Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2001-03-14
2004-06-22
Killos, Paul J. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
Reexamination Certificate
active
06753441
ABSTRACT:
A subject of the present invention is a process for the preparation of optionally substituted p-hydroxymandelic compounds and derivatives.
In the disclosure of the invention which follows, the term, “optionally substituted p-hydroxymandelic compounds” is used to refer to an aromatic compound which carries at least one —CHOH—COOH group in para position of a hydroxyl group.
The present invention relates, more particularly, to the preparation of p-hydroxymandelic acid and 3-methoxy p-hydroxymandelic acid.
One of the conventional synthesis routes for p-hydroxymandelic acids consists in carrying out the condensation, in alkaline medium, of glyoxylic acid on phenol and/or its corresponding derivatives.
The yield is limited by the fact that the condensation reaction is not selective and also produces o-hydroxymandelic acids and dimandelic acids.
Furthermore, the reaction yield is reduced due to a parasitic secondary reaction. In fact, glyoxylic acid in aqueous alkaline medium is converted according to Caniizaro's reaction into oxalic and glycolic acids.
In order to prevent this Cannizaro's reaction from becoming dominant and destroying the glyoxylic acid, a proposal has been made in FR-A 2 132 364 for the condensation reaction to be carried out in a dilute aqueous medium and at low temperature or ambient temperature.
In view of the difficulty in obtaining satisfactory reaction yields, it is important to control the various parameters of the process, and, in particular, the quality of the glyoxylic acid used.
The most worthwhile process from an industrial viewpoint for the preparation of glyoxylic acid consists in oxidising the glyoxal with nitric acid. In this way, aqueous solutions of glyoxylic acid are obtained, which, in addition to unreacted glyoxal, also contain oxalic acid, organic acids, such as formic acid, acetic acid, glycolic acid, and nitric acid.
Until now, new methods have been constantly sought for the separation and purification of glyoxylic acid.
Therefore, a process was proposed in DE-A 1 198 339 which first and foremostly permitted the nitric acid to be eliminated, followed by the oxalic acid using basic ion exchange resins, followed by the glyoxal and the other impurities by over-concentration of the solution and crystallisation.
In DE-A 2 501 743, a process was disclosed in which the glyoxylic acid is separated from these impurities by extraction using aliphatic or cycloaliphatic alcohols, or aliphatic esters of alcohols with low carbon condensation.
A process for obtaining aqueous solutions of glyoxylic acid free from other acids has also been described in FR-A 2 552 426 which consists in treating the starting solution with an organic nitrogenous compound, preferably a tertiary amine, at a temperature which is at the most equal to 50° C., then in extracting the glyoxylic acid by extraction of the organic phase with water, at a higher temperature.
A constant concern has therefore been noted in the prior art of providing a solution of glyoxylic acid which is free of impurities.
Running counter to this teaching, it has been found that within the scope of preparing optionally substituted p-hydroxymandelic compounds condensation of glyoxylic acid and of the corresponding phenol is carried out with an increased yield, provided that said reaction is carried out in the presence of a dicarboxylic acid used in a certain quantity.
A precise subject of the present invention is a process for the preparation of optionally substituted p-hydroxymandelic compounds and derivatives, which consists in carrying out the condensation, in water, in the presence of an alkaline agent, of an aromatic compound with at least one hydroxyl group and the para position of which is free, with glyoxylic acid, said process being characterised in that the reaction is carried out in the presence of an effective quantity of a catalyst compound with at least two carboxylic functions.
In accordance with the process of the invention, the use of a catalyst according to the invention allows the reaction yield to be increased.
Another advantage of the process according to the invention is that it can involve a more technical glyoxylic acid containing, inter alia, oxalic acid.
The process according to the invention is used, most particularly, with phenol but also with substituted phenols which have at least one non-substituted para position.
The aromatic nucleus has at least one hydroxyl group, but it can also have one or more other substituents. Generally, “several substituents” means less than four substituents per aromatic nucleus.
Any substituent can be present provided that it is does not interfere in the reaction of the invention.
Therefore, the process according to the invention is well suited for use with hydroxylated aromatic compounds corresponding to the following formula (I):
in which formula (I):
the para position is free,
x is an integer between 1 and 4,
R represents:
a hydrogen atom,
a hydrocarbon group having from 1 to 20 carbon atoms selected from the alkyl, alkoxy, hydroxyalkyl, cycloalkyl, aryl, phenoxy, alkoxyalkyl, fluoroalkyl, hydroxyalkoxyalkylene groups,
a hydroxyl group,
a —CHO group,
an acyl group having from 2 to 6 carbon atoms,
a halogen atom, preferably a fluorine, chlorine or bromine atom,
two R groups placed on two vicinal carbon atoms can form together with the carbon atoms to which they are attached, a benzene ring.
Examples of R radicals which can be attached to the aromatic nucleus are given hereinafter:
alkyl radicals, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-octyl, 2-ethyl hexyl, decyl, octadecyl, eicosly,
alkoxy radicals, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, hexyloxy, decyloxy, hexadecylocy, octadecylocy, or a phenoxy radical,
hydroxyalkyl radicals, such as hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxyhexyl, hydroxydecyl,
cycloalkyl radicals, such as cylcopentyl, cyclohexyl, cycloheptyl,
fluoroalkyl radicals, such as fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, 1,1,1-trifluoro ethyl, pentafluoroethyl, fluoropropyl, fluorobutyl, tribluoroamyl,
hydroxyalkyoxyalkylene radicals, such as hydroxymethyloxyethylene, hydroxyethyl di-(oxyethylene), hydroxyethyl tri-(oxyethylene), 1,2-hydroxyethyloxypropylene, hydroxyethyloxybutylene, hydroxypropyloxypropylene, hydroxybutyloxybutylene, hydroxybutyl di-(oxybutylene),
halogen atoms, such as fluorine, chlorine, bromine, or iodine.
Quite preferably, hydroxylated aromatic compounds are used in the process of the invention, corresponding to the general formula (I), in which:
x is equal to 0, 1,2 or 3,
R represents one of the following groups or functions:
a hydrogen atom,
a linear or branched alkyl radical having from 1 to 10 carbon atoms, and preferably from 1 to 4 carbon atoms,
a linear or branched alkoxy radical having from 1 to 10 carbon atoms, preferably from 1 to 4 carbon atoms,
an—OH group,
a —CHO group,
a halogen atom,
a —CF
3
group.
Still more preferably, the compounds of formula (I) are selected in which the R radicals which are identical or different are a hydrogen atom, a linear or branched alkyl radical with 1 to 4 carbon atoms, such as the methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl radicals, a linear or branched alkoxy radical having 1 to 4 carbon atoms, such as the methoxy or ethoxy radicals, a —CHO group, or a chlorine atom, and x is preferably equal to 0 or 1.
By way of illustration of compounds corresponding to formula (I), the following can be mentioned:
those corresponding to formula (I) in which x is equal to 0, such as phenol,
those corresponding to formula (I) in which x is equal to 1, such as
pyrocatechin
resorcin
o-cresol
m-cresol
2-ethyl phenol
3-ethyl phenol
2-propyl phenol
2-sec-butyl phenol
2-tert-butyl phenol
3-tert-butyl phenol
2-methoxy phenol (guaiacol)
3-methoxy-phenol
2-ethoxy phenol (guetol)
2-isopropoxy phenol
salicylic aldehyde
methyl salicylate
2-chloro phenol
3-chloro phenol
3-nitro phenol
those corresponding to formula (I) in which x is equal to 2, such as
Fournet Frederic
Fragnon Jean
Jouve Isabelle
Killos Paul J.
Rhodia Chimie
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