Derivatives of poly-3-hydroxyalkanoate and preparation method thereof

Abstract

The invention relates to a method for producing poly-3-hydroxyalkanoates of the general formula VI having ester units as functional groups at one chain end and another functional group at the other chain end, comprising the following steps: step 1: ring-opening polymerization, wherein at least one beta-lactone of general formula I is reacted with at least one unsaturated carboxylic acid of general formula II in the presence of at least one heterogeneous catalyst to obtain poly-3-hydroxyalkanoate of general formula III; step 2: chlorination in which the poly-3-hydroxyalkanoate of general formula III is reacted with at least one chlorinating agent Cl to form a poly-3-hydroxyalkanoate carbonyl chloride of general formula IV; and step 3: derivatization in which the poly-3-hydroxyalkanoate carbonyl chloride of general formula IV is reacted with at least one compound of general formula V comprising at least one functional group X-Y to obtain a poly-3-hydroxyalkanoate of general formula VI by elimination of Y-Cl. # imgabs0 #

Description

[0001] The present invention relates to derivatives of poly-3-hydroxyalkanoates and a process for their production.

[0002] Poly-3-hydroxyalkanoates, also referred to hereinafter as PHA, are linear aliphatic polyesters which, because of their properties at high molar masses (insoluble in water, UV-resistant, non-toxic, biocompatible, thermoplastic and biodegradable), are of particular interest as sustainable alternatives to conventional polymers (see V. Sharma et al., Polymer 212 (2021) 123161). Representatives of high molar mass (50 kDa - 1000 kDa) can be present as storage substances in many microorganisms and can also be isolated from these microorganisms on an industrial scale. In particular, the most frequently occurring poly-3-hydroxybutyrate, also referred to hereinafter as PHB, because of its material properties, can be used as a biodegradable and biocompatible alternative to conventional petroleum-based plastics such as polypropylene, in particular as a food packaging material, in agricultural and biomedical applications.

[0003] However, the disadvantages of biotechnological production processes include unfavourable space-time yields, since bacterial growth is naturally limited, thus restricting yields, and sometimes the starting compounds are complex. The production costs, which are 15 times those of comparable petroleum-based products, also make marketing more difficult.

[0004] This applies not only to representatives of high molar mass PHA, but especially to low molecular weight polymers or oligomers with a molar mass of around 1000 g / mol which cannot be obtained by fermentation. Their properties (non-toxic, biodegradable, biocompatible) make them particularly suitable for the chemical modification of pharmaceutical active ingredients (see G. Adamus et al., Polymers 13 (2021) 4365) or pesticides with controlled delayed release of the active ingredient (see I. Kwiecień et al., PLoS ONE, DOI: 10.1371 / Journal.pone.0120149). In addition, an intrinsic antimicrobial activity of carboxyl-functional oligomers has recently been discovered (see L. Ma et al., Macromol. Biosci. 19 (2019) 1800432).

[0005] These can be produced by decomposing bioderived high molecular weight PHB with alcohols, diols or carboxylic acids, although this is inconvenient and costly. The high molecular weight PHB must first be produced, separated and purified by biotechnological means, followed by a second step of chemically decomposing it into smaller fragments, which also involves expensive and inconvenient post-treatment steps (see M.A. Abdelwahab et al., International Journal of Biological Macromolecules 122 (2019) 793). Additionally, this route does not allow for the specific production in one step of products having a free OH or NH functional group only at one end group or A-B-A block copolymers.

[0006] Therefore, a great deal of work has been carried out to chemically produce these short-chain one-sided functionalized PHAs by ring-opening polymerization of strained β-lactones.

[0007] In particular, the anionic ring-opening polymerization of β-butyrolactone to obtain PHB has often been described in the literature because commercially available nucleophiles can be used as initiators.

[0008] It is evident in most ring-opening polymerizations using β-butyrolactone that not only the nucleophile used as an initiator can be detected at the start of the chains of the resulting polymer, but also up to 100% of crotonate groups, the formation of which is attributed to base-induced rearrangements on the polymer or monomer (see I. Kwiecień et al., DOI: 10.1080 / 15685551.2013.840505), as well as free crotonic acid (see A. Duda, Journal of Polymer Science: Polymer Chemistry 30 (1992) 21), thus making the purification of the polymer significantly more difficult.

[0009] Therefore, anionic ring-opening polymerization requires reactants to have high purity, and thus the industrial quality of the monomers requires expensive and inconvenient pretreatment, the exclusion of moisture and long reaction times. The potassium salts preferably used as initiators also need to be activated by expensive and health-hazardous complexing agents such as 18-crown-6 or cryptands (see Z. Grobelny et al., Polymer Bulletin 76 (2019) 4951), which are also difficult to separate after the reaction.

[0010] Additionally, the space-time yield is reduced due to the need to use solvents such as THF or DMSO.

[0011] All these factors are disadvantageous for the specific and economic production of oligo- or low-molecular weight PHA derivatives which have an ester unit as a functional group at one chain end and another functional group at the other chain end. These are of interest as biodegradable additives in a variety of applications such as cosmetics, hair, textiles and leather treatment, as plasticizers for polymers and as a basis for A-B-A block copolymers. They can also be used as intermediates for crosslinkable polymers.

[0012] The selectivity can be increased if the salts of crotonic acid are used as initiators from the start. The prior art has described the use of potassium crotonate anhydrous, although this is expensive and inconvenient for production and requires the complexing agent 18-crown-6 for activation and THF as a solvent (see M. Michalak et al., Polymer Degradation and Stability 97 (2012) 1861). This forms a PHB polymer which has a crotonate unit at one end and a potassium carboxylate functional group at the other end. Although the potassium carboxylate end group can be derivatized by nucleophilic substitution, the choice of nucleophilic reaction participants is severely restricted.

[0013] A conventional method is to derivatize at the free carboxylic acid functional group of the polymer, for example via alcohol esterification or amine amidation after release from the potassium salt by an acid. However, the typical reaction conditions of these reactions also carry the risk of decomposition of the polyester chain (see also Comparative Example 1 in this regard).

[0014] Derivatization of the less reactive crotonate end group can preferably be achieved by epoxidation. However, this is time-consuming and requires an excess of the expensive epoxidizing reagent m-chloroperbenzoic acid and thus expensive and inconvenient purification (see M. Michalak et al., Polymer Degradation and Stability 97 (2012) 1861). Although the reactive epoxy functional group is suitable for further reactions, these epoxidized PHA derivatives are not suitable for industrial processes because they are expensive and complex, thus uneconomical to synthesize, and there are limited downstream reactions as intermediates for the production of specific derivatives.

[0015] Therefore, the selective production of one-sided monofunctional substituted PHA representatives with a carboxylic acid ester group is a valuable goal for which there has so far been no economic route.

[0016] Accordingly, it is an object of the present invention to provide a method for producing low-molecular weight poly-3-hydroxyalkanoate derivatives which are characterized in that they have an ester unit as a functional group at one chain end and another functional group at the other chain end, and which method does not exhibit the above-mentioned disadvantages.

[0017] This object is achieved by the present invention.

[0018] Accordingly, the present invention provides a method for producing a poly-3-hydroxyalkanoate of the general formula VI which has an ester unit as a functional group at one chain end and another functional group at the other chain end, the method comprising the following steps:

[0019] Step 1: Ring-opening polymerization, in which at least one β-lactone of the general formula I is reacted with at least one unsaturated carboxylic acid of the general formula II in the presence of at least one heterogeneous catalyst to obtain a poly-3-hydroxyalkanoate of the general formula III

[0020]

[0021] Step 2: Chlorination, in which the poly-3-hydroxyalkanoate of the general formula III is reacted with at least one chlorinating agent Cl to form a poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV

[0022]

[0023] and

[0024] Step 3: Derivatization, in which the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV is reacted with at least one compound of the general formula V containing at least one functional group X-Y to obtain a poly-3-hydroxyalkanoate of the general formula VI by eliminating Y-Cl,

[0025]

[0026] wherein

[0027] R 1 、R 2 、R 3 independently of one another represent a hydrogen atom, a halogen atom, a straight-chain, (bi)cyclic or branched, substituted or unsubstituted C1-C 18 hydrocarbon group, optionally interrupted by a heteroatom selected from O, S or N, where the groups R 1 、R 2 、R 3 can also be connected in pairs and exist as components of a cyclic structure,

[0028] R 5represents a linear, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbyl group having 1 to 100 carbon atoms;

[0029] X represents -O- or -NR 11 -,

[0030] wherein

[0031] R 11 independently represents, each time it appears, a hydrogen atom, or a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a group of the general formula -C(=O)-R 12 ;

[0032] wherein

[0033] R 12 represents a hydrogen atom, or a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a primary, secondary or tertiary amine group -NR 8 R 9 ,

[0034] wherein

[0035] R 8 and R 9 independently of one another represent a hydrogen atom, or a hydrocarbyl group having 1 to 6 carbon atoms, and the two groups R 8 and R 9 can be joined pairwise to be present as components of a cyclic structure;

[0036] Y represents a hydrogen atom, a metal group or a metal-containing group, wherein the metal is selected from alkali metals, alkaline earth metals, silicon, titanium, zinc, tin, iron, manganese or copper;

[0037] n is from 4 to 1400;

[0038] o is from 1 to 16;

[0039] and

[0040] p ≤ o.

[0041] In the description of the present invention, in order not to generate too many pages, only the preferred embodiments of each feature are described below.

[0042] However, expert readers should clearly understand that this type of disclosure means that every combination of different preference levels is also clearly disclosed and clearly expected.

[0043] In a preferred embodiment, R 1 and R 2It can be interchanged at the double bond to the E- or Z-isomer or a mixture thereof.

[0044] In a preferred embodiment, R 5 represents a linear, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbyl group having 3 to 100 carbon atoms.

[0045] The functional group X-Y preferably represents -OH, -NHR 11 , an alkoxide of Li, Na, K, Mg or Ca or an oxygen-bonded silyl group, particularly preferably an alkoxide of -OH, Na or K or an oxygen-bonded trialkylsilyl group, wherein the alkyl group contains 1 to 5 carbon atoms, very particularly preferably -OH or an oxygen-bonded trimethylsilyl group.

[0046] n is preferably from 4 to 100, very particularly preferably from 4 to 20.

[0047] It has surprisingly been found that industrially pure β-lactones can be converted to poly-3-hydroxyalkanoates of the general formula III . Industrially pure β-lactones are to be understood as meaning that the main impurities present are carboxylic acids isomeric with the β-lactone. The purity of the β-lactone is generally ≥98% by weight, preferably ≥95% by weight. The β-lactones of the general formula I used are very particularly preferably industrially pure β-lactones with a purity of at least ≥90% by weight.

[0048] From the structure of the resulting polymer it can be deduced that it is at least one unsaturated carboxylic acid of the general formula II which corresponds to the isomer of the β-lactone of the general formula I and is preferably used as an initiator for the ring-opening polymerization in step 1. The acid is formed during the polymerization by rearrangement of the β-lactone of the general formula I or was already present as a typical minor component at the start in the industrially pure β-lactones of the general formula I . It is only activated by the heterogeneous catalyst. It was not foreseeable that neither a solvent nor an activation complexing agent was required for this.

[0049] The process according to the invention further comprises, in step 2, subsequently converting the carboxyl end groups of the poly-3-hydroxyalkanoates of the general formula III into reactive carbonyl chloride functional groups. Here too, it is surprising that the reaction takes place without significant side reactions or significant polymer decomposition.

[0050] Another step of the process according to the invention is step 3, converting the general formula IVThe reactive carbonyl chloride end groups in the poly-3-hydroxyalkanoate carbonyl chloride (preferably having an OH group or an NH group) are converted into downstream products (preferably esters or amides). Preferably no solvent is used, especially in the reaction with OH compounds, and the resulting hydrogen chloride is removed directly from the equilibrium by applying a vacuum. Thus, the hydrogen chloride can be sent for recycling, making the process resources efficient.

[0051] Therefore, the process according to the invention preferably comprises three steps, where in batch operation, at least two consecutive steps are carried out in the same reaction vessel without intermediate purification, or in a semi-continuous or fully continuous process, all steps are carried out in reactors arranged in series, thus representing a further, especially economic advantage.

[0052] The process is further characterized in that steps 1 to 3 are preferably carried out solvent-free. Any impurities resulting from solvent residues in the reactants or intermediates can be included.

[0053] The invention also provides poly-3-hydroxyalkanoate carbonyl chlorides of the following general formula:

[0054]

[0055] where

[0056] R 1 、R 2 、R 3 independently of one another represent a hydrogen atom, a halogen atom, a straight-chain, (bi)cyclic or branched, substituted or unsubstituted C1-C 18 hydrocarbon radical, optionally interrupted by a heteroatom selected from O, S or N, where the groups R 1 、R 2 、R 3 can also be connected in pairs and be present as components of a cyclic structure

[0057] and

[0058] n is from 4 to 1400.

[0059] The invention also provides poly-3-hydroxyalkanoates of the following general formula:

[0060]

[0061] where

[0062] R 1 、R 2 、R 3 independently of one another represent a hydrogen atom, a halogen atom, a straight-chain, (bi)cyclic or branched, substituted or unsubstituted C1-C 18 hydrocarbon radical, optionally interrupted by a heteroatom selected from O, S or N, where the groups R1 , R 2 , R 3 can also be connected in pairs and exist as components of a cyclic structure.

[0063] R 5 represents a linear, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbon group having 1 to 100 carbon atoms;

[0064] X represents -O- or -NR 11 -,

[0065] wherein

[0066] R 11 independently represents a hydrogen atom, or a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a group of the general formula -C(=O)-R 12 .

[0067] wherein

[0068] R 12 represents a hydrogen atom, or a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a primary, secondary or tertiary amine group -NR 8 R 9 ,

[0069] wherein

[0070] R 8 and R 9 independently represent a hydrogen group, or a hydrocarbon group having 1 to 6 carbon atoms, and the two groups R 8 and R 9 can be connected in pairs and exist as components of a cyclic structure.

[0071] Y represents a hydrogen atom, a metal group or a metal-containing group, wherein the metal is selected from alkali metals, alkaline earth metals, silicon, titanium, zinc, tin, iron, manganese or copper.

[0072] n is from 4 to 1400,

[0073] o is from 1 to 16

[0074] and

[0075] p ≤ o.

[0076] In the poly-3-hydroxyalkanoate of the general formula VI of the present invention

[0077] R 5Preferably represents a linear, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbon group having 3 to 100 carbon atoms

[0078] and

[0079] The functional group X-Y preferably represents -OH, -NHR 11 , an alkoxide or oxygen-bonded silyl of Li, Na, K, Mg or Ca, particularly preferably an alkoxide of -OH, Na or K or an oxygen-bonded trialkylsilyl, wherein the alkyl contains 1 to 5 carbon atoms, very particularly preferably -OH or an oxygen-bonded trimethylsilyl.

[0080] In the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV or the poly-3-hydroxyalkanoate of the general formula VI , n is preferably from 4 to 100, particularly preferably from 4 to 20.

[0081] The poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV and the poly-3-hydroxyalkanoate of the general formula VI and their production methods according to the invention are described in more detail below:

[0082] Step 1: Ring-opening polymerization

[0083] The following β-lactones of the general formula or mixtures of different β-lactones commercially available or obtainable by known methods (see, for example, WO2010118128 or WO2022143914),

[0084]

[0085] wherein

[0086] R 1 , R 2 , R 3 are each independently a hydrogen atom, a halogen atom, preferably F, Cl and Br, particularly preferably F and Cl, a linear, (bi)cyclic or branched, substituted or unsubstituted C1-C 18 hydrocarbon group, preferably selected from alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl or aryl, optionally interrupted by a heteroatom selected from O, S or N

[0087] and wherein

[0088] R 1 , R 2 , R 3 can also be connected in pairs as components of a cyclic structure.

[0089] In a preferred embodiment, R 1 , R 2, R 3 Each independently is a hydrogen atom, a halogen atom, preferably F, Cl and Br, particularly preferably F and Cl, linear, (bi)cyclic or branched, substituted or unsubstituted C1-C 18 hydrocarbyl group, selected from alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl or aryl, optionally interrupted by -NR 4 -, where two heteroatoms are never directly adjacent, optionally substituted by a halogen atom, a carboxyalkyl group, an alkoxy group or an amino group,

[0090] wherein

[0091] R 4 represents a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms.

[0092] C1-C 18 hydrocarbyl group R 1 , R 2 , R 3 and R 4 Non-exhaustive examples of R

[0093] Preferred groups R 1 , R 2 , R 3 and R 4 represent linear or branched, substituted or unsubstituted alkyl groups having 1 to 8 carbon atoms,

[0094] Particularly preferably methyl, ethyl, 1-propyl, 2-propyl, phenyl, vinyl, n-hexyl, 1-phenylethyl, 2-phenylethenyl, very particularly preferably propyl and methyl, especially methyl,

[0095] wherein very particularly preferably R1 represents methyl, 1-propyl or 2-propyl, and the group R 2 , R 3 represents a hydrogen atom.

[0096] The general formula I β-lactones, in particular β-butyrolactones.

[0097] Based on the weight of the reactants, the β-lactones of the general formula I are preferably reacted in the presence of a solid base catalyst in an amount of 0.1 to 20% by weight, particularly preferably 0.1 to 10% by weight, very particularly preferably 0.5 to 5% by weight, especially 1 to 3% by weight. The catalyst is preferably selected from alkali metal oxides, hydroxides, carbonates and hydrogencarbonates or alkali metal fluorides, optionally supported on a support material such as basic, acidic or neutral alumina, titanium dioxide, zirconium oxide, precipitated or fumed silica as described, for example, in US 5223595 A (= corresponding DE 4116014 A1) or alkaline earth metal oxides or hydroxides. Due to their commercial availability and reactivity, the catalyst used is preferably a potassium salt, particularly preferably potassium carbonate and potassium fluoride * alumina in a molar ratio of 1:1, very particularly preferably anhydrous potassium carbonate.

[0098] Based on the amount of the β-lactone of the general formula I , the β-lactone of the general formula I is preferably added with 0 - 10 mol%, particularly preferably 0 - 5 mol%, especially 0 - 1 mol% of an initiator for ring-opening polymerization, which is selected from carboxylic acids having 1 to 22 carbon atoms, preferably the general formula corresponding to the β-lactone of the general formula used I isomeric unsaturated carboxylic acids of the general formula II , such as E-crotonic acid or E-2-hexenoic acid, formic acid, acetic acid, benzoic acid, cinnamic acid, acrylic acid, methacrylic acid, sorbic acid, octanoic acid, nonanoic acid, undecenoic acid, lauric acid, oleic acid, linoleic acid, linolenic acid, palmitic acid, stearic acid, erucic acid, wherein the molar ratio of the β-lactone of general formula I and the optionally added initiator is preferably selected such that the desired degree of polymerization or the desired molar amount of the general formula III poly-3-hydroxyalkanoate is achieved in the ring-opening polymerization, and the reaction is carried out until the desired conversion is achieved. The target conversion is preferably optimized via reaction conditions such as reaction duration, temperature, catalyst type, catalyst concentration or initiator concentration such that the maximum yield of the poly-3-hydroxyalkanoate of the general formula III is accompanied by the least amount of unwanted by-products, especially the general formula formed from the β-lactone of general formula I IIHeterogeneous unsaturated carboxylic acids, such as crotonic acid formed from β-butyrolactone. This can be easily determined in preliminary experiments by using analytical methods, preferably IR, Raman, NMR, MALDI-TOF or ESI-MS spectroscopy, or LC or SEC chromatography.

[0099] The reaction is preferably carried out in the temperature range between 0 °C and 200 °C, particularly preferably between 20 °C and 150 °C, especially within the boiling range of the reaction mixture and at the pressure of the ambient atmosphere, optionally also at higher or lower pressures. For safety reasons and to exclude moisture, the reaction is preferably carried out under a dry inert gas such as nitrogen or argon.

[0100] The polymerization can be terminated by removing the unreacted β-lactone of the general formula I by distillation or cooling of the reaction mixture, or by separating the solid catalyst by filtration, centrifugation or decantation (e.g., in a bypass of the reaction vessel), or by its chemical deactivation (e.g., neutralization).

[0101] A continuous reaction mode is suitable because the reaction mixture can be recycled through a fixed bed of catalyst in a loop reactor until the desired conversion is achieved.

[0102] The average molar mass M of the poly-3-hydroxyalkanoate of the general formula III from step 1 of the process according to the invention is preferably in the range from 300 g / mol to 100,000 g / mol, particularly preferably between 300 g / mol and 30,000 g / mol, especially between 300 g / mol and 5000 g / mol. The molar mass when the polymer is liquid at room temperature is very particularly preferred. Depending on the molar mass of the monomers used, the value of the index n in the poly-3-hydroxyalkanoate of the general formula w is determined to be from 4 to 1400. For the poly-3-hydroxyalkanoate of the general formula III the index n is preferably from 4 to 100, particularly preferably in the range from 4 to 20. For the poly-3-hydroxyalkanoate carbonyl chloride of the general formula III and the poly-3-hydroxyalkanoate of the general formula IV the index n is preferably in the same range or slightly lower, since the subsequent steps can cause a slight decomposition of the polymer chains. VI

[0103] The average molar mass M w can be determined, for example, by NMR spectroscopy, SEC, GPC, LC, MALDI-TOF or ESI-MS.

[0104] Step 2: Chlorination

[0105] III The general formula obtained in step 1 IIIPoly-3-hydroxyalkanoates with typical chlorinating agents for carboxylic acids Cl The mixture is mixed and reacted until the carboxylic acid group at one end of the poly-3-hydroxyalkanoate of the general formula III is completely converted to the corresponding phosgene group.

[0106] Chlorinating agent used Cl Thionyl chloride, phosgene or phosphorus(V) chloride are preferred, with thionyl chloride being particularly preferred. Its advantages include relatively low toxicity and mild chlorination to form only highly volatile cleavage products SO2 and HCl, both of which can be sent for recycling.

[0107] For the general formula IV For the workup of the poly-3-hydroxyalkanoate phosgene, devolatilization or distillation of the volatile components is sufficient. In addition, no prior separation of the heterogeneous catalyst is required. In the case of alkali metal oxides, carbonates or hydroxides, the catalyst is neutralized by the chlorinating agent and thus deactivated. This may require the addition of a chlorinating agent to the catalyst. Cl With general formula III Any neutralization products of the catalyst formed, which are usually solid, do not need to be separated before the next derivatization step, since they are inert. They are preferably separated only after the derivatization step 3 by filtration, sedimentation or centrifugation. It is advantageous when the catalyst or their deactivated downstream products are in the form of salts and can therefore be easily separated as solids, thus making it possible to achieve high purity of the general formula according to the invention VI Water-soluble by-products can also be separated from the polymer by water washing.

[0108] Typical minor components are such as those used in the general formula I The general formula of β-lactone isomers II Unsaturated carboxylic acids or other incompletely reacted carboxylic acids used as initiators are also converted into phosgene during the chlorination. Due to their lower boiling and melting points, these can be removed more gently by distillation than the corresponding free carboxylic acids.

[0109] Based on the general formula used from step 1 of the method according to the invention III Poly-3-hydroxyalkanoate, preferably a chlorinating agent Cl The amount used is in the range of equimolar to 5-fold molar excess. Based on the carboxylic acid content in the reaction mixture, it is particularly preferred to use 1.1 to 3-fold molar excess, especially 1.1 to 2-fold molar excess. The reaction mixture is preferably composed of the general formula III The poly-3-hydroxyalkanoate and optionally unreacted carboxylic acid or the general formula II The β-lactone formed is composed of carboxylic acids.

[0110] Chlorinating agentsCl It can be preferably added completely at the beginning or added continuously until complete conversion. For this purpose, a solid or gaseous chlorinating agent dissolved in a solvent can be used. Thionyl chloride is preferably added completely at the beginning.

[0111] The chlorinating agent, preferably thionyl chloride, can be used in industrial quality. Industrial quality includes a purity of generally ≥ 98% by weight, preferably ≥ 95% by weight, and very particularly preferably ≥ 90% by weight. The unreacted proportion of the chlorinating agent Cl can be simply removed by distillation and reused. In this regard, an excess of thionyl chloride can be used simultaneously to reduce the viscosity of the reaction mixture in step 2.

[0112] The reaction temperature is preferably between -10 °C and 100 °C typical for these reactions, particularly preferably between 20 °C and 70 °C, especially in the range between 20 °C and 50 °C. A temperature ramp can also be used, where preferably the temperature is increased stepwise or continuously during the reaction to accelerate the reaction with as few side reactions as possible at the end. The reaction is preferably carried out at ambient atmospheric pressure or under reduced pressure in order to quickly remove volatile by-products from the reaction mixture and minimize or even avoid side reactions. In the case where Y represents a hydrogen atom, the addition reaction of HCl to the double bond of the unsaturated ester functional group is a typical side reaction to produce a 3-chloro-carboxylate end group. If this reaction is desired, the unsaturated ester end group can be completely converted to the 3-chloro-carboxylate end group by correspondingly extending the reaction time without removing hydrogen chloride from the reaction mixture or additionally introducing hydrogen chloride gas.

[0113] However, this reaction is particularly preferably carried out under reduced pressure, preferably at 10 - 900 hPa, especially at 50 - 200 hPa. An inert gas stream such as nitrogen, carbon dioxide or argon can also be optionally used in combination with reduced pressure as an auxiliary means.

[0114] The method is characterized in that step 2 is preferably carried out solvent-free. Any impurities resulting from solvent residues in the reactants or intermediates can be included.

[0115] For example, a solvent can be added to improve mixing. Preferred solvents have good solvent properties, are inert towards the components of the reaction mixture, are easy to remove subsequently, for example for recycling, are commercially available, and ideally have no health and safety concerns.

[0116] Non-exhaustive examples thereof include anisole, xylene, alkanes such as n-heptane, n-octane, n-decane, isoparaffins such as those from Exxon E, ethers such as di-n-butyl ether, 2-methyltetrahydrofuran, methyl tert-butyl ether or mixtures thereof. Anisole is particularly preferred.

[0117] Other possible solvents are toluene, tetrahydrofuran, chlorobenzene, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane or chloroform.

[0118] The end point of the reaction can be determined using spectroscopy, for example by 1 H or 13 C-NMR spectroscopy, by sampling from the reaction mixture or by monitoring the evolution of gas or by quantitatively determining the cleavage products released.

[0119] The average molar mass M of the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV from step 2 of the process according to the invention is preferably within the range of the average molar mass of the poly-3-hydroxyalkanoate of the general formula w preferably within the range of the average molar mass of the poly-3-hydroxyalkanoate of the general formula III of the poly-3-hydroxyalkanoate.

[0120] The average molar mass M w can be determined, for example, by NMR spectroscopy, SEC, GPC, LC, MALDI-TOF or ESI-MS.

[0121] Step 3: Derivatization

[0122] The poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV obtained in step 2 of the process according to the invention is preferably subsequently immediately reacted with at least one compound of the general formula V having at least one functional group X-Y

[0123] R 5 -(X-Y) o

[0124] V

[0125] to eliminate Y-Cl, where Cl represents chlorine.

[0126] R 5 represents a straight-chain, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbon radical having 1 to 100 carbon atoms, preferably a straight-chain, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbon radical having 3 to 100 carbon atoms.

[0127] X represents -O- or -NR 11 -,

[0128] where

[0129] R 11independently represents a hydrogen atom, or a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a group of the general formula -C(=O)-R 12 at each occurrence,

[0130] wherein

[0131] R 12 represents a hydrogen atom, or a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a primary, secondary or tertiary amine group -NR 8 R 9 ,

[0132] wherein

[0133] R 8 and R 9 each independently represent a hydrogen atom, or a hydrocarbon group having 1 to 6 carbon atoms, and the two groups R 8 and R 9 can be joined in pairs and exist as components of a cyclic structure (alkylene or arylene).

[0134] Y represents a hydrogen atom, a metal group or a metal-containing group, wherein the metal is selected from alkali metals, preferably lithium, sodium, potassium or cesium, particularly preferably sodium and potassium, alkaline earth metals, preferably magnesium or calcium, silicon, titanium, zinc, tin, iron, manganese or copper.

[0135] In the case of a metal group, the metal ion is mainly ionically bonded or coordinated to an organic group, such as, for example, in a metal alkoxide.

[0136] In the case of a metal-containing group, the organic group or organic compound is directly bonded to the metal atom. These compounds are called organometallic compounds. Organometallic compounds also include derivatives of elements that do not form metals in the elemental state but have a low electronegativity, such as silicon. Thus, an organometallic compound contains at least one carbon atom and at least one metal or electropositive element atom, which are bonded to each other. The bond is a more or less polar covalent bond. The organic group can be bonded to the element via a single bond, a double bond or even a triple bond, or be attached to the element atom multiple times.

[0137] The functional group X-Y preferably represents -OH, -NHR 11 , an alkoxide of Li, Na, K, Mg or Ca, or an oxygen-bonded silyl group, particularly preferably an alkoxide of -OH, Na or K, or an oxygen-bonded trialkylsilyl group, wherein the alkyl group contains 1 to 5 carbon atoms, very particularly preferably -OH or an oxygen-bonded trimethylsilyl group.

[0138] Preferably, the general formula VTwo or more different units X-Y may also be present in the compound, or a mixture of at least two compounds of the general formula V may be used.

[0139] o is from 1 to 16, preferably from 1 to 8, very particularly preferably from 1 to 3, especially 1 or 2.

[0140] In order to react completely all the groups X-Y present in the compound of the general formula V , preferably o mol of the poly-3-hydroxyalkanoate carbonyl chloride of the general formula V is used per mol of the compound of the general formula IV , and thus p = o corresponds.

[0141] If the poly-3-hydroxyalkanoate of the general formula VI is intended to still contain free X-Y groups, the selected molar amount p of the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV is preferably correspondingly smaller. Thus, preferably p < o. If in this case Y does not represent a hydrogen atom and the poly-3-hydroxyalkanoate of the general formula VI is intended to contain free X-H groups, these can be released from the free X-Y groups by an acid, which is preferably selected from inorganic acids such as hydrogen chloride, sulfuric acid, nitric acid, orthophosphoric acid, metaphosphoric acid or their acid salts or esters, or organic acids such as formic acid, acetic acid, benzenesulfonic acid or methanesulfonic acid.

[0142] R in the general formula V 5 may preferably contain a functional group selected from the following: a tertiary amine functional group or their ammonium salts, N-containing heterocycles, O-containing heterocycles, S-containing heterocycles, O,N-containing heterocycles, quaternary ammonium groups, nitro functional groups, nitrile functional groups, ketone functional groups, monomeric, oligomeric or polymeric ether units, monomeric, oligomeric or polymeric carboxylic acid ester units, phosphonate or phosphate ester units, groups containing carbon-carbon double bonds or carbon-carbon triple bonds, particularly preferably tertiary amine functional groups and oligomeric and polymeric polyether units, especially tertiary amine groups and polyethylene glycol groups.

[0143] In the compound of the general formula V , R 5 represents a hydrocarbon group having 1 - 100 carbon atoms, preferably straight-chain, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted, having 3 - 100 carbon atoms.

[0144] In a preferred embodiment, R 5 is selected from alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl or aryl, optionally interrupted one or more times by a heteroatom selected from O, S, N or -NR 13 -.

[0145] wherein ​

[0146] The two heteroatoms are never directly adjacent,

[0147] and

[0148] R 13 represents a straight-chain, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms.

[0149] For the general formula where o = 1 V the group R in the compound of 5 non-exhaustive examples include

[0150] alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl such as n-hexyl, heptyl such as n-heptyl, octyl such as n-octyl and isooctyl such as 2,2,4-trimethylpentyl, nonyl such as n-nonyl, decyl such as n-decyl, n-tetradecyl, n-hexadecyl, n-octadecyl, cycloalkyl groups such as cyclopentyl, cyclohexyl, 4-ethylcyclohexyl, cycloheptyl, norbornyl and methylcyclohexyl, or alkenyl groups such as 2-propen-2-yl, allyl, 3-buten-1-yl, 5-hexen-1-yl, 10-undecen-1-yl, Z-9-octadecenyl, cycloalkenyl groups such as 2-cyclohexenyl, 3-cyclohexenyl, cyclopentadienyl, 2-(cyclohex-3-en-1-yl)ethyl, aryl groups such as phenyl, biphenyl, naphthyl, alkaryl groups such as o-tolyl, m-tolyl, p-tolyl, phenethyl such as 2-phenethyl, 1-phenethyl, E-2-styren-1-yl, aralkyl groups such as benzyl, substituents such as haloalkyl groups such as chloroethyl, chloropropyl and 3,3,3-trifluoropropyl, alkoxyalkyl groups such as 1-n-butoxymethyl, 2-methoxyethyl, tetrahydro-2-furanylmethyl, 2-furanylmethyl, epoxyalkyl groups such as epoxy methyl, 1,2-epoxyethyl, 1,2-epoxy-3-propyl or 1,2-epoxy-4-butyl, polyethylene glycol alkyl groups such as 2-ω-methyl-polyethylene glycol ethyl, aminoalkyl groups such as N,N-dimethylaminoethyl and N,N-dimethylaminopropyl, quaternary ammonium groups such as 2-trimethylammonium chloride-1-ethyl.

[0151] For the general formula where o = 2 V the group R in the compound of 5 non-exhaustive examples include alkylene groups such as 1,2-ethylene, 1,2-propylene, 1,3-propylene, 1,4-butylene, arylene groups such as 1,2-phenylene, ethylene glycol group, propylene glycol group, butylene glycol group, polyethylene glycol group, polypropylene glycol group or polybutylene glycol group, or aminoalkylene groups such as N-methylamino-bis-ethylene.

[0152] For the general formula where o = 1 V non-exhaustive examples of the compounds of

[0153] Methanol, ethanol, n-propanol, 2-propanol, 1-n-butanol, sodium n-butoxide, isobutanol, 2-butanol, tert-butanol, potassium tert-butoxide, sodium tert-butoxide, 1-n-pentanol, 3-methylbutan-1-ol, 3-pentanol, 1-n-octanol, 2-ethylhexan-1-ol, 1-n-dodecanol, 1-n-hexadecanol, 2,2-dimethylpropan-1-ol,

[0154] 1-n-butoxymethanol, 3-methoxypropan-1-ol, 3-methoxybutan-1-ol, tetrahydro-2H-pyran-2-methanol, 2-chloroethanol, 3-chloropropan-1-ol, 3,3,3-trifluoropropanol, 2-bromoethanol, 2-iodoethanol, 3-iodopropan-1-ol, 3-bromopropan-1-ol, 4-chlorobutanol, glycidyl ether, glycerol carbonate, 2-glycidyloxyethanol,

[0155] Ethanolamine hydrochloride, N,N-dimethylaminoethanol,

[0156] Propargyl alcohol, 2-butyn-1-ol, 3-butyn-1-ol, 3-butyn-2-ol,

[0157] Allyl alcohol, 2-allyloxyethanol, 2-methylprop-2-en-1-ol, E-crotyl alcohol, Z-crotyl alcohol, 3-buten-1-ol, 3-buten-2-ol, 10-undecen-1-ol, oleyl alcohol,

[0158] Poly(ethylene glycol) monomethyl ethers of different molar masses such as mPEG6-OH, mPEG7-OH, mPEG12-OH,

[0159] Poly(ethylene glycol) monoallyl ethers of different molar masses,

[0160] Poly(propylene glycol) monomethyl ethers of different molar masses,

[0161] (monobutyl PEG / PPG copolymer),

[0162] Hydroxypropionitrile, DL-lactonitrile, hydroxyacetone,

[0163] 2-Hydroxyethyl acrylate, 3-hydroxypropyl acrylate, 4-hydroxybutyl acrylate, 2-hydroxyethyl methacrylate, 3-hydroxypropyl methacrylate, 4-hydroxybutyl methacrylate,

[0164] Triethyl citrate,

[0165] Diglycerides of fatty acids,

[0166] Dodecylamine, oleylamine,

[0167] Acetamide, N-methylacetamide, lauramide, oleamide, lauryl erucamide,

[0168] Maleimide, succinimide, N-hydroxysuccinimide, N-2-hydroxyethyl succinimide,

[0169] 2-phenylethanol, cinnamyl alcohol, methyl salicylate,

[0170] Phenol, 3-methoxyphenol, 2-methoxyphenol, 3-chlorophenol,

[0171] Aniline, N-methylaniline, morpholine, pyrrolidine, imidazoline, piperidine, cysteine or choline.

[0172] General formula with o = 2 V Non-exhaustive examples of the compounds of

[0173] 1,2-ethanediol, 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, 1,2-butanediol, 1,5-pentanediol, 2-methyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, 1,9-nonanediol,

[0174] 2-butyne-1,4-diol, Z-2-butene-1,4-diol, 3-methyl-2-buten-1-ol,

[0175] Ethanolamine, O-(2-aminoethyl) polyethylene glycol, 3-amino-1-propanol, 4-amino-1-butanol, 2-(methylamino)ethanol, amino-2-propanol, DL-alaninol, tetrahydro-2,5-furandimethanol,

[0176] Diethylene glycol, triethylene glycol, polyethylene glycol bis(aminopropylamine), lysine,

[0177] Monoacylglycerols such as glycerol monostearate,

[0178] Bisphenol A, 4,4'-(1-methylethylidene)bisphenol,

[0179] Dihydroxyacetone,

[0180] Ethylenediamine, 1,4-diaminobutane, 1,6-diaminohexane,

[0181] N,N'-dimethylethylenediamine, imidazolidine, piperazine, polyoxyalkyleneamine T403, triethanolamine,

[0182] NN'-dimethylurea, 1,3-bis(hydroxymethyl)urea

[0183] 2,2'-thiodiethanol.

[0184] General formula with o > 3V Non-exhaustive examples of the compounds include

[0185] glycerol, pentaerythritol, dipentaerythritol, sorbitol, mannitol, isomalt, maltitol, lactitol, xylitol, erythritol, 1,1,1-trimethylolpropane, 1,1,1-trimethylethane,

[0186] sugars: glucose, sucrose, galactose, lactose, maltose, diethanolamine, polyethyleneimine or 1,3-diamino-2-propanol.

[0187] In order to react the compound of the general formula V with the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV it is preferred to first add the latter and then add the compound of the general formula V The advantage is that no decantation operation is required.

[0188] In order to completely convert all X-Y functional groups in the compound of the general formula V it is preferred to select an equimolar ratio of the Cl functional group in the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV to the X-Y functional group in the compound of the general formula V If monofunctional (o = 1) and easily separable compounds of the general formula V are involved, these compounds can preferably be used in a molar excess relative to the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV preferably 1.1 to 10-fold molar excess, particularly preferably 1.1 to 2-fold molar excess to accelerate the reaction. If desired, at the end of the reaction, the unreacted portion can be separated, for example, by distillation or by phase separation.

[0189] If only incomplete conversion of the X-Y groups in the compound of the general formula V with o > 1 is desired, it is preferred to use an excess of the compound of the general formula V The optimal molar ratio of the compound of the general formula V to the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV can be easily determined in preliminary tests. It depends on the X-Y content in the compound of the general formula V and the desired degree of conversion of the X-Y groups present. Kinetic control can also be achieved by the following addition: first add the compound of the general formula V preferably in excess, and then add the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV

[0190] ​This reaction is preferably carried out at a temperature in the range between 0 °C and 150 °C, preferably between 20 °C and 100 °C, particularly preferably between 50 °C and 90 °C, under the pressure of the ambient atmosphere, where higher or lower pressures can also be established. If Y-Cl is a volatile compound, the removal of Y-Cl from the reaction mixture can be advantageously accelerated to reduce the pressure, preferably reduced to the range of 10 hPa to 900 hPa, particularly preferably between 100 hPa and 600 hPa, especially between 100 hPa and 300 hPa. An inert gas can optionally be combined with the pressure reduction as an auxiliary means through the reaction mixture.

[0191] The conditions are preferably selected such that the components of the reaction mixture are not removed by distillation during the reaction.

[0192] When Y represents a hydrogen atom, the removal of the released hydrogen chloride, especially when using amines, preferably auxiliary bases such as ammonia, tertiary amines such as triethylamine or tri-n-butylamine, if there is basic nitrogen in the compound of the general formula V a corresponding excess of the compound of the general formula V or a basic salt such as an alkali metal oxide, hydroxide, carbonate, amide, hydride or an alkaline earth metal oxide, hydroxide, carbonate, amide, hydride is used. The amount of the auxiliary base depends on the amount of HCl released. Calculated in terms of the base equivalent per mol of HCl, preferably 1 - 5 mol, particularly preferably 1.05 - 2 mol, especially 1.05 - 1.2 mol of the base is used. The separation of the neutralization product is preferably carried out during the post-treatment of the poly-3-hydroxyalkanoate of the general formula VI by filtration, sedimentation, centrifugation or washing together with the catalyst or the deactivated catalyst.

[0193] This method is characterized in that step 3 is preferably carried out solvent-free. Any impurities caused by solvent residues in the reactants or intermediates can be included.

[0194] For example, a solvent can be added to improve mixing. Preferred solvents have good solvent properties, are inert to the components of the reaction mixture, are easily removed subsequently, for example for recycling, are commercially available, and ideally have no health and safety concerns.

[0195] Non-exhaustive examples thereof include anisole, xylene, alkanes such as n-heptane, n-octane, n-decane, isoalkanes such as E from Exxon, ethers such as di-n-butyl ether, 2-methyltetrahydrofuran, methyl tert-butyl ether, methyl acetate, ethyl acetate, butyl acetate or mixtures thereof. Anisole is particularly preferred. Other possible solvents are toluene, tetrahydrofuran, chlorobenzene, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane or chloroform.

[0196] The released HCl gas can optionally be sent for recycling after appropriate post-treatment, for example, in a scrubber. Any amine hydrochloride salts formed can also be sent for recycling.

[0197] The average molar mass M of the poly-3-hydroxyalkanoate from step 3 of the process according to the invention IV is preferably in the range of the general formula w Preferably in the general formula III of the poly-3-hydroxyalkanoate or the general formula IV of the average molar mass M of the poly-3-hydroxyalkanoate carbonyl chloride. w within the range.

[0198] The average molar mass M w can be determined, for example, by NMR spectroscopy, SEC, GPC, LC, MALDI-TOF or ESI-MS.

[0199] The present invention also provides the use of the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV for the chemical modification of pharmaceutically active ingredients.

[0200] The present invention also provides the use of the poly-3-hydroxyalkanoate of the general formula VI in cosmetic compositions such as, for example, body or hair care products, pesticides, adhesives, textile or leather treatment / care or as a plasticizer.

[0201] The process according to the invention has the following advantages: The reaction steps can be carried out continuously very simply and effectively, thus making it possible to dispense with expensive and inconvenient post-treatment steps and to produce the desired poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV in a targeted manner and with good atom economy and to obtain the desired poly-3-hydroxyalkanoate of the general formula VI

[0202] In addition to the economic advantages, the functional group tolerance of the process according to the invention allows the synthesis of a variety of poly-3-hydroxyalkanoate carbonyl chloride structures of the general formula IV and poly-3-hydroxyalkanoate structures of the general formula VI which can be used, for example, for the modification of drugs or as biodegradable silicone alternatives in typical silicone applications. What is particularly advantageous about the reaction mode according to the invention is that the synthesis of the poly-3-hydroxyalkanoate of the general formula III can directly use the industrial quality of the β-lactone of the general formula I

[0203] ​​Another advantage is the short reaction time, from a few minutes to a few hours, and both high selectivity and high conversion are achieved. Unreacted reaction products can be easily distilled off and reused. The heterogeneous catalyst is usually commercially available, can be used without pretreatment, and can be easily separated. A solvent is not necessary.

[0204] Therefore, the process according to the invention makes a considerable contribution to economic and environmental sustainability.

[0205] The subject matter of the invention will be illustrated by the following examples, which are not limited to the content disclosed therein.

[0206] Unless otherwise stated, the following examples are carried out at the pressure of ambient atmospheric pressure (i.e., about 1000 hPa) and at room temperature (i.e., about 20 °C), or at the temperature that results when the reactants are combined at room temperature without additional heating or cooling.

[0207] Example 1: Production of PHB - propylene glycol derivatives

[0208] Step 1: Ring - opening polymerization

[0209] In a 1 L three - necked flask equipped with a distillation apparatus, 600 g of β - butyrolactone (source: Sigma - Aldrich, containing 1% crotonic acid according to 1 1H - NMR spectroscopy) was mixed with 12 g of potassium carbonate (anhydrous, Merck). The suspension was stirred in an oil bath at 95 - 99 °C for 1.5 hours. The conversion of the sampled material was determined by 1 1H - NMR: The conversion was 83% of the β - butyrolactone used. Based on the resulting poly - 3 - hydroxybutyrate carboxylic acid, 3% crotonic acid was formed.

[0210] The mixture was devolatilized under reduced pressure (150 hPa) up to 160 °C. Thus, the unreacted β - butyrolactone was removed by distillation. It can be used for further reactions. A sample was taken from the residue and filtered. Its 1 1H - NMR spectrum gave the following average composition of the resulting poly - 3 - hydroxybutyrate carboxylic acid:

[0211] (H3C - CH=CH - C(O)-O - [CH(CH)3 - CH2 - C(O)O] 8.5 CH(CH3)CH2 - C(O)OH)

[0212] Step 2: Chlorination

[0213] At 40 °C, the reaction mixture from step 1 was mixed with 190 g of thionyl chloride (Merck) and stirred at 40 °C for 1.5 h. The conversion was easily monitored via gas evolution. After the reaction was terminated, the mixture was devolatilized at 50 °C under reduced pressure. A sample was taken from the residue and filtered. It 1 The 1H-NMR spectrum gave the following average formula of the resulting poly-3-hydroxybutyrate carbonyl chloride at a conversion of 99%:

[0214] (H3C-CH=CH-C(O)-O-[CH(CH)3-CH2-C(O)O] 7.8 CH(CH3)CH2-C(O)Cl)

[0215] Step 3: Derivatization with 1,2-propanediol

[0216] The reaction mixture from step 2 was mixed with 200 g of dichloromethane to improve stirrability and then 122 g of 1,2-propanediol was added within 20 min at 40 °C. The mixture was stirred at 40 °C for 2 h and then a water jet vacuum of 100 hPa was applied at 40 °C for 1 h. Finally, the mixture was baked to 100 °C and 1 hPa. The residue was filtered. 310 g of a clear brown filtrate was obtained, the 1 1H-NMR spectrum showed complete conversion of the carbonyl chloride groups to hydroxyalkoxy groups. The derived poly-3-hydroxybutyrate could be assigned by 1 the 1H-NMR spectrum to the following average formula:

[0217]

[0218] Steps 1 and 2 of Example 1 were repeated. The composition of the poly-3-hydroxybutyrate carbonyl chloride was determined by 1 1H-NMR spectroscopy of the filtered samples. Thus, it had the following average composition:

[0219] (H3C-CH=CH-C(O)-O-[CH(CH)3-CH2-C(O)O] 8.5 CH(CH3)CH2-C(O)Cl)

[0220] The resulting amount of poly-3-hydroxybutyrate carbonyl chloride was dispensed and derivatized with different reaction participants as described in Examples 2 to 6 below.

[0221] Example 2: Production of PHB oleyl ester

[0222] Step 3: Derivatization with oleyl alcohol

[0223] In a 100 ml three-necked flask, 30 g of the unfiltered reaction mixture from step 2 of Example 1 was mixed dropwise with 8.9 g of oleyl alcohol (Sigma-Aldrich, 90%, remainder: isomers and other fatty acids in the same molar mass range) at 80 °C and a gentle water jet vacuum (100 hPa). The mixture was stirred at 80 °C for a further 1 hour, then 0.2 g of hexamethyldisiloxane (Wacker Chemie AG) was added to neutralize residual acid and to silylate any OH groups present. The mixture was then baked at 120 °C / 1 hPa for one hour. At 50 °C, the brown residue was filtered using a Büchner funnel through a Pall T1000 depth filter (10 - 25 μm). 38.2 g of a clear brown oil was isolated. According to 1 1H-NMR spectroscopy, the derived poly-3-hydroxybutyrate has the following average formula:

[0224]

[0225] Example 3: Production of PHB-2-(N,N-dimethylamino)ethyl ester

[0226] Step 3: Derivatization with 2-N,N-dimethylaminoethanol

[0227] In a 100 ml three-necked flask, 20 g of the unfiltered reaction mixture from step 2 of Example 1 was dissolved in 20 g of dichloromethane (Merck, 99.9%) at 24 °C. Then, a 50% dichloromethane solution of 3.9 g of 2-N,N-dimethylaminoethanol (Sigma-Aldrich) was added dropwise with stirring. White smoke formed and the temperature of the mixture rose to 37 °C. The mixture was stirred at 25 °C for a further 5.5 hours and washed three times in each case with 3.9 g of 5% aqueous sodium bicarbonate solution. The organic phase was dried over anhydrous magnesium sulfate, the reaction mixture was filtered through a Beco KD3 filter (2 - 3.5 μm), and the clear brown filtrate was devolatilized at 80 °C / 1 hPa. 14.5 g of a clear brown oil was isolated.

[0228] According to 1 1H-NMR spectroscopy, the derived poly-3-hydroxybutyrate has the following average formula:

[0229]

[0230] Example 4: Production of PHB-2-(N,N-dimethylamino)ethyl ester hydrochloride

[0231] Step 3: Derivatization with N,N-dimethylaminoethanol

[0232] In a 100 ml three-necked flask, 10 g of the unfiltered reaction mixture from Step 2 of Example 1 was dissolved in 10 g of anisole (Sigma-Aldrich, for synthesis) at 24 °C. Then, 0.9 g of N,N-dimethylaminoethanol (Sigma-Aldrich) was added dropwise with stirring. The mixture was stirred at 25 °C for 4 hours and heated at 50 °C / 1 hPa for half an hour. 10.9 g of a viscous, transparent brown oil was isolated. According to 1 1H-NMR spectroscopy, the derived poly-3-hydroxybutyrate has the following average formula:

[0233]

[0234] Example 5: Production of PHB-PEG-350-Me ester

[0235] Step 3: Derivatization with methoxypolyethylene glycol 350

[0236] In a 100 ml three-necked flask, 30 g of the unfiltered reaction mixture from Step 2 of Example 1 was mixed dropwise with 11.6 g of methoxypolyethylene glycol 350 (average molar weight 350 g / mol, Sigma-Aldrich) at 80 °C and a slight water jet vacuum (100 hPa) over 20 minutes. The mixture was continuously stirred at 80 °C for 1 hour, then 0.2 g of hexamethyldisiloxane (Wacker Chemie AG) was added to neutralize the residual acid and silylate any OH groups present. The mixture was then baked to 120 °C / 1 hPa for one hour. At 60 °C, the brown residue was filtered using a Buchner funnel through a Pall T1000 depth filter (10 - 25 μm). 30.1 g of a transparent brown oil was isolated. According to 1 1H-NMR spectroscopy, the derived poly-3-hydroxybutyrate has the following average formula:

[0237]

[0238] Example 6: Production of PHB-2-methyl-prop-1-yl-3-ol ester

[0239] Step 3: Derivatization with 2-methyl-1,3-propanediol

[0240] In a 100 ml three-necked flask, 30 g of 2-methyl-1,3-propanediol (Sigma-Aldrich, 99%) was first added at 40 °C and 100 hPa. A 50% filtered solution of anisole (Sigma-Aldrich, for synthesis) from the reaction mixture of step 2 in Example 1 (60 g) was added within 50 minutes. The mixture was continuously stirred at 40 °C and 80 - 100 hPa for 5 hours, and then baked to 140 °C / 0.1 hPa for one hour. 30.1 g of a transparent brown oil was separated out. According to 1 1H-NMR spectroscopy, the derived poly-3-hydroxybutyrate has the following average formula:

[0241]

[0242] Example 7: Production of PHB-PEG-A-B-A block copolymer

[0243] Step 1: Ring-opening polymerization

[0244] In a 100 mL three-necked flask equipped with a distillation device, 60 g of β-butyrolactone (source: Sigma-Aldrich, containing 1% crotonic acid according to 1 1H-NMR spectroscopy) was mixed with 1.2 g of KF*Al2O3. The suspension was stirred in an oil bath at 95 - 99 °C for two hours. The conversion rate of the sample taken out was determined by 1 1H-NMR: The conversion rate was 67% of the β-butyrolactone used. Based on the resulting poly-3-hydroxybutyrate carboxylic acid, 1.5% crotonic acid was formed. The mixture was devolatilized under reduced pressure (150 hPa) up to 160 °C. Thus, the unreacted β-butyrolactone was removed by distillation. It can be used for further reactions.

[0245] The production method of the catalyst KF*Al2O3 is as follows:

[0246] In a mortar under nitrogen purge, 31 g of alumina (Merck) was ground together with 17.7 g of potassium fluoride (VWR). The mixture was heated in a drying oven at 200 °C for 24 h. The white powder was stored under nitrogen.

[0247] Step 2: Chlorination

[0248] At 40 °C, the reaction mixture from step 1 was mixed with 28.6 g of thionyl chloride (Merck) and stirred at 40 °C for 2.5 hours. This conversion was easily monitored via gas evolution. After the reaction terminated, the mixture was devolatilized under reduced pressure at 50 °C. The residue was a viscous oil, which according to 1 1H-NMR, had the following composition:

[0249] (H3C-CH=CH-C(O)-O-[CH(CH)3-CH2-C(O)O] 7.44 CH(CH3)CH2-C(O)-Cl)

[0250] Step 3: Derivatization with PEG400

[0251] At 80 °C / 200 hPa, 4.5 g of the poly-3-hydroxybutyrate carbonyl chloride from Step 2 was mixed dropwise with 1 g of polyethylene glycol 400 (Fluka). The mixture was continuously stirred under these conditions for 1 h, the vacuum was broken with nitrogen, 0.02 g of hexamethyldisilazane (Wacker Chemie AG) was added to scavenge acid groups, and the mixture was continuously stirred for 5 min. The mixture was devolatilized until 120 °C / 1 hPa. The residue was filtered. 5 g of a transparent orange oil was isolated, and according to 1 1H-NMR spectroscopy, it had the following composition:

[0252] (H3C-CH=CH-C(O)O[CH(CH)3-CH2-C(O)O] 8.4 CH(CH2CH2O) 8.7 [(O)CCH2-CH(CH3)-O] 8.4 -C(O)-CH=CH-CH3)

[0253] Example 8: Production of PHB-4-acryloxybutyrate

[0254] Step 1: Ring-opening polymerization

[0255] Example 1 was repeated, except that in Step 1, after 60% conversion, the reaction was terminated by distilling off the unreacted β-butyrolactone at 100 °C / 1.5 hPa. 1.7% of crotonic acid was formed based on the resulting poly-3-hydroxybutyrate carboxylic acid. According to the 1 1H-NMR spectrum of the withdrawn sample, the poly-3-hydroxybutyrate formed as an intermediate had the following average composition:

[0256] (H3C-CH=CH-C(O)-O-[CH(CH)3-CH2-C(O)O] 13.5 CH(CH3)CH2-C(O)OH)

[0257] Step 2: Chlorination

[0258] For chlorination, the residue was mixed with 5 molar equivalents of thionyl chloride based on the carboxyl groups of the poly-3-hydroxybutyrate carboxylic acid at 40 °C. The mixture was reacted at 40 °C for 2 h, and the volatile components were removed at 0.5 hPa and up to 50 °C. According to 1H-NMR spectroscopy showed that the light yellow viscous residue had the following composition:

[0259] (H3C-CH=CH-C(O)-O-[CH(CH)3-CH2-C(O)O] 12.5 CH(CH3)CH2-C(O)Cl)

[0260] Step 3: Derivatization with 4-hydroxybutyl acrylate

[0261] In a 250 ml three-necked flask, 39.6 g of the unfiltered reaction mixture from Step 2 was mixed dropwise with 7.6 g of 4-hydroxybutyl acrylate (TCI, 90%) at 40 °C and under a slight water jet vacuum (100 hPa). The mixture was continuously stirred at 40 °C for 1 hour. Subsequently, it was baked to 100 °C / 0.4 hPa for 15 minutes. At 40 °C, using a Buchner funnel, the light brown viscous residue was filtered through a Pall T1000 depth filter (10 - 25 μm). 42 g of a transparent brown oil was separated. According to 1 H-NMR spectroscopy, the derived poly-3-hydroxybutyrate had the following average formula:

[0262]

[0263] UV crosslinking:

[0264] 2 g of acryloyl-functionalized poly-3-hydroxybutyrate was mixed with the photoinitiator 1173 (Sigma-Aldrich, 2-methyl-1-phenyl-propan-2-ol-1-one). A portion of the transparent mixture was poured into a glass cell at a layer thickness of approximately 0.1 mm and crosslinked by UV irradiation in a UV chamber (Uvacube, Hg halide lamp, 290 - 415 nm, 2000 W) to obtain a transparent elastic vulcanized rubber within 15 seconds.

[0265] Comparative Example 1: Esterification of poly-3-hydroxybutyrate carboxylic acid with PEG400 according to the prior art

[0266] On a water separator, 25 g of poly-3-hydroxybutyrate carboxylic acid with crotonate end groups and carboxylic acid end groups of the average formula (H3C-CH=CH-C(O)-O-[CH(CH)3-CH2-C(O)O] 8.67 H) was produced according to Step 1 (devolatilization and filtration) of Example 1 and refluxed with 5.9 g of polyethylene glycol 400 (Fluka), 10 g of anisole (Merck), and 0.1 g of titanium tetraisopropoxide (Merck) until no more water was evolved (5.5 hours).

[0267] Due to the decomposition of the polymer, solid crystalline deposits of crotonic acid are deposited in the vapor chamber.

[0268] According to the 1 1H-NMR spectrum, the conversion rate of carboxylic acid functional groups to ester functional groups is 60%. The number of ester units decreased from 8.67 to 3.6, which confirmed the degradation to crotonic acid.

[0269] The polyester chains are extensively degraded under these reaction conditions commonly used for esterification.

Claims

1. A method for producing a poly-3-hydroxyalkanoate of the general formula VI wherein the poly-3-hydroxyalkanoate has an ester unit as a functional group at one chain end and another functional group at the other chain end, The method comprises the following steps: Step 1: Ring-opening polymerization, in which at least one β-lactone of the general formula I is reacted with at least one unsaturated carboxylic acid of the general formula II in the presence of at least one heterogeneous catalyst to obtain a poly-3-hydroxyalkanoate of the general formula III , Step 2: Chlorination, in which the poly-3-hydroxyalkanoate of the general formula III is reacted with at least one chlorinating agent Cl to form a poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV ​ and Step 3: Derivatization, in which the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV is reacted with at least one compound of the general formula V containing at least one functional group X-Y, and the poly-3-hydroxyalkanoate of the general formula VI is obtained by eliminating Y-Cl. wherein R 1 、 R 2 、 R 3 each independently represents a hydrogen atom, a halogen atom, a linear, (bi)cyclic or branched, substituted or unsubstituted C1-C 18 hydrocarbyl group, optionally interrupted by a heteroatom selected from O, S or N, wherein the groups R 1 、 R 2 、 R 3 may also be joined pairwise and exist as components of a cyclic structure R 5 represents a linear, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbyl group having 1 to 100 carbon atoms; X represents -O- or -NR 11 -, wherein R 11 independently represents, each time it appears, a hydrogen atom, or a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a group of the general formula -C(=O)-R 12 group wherein R 12 represents a hydrogen atom, or a straight-chain, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a primary, secondary or tertiary amine group -NR 8 R 9 , wherein R 8 and R 9 each independently represents a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, and the two groups R 8 and R 9 can be connected in pairs to exist as components of a cyclic structure Y represents a hydrogen atom, a metal group or a metal-containing group, wherein the metal is selected from alkali metals, alkaline earth metals, silicon, titanium, zinc, tin, iron, manganese or copper, n is from 4 to 1400, o is from 1 to 16 and p ≤ o.

2. The method according to claim 1, characterized in that, General formula used I The β-lactones used are of industrial quality with a purity of at least ≥90% by weight.

3. The method according to claim 1 or 2, characterized in that, It is at least one unsaturated carboxylic acid of the general formula II which corresponds to an isomer of the β-lactone of the general formula I and is used as an initiator for the ring-opening polymerization.

4. The method according to claim 1, 2 or 3, characterized in that, The catalyst used is a solid basic catalyst selected from alkali metal oxides, hydroxides, carbonates and hydrogencarbonates or alkali metal fluorides, and the solid basic catalyst is optionally supported on a support material or an alkaline earth metal oxide or hydroxide.

5. The method according to any one of claims 1 to 4, characterized in that The chlorinating agent used Cl is thionyl chloride, phosgene or phosphorus(V) chloride.

6. The method according to any one of claims 1 to 5, characterized in that In batch operation, at least two consecutive steps are carried out in the same reaction vessel without intermediate purification, or in a semi-continuous or fully continuous process, all steps are carried out in reactors arranged in series.

7. The method according to any one of claims 1 to 6, characterized in that, R 5 represents a linear, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbyl group having 3 to 100 carbon atoms.

8. The method according to any one of claims 1 to 7, characterized in that The functional group X-Y represents -OH, -NHR 11 , an alkoxide of Li, Na, K, Mg or Ca, or an oxygen-bonded silyl group.

9. The method according to any one of claims 1 to 8, characterized in that, n is from 4 to 100.

10. The method according to any one of claims 1 to 9, characterized in that, Steps 1 to 3 are carried out without solvent.

11. Poly-3-hydroxyalkanoate carbonyl chloride of the following general formula, wherein R 1 、R 2 、R 3 each independently represents a hydrogen atom, a halogen atom, a linear, (bi)cyclic or branched, substituted or unsubstituted C1-C 18 hydrocarbyl group, optionally interrupted by a heteroatom selected from O, S or N, wherein the groups R 1 、R 2 、R 3 may also be joined pairwise and exist as components of a cyclic structure and n is from 4 to 1400.

12. Poly-3-hydroxyalkanoate of the following general formula, wherein R 1 、R 2 、R 3 each independently represents a hydrogen atom, a halogen atom, a linear, (bi)cyclic or branched, substituted or unsubstituted C1-C 18 hydrocarbyl group, optionally interrupted by a heteroatom selected from O, S or N, wherein the groups R 1 、R 2 、R 3 may also be joined in pairs and exist as components of a cyclic structure R 5 represents a linear, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbyl group having 1 to 100 carbon atoms; X represents -O- or -NR 11 -, wherein R 11 independently represents, each time it appears, a hydrogen atom, or a linear, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a group of the general formula -C(=O)-R 12 group wherein R 12 represents a hydrogen atom, or a straight-chain, cyclic or branched, substituted or unsubstituted alkyl group having 1 to 18 carbon atoms, or an aryl group having 6 to 18 carbon atoms, or a primary, secondary or tertiary amine group -NR 8 R 9 , wherein R 8 and R 9 each independently represents a hydrogen group or a hydrocarbon group having 1 to 6 carbon atoms, and the two groups R 8 and R 9 can be connected in pairs and exist as components of a cyclic structure Y represents a hydrogen atom, a metal group or a metal-containing group, wherein the metal is selected from alkali metals, alkaline earth metals, silicon, titanium, zinc, tin, iron, manganese or copper, n is from 4 to 1400, o is from 1 to 16 and p ≤ o.

13. A poly-3-hydroxyalkanoate of the general formula according to claim 12 VI wherein R 5 represents a linear, branched or (bi)cyclic, saturated or unsaturated, monomeric or polymeric, substituted or unsubstituted hydrocarbon group having 3 to 100 carbon atoms.

14. A poly-3-hydroxyalkanoate of the general formula according to claim 12 or 13, characterized in that, VI and The functional group X-Y represents -OH, -NHR 11 , an alkoxide or an oxygen-bonded silyl group of Li, Na, K, Mg or Ca.

15. The general formula according to claim 11 IV of poly-3-hydroxyalkanoate carbonyl chloride or the general formula according to claim 12, 13 or 14 VI of poly-3-hydroxyalkanoate, characterized in that n is from 4 to 100.

16. Use of the poly-3-hydroxyalkanoate carbonyl chloride of the general formula IV for the chemical modification of a pharmaceutically active ingredient.

17. Use of the poly-3-hydroxyalkanoate of the general formula according to any one of claims 12 to 15 VI in cosmetic compositions, pesticides, adhesives, in textile or leather treatment / care or as a plasticizer.

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