Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-05-25
2002-03-26
Davis, Zinna Northington (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06362340
ABSTRACT:
The present invention relates to a process for preparing 4-hydroxyquinolines and/or their tautomeric forms. More particularly, the invention relates to 5,7-dichloro-4-hydroxyquinoline and/or its tautomeric forms.
5,7-dichloro-4-hydroxyquinoline (DCHQ) is an intermediate used in the plant protection field.
The industrial scale preparation of such a product is a problem, and existing processes are in need of refining.
C. C. Price et al. (Organic Synthesis 3, p. 272) disclose the preparation of 4-hydroxyquinolines using a process consisting of decarboxylation of 4-hydroxy-3-quinolinecarboxylic acids that have been obtained by alkaline or acid hydrolysis of the corresponding esters. However, decarboxylation is carried out at a high temperature of more than 230° C.
U.S. Pat. No. 5,731,440 proposes improving that process by carrying out the decarboxylation step at a lower temperature in the range 120° C. to 165° C., but uses a strong acid medium such as sulphuric acid, phosphoric acid or hydrochloric acid. The disadvantage of that process is that the medium is highly corrosive because of the presence of a strong acid.
The Applicant has discovered an improved hydroxyquinoline preparation process.
The process of the invention is characterized in that a 4-hydroxyquinolinecarboxylic acid, a derivative or precursor thereof, is heated to a temperature of at most 200° C. in the presence of a base.
It has unexpectedly been discovered that it is possible to carry out decarboxylation of 4-hydroxyquinolinecarboxylic acids and esters thereof at a low temperature, advantageously in the range 90° C. to 160° C., in good reaction yields. This is of enormous advantage from an industrial viewpoint.
The process of the invention uses a quinolinic compound.
The term “quinolinic compound” means a heterocyclic compound comprising a quinoline moiety. This term is also used for naphthpyridine type compounds that are also included in the scope of the process of the invention.
The heterocycle of the quinolinic compound carries at least one hydroxyl group in the 4-position and a functional group in the position &agr; to the hydroxyl group. Other substituents can also be present in particular in the 5- and/or 7-position.
Regarding the nature of the functional group that is shown in formula (I) below by the symbol Y, this is a carboxylic group (COOH), a precursor group (nitrile) or a derivative group (ester or amide).
The starting quinolinic compound of the invention can be represented by the following general formula:
in which formula (I):
R
1
, which may be identical or different, represents:
a linear or branched alkyl group containing 1 to 12 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl;
a linear or branched alkyl group carrying one or more halogen atoms, containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl;
a linear or branched alkenyl group containing 2 to 12 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyl or allyl,
a cyclohexyl, phenyl or benzyl group;
a linear or branched alkoxy or thioether group containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as a methoxy, ethoxy, propoxy, isopropoxy or butoxy radical;
an acyl group containing 2 to 6 carbon atoms;
a nitro group;
an amino group, optionally substituted by alkyl groups containing 1 to 6 carbon atoms;
a halogen atom, preferably a chlorine or bromine atom;
a trifluoromethyl group;
an alkenylene group containing 3 or 4 carbon atoms that can form a ring with the carbon atoms adjacent to the phenyl ring;
Y represents one of the following groups:
a CN group;
a COOR
2
group;
a CONR
3
R
4
group;
in which groups R
2
, R
3
or R
4
, which may be identical or different, represent a hydrogen atom or an alkyl, cyclohexyl, phenyl or benzyl group;
n is a number in the range 1 to 4, preferably 1 or 2.
Particularly suitable substituents in the 5- and/or 7-position are halogen atoms such as fluorine, chlorine, bromine, iodine or a —CF
3
type group.
Preferred non-limiting illustrative examples from the list of substituents are the chlorine atom, methyl radical and methoxy radical.
The nature of R
2
, R
3
and R
4
is not critical provided that the carboxylate group is eliminated. For reasons of economy, it is usually a linear or branched alkyl group containing 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, but it is possible to use other groups, for example cyclohexyl, phenyl or benzyl groups, or any other group.
More particular compounds with formula (I) for use in the process of the invention that can be cited are 4-hydroxy-5,7-dichloroquinoline-3-carboxylic acid, and methyl or ethyl 4-hydroxy-5,7-dichloroquinoline-3-carboxylate.
The starting quinolinic compounds with formula (I) are known products that can in particular be obtained by reacting substituted anilines with alkyl alkoxymethylenemalonates (cf. C. C. Price et al., Organic Synthesis 3, p. 272).
It should be noted that the invention is applicable to quinolinic compounds with formula (I) and also to tautomeric forms that can be represented by formula (II):
in which formula (II), R
1
, Y and n have the meanings given above for formula (I).
In accordance with the process of the invention, the quinolinic compound is decarboxylated in the presence of a base.
A mineral or organic base can be used in the process of the invention.
Preferably, a sufficiently strong base is selected, i.e., a base with an associated acid the pKa of which is more than 5 or close to 5: the pKa is defined as the cologarithm of the dissociation constant of the acid, in an aqueous medium, at 25° C.
Particularly suitable bases for carrying out the process of the invention that can be cited are alkaline bases derived from alkali metals or alkaline-earth metals.
The term “alkali metals” as used in the present text means elements from column 1A of the periodic table, preferably alkali metals such as lithium, sodium, potassium, rubidium and caesium.
The term “alkaline-earth metal” as used in the present text means elements from column 2A of the periodic table, preferably alkaline-earth metals such as beryllium, magnesium, calcium, strontium and barium.
For a definition of the elements, reference should be made to the periodic table published in the “Bulletin de la Société Chimique de France”, N
o
1, (1966).
The process of the invention preferably employs an alkali metal hydroxide, preferably potassium hydroxide or sodium hydroxide, or an alkali metal bicarbonate or carbonate, preferably potassium or sodium bicarbonate or carbonate.
It is also possible to use a quaternary ammonium hydroxide.
Examples of quaternary ammonium hydroxides that are preferably used are tetraalkylammonium or trialkylbenzylammonium hydroxides wherein the alkyl radicals, which may be identical or different, represent a linear or branched alkyl chain containing 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms.
Preferably, tetramethylammonium hydroxide, tetraethylammonium hydroxide or tetrabutylammonium hydroxide are used.
It is also possible to use trialkylbenzylammonium hydroxides, in particular trimethylbenzylammonium hydroxide.
The process of the invention can also employ monofunctional or bifunctional primary, secondary or tertiary aliphatic, carbocyclic or heterocyclic, aromatic or non aromatic amines.
More specific examples that can be mentioned are tri-n-butylamine, di-n-butylamine, hexamethylenediamine, cyclohexylamine, N-methylpyrrolidine, 4-dimethylaminopyridine, morpholine, quinoline, pyridine, 3-picoline and 5-picoline.
From an economic and practical viewpoint, the base that is selected is preferably potassium or sodium hydroxide.
The base is advantageously used in the form of an aqueous solution.
The concentration of the basic solution is preferably in the range 2% to 45% by weight, more preferably in the range 5% to 30%.
The quantity of based used, expressed as the mole ratio between the number of moles of base (or equivalents of base) and the nu
Chimie Rhodia
Davis Zinna Northington
LandOfFree
Method for preparing 4-hydroquinolines and/or tautomeric... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for preparing 4-hydroquinolines and/or tautomeric..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for preparing 4-hydroquinolines and/or tautomeric... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2847955