WO1999000440A1

WO1999000440A1 - Synthesis of a dendritic polyalcohol

Info

Publication number: WO1999000440A1
Application number: PCT/SE1998/001229
Authority: WO
Inventors: Henrik Ihre; Anders Hult
Original assignee: Perstorp AB
Current assignee: Perstorp AB
Priority date: 1997-06-26
Filing date: 1998-06-24
Publication date: 1999-01-07
Anticipated expiration: 1999-12-26
Also published as: SE9702447L; SE9702447D0; AU7951098A; SE510088C2

Abstract

A process for a double stage convergent synthesis of a polymeric polyalcohol substantially and preferably built up from polyester units and composed of a monomeric or polymeric core to which at least one hyperbranched dendritic branch (dendron) consisting of a number of branching generations is added. The branching generations comprise a polymeric or monomeric branching chain extender having three reactive functions of which two are hydroxyl groups and one is a carboxyl group. The two hydroxyl groups of the branching chain extender is in a first step ketal protected by reacting said two hydroxyl groups with a ketal. A second step includes protection of the carboxyl group of said branching chain extender. The ketal protected branching chain extender and the carboxyl protected chain extender are then employed for repeated addition in a number of step yielding a predetermined number of branching generations. The thus synthesized dendron is finally added to a core having reactive hydroxyl or epoxide groups and the ketal protected hydroxyl groups are optionally deprotected.

Description

SYNTHESIS OF A DENDRITIC POLYALCOHOL

The present invention relates to a process for a double stage convergent synthesis of a polymeric polyalcohol (polyol) substantially and preferably built up from polyester units, optionally in combination with ether or polyether units The polymeric polyalcohol is a hyperbranched dendritic polyester alcohol having reactive or protected terminal hydroxyl groups The polyester alcohol is synthesized by repeated addition of ketal protected chain extenders, producing a dendron, followed by addition of said dendron to a core The core has n reactive unprotected hydroxyl or epoxide groups to which n branches each consisting of g branching generations are added, whereby n and g are integers and at least 1 The branching generations comprises at least one polymeric or monomeric branching chain extender having three reactive groups of which two are hydroxyl groups

Compounds with a highly branched, treelike, molecular structure have been known for a long time Literature discussing various hyperbranched and dendritic molecules and macromolecule include

- "Polybenzyl Type Polymers" by Howard C Haas et al published in J. Polymer Sci. vol XV ( 1955) pp 503-5 15, wherein nonrandomly substituted highly branched benzyl type polymers are synthesized and analysed

- "Strukturuntersuchungen an Sternmolekulen mit Glykogen als Kern" by Walther Burchard et al published in Makromolekulare Chetnie 150 ( 1971 ) pp 63-71 , wherein the structure of molecules having treelike amylose chains and a glycogen core are disclosed

- " Statistical Mechanism of Random Coil Networks" and "Elasticity and Chain Dimensions in Gaussian Networks", by William W Graessley published in Macromolecules vol 8 no 2 (1975) pp. 186- 190 and vol 8 no. 6 (1975) pp 865-868, wherein molecules comprising tri and tetrafunctional central cores (initiators) and concentrically treelike (dendritic) branches are disclosed The term micronetworks is introduced to describe these molecules

- " Static and Dynamic Scattering Behavior of Regularly Branched Chains A Model of Soft-Sphere Microgels" by Walther Burchard et al published in J. Polymer Sci. Polym. Phys. Ed. vol 20 ( 1982) pp 157- 171 , wherein is disclosed, among other models, the theory behind a molecular model comprising a trifunctional core being symmetrically branched whereby continued branch replication yields increased branch multiplicity and an increased number of terminal groups The birth of dendritic or "cascade" chemistry is formally realized in the first reported preparation, separation and characterization of structures with branched topologies obtained via an iterative methodology "'Cascade' - and 'Nonskid-Chain-Like' Synthesis of Molecular Cavity Topologies" - Synthesis 1978, pp 155- 158, E. Buhleier et al.

Structures such as starbranched, dense starbranched, dendrimers and hyperbranched dendritic molecules and macromolecules are from these and a large number of similar works published in the 1950's, 1960's and especially in the 1970's easily visualized but not easily synthesized.

Various hyperbranched and dendritic materials have during the last one or two decades attracted general attention. Patents, patent applications and other works issued or published during the last decades are summarized by for instance H. Galina et al in Polymery, English translation in Int. Polym. Sci. Tech. 1995, 22, 70.

Hyperbranched dendritic macromolecules, including dendrimers, can generally be described as three dimensional highly branched molecules having a treelike structure. Dendrimers are highly symmetric, while similar macromolecules designated as hyperbranched and/or dendritic may to a certain degree hold an asymmetry, yet maintaining the highly branched treelike structure. Dendrimers can be said to be monodisperse - determined molecular weight (M_w)/nominal molecular weight (M_n) = 1 - or substantially monodisperse (M^/M^ « 1 ) hyperbranched macromolecules. Hyperbranched and dendritic macromolecules normally consist of an initiator or core having one or more reactive sites and a number of branching layers and optionally a layer of chain terminating molecules. Continued replication of branching layers normally yields increased branch multiplicity and, where applicable or desired, increased number of terminal groups. The layers are usually called generations and the branches dendrons, which are designations herein used.

Synthesis of perfect dendritic material, that is substantially monodisperse molecules comprising symmetrical treelike (dendritic) branches which optionally emanate symmetrically as well as concentrically from a core or initiator molecule, is a challenging task as high yield and selectivity is required in all reaction steps. Various processes have been suggested for dendritic, near dendritic and perfect dendritic products, but complex and inefficient synthesis is still an obstacle to technical and commercial use of monodisperse dendritic products. Most disclosed processes yield either polydisperse and/or too expensive products. A number of patents and patent applications disclosing various hyperbranched and/or dendritic macromolecules and processes for synthesis thereof have for various types of products been issued or published and include EP 0 1 15 771 , SE 468 771 , WO 93/18075, EP 0 575 596, SE 503 342 and US 5,561 ,214

EP 0 1 15 771 claims a dense star polymer having at least three symmetrical core branches, each core branch having at least one terminal group, and a ratio terminal groups to core branches being greater than 2 1 The properties of claimed polymer is specified through a comparative relation to an unspecified and allegedly known star polymer Claim 1 can due to inoperable teaching of terminal groups and unspecified comparison not be interpreted EP 0 1 15 771 also relates to a process, which process substantially also is disclosed in US 4,410,688, for synthesis of a symmetrical dense star polymer The process teaches a repeated and alternately addition of alkyl acrylate and alkylene diamine to a core consisting of ammonia

SE 468 771 discloses a hyperbranched dendritic macromolecule substantially built up from polyester units and a process for synthesis of said macromolecule The macromolecule is composed of an initiator, having at least one hydroxyl group, to which initiator at least one branching generation comprising at least one chain extender, having at least one carboxyl group and at least two hydroxyl groups, is added The macromolecule is optionally chain terminated The process for synthesis of said macromolecule teaches a co-esterification of the initiator and the chain extender, optionally followed by a chain termination The process yields inexpensive polydisperse hyperbranched dendritic macromolecules

WO 93/18075 teaches a hyperbranched polymer having at least six terminal hydroxyl or carboxyl groups and a process for its synthesis The hyperbranched polymer is synthesized by repeated and alternately addition of a compound having at least one anhydride group followed by a compound having at least one epoxide group to a core having at least one hydroxyl group

EP 0 575 596 discloses a dendritic macromolecule comprising a core having 1 - 10 functional groups and branches synthesized from vinyl cyanide units as well as a process for synthesis thereof The process involves three repeated steps beginning with a reaction between the core and monomeric vinyl cyanide units followed by reduction of incorporated nitrile groups to amine groups In a third step said amine groups are reacted with monomeric vinyl cyanide units

SE 503 342 discloses a hyperbranched dendritic macromolecule of polyester type and a process for synthesis of said macromolecule The macromolecule is substantially composed of a core, having at least one epoxide group, to which core at least one branching generation comprising at least one chain extender, having at least three reactive functions of which at least one is a carboxyl or epoxide group and at least one is a hydroxyl group, is added. The macromolecule is optionally chain terminated. The process teaches self condensation of the chain extender molecules yielding a dendron (a core branch), which dendron in a second step is added to the core. The process also comprises an optionally further chain extension by addition of spacing or branching chain extenders and/or an optional chain termination. The process yields inexpensive polydisperse hyperbranched dendritic macromolecules.

US 5,561 ,214 relates to highly asymmetrical hyperbranched polydisperse polyaspartate esters and a process for their synthesis. The process comprises self condensation, via transesterification, of at least a portion of the hydroxyl or ester groups of a hydroxyaspartate.

Recent developments in the synthesis and characterization of dendritic molecules are disclosed in for instance "Synthesis, Characterization, and H-NMR Self-Diffusion Studies of Dendritic Aliphatic Polyesters Based on 2,2-Bis(hydroxymethyl)propionic acid and l , l , l -Tris(hydroxyphenyl)ethane" by Henrik Ihre et al published in J. Am. Chem. Soc. vol. 1 18 ( 1996) pp. 6388-6395, wherein dendritic polyesters of one, two, three and four generations are synthesized and characterized. The dendrimers are synthesized in the convergent fashion, whereby dendrons (core branches) first are synthesized from acylated 2,2-Bis(hydroxymethyl)propanoic acid and then coupled to a polyfunctional phenolic core molecule. A further disclosure of recent developments is "Hyperbranched Aliphatic Polyesters - Synthesis, Characterization and Applications" by Eva Malmstrόm, Royal Institute of Technology, Stockholm 1996, wherein hyperbranched dendritic polyesters of the type disclosed in SE 468 771 are studied and discussed.

Hyperbranched dendritic, including dendrimers, polyalcohols substantially built up from polyester units give, due to the symmetrical or near symmetrical highly branched structure, in comparison to ordinary polyalcohols and randomly branched, polydisperse, polyester polyalcohols great advantages. Said hyperbranched dendritic polyalcohols exhibit a low polydispersity and can, due to the structure, be formulated to give a very high molecular weight yet exhibiting a very low viscosity Hyperbranched dendritic, including dendrimers, polyester polyalcohols can advantageously be used for further processing, such as chain termination and/or functionalization, thus yielding dendritic products having for instance a fatty acid chain termination, alkenyl groups, such as allyl, vinyl or acryl, primary or secondary epoxide groups, isocyanate groups and/or undergo similar conversion of or reaction involving the hydroxyl groups of said polyalcohol.

The inexpensive, readily available and easy to handle material used in the process of the present invention provide quite unexpectedly possibility to formulate an easy, reliable and reproducible process for the synthesis of monodisperse or substantially monodisperse polyester alcohols, that is dendritic polyesters having terminal unprotected or protected hydroxyl groups. The process of the present invention is easily and conveniently adjusted to desired processing conditions and desired final structure and properties of yielded dendritic polyalcohol.

The present invention relates to a process for a double stage convergent synthesis of a polymeric polyalcohol having reactive or protected terminal hydroxyl groups, which polymeric polyalcohol is composed of a monomeric or polymeric core having n reactive hydroxyl or epoxide groups (A), to which n dendritic branches (dendrons), each consisting of g branching generations, are coupled by addition, whereby n and g are integers and at least 1 . The dendrons are first synthesized and then coupled/added to said core. The branching generations of said dendron comprise at least one polymeric or monomeric branching chain extender having three functional groups of which two are reactive hydroxyl groups (B) and one is a reactive carboxyl group (C). The two hydroxyl groups of the branching chain extender are ketal protected during addition. Ketals are yielded together with water from a reaction between an alcohol, having at least two hydroxyl groups and a ketone, such as acetone.

The process of the present invention employs two types a monomeric or polymeric branching chain extenders, one wherein said two hydroxyl groups (B) are two ketal protected hydroxyl groups (B') and one wherein said carboxyl group is a protected, preferably ester protected, carboxyl group (C). Ketal protection - Step (i) - is obtained by reaction between said two hydroxyl groups (B) and a ketone, yielding a branching chain extender having two ketal protected hydroxyl groups (B') and one reactive carboxyl group (C). Protection, ester protection, of the carboxyl group - Step (ii) - is obtained by reacting said carboxyl group with a carboxyl protective compound, such as an alkyl or arylhalide, preferably benzyl chloride, benzyl bromide, allyl chloride, allyl bromide or combinations thereof or by reaction with an alcohol, such as allyl or benzyl alcohol, yielding a branching chain extender having two reactive hydroxyl groups (B) and one protected carboxyl group (C). The branching chain extenders yielded in said Steps (i) and (ii) are in a Step (iii) reacted at a molar ratio reactive carboxyl groups (C) to reactive hydroxyl groups (B) of at least 1 : 1 , yielding a polymer having four ketal protected hydroxyl groups (B') and one protected carboxyl group (C). The protected hydroxyl groups (B¹) of a polymer yielded according to Step (iii) is in a fourth step - Step (iv) - deprotected yielding a polymer having four reactive hydroxyl groups (B) and one protected carboxyl group (C). The protected carboxyl group of a Step (iii) polymer is in an optional Step (v) deprotected yielding a polymer having ketal protected hydroxyl groups (B') and one reactive carboxyl group (C). In case g > 1 , a sixth step - Step (vi) - of the present process include reacting, in a number of Steps yielding g branching generations, the product yielded in Step (iv) or a hydroxyl deprotected product yielded in present Step (vi) with the product yielded in Step (i) or Step (v) at a molar ratio reactive hydroxyl groups (B) to reactive carboxyl groups (C) of at least 1 : 1 , yielding a product having ketal protected hydroxyl groups (B') and one reactive carboxyl group (C) or one protected carboxyl group (C). The in the final repetition of Step (vi), the step that results in generation g, yielded dendron or the dendron yielded in Step (iii) is now in a Step (vii), after deprotection of the optionally protected carboxyl group (C), added to the core at a molar ratio core to said Step (vi) product of 1 : 1 to \ :n, yielding a dendritic polymer having at least one dendritic branch emanating from said core. An optional Step (viii) include deprotection of the ketal protected hydroxyl groups (B') of the hyperbranched dendritic polyalcohol obtained in Step (vii), yielding terminal reactive hydroxyl groups (B).

Each additions of a branching generation - Step (iii) or Steps (vi) - to the initially synthesized dendron can according to various embodiments individually employ a ketal protected branching chain extender being a reaction product of the same or a different branching chain extender and/or the same or a different ketone as well as employ a protected branching chain extender being a reaction product between the same or a different branching chain extender and/or the same or a different carboxyl protective compound, such as said alkyl or aryl halide

The integer value of n is in preferred embodiments between 1 and 20, preferably between 2 and 12 and most preferably between 2 and 8 and the integer value of g is in likewise preferred embodiments between 1 and 50, preferably between 2 and 20 and most preferably between 2 and 8.

The polymeric polyalcohol yielded from the process according to the present invention has in its preferred embodiments n identical and/or symmetrical dendritic branches, whereby n is an integer and at least 2. Dendrons having continued branching chain extension yields in these embodiments polymeric polyalcohols having increased branching density and increased number of reactive hydroxyl groups (B) or ketal protected hydroxyl groups (B¹). Addition of branching generations and addition of said dendron, for instance the product obtained in Step (iii) or Step (vi), to said core are preferably performed at a temperature of -30- 150°C, such as - 10-80°C or 10-50°C.

Especi ally preferred embodiments of the present invention employ ketal protected branching chain extenders selected from the group consisting of dihydroxyfunctional monocarboxylic acids or adducts between dihydroxyfunctional monocarboxylic acids and at least one alkylene oxide, which adduct has two hydroxyl groups and one carboxyl group. Preferred alkylene oxides are ethylene oxide, propylene oxide, butylene oxide, phenylethylene oxide and mixtures thereof.

The branching chain extender used to produce the ketal protected branching chain extender is in the most preferred embodiments of the present invention a dihydroxyfunctional monocarboxylic acid, such as 2,2-bis(hydroxy- methyl)propanoic acid, 2,2-bis(hydroxymethyl)butanoic acid, 2,2-bis(hydroxy- methyl)pentanoic acid or 2,3-dihydroxypropanoic acid.

Ester protection, such benzyl ester protection can suitable be obtained by first forming an alkali metal salt and in a second step reacting the salt with for instance benzyl bromide or by reaction with for instance benzyl alcohol. The benzyl ester group can be removed selectively in very high yield by catalytic hydrogenolysis without affecting the ester bonds formed in the synthesized dendritic polymer. Deprotection can for instance be performed at atmospheric pressure using a catalyst, such as a palladium catalyst on activated carbon (Pd/C). Suitable to above disclosed protection/deprotection method alternative methods for protection/deprotection of carboxyl groups are disclosed in for instance "Protective Groups in Organic Synthesis" by Theodora W. Greene and Peter G.M. Wuts, Chapter 5 "Protection for the Carboxyl Group" - John Wiley & Sons Inc., New York 1991.

Activation (for esterification) of carboxyfunctional chain extenders, as disclosed above, for acylation, that is addition to reactive groups (A) or (B), include activation as (a) anhydride, formed in situ, for instance aided by dicyclohexylcarbodiimide, or prefabricated; (b) acid chloride, for instance from oxalyl chloride, (c) mixed anhydride, for instance carboxylic acid and trifluoroacetic anhydride, or (d) as imidazolide The acylation is preferably performed in the presence of a solvent or solvent combination, such as methylene chloride, ethylene chloride, chloroform, pyridine, toluene, dimethoxyethane, diethyl ether, dipropyl ether, triethylamine, nitrobenzene, chlorobenzene and/or acetonitrile Esterification is advantageously performed in for instance dichloromethane through a dicyclohexylcarbodiimide coupling using 4-(dimethyl- amino)pyridinium 4-toluenesulphonate as catalyst.

Deprotection of the two ketal protected hydroxyl groups of the monomeric or polymeric branching chain extender is suitably performed by a mild solvolytic decomposition, such as a methanolysis, under acidic conditions. Decomposition of built up dendrimers and dendritic structures is thus highly unlikely and not observed during deprotection. Acetonide protected hydroxyl groups can for instance smoothly be removed by stirring the acetonide derivative in methanol in the presence of for instance a Dowex H resin.

The core is preferably selected from the group consisting of aliphatic, cycloaliphatic or aromatic mono, di, tri or polyalcohols and adducts thereof, such as hydroxysubstituted allyl ethers, formals and alkoxylates, or from the group consisting of glycidyl ethers, glycidyl esters, epoxides of unsaturated carboxylic acids and triglycerides, aliphatic, cycloaliphatic or aromatic epoxy polymers and epoxidized polyolefines. Suitable cores are for instance 4-hydroxymethyl- - 1 ,3-dioxolane, 5-methyl-5-hydroxymethyl- l ,3-dioxane, 5-ethyl-5-hydroxymethyl- - 1 ,3-dioxane, ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, neopentyl glycol, dimethylolpropane, 5,5-dihydroxymethyl- l ,3-dioxane, glycerol, trimethylolethane, trimethylolpropane, pentaerythritol, ditrimethylol- ethane, ditrimethylolpropane, anhydroennea-heptitol, dipentaerythritol, sorbitol and mannitol; hydroxysubstituted allyl ethers, such as glycerol monoallyl ether, glycerol diallyl ether, trimethylolpropane monoallyl ether, trimethylolpropane diallyl ether, pentaerythritol monoallyl ether, pentaerythritol diallyl ether or pentaerythritol triallyl ether; and alkoxylates of said alcohols and said hydroxysubstituted allyl ethers.

Alkoxylates are adducts between an alcohol and an alkylene oxide, such as ethylene oxide, propylene oxide, butylene oxide and/or phenylethylene oxide, and can suitably be exemplified by glycerol propoxylates, trimethylolethane ethoxylates, trimethylolethane propoxylates, trimethylolpropane ethoxylates, trimethylolpropane propoxylates, pentaerythritol ethoxylates and pentaerythritol propoxylates as well as ethoxylates or propoxylates of hydroxysubstituted allyl ethers, such as trimethylolpropane diallyl ether. Further preferred embodiments include as core phenolic alcohols, such as xylyLene alcohols, hydroxyphenylalkanes and hydroxybenzenes. These cores are advantageously exemplified by xylylene glycol, l , l , l -(trishydroxyphenyl)ethane, dihydroxybenzene and trihydroxybenzene.

Core molecules, such as 1 ,3-dioxane and 1 ,3-dioxolane alcohols, which are formals having two protected hydroxyl groups, can after completed addition of branching chain extenders be deprotected yielding hydroxyl groups according to methods disclosed in for instance "Protective Groups in Organic Synthesis" by Theodora W. Greene and Peter G.M. Wuts, Chapter 2 "Protection for the Hydroxyl Group" - John Wiley & Sons Inc., New York 1991 .

Epoxyfunctional cores can be exemplified by glycidyl ethers, such as 3-allyloxy- l ,2-epoxypropane, l ,2-epoxy-3-phenoxypropane and l -glycidyloxy-2- -ethylhexane; glycidyl ethers of phenols or reaction products thereof, such as condensation products between at least one phenol and at least one aldehyde or ketone; mono, di or triglycidyl substituted isocyanurates; and glycidyl esters, such

(R) as the Cardura compounds, which compounds are glycidyl esters of a highly branched saturated synthetic monocarboxylic acid named Versatic acid (Cardura and Versatic are trademarks of Shell Chemicals).

The process of the present invention offers several major advantages of technical and commercial value. Most noted is the unexpectedly high reactivity of ketal protected acylating agents, such as acetonide protected dihydroxyfunctional monocarboxylic acids, used according to the present invention as chain extenders and branching fragments in the construction of dendrimers and hyperbranched dendritic structures. Hydroxyfunctional carboxylic acids protected with other groups such as acetate or benzyl do not show the same high reactivity, thus construction of dendrimers from such molecules is highly complicated and of no practical importance.

These and other objects and the attendant advantages will be more fully understood from the following detailed description, taken in conjunction with embodiment Examples 1 -9. Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. Embodiment Examples 1 discloses synthesis of a ketal protected branching chain extender and Example 2 discloses synthesis of an ester protected branching chain extender, both employed in embodiments of the present invention. Examples 3-7 disclose various steps in the synthesis of a hyperbranched dendron and Examples 8 and 9 disclose synthesis of a tridendron hyperbranched dendritic polyalcohol. All Examples are in accordance with one preferred embodiment of the process of the present invention.

1 13

It was evidenced by H-NMR and C-NMR that products obtained in Examples 1 -9 were reported protected branching chain extenders (Example 1 -2), dendrons having reported number of branching generations and terminal protected or reactive hydroxyl groups (Example 3-7) and a hyperbranched dendritic polyester polyalcohol having reported number of dendritic branches of substantially identical and symmetrical structure and reported number of protected or reactive hydroxyl groups (Example 8 and 9).

Example 1

Synthesis of isopropylidene-2,2-bis(methoxy)propanoic acid.

10.0 g of 2,2-bis(hydroxymethyl)propanoic acid, 13.8 ml of 2,2-dimethoxypropane and 0.71 g of -toluenesulphonic acid monohydrate as catalyst were dissolved in 50 ml of acetone. The reaction mixture was stirred for 2 hours at room temperature. The catalyst was now neutralized by addition of « 1 ml of a solution of ammonia in ethanol (50: 50). The solvent was evaporated at room temperature and the residue was dissolved in 250 ml of dichloromethane and extracted with two portions of 20 ml of water. The organic phase was dried with MgSO₄ and evaporated to yield 12.0 g of isopropylidene-2,2-bis(methoxy)propanoic acid as white crystals. Yield: 92%.

Example 2

Synthesis of benzyl-2,2-bis(methylol)propanoate.

9.0 g of 2,2-bis(hydroxymethyl)propanoic acid and 4.3 g of potassium hydroxide were dissolved in 50 ml of dimethylformamide. The potassium salt was allowed form at 100°C for 1 hour. 13.8 g of benzyl bromide was now added and the reaction mixture was stirred at 100°C for 1 5 hours, after which added dimethylformamide was evaporated. The residue was dissolved in 200 ml of dichloromethane and extracted with two portions of 50 ml of water The crude product was recrystallized from hexane/dichloromethane to yield 10 0 of benzyl-2,2-bis(methylol)propanoate as white crystals Yield 67%

Example 3

Synthesis from the products of Examples 1 and 2 of a second generation dendron having protected hydroxyl and carboxyl groups

6 52 g of the product of Example 1 , 4 00 g of the product of Example 2 and 2 10 g of 4-(dimethylamino)pyridinium 4-toluenesulphonate as catalyst were charged in a reaction flask and dissolved in 60 ml of dichloromethane The reaction flask was flushed with argon for a few minutes followed by addition of 9 20 g of dicyclohexylcarbodiimide The reaction mixture was stirred, under argon atmosphere, at room temperature for 1 5 hours Dicyclohexylcarbodiimide urea was after completed reaction removed by filtration and washed with minor volumes of dichloromethane The crude product was purified by liquid chromatography on silica gel eluating with hexane gradually increasing to 40 60 ethyl acetate/hexane 8 00 g of a second generation dendron having four ketal protected hydroxyl groups and one ester protected carboxyl group was after said purification yielded Yield 84%

Example 4

Deprotection of the ester protected carboxyl group of a product according to Example 3

A solution of 3 60 g of the product of Example 3 in 30 ml of ethyl acetate and 0 36 g of Pd/C (10%) - palladium catalyst on activated carbon, 10% Pd - were charged in an apparatus for catalytic hydrogenolysis The apparatus was evacuated from air and filled with hydrogen Approximately 170 ml hydrogen were consumed during the hydrogenolysis The catalyst was after completed hydrogenolysis removed by filtration and carefully washed with ethyl acetate The filtrate was evaporated to yield as white crystals 2 90 g of a second generation dendron having four ketal protected hydroxyl groups and one reactive carboxyl group Yield 97%

Example 5

Deprotection of the ketal protected hydroxyl groups of a product according to Example 3 4.00 g of the product of Example 3 was dissolved in 50 ml of methanol and one teaspoon of Dowex H resin was added. The reaction mixture was stirred for three hours at room temperature. The Dowex H resin was, when the reaction was completed, removed by filtration and carefully washed with methanol. The filtrate was evaporated to yield as white crystals 3.35 g of a second generation dendron having four reactive hydroxyl groups and one ester protected carboxyl group. Yield: 98%.

Example 6

Synthesis from the products of Examples 4 and 5 of a fourth generation dendron having protected hydroxyl and carboxyl groups.

1 1 .74 g of the product of Example 4, 2.00 g of the product of Example 5, 5. 16 g of 4-(dimethylamino)pyridinium 4-toluenesulphonate and 5.88 g of dicyclohexylcarbodiimide were reacted according to the procedure disclosed in Example 3. The reaction time at room temperature was 48 hours in 100 ml of dry dichloromethane. The crude product was purified by liquid chromatography on silica gel eluating with hexane gradually increasing to 80:20 ethyl acetate/hexane. 8.70 g of a fourth generation dendron having sixteen ketal protected hydroxyl groups and one ester protected carboxyl group was after said purification yielded. Yield: 91%.

Example 7

Deprotection of the ester protected carboxyl group of the product of Example 6.

8.28 g of the product of Example 6 was dissolved in 120 ml of ethyl acetate and 0.83 g of Pd/C(10%) was added. Deprotection of the ester protected carboxyl group was performed in accordance with Example 4 yielding as a colourless viscous oil 7.44 g of a fourth generation dendron having sixteen ketal protected hydroxyl groups and one reactive carboxyl group. Yield: 97%.

Example 8

Synthesis of a tridendron hyperbranched dendritic polyalcohol, wherein the core is a phenolic alcohol and the dendrons are the product of Example 7.

7.22 g of the product of Example 7, 272 mg of l , l , l -tris(hydroxyphenyl)ethane, 782 mg of 4-(dimethylamino)pyridinium 4-toluenesulphonate as catalyst and 732 mg of dicyclohexylcarbodiimide were in accordance with the procedure of Example 3 reacted for 24 hours in 10 ml of dichloromethane. The crude product was purified by liquid chromatography on silica gel eluating with hexane^~gradually increasing to 100% ethyl acetate to yield as a colourless viscous oil 5.30 g of a hyperbranched dendritic polyalcohol having 48 ketal protected hydroxyl groups on three dendrons each having four generations and 16 ketal protected hydroxyl groups. Yield: 85%.

The product was, beside said NMR determinations characterized by elementary analysis regarding carbon and hydrogen, giving results within expected range, and by Size Exclusive Chromatography (SEC) giving below result. Since no adequate SEC standards are available, linear polystyrene was used as standard. As expected, the molecular weights determined were not in agreement with the theoretical molecular weights. This is explained by differences in the hydrodynamic volume of linear polystyrene standards and the synthesized hyperbranched dendritic product (dendrimer). SEC analyses exhibited a polydispersity value (M_w/M_n) close to that of linear polystyrene standards (M^/M_jj = 1 .02).

Theoretical molecular weight: 6493

Determined molecular weight (M_w), SEC: 4395

Nominal molecular weight (M_n), SEC: 4267

Polydispersity value, (M M_n), SEC: 1 .03

Example 9

Deprotection of the ketal protected hydroxyl groups of the product of Example 8.

4.50 g of the product of Example 8 was dissolved in 100 ml of methanol and the ketal protected hydroxyl groups were deprotected according to the procedure of Example 5 yielding after 48 hours of reaction 3.60 g as a white glass of a hyperbranched dendritic polyalcohol having 48 reactive hydroxyl groups on three dendrons each having four generations and 16 reactive hydroxyl groups. Yield: 92%.

Theoretical molecular weight: 553 1

Claims

1. A process for a double stage convergent synthesis of a dendritic polymeric polyalcohol having reactive or protected terminal hydroxyl groups, which polymeric polyalcohol has n dendritic branches emanating from a monomeric or polymeric core having n reactive hydroxyl or epoxide groups (A), whereby each branch comprises g branching generations each generation comprising at least one polymeric or monomeric branching chain extender having three functional groups of which two are reactive hydroxyl groups (B) and one is a reactive carboxyl group (C) and whereby n and g are integers and at least 1 , c h a r a c t e r i z e d i n, that the process includes the Steps of i) ketal protecting the two hydroxyl groups (B) of a monomeric or polymeric branching chain extender by reaction with at least one ketone, yielding a branching chain extender having two ketal protected hydroxyl groups (B') and one reactive carboxyl group (C), ii) protecting the carboxyl group of a polymeric or monomeric branching chain extender by reaction with a carboxyl protective compound, yielding a branching chain extender having two reactive hydroxyl groups (B) and one protected carboxyl group (C), iii) reacting the branching chain extender yielded in Step (i) and the branching chain extender yielded in Step (ii) at a molar ratio reactive carboxyl groups (C) to reactive hydroxyl groups (B) of at least 1 : 1 , yielding a polymer having four ketal protected hydroxyl groups (B¹) and one protected carboxyl group (C), iv) deprotecting the ketal protected hydroxyl groups (B¹) of a polymer synthesized according to Step (iii) yielding a polymer having four reactive hydroxyl groups (B) and one protected carboxyl group (C), v) optionally deprotecting the protected carboxyl group (C) of a polymer synthesized according to Step (iii) yielding a polymer having ketal protected hydroxyl groups (B¹) and one reactive carboxyl group (C), vi) reacting, in case g > 1 and in a number of repeated steps yielding g branching generations, the product yielded in Step (iv) or a hydroxyl deprotected product yielded in present Step (vi) with the product yielded in Step (i) or Step (v) at a molar ratio reactive hydroxyl groups (B) to reactive carboxyl groups (C) of at least 1 : 1 , yielding a product having ketal protected hydroxyl groups (B¹) and one reactive carboxyl group (C) or one protected carboxyl group (C), vii) adding the product yielded in Steps (iii) or (vi), after deprotection of the optionally protected carboxyl group (C), to the core at a molar ratio core to said Step (ii) or Step (vi) product of 1:1 to \:n, yielding a dendritic polymer having at least one dendritic branch emanating from said core, and viii) optionally deprotecting the ketal protected hydroxyl groups (B') of the product obtained in Step (vii), yielding terminal reactive hydroxyl groups (B).

2. A process according to Claim 1 ch a racterized i n, that n is an integer between 1 and 20, preferably between 2 and 12 and most preferably between 2 and 8.

3. A process according to Claim 1 or 2 c h aracterized in, that g is an integer between 1 and 50, preferably between 2 and 20 and most preferably between 2 and 8.

4. A process according to any of the Claims 1-3 c h a racterized i n, that the polymeric polyalcohol is built up from polyester units, optionally in combination with ether or polyether units.

5. A process according to any of the Claim 1-4 c h aracterized in, that the polymeric polyalcohol has two or more identical and/or symmetrical dendritic branches and that continued branching chain extension yields a polymeric polyalcohol having increased branching density and increased number of reactive hydroxyl groups (B) or ketal protected hydroxyl groups (B^*).

6. A process according to any of the Claims 1-5 c h a racterized in, that each addition of a branching generation individually employs a ketal protected branching chain extender being a reaction product between the same or a different branching chain extender and/or the same or a different ketone.

7. A process according to any of the Claims 1-6 c h a ra cterized i n, that the ketone is acetone, cyclohexanone and/or 2,2-dimethoxypropane

8. A process according to any of the Claims 1-7 ch a ra cterized i n, that the protected carboxyl group (C) is ester protected.

9. A process according to any of the Claims 1-8 ch a ra cte rized i n, that the carboxyl protective compound is an alkyl and/or arylhalide.

10. A process according to Claim 9 ch aracterized in, that the alkyl or arylhalide is allyl chloride, allyl bromide, benzyl chloride, benzyl bromide or combinations thereof.

11. A process according to any of the Claims 1-8 ch a racterized i n, that the carboxyl protective compound is allyl or benzyl alcohol.

12. A process according to any of the Claims 1-11 ch ara cterized i n, that each addition employing a protected branching generation individually employs a protected branching chain extender being a reaction product between the same or a different branching chain extender and/or the same or a different carboxyl protective compound.

13. A process according to any of the Claims 1-12 ch aracterized in, that addition of branching generations and addition to said core of said Step (iii) or Step (vi) product are performed at a temperature of -30-150°C, such as -10-80°C or 10-50°C.

14. A process according to any of the Claims 1-13 c h aracterized i n, that the branching chain extender is a dihydroxyfunctional monocarboxylic acid or an adduct between a dihydroxyfunctional monocarboxylic acid and at least one alkylene oxide, which adduct has two hydroxyl groups and one carboxyl group.

15. A process according to Claim 14 characterized in, that the branching chain extender is 2,2-bis(hydroxymethyl)propanoic acid, 2,2-bis(hydroxymethyl)butanoic acid, 2,2-bis(hydroxymethyl)pentanoic acid or 2,3-dihydroxypropanoic acid.

16. A process according to Claim 14 ch aracterized in, that the alkylene oxide is ethylene oxide, propylene oxide, butylene oxide, phenylethylene oxide or a mixture thereof.

17. A process according to any of the Claims 1-16 characterized in, that the branching chain extender is activated for acylation as anhydride, as acid chloride, as mixed anhydride or as imidazolide.

18. A process according to Claim 17 c h aract erized in, that acylation is performed in the presence of a solvent or solvent combination selected from the group consisting of methylene chloride, ethylene chloride, chloroform, pyridine, toluene, dimethoxyethane, diethyl ether, dipropyl ether, ethoxyethanol, nitrobenzene, chlorobenzene and acetonitrile.

19. A process according to any of the Claims 1-18 ch a racterized in, that deprotection of the ketal protected hydroxyl groups (B¹) is performed by solvolytic decomposition, such as methanolysis, under acidic conditions.

20. A process according to any of the Claims 1-19 ch a racterized i n, that the core is an aliphatic, a cycloaliphatic or an aromatic mono, di, tri or polyalcohol or an adduct, such as a hydroxysubstituted allyl ether, an alkoxylate or a formal, thereof.

21. A process according to Claim 20 ch aracterized in, that the core is an alkoxylate obtained by reacting glycerol, trimethylolethane, trimethylolpropane or pentaerythritol with at least one alkylene oxide.

22. A process according to Claim 21 ch aracte rized i n, that the alkylene oxide is ethylene oxide, propylene oxide, butylene oxide, phenylethylene oxide or a mixture thereof.

23. A process according to Claim 20 c h a racterized i n, that the core is a hydroxysubstituted allyl ether, such as glycerol monoallyl ether, glycerol diallyl ether, trimethylolpropane monoallyl ether, trimethylolpropane diallyl ether, pentaerythritol monoallyl ether, pentaerythritol diallyl ether or pentaerythritol triallyl ether.

24. A process according to any of the Claims 20-23 ch a ra cterized i n, that the core is ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, neopentyl glycol, dimethylolpropane, glycerol, trimethylolethane, trimethylolpropane, pentaerythritol, ditrimethylolethane, ditrimethylolpropane, anhydroennea-heptitol, dipentaerythritol, sorbitol, mannitol, trimethylolpropane triethoxylate, trimethylolpropane tripropoxylate, pentaerythritol triethoxylate or pentaerythritol pentaethoxylate.

25. A process according to Claim 20 c h a ra ct erized in, that the core is a formal such as a 1,3-dioxane or a 1,3-dioxolane alcohol.

26. A process according to Claim 25 ch a racterized i n, that the formal is 4-hydroxymethyl-l,3-dioxolane, 5-methyl-5-hydroxymethyl- -1,3-dioxane, 5-ethyl-5-hydroxymethyl-l,3-dioxane or 5,5-dihydroxymethyl- -1,3-dioxane.

27. A process according to Claim 25 or 26 ch a ract erized i n, that the formal after completed addition of branching chain extenders is decomposed yielding reactive hydroxyl groups.

28. A process according to any of the Claims 1-20 ch aracterized in, that the core is a phenolic alcohol, such as a xylylene alcohol or a hydroxyphenylalkane

29. A process according to Claim 28 ch a ra cterized in, that the hydroxyphenylalkane is dihydroxybenzene, trihydroxybenzene or 1,1,1 -tris(hydroxyphenyl)ethane.

30. A process according to any of the Claims 1-20 ch a ra cterized i n, that the core is selected from the group consisting of a glycidyl ether, a glycidyl ester, an epoxide of an unsaturated carboxylic acid or triglyceride, an aliphatic epoxy polymer, a cycloaliphatic epoxy polymer, an aromatic epoxy polymer and an epoxidized polyolefine.