GB2447269A

GB2447269A - Catalyst for the ring-opening polymerisation of a cyclic organic compound

Info

Publication number: GB2447269A
Application number: GB0704243A
Authority: GB
Inventors: Barbara Iacono; Matthew David Gwydion Lunn
Original assignee: Johnson Matthey PLC
Current assignee: Johnson Matthey PLC
Priority date: 2007-03-06
Filing date: 2007-03-06
Publication date: 2008-09-10
Also published as: GB0704243D0

Abstract

A compound comprising the reaction of a titanium, zirconium, hafnium or aluminium compound, selected from an alkoxide, a condensed alkoxide, a halide, haloalkoxide, amide or oxyhalide with a carbohydrate, such as a monosaccharide containing a 5- or 6- membered carbon chain or cyclic system or a disaccharide or polysaccharide based on a 5- or 6-membered carbon chain or cyclic system is used as a catalyst for the ring-opening polymerisation of a cyclic organic compound, such as a lactone, lactam, cyclic ether, cyclic carbonate, cyclic carbamate or lactide. Also disclosed is a polymerisable mixture comprising at least one lactone, lactam, cyclic ether, cyclic carbonate, cyclic carbamate, lactide or other cyclic compound which is susceptible to ring opening polymerisation, and a catalyst comprising a complex formed from the reaction of a titanium, zirconium, hafnium or aluminium compound with a carbohydrate.

Description

Polymerisation Reaction and Catalyst Therefor This application concerns

catalyst compositions, for use as catalysts for the ring-opening polymerisation of oxygen-and nitrogen-containing cyclic compounds, polymerisable mixtures containing these catalyst compositions, methods for their preparation and methods of carrying out ring-opening polymerisation reactions using the catalyst compositions of the invention Ring-opening polymerisations are an important route to polylactones and polylactides, which are useful as biocompatible and biodegradable polymers Conventional ring-opening polymerisations are carried out using a catalyst such as tin octanoate. However in these systems it has been difficult to obtain a polymer having a narrow molecular weight distribution (as indicated by a low polydispersity M/M).

Aida eta! (Macromolecules 2000, , 725-729) have described the use of bulky titanium bis(phenolate) complexes as initiators for living anionic polymerisation of c-caprolactone to produce polyesters with a narrow molecular weight distribution The ligands used were methylene-bridged bisphenols containing bulky tert-butyl-or phenyl-substituents EP-A-0943641 describes a process for the preparation of monodisperse polymers from cyclic lactone and / or carbonate monomers by ring-opening polymerisation using a titanium-or aluminium-based Lewis acid catalyst which is a metal alkoxide of a substituted phenol, and an initiator Lin et a! (Organometallics 2001, Q, 5076 -5083) describe the ring-opening polymerisation of c-caprolactone and 6-valerolactone using as initiator a dimeric compound of 2,2'-methylenebis(4-chloro-6-isopropyl-3-methylphenol) and isopropanol with aluminium. Chisholm eta! (J. Am. Chem. Soc. 2000, 122, 11845-11854) have described the formation of polylactides by ring-opening polymerisation using magnesium and zinc alkoxides with trispyrazolyl and trisindazolylborate ligands. Kim and Verkade describe the formation of polylactides by ring-opening polymensation using titanatranes (Organometallics, 2002, 21, 2395-2399).

EP-A-0710685 describes the preparation of biodegradable aliphatic polyesters prepared by polycondensing cyclic acid anhydrides with cyclic ethers in the presence of ring-opening polymerisation catalysts such as alkoxyzirconium compounds or oxyzirconium salts. JP-04- 257545 describes the preparation of co-polyesters of polycaprolactone and hydroxyalkyl (meth)acrylate by ring-opening polymerisation of E-caprolactone in the presence of hydroxyalkyl (meth)acrylate and titanium tetra-butoxide.

DE-A-2947978 describes the use of Mo(OPr)4, V(OBu)3, VO(OBu)3, Mo(VI) acetylacetonate, Mo or V naphthenate, zinc bis(acetylacetonate), bis(acetylacetonato)titanium oxide, and similar compounds as catalysts for the ring-opening polymerisation of E-caprolactone, 6-va lerolactone, dodecanolactone and similar lactones.

It is an object of the present invention to provide an alternative catalyst system for ring-opening polymerisation reactions. It is a further object of the invention to provide novel compositions which are useful as catalysts and a method for their manufacture.

According to the invention, we provide a compound suitable for use as a catalyst for the ring-opening polymerisation of a cyclic organic compound comprising a compound formed from the reaction of a reactive titanium zirconium, hafnium or aluminium compound with a carbohydrate.

The reactive titanium, zirconium, hafnium or aluminium compound is preferably selected from an alkoxide, a condensed alkoxide, a halide, haloalkoxide, amide or oxyhalide; although other compounds may also be used The catalyst compound is especially useful as a catalyst for the ring opening polymerisation of a lactone, lactam, cyclic ether, cyclic carbonate, cyclic carbamate, lactide, or other cyclic compound, which is susceptible to ring-opening polymerisation, especially for synthesis of polyesters, polyamides, polyethers and polyurethanes.

According to a further aspect of the invention we provide a polymerisable mixture comprising at least one lactone, lactam, cyclic ether, cyclic carbonate, cyclic carbamate, lactide, or other cyclic compound which is susceptible to ring-opening polymerisation, and a catalyst comprising a compound formed from the reaction of a reactive titanium, zirconium, hafnium or aluminium compound selected from an alkoxide, a condensed alkoxide, a halide, an amide, a haloamide or a haloalkoxide; with a carbohydrate An alkoxide of titanium zirconium, hafnium or aluminium has the formula M(OR) where M represents the metal, R is an alkyl group, and v = 3 or 4 according to the valency of the metal M Each R is preferably the same but may be different from one or each other R More preferably, R contains 1 to 8 carbon atoms and particularly suitable alkoxides include tetra-methoxytitanium, tetra-ethoxytitanium, tetra-isopropoxytitan urn, tetra-n-propoxytitani urn, tetrabutoxytitan i urn, tetraethylhexyltita nium, tetra-propoxyzi rconiu m, tetra-isopropoxyzi rconium tetra-butoxyzirconium, tetra-n-propoxyhafnium, tetra-n-butoxyhafnium and triisopropoxyaluminium.

Condensed alkoxides of titanium, zirconium or hafnium can be represented by the general formula RO[M(OR)2O] R, wherein M and R have the same meaning as discussed above and n is an integer. Generally, these condensed alkoxides consist of a mixture containing compounds of the above formula with n having a range of values. Preferably n has an average value ri the range 2 to 16 and, more preferably, in the range 2 to 8. A condensed alkoxide is usually prepared by the controlled addition of water to an alkoxide, followed by removal of alcohol which is displaced. Suitable condensed alkoxides include the compounds known as polybutyl titanate, polybutyl zirconate and polyisopropyl titanate.

Halides and mixed halo-alkoxides of titanium, zirconium and hafnium can be represented by the general formula MX (OR). wherein X is a halogen atom, preferably Cl. M and R have the same meaning as discussed above, x is a positive integer having a value of 1,2,3 or 4 and v is the valency of the metal. Preferred metal oxyhalides comprise titanium, zirconium, hafnium or aluminium oxychlorides, especially zirconium oxychioride Preferably, the reactive titanium zirconium, hafnium or aluminium compound is a titanium or zirconium compound, and most preferably it is a zirconium compound Preferably, the titanium zirconium, hafnium or aluminium compound is an alkoxide.

The use of carbohydrates as ligands in organometallic compounds is known. The chemistry is described by U. Piarulli and C. Floriani in Progress in Inorganic Chemistry Vol 45 (ISBN 0-471- 16357-0), 1997. The carbohydrate is a monosaccharide containing a 5-or 6-membered carbon chain or cyclic system (i.e a C5 or C6 carbohydrate unit) or a disaccharide or polysaccharide based on a C5 or C6 carbohydrate unit. The carbohydrate may be derivitised, e.g by the formation of ketone derivatives prior to complexation in order to reduce the number of active hydroxyl groups in the carbohydrate molecule which may react with the metal compound to form a complex. The carbohydrate may alternatively be derivitised by formation of an ester or ether according to known methods in the art, but these are less preferred if they form a derivative such as an acyl group which is reactive towards the metal compound Derivitisation by other means may also be performed, e.g. by hydrogenation to form a hydrogenated derivative e.g. a hexa-alcohol sorbitol and related compounds. The use of derivitisation to protect or direct the reactivity of a carbohydrate is already known in the art of carbohydrate complex chemistry and the present invention is not limited to particular forms of derivatives for use in making the carbohydrate complexes with the titanium, zirconium, hafnium or aluminium compounds A preferred carbohydrate comprises an optionally derivitised glucose or xylose. A preferred glucose derivitive comprises diacetone glucose (1,2:5,6-di-O-isopropylidene-a-D-glucofuranose) A preferred xylose derivitive comprises 1,2-O-isopropylidene-a-D-xylofuranose The compounds of the invention may comprise one or more than one metal atom The complexing compounds, being capable of forming more than one bond with a metal atom, may form bridges between metal atoms to form larger molecules. For example, in a complexing compound containing more than one hydroxy group, each may form a bond to the same or a different metal atom. In this way the architecture of the compound of the invention may be controlled by careful selection of a complexing compound of appropriate functionality.

The catalyst compound preferably comprises a compound having the general formula XM(L)a(OR)(xv)(aw), where OR is an alkoxide, L is a fully or partially deprotonated, optionally derivatised, carbohydrate ligand, M represents a metal selected from titanium, zirconium, hafnium or aluminium x is the number of metal atoms, v is a number equal to the valency of the metal M, a is a number from ito xv, and w is the number of deprotonated groups on each carbohydrate ligand The catalyst compound is preferably a compound having the general formula M(L)2(OR)2, where OR is an alkoxide, L is a deprotonated derivitised carbohydrate residue and M preferably represents titanium or zirconium.

The cyclic compound which is susceptible to ring-opening polymerisation, (monomer) used is a heterocyclic compound, usually having at least one oxygen-or nitrogen-containing ring, which is susceptible to ring-opening polymerisation. Such compounds have the general structure Where X' and 0 are linked by a linking group, normally containing carbon and hydrogen and

II

C

x7 X' = CR, NR, 0, S optionally oxygen atoms and R is H or alkyl. Examples of such compounds include lactones, lactides, lactams and cyclic ethers such as ó-valerolactone, c-caprolactone, and substituted versions thereof; lactide, DL dilactide, diglycolide; cyclic carbonates such as propylene carbonate, 2-methyl-i,3-propane diol carbonate[1,3]dioxan-2-one, [1,3]dioxepan-2-one, 5- methylene-[1,3]dioxan-2-one; cyclic carbamates, including substituted carbamates. Co-polymers produced by ring-opening polymerisation of more than one monomer of the same type or of different types, e.g. a lactone-carbonate polymer may be made by the process of the invention. One preferred monomer is lactide The process is especially useful for making block-copolymers because the ring-opening polymerisation using the catalysts of the invention is a living polymerisation system Other types of copolymer may also be made by this method The carbohydrate complexes are normally viscous liquids or waxy solids at room temperature.

They are normally added to the polymerisable cyclic compound neat, i.e. undiluted, although they may be added in a solvent or diluent if required. The complex catalysts are effective at concentrations below 1% by weight based on the metal The amount of catalyst used in the polymerisation is generally within the range from 0001 to 1% by weight based on the titanium, zirconium, hafnium or aluminium in the catalyst complex.

The carbohydrate complexes of titanium, zirconium, hafnium or aluminium are made by mixing together the metal compound with a solution of the selected carbohydrate. The mixture may be heated, in particular to remove solvent, and by-products if required When the metal compound is a metal alkoxide, reaction with one mole of the carbohydrate liberates one or more moles of alcohol, which may be removed by distillation or evaporation if required If the metal compound is a chloride or oxychloride a base may be added to the reaction and the resulting chloride salt removed by filtration The formed complex may be used as a catalyst without further purification steps. Appropriate measures should be taken to avoid so far as possible degradation, hydrolysis or other deleterious side-reactions. For example, where a metal alkoxide is used, it should be handled in dry conditions under a suitable dry atmosphere to avoid hydrolysis of the metal alkoxide. Normally distillation conditions should be mild, e.g. distillation under reduced pressure is preferred The skilled person is acquainted with the various methods used and the precautions necessary for the particular reactants selected The ring-opening polymerisation reaction is performed using standard methods known in the art. The reactions may proceed in the presence of an initiator, e g an alcohol, however, using the catalysts of the invention a separate initiator is not always required. The reaction may be quenched using acetic acid, water or other suitable compound. The reactions are living polymerisation systems and, if not quenched, may be resumed upon addition of further monomer, which may be different from the first monomer, leading to the generation of a block copolymer The ring-opening polymerisation reactions may be carried out in a solvent such as toluene, benzene, other aromatic solvent, hexane, heptane, aliphatic hydrocarbons, halogenated hydrocarbons, ethers or other suitable solvent for the type of monomer and conditions used.

The reaction conditions are selected to be suitable for the particular reaction to be carried out.

The reaction is generally carried out at a temperature in the range from about 10 C to 2'0 C, but higher or lower temperatures may be used if required.

The invention will be demonstrated in the following examples, in which the following abbreviations are used: DAG diacetone glucose (1,2:5,6-di-O-isopropypidene-a-D-glucofuranose) Xylofu ra nose: 1,2-O-isopropyl iden e-o-D-xylofu ranose Pr* isopropyl Et: ethyl Pr n-propyl Example 1 Synthesis of Ti(O[DAG])2(O'Pr)2 Under a nitrogen atmosphere in a glove-box, tetraisopropoxy titanium (0.4 g 0.0014 mol), was added drop-wise with stirring to a colourless solution of diacetone glucose (DAG) (0 732 g 0.00281 mol) in anhydrous toluene The resulting colourless solution was heated to the boiling point of the solvent, and then left stirring overnight. The volatiles (including the solvent and isopropanol) were then removed by distillation under reduced pressure and the resulting solid was collected and stored in a glove box.

Example 2 Synthesis of Zr(ODAG)2(OEt)2 The procedure of Example 1 was followed, substituting an approximately equimolar quantity of tetraethoxy zirconium for the tetraisopropoxy titanium Example 3 Synthesis of Zr(O'Pr)2(O-xylofura nose)2 Under a nitrogen atmosphere in a glove-box, ig of VERTECIM NPZ (74% tetra-n-propoxy zirconium in n-propanol, 0 00225 mol) and l,2-O-isopropylidene-xylofuranose (0858 g 0.0045 mol) were mixed together in a Schlenk round bottomed flask. The flask was then put in a preheated oil bath maintained above 150 C and the molten mixture obtained was stirred for approximately 15 minutes under vacuum. The flask was then cooled and the solid obtained was stored under nitrogen.

Example 3 Polymerisation of L lactide L lactide was purified by sublimation under nitrogen atmosphere twice at 95-100 C under vacuum and then finally more slowly at 90-95 . The sublimation apparatus and glass storage jars were all prepared by heating overnight in an oven at 120 C.the purified lactide was stored in a sealed jar in a glove-box In a glove-box, a 50 ml Schlenk round bottomed flask was charged with 1 g of purified L lactide (0.00699 mol) and an amount of catalyst corresponding to a ratio of (moles of lactide)/ (moles of metal) =100. The mixture was put under a small nitrogen flux with an overhead stirrer in a preheated oil bath at 160 C. When the monomer was completely molten, the temperature was increased to 185-190 C and maintained for 20 minutes. The mixture was then allowed to cool and the resulting polymer dissolved in dichloromethane and precipitated with methanol. The white suspension of precipitated polymer was separated from the supernatant by centrifuge and the solid polymer obtained was dried overnight in a ventilated oven at 120C The product was analysed by NMR and gel permeation chromatography. Results are shown in the Table Table 1 Average molecular weights of Dolymer form ExamDle 3 by GPC Catalyst complex Mn Mw PDI Example 2 16400 20900 1.28 Example 3 34500 55400 1.61 ExamDle 4 A polymerisation of lactide was carried out in toluene solution at 80 C using the catalyst made in Example 1 0 050 g (3 46*10-4 mol)of lactide and the amount of catalyst corresponding to a lactide/catalyst metal ratio of between 40 and 50 are mixed together with deuterated toluene in a 5 mm NMR tube. As quickly as possible the tube is transferred to the NMR spectrometer.

After having performed a first spectrum at room temperature as reference, the temperature of the probe was increased to 80 C and the NMR spectrum was recorded every 10 minutes The following parts of the NMR spectra were used to estimate the conversion of lactide monomer to polymer 400 MHz (1H NMR toluene d8 at 80 C) methine CH signal of the monomer (q, 4 ppm) and the polymer (q, 5.15 ppm) The results are shown in Table 2

Table 2

LTme(min) 15 35 45 90 120 LConversion % 23.9 49.9 66 0 76.1 90.0

Claims

Claims 1 Use of a compound formed from the reaction of a titanium,

zirconium, hafnium or aluminium compound with a carbohydrate as a catalyst for the ring-opening polymerisation of a cyclic organic compound 2 The use claimed in claim 1, wherein said cyclic organic compound comprises a lactone, lactam, cyclic ether, cyclic carbonate, cyclic carbamate or lactide 3 The use claimed in claim 1 or claim 2, wherein said titanium, zirconium, hafnium or aluminium compound is selected from an alkoxide, a condensed alkoxide, a halide, haloalkoxide, amide or oxyhalide.

4. The use claimed in any one of the preceding claims, wherein the carbohydrate is a monosaccharide containing a 5-or 6-membered carbon chain or cyclic system or a disaccharide or polysaccharide based on a 5- or 6-membered carbon chain or cyclic system 5. The use claimed in any one of the preceding claims, wherein the carbohydrate is derivitised, by the formation of a ketone, an ester or an ether or by hydrogenation to form a hydrogenated derivative.

6 The use claimed in any one of the preceding claims, wherein the catalyst compound comprises a compound having the general formula XM(L)a(OR)(xv)(aw), where OR is an alkoxide, L is a fully or partially deprotonated, optionally derivatised, carbohydrate ligand, M represents a metal selected from titanium, zirconium, hafnium or aluminium, x is the number of metal atoms, v is a number equal to the valency of the metal M, a is a number from 1 to xv and w is the number of deprotonated groups on each carbohydrate ligand.

7 The use claimed in claim 6, wherein the catalyst compound comprises a compound having the general formula M(L)2(OR)2, where OR is an alkoxide, L is a deprotonated, derivitised carbohydrate residue and M represents titanium or zirconium 8. A polymerisable mixture comprising at least one lactone, lactam, cyclic ether, cyclic carbonate, cyclic carbamate, lactide, or other cyclic compound which is susceptible to ring-opening polymerisation, and a catalyst comprising a complex formed from the reaction of a titanium, zirconium, hafnium or aluminium compound with a carbohydrate 9. A polymerisable mixture as claimed in claim 8, wherein the carbohydrate is a monosaccharide containing a 5-or 6-membered carbon chain or cyclic system or a disaccharide or polysaccharide based on a 5-or 6-membered carbon chain or cyclic system A polymerisable mixture as claimed in claim 8 or claim 9, wherein the carbohydrate is derivitised, by the formation of a ketone, an ester or an ether or by hydrogenation to form a hydrogenated derivative 11 A polymerisable mixture as claimed in any one claims 8 -10, wherein the catalyst compound comprises a compound having the general formula xM(L)a(OR)(xv)(aw), where OR is an alkoxide, L is a fully or partially deprotonated, optionally derivatised, carbohydrate ligand, M represents a metal selected from titanium, zirconium, hafnium or aluminium, x is the number of metal atoms, v is a number equal to the valency of the metal M, a is a number from 1 to xv and w is the number of deprotonated groups on each carbohydrate ligand.

12. A polymerisable mixture as claimed in any one of claims 8 -11, wherein the catalyst compound comprises a compound having the general formula M(L)2(OR)2, where OR is an alkoxide, L is a deprotonated, derivitised carbohydrate residue and M represents titanium or zirconium