Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus esters
Reexamination Certificate
2001-11-09
2003-09-23
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Phosphorus esters
C568S014000, C568S012000
Reexamination Certificate
active
06624322
ABSTRACT:
This application is the national stage of PCT FR 09/03255 filed Dec. 22, 1999, now WO 00/040526.
A subject matter of the present invention is a process for the preparation of &bgr;-phosphorated nitroxide radicals of formula:
in which R
1
, R
2
, R
3
, R
4
and R
5
will be defined subsequently. These compounds are used in particular as regulators of radical polymerization.
These compounds can be obtained in particular by the oxidation of N-alkylaminophosphonates of formula:
The N-alkylaminophosphonates (II) can be obtained in a known way by reacting a carbonyl compound R
1
R
2
C(O), a primary amine R
3
NH
2
and a phosphorus compound HP(O)R
4
R
5
having a mobile hydrogen according to a Mannich-type reaction:
A process is disclosed in international patent application WO 96/24620 which consists in reacting, in a first stage, a carbonyl compound R
1
R
2
C(O) with a primary amine R
3
NH
2
according to a carbonyl compound/primary amine molar ratio substantially equal to 1 and then, in a second stage, in adding, to the compound obtained in the first stage, a phosphorus compound HP(O)R
4
R
5
according to a phosphorus compound/product obtained in the first stage molar ratio ranging from 1.5 to 2.5, indeed even more. There are several disadvantages to this way of proceeding.
Thus, the water formed in the first stage during the reaction of the carbonyl compound with the primary amine which results in the formation of an imine according to the scheme:
>C═O+—NH
2
→>C═N—+H
2
O
is not removed before the addition of the phosphorus compound, which may be of such a nature as to result in a possible hydrolysis of said phosphorus compound, in particular when the latter is a phosphite.
In addition, the use of a very large excess of phosphorus compound (150% to 250%, indeed even more) with respect to the compound obtained in the first stage (imine) is prohibitory for an industrial process.
Furthermore, this excess, in addition to the fact of the difficulties in removing it, is of such a nature as to generate numerous impurities by reaction with, in particular, the unconverted carbonyl compound to result in hydroxyphosphonates (>C(OH)—P(O)<) in the case where the phosphorus compound used is a phosphite. This excess of phosphorus compound can also result in the formation of heavy products resulting from the reaction between (II), the carbonyl compound and the excess phosphorus compound HP(O)R
4
R
5
.
All these impurities liable to be present in the crude product (II) make the purification of the N-alkylaminophosphonate (II) difficult and consequently render its subsequent use difficult.
The &bgr;-phosphorated nitroxide (I) can be obtained by oxidation of the N-alkylaminophosphonate (II) by replacing the hydrogen of >N—H with an oxygen atom.
This oxidation can be carried out according to various techniques known to a person skilled in the art. A few appropriate techniques are listed below in a nonexhaustive fashion:
reaction of a secondary amine with aqueous hydrogen peroxide solution in the presence of a solid catalyst (titanium silicalite), the principle of which is disclosed in patent U.S. Pat. No. 5,218,116;
reaction of a secondary amine with a dioxirane or its carbonyl precursors in combination with oxone®, the technique of which is disclosed in patent U.S. Pat. No. 5,087,752,
reaction of a secondary amine with metachloroperbenzoic acid, according to a protocol described in the Journal of the American Chemical Society, 1967, 89 (12), pages 3055-3056.
According to international application WO 96/24620, diethyl 2,2-dimethyl-1-(1,1-dimethylethylamino)propylphosphonate could only be efficiently oxidized by means of meta-chloroperbenzoic acid (mCPBA) according to a protocol which consists in introducing the mCPBA, in solution in CH
2
Cl
2
, into a CH
2
Cl
2
solution of the abovementioned aminophosphonate. The &bgr;-phosphorated nitroxide obtained is purified by passing through a column of silica gel, which involves the use of a large volume of elution solvent.
This way of operating can only be applied to the preparation of small amounts of (I). In addition, the analysis of this product by HPLC has shown that this technique results in nitroxides with a purity of less than 80%.
In order to improve the process for the oxidation of the aminophosphonate (II) by mCPBA, the assignee of the present application has carried out the preliminary drying of the technical mCPBA, on the one hand, and optimized the mCPBA/aminophosphonate molar ratio, on the other hand.
Although a satisfactory yield of &bgr;-phosphorated nitroxide is obtained, this way of operating produces amounts of effluents (metachlorobenzoic acid salt) which are difficult to remove.
Furthermore, even the optimized use of mCPBA does not make possible viable translocation to the industrial scale.
The applicant has found that, by using nonhalogenated organic peracids in a water/organic solvent two-phase medium with an aqueous phase buffered at a pH ranging from 5 to 12, it can oxidize aminophosphonates (II) to &bgr;-phosphorated nitroxides (I) while significantly reducing the manufacturing costs and while generating effluents which can be easily removed.
A subject matter of the present invention is thus a process for the manufacture of compounds of general formula:
in which R
1
and R
2
, which are identical or different, represent a hydrogen atom, a linear, branched or cyclic alkyl radical having a number of carbon atoms ranging from 1 to 10, an aryl radical, or an aralkyl radical having a number of carbon atoms ranging from 1 to 10, or else R
1
and R
2
are connected to one another so as to form a ring which includes the carbon atom carrying said R
1
and R
2
said ring having a number of carbon atoms, including the carbon carrying the R
1
and R
2
radicals, ranging from 3 to 8; R
3
represents a linear or branched and saturated or unsaturated hydrocarbonaceous radical which can comprise at least one ring, said radical having a number of carbon atoms ranging from 1 to 30; and R
4
and R
5
, which are identical or different, represent a linear or branched alkyl radical having a number of carbon atoms ranging from 1 to 20 or a cycloalkyl, aryl, alkoxyl, aryloxyl, aralkyloxyl, perfluoroalkyl, aralkyl, dialkyl- or diarylamino, alkylarylamino or thioalkyl radical, or else R
4
and R
5
are connected to one another so as to form a ring which includes the phosphorus atom, said heterocycle having a number of carbon atoms ranging from 2 to 4 and being able in addition to comprise one or more oxygen, sulfur or nitrogen atoms;
said process consisting in oxidizing an aminophosphonate of formula
obtained by reaction of a carbonyl compound R
1
R
2
C(O), of a primary amine R
3
NH
2
and of a phosphorus compound HP(O)R
4
R
5
, R
1
, R
2
, R
3
, R
4
and R
5
having the meanings given above; said process being characterized in that it consists first in preparing and optionally in isolating the compound II and then subsequently in oxidizing it by carrying out the following (successive) stages:
a) a carbonyl compound R
1
R
2
C(O) is reacted with a primary amine R
3
NH
2
according to an R
1
R
2
C(O)/R
3
NH
2
molar ratio of between 0.8 and 1.5 and preferably between 0.9 and 1.1 at a temperature of between 0° C. and 120° C. and a pressure ranging from 1 to 10 bar; then the water formed is removed from the reaction medium;
b) the compound obtained in a) is reacted with a phosphorus compound HP(O)R
4
R
5
used according to an HP(O)R
4
R
5
/compound a) molar ratio at most equal to 1.5 and preferably of between 1 and 1.5 at a temperature of between 0° C. and 120° C.;
c) an acidic treatment of the reaction medium obtained in b) is carried out, an organic solvent is subsequently added, separation by settling is carried out, the aqueous phase is recovered and then a basic treatment of said aqueous phase is carried out;
d) the aminophosphonate is extracted by means of an organic solvent identical to that used previously in c);
e) said solvent is then completely removed and said aminophosphorate (II) is isolated and is oxid
Gillet Jean-Philippe
Guerret Olivier
Tordo Paul
Atofina
Millen White Zelano & Branigan P.C.
Vollano Jean F.
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