SE510088C2 - Synthesis of a dendritic polyalcohol - Google Patents

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

510 us 2 Structures such as star-branched, dense star-branched, dendrimers and hyperbranched dendritic molecules and macromolecules can be easily visualized from these and a large number of similar works published during the 1950s, 1960s and especially the 1970s but not easily synthesized.

Various hyperbranched and dendritic materials have attracted general attention over the past decade or two. Patents, patent applications and other works issued or published in recent decades are summarized by, for example, H.

Galina m fl. iPolymery, English translation in Int. Polym. Sci. Tech. 1995, 22, 70.

Hyperbranched dendritic macromolecules, including dendrimers, can be generally described as three-dimensional, highly branched molecules with a tree-like structure. Dendrimers are strongly symmetrical, while similar macromolecules referred to as hyperbranched or dendritic may to some extent be asymmetrical, but with a strongly branched tree-like structure. Dendrimers can be said to be monodisperse - actual molecular weight (MW) / nominal molecular weight (Mn) = 1 - or mainly monodisperse (MW / Mn z 1) hyperbranched macromolecules. Hyperbranched and dendritic macromolecules normally consist of an initiator or core with one or more reactive regions and of a number of branching layers and possibly a layer of terminating molecules. Continued replication of branching layers results in an increased degree of branching and, where relevant or desirable, an increased number of tenninal groups. The layers are usually called generations and the branches dendrons, which are terms used hereafter.

Synthesis of perfect dendritic materials, i.e. mainly monodisperse molecules comprising symmetrical tree-like (dendritic) branches, which may emanate oxygenetrically as well as concentrically from a core or initiator molecule, is a challenging task as high yield and high selectivity are required. Various procedures have been proposed for dendritic, near-dendritic and perfectly dendritic products, but complex and unsatisfactory syntheses are still an obstacle to the technical and commercial use of monodisperse dendritic products. Most of the processes shown result in either polydisperse and / or overly expensive products. A number of patents and patent applications showing various hyperbranched and / or dendritic macromolecules and methods for their synthesis have been issued or published for various types of products and include EP 0 115 771, SE 468 771, WO 93/18075, EP 0 575 569, SE 503 342 and US 5.56l, 214.

EP 0 115 571 relates to a dense star polymer with at least three symmetrical core branches, each core branch having at least one tenninal group and the ratio of terminal groups to core branches being greater than 2: 1. The properties of the intended polymer are specified by comparison with an unspecified and purported known star polymer. Requirement l can not be interpreted due to inoperative 3,510 us terminal group determinations and Unspecified comparison. EP 0 115 771 further relates to a process, which process can also be mainly read from US 4,410,688, for synthesis of a symmetrically dense stamp polymer. The process shows repeated and alternating addition of alkyl acrylate and alkylenediarnin to a core consisting of ammonia.

SE 468 771 discloses a hyperbranched dendritic macromolecule which is mainly composed of ester units and a method for synthesis of said macromolecule.

The macromolecule is composed of an initiator having at least one hydroxyl group, to which initiator at least one branched generation comprising at least one chain extender having at least one carboxyl group and at least two hydroxyl groups has been added. The macromolecule may be chain terminated. The process for synthesizing said macromolecule indicates co-esterification of the initiator and the chain extender, possibly followed by chain termination.

The process results in inexpensive polydisperse hyperbranched dendritic macromolecules.

WO 93/18075 discloses 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 alternating addition to a core having at least one hydroxyl group, of a compound having at least one anhydride group followed by a compound having at least one epoxide 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 a method for synthesizing them. The process comprises three repeated steps which begin with a reaction between the core and a monomeric vinyl cyanide unit followed by reduction of incorporated nitrile groups to anine groups. In a third step, said amine groups are reacted with monomeric vinyl cyanide units.

SE 503 342 discloses a hyperbranched dendritic macromolecule of the polyester type and a process for the synthesis of said macromolecule. The macromolecule is mainly composed of a core having at least one epoxide group, to which core at least one branching generation comprising at least one chain extender, which has at least three reactive functions of which at least one is a carboxyl or epoxide group and at least one is a hydroxyl group, .

The macromolecule is optionally chain terminated. The process shows self-condensation of the chain-extending molecules resulting in a dendron (core branch), which dendron is added to the core in a second step. The method also includes an optional further chain extension by the addition of extending or branching chain extenders and / or an optional chain tenin. The process results in inexpensive polydisperse hyperbranched dendritic macromolecules. U.S. 5,561,214 relates to highly asymmetric hyperbranched polydisperse polyaspartate esters and to a process for their synthesis. The process involves self-condensation, via transesterification, of at least a portion of the hydroxyl or ester groups of hydroxyaspartate.

The latest developments in the synthesis and characterization of dendritic molecules are given in, for example, "Synthesis, Characterization, and 1 H-NMR Self-Diffusion Studies of Dendritic Aliphatic Polyesters Based on 2,2-Bis (hydroxymethyl) propionic acid and 1,1,1 Tris (hydroxyphenyl) ethane "by Henrik Ihrc m fl. published in J. Am. Chem. Soc. vol. 118 (1996) p. 6388-6395, wherein one, two, three and four generations of dendritic polyesters are synthesized and characterized. The dendrimers are synthesized according to a convergent procedure, whereby dendrons (core branches) are first synthesized from acylated 2,2-bis (hydroxymethyl) propionic acid and then coupled to a poly-n-ionic phenolic core molecule. A further description of the latest development is "Hyperbranched Aliphatic Polyesters - Synthesis, Charaterization and Applications" by Eva Malmström, Royal Institute of Technology, Stockholm 1996, in which hyperbranched dendritic polyesters of the type shown in SE 468 771 are studied and discussed.

Hyperbranched dendritic, including dendrimers, polyalcohols which are mainly composed of polyester units give, depending on the symmetrical or next symmetrical strongly branched structure, great advantages over ordinary polyalcohols and randomly branched polyester polyalcohols. Said hyperbranched dendritic polyalcohols have a low dispersity and can, depending on the structure, be formulated to give a very high molecular weight and still have a very low viscosity. Hyperbranched dendritic, including dendrimers, polyester polyalcohols can be advantageously used for further process processing, such as chain termination and / or functionalization, and thus result in dendritic products with, for example, fatty acid termination, alkenyl groups, such as allyl, vinyl or alayl epoxides, primary groups or / or undergo similar conversion or reaction with the hydroxyl groups of said polyalcohol.

The inexpensive, easily accessible and easy-to-handle materials used in the process of the present invention quite unexpectedly provide an opportunity to formulate a simple, reliable and reproducible process for the synthesis of monodisperse or substantially monodisperse polyester alcohols, i.e. dendritic polyesters with teiminally unprotected or protected hydroxyl. The process of the present invention is simple and convenient to adapt to the desired process conditions and desired final structure and desired final properties of the obtained dendritic polyalcohol.

The present invention relates to a two-step convergent synthesis of a polymeric polyalcohol having reactive or protected terminal hydroxyl groups, which polymeric alcohol is composed of a monomeric or polyurethane nucleus having n reactive hydroxyl or epoxide groups (A), to which n dendritic branches (dendrons) are connected by addition, each branch consisting of g branching generations and wherein n and g are integers and at least l.

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, which has three functional groups, two of which 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 obtained 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 comprises two different types of 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, whereby a branching chain extender with two ketal-protected hydroxyl groups (B ') and a reactive carboxyl group is obtained. Protection, ester protection, of the carboxyl group - step (ii) - is obtained by reacting said carboxyl group with a carboxyl-protecting compound, such as an alkyl or aryl halide, preferably benzyl chloride, benzyl bromide, allyl chloride, allyl bromide or combinations thereof, or by reaction with an alcohol allyl or benzyl alcohol, whereby a branching chain extender with two reactive hydroxyl groups (B) and a protected carboxyl group (C ') is obtained. The branching chain extensions obtained in approximate steps (i) and (ii) are reacted in a step (iii) at a molar ratio of reactive carboxyl groups (C) to reactive hydroxyl groups (B) of at least 1: 1, a polymer having four ketal-protected hydroxyl groups (B ') and a protected carboxyl group (C') is obtained. The protected hydroxyl groups (B ') of a polymer obtained according to step (iii) are deprotected in a fourth step - step (iv) -, whereby a polymer having four reactive hydroxyl groups (B) and a protected carboxyl group (C') is obtained. The protected carboxyl group of a step (iii) polymer is deprotected in an optional step (v), whereby a polymer having ketal-protected hydroxyl groups (B ') and a reactive carboxyl group is obtained. In cases where g> 1, the present process comprises a sixth step - step (vi) - wherein the product obtained in step (iv), a number of times resulting in branching generations, or a hydroxy-protected product obtained in the present step (vi) is reacted with the product obtained in step (i) or step (v) at a molar ratio of reactive hydroxyl groups (B) to reactive carboxyl groups (C) of at least 1: 1, a product having ketal-protected hydroxyl groups (B ') and a reactive carboxyl group (C) or a protected carboxyl group (C ') is obtained. The one in the last iteration of step (vi), i.e. the step resulting in generation g, the obtained dendron or the dendron obtained in step (iii) is now added in a step (vii), after deprotection of the optionally protected carboxyl group (C '), to the core at a molar ratio of core to said step (vi) 510,088 product of 1: 1 to 1zn, whereby a polymer having at least one dendritic branch starting from said core is obtained. An optional step (viii) comprises deprotecting the ketal-protected hydroxyl groups (B ') of the hyperbranched dendritic polyalcohol obtained in step (vii), whereby tenninal reactive hydroxyl groups (B) are obtained.

Each addition of a dry-branched generation - step (iii) or step (vi) - to an initially synthesized dendron may, according to various embodiments, individually comprise a ketal-protected branching chain extender, which is a reaction product between the same or different branching chain extenders and / or the same or different ketones. , as well as comprising a protected branching chain extender, which is a reaction product between the same or different branching chain extenders and / or the same or different carboxyl-protecting compounds, such as said alkyl or aryl halide.

The integer value for 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 for g is in equally preferred embodiments between 1 and 50, preferably between 2 and 20 and most preferably between 2 and 8.

The polyurethane polyalcohol obtained by the process of the present invention has in its preferred embodiments n identical and / or acidic dendritic branches, n being an integer and at least 2. Dendrons with repeated branching result in these embodiments in polymeric polyalcohols with increased number of precursors. reactive hydroxyl groups (B) or ketal protected hydroxyl groups (B ').

Addition of branching generations and addition of said dendrons, for example products obtained in step (iii) or step (vi), to said core is preferably carried out at a temperature of -30-150 ° C, such as -10-80 ° C or -50 ° C.

Particularly preferred embodiments of the present invention include ketal-protected branched chain extenders from the group of dihydroxy-functional monocarboxylic acids or adducts between dihydroxy-functional monocarboxylic acids and at least one alkylene oxide, which adduct has two hydroxyl groups and a carboxyl group. Preferred alkylene oxides are ethylene oxide, propylene oxide, butylene oxide, phenylethylene oxide and mixtures thereof.

The branching chain extender used to make the ketal-protected branching chain extender is in the most preferred embodiments of the present invention a dihydroxy-functional monocarboxylic acid, such as 2,2-bis (hydroxymethyl) propanoic acid, 2,2-bis- (hydroxymethyl) 2,2-acid-, hydroxymethyl) bis (hydroxymethyl) pentanoic acid or 2,3-dihydroxypropionic acid. Ester protection, such as benzyl ester protection, can be conveniently obtained by first forming an alkali metal salt and in a second step reacting the salt with, for example, benzyl bromide or by reaction with, for example, benzyl alcohol. The benzyl ester group can be selectively removed in very high yield by catalytic hydrogenolysis without affecting the ester bonds formed in synthesized dendritic polymer. Deprotection can be performed at atmospheric pressure in the presence of a catalyst, such as a palladium catalyst on activated carbon (Pd / C). Appropriate to the above methods for protecting / protecting alternative methods for protecting / protecting carboxyl groups are reported in, for example, "Protective Groups in Organic Synthesis" by 'Iheodora W. Greene and Peter G.M. Wuts, Chapter 5 "Protection for the Carboxyl Group" - John Wiley & Sons Inc., New York 1991.

Activation of carboxylfurictional chain extenders, as described above, for acylation (esterification), i.e. addition to reactive groups (A) or (B), comprises activation as (a) anhydride, formed in situ, by means of, for example, dicyclohexylcarbodiimide, or prefabricated, (b) acid chloride, for example from oxalyl chloride, (c) mixed anhydride, for example carboxylic acid and trifluoroacetic acid, or (d) as imidazolide. Acylation is preferably carried out in the presence of a solvent or a combination of solvents, such as methylene chloride, ethylene chloride, chloroform, pyridine, toluene, dimethoxyethane, diethyl ether, dipropyl ether, triethylamine, nitrobenzene, chlorobenzene and / or acetonitrile. Esterification is advantageously carried out in, for example, dichloromethane by dicyclohexylcarbodiimide coupling using 4- (dimethylamino) pyridine 4-toluenesulfonate as catalyst.

Deprotection of the two ketal-protected hydroxyl groups of the monomeric or polymeric branching chain extender is conveniently accomplished by mild solvolytic degradation, such as methanolysis, under acidic conditions. Degradation of built-up dendrimers and dendritic structures is not particularly probable and is not observed during deprotection. Acetonide protection of hydroxyl groups can, for example, be easily removed by stirring the acetonide derivative in methanol in the presence of, for example, a Dowex® H * resin.

The core is preferably from the group of aliphatic, cycloaliphatic or aromatic mono-, di-, tri- or polyalcohols and adducts thereof, such as hydroxy-substituted allyl ethers, formulas and alkoxylates, or from the group of glycidyl ethers, glycidyl esters, epoxides of unsaturated carboxylacylic acids, aromatic epoxy polymers and epoxidized polyolefins. Suitable nuclei are, for example, 4-hydroxymethyl-1β-dioxolane, 5-methyl-5-hydroxymethyl-1β-dioxane, S-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-1,3-dioxane, glycerol, trimethylolethane, trimethylolpropane, pentaerythritol, ditrimethylolethane, ditrimethylolpropane, mannitololipropane, anhydroenolitholipropane, anhydrolytolipropane hydroxy-substituted allyl ethers, such as glycerol monoallyl ethers, glycerol diallyl ethers, trimethylolpropane monoallyl ethers, trimethylolpropanedial ethers, pentaerythritol monoallyl ethers, pentaerythritol diallyl ethers or pentaerythritol triallyl ethers; and alkoxylates of said alcohols and said hydroxy-substituted 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 conveniently exemplifying fi ed with glycerolpropoxylater, trimetyloletanetoxylater, trimetyloletanpropoxylater, trimethylolpropane ethoxylates, trimetylolpropanpropoxylater, pentaerytritoletoxylater and pentaerythritol propoxylates as well as ethoxylates and propoxylates of hydroxy-substituted allyl ethers, such as trimethylolpropanedial ethers.

Further preferred embodiments include as core phenolic alcohols, such as xylylene alcohols, hydroxyphenylalkanes and hydroxybenzenes. These nuclei can be advantageously exemplified by xylylene glycol, 1,1,1,1- (trihydroxyphenyl) ethane, dihydroxybenzene and trihydroxybenzene.

Core molecules, such as 1,3-dioxane and β-dioxolane alcohols, which are formals with two protected hydroxyl groups, can be deprotected after completion of the addition of branching chain extenders, resulting in hydroxyl groups, according to methods described in, for example, "Protective Groups in Organic Synthesis" of Theodora W. Greene and Peter GM Wuts, Chapter 2 "Protection for the Hydroxyl Group" - John Wiley & Sons Inc., New York 1991.

Epoxy-friction cores can be exemplified by glycidyl ethers such as 3-allyloxy-1,2-epoxypropane, 1,2-epoxy-3-phenoxypropane and 1-glycidyloxy-Z-ethylhexane; glycidyl ethers of phenols or reaction products thereof, such as condensation products of at least one phenol and at least one aldehyde or ketone; mono-, di- or trisubstituted isocyanurates; and glycidyl esters, such as the Cardura® compounds, which compounds are glycidyl esters of highly branched synthetic monocarboxylic acids called Versatic® acid (Cardura and Versatic are trademarks of Shell Chemicals).

The process of the present invention offers many advantages of technical and commercial value. Most notable is the unexpectedly high reactivity of ketal-protected acylating agents, such as acetonide-protected dihydroxy-functional monocarboxylic acids, used in the present invention as chain extenders and branching fragments in the construction of dendrimers and hyperbranched dendritic structures. Hydroxy-functional carboxylic acids protected with other groups, such as acetate or benzyl, do not show the same reactivity, so the construction of dendrimers from such molecules is extremely complicated and without practical significance.

These and other aspects as well as associated advantages will be better understood from the following detailed description, which is given in connection with Embodiments 1-9. It is believed, without further explanation, that one skilled in the art may, by the foregoing description, fully practice the present invention. The following preferred embodiments are therefore intended to be illustrative only and not limit the remaining record in any way.

Example 1 shows the synthesis of a ketal-protected branching chain extender and Example 2 shows the synthesis of an ester-protected branching chain extender, both used in embodiments of the present invention. Examples 3-7 show different steps in the synthesis of a hyperbranched dendron and Examples 8 and 9 show the synthesis of a hyperbranched dendritic polyalcohol with three dendrons. The examples are according to a preferred embodiment of the method according to the present invention.

It was shown by 1 H-NMR and UC-NMR that the products obtained by Examples 1-9 were indicated protected branching chain extenders (Example 1-2), dendrons with the indicated number of branching generations and terminal protected hydroxyl groups (Example 3-7) and a hyperbranched dendritic polyester polyalcohol having the indicated number of dendritic branches having substantially identical and symmetrical structure and the indicated number of protected or reactive hydroxyl groups (Examples 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 the monohydrate of p-toluenesulfonic acid as catalyst were dissolved in 50 ml of acetone.

The reaction mixture was stirred for 2 hours at room temperature. The catalyst was then neutralized by adding z 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 diclonnetane and extracted with two 20 ml portions of water. The organic phase was dried over MgSO 4 and evaporated to give 12.0 g of isopropylidene-2,2-bis (methoxy) propanoic acid as white crystals.

Yield: 92%. 510 oss w Example 2 Synthesis of benzyl 2,2-bis (methylol) propanoate. 10.0 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 to form at 100 ° C for 1 hour. 13.8 g of benzyl bromide were then added and the reaction mixture was stirred at 100 ° C for 15 hours, after which the added dimethylformamide was evaporated. The residue was dissolved in 200 ml of dichloromethane and extracted with two 50 ml portions of water. The crude product was recrystallized from hexari / dichloromethane to give 10.0 g of benzyl 2,2-bis (methylol) propanoate as white crystals.

Yield: 67%.

Example 3 Synthesis of a dendron, of two generations and with protected hydroxyl and carboxyl groups, from the products of Examples 1 and 2. 6.52 g of the product of Example 1, 4.00 g of the product of Example 2 and 2.10 g 4- (Dimethylamino) pyridine 4-toluenesulfonate as catalyst was charged to a reaction flask and dissolved in 60 ml of dichloromethane. The reaction flask was purged with argon for a few minutes followed by the addition of 9.20 g of dicyclohexylcarbodiimide. The reaction mixture was stirred, under argon atmosphere, at room temperature for 15 hours. Dicyclohexylcarbodiimidurea was removed by filtration when the reaction was completed and washed with smaller volumes of dichloromethane. The crude product was purified by liquid chromatography on silica gel eluting with hexane gradually increasing to 40:60 ethyl acetate / hexane. 8.00 g of a two-generation dendron having four ketal-protected hydroxyl groups and an ester-protected carboxyl group were obtained after close purification. Yield: 84%.

Example 4 Deprotection of the ester protected carboxyl group on product of Example 3.

A solution of 3.60 g of product according to Example 3 in 30 ml of ethyl acetate and 0.36 g of Pd / C (10%) - palladium catalyst on activated carbon, 10% Pd - was charged to a catalytic hydrogenolysis apparatus. The apparatus was evacuated on lu fi and filled with hydrogen. About 170 ml of hydrogen were consumed during the hydrogenolysis. The catalyst was removed by filtration after completion of 510 os of hydrolysis and washed thoroughly with ethyl acetate. The filtrate was evaporated to give 2.90 g of dendron of two generations and having four ketal-protected hydroxyl groups and a reactive carboxyl group as white crystals. Yield: 97%.

Example 5 Deprotection of the ketal protected hydroxyl groups on product of Example 3. 4.00 g of product of Example 3 were dissolved in 50 ml of methanol and a teaspoon of Dowex® H * resin was added. The reaction mixture was stirred at room temperature for 3 hours. When the reaction was complete, the Dowex® H * resin was removed by filtration and washed thoroughly with methanol. The filtrate was evaporated to give 3.35 g of dendron of two generations and having four reactive hydroxyl groups and an ester protected carboxyl group as white crystals. Yield: 98%.

Example 6 Synthesis of a dendron, of four generations and with protected hydroxyl and carboxyl groups, from the products of Examples 4 and 5. 11, 742 g of the product of Example 4, 2.00 g of the product of Example 5, 5.16 g 4- (Dimethylamino) pyridine 4-toluenesulfonate and 5.88 g of dicyclohexylcarbodiimide were reacted according to the procedure shown 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 eluting with hexane gradually increasing to 80:20 ethyl acetate / hexane. 8.70 g of a dendron of four generations which had sixteen ketal protected hydroxyl groups and an ester protected carboxyl group were obtained after said purification. Yield: 91%.

Example 7 Deprotection of the ester protected carboxyl group on the product of Example 6. 8.28 g of the product of Example 6 was dissolved in 120 ml of ethyl acetate and 0.36 g of Pd / C (10%) was added. Deprotection was carried out in accordance with Example 4 to give 7.44 g of dendron of four generations and with sixteen ketal protected hydroxyl groups and a reactive carboxyl group in the form of a viscous oil. 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 1,1,1,1-tris (hydroxyphenyl) ethane, 782 mg of 4- (dimethylamino) pyridine 4-toluenesulfonate cocatalyst and 732 mg of dicyclohexylcarbodiimide were reacted, according to the procedure of Example 3, for 24 hours in 10 ml of dichloromethane. The crude product was purified by liquid chromatography on silica gel eluting with hexane gradually increasing to 100% ethyl acetate to give a hyperbranched dendritic polyalcohol having 48 ketal protected hydroxyl groups on three dendrons of 4 generations each and 16 hydroxyl groups in the form of an colorless oil. Yield: 85%.

The product was characterized, in addition to NMR, by elemental analysis for carbon and hydrogen, which gave results within expected ranges, and SEC (Size Exclusive Chromatography) which gave results below. When adequate SEC standards are not available, linear polystyrene was used as standard. Analyzed molecular weight was, as expected, not consistent with the theoretical molecular weight. This is explained by the differences in hydrodynamic volume between the linear polystyrene standard and the synthesized hyperbranched dendritic product (the dendrimer). The SEC analyzes showed a polydispersity value (MW / Mn) close to that of linear polystyrene standard (MW / Mn = 1.02).

Theoretical molecular weight 6493 Analyzed molecular weight (MW), SEC: 4395 Nominal molecular weight (Mn), SEC: 4267 Polydispersity value (MW / Mn), SEC: 1,03 13 510 088 Example 9 Deprotection of the ketal-protected hydroxyl groups on the product according to Example 8 50 g of the product of Example 8 were dissolved in 100 ml of methanol and the ketal protected hydroxyl groups were deprotected according to the procedure of Example 5 to give 3.60 g of a hyperior branched dendritic polyalcohol having 48 reactive hydroxyl groups on three dendrons of four generations each and 16 reactive hydroxyl groups. is a 48 hour reaction in the form of white crystals. Yield: 92%.

Theoretical molecular weight: 5531

Claims (1)

A process for double step convergent synthesis of a dendritic polymeric polyalcohol having reactive or protected hydroxyl groups, which polymeric polyalcohol has n dendritic branches starting from a monomeric or polymeric core having n reactive hydroxyl or epoxide groups (A), wherein each branch comprises g branched generations and each generation comprises at least one polymeric or monomeric branching chain extender having three reactive groups of which two are reactive hydroxyl groups (B) and one is a reactive carboxyl group (C) and wherein n and g are integers and at least 1, characterized in that process comprises steps i) iii) iv) vi) ketal protection of the two hydroxyl groups (B) on a monomeric or polymeric branching chain extender by reaction with at least one ketone, wherein a branching chain extender having two ketal protected hydroxyl groups and (B ') a reactive carboxyl group (C) is obtained, protecting the carboxyl group (C) on a polymeric or monomeric chain extender by reaction with a carboxyl protecting compound, whereby a branching chain extender with two reactive hydroxyl groups (B) and a protected carboxyl group (C ') is obtained, reaction between the branching chain extender obtained in step (i) and the branching chain extender obtained in step (i) a molar ratio of reactive carboxyl groups (C) to reactive hydroxyl groups (B) of at least 1: 1, whereby a polymer having four ketal-protected hydroxyl groups (B ') and a protected carboxyl group (C') is obtained, deprotecting the ketal-protected hydroxyl groups (B ') on a polymer formed according to step (iii), wherein a polymer having four reactive hydroxyl groups (B) and a protected carboxyl group (C ') is obtained, optionally deprotecting the protected carboxyl group (C') on a polymer prepared according to step (iii), wherein a polymer having ketal-protected hydroxyl groups (B ') and a reactive carboxyl group (C) is obtained, reaction, in cases where g> 1 and in a number of repeated steps whereby g branched generations are obtained lls, between product obtained in step (iv) or a hydroxy-protected product obtained in the present step (vi) and product obtained in step (i) or step (v) at a molar ratio of reactive hydroxyl groups (B) to reactive carboxyl groups (C) of at least 1: 1, whereby a product with ketal-protected hydroxyl groups (B ') and a reactive carboxyl group (C) or a protected carboxyl group (C') is obtained, after addition of optionally protected carboxyl group (C '). ), of product obtained in step (iii) or (vi) to a core at a molar ratio of core to said step (ii) or step (vi) product of lzl to lzn, wherein a dendritic polymer having at least one dendritic branch starting from said core is obtained, and viii) optionally deprotecting ketal-protected hydroxyl groups (B ') on product obtained in step (vii), whereby terminal reactive hydroxyl groups are obtained. A method according to claim 1, characterized in that n is an integer between 1 and 20, preferably between 2 and 12 and most preferably between 2 and 8. A method according to claim 1 or 2, characterized in that g is an integer between 1 and 50, preferably between 2 and 20 and most preferably between 2 and 8. A process according to any one of claims 1-3, characterized in that the polymeric polyalcohol is composed of polyester units, optionally in combination with ether or polyether units. A process according to any one of claims 1-4, characterized in that the polymeric polyalcohol has two or more identical and / or symmetrical dendritic branches and that repeated dry branching results in a polymeric polyalcohol with increased degree of branching and increased number of reactive hydroxyl groups (B) or ketal-protected hydroxyl groups. (B '). A method according to any one of claims 1-5, characterized in that each addition of a branching generation individually comprises a ketal-protected branching chain extender which is a reaction product between the same or different branching chain extenders and / or the same or different ketones. A process according to any one of claims 1-6, characterized in that the ketone is acetone, cyclohexanone and / or 2,2-dimethoxypropane. A process according to any one of claims 1 to 7, characterized in that the protected carboxyl group (C ') is ester protected. 510 088 10. 11. 12. 13. 14. 15. A process according to any one of claims 1 to 8, characterized in that the carboxyl-protecting compound is an alkyl or aryl halide. A process according to claim 9, characterized in that the alkyl or aryl halide is allyl chloride, allyl bromide, benzyl chloride, benzyl bromide or combinations thereof. A process according to any one of claims 1 to 8, characterized in that the carboxyl-protecting compound is allyl or benzyl alcohol. A method according to any one of claims 1-11, characterized in that each addition comprising a protected branching generation individually comprises a protected branching chain extender which is a reaction product between the same or different branching chain extenders and / or the same or different kaboxyl-protecting compounds. A process according to any one of claims 1-12, characterized in that addition of dry branching generations and addition to said core of step (iii) or step (vi) product is carried out at a temperature of -30-150 ° C, such as -10-80 ° C or 10-50 ° C. A process according to any one of claims 1 to 13, characterized in that the branching chain extender is a dihydroxy-functional monocarboxylic acid or an adduct of a dihydroxy-frictional monocarboxylic acid and at least one alkylene oxide, which adduct has two hydroxyl groups and a carboxyl group. 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 Zβ-dihydroxypropanoic acid. 16. 17. 19. 19. 20. 21. 22. 1, 510 us A process according to claim 14 characterized in that the alkylene oxide is ethylene oxide, propylene oxide, butylene oxide, phenylethylene oxide or a mixture thereof. A process according to any one of 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. A process according to claim 17, characterized in that acylation is carried out in the presence of a solvent or a combination of solvents from the group of methylene chloride, ethylene chloride, chloroform, pyridine, toluene, dimethoxyethane, diethyl ether, dipropyl ether, ethoxyethanol, nitrobenzene and acetonitrile. A process according to any one of claims 1 to 18, characterized in that deprotection of ketal-protected hydroxyl groups (B ') is carried out by solvolytic decomposition, such as methanolysis, under acidic conditions. A process according to any one of claims 1-19, characterized in that di-, tri- or polyalcohol or an adduct, such as a hydroxy-substituted allyl ether, an alkoxylate or a formal, thereof. The process is an aliphatic, a cycloaliphatic or an aromatic mono-. A process according to claim 20, characterized in that the core is an alkoxylate obtained by reacting glycerol, trimethylolethane, trimethylolpropane or pentaerythritol with at least one alkylene oxide. A process according to claim 21, characterized in that the alkylene oxide is ethylene oxide, propylene oxide, butylene oxide, phenylethylene oxide or a mixture thereof. A process according to claim 20 characterized in that the core is a hydroxy-substituted allyl ether, such as glycerol monoallyl ethers, glycerol diallyl ethers, trimethylolpropane monoallyl ethers, trimethylolpropane diallyl ethers, pentaerythritol etheritrile ether, . A process according to any one of claims 20-23, characterized in that the core is ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, neopentyl glycol, in pentaerythritol, arrhydroennea dipole ethrolitholeproletol, dimetholithroletol trimethylolpropane, ditrimethylolethane, ditrimethylolpropane, trimethylolpropane triethoxylate, marmitol, trimethylolpropane tripropoxylate, pentaerythritol triethoxylate or pentaerythritol pentaethoxylate. A process according to claim 20, characterized in that the core is a formal such as an β-dioxane or an β-dioxolane alcohol. A process according to claim 20, characterized in that 4-hydroxymethyl-1β-dioxolane, the formula is S-methyl-S-hydroxymethyl-1,3-dioxane, S-ethyl-S-hydroxymethyl-1β-dioxane or 5,5- dihydroxymethyl-1,3-dioxane. A process according to claim 25 or 26, characterized in that the formal or complete addition of precursor chain extenders is decomposed to give reactive hydroxyl groups. A process according to any one of claims 1 to 20, characterized in that the core is a phenolic alcohol, such as a xylylene alcohol or a hydroxyphenyl alkane. A process according to claim 28, characterized in that the hydroxyphenylalkane is dihydroxybenzene, trihydroxybenzene or 1,1,1-tris (hydroxyphenyl) ethane. A process according to any one of claims 1 to 20, characterized in that the core is from the group consisting of glycidyl ethers, glycidyl esters, epoxides of unsaturated carboxylic acids or triglycerides, aliphatic epoxy polymers, cycloaliphatic epoxy polymers, aromatic epoxy polymers and epoxy polymers.