compounds of general formula (I) (R1- m- Ro - + OR) n (I) in which - m and n are whole numbers greater than or equal to 1 with, preferably , m + n between 2 and 6, - Ro represents an aromatic cyclic radical having at least 5 atoms in the ring, optionally substituted, and representing at least one of the following radicals. an aromatic, monocyclic or polycyclic carbocyclic radical,. an aromatic, monocyclic or polycyclic heterocyclic radical comprising at least one of the heteroatoms O, N and S, - R represents a hydrocarbon radical having from 1 to 12 carbon atoms, which can be an acyclic, saturated or unsaturated, linear or branched aliphatic radical ; a cycloaliphatic radical, saturated or unsaturated, monocyclic or polycyclic; a cycloaliphatic- or arylaliphatic radical, saturated or unsaturated, linear or branched, ~ R1 is an alkyl radical, linear or branched having from 1 to 6 carbon atoms, process characterized in that the following steps are carried out successively 1 - An aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponding to the general formula (II) is reacted :: (HO + mr- Ro - + x) n (II) in which - m and n are whole numbers greater than or equal to 1 with, preferably, m + n between 2 and 6, - X represents an iodine, bromine or chlorine atom, - Ro represents an aromatic cyclic radical having at least 5 atoms in the ring, optionally substituted, and representing at least one of the following radicals. an aromatic, monocyclic or polycyclic carbocyclic radical,. an aromatic, monocyclic or polycyclic heterocyclic radical comprising at least one of the heteroatoms O, N and S, - and an alkali or alkaline earth metal alcoholate of general formula (III) MW + [O - RJ (III) in which - M represents an alkali or alkaline earth metal, - w represents the valence of the alkali or alkaline earth metal, - R represents a hydrocarbon radical having from 1 to 12 carbon atoms, which can be an acyclic aliphatic radical, saturated or unsaturated, linear or branched; a cycloaliphatic radical, saturated or unsaturated, monocyclic or polycyclic; a cycloaliphatic- or arylaliphatic radical, saturated or unsaturated, linear or branched, in the presence of a copper catalyst which is copper and / or a copper compound and an effective amount of a co-catalyst chosen from organic carbonates, mixed organometallic carbonates, carbon dioxide or compounds capable of forming carbon dioxide, 20 - O-alkylation of the hydroxyl group (s) of the product obtained above after alkoxylation is carried out, by addition directly to the organic reaction medium of an alkylating agent chosen from lower alkyl halides, dialkylsulphates, dialkylcarbonates. 2 - Process according to claim 1 characterized in that the aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponds to the general formula (II) in which Ro symbolizes 10 - a carbocyclic radical aromatic, monocyclic or polycyclic. - an aromatic, monocyclic or polycyclic heterocyclic radical. 30 - a divalent radical constituted by a chain of groups, as defined in paragraphs 1 and / or 2 linked together  by a valential link,. by an alkylene or alkylidene radical having from 1 to 4 atoms of  carbon, preferably a methylene or isopropylidene radical,. by one of the following groups +, O-,  -S-, -SO-, -S02-

 in these formulas, R2 representing a hydrogen atom or a radical  alkyl having from 1 to 4 carbon atoms, a cyclohexyl radical or  phenyl. 3 - Method according to one of claims 1 and 2 characterized in that the aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponds to the general formula (II} in which Ro is substituted by one or more substituents such as  a radical of formula -R3-OH in which the radical R3 represents  a valential bond or a divalent, linear or  branched, saturated or unsaturated having from 1 to 4 carbon atoms, such as  for example, methylene, ethylene, propylene, isopropylene,  isopropylidene,  an alkyl radical, linear or branched, having from 1 to 6 atoms of  carbon, preferably from 1 to 4 carbon atoms, such as methyl,  ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, tert-butyl,  . a linear or branched alkenyl radical having from 2 to 6 carbon atoms  bone, preferably from 2 to 4 carbon atoms, such as vinyl,  allyle,  . a linear or branched alkoxy radical having from I to 6 atoms of  carbon, preferably from 1 to 4 carbon atoms such as the radicals  methoxy, ethoxy, propoxy, isopropoxy, butoxy,  . a -CHO group,  . an acyl group having from 2 to 6 carbon atoms,  . a radical of formula -R3-COOH, R3 having the given meaning  previously,  . a radical of formula -R3-COOR4 in which R3 has the meaning  given above and R4 represents an alkyl radical, linear or  branched, having from 1 to 6 carbon atoms,  . a radical of formula -R3-NH2 with an N-protected NH2 group, R3 having  the meaning given above,  a radical of formula -R3-N (R'4) in which R3 has the meaning  given previously and the identical or different radicals R'4 represent  feel a hydrogen atom or an alkyl radical, linear or branched,  having from 1 to 6 carbon atoms,  . a radical of formula -R3-CO-N (R'4), R3 and R'4 having the meaning  previously given,  . a radical of formula -R3-Z in which R3 has the meaning  given above and Z symbolizes a halogen atom X, such that  previously defined, a fluorine atom or a CF3 group. 4 - Method according to one of claims 1 to 3 characterized in that the aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponds to the general formula (II) in which Ro is a benzene nucleus. 5 - Method according to one of claims 1 to 4 characterized in that the aromatic compound carrying at least one halogen atom and at least one hydroxyl group corresponds to the general formula (II) is chosen from  - 2-bromo phenol  - 3-bromo phenol  - 4-bromo phenol  - bromo-1 naphthol-2  - bromo-6 naphthol-2  - 2-bromo-4-methylphenol  - 4-bromo-2,6-dimethylphenol  - 4-bromo-3,5 dimethyl phenol  - 2,6-dibromo-4-methylphenol  - bromo-2-p-cresol  - 2-bromo-4 chloro-phenol  - 4-bromo-2 chloro-phenol  - 4-bromo-chloro-6-o-cresol  - bromofluorophenols  - bromo bis-phenols  - isopropylidene-4,4 'bis-phenols bromo  6 - Method according to one of claims 1 to 5 characterized in that it comprises the following steps 10 - Reacting a halo hydroxy benzaldehyde corresponding to the general formula (IIa):

 in which  - x represents an iodine, bromine or chlorine atom,  - R7 represents a hydrogen atom, an iodine, bromine atom, a  chlorine atom, an alkyl radical having from 1 to 4 carbon atoms,  an alkoxy radical having from 1 to 4 carbon atoms, a radical  hydroxyl,  in said formula (IIa), the hydroxyl radical possibly being  ortho- or meta- position of the aldehyde function, with an alkali or alkaline earth metal alcoholate having from 1 to 4 carbon atoms, in the presence of a copper catalyst which is copper and / or a copper compound and an effective amount of a co-catalyst chosen from organic carbonates, mixed organometallic carbonates, carbon dioxide or compounds capable of forming carbon dioxide,  20 - O-alkylation of the hydroxyl group (s) of the product obtained above is carried out after alkoxylation, by adding directly to the organic reaction medium an alkylating agent providing the alkyl residue R'1 having from 1 to 4 carbon atoms . 7 - Process according to claim 6 characterized in that one halo hydroxy benzaldehyde corresponds to one of the following formulas

 in which  - X and R7 have the meanings given above. 8 - Method according to one of claims 1 to 7 characterized in that the halo hydroxy benzaldehyde is chosen from  - 4-bromo-3-hydroxy benzaldehyde  - iodo-4 hydroxy-3 benzaldehyde  - 3-bromo-2-hydroxy benzaldehyde  - iodo-3 hydroxy-2 benzaldehyde  - 5-bromo-2-hydroxy benzaldehyde  - 5-iodo-2-hydroxy-benzaldehyde 9 - Method according to one of claims 1 to 8 characterized in that the alkali metal alcoholate is a sodium or potassium alcoholate of a primary or secondary alkanol having 1 to 4 carbon atoms. 10 - Method according to one of claims 1 to 9 characterized in that the alkali metal alcoholate is sodium methylate or sodium ethylate. 11 - Method according to one of claims 1 to 10 characterized in that the catalyst is an organic or inorganic compound of copper I or copper II, chosen from cuprous chloride, cupric chloride, basic copper carbonate II, cuprous nitrate, cupric nitrate, cupric sulfate, cupric acetate, cupric trifluoromethylsulfonate, cupric hydroxide, copper picolinate II, copper methylate I, copper methylate II, copper chelate II of 8-quinoline, the copper compounds of formula ClCuOCH3, Cu2 (OCH3) 2 (acac) 2. 12 - Method according to one of claims 1 to 11 characterized in that the co-catalyst is a carbonate of general formula (IV):  R8 - O - CO - O - Rg (IV) in which - R8 represents  . an alkyl radical, linear or branched, having 1 to 6 atoms of  carbon,  . a cycloalkyl radical having 5 to 6 carbon atoms,  . a cycloalkyl radical, having 5 or 6 carbon atoms substituted by  one or two alkyl radicals having 1 to 4 carbon atoms,  a phenyl radical,  a phenyl radical substituted by 1 or 2 alkyl radicals having 1 to 4  carbon atoms,  . a radical R10 - O - CO - in which R10 represents a radical  alkyl, linear or branched having 1 to 6 carbon atoms, one  phenyl radical, a cycloalkyl radical having 5 or 6 atoms of  carbon - Rg represents  an alkyl radical, linear or branched, having 1 to 6 atoms of  carbon,  . a cycloalkyl radical having 5 or 6 carbon atoms,  . a cycloalkyl radical having 5 or 6 carbon atoms substituted by  one or two alkyl radicals having 1 to 4 carbon atoms,  . a phenyl radical,  . a phenyl radical substituted by one or two alkyl radicals having 1 to  4 carbon atoms,  . a sodium or potassium atom, - R8 and Rg may together form an alkylene radical having 2 to 6  carbon atoms. 13 - Method according to one of claims 1 to 12 characterized in that the co-catalyst is a carbonate of general formula (IVa)  R8 - O - CO - O - Rg (IVa) in which - R8 represents  . an alkyl radical, linear or branched, having 1 to 6 atoms of  carbon,  . a cycloalkyl radical having 5 to 6 carbon atoms,  . a cycloalkyl radical, having 5 or 6 carbon atoms substituted by  one or two alkyl radicals having 1 to 4 carbon atoms,  . a phenyl radical,  . a phenyl radical substituted by 1 or 2 alkyl radicals having 1 to 4  carbon atoms,  . a radical R10 - O - CO - in which R10 represents a radical  alkyl, linear or branched having 1 to 6 carbon atoms, one  phenyl radical, a cycloalkyl radical having 5 or 6 atoms of  carbon - Rg represents  . an alkyl radical, linear or branched, having 1 to 6 atoms of  carbon,  . a cycloalkyl radical having 5 or 6 carbon atoms,  . a cycloalkyl radical having 5 or 6 carbon atoms substituted by  one or two alkyl radicals having 1 to 4 carbon atoms,  . a phenyl radical,  . a phenyl radical substituted by one or two alkyl radicals having 1 to  4 carbon atoms,  . a sodium or potassium atom, - R8 and Rg may together form an alkylene radical having 2 to 6  carbon atoms. 14 - Method according to one of claims 1 to 13 characterized in that the co-catalyst is carbon dioxide. 15 - Method according to one of claims 1 to 14 characterized in that the alkali metal alkali or alkaline earth metal is used in an amount corresponding to the stoichiometric amount necessary to salify the hydroxyl groups plus an equal amount of 1 to 5 times, and preferably 1 to 3 times, the stoichiometric amount necessary to transform the halogen atom (s) into alkoxy groups. 16 - Process according to claim 1 to 15 characterized in that the concentration of the alkali metal alkali or alkaline earth metal alcoholate is greater than 1 mole / liter and, preferably between 1 and 5 moles / liter. 17 - Method according to one of claims 1 to 16 characterized in that the molar ratio of copper / compound of formula (II) is from 1% to 50% and, preferably, from 2% to 20%. 18 - Method according to one of claims 1 to 17 characterized in that the reaction is carried out in a solvent consisting of the alkanol corresponding to the alkali metal alcoholate used. 19 - Method according to one of claims 1 to 18 characterized in that the co-catalyst / copper compound molar ratio is from 1 to 10 and, preferably, from 1 to 5. 20-- Method according to one of claims 1 to 19, characterized in that the alkoxylation reaction is carried out at a temperature of 600C to 2200C and, preferably, from 1000C to 1800C. 21 - Method according to one of claims 1 to 20 characterized in that the alkylating agent in the O-alkylation reaction is dimethylsulfate or dimethylcarbonate. 22 - Method according to one of claims 1 to 21 characterized in that the alkylating agent is a lower alkyl halide corresponding to the general formula (V) Rî-X (V) in said formula, X represents a bromine, chlorine or iodine atom and R1 represents a linear or branched alkyl radical having from 1 to 6 carbon atoms. 23 - Process according to claim 22 characterized in that the alkylating agent is methyl chloride, chloroethane, methyl bromide and bromoethane. 24 - Method according to one of claims 1 to 23 characterized in that the amount of alkyl halide expressed relative to the amount of compound of formula (II) varies from the stoichiometric amount to an excess of up to 200% , preferably equal to the stoichiometric amount 25 - Method according to one of claims 1 to 24 characterized in that there is introduced before the alkylating agent, a salt in the form of an alkali metal iodide, preferably sodium. 26 - Method according to one of claims 1 to 25 characterized in that one carries out the O-alkylation reaction at a pH of reaction mixture between 6 and 12. 27 - Method according to one of claims 1 to 26 characterized in that one operates the O-alkylation reaction in the presence of a catalyst chosen from primary, secondary or tertiary amines and quaternary ammonium salts. 28 - Method according to one of claims 1 to 27 characterized in that one operates the O-alkylation reaction between 800C and 2000C and, preferably, between 1000C and 1600C.