FR2734268A1 - New dendrimer(s) having terminal phosphorus-contg. groups - Google Patents

Abstract

New functional dendrimers comprises a molecule of a base dendrimer formed of a core, and at least four layers of dendritic branches superimposed over this and defining at the molecule surface one or more peripheral terminal sites. It has at least a plurality of identical complementary functional gps., each group being distinct from a dendritic branch, and each plurality of gps. being grafted by substitution or addition on all of at least one terminal peripheral site of the base dendrimer. At least one of the gps. carries a functional phosphorus group of formula R-P; where P is one of -P(R1)(R1'), -P(=Y1)(R2)(R2'), -P(?>M)(R3)(R3'), -O-P(=Y2)(R4)(R4'), -P(R5)(R5')(R5")(R5"') or a gp. (i); R1, R1' = H, amino, alkyl, aryl, alkoxy or aryloxy; R2, R2', R3, R3' = H, halogen, hydroxy, amino, alkyl, aryl, alkoxy or aryloxy, or an alkyl or aryl radical substd by at least one silylated or phosphorylated group; M = a metal or a metallic or boron group that can complex with the phosphorus; R4, R4' = H, halogen, hydroxy, amino, alkyl, aryl, alkoxy or aryloxy; Y1 = O, S or N-R11; R11 = H, alkyl, aryl, or a silylated group; Y2 = O, S, an electron doublet, or NR11; R5, R5', R5", R5"' = H, amino, alkyl, alkoxy, aryloxy, or aryl; R6, R6' = 4 - 6 membered homocyclic or heterocyclic chains closed through the P atom; and R = a group containing a carbon attached to the functional group P and attached through a covalent bond to the rest of the dendrimer molecule thus formed.

Description

NEW FUNCTIONAL DENDRIMERS WITH TERMINATIONS
PHOSPHORUSES AND THEIR PREPARATION PROCESS
The invention relates to novel functional dendrimers with phosphorus-terminated endings.

 Dendrimers (also called cascade molecules, fractal molecules or arborols) are polymer molecules with a structure in a burst star ("starburst" in English) obtained by successive grafting of repeating units from a heart.

Definitions and examples of dendrimers and their methods of preparation can be found in patents US-4,507,466, US-4,558,120, US-4,568,737,
US-4,587,329 and US-4,631,337, and EP-A-0 271 180.

 Although the theoretical principles underlying dendrimers are known, in particular from the patents raised, the effective synthesis of these macromolecules in a homogeneous, pure manner and under economic conditions compatible with industrial exploitation poses many unsolved problems.

 Thus, dendrimers having various terminal ends directly after their synthesis in successive generations have been theoretically cited, in particular in certain patents raised. It is indeed a well known advantage of dendrimers to present a high density of terminations, and therefore of functions, at their periphery. However, no concrete example is given of such molecules having phosphorus-containing functions (phosphines, phosphinates, phosphates, phosphonates, phosphoranes, spirophosphoranes ...).

 However, the preparation of such macromolecules and the selective surface grafting of determined phosphorus functions have not been possible until now.

This is particularly true for dendrimers whose number of generations is high, -notably greater than or equal to 4- to present an interesting density of peripheral functions and in particular a number of surface functions greater than 1000, more particularly greater than 5 000-.

 In addition, certain dendrimers presenting terminal peripheral sites with neutral phosphorus or phosphonium have been described. Nevertheless, it is clear that the structure of the terminal site obtained, and its properties, are closely dependent on the structure of the internal repeating units of the dendrimer, which is chosen to obtain the dendrimer with a number of generations as high as possible.

So the publication "A General Synthetic
Strategy For Neutral Phosphorus - Containing Dendrimers ",
Nathalie Launay, Anne-Marie Caminade, Roger Lahana, Jean
Pierre Majoral, Angew. Chem. Int. Ed. Engl. 1994, 33,
No. 15/16, p. 1589-1592, illustrates an example of a four-generation phosphorus dendrimer.

More recently, the publication "Synthesis and Reactivity of Unusual Phosphorus Dendrimer - A Useful
Divergent Growth Approach Up to the Seventh Generation ",
Nathalie Launay, Anne-Marie Caminade, Jean-Pierre Majoral,
Journal of American Chemical Society, 1995, volume 117, pages 3382-3383, describes an example of this dendrimer until the seventh generation. In addition, this last publication describes the reactivity of this dendrimer with organic compounds such as acetylmethylene triphenylphosphorane, piperazine, 4-aminobenzo-15-crown-5 and bisallylamine.

 On the other hand, the reactivity and the grafting of specific functions with neutral phosphorus where the phosphorus is linked to three atoms (for example phosphines or phosphinates), or to four atoms (for example, phosphonates, and more particularly still phosphates) , phosphoranes and spirophosphoranes are poorly controlled and pose problems. Indeed, these functions have specific reaction behaviors which can be very different from one function to another depending in particular on the phosphorus coordination index.

 In this context, the invention aims to propose new functional dendrimers, and their preparation process, which may have various phosphorous functional endings.

 Thus, the invention aims to solve the general problem of grafting various uncharged phosphorus functional terminations (electronically neutral) on a dendrimer, under economic conditions compatible with industrial exploitation, that is to say with quantitative yields, from inexpensive starting materials, and short reaction times.

 The invention also aims to propose dendrimers as mentioned above which can have a high number of generations - in particular at least four and which can go up to twelve - whose terminal peripheral sites include phosphorous functional endings selectively grafted to the surface of the dendrimer.

 The invention aims more particularly to propose a dendrimer comprising on the surface more than 1,000, in particular more than 6,000, or even more than 10,000 phosphorus-containing functions.

 The invention also aims to propose new dendrimers comprising at the surface functions incorporating at least one trivalent phosphorus atom (whose coordination index is three), and / or phosphine and / or phosphinate functions.

 The invention also aims to propose new dendrimers as mentioned above which, moreover, have great stability.

A dendrimer is a monodispersed polymer whose structural characteristics are
1) a heart, called a dendritic heart, formed either of a simple atom on which are grafted a certain number of functional groups, or of a set of determined atoms forming a group, a heterocycle or even a macrocycle, this heart being able be exclusively organic, or inorganic, or have both organic and inorganic groups
2) at least two identical or non-superimposed layers from the core, each layer comprising at least one series of identical branches known as dendritic branches, each dendritic branch consisting of a set of atoms forming a determined structure which diverges at the periphery of the corresponding layer.

 The number of dendritic branches of each layer is an integer multiple, of multiplying coefficient at least equal to 2, of the number of dendritic branches of the previous internal layer on which this layer is superimposed. In particular, the numbers of dendritic branches of the different layers form a geometric sequence of integer reason equal to 2 or greater than 2.

 The last outer layer comprises a plurality of identical chemical functions distributed around the periphery, each function constituting or extending the free end of one of said dendritic branches of the last layer.

 The number of these functions is an integer multiple, of multiplying coefficient at least equal to 2, of the number of dendritic branches of said last outer layer.

 Most often the dendritic branches of all the internal layers of the dendrimer are identical and therefore constitute repeating units.

The different layers are obtained in successive generations by various processes of the divergent type (if one starts from the heart) or convergent (if one starts from one or more dendritic branches) in one or more stages. The dendrimers obtained in each generation, that is to say having a determined number of layers, can be isolated;
The different layers (internal or external) can be, like the heart, organic, inorganic, or consist of organic and inorganic elements.

 The construction of these dendrimers can be rigorously controlled. For example, to build a dendrimer, a series of dendritic branches is fixed to the heart and forms a first layer (generation 1) comprising on the periphery the same external functions and, by repeating the sequence of reactions used to build the first generation, a second layer is fixed (generation 2) then a third, a fourth, etc ...

 The shape of the molecule generally has a spherical shape from generations 4 or 5. A dendrimer has a set of chemical functions and locations of the same chemical environment allowing the grafting of one or more functional group (s) distributed on the periphery of the dendrimer.

Throughout the text of the present application, the expression “terminal peripheral site” designates such a set of chemical functions and peripheral locations of the same chemical environment.

où P est le phosphore,
R7, R1' sont des groupes identiques ou différents formés de l'hydrogène, ou d'un radical amino, ou d'un radical alkyle ou aryle ou alcoxyle ou aryloxyle,
R2, R2' sont des groupes identiques ou différents formés d'un hydrogène, ou d'un halogène, ou d'un radical hydroxyle ou amino, ou d'un radical alkyle ou aryle ou alcoxyle ou aryloxyle, ou d'un radical alkyle ou aryle substitué par au moins un groupement silylé ou phosphore,
R3, R3' sont des groupes identiques ou différents formés d'un hydrogène, d'un halogène, ou d'un radical hydroxyle ou amino, ou d'un radical alkyle ou aryle ou alcoxyle ou aryloxyle, ou d'un radical alkyle ou aryle substitué par au moins un groupement silylé ou phosphore,
M est un métal ou un groupement métallique ou boré apte à former un complexe avec le phosphore,
R4, R4' sont des groupes identiques ou différents formés d'un hydrogène, ou d'un halogène, ou d'un radical hydroxyle ou amino, ou d'un radical alkyle ou aryle ou alcoxyle ou aryloxyle,
Y1 est l'oxygène, ou le soufre, ou un radical N-R11 ou
R11 est un hydrogène, ou un radical alkyle ou aryle, ou un radical silylé,
Y2 est l'oxygène, ou le soufre, ou un doublet électronique, ou un radical N-R11 où R11 est un hydrogène, un radical alkyle ou aryle ou un radical silylé,
R5, R5', R5", R5"' sont des groupes identiques ou différents formés de l'hydrogène, ou d'un radical amino, ou d'un radical alkyle ou alcoxyle ou aryloxyle ou aryle,
R6, R6' sont des chaînes homocycliques ou hétérocycliques identiques ou différentes fermées sur le phosphore et ayant un nombre d'atomes dans la chaîne principale compris entre 4 et 6,
et où R est un groupe qui comprend un atome de carbone lié au radical fonctionnel phosphoré [P] et qui est lié par une liaison covalente au reste de la molécule du dendrimère ainsi formé.The invention therefore relates to a functional dendrimer comprising a molecule of a basic dendrimer formed by a heart, at least four superimposed layers of dendritic branches from the heart and defining, on the surface of the molecule, one or more terminal peripheral sites. , characterized in that it comprises at least a plurality of identical complementary functional groups, each complementary functional group being distinct from a dendritic branch, each plurality of complementary functional groups being grafted by substitution or addition on the totality of at least one terminal peripheral site of the base dendrimer, with a complementary functional group grafted onto each location of said terminal peripheral site, and in that at least one such complementary functional group comprises at least one phosphorus functional group of formula
--- R - [P] where [P] is a phosphorus functional radical chosen from one of the radicals of formula

where P is phosphorus,
R7, R1 ′ are identical or different groups formed from hydrogen, or from an amino radical, or from an alkyl or aryl or alkoxyl or aryloxyl radical,
R2, R2 'are the same or different groups formed of a hydrogen, or a halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical, or an alkyl radical or aryl substituted by at least one silyl or phosphorus group,
R3, R3 'are identical or different groups formed by hydrogen, halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical, or an alkyl radical or aryl substituted with at least one silyl or phosphorus group,
M is a metal or a metallic or boron group capable of forming a complex with phosphorus,
R4, R4 ′ are identical or different groups formed of a hydrogen, or a halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical,
Y1 is oxygen, or sulfur, or an N-R11 radical or
R11 is hydrogen, or an alkyl or aryl radical, or a silylated radical,
Y2 is oxygen, or sulfur, or an electronic doublet, or an N-R11 radical where R11 is a hydrogen, an alkyl or aryl radical or a silylated radical,
R5, R5 ', R5 ", R5"' are identical or different groups formed from hydrogen, or from an amino radical, or from an alkyl or alkoxyl or aryloxyl or aryl radical,
R6, R6 ′ are identical or different homocyclic or heterocyclic chains closed on phosphorus and having a number of atoms in the main chain between 4 and 6,
and where R is a group which comprises a carbon atom linked to the phosphorus functional radical [P] and which is linked by a covalent bond to the rest of the dendrimer molecule thus formed.

 According to the invention, the dendrimer comprises at least one phosphorus functional group in the extreme peripheral position of said complementary functional group, and of the molecule of the functional dendrimer. Advantageously and according to the invention, each phosphorus functional group is terminal, that is to say located at the end of a branch of said complementary functional group, and preferably at the surface of the molecule.

 A functional group complementary to a dendrimer according to the invention is an organic group whose structure is determined to provide a determined property to the molecule (for example catalyst, insecticide, fungicide, pesticide, cosmetic, therapeutic agent, etc.) and which is a complement to the base dendrimer, in the sense that it is distinct from a dendritic branch or from a repeating unit and is not normally present at the end of a step of generation of the base dendrimer.

 A dendrimer according to the invention can comprise a plurality of identical complementary functional groups occupying the whole of a terminal peripheral site. Thus, each of the peripheral locations of the terminal peripheral site is occupied by this complementary functional group which is distributed over the surface of the dendrimer molecule. In other words, the number of complementary functional groups of each plurality of identical complementary functional groups is the same as the number of locations from the terminal peripheral site to the periphery of the dendrimer.

 A dendrimer according to the invention can comprise a plurality of identical complementary functional groups occupying several terminal peripheral sites, or even all the terminal peripheral sites. The dendrimer obtained is then monofunctional if the complementary functional group is mono functional itself.

 A dendrimer according to the invention can also be multifunctional and include several pluralities of complementary functional groups respectively occupying different terminal peripheral sites.

 A dendrimer according to the invention can also be multifunctional and comprise a complementary functional group which is itself multifunctional in the sense that it comprises several different phosphorus functional groups (of different functions), for example a phosphine functional group and a functional group. phosphinate.

 Also, the same functional group complementary to a dendrimer according to the invention may comprise several identical phosphorus functional groups in the extreme position of the same branch or of different branches. Thus, each complementary functional group can be monophosphorus or, on the contrary, polyphosphorus.

 Likewise, each phosphorus-containing functional group can also be monophosphorus or polyphosphorus.

As an example of a polyphosphorus functional group, mention may be made of ... CH [phosphine] [phosphinate]. Thus, the terminal carbon of R can be linked to two identical or different phosphorus radicals [P].

We can classify the phosphorus radicals which can be incorporated into a phosphorus functional group of a dendrimer according to the invention into families each presenting particularities and advantages
- radicals where the phosphorus is linked by three covalent bonds to three atoms (coordination index equal to 3) phosphines, phosphinates ...

the corresponding metal or boron complexes

phosphates ... :

- radicals where the phosphorus is linked by four covalent bonds to four atoms (coordination index equal to 4):
phosphonates ...:

phosphates ...:

spirophosphoranes

- radicals where the phosphorus is linked by five covalent bonds to five atoms (coordination index equal to 5) phosphoranes

spirophosphoranes

 The invention relates to each of these families, as well as their combinations on the same dendrimer.

Thus, the invention relates more particularly
a dendrimer comprising at the surface at least one phosphine group or a metallic or boron complex of phosphine group,
a dendrimer comprising at the surface at least one phosphinate group or a metallic or boron complex of phosphinate group,
a dendrimer comprising at the surface at least one phosphorane group,
- A dendrimer comprising at the surface at least one spirophosphorane group.

où C est le carbone, et K1, K2 sont des chaînes organiques dont l'une au moins comprend au moins un hétéroatome choisi parmi l'azote, l'oxygène, le phosphore, le silicium, le bore, le soufre, l'arsenic ou le germanium, K1 étant liée par une liaison covalente au reste de la molécule du dendrimère ainsi formé.The invention also relates to a dendrimer characterized in that it comprises at least a plurality of identical complementary functional groups of formula

where C is carbon, and K1, K2 are organic chains, at least one of which comprises at least one heteroatom chosen from nitrogen, oxygen, phosphorus, silicon, boron, sulfur, arsenic or germanium, K1 being linked by a covalent bond to the rest of the dendrimer molecule thus formed.

 More particularly, the invention relates to a dendrimer characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula --- A1 - R '- [P] where Al is a heteroatom chosen from nitrogen, l 'oxygen, phosphorus, silicon, boron, sulfur, arsenic or germanium, and R' is a carbon atom or a carbon chain interposed between A1 and [P].

More particularly, A1 is nitrogen and the dendrimer according to the invention comprises at least a plurality of identical phosphorus functional groups of formula
- N - R1 ~ [p]
or
- N = R2 - [p] where N is nitrogen,
R1 and R2 represent a carbon atom or a carbon chain interposed between N and [P].

 Advantageously, R1 or R2 represents a hydrocarbon chain. More particularly, the invention relates to such a dendrimer where R1 or R2 comprises a carbon atom connecting nitrogen A1 to a phosphorus of the phosphorus radical [P].

More particularly, the invention relates to a dendrimer characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula

où R3 est l'hydrogène ou un radical alkyle ou aryle,
R4 est l'hydrogène ou un radical alkyle -notamment méthyle- ou aryle, ou un autre groupement fonctionnel phosphoré identique ou différent du groupement fonctionnel phosphoré greffé sur le même atome d'azote,
K3 est une fraction de branche dendritique directement greffée, dans le dendrimère de base, à une branche dendritique de la génération précédente. Avantageusement et selon l'invention, K3 est le groupe de formule
- O - C6H4 où O est l'oxygène, et C6H4 est un noyau benzénique.The invention also relates to a dendrimer characterized in that it comprises at least a plurality of identical complementary functional groups, each complementary functional group being grafted on a location of said terminal peripheral site by means of a hydrazone motif of general formula
-C = NN or
-NN = C
More particularly, the invention relates to a dendrimer characterized in that it comprises at least a plurality of identical complementary functional groups of formula

where R3 is hydrogen or an alkyl or aryl radical,
R4 is hydrogen or an alkyl radical - notably methyl- or aryl, or another phosphorus functional group identical or different from the phosphorus functional group grafted on the same nitrogen atom,
K3 is a fraction of a dendritic branch directly grafted, in the base dendrimer, to a dendritic branch of the previous generation. Advantageously and according to the invention, K3 is the group of formula
- O - C6H4 where O is oxygen, and C6H4 is a benzene nucleus.

où R5 et R6 sont l'hydrogène, ou un radical alkyle ou aryle.Also advantageously, R is the group of formula

where R5 and R6 are hydrogen, or an alkyl or aryl radical.

où R7 et R8 sont l'hydrogène ou des radicaux alkyles ou aryles identiques ou différents, et
R9 est l'hydrogène, ou un radical alkyle, propargyle, alkyle ou aryle, ou un groupe

identique ou différent du groupe

greffé sur le même atome d'azote. Avantageusement et selon l'invention, ledit groupement fonctionnel phosphoré est greffé sur un site périphérique terminal et forme un groupe fonctionnel complémentaire du dendrimère.The invention also relates to a dendrimer characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula

where R7 and R8 are hydrogen or identical or different alkyl or aryl radicals, and
R9 is hydrogen, or an alkyl, propargyl, alkyl or aryl radical, or a group

identical or different from the group

grafted on the same nitrogen atom. Advantageously and according to the invention, said phosphorus-containing functional group is grafted onto a terminal peripheral site and forms a functional group complementary to the dendrimer.

où A2 est un hétéroatome choisi parmi l'azote, l'oxygène, le phosphore, le silicium, le bore, le soufre,
Rm sont m (m > 1) groupes choisis parmi l'hydrogène, ou un radical silylé, phosphore, ou boré, ou un radical alkyle ou aryle,
R10 est l'hydrogène ou un radical alkyle ou aryle. Plus particulièrement et selon l'invention, le dendrimère comporte au moins une pluralité de groupes fonctionnels complémentaires identiques de formule

où K3 est une fraction de branche dendritique directement greffée, dans le dendrimère de base, à une branche dendritique de la couche interne précédente. Par exemple,
K3 est le groupe de formule
- O - C6H4 où O est l'oxygène et C6H4 est un noyau benzénique.The invention also relates to a dendrimer characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula

where A2 is a heteroatom chosen from nitrogen, oxygen, phosphorus, silicon, boron, sulfur,
Rm are m (m> 1) groups chosen from hydrogen, or a silylated, phosphorous or boron radical, or an alkyl or aryl radical,
R10 is hydrogen or an alkyl or aryl radical. More particularly and according to the invention, the dendrimer comprises at least a plurality of identical complementary functional groups of formula

where K3 is a fraction of a dendritic branch directly grafted, in the base dendrimer, to a dendritic branch of the preceding internal layer. For example,
K3 is the formula group
- O - C6H4 where O is oxygen and C6H4 is a benzene nucleus.

où P est le phosphore,
Y3 est l'oxygène, le soufre, ou un radical N - R111 où R11 est un radical alkyle ou aryle.En outre, avantageusement et selon l'invention, les branches dendritiques Bi sont de formule

où O est l'oxygène,
C est le carbone,
H est l'hydrogène,
N est l'azote,
C6H4 est le noyau benzénique,
P est le phosphore,
Me est le radical méthyle,
Y4 est l'oxygène, le soufre ou un radical N-R11 où
R11 est un hydrogène, un radical alkyle ou aryle, ou un radical silylé.Advantageously and according to 1 invention, the dendrimer corresponds to the formula
Do - (Bi) n - T - Gk where Do is a dendritic core, n is the number of generations of the base dendrimer Bi are dendritic branches of the n layers of the base dendrimer,
T represents the terminal peripheral site (s) of the last layer of the base dendrimer, and
Gk represents one (or more) of identical complementary functional groups. n can be between 4 and 12. A dendrimer according to the invention advantageously comprises at least one terminal peripheral site T of formula

where P is phosphorus,
Y3 is oxygen, sulfur, or an N - R111 radical where R11 is an alkyl or aryl radical.In addition, advantageously and according to the invention, the dendritic branches Bi are of formula

where O is oxygen,
C is carbon,
H is hydrogen,
N is nitrogen,
C6H4 is the benzene nucleus,
P is phosphorus,
Me is the methyl radical,
Y4 is oxygen, sulfur or an N-R11 radical where
R11 is hydrogen, an alkyl or aryl radical, or a silylated radical.

The dendritic core Do of a dendrimer according to the invention is advantageously a phosphorus core such that X = P Cl3 (where X is oxygen or sulfur), or
P3 N3 Cl6 ...

 A dendrimer according to the invention comprises on the surface more than 1,000 - in particular more than 6,000 -, or even more than 10,000 phosphorus-containing functional groups. More particularly, according to the invention and in the tests carried out mentioned below, a dendrimer according to the invention comprises on the surface a number of functional phosphorus groups of between 24 and 6,144. A twelfth generation dendrimer according to l invention comprising 12,288 phosphorus functional groups.

où P est le phosphore,
R1, R1' sont des groupes identiques ou différents formés de l'hydrogène, ou d'un halogène ou d'un radical amino, ou d'un radical alkyle ou aryle ou alcoxyle ou aryloxyle,
R2, R2' sont des groupes identiques ou différents formés d'un hydrogène, ou d'un halogène, ou d'un radical hydroxyle ou amino, ou d'un radical alkyle ou aryle ou alcoxyle ou aryloxyle, ou d'un radical alkyle ou aryle substitué par au moins un groupement silylé ou phosphore,
R3, R3' sont des groupes identiques ou différents formés d'un hydrogène, d'un halogène, ou d'un radical hydroxyle ou amino, ou d'un radical alkyle ou aryle ou alcoxyle ou aryloxyle, ou d'un radical alkyle ou aryle substitué par au moins un groupement silylé ou phosphore,
M est un métal ou un groupement métallique ou boré apte à former un complexe avec le phosphore,
R4, R4' sont des groupes identiques ou différents formés d'un hydrogène, ou d'un halogène, ou d'un radical hydroxyle ou amino, ou d'un radical alkyle ou aryle ou alcoxyle ou aryloxyle,
Y1 est l'oxygène, ou le soufre, ou un radical N-R11 où
R11 est un hydrogène, ou un radical alkyle ou aryle, ou un radical silylé,
Y2 est l'oxygène, ou le soufre, ou un doublet électronique, ou un radical N-R11 où R11 est un hydrogène, un radical alkyle ou aryle ou un radical silylé,
R5, R5', R5", R5"' sont des groupes identiques ou différents formés de l'hydrogène, ou d'un radical amino, ou d'un radical alkyle ou alcoxyle ou aryloxyle ou aryle,
R6, R6' sont des chaînes homocycliques ou hétérocycliques identiques ou différentes fermées sur le phosphore et ayant un nombre d'atomes dans la chaîne principale compris entre 4 et 6,
et où R est un groupe comprenant un atome de carbone lié au radical fonctionnel phosphoré [P],
- en ce qu'on choisit R et [P] pour que ledit groupe fonctionnel complémentaire puisse être greffé sur la totalité d'au moins un site périphérique terminal du dendrimère de base,
- et en ce qu'on greffe par substitution ou addition ledit groupe fonctionnel complémentaire sur la totalité dudit site périphérique terminal du dendrimère de base.The invention further relates to a process for the preparation of a functional dendrimer according to the invention in which a molecule of a basic dendrimer formed from a heart is prepared, at least four layers of dendritic branches superimposed from the heart and defining, at the surface of the molecule, one or more terminal peripheral sites, characterized
- in that one chooses at least one complementary functional group, which is distinct from a dendritic branch, and which comprises at least one phosphorus functional group of formula
--- R - [P] where [P] is a phosphorus functional radical chosen from one of the radicals of formula

where P is phosphorus,
R1, R1 ′ are identical or different groups formed from hydrogen, or from a halogen or from an amino radical, or from an alkyl or aryl or alkoxyl or aryloxyl radical,
R2, R2 'are the same or different groups formed of a hydrogen, or a halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical, or an alkyl radical or aryl substituted by at least one silyl or phosphorus group,
R3, R3 'are identical or different groups formed by hydrogen, halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical, or an alkyl radical or aryl substituted with at least one silyl or phosphorus group,
M is a metal or a metallic or boron group capable of forming a complex with phosphorus,
R4, R4 ′ are identical or different groups formed of a hydrogen, or a halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical,
Y1 is oxygen, or sulfur, or an N-R11 radical where
R11 is hydrogen, or an alkyl or aryl radical, or a silylated radical,
Y2 is oxygen, or sulfur, or an electronic doublet, or an N-R11 radical where R11 is a hydrogen, an alkyl or aryl radical or a silylated radical,
R5, R5 ', R5 ", R5"' are identical or different groups formed from hydrogen, or from an amino radical, or from an alkyl or alkoxyl or aryloxyl or aryl radical,
R6, R6 ′ are identical or different homocyclic or heterocyclic chains closed on phosphorus and having a number of atoms in the main chain between 4 and 6,
and where R is a group comprising a carbon atom linked to the phosphorus functional radical [P],
- in that one chooses R and [P] so that said complementary functional group can be grafted onto the whole of at least one terminal peripheral site of the base dendrimer,
- And in that one graft by substitution or addition said complementary functional group on the whole of said terminal peripheral site of the base dendrimer.

 According to the invention, at least one complementary functional group and / or at least one phosphorus functional group is chosen from those described above with reference to the dendrimers according to the invention.

et, pour greffer le(les) groupe(s) fonctionnel(s) complémentaire(s)
on fait réagir le dendrimère de base avec une R13-hydrazine de façon à former, à partir de chaque fonction carbonyle, une terminaison hydrazone de formule

où R13 est l'hydrogène, ou un radical alkyle ou aryle,
R12 est l'hydrogène ou un radical alkyle ou aryle,
on greffe ensuite au moins un groupement fonctionnel phosphoré (tel que sus-mentionné) sur chaque terminaison hydrazone.Advantageously, according to the invention, in a first variant of the process, a base dendrimer is prepared having carbonyl functions on the surface

and, to graft the complementary functional group (s)
reacting the base dendrimer with an R13-hydrazine so as to form, from each carbonyl function, a hydrazone termination of formula

where R13 is hydrogen, or an alkyl or aryl radical,
R12 is hydrogen or an alkyl or aryl radical,
then grafted at least one phosphorus functional group (as mentioned above) on each hydrazone termination.

où R15 est le radical R13 ou un autre groupement fonctionnel phosphoré identique ou différent de celui greffé sur le même atome d'azote.In this way; a dendrimer with intermediate hydrazone units is prepared. For example, and according to the invention, reacting at least one phosphorus alcohol of formula
HO - R - [P] on the hydrazone-terminated dendrimer, so as to obtain a substituted substituted functional dendrimer

where R15 is the radical R13 or another phosphorus functional group identical or different from that grafted on the same nitrogen atom.

ou P est le phosphore,
Y3 est l'oxygène, le soufre ou un radical N-R111 où
R11 est un radical alkyle ou aryle,
X est un halogène, et pour greffer le(les) groupe(s) fonctionnel(s) complémentaire(s),
on réalise une double amination des terminaisons halogénées de façon à obtenir en surface des terminaisons aminées de formule

où chacun de R16, R17, R18 est l'hydrogène ou un radical alkyle, propargyle, alkyle, ou aryle,
et on fait régir ces terminaisons aminées avec un alcool phosphoré
HO - R - [P] de façon à obtenir un dendrimère fonctionnel substitué à terminaisons

ou R19, R20, R21 sont respectivement R16, R17, R18 ou un autre groupement fonctionnel phosphoré identique ou différent.According to the invention and in a second variant of the process, a base dendrimer with terminations is prepared

where P is phosphorus,
Y3 is oxygen, sulfur or an N-R111 radical where
R11 is an alkyl or aryl radical,
X is a halogen, and to graft the complementary functional group (s),
a double amination of the halogenated terminations is carried out so as to obtain on the surface amine terminations of formula

where each of R16, R17, R18 is hydrogen or an alkyl, propargyl, alkyl, or aryl radical,
and we govern these amino terminations with a phosphorus alcohol
HO - R - [P] so as to obtain a substituted functional dendrimer with endings

or R19, R20, R21 are respectively R16, R17, R18 or another identical or different phosphorus functional group.

et pour greffer le(les) groupe(s) fonctionnel(s) complémentaire(s), on fait réagir le dendrimère de base avec un composé phosphoré de formule H - [P], de façon à former, à partir de chaque fonction carbonyle, une terminaison de formule

où R12 est l'hydrogène ou un radical alkyle ou aryle.According to the invention and in a third variant of the process, a base dendrimer is prepared having carbonyl functions on the surface

and to graft the complementary functional group (s), the base dendrimer is reacted with a phosphorus compound of formula H - [P], so as to form, from each carbonyl function , a termination of formula

where R12 is hydrogen or an alkyl or aryl radical.

The invention thus makes it possible to have functional dendrimers having phosphorus-containing functions on the surface and which, in addition
can be prepared from inexpensive starting materials such as SPCl3, OPCl3,
HOC6H4CHO, HNCH3NH2, Ph2PH, (HCHO) n, and with excellent yields, that is to say under economic conditions compatible with exploitation on an industrial scale,
are perfectly stable, thanks in particular to the presence of the carbon group R connecting each phosphorus functional radical [P] to the rest of the molecule,
are perfectly soluble in most common organic solvents (THF, chloroform, dichloromethane, dioxane ...),
can have various phosphorous functions, and be mono or multifunctional,
may contain a considerable number and therefore a high density of phosphorus-containing functions.

 The invention further relates to new functional dendrimers and to their method of manufacture having in combination all or part of the characteristics above or below mentioned.

Other characteristics and advantages of the invention will appear from the examples and figures in which
FIG. 1 is a schematic plan view of an example of a tenth generation base dendrimer (with 10 layers) which can serve as a starting product for the preparation of a functional dendrimer according to the invention,
FIG. 2 is a reaction diagram illustrating an example of a process for the preparation of base dendrimers up to generation 12 similar to the base dendrimer of FIG. 1,
FIGS. 3 to 19 are reaction diagrams illustrating the methods of preparation according to the invention of the functional dendrimers according to the invention described in examples 1 to 17 below,
- Figure 20 is a schematic plan view of the functional dendrimer according to the invention of Example 16 below.

 Traditionally, throughout the present application and in the figures, "Ph" represents a phenyl, "Me" represents a methyl, "Et" represents an ethyl, and the broken lines represent carbon chains.

 First of all, a base dendrimer is prepared comprising between 4 and 12 layers of dendritic branches (generations 4 to 12), for example using the synthesis process represented in FIG. 2 and described below.

 FIG. 2 shows the formation of the first layer (that is to say the first generation), which is done in several stages starting from the dendritic core SPCl3 (trichlorothiophosphine).

 The base dendrimer may present, for each generation, either halogenated peripheral functions, in particular chlorinated, or carbonyl peripheral functions, in particular aldehydes.

In a first step, an aldehyde sort is prepared in the following manner
To a heterogeneous solution of 0.1 mol (2.4 g) of sodium hydride in 100 ml of THF is added dropwise at room temperature and under argon a solution of 0.082 mole (10 g) of hydroxybenzaldehyde in 150 ml of THF. A gas evolution of hydrogen is formed and a brown precipitate which is the sodium salt of hydroxybenzaldehyde. The mixture is left stirring for 2 hours at room temperature, then filtered. The precipitate is washed with 50 ml of THF, then evaporated to dryness to give a brown powder.

 A solution of 0.025 mole (2.54 ml) of trichlorothiophosphine in 300 ml of THE is added to the brown powder of the sodium salt of the hydroxybenzaldehyde obtained above, at room temperature. This mixture is left for 20 hours with stirring. The sodium salt formed is removed by centrifugation. The phosphorus trialdehyde is obtained after evaporation to dryness of the solvent and washing of the powder with ether (3 x 30 ml). This trialdehyde is characterized by NMR 31P, 1H, 13C, infrared and elementary analysis. The yield is greater than 93%.

 In a second step, the first generation of the base dendrimer with chlorinated peripheral ends is prepared in the following manner.

To a solution of 0.025 mole of
H2N-N (Me) P (S) Cl2 in 100 ml of chloroform, 0.008 mol (3.40 g) of the trialdehyde obtained previously is added. The mixture is left under stirring at room temperature for 12 hours. Evaporated to dryness and the powder obtained is washed three times with a pentane / ether mixture (1/2).

The first generation base dendrimer (6 ends
Cl) is thus obtained in the form of a white powder. The yield is quantitative.

 This dendrimer is characterized by NMR 31P, 1H, 13C, infrared, mass spectrometry and elementary analysis.

 The first generation of the base dendrimer with aldehyde ends is then prepared in the following manner.

 The procedure is identical to that described in the first step, using 0.05 mole of sodium salt of hydroxybenzaldehyde and 0.008 mole of the first generation dendrimer (with Cl ends). The dendrimer with 6 CHO ends is obtained with a yield greater than 95% and characterized by NMR 31P, 1H, 13C, infrared, mass spectrometry and elementary analysis.

 For the synthesis of the second generation of the base dendrimer (12 Cl ends), the procedure is identical to that of the second step described above, using 0.025 mole of H2N-N (Me) P (S) Cl2 and 0.004 mole (5.7 g) of first generation dendrimer with 6 aldehyde ends.

The second generation dendrimer (12 Cl ends) is isolated in the form of a white powder with a yield greater than 93% and characterized by
31P NMR, 1H, 13C, infrared, mass spectrometry and elementary analysis.

 The construction of the base dendrimer can be continued to obtain the higher generations by alternately using the procedures described in the first and second stages. All the products were isolated, with yields greater than 92% and characterized by NMR 31P, 1H, 13C, infrared and elemental analysis up to the twelfth generation (12,288 chlorine ends).

 Figure 1 is a plan view showing a representation of the tenth generation base dendrimer which can thus be obtained with a chlorine or aldehyde terminal peripheral site.

This basic dendrimer therefore corresponds to the formula: DO - (Bi) 10 - T where Do is S =

T is chlorine or O-C6H4-CH = O
From these basic dendrimers, functional dendrimers according to the invention were prepared in accordance with Examples 1 to 17 below.

 In FIGS. 3 to 19 representing the reaction schemes used in these examples, only one end of a dendritic branch of the last layer of each dendrimer has been shown. It is understood that all the dendritic branches of this last extreme layer have the same ends. The number of these ends is indicated by subscript in the rectangles which schematize the dendrimers.

 The dendrimers described in the examples are characterized by nuclear magnetic resonance 31p, 1H, 13c, infrared spectroscopy and elementary analysis.

EXAMPLE 1
A 10th generation functional dendrimer with phosphine ends is prepared by substitution of methylhydrazone at the terminal peripheral sites with aldehyde ends. The reaction scheme is that shown in FIG. 3.

In a first step, a dendrimer substituted with methylhydrazone is prepared in the following manner
To a solution of the 10th generation base dendrimer (FIG. 1) with aldehyde ends (1.02 g; 10-6 mole) in 20 ml of chloroform, a solution of monomethylhydrazine (0.33) is added dropwise and very slowly. ml; 6,2.10-3 mole, i.e. 100% excess) in 15 ml of chloroform and at room temperature. This mixture is left to react for 2 hours at room temperature, then the solvent is evaporated under vacuum, as well as the excess of methylhydrazine. A white powder is obtained, which is washed with 10 ml of ether. The dendrimer with methylhydrazone ends is isolated in the form of a white powder with a yield greater than 90%.

 In a second step, phosphine groups (a phosphine by methylhydrazone) are grafted (by substitution) in the following manner.

 A solution of the dendrimer with methylhydrazone ends obtained previously (1.11 g; 10-6 mole) in 20 ml of tetrahydrofuran THF, is added to a solution of Ph2PCH20H (0.67 g; 3.072.10-3 mole) in 10 ml of tetrahydrofuran THF. The reaction mixture is then heated to 650C for three days in a closed container.

The solvent is then evaporated to dryness, to give a yellow oil which is washed twice with 13 ml of a pentane / ether mixture (1/1). A functional dendrimer with phosphine ends is then obtained in the form of a white powder, with a yield greater than 85%.

 The characterization of this white powder by the characterization methods demonstrates the presence of 3072 functional phosphine groups --- CH2-PPh2.

où K3 est -O-C6H4
R3 est l'hydrogène,
R4 est le méthyle,
R est CH2
[P] est -PPh2
EXEMPLE 2
On prépare un complexe du fer sous forme
Fe(CO)4 du dendrimère fonctionnel de 10ème génération à extrémités phosphines préparé à l'exemple 1. Le schéma réactionnel est celui représenté figure 4.This functional dendrimer therefore comprises 3072 complementary functional groups of formula

where K3 is -O-C6H4
R3 is hydrogen,
R4 is methyl,
R is CH2
[P] is -PPh2
EXAMPLE 2
We prepare an iron complex in the form
Fe (CO) 4 of the 10th generation functional dendrimer with phosphine ends prepared in Example 1. The reaction scheme is that shown in FIG. 4.

 To a solution of the 10th generation functional dendrimer with phosphine ends obtained in Example 1 (1.72 g; 10-6 mole) in 30 ml of THF, 1.13 g is added at room temperature (3.1.10-3 mole) of Fe2 (CO) 9 in powder form. The mixture is allowed to stir for 12 hours, then filtered and the solvent is evaporated to dryness. A brown oil is obtained, which is washed twice with ether. The final complex is isolated in the form of a brown powder, with a yield greater than 85%.

The complex is characterized by
31P NMR, 1H, 13C, infrared and elementary analysis. It is a functional dendrimer having 3072 phosphorus functional groups of formula

EXAMPLE 3
A functional 10th generation dendrimer with phosphine ends is prepared by substitution of hydrazone according to the reaction scheme of FIG. 5.

In a first step, a dendrimer substituted by hydrazone is prepared in the following manner
To a biphasic solution of [H2NNH2 1.5% H2O] (32 ml; 1 mole; very large excess) in 30 ml of dichloromethane, a solution of 10th generation base dendrimer (drop 1) is added dropwise aldehydes (1.02 g; 10-6 mole) at room temperature and with very vigorous stirring. Stirring is continued for two hours, then the reaction mixture is allowed to settle. The organic phase (lower) is kept, the solvent of which is evaporated. The residue thus obtained is washed with 3 x 10 ml of ether, to give a dendrimer with hydrazone ends in the form of a white powder, with a yield greater than 90%.

 In a second step, phosphine groups (two phosphines per hydrazone) are grafted as follows.

 A solution of the dendrimer with hydrazone ends obtained previously (1.06 g; 10-6 mole) in 20 ml of THF is added to a solution of Ph2 PCH2 OH (1.34 g; 6.144.10-3 mole) in 15 ml of THF . The mixture is stirred for 24 hours at room temperature, then the solvent is evaporated to give a yellow oil, which is washed twice with 20 ml of a pentane / ether mixture (1/1). A functional dendrimer with phosphine ends is obtained in the form of a white powder with a yield greater than 90%.

 The characterization of this white powder by the characterization methods described above demonstrates the presence of 6144 functional phosphine groups - - - CH2-PPh2.

EXAMPLE 4
A 10th generation functional dendrimer with phosphinate ends is prepared according to the reaction scheme of FIG. 6.

 A solution of dendrimer with methylhydrazone ends obtained at the end of the first step of Example 1 (1.11 g; 10-6 mole) in 20 ml of tetrahydrofuran is added to a solution of (PhO) 2 P-CH2 -OH (0.762 g; 3.072.10-3 mole) in 10 ml of tetrahydrofuran. The reaction mixture is then heated to 650C for two days. The solvent is then evaporated to dryness and the residue is washed twice with 15 ml of a pentane / ether mixture (1/1). A functional dendrimer with phosphinate ends is obtained in the form of a white powder with a yield greater than 80%.

 The characterization demonstrates the presence of 3072 functional phosphinate groups - - - CH2-P (OPh) 2.

EXAMPLE 5
A 10th generation functional dendrimer with phosphate ends is prepared according to the reaction scheme in FIG. 7.

(1,09 g ; 3,072.10-3 mole) dans 10 ml de dichlorométhane est ajoutée à une solution du dendrimère à extrémités hydrazones décrit dans l'exemple 3 (1,06 g ; 10-6 mole) dans 20 ml de dichlorométhane. Après 24 heures d'agitation à température ambiante, le solvant est évaporé, et un dendrimère fonctionnel à extrémités phosphates est obtenu sous forme d'une poudre blanche avec un rendement supérieur à 95 %.A solution of

(1.09 g; 3.072.10-3 mole) in 10 ml of dichloromethane is added to a solution of the dendrimer with hydrazone ends described in Example 3 (1.06 g; 10-6 mole) in 20 ml of dichloromethane. After 24 hours of stirring at room temperature, the solvent is evaporated, and a functional dendrimer with phosphate ends is obtained in the form of a white powder with a yield greater than 95%.

Characterization demonstrates the presence of 3072 terminal phosphate functions

Thus, the dendrimer comprises 3072 phosphorus-containing functional groups of formula

where R2 is CH-C6H4
Y2 is oxygen
R4 and R4 'are O-Ph
EXAMPLE 6
A 10th generation functional dendrimer with phosphate ends is prepared according to the reaction scheme in FIG. 8.

 In a first step, a dendrimer with methylhydrazine ends is prepared in the following manner.

 To a solution of monomethylhydrazine (26.5 ml; 0.5 mol, very large excess) in 50 ml of chloroform, a solution of the 10th generation basic dendrimer of base generation (FIG. 1) is added very slowly and at -50 ° C. chlorinated (0.757 g; 10-6 mole) in 30 ml of chloroform. The mixture is allowed to stir for two hours at this temperature, then allowed to slowly return to room temperature (overnight).

The mixture is then centrifuged to remove the methylhydrazine hydrochloride. The solution is then evaporated to dryness (under vacuum) to give a residue which is washed twice with 20 ml of ether. A dendrimer with 3072 methylhydrazine ends is then obtained in the form of a white powder with a yield greater than 85%.

 In a second step, phosphate groups (a phosphate by methylhydrazine) are grafted as follows.

(1,09 g ; 3,072.10-3 mole) dans 10 ml de dichlorométhane est ajoutée à une solution du dendrimère à extrémités méthylhydrazines obtenu précédemment (0,786 g ; 10-6 mole) dans 20 ml de dichlorométhane. Après 24 heures d'agitation à température ambiante, le solvant est évaporé.On obtient un dendrimère fonctionnel sous forme d'une poudre blanche avec un rendement quantitatif (supérieur à 95
La caractérisation démontre la présence de 3072 fonctions terminales phosphates

A solution of

(1.09 g; 3.072.10-3 mole) in 10 ml of dichloromethane is added to a solution of the dendrimer with methylhydrazine ends obtained previously (0.786 g; 10-6 mole) in 20 ml of dichloromethane. After 24 hours of stirring at room temperature, the solvent is evaporated. A functional dendrimer is obtained in the form of a white powder with a quantitative yield (greater than 95
Characterization demonstrates the presence of 3072 terminal phosphate functions

In addition, these functions are grafted onto the terminal phosphorus of the base dendrimer via the hydrazone motif.

ou R2 est CH-C6H4
Y2 est l'oxygène
R4 et R4' sont O-Ph
EXEMPLE 7
On prépare un dendrimère fonctionnel de 10ème génération à extrémités spirophosphoranes selon le schéma réactionnel de la figure 9.In other words, the functional dendrimer obtained comprises 3072 functional groups of formula

where R2 is CH-C6H4
Y2 is oxygen
R4 and R4 'are O-Ph
EXAMPLE 7
A 10th generation functional dendrimer with spirophosphorane ends is prepared according to the reaction scheme of FIG. 9.

 A solution of spirophosphorane (OCH2 - CH2O) 2 (P - OC6H4CHO) (0.8 g; 3.08.10-3 mole) in 10 ml of dichloromethane is added to a solution of the dendrimer with hydrazone ends obtained at the end of the first step of Example 3 (1.06 g; 10-6 mole) in 20 ml of dichlorometane. After 24 hours of stirring at room temperature, the solvent is evaporated after washing with 15 ml of a pentane / ether mixture (1/1). A functional dendrimer is obtained which has 3072 functional spirophosphorane groups on the surface with a yield greater than 90%.

EXAMPLE 8
A functional dendrimer with phosphine ends complexed with the boron group BH3 (borane) is prepared according to the reaction scheme of FIG. 10.

 To 1.02 g of the 10th generation basic dendrimer (FIG. 1) with aldehyde ends (10-6 mole) dissolved in 10 ml of freshly distilled THF, 0.615 g (3.072 10 3 mole) of diphenylphosphine borane (C6H5) is added. 2 PH (BH3) and 2 μl of triethylamine (1.75 10-6 mole) used as basic catalyst. The reaction mixture is stirred at 50 OC for 48 hours. After evaporation of the solvent and successive washings with ether (2 × 10 ml) then with acetonitrile (10 ml), a functional dendrimer is obtained comprising 3072 functional groups with borane phosphine ends with a yield of 94% in the form of a white powder.

où K3 est -O-C6H4
A2 est l'oxygène
Rm est l'hydrogène
R10 est l'hydrogène
[P] est le radical -P(Ph)2
BH3
EXEMPLE 9
On prépare un dendrimère fonctionnel à extrémités phosphinates complexées par le groupement borane
BH3 (borane) selon le schéma réactionnel de la figure 11.This functional dendrimer, obtained by grafting by addition to the aldehyde ends of base dendrimer, therefore comprises 3072 complementary functional groups grafted on the terminal phosphorus of the base dendrimer, and the formula of which is

where K3 is -O-C6H4
A2 is oxygen
Rm is hydrogen
R10 is hydrogen
[P] is the radical -P (Ph) 2
BH3
EXAMPLE 9
A functional dendrimer with phosphinate ends complexed by the borane group is prepared
BH3 (borane) according to the reaction scheme of Figure 11.

 To 1.02 g of the 10th generation base dendrimer (FIG. 1) with 10-6 mole aldehyde ends) dissolved in 10 ml of freshly distilled THF, 0.713 g (3.072 10 3 mole) of diphenoxyphosphine borane (C6H5O) 2 is added. PH (BH3) and 2 μl of triethylamine (1.75 10-6 mole) used as basic catalyst. The reaction mixture is stirred at 50 OC for 48 hours. After evaporation of the solvent and successive washes with ether (2 x 10 ml) and then with acetonitrile (10 ml), a functional dendrimer is obtained comprising 3072 functional groups with borane phosphinate ends with a yield of 89% in the form of a white powder.

EXAMPLE 10
A functional dendrimer with phosphonate ends is prepared according to the reaction scheme of FIG. 12.

1.02 g of the 10th generation dendrimer with aldehyde ends (10-6 mole) dissolved in 10 ml of
Freshly distilled THF, 0.424 g (3.072.10-3 mole) of diethoxyphosphine oxide (veto) 2 P (O) H and 2 μl of triethylamine (1.75.10-6 mole) used as basic catalyst are added. The reaction mixture is stirred at 50 OC for 48 hours. After evaporation of the solvent and successive washes with ether (2 x 10 ml) and then with acetonitrile (10 ml), a functional dendrimer is obtained comprising 3072 functional groups with phosphonate ends with a yield of 84% in the form of a White powder.

EXAMPLE 11
A functional dendrimer with phosphonate ends is prepared according to the reaction scheme of FIG. 13 by direct grafting onto the aldehyde functions of the terminal peripheral site of a base dendrimer.

To a solution in chloroform of the generation 4 base dendrimer prepared as indicated above (FIG. 2) having 48 terminal aldehyde functions, a solution of the phosphorus-containing amine H2N (CH2) 2 P (O) is added dropwise. (OEt) 2 (2 equivalents per CHO group) in chloroform. This mixture is allowed to react for two hours at room temperature. After evaporation to dryness the reaction mixture is obtained in the form of a white powder which is washed twice with 10 ml of ether. The final product is obtained in the form of a white powder with a yield of 94%. Analyzes demonstrate that it is a functional dendrimer having 48 functional groups with phosphonate ends, of formula

EXAMPLE 12
A functional dendrimer with phosphonate ends is prepared by direct grafting onto the chlorinated functions of the terminal peripheral site of a base dendrimer, according to the reaction scheme of FIG. 14
To a solution of amino B phosphonate
H2N (CH2) 2 P (O) (OEt) 2 (0.639 mmol) in 20 ml of THF, a stoichiometric amount of freshly distilled triethylamine (0.639 mmol) is added at room temperature and to the microsyringe. The reaction medium is left to react for 30 min at room temperature, then the reaction mixture is added dropwise to a solution of 0.0133 mmol (150 mg) of the 4th generation base dendrimer prepared as indicated above (FIG. 2) having 48 functions. of phosphorus-chlorine ends in 10 ml of THF at O OC. The mixture is left to stir at ambient temperature for two hours. After removing the precipitate of triethylamine hydrochloride by centrifugation and evaporating the solvent to dryness, a powder is obtained which is washed with 2 × 20 ml of diethyl ether. The final product obtained in the form of a white powder, with a yield greater than 85%, is a functional dendrimer having 48 functional groups of phosphonate ends, of formula

EXAMPLE 13
A functional dendrimer with phosphine ends is prepared according to the reaction scheme of FIG. 15.

 In a first step, a dendrimer with monoallylamine ends - - -NH-CH2-CH = CH2 is prepared in the following manner.

 To a solution of diallylamine (two equivalents per chlorine function, or in this case 768 equivalents) in THF, a stoichiometric quantity of freshly distilled triethylamine is added at room temperature and this mixture is allowed to stir at room temperature for 30 minutes. This reaction mixture is added to a THF solution of the base dendrimer prepared as indicated above (FIG. 2) of the seventh generation having 384 phosphorus-chlorine bonds. This mixture is allowed to react at room temperature for one week. After elimination of the precipitate of triethylamine hydrochloride by centrifugation and evaporation to dryness of the solvent and the excess of reagents used, a yellowish powder is obtained which can be purified by washing with 10 ml of ether and by chromatography on a silica column using as eluting with ethyl acetate.

 The final product is a dendrimer having 384 monoallylamine ends forming two terminal peripheral sites respectively on the two nitrogen atoms linked to the initial phosphorus at the end of the base dendrimer.

 In a second step, phosphine functions are grafted onto only one of the two terminal peripheral sites with monoallylamine ends.

 0.65 ml of diphenylphosphine Ph2PH (3.76 mmol, 0.700 g) and 0.11 g of (CH2O) n (3.76 mmol) are heated in a closed Schlenk tube for 90 minutes at 120 ° C. 1 g of the 7th generation dendrimer obtained in the first step above containing 384 monoallylamine groups (0.0098 mmol) is added in 5 ml of THF.

The whole is heated to 80 ° C. for three days. The solvent is then evaporated to give a yellow oil.

After two washes with 10 ml of a 1/1 pentane / ether mixture, the final product is obtained in the form of a white powder with a yield of 93%.

que l'on peut aussi écrire

This product is a functional dendrimer having 192 functional end groups

that we can also write

where R1 is CH2
and [P] is P (Ph) 2
It should be noted that this example can also be carried out from the base dendrimer of generation 10, or of generation 12, and 1536 or 6144 functional groups are obtained as mentioned above.

EXAMPLE 14
A functional dendrimer with phosphine ends is prepared according to the three-step reaction scheme of FIG. 16.

 In a first step, a group -NH-CH2-C = CH is grafted onto a chlorinated terminal peripheral site of the base dendrimer.

 To a solution of monopropargylamine (0.319 mmol, 22 μl) in 7 ml of THF, a stoichiometric quantity of freshly distilled triethylamine (0.319 mmol, 45 μl) is added at room temperature and to the microsyringe. The reaction medium is left to react for 30 minutes at room temperature, then the reaction mixture is added dropwise and very slowly to a solution in 7 ml of THF at O OC of 0.0133 mmol (150 mg) of the base dendrimer of 4th generation base. prepared as indicated above (Figure 2) having 48 phosphorus-chlorine bonds. The mixture is left to stir at ambient temperature for two hours.

After removing the precipitate of triethylamine hydrochloride by centrifugation and evaporating the solvent to dryness, a powder is obtained which is purified by chromatography on a silica column with ethyl acetate to remove the remainder of hydrochloride.

 The final product is the dendrimer shown at the end of the first step in FIG. 16, which is obtained with a yield of 60% in the form of a yellowish powder fully characterized by the analyzes, and having a decomposition point at 47 OC.

 In a second step, a group -NH-CH2-C = CH is grafted onto the second chlorinated terminal peripheral site of the base dendrimer.

 To a solution of monopropargylamine (0.320 mmol, 45 μl) in 7 ml of THF, a stoichiometric quantity of freshly distilled triethylamine (0.320 mmol, 89 μl) is added at room temperature and to the microsyringe. The reaction mixture is left to react for 30 minutes at room temperature and then the reaction mixture is added dropwise and very slowly to a solution in 7 ml of THF at room temperature of 0.0133 mmol (150 mg) of the 4th generation dendrimer obtained at the end of the first stage having 24 phosphorus-chlorine bonds and 24 monopropargylamine groups. Stirred at room temperature for twelve hours. After removing the precipitate of triethylamine hydrochloride by centrifugation and evaporation to dryness of the solvent, a powder is obtained which is purified by chromatography on a silica column with ethyl acetate to remove the rest of hydrochloride.

 The final product is the dendrimer shown at the end of the second step in FIG. 16, which is obtained with a yield of 58% in the form of a yellow powder and a decomposition point at 60 OC.

 In a third step, a phosphine radical is selectively grafted on one of the terminal peripheral sites monopropargylamine.

 0.65 ml of diphenylphosphine Ph2PH (3.76 mmol, 0.700 g) and 0.11 g of (CH2O) n (3.76 mmol) are heated in a closed Schlenk tube for 90 minutes at 120 ° C., then 0, 16 g of the 4th generation dendrimer obtained in the second step comprising 48 monopropargylamine groups in 7 ml of THF are added and the whole is heated to 80 ° C. for three days. The solvent is then evaporated to give a yellow oil.

After two washes with 10 ml of a 1/1 pentane / ether mixture the final product is obtained in the form of a white powder with a yield of 91%.

The functional dendrimer obtained has 24 functional end groups

EXAMPLE 15
A functional dendrimer is prepared having phosphine functional groups complexed with gold in AuCl form according to the reaction scheme of FIG. 17.

To a solution of the generation 6 functional dendrimer prepared as indicated above in Example 1 (FIG. 3) but from a generation 6 base dendrimer, and having 192 terminal phosphine functions (0.83 g; 7 , 8 pmol) in 20 ml of dichloromethane, an AuCl complex (tetrahydrothiophene) (0.48 g; 1.5 mmol) is added at room temperature. After stirring the resulting mixture for two hours, the solution is concentrated to 2 ml. The addition of diethyl ether (15 ml) makes it possible to precipitate the complex in the form of a white solid which is washed with diethyl ether (2 x 10 ml). The final product is obtained with a yield of 65%. Analyzes demonstrate that it is the functional dendrimer represented in FIG. 17, having 192 terminal functional groups

 This dendrimer can find applications, for example as a medicament, in particular in the treatment of arthritis by the general route, such as the monomer with the same termination.

selon le schéma réactionnel de la figure 18.EXAMPLE 16
A functional dendrimer is prepared having phosphine functional groups complexed with rhodium in Rh (Co) (acac) form where acac is the group

according to the reaction scheme of Figure 18.

greffés sur les 24 atomes de phosphores terminaux du dendrimère de base.First of all, a functional dendrimer with phosphine ends is prepared, using the method described in Example 1, but from a fourth generation base dendrimer, so as to obtain a dendrimer having 48 functional phosphine groups.

grafted onto the 24 terminal phosphorus atoms of the base dendrimer.

 To a solution of this dendrimer in 20 ml of chloroform, Rh (acac) (CO) 2 (52 equivalents) is added at room temperature. The resulting solution is stirred for 3 hours then the solvent is partially evaporated until 2 ml of solution are obtained to which 15 ml of diethyl ether are added. The final orange complex precipitates and is washed twice with 5 ml of diethyl ether.

 The functional dendrimer obtained (yield greater than 85 t) is shown in planar projection in FIG. 20, where [Rh] is Rh (CO) (acac).

Analyzes demonstrate the presence of 48 complexed phosphine groups

 This dendrimer is applicable as a catalyst during, for example, the hydroformylation of olefins (homogeneous catalysis).

EXAMPLE 17
A multifunctional dendrimer having phosphonate functional groups on a terminal peripheral site and phosphine functional groups on another terminal peripheral site is prepared, according to the reaction scheme of FIG. 19.

First of all, a fourth generation dendrimer with the terminal motif P (S) (OC6H4CHO) NH (CH2CH = CH2) is prepared in the following manner
a) To a solution of monoallylamine (24 mmol) in 100 ml of THF, 24 mmol of triethylamine is added at room temperature. This mixture is left stirring for half an hour and is added by a very slow drip to a solution of 1 mmol of fourth generation base dendrimer with Cl ends as mentioned above (Figure 2) in 50 ml of THF, at 0 C.

It is slowly allowed to return to room temperature and, 12 hours later, part of the triethylamine hydrochloride is removed by centrifugation.

 After purification by chromatography on a silica column (yield 82%), a dendrimer is obtained comprising - P (S) Cl ends (NH-CH2CH = CH2).

b) To a heterogeneous solution of
NaO-C6H4-CHO (19.2 mmol) in THF, (50 ml) is added at room temperature and dropwise a fourth generation dendrimer solution with ends
P (S) Cl [NH-CH2CH = CH2] prepared above (0.8 mmol) in 50 ml of THF. Stirring is carried out for 12 hours, then the sodium salt is separated by centrifugation and the solvent is evaporated to obtain a powder which is washed with 3 x 10 ml of ether. A fourth generation dendrimer is obtained with a yield of 85%. This dendrimer comprises 24 P (S) [O-C6H4-CHO] [NH-CH2-CH = CH2] ends as shown as the starting product of the reaction scheme of FIG. 19.

 In a second step, the phosphonate functional groups are grafted as follows.

 To a solution of the fourth generation dendrimer having the terminal motif P (S) (oC6H4CHo) NH (CH2CH = CH2) (0.600 mmol) in 20 ml of THF, phosphonate (EtO) 2P (O) is added at room temperature, (14.4 mmol) and a catalytic amount of triethylamine (0.06 mmol). The mixture is stirred for 24 hours at 60 OC. Evaporation of the solvent and purification of the white powder obtained by successive washings with 2 x 20 ml of diethyl ether makes it possible to isolate the fourth generation dendrimer having as terminal motif P (S) OC6H4CHOHP (O) (OEt) 2. This new dendrimer is characterized by 31 P, 1 H, 13 C NMR and by elemental analysis. The yield is 90%.

 In a third step, the phosphine functional groups are grafted as follows.

 To a solution of the latter dendrimer (0.6 mmol) in 20 ml of THF is added at room temperature the phosphine Ph2PCH2OH (14.4 mmol). The reaction mixture is heated to 65 ° C. for 3 days. After removal of the solvent, the dendrimer obtained is purified by successive washing with 3 x 20 ml of diethyl ether (yield 84%) and characterized by 31 P, 1 H, 13 C NMR and by elemental analysis.

Claims (28)

 1 / - New functional dendrimer comprising a molecule of a base dendrimer formed by a heart, at least four layers of dendritic branches superimposed from the heart and defining, on the surface of the molecule, one or more terminal peripheral sites, characterized in that it comprises at least a plurality of identical complementary functional groups, each complementary functional group being distinct from a dendritic branch, each plurality of complementary functional groups being grafted by substitution or addition to the whole of at least one site terminal peripheral device of the base dendrimer, with a complementary functional group grafted onto each location of said terminal peripheral site, and in that at least one such complementary functional group comprises at least one phosphorus functional group of formula  --- R - [P] where [P] is a phosphorus functional radical chosen from one of the radicals of formula

 and where R is a group which comprises a carbon atom linked to the phosphorus functional radical [P] and which is linked by a covalent bond to the rest of the dendrimer molecule thus formed.  R6, R6 ′ are identical or different homocyclic or heterocyclic chains closed on phosphorus and having a number of atoms in the main chain between 4 and 6,  R5, R5 ', R5 ", R5"' are identical or different groups formed from hydrogen, or from an amino radical, or from an alkyl or alkoxyl or aryloxyl or aryl radical,  Y2 is oxygen, or sulfur, or an electronic doublet, or an N-R11 radical where R11 is a hydrogen, an alkyl or aryl radical or a silylated radical, R11 is hydrogen, or an alkyl or aryl radical, or a silylated radical,  Y1 is oxygen, or sulfur, or an N-R11 radical where  R4, R4 ′ are identical or different groups formed of a hydrogen, or a halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical,  M is a metal or a metallic or boron group capable of forming a complex with phosphorus,  R3, R3 'are identical or different groups formed by hydrogen, halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical, or an alkyl radical or aryl substituted with at least one silylated or phosphorus group,  R2, R2 'are the same or different groups formed of a hydrogen, or a halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical, or an alkyl radical or aryl substituted by at least one silyl or phosphorus group,  R1, R1 ′ are identical or different groups formed from hydrogen, or from an amino radical, or from an alkyl or aryl or alkoxyl or aryloxyl radical,  where P is phosphorus,

 where C is carbon, and K1, K2 are organic chains, at least one of which comprises at least one heteroatom chosen from nitrogen, oxygen, phosphorus, silicon, boron, sulfur, arsenic or germanium, K1 being linked by a covalent bond to the rest of the dendrimer molecule thus formed.

 2 / - New dendrimer according to claim 1, characterized in that it comprises at least a plurality of identical complementary functional groups of formula  3 / - New dendrimer according to one of claims 1 and 2, characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula --- A1 - R '- [P] where Al is a chosen heteroatom among nitrogen, oxygen, phosphorus, silicon, boron, sulfur, arsenic or germanium, and R 'is a carbon atom or an organic group comprising a carbon chain interposed between Al and [P ].  4 / - New dendrimer according to claim 3, characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula  - N - R1 ~ [p]  or  - N = R2 - [P] where N is nitrogen,  R1 and R2 represent carbon or an organic group comprising a carbon chain interposed between N and [P].  5 / - New dendrimer according to claim 4, characterized in that R1 or R2 represents a hydrocarbon chain.  6 / - New dendrimer according to claim 4, characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula

 7 / - New dendrimer according to one of claims 1 to 6, characterized in that it comprises at least a plurality of identical complementary functional groups, each complementary functional group being grafted on a location of said terminal peripheral site by means of '' a hydrazone unit of general formula  -C = N-N or  -N-N = C  8 / - New dendrimer according to claim 7, characterized in that it comprises at least a plurality of identical complementary functional groups of formula

 where R3 is hydrogen or an alkyl or aryl radical,  R4 is hydrogen or an alkyl radical, in particular methyl- or aryl, or another phosphorus functional group identical to or different from the phosphorus functional group grafted onto the same nitrogen atom,  K3 is an identical branch fraction directly grafted, in the base dendrimer, to a dendritic branch of the previous generation.  9 / - New dendrimer according to claim 8, characterized in that K3 is the group of formula  - O - C6H4 where O is oxygen, and C6H4 is a benzene nucleus.  10 / - New dendrimer according to one of claims 8 and 9, characterized in that R is the group of formula

 where R5 and R6 are hydrogen, or an alkyl or aryl radical.  11 / - New dendrimer according to one of claims 4 to 10, characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula

 where R7 and R8 are hydrogen or identical or different alkyl or aryl radicals, and  R9 is hydrogen, or an alkyl, propargyl, alkyl or aryl radical, or a group

 identical or different from the group

 grafted on the same nitrogen atom.  12 / - New dendrimer according to claim 11, characterized in that said phosphorus functional group is grafted on a terminal peripheral site and forms a functional group complementary to the dendrimer.  13 / - New dendrimer according to one of claims 1 to 12, characterized in that it comprises at least a plurality of identical phosphorus functional groups of formula

 where A2 is a heteroatom chosen from nitrogen, oxygen, phosphorus, silicon, boron, sulfur,  Rm are m (m> 1) groups chosen from hydrogen, or a silylated, phosphorous or boron radical, or an alkyl or aryl radical,  R10 is hydrogen or an alkyl or aryl radical.  14 / - New dendrimer according to claim 13, characterized in that it comprises at least a plurality of identical complementary functional groups of formula

 where K3 is a fraction of a dendritic branch directly grafted, in the base dendrimer, to a dendritic branch of the preceding internal layer.  15 / - New dendrimer according to claim 14, characterized in that K3 is the group of formula  - O - C6H4 where O is oxygen and C6M4 is a benzene nucleus.  16 / - New dendrimer according to one of claims 1 to 15, characterized in that it corresponds to the formula  Do - (Bi) n - T - Gk where Do is a dendritic core, Bi are dendritic branches of the n layers of the base dendrimer,  T represents the terminal peripheral site (s) of the last layer of the base dendrimer, and  Gk represents one (or pluralities of) identical complementary functional groups.  17 / - New dendrimer according to claim 16, characterized in that n is between 4 and 12.  18 / - New dendrimer according to one of claims 16 and 17, characterized in that it comprises at least one terminal peripheral site T of formula

 where P is phosphorus,  Y3 is oxygen, sulfur, or an N - R11 radical, where R11 is an alkyl or aryl radical.  19 / - New dendrimer according to one of claims 16 to 18, characterized in that the dendritic branches Bi are of formula

 where O is oxygen,  C is carbon,  H is hydrogen,  N is nitrogen,  C6H4 is the benzene nucleus,  P is phosphorus,  Me is the methyl radical,  Y4 is oxygen, sulfur or an N-R11 radical, where R11 is hydrogen, an alkyl or aryl radical, or a silylated radical.  20 / - New dendrimer according to one of claims 16 to 19, characterized in that Do is a phosphorous dentritic heart.  21 / - New dendrimer according to one of claims 16 to 20, characterized in that it comprises on the surface more than 1,000 - in particular more than 6,000 - phosphorus functional groups.  22 / - New dendrimer according to one of claims 16 to 21, characterized in that it comprises on the surface a number of functional phosphorus groups of between 24 and 6,144.  23 / - Process for the preparation of a functional dendrimer in which a molecule of a basic dendrimer is prepared formed from a heart, at least four layers of dendritic branches superimposed from the heart and defining, at the surface of the molecule, one or more terminal peripheral sites, characterized  - in that one chooses at least one complementary functional group, which is distinct from a dendritic branch, and which comprises at least one phosphorus functional group of formula  --- R - [P] where [P] is a phosphorus functional radical chosen from one of the radicals of formula

 where P is phosphorus,  R1, R1 ′ are identical or different groups formed from hydrogen, or from a halogen or from an amino radical, or from an alkyl or aryl or alkoxyl or aryloxyl radical,  R2, R2 'are the same or different groups formed of a hydrogen, or a halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical, or an alkyl radical or aryl substituted by at least one silyl or phosphorus group,  R3, R3 'are identical or different groups formed from hydrogen, halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical, or an alkyl radical or aryl substituted with at least one silyl or phosphorus group,  M is a metal or a metallic or boron group capable of forming a complex with phosphorus,  R4, R4 ′ are identical or different groups formed of a hydrogen, or a halogen, or a hydroxyl or amino radical, or an alkyl or aryl or alkoxyl or aryloxyl radical,  Y1 is oxygen, or sulfur, or an N-R11 radical where R11 is hydrogen, or an alkyl or aryl radical, or a silylated radical,  Y2 is oxygen, or sulfur, or an electronic doublet, or an N-R11 radical where R11 is a hydrogen, an alkyl or aryl radical or a silylated radical,  R5, R5 ', R5 ", R5"' are identical or different groups formed from hydrogen, or from an amino radical, or from an alkyl or alkoxyl or aryloxyl or aryl radical,  R6, R6 ′ are identical or different homocyclic or heterocyclic chains closed on phosphorus and having a number of atoms in the main chain between 4 and 6,  and where R is a group comprising a carbon atom linked to the phosphorus functional radical [P],  - in that one chooses R and [P] so that said complementary functional group can be grafted onto the whole of at least one terminal peripheral site of the base dendrimer,  - And in that one graft by substitution or addition said complementary functional group on the whole of said terminal peripheral site of the base dendrimer.  24 / - Process according to claim 23, characterized in that at least one complementary functional group and / or at least one phosphorus functional group according to one of claims 1 to 21 is chosen.  then grafted at least one functional phosphorus group on each hydrazone termination.  R12 is hydrogen or an alkyl or aryl radical,  where R13 is hydrogen, or an alkyl or aryl radical,

 reacting the base dendrimer with an R13-hydrazine so as to form, from each carbonyl function, a hydrazone termination of formula  and in that, to graft the complementary functional group (s)

 25 / - Method according to one of claims 23 and 24 characterized in that a base dendrimer is prepared having carbonyl functions on the surface  where R15 is the radical R13 or another phosphorus functional group identical or different from that grafted on the same nitrogen atom.

 HO - R - [P] on the hydrazone-terminated dendrimer, so as to obtain a substituted substituted functional dendrimer  26 / - Process according to claim 25, characterized in that at least one phosphorus alcohol of formula is reacted  27 / - Process according to claim 23, characterized in that a base dendrimer having endings is prepared

 where P is phosphorus,  Y3 is oxygen, sulfur or an N-R11 radical, where R11 is an alkyl or aryl radical,  X is a halogen, and in that to graft the complementary functional group (s),  a double amination of the halogenated terminations is carried out so as to obtain on the surface amine terminations of formula

 where each of R16, R17 R18 is hydrogen or an alkyl, propargyl, alkyl, or aryl radical,  and we govern these amino terminations with a phosphorus alcohol  HO - R - [P] so as to obtain a substituted functional dendrimer with endings

 where R191 R20, R21 are respectively R16, R17, R18 or another identical or different phosphorus functional group.  28 / - Process according to claim 23, characterized in that a base dendrimer is prepared having carbonyl functions on the surface

 where R12 is hydrogen or an alkyl or aryl radical.

H - [P], so as to form, from each carbonyl function, a termination of formula  and in that in order to graft the complementary functional group (s), the base dendrimer is reacted with a phosphorus compound of formula