Method for sequentially synthesising poly(alkoxyamine amide)s, copolymers obtained and uses thereof

Abstract

Synthesizing poly(alkoxyamine amide)s, which have a monomer chain with at least one thermolabile bond between monomers from an acid monomer of a monohalogenated carboxylic acid X—C(R,R′)—Y—COOH and an amine monomer having a free terminal free-radical nitroxide group >N—O.sup.∘ and a free terminal primary amine —NH.sup.2. The synthesis involves two separate and chemically selective chemical reactions. One reacts the —COOH and —NH.sub.2 groups to obtain an amide bond —NH—CO—Y—C(R, R′)—, and the other reacts the —Y—C(R, R′).sup.∘ free-radical with the nitroxide function >N—O.sup.∘ in order to obtain an alkoxyamine bond —Y—C(R, R′)—O—N<. The chemical reactions are performed in alternating fashion with catalysts and a novel halogenated acid monomer X—C(R,R′)—Y—COOH or a novel free-radical amine monomer having a free terminal group >N—O.sup.∘ and a free terminal primary amine —NH.sub.2, until a complete copolymer chain is obtained. Also the polymers obtained and the uses thereof.

Claims

1. Method for synthesizing poly(alkoxyamine amide) macromolecules or copolymers comprising (A) reacting a first monohalogenated carboxylic acid monomer of the formula X—CRR′—Y—COOH with a first amine monomer having a free terminal nitroxide free radical group (N—O—) and a terminal primary amine group (—NH.sub.2) where the reacting consists of two chemical reactions, the first reaction consisting of a reaction between the —COOH groups and the —NH.sub.2 group to form an amide group (—NH—CO—Y—CRR′—) and the second reaction consisting of a reaction between the halogen X on the monohalogenated carboxylic acid monomer (—Y—CRR′—X) with a catalyst to form a radical (—Y—CRR′—) which reacts with the nitroxide free radical group (N—O—) to form an alkoxyamine group (—Y—CRR′—O—N—), (B) repeating the reaction of step (A) with the same or a different monohalogenated carboxylic acid monomer and the same or a different amine monomer to form a poly(alkoxyamine amide) macromolecule or copolymer, where each X is independently a halogen, where each R is independently selected from the group consisting of H, CH.sub.3, an alkyl group that has 2 to 6 carbon atoms optionally substituted, where each R′ is independently selected from the group consisting of H,CH.sub.3, an alkyl group that has 2 to 6 carbon atoms optionally substituted, where each Y is independently selected from the group consisting of a covalent bond and —COO—Z— where Z is a linear, branched, or cyclic hydrocarbon chain with 1 to 15 carbon atoms which is optionally substituted by a functional group selected from the group consisting of —OH, —NH.sub.3, —COOH, —CN, an alkyne group, an alkene group —N.sub.2, —SO.sub.3, where the poly(alkyoxyamine amide) macromolecule or copolymer has at least one thermolabile bond between the monomers where the thermolabile bond has a dissociation temperature and the dissociation temperature is greater than 30° C. and less than 150° C., and where the reaction of step (A) takes place in solution or on a solid substrate.

2. The method according to claim 1, wherein the reaction of step (A) is initiated on a solid substrate equipped with a chemically reactive primer group, which reacts with either the first amine or the first monohalogenated carboxylic acid monomer to fix a monomer to the substrate.

3. The method according to claim 2, wherein the chemically reactive primer group on the solid substrate is selected from the group consisting of —NH.sub.2, —Br, —Cl, —COOH, and a terminal free radical nitroxide.

4. The method according to claim 1, wherein for the first monohalogenated carboxylic acid X—C(R,R′)—Y—COOH, X is independently selected from the group consisting of Br and Cl.

5. The method according to claim 4, wherein prior to step (A), the first monohalogenated carboxylic acid is obtained by separating the first monohalogenated carboxylic acid from a corresponding dihalogenated symmetrical anhydride of the formula X—CRR′—Y—CO—O—CO—Y—CRR′—X.

6. The method according to claim 1, wherein the catalyst that is used is a halogenated metal salt.

7. The method according to claim 1, wherein the first amine monomer is selected from the group consisting of: ##STR00005##

8. The method according to claim 1, wherein first monohalogenated carboxylic acid monomer is Br—C(CH.sub.3).sub.2—COOH and first amine monomer is ##STR00006## and the catalyst is CuBr.

9. Poly(alkoxyamine amide) that is obtained by the method according to claim 1.

10. The poly(alkoxyamine amide) according to claim 9, comprising more than one different monohalogenated carboxylic acid monomer and more one than different amine monomer resulting in more than one thermolabile bond.

11. The poly(alkoxyamine amide) according to claim 10, wherein the more than one thermolabile bonds have identical or different dissociation temperatures.

12. A method of making a coded message or data store, comprising forming an element of a code or data to be stored from the poly(alkoxyamine amide) according to claim 9, wherein said element is selected from the group consisting of a binary code, a multinary code, a letter and a sign of the alphanumeric.

13. The method according to claim 12, wherein the thermolabile bond(s), during a heating stage of the poly(alkoxyamine amide) above a dissociation temperature of said thermolabile bond(s), breaks said thermolabile bond(s) and thus at least alters permanently the coded message or the stored data resulting in the coded message or the stored data becoming at least partially incomprehensible and/or unusable.

14. A coded message or data store, comprising the poly(alkoxyamine amide) correspond to claim 9, wherein different monomers of the poly(alkoxyamine amide) correspond to a predefined element of said code or data to be stored, and wherein thermolabile bond(s) of the poly(alkoxyamine amide) during a heating stage of the poly(akoxyamine amide) above a dissociation temperature of said thermolabile bond(s), breaks said thermolabile bond(s) and thus at least alters permanently the coded message or the stored data in such a way that the coded message or the stored data becomes at least partially incomprehensible and/or unusable.

Description

EXAMPLE 1: REACTION OF 2-BROMOISOBUTYRIC ACID ANHYDRIDE WITH A PRIMARY AMINE IMMOBILIZED ON A SOLID SUBSTRATE

(1) In this example, 0.3 g (0.237 mmol, 1 equivalent) of a Wang-PS-type commercial resin, functionalized by a glycine protected by an Fmoc-type protective group (functionality of 0.79 mmol/g), was used as a solid substrate. The resin was introduced into a sintered column making possible the solid-phase synthesis. The resin was then inflated by dichloromethane for 30 minutes while being stirred. Then, the Fmoc protective group of the resin was cleaved by a treatment of two times ten minutes in the presence of an equivolumetric mixture of piperidine and dichloromethane. The formation of a primary amine group on the resin was confirmed by a Kaiser-type colorimetric test. Next, a solution of 2-bromoisobutyric acid anhydride (0.37 g, 5 equivalents) and N,N-diisopropylethylamine (0.95 ml) in 4 ml of anhydrous dimethylformamide was added into the column and brought into the presence of resin for 50 minutes while being stirred mechanically at ambient temperature. After reaction, the modified resin was filtered and washed several times with dimethylformamide and then was characterized by a Kaiser-type colorimetric test confirming the quantitative disappearance of the primary amines.

EXAMPLE 2: REACTION OF 2-BROMOPROPANOIC ACID ANHYDRIDE WITH A PRIMARY AMINE IMMOBILIZED ON A SOLID SUBSTRATE

(2) In this example, the conditions of Example 1 were used with the exception of the 2-bromopropanoic acid anhydride that was replaced by the 2-bromoisobutyric acid anhydride.

EXAMPLE 3: REACTION OF 4-AMINO-TEMPO WITH A SOLID SUBSTRATE FUNCTIONALIZED BY AN ALKYL HALIDE

(3) In this example, a glycine-Wang-PS-type resin, functionalized by an alkyl halide (i.e., a modified resin obtained by following the experimental conditions of Example 1 or Example 2), was used as a solid substrate. This resin was placed in a sintered column making possible the solid-phase synthesis and then brought into the presence of a mixture of 4-amino-TEMPO (0.12 g, 3 equivalents), 0.044 g of copper bromide (I) (1.3 equivalents) and 0.07 ml of tris(2-dimethylaminoethyl)amine (1.3 equivalents) in 5 ml of dimethyl sulfoxide. The column was closed by a skirt plug, and the reaction medium was degassed by bubbling argon through it for several minutes. Next, the reaction mixture was stirred for 15 minutes under an inert atmosphere at ambient temperature. After reaction, the modified resin was filtered and then washed several times with dimethylformamide. The resin was characterized by a Kaiser-type colorimetric test confirming its functionalization by primary amines.

EXAMPLE 4: SYNTHESIS OF A MONODISPERSE POLY(ALKOXYAMINE AMIDE) ON A SOLID SUBSTRATE

(4) Monodisperse poly(alkoxyamine amide)s of different sizes have been synthesized on a glycine-Wang-PS-type commercial resin. The experimental procedure consists in alternating Example 1 (or Example 2) and Example 3 a certain number of times so as to construct a macromolecular chain of a desired length. For the amidification stage, the experimental conditions of Example 1 and Example 2 can be used interchangeably. Thus, the 2-bromopropanoic acid anhydride (Example 1) and the 2-bromoisobutyric acid anhydride (Example 2) can be used in a predefined order during the same synthesis so as to create binary-type controlled monomer sequences. When the required size is reached for the polymer, the latter can be removed from the substrate by reacting the modified resin with an equivolumetric mixture of trifluoroacetic acid and dichloromethane for 2 hours. The poly(alkoxyamine amide) is then isolated by precipitation in the cold diethyl ether. The polymers that are formed were characterized by NMR of the proton and by steric exclusion chromatography in tetrahydrofuran. In all of the cases, the NMR of the proton confirmed the formation of a poly(alkoxyamine amide). In addition, the measurements of steric exclusion chromatography confirm the formation of isomolecular radicals (the polymolecularity indices are between 1.00 and 1.05 according to the tests). For example, for a polymer that is obtained after 9 successive synthesis stages, a mean molar mass of an apparent number of approximately 1270 g mol.sup.−1 and a polymolecularity index of 1.03 have been determined by steric exclusion chromatography.

EXAMPLE 5: REACTION OF 4-AMINO-TEMPO WITH A SOLUBLE POLYSTYRENE SUBSTRATE HAVING AN ALKYL HALIDE AT THE END OF THE CHAIN

(5) In this example, linear polystyrene chains (M.sub.n=4,000 g.Math.mol.sup.−1, M.sub.w/M.sub.n=1.11), prepared by free-radical polymerization controlled by atom transfer, were used as a soluble substrate. One of the two chain ends of this polystyrene is functionalized by a bromine atom, with the other end being functionalized by an inert group. 1.8 g of this soluble polystyrene substrate (1 equivalent), 0.23 g of 4-amino-TEMPO (3 equivalents), 0.084 g of copper (I) bromide (1.3 equivalents), and 0.14 ml of tris(2-dimethylaminoethyl)amine (1.3 equivalents) were introduced into a glass flask and then dissolved in a mixture of tetrahydrofuran (2.8 ml) and dimethyl sulfoxide (1.7 ml). The flask was closed by a skirt plug, and the reaction medium was degassed by bubbling argon through it for several minutes. Next, the reaction mixture was stirred for 15 minutes under an inert atmosphere at ambient temperature. After reaction, the modified polystyrene was purified by precipitation in methanol, washed and then dried under vacuum. The formed polymer was characterized by NMR of the proton and by steric exclusion chromatography in tetrahydrofuran. These two methods confirmed the attachment of a 4-amino-TEMPO unit on the polystyrene chain.

EXAMPLE 6: REACTION OF 2-BROMOISOBUTYRIC ACID ANHYDRIDE WITH A SOLUBLE POLYSTYRENE SUBSTRATE HAVING A PRIMARY AMINE AT THE END OF THE CHAIN

(6) In this example, linear polystyrene chains having a primary amine at the end of the chain (i.e., a modified polymer obtained by following the experimental conditions of Example 5) were used as a soluble substrate. 1.75 g of this soluble polystyrene substrate (1 equivalent), 0.69 g of 2-bromoisobutyric acid (5 equivalents), and 1.75 ml of N,N-diisopropylethylamine were introduced into a glass flask and dissolved in 4 ml of anhydrous dichloromethane. The reaction medium was then stirred for 50 minutes at ambient temperature. After reaction, the modified polystyrene was purified by precipitation in methanol, washed, and then dried under vacuum. The formed polymer was characterized by NMR of the proton and by steric exclusion chromatography in tetrahydrofuran. These two methods confirmed the attachment of a 2-bromoisobutyric acid unit on the polystyrene chain.

EXAMPLE 7: SYNTHESIS OF A MONODISPERSE POLY(ALKOXYAMINE AMIDE) ON A SOLUBLE SUBSTRATE

(7) Poly(alkoxyamine amide)s of different sizes were synthesized on soluble polystyrene substrates having a terminal bromine atom. The experimental procedure consists in alternating Example 5 and Example 6 a certain number of times so as to construct a macromolecular chain of a desired length. After each synthesis stage, the formed polymers were characterized by NMR of the proton and by steric exclusion chromatography in tetrahydrofuran. These two methods of analysis confirmed the iterative formation of a poly(alkoxyamine amide).

EXAMPLE 8: FAST THERMAL DESTRUCTION OF A MONODISPERSE POLY(ALKOXYAMINE AMIDE

(8) In this example, 50 mg of monodisperse poly(alkoxyamine amide) (M=1143 g.Math.mol.sup.−1) was introduced into a flask and dissolved in 8.75 ml of anisole. The mixture is heated to 125° C. for 3 hours. The formed polymer was characterized by steric exclusion chromatography in tetrahydrofuran. This method of analysis showed the transformation of the monodisperse polymer into a polydisperse radical.

EXAMPLE 9: SLOW THERMAL DESTRUCTION OF A MONODISPERSE POLY(ALKOXYAMINE AMIDE)

(9) In this example, 60 mg of monodisperse poly(alkoxyamine amide) (M=1143 g.Math.mol.sup.−1) was introduced into a flask and dissolved in 10.5 ml of anisole. The mixture is heated to 75° C. for 24 hours. The formed polymer was characterized by steric exclusion chromatography in tetrahydrofuran. This method of analysis showed the transformation of the monodisperse polymer into a polydisperse radical.

(10) The method according to the invention makes it possible to produce poly(alkoxyamine amide)s that typically have up to 100 monomer units, preferably 5 to 100 units, more preferably 5 to 50 monomer units, and even more preferably 5 to 25 monomer units.

(11) Of course, the invention is not limited to the embodiments described. Modifications remain possible, in particular from the standpoint of the composition of the various elements or by substitution of equivalent techniques, without thereby exceeding the scope of protection of the invention.