EP0979300A2 - Synthese enzymatique - Google Patents

Synthese enzymatique

Info

Publication number
EP0979300A2
EP0979300A2 EP98925849A EP98925849A EP0979300A2 EP 0979300 A2 EP0979300 A2 EP 0979300A2 EP 98925849 A EP98925849 A EP 98925849A EP 98925849 A EP98925849 A EP 98925849A EP 0979300 A2 EP0979300 A2 EP 0979300A2
Authority
EP
European Patent Office
Prior art keywords
polyester
process according
enzyme
acid
lipase
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP98925849A
Other languages
German (de)
English (en)
Inventor
Alan Taylor
Falmai Binns
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lanxess Urethanes UK Ltd
Original Assignee
Baxenden Chemicals Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Baxenden Chemicals Ltd filed Critical Baxenden Chemicals Ltd
Publication of EP0979300A2 publication Critical patent/EP0979300A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
    • C08G63/60—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from the reaction of a mixture of hydroxy carboxylic acids, polycarboxylic acids and polyhydroxy compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C08G18/4236—Polycondensates having carboxylic or carbonic ester groups in the main chain containing only aliphatic groups
    • C08G18/4238—Polycondensates having carboxylic or carbonic ester groups in the main chain containing only aliphatic groups derived from dicarboxylic acids and dialcohols
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/78—Preparation processes
    • C08G63/82—Preparation processes characterised by the catalyst used
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters
    • C12P7/625—Polyesters of hydroxy carboxylic acids

Definitions

  • the present invention relates to a process for producing polyesters by enzyme catalysed reaction of monomers and to polyesters obtained by that process .
  • Polyesters are well known industrial products finding applications principally as moulded articles m, for instance, the car industry. They are also of interest as the intermediates m the production of polyurethanes , which are also used to form moulded articles. Polyesters are reacted with isocyanates to form polyurethanes. The characteristics of the resulting polyurethane depend at least m part on those of the polyester.
  • Polyesters are typically produced by chemically catalysed reactions using elevated temperatures, strong acids and long reaction times. Competition between esterification, transesterification and hydrolysis limits the molecular weight of the products. Moreover these processes are accompanied by the formation of quantities of unwanted by-products, such as cyclic esters, and have the added disadvantage that the catalyst is difficult to remove. Polyesters produced by conventional processes generally contain at least 0.5% or more, for instance up to 1.5% or more by weight of cyclic diester impurities such as the cyclic ester 1,6- d ⁇ oxacyclododecane-7 , 12-d ⁇ one . Furthermore, it is necessary to remove the water produced by the reaction m order to force the equilibrium towards products. If the presence of byproducts and residual catalyst is not to degrade the properties of the desired material, complex arrangements are required to prevent their formation or remove them after the main reaction (see e.g. EP-A-0425201) .
  • the present invention seeks to overcome the difficulties of chemically catalysed reactions by use of lipase enzymes.
  • lipases have been known for some time for simple este ⁇ fication and transesterification reactions (see, e.g. EP-A-0383 405) and stereoselective oligomerisations (see, e.g. Margolin A. L. et al . , Tet . Letters, 28 ; 1607-1610, (1987)), only limited use has been made of lipases m polyeste ⁇ fication.
  • GB-A-2 272 904 discloses the use of a lipase to make polyesters m the presence of an organic solvent.
  • GB-A-2 286 401 discloses a solvent free process for obtaining polyesters having desirable properties.
  • the process of polyester formation using a lipase can be considered as proceeding in two stages, the first stage being the oligomerisation stage and the second being the conversion of the resulting oligomers to a polyester. It is also known to use supported lipase in such a process and that the lipase can be removed from the reaction mixture at the end of either stage. In the case where the supported lipase is removed at the end of the oligomerisation stage the subsequent conversion of oligomer to high molecular weight polyester was thought originally to be due to a self assembly process as all of the enzyme catalyst was believed to have been removed at the previous stage.
  • the leaching of the enzyme is related to the hydrophobic/hydrophilic balance of the reaction medium, primarily influenced by the nature of the monomers as discussed further below.
  • the present invention relates to an improved enzymatic polyesterification process which is capable of reducing the cost and increasing the efficiency of production of a polyester by enzymatic methods particularly when carrying out such a process on a commercial scale.
  • the present invention relates to a polyester product which is resistant to degradation by hydrolysis particularly m the presence of water and heat and a process for its production.
  • the present invention m one aspect provides a process for producing a polyester comprising as repeated units d) residues of at least one aliphatic hydroxycarboxylic acid or a carboxylic acid derivative thereof ; or
  • R 1 is a bond or divalent radical of a substituted or unsubstituted straight, branched or cyclic C x to C 12 alkyl group optionally having one or more carbon-carbon double bonds and optionally having one or more carbon-carbon triple bonds.
  • Suitable aliphatic dicarboxylic acids include those of formula (2) :
  • R 2 is a bond or a divalent radical defined as for R 1 .
  • Suitable aliphatic diols include those of formula (3) :
  • R 3 is a bond or a divalent radical defined as for R 1 or a divalent radical comprising a straight or branched C 2 to C 12 alkyl group or a cyclic C 4 to C 12 alkyl group optionally comprising at least one hetero atom, such as nitrogen or oxygen, interrupting the carbon chain.
  • diols include higher molecular weight materials such as polytetramethylene glycol , polypropylene glycol , polyethylene glycol and polycaprolactone .
  • Preferred such diols have hydroxyl values m the range from 10 to 450 mg KOH/g, more preferably 20 to 280 mg KOH/g .
  • Suitable aliphatic polyols include those of formula
  • R 4 is a divalent radical defined as for R 1 and bearing at least one hydroxyl substituent.
  • Each of the C x to C 12 alkyl groups mentioned above may be substituted or unsubstituted and may be cyclic, branched or straight chain, optionally having at least one carbon-carbon double bond, either m the cis- or trans- conformation and optionally having at least one carbon-carbon triple bond.
  • the C j ⁇ to C 12 alkyl group has more than one double or triple carbon-carbon bond, these bonds may be conjugated or non-conjugated.
  • the C x to C 12 alkyl group is optionally substituted with one or more substituents (which, when there are two or more substituents, may be the same or different) each selected from halogen atoms, for example fluorine, chlorine or bromine; hydroxyl; -NHR S where R 5 is hydrogen or a C 1 to C 12 alkyl; carboxyl; and -C0 2 R 6 where R 6 is hydrogen or a C ⁇ or C 12 alkyl .
  • substituents for example fluorine, chlorine or bromine
  • hydroxyl -NHR S where R 5 is hydrogen or a C 1 to C 12 alkyl; carboxyl; and -C0 2 R 6 where R 6 is hydrogen or a C ⁇ or C 12 alkyl .
  • the hydroxycarboxylic acid has from 2 to 14 carbon atoms, for example glycolic acid, lactic acid, 2- hydroxybuty ⁇ c acid, 2-hydroxy ⁇ sobutyr ⁇ c acid, 2-hydroxy- caproic acid, 2-hydroxy ⁇ socapro ⁇ c acid, citric acid or malic acid.
  • the hydroxyacids must have a non-ste ⁇ cally hindered primary or secondary hydroxyl .
  • Preferred hydroxy acids are hydroxy- straight chain aliphatic carboxylic acids.
  • the dicarboxylic acid has from 3 to 14 carbon atoms, for example, succinic acid, fumaric acid, citric acid, malic acid, malonic acid, maleic acid, adipic acid or sebacic acid. Most preferably it is adipic acid.
  • succinic acid for example, succinic acid, fumaric acid, citric acid, malic acid, malonic acid, maleic acid, adipic acid or sebacic acid. Most preferably it is adipic acid.
  • carboxylic acid derivative refers to esters and acid anhydrides.
  • An ester of a diacid may be a monoester or a diester, for example a mono or dialkyl ester.
  • the alkyl groups are each of 1 to 4 carbon atoms, and more preferably the derivative is a methyl or ethyl ester or diester, most preferably methyl adipate or dimethyl adipate .
  • the diol has from 2 to 14 carbon atoms and is an ⁇ , ⁇ -d ⁇ ol, for example 1 , 4-butaned ⁇ ol , diethylene glycol, ethylene glycol, propylene glycol, 1 , 5-pentaned ⁇ ol , 1,6- hexanediol or 1 , 12 -dodecane diol, most preferably 1,4- butanediol or 1 , 6-hexaned ⁇ ol .
  • the diol is preferably diethanolamme or diethylene glycol .
  • the polyol has at least three hydroxyl groups of which at least two must be non-sterically hindered primary or secondary hydroxyl groups. Preferably the polyol has 3 , 4 or 5 hydroxy groups. Tertiary hydroxyl and sterically hindered primary and secondary hydroxyls are unlikely to react under the conditions of the present invention but will nevertheless provide branch points when subsequently reacted with isocyanates. Suitable polyols include pentaerythritol and t ⁇ ols, especially glycerol . Use of glycerol generally results m a linear polymer as the enzyme preferentially esterifies the primary hydroxyls, the secondary hydroxyl being sterically hindered, but branched products may be obtained using certain enzymes.
  • the polyesters produced by the present process may comprise or consist of repeating units derived from the following components: a diacid and a diol; a diacid and a polyol; a diacid, a diol and a polyol; a diacid, a diol and a hydroxy acid; a diacid, a polyol and a hydroxy acid; a diacid, a diol, a polyol and a hydroxy acid, or any other suitable combination of repeating units of such monomers, for example combinations m which the diacid is used m the form of its methyl or ethyl ester or diester derivative.
  • Preferred combinations of monomers are adipic acid/1 , 4-butaned ⁇ ol , d ⁇ methylad ⁇ pate/1 , 4-butaned ⁇ ol , adipic acid/glycerol , adipic acid/1 , 4-butaned ⁇ ol , adipic acid/diethylene glycol, adipic acid/diethylene glycol/t ⁇ methylolpropane, diethylene glycol/adipic acid/dimethylolpropionic acid, adipic acid/1 , 6-hexaned ⁇ ol .
  • a further option is to incorporate into the polymer blocks of preformed polyester.
  • the enzyme catalysed reaction will incorporate such blocks without any significant degradation thereof. It is thus a further aspect of the invention that the polymers optionally comprise two or more blocks of polyester wherein the composition of monomer residues in at least one of said blocks is different from the composition of monomer residues m at least one other of said blocks .
  • Preformed polymer blocks may be included m the polymerisation reaction medium at any stage of the polymerization reaction.
  • the preformed polymer blocks may themselves be produced by enzymatic polyesterification reactions or may be produced by conventional polymerization processes.
  • Preferred preformed polyester blocks have acid numbers less than 40 mg KOH/g, more preferably less than 30 mg KOH/g .
  • the reactive carboxylic acid groups and reactive hydroxy groups of the reactants are generally present m substantially equal numbers.
  • the reaction may be carried out with a stoichiometric imbalance, but this generally results m a product having a lower weight average molecular weight than if the reactants are used m equimolar amounts.
  • the proportions may be adjusted slightly such that a polyester having terminal acid units or terminal hydroxy units is obtained. Polyesters having terminal acid units are useful in a variety of coating compositions whereas those with terminal hydroxy units may be - lo used as the soft segments in production of polyurethanes.
  • the molar ratio of acid groups to hydroxyl groups is from 1:1 to 1:1.1 such that a hydroxyl - terminated product is obtained.
  • the length of the polymer may be varied by varying the excess of hydroxyl groups present m the initial reaction mixture. For example, increasing the amount of hydroxyl groups relative to the number of acid groups m the reaction mixture will give rise to polymers of shorter chain length.
  • a tertiary amme is included m the reaction mixture.
  • Tertiary amines suitable for use m the process of the present invention are any tertiary amines which are suitably volatile so as to be removed by the vacuum treatment at the polymerisation stage.
  • the amme is a trialkyl amme and most preferably a t ⁇ -Ci 4 -alkyl amme such as t ⁇ ethylamme .
  • an amme is used m the process of the present invention it is included an amount suitable to prevent coating of the enzyme bead with an impermeable layer of polymer, preferably in an amount of 0.05 to 5% by weight of the monomers, preferably 0.1 to 1% by weight of the monomers and most preferably 0.8% by weight of the monomers.
  • the enzyme used in the process of the present invention may be bound on an inert carrier, for instance a polymer such as an anion exchange resin, an acrylic resin or a polypropylene, polyester or polyurethane resin or may be used m free form. When the enzyme is bound on an inert carrier it can easily be removed from the reaction mixture (e.g. by filtration) without the need for complicated purification steps.
  • the bound enzyme is recovered from the reaction mixture and reused. At least some enzyme must be present in the reaction vessel until the reaction reaches completion. Where bound enzyme is used the bound enzyme may be removed from the reaction vessel after the initial oligomerisation step of the reaction has reached completion. Where the bound enzyme is removed at the end of the oligomerisation step the acid number of the resulting mixture of oligomers is preferably less than 200 mg KOH/g and more preferably between 170 and 20 mg KOH/g but may be lower, for instance, down to about 15 mg KOH/g. In the case where hydroxyl groups are present m excess, the oligomerisation step is complete when all the carboxylic acid bearing monomers have reacted to form an acid/base adduct . The bound enzyme may be removed after completion of the first step of the reaction for example by filtration.
  • the bound enzyme is reused, it is preferably reused m a further polymerisation of components to make a polyester, preferably the bound enzyme is reused m a further implementation of a process of this invention.
  • virgin enzyme When the re-used bound enzyme is supplemented with virgin enzyme it is preferred to include virgin enzyme in an amount of 1 to 25%, preferably 2 to 15%, more preferably 4 to 12% and most preferably 5 to 10% by weight of the recovered bound enzyme.
  • the further step of converting the resulting oligomers into a polyester must be carried out m the presence of enzyme and with removal of water, or other condensation products (e.g. methanol or ethanol when methyl or ethyl esters of carboxylic acids are used as monomers) which then drives the reaction to form high molecular weight products.
  • condensation products e.g. methanol or ethanol when methyl or ethyl esters of carboxylic acids are used as monomers
  • the enzyme present may be an enzyme that has become detached from the support and that has leached into the polymerising mixture. This applies at least with one preferred enzyme, the Candida antarctica lipase mentioned below.
  • the enzyme may not be leached from the support.
  • the conversion of oligomer to polymer may be effected or accelerated by the addition at an appropriate stage of the reaction of further enzyme in free form (i.e. not bound to a support) .
  • This non-bound enzyme can be added before, during or after removal of the bound enzyme, preferably non-bound enzyme is added after removal of the bound enzyme.
  • the conversion of oligomer to polyester may be accelerated by raising the reaction temperature to at least 80°C, for example at least 85°C, 90°C, 95°C or 100°C.
  • Suitable enzymes are commercially available lipases. Not all lipases function as polyesterification catalysts m the presence of substantial quantities of water (an example is the lipase from Mucor meihei ) so it may be necessary either to remove water during the reaction to retain the activity of the enzyme or to select enzymes which function when water is present .
  • a preferred enzyme for use in the present process is the lipase derived from Candida antarcti ca , a non-specific triacylglycerol lipase [E.C. no.
  • ovozyme 435 is a registered Trade Mark " ovozyme 525 is a registered Trade Mark Boehrmger Mannheim GmbH, Chirazyme *** L-2, c-f, Lyo, where the enzyme is immobilised by covalent binding to its support and ChirazymeTM L-2, Lyo, BM, where the enzyme is not immobilised.
  • Other suitable lipases can be identified by simple trial-and- error experimentation within the ability of those skilled m the art .
  • the activity of the enzyme may be affected by materials present m the reaction mixture, for example the lipase from C. antarctica is inhibited by glycerol. At least with this enzyme it is preferable not to include polyfunctional monomers, particularly those with secondary alcohol groups, in the initial reaction mixture, but to delay their addition until after the reaction is started. Preferably polyfunctional monomers (which would be used to generate branch or graft points) are not added to the reaction mixture until after the initial oligomerisation step.
  • the amount of enzyme used is not critical and is generally limited by economic considerations. Too little enzyme will result m a slow reaction whereas too much enzyme simply increases the cost unnecessarily.
  • the lipase from Candida antarctica Novo Industri AS Catalogue Novozyme 435TM or Novozyme 525TM
  • these amounts refer to the amount of recovered enzyme.
  • Lipase from Candida an tarcti ca has been found to be such an enzyme.
  • Processes using lipase from Candida antarc ti ca are preferably carried out in the presence of a small amount of water preferably an amount of 0.5 to 5%, more preferably 1 to 3% and most preferably 1.9% by weight of the monomers.
  • the oligomerisation stage of the process is carried out at from 10 to 90°C preferably 20 to 70°C and more preferably 40 to 60 °C and at atmospheric or reduced pressure. Where the process is carried out at reduced pressure the preferred pressure is from 60-100 mbar.
  • the polymerisation stage of the process is carried out at from 10 to 120°C preferably 40 to 110°C most preferably 60 to 100°C, at atmospheric or, preferably, reduced pressure.
  • the water is conveniently removed by reducing the pressure under which the reaction is carried out and maintaining the pressure at, for example 5 to 10 kPa (50 to 100 mbar) at the start reducing to as low as 0.5 kPa (5 mbar) at the end.
  • the water may be removed with a wiped film evaporator under reduced pressure, for instance, 0.6666 kPa (5 mm Hg) or even 133.322 Pa (1 mm Hg) or less.
  • a desiccant such as a molecular sieve is used, taking precautions to avoid physical damage to support enzymes due to abrasion between the desiccant and the enzyme support .
  • a bleed or sparge can be utilized to agitate the reaction mixture and help to evaporate water from the mixture.
  • the gas used the bleed or sparge can be air or nitrogen which is preferably pred ⁇ ed, and is most preferably nitrogen.
  • the total reaction time is generally from 6 to 48 hours, preferably from 12 to 24 hours.
  • the reaction mixture preferably has an acid number of less than 1 mg KOH/g.
  • the process of the present invention can be operated efficiently and cost effectively on a commercial scale an industrial plant. This means producing batches of finished product of 100 kg or greater in a single implementation or
  • the process can be subjected to control by a suitable computerized laboratory or plant management system.
  • the process may be, without prejudice, carried out a batch, continuous or single run fashion.
  • the process is run m a "fed batch" manner.
  • the invention provides a process for producing a catalyst free or substantially catalyst free polyester which process comprises (I) treating polyester made by an enzymatic polymerisation process a manner so as to denature the enzyme or (n) using monomers and/or reaction conditions which do not permit the catalyst to leach through into the final product.
  • said polyester can be any polyester which is made by polymerisation catalysed by a lipase, and is preferably a polyester made using the preferred lipase of this invention and most preferably is a polyester made by a process of this invention.
  • the treatment used can involve exposure to any conditions which cause the denaturing of the enzyme.
  • the denaturing treatments used are preferably heat treatments, more preferably heat treatment to above 150 °C. Such heat treatments can be carried out by for example heating in a conventional flash heater or thin film heater.
  • denaturing means rendering an active enzyme catalyst inactive by destruction of the native conformation and hence active state or configuration of the molecule .
  • the invention also provides a polyester comprising as repeated units
  • polyesters of this invention are catalyst free this means that there is no or very little active enzyme catalyst contained m the polyester.
  • Such polyesters can preferably withstand an extended period of exposure to water and heat without decomposition by hydrolysis.
  • Preferred polyesters are able to retain their original acid number for an extended period of time when exposed to 0.2% water by weight of the polyester and heat treatment to 60 °C.
  • the most preferred polyesters have an acid number of less than 1 mg KOH/g after being made up to 0.2% water by weight of the polyester and being incubated for 15 days at 60°C.
  • Generally processes of the present invention enable the production of high weight average molecular weight polyesters, for instance up to or higher than 8 kDa, especially up to or higher than 10 kDa.
  • the polyesters produced by the process of the present invention generally have a minimum weight average molecular weight of 200 Da, preferably 600 Da, more preferably 1000 Da and most preferably 4 kDa.
  • the weight average molecular weight of the polyester is measured using gel permeation chromatography .
  • the polyesters produced by the process of the present invention generally comprise from 6 to 50 monomer units, preferably from 10 to 40 monomer units and most preferably from 30 to 40 monomer units. Generally it has an acid number of from 0 to 50, preferably from 0 to 25 and more preferably from 0.5 to 10. Most preferably the polyester has an acid number of about 1.
  • the polyesters produced by the process of the invention generally have a dispersity of 2.5 or less. Dispersities of 2.1 or 2.0 may be achieved and in one aspect of the invention the polyesters have a dispersity of 1.5 or less, preferably 1.3 or less, in particular when the process is carried out m solvent free conditions such as those described GB-A-2 286 401.
  • Number Average Molecular Weight the number and weight average molecular weights may be obtained by methods well known to those skilled in the art such as gel permeation chromatography.
  • Polyesters which contain cyclic diester impurities may, if required, have their cyclic diester content reduced by methods such as wiped film evaporation or high vacuum distillation. After application of such methods, contents of from as low as 0.3 to 0.7% by weight of the cyclic diester impurities can be achieved.
  • the presence of cyclic diester impurities can be detected using gas chromatography, mass spectrometry or High Performance Liquid Chromatography (HPLC)
  • the polyesters having hydroxy terminal groups are further reacted with at least one lsocyanate to produce polyurethanes. Generally the bound enzyme is removed from the polyester before the reaction with isocyanate.
  • the enzyme remaining in the polyester is denatured before the reaction with isocyanate.
  • water produced during the polyesterification is also removed before reaction with isocyanate .
  • the polyesters of the invention have sharp melting points (unlike conventionally produced polyesters) and impart to the polyurethanes excellent physical properties such as desirable combinations of hardness and flexural and tensile strength.
  • polyesters produced m accordance with the present invention are novel materials and form further aspects of the invention.
  • Polyesters and polyurethanes and polymer compositions comprising polyesters and polyurethanes of the present invention find uses as shaped articles and foams, particularly for motor vehicles .
  • Any polymer of the invention can be incorporated into a polymer composition.
  • the butanediol, water, triethylamme and adipic acid were charged sequentially to a 500ml flange flask and the flask heated m an oil bath at 40°C.
  • the flange flask was fitted with a condenser m reflux mode, a vacuum purge tap and an overhead stirrer unit.
  • the reagents were stirred using an overhead stirrer at a speed of 160 rpm for a period of 2 hours at 40°C.
  • the stirrer speed was adjusted down to 120 rpm and the Novozyme 435TM added. Stirring was continued for a further 4 hour period at atmospheric pressure.
  • the bath temperature was raised to 60 °C.
  • the condenser was changed over to distillation mode and a receiver flask and a vacuum adaptor fitted. Vacuum of 10 kPa (100 mbar) level was applied to the rig by means of a diaphragm vacuum pump linked to the vessel via a digital controller, for an overnight period of 16 hours. By morning a clear mobile solution had formed with only the immobilized enzyme insoluble; the latter was filtered off using a nylon filter cloth of mesh size 74 ⁇ m. The crude enzyme was reserved and used without further purification m a subsequent fed-ba tch operation - see Example 2. The filtered oligomer was tested for acid number characteristic, shown to be 158mg KOH/g.
  • Novozyme 435TM crude recovered grade, bulk recovered from previous fed-ba tch run (no. 8 of the series) .
  • Novozyme 435TM bx. ref. no. LC 0015-8, activity certified as 8200 propyl laurate units/g, Novo, 0.2g (10% by weight of original benchmark run - see Example no. 1 above) .
  • the crude enzyme was reserved as before and used without further purification m a subsequent fed -ba tch operation.
  • the filtered oligomer was tested for acid number characteristic, shown to be 150mg KOH/g; consistent with ⁇ 10 % deactivation of the enzyme catalyst from run to run.
  • Novozyme 435TM bx. ref. no. LC 20001, activity certified as 7600 propyl laurate units/g, Novo, 3. Og (0.77% by weight of monomers) .
  • Hexanediol and water were dosed to the 1 litre pot of a BuchiTM laboratory reactor, fitted with MidilabTM computer control of both the temperature of the heating jacket and the vacuum applied to the vessel; continuous monitoring display was available by means of a PC linked to the Midilab units.
  • the jacket temperature was raised to 60°C, and the mix melted out with slow stirring.
  • the stirring speed was raised to 200 rpm and adipic acid charged slowly; the mix was then stirred for 2 hours.
  • a fine needle valve was m place on one of the vessel ports venting to atmosphere through an air- flow monitor, to allow the application of an air-bleed to the vessel _ ⁇ n vacuo .
  • the vessel was fitted with a condenser m vertical distillation mode connected to a take-off adaptor, with vent to the vacuum line, leading to a receiver flask.
  • the vacuum line led from the adaptor through a Dreschel bottle and then to the necessary automated on-off control valve; subsequently to a second on-line needle valve selected m capacity to permit the balancing of vacuum and air-bleed such that a continuous controlled bl eed could be administered, further facilitating the removal of water vapour.
  • the stirrer speed was adjusted down to 120 rpm and the Novozyme 435TM added.
  • the set computer programme was initiated, instructing a further 4 hour period at atmospheric pressure, followed by the slow application of a vacuum by means of a diaphragm vacuum pump to a level of 15.5 kPa (155 mbar) ; a tiny air bleed being set by opening the large needle valve directly attached to the vessel .
  • Controlled conditions were achieved by opening the aperture of the on-line needle valve such that the system attained balance and PC monitoring showed a steady state.
  • the process was run for an overnight period of 16 hours. By morning a clear mobile solution had formed with only the immobilized enzyme insoluble; the process was validated by monitoring of the PC programme.
  • the enzyme was filtered off using a nylon filter cloth of mesh s ze 74 ⁇ m. The filtered oligomer was tested for acid number characteristic revealed as 48 mg KOH/g.
  • the process was run on pilot plant scale using a 500 litre vessel, equipped with an oil jacket and heating coils; vacuum application was by means of a water-ring pump. A nitrogen sparge could be applied through a dip-tube. Hexanediol and water were charged to the reaction vessel and heated with stirring at 60°C until molten; adipic acid was added and the mix left to stir for an overnight period.
  • Enzyme was dosed early the next morning and after a 2 hour period, vacuum was applied with an air bleed m operation, such that the vacuum was around 60 mbar. After overnight processing the pot contents had reached acid number 25 mg KOH/g. The vessel was emptied and the pot contents filtered through a nylon cloth (74 ⁇ m mesh size) . The immobilized enzyme was recovered and retained its activity such that a further batch operation was possible on this scale without further purification.
  • the filtered oligomer was transferred back to the vessel; the temperature of the pot was set at 100°C, the vacuum level at 4 kPa (40 mbar) and a nitrogen sparge applied at a level of lOL/m . After overnight processing, the product reached acid number of 2.9 mg KOH/g. To attain material of the desired specification a further overnight process was operated; characteristics of the finished products are set out m Table 1 below, compared to the conventionally derived analogue, DynacollTM 7360.
  • Hexylene adipate - regimen for small scale conversion of oligomer to polymer is
  • oligomer was transferred to a small cylindrical cell reactor of 100ml capacity and placed m an oil bath set at 100°C on a magnetic stirrer unit; a rugby ball stirrer bar was added to the reactor and the oligomer melted out.
  • Vacuum of 1 kPa (10 mbar) was applied using a rotary o l pump through a digital controller to the vessel via a take - off adaptor fitted with a vent valve. The mix was stirred overnight for a period of 17 hours. By morning the viscosity had increased and acid number monitoring gave characteristic of 1.5 mg KOH/g showing conversion to a polymer.
  • the polyester under test was melted out at 100°C and transferred to an electrically heated bath, capable of rapid heating to >200°C; a contact thermometer was placed the molten liquid, stirring was commenced and a foil jacket fitted. The head-space was placed under a nitrogen blanket. The pot contents were rapidly heated to 200°C and the temperature held for 3 minutes before the heat setting was reduced to 60°C. The water content of the mix was measured to be 0.01% by weight, and the water content was further adjusted to 0.2%. Similarly the water content of a commercial sample of DynacollTM 7360 was checked and found to be 0.09% by weight.
  • the product is now completely catalyst free - the acid number being ⁇ 1 mg KOH/g.
  • the GPC results show that the molecular weight showed no significant deviation following heat treatment .
  • the process was run on pilot plant scale using a 500 litre vessel, equipped with an oil jacket and heating coils; vacuum application was by means of a water - ring pump. A nitrogen sparge could be applied through a dip-tube. Hexanediol and water were charged to the reaction vessel and heated with stirring at 60°C until molten; adipic acid was added and the mix left to stir for an overnight period. Enzyme was dosed early the next morning and after a 2 hour period, vacuum was applied with an air bleed operation, such that the vacuum was around 6 kPa (60 mbar) . After overnight processing the pot contents had reached acid number 25 mg KOH/g. The vessel was emptied and the pot contents filtered through a nylon cloth (74 ⁇ m mesh size) . The immobilized enzyme was recovered and retained its activity such that a further batch operation was possible on this scale without further purification.
  • the filtered oligomer was transferred back to the vessel; the temperature of the pot was set at 100°C, the vacuum level at 4 kPa (40 mbar) and a nitrogen sparge applied at a level of lOL/min. After overnight processing, the product reached acid number of 2.9 mg KOH/g To attain material of the desired specification a further overnight process was operated.
  • the temperature of the pot was then immediately raised to 180°C whilst maintaining the vacuum level. After 4 hours the mixture was cooled and discharged from the pot . Analysis of the finished product as detailed for Example 5 showed that the enzyme had been denatured.
  • the hexanediol, water (7.3g) and adipic acid were charged sequentially to a 500ml flange flask and the flask heated m an oil bath at 40°C.
  • the flange flask was fitted with a condenser reflux mode, a vacuum purge tap and an overhead stirrer unit.
  • the reagents were stirred at a speed of 160 rpm for a period of 2 hours at 40°C.
  • the stirrer speed was then adjusted down to 120 rpm and the recovered Novozyme 435TM was added.
  • a solution of Novozyme 525TM (non-immobilised Candida an tarcti ca) in water (0.5g) was prepared advance and, having stood overnight, was added to the mixture immediately after the Novozyme 435TM. Stirring was continued for a further 4 hour period at atmospheric pressure. The bath temperature was then raised to 60 °C and the condenser changed over to distillation mode, a receiver flask and vacuum adaptor being fitted. A vacuum of 10 kPa (100 mbar) was then applied to the apparatus by means of a diaphragm vacuum pump, linked to the vessel via a digital controller, for an overnight period of 16 hours. A clear mobile solution was formed which contained the insoluble immobilised enzyme.
  • the mixture was filtered through a nylon filter cloth of mesh size 74 ⁇ m.
  • the residual crude immobilized enzyme was reserved for use m a subsequent batch- fed operation.
  • the filtered oligomer was tested for acid number characteristic which was shown to be 60 mg KOH/g.
  • Hexylene adipate - non- immobilised Candida antarctica as a supplement in the conversion of oligomer to polymer.
  • Novozyme 435 A Novo, bx . ref. no. LC 20004, recovered from pilot plant batch detailed as Example 3, previous activity certified as 10820 LU/g, 2.2g (0.57% by weight of monomers) .
  • Hexylene adipate oligomer (ref FB 417/1) was formed using the process of Example 7 except that virgin Novozyme 435TM was used as a supplement instead of Novozyme 525TM solution. After the insoluble immobilized enzyme had been removed a 30g aliquot was transformed to a small cylindrical cell reactor of 100ml capacity. A solution of Novozyme 525TM m water (0.5g) was prepared m advance and, having stood overnight, was added to the reactor. The reactor was then placed in an oil bath set at 100 °C on a magnetic stirrer unit; a rugby ball stirrer bar was added to the reactor and the oligomer and lipase melted out.
  • Example 8 was repeated except that the amount of Novozyme 525TM pre-dissolved in 0.5g of water was 44 mg .
  • the resulting hexylene adipate polymer had an acid characteristic of 4.4 mg KOH/g.
  • Example 8 was repeated except that 0.5g of water containing no enzyme was added to the oligomer in place of the solution of Novozyme 525TM.
  • the resulting hexylene adipate polymer had an acid number characteristic of 9.8 mg KOH/g.

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  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Polymers & Plastics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Wood Science & Technology (AREA)
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  • Genetics & Genomics (AREA)
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  • Preparation Of Compounds By Using Micro-Organisms (AREA)
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Abstract

Il est possible de compenser la puissance réactive d'un réseau de distribution en installant une série de prises sur l'alimentation en tension et des commutateurs rapides associés aux prises.
EP98925849A 1997-06-05 1998-06-05 Synthese enzymatique Withdrawn EP0979300A2 (fr)

Applications Claiming Priority (3)

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GB9711680 1997-06-05
GBGB9711680.0A GB9711680D0 (en) 1997-06-05 1997-06-05 Enzymatic synthesis
PCT/GB1998/001658 WO1998055642A2 (fr) 1997-06-05 1998-06-05 Compensation de la puissance reactive

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DE19856948A1 (de) * 1998-12-10 2000-06-21 Cognis Deutschland Gmbh Enzymatische Veresterung
DE10163163A1 (de) 2001-12-20 2003-07-03 Basf Ag Verfahren zur Herstellung hochfunktioneller, Hyperverzweigter Polyester durch enzymatische Veresterung
DE102005014032A1 (de) * 2005-03-23 2006-09-28 Basf Ag Zwei-stufiges Verfahren zur Herstellung von Polyesterolen
EP2620462A1 (fr) 2012-01-24 2013-07-31 AMBIENTE E NUTRIZIONE S.r.l. Procédé pour la production de polyesters par synthèse catalysée par enzyme
IT201600078950A1 (it) * 2016-07-27 2018-01-27 Versalis Spa Metodo di sintesi regioselettiva di poliesteri da dioli asimmetrici.

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GB9225030D0 (en) * 1992-11-30 1993-01-20 Baxenden Chem Solvent based enzymatic synthesis
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