Kinetics and mechanisms in anionic ring-opening polymerization

Recent advances in the anionic ring-opening polymerization (AROP), including covalent (pseudoanionic) polymerization, are reviewed. Thermodynamics, kinetics, and mechanisms of AROP are discussed, covering mostly polymerization of oxiranes, lactones and cyclic siloxanes as monomers. The following general problems of AROP are discussed: anionic polymerizability, thermodynamics - particularly of the monomers exhibiting low ring strain, chemistry of initiation, structures and reactivity of active species. New phenomena, particularly polymerization with reversibly aggregating species are analyzed in more detail. Chain transfer to polymer - the major side reaction - is analyzed quantitatively, by introducing the selectivity parameter β, expressed by the ratio k_p/k_tr. This parameter has been determined for the anionic and pseudoanionic polymerization of ϵ-caprolactone.     

Investigation on lipase-catalyzed solution polymerization of cyclic carbonate

In this study, 26-membered macrocyclic carbonate, cyclobis(decamethylene carbonate) [(DMC)₂] was attempted to undergo ring-opening polymerization by lipase catalysis in toluene. Novozym-435 exhibited even higher catalytic activity towards (DMC)₂ polymerization compared with SnOCt₂ while high molecular weight (M_n) of 5.4 × 10⁴ and yield of 99% was still achieved at ultra-low enzyme/substrate (E/S) weight ratio of 1/200. ¹H NMR spectra demonstrated the existence of terminal hydroxyl group. Solid phase polymerization in the absence of toluene unexpectedly took place at the temperature lower than (DMC)₂’s melting point of 110 °C. Compared with solvent-free case, the addition of toluene solvent resulted in marked increase in reaction rate. As to the polymerization during 48 h with the E/S weight ratio of 1/100, a region existed at around toluene/carbonate (vol/wt, ml/g) ratio of 1∼2 where the polymerizations gave optimal results in terms of both higher molecular weight and monomer conversion. It was found that much higher molecular weight polymers may be obtained by decreasing enzyme concentrations. Plots of ln{[M]₀:[M]_t} versus reaction time were in linear agreement, indicating no chain termination, and monomer consumption follows a first-order rate law. The Novozym-435 catalyzed polymerization of (DMC)₂ in toluene presented pseudo-living characteristic. Compared with 6-membered trimethylene carbonate, much lower reaction activity of large-sized (DMC)₂ is observed, which is opposite to the result concerning the enzymatic polymerization of lactones with different ring-size.     

Enzymatic Ring-Opening Polymerization of Lactones by Lipase Catalyst: Mechanistic Aspects

Mechanistic aspects of lipase-catalyzed ring-opening polymerization (ROP) of lactones to give polyesters are discussed from accumulated experimental data and new insight. Comparison of the ROP reactivity by lipase catalyst with the anionic ROP reactivity by a metal-catalyst clearly demonstrates the characteristics of lipase catalysis; the larger ring-sized monomers with lower ring strain showed higher polymerizability than medium ring-sized ones, in contrast to the anionic ROP showing the reverse direction where the ring strain of monomer is operative. The enzyme-catalysis involves an acyl-enzyme intermediate formation as a key-step. From the copolymerization results a new mechanism is proposed, that involves the formation of the acyl-enzyme intermediate (acylation step) and/or the nucleophilic attack of the propagationg alcohol end to the carbonyl carbon of the intermediate to open the monomer ring (deacylation step) as the rate-determining step. The structure of the propagating alcohol end (primary or secondary) affects much on which step is more operative.     

Lipase-catalyzed ring-opening polymerization of 1,3-dioxan-2-one

Enzymatic ring-opening polymerization of a 6-membered cyclic carbonate, 1,3-dioxan-2-one, was investigated by using lipase as catalyst in bulk. Supported lipase derived from Candida antarctica catalyzed the polymerization to give the corresponding aliphatic polycarbonate. Unchanged monomer was recovered in the absence of the enzyme or using an inactivated enzyme, indicating that the present polymerization proceeds through enzymatic catalysis.     

Lipase-catalyzed ring-opening polymerization of α-methyl-δ-valerolactone and α-methyl-ε-caprolactone

Lipase-catalyzed ring-opening polymerization of α-methyl-substituted medium-size lactones, α-methyl-δ-valerolactone and α-methyl-ε-caprolactone, were carried in bulk. Immobilized lipase derived from Candida antarctica is active in the polymerization of both monomers. The polymerization proceeds under mild reaction conditions to give the corresponding aliphatic polyester having a hydroxy group at one end and a carboxylic acid group at the other.     

Zinc Glutarate Catalyzed Synthesis and Biodegradability of Poly(carbonate-co-ester)s from CO2, Propylene Oxide,and ϵ-Caprolactone

A zinc glutarate (ZnGA) catalyst was prepared from the reaction of zinc oxide and glutaric acid in dry toluene. ZnGA was found to exhibit a catalytic activity for the copolymerization of carbon dioxide (CO₂) and propylene oxide (PO) and the homopolymerization of PO but to reveal no catalytic activity for the homopolymerization of ϵ-caprolactone (CL). The ZnGA-catalyzed polymerization was extended for the terpolymerization of CO₂ with PO and CL, producing poly(propylene carbonate-co-ϵ-caprolactone)s (PPCCLs) with a reasonably high molecular weight in high yields. In the terpolymerization, PO and CL were used as both co-monomers and reaction media, after the reaction completed, the excess co-monomers were easily recovered and reused in the next terpolymerization batch. For the synthesized polymers, enzymatic and biological degradability were investigated.     

Melt block copolymerization of ϵ-caprolactone and L-lactide

AB block copolymers of ϵ-caprolactone and (L )-lactide could be prepared by ring-opening polymerization in the melt at 110°C using stannous octoate as a catalyst and ethanol as an initiator provided ϵ-caprolactone was polymerized first. Ethanol initiated the polymerization of ϵ-caprolactone producing a polymer with ϵ-caprolactone derived hydroxyl end groups which after addition of L -lactide in the second step of the polymerization initiated the ring-opening copolymerization of L -lactide. The number-average molecular weights of the poly(ϵ-caprolactone) blocks varied from 1.5 to 5.2 × 10³, while those of the poly(L -lactide) blocks ranged from 17.4 to 49.7 × 10³. The polydispersities of the block copolymers varied from 1.16 to 1.27. The number-average molecular weights of the polymers were controlled by the monomer/hydroxyl group ratio, and were independent on the monomer/stannous octoate ratio within the range of experimental conditions studied. When L -lactide was polymerized first, followed by copolymerization of ϵ-caprolactone, random copolymers were obtained. The formation of random copolymers was attributed to the occurrence of transesterification reactions. These side reactions were caused by the ϵ-caprolactone derived hydroxyl end groups generated during the copolymerization of ϵ-caprolactone with pre-polymers of L -lactide. The polymerization proceeds through an ester alcoholysis reaction mechanism, in which the stannous octoate activated ester groups of the monomers react with hydroxyl groups. © 1997 John Wiley & Sons, Inc.     

Enzymatic polyesterification in organic media. Enzyme-catalyzed synthesis of linear polyesters. I. Condensation polymerization of linear hydroxyesters. II. Ring-opening polymerization of ϵ-caprolactone

With the object to synthesize polyesters by enzymatic catalysis in organic media, two directions have been investigated: (1) the condensation polymerization of linear ω-hydroxyesters and (2) the ring-opening polymerization of lactones. The commercially-available crude porcine pancreatic lipase (PPL), suspended in organic solvents, was the preferred enzyme for the reactions. In order to determine the optimal conditions for the condensation polymerization, the bifunctional methyl 6-hydroxyhexanoate was used as a model compound to study the influence of the following parameters: type of the enzymecatalyst, kind of solvent, concentration, temperature, duration, size of the reaction mixture, and stirring. Film-forming polyesters with a degree of polymerization (DP) up to about 100 were obtained from linear aliphatic hydroxyesters in n-hexane at reflux temperature (69°C). Yet concurrently with the intermolecular condensation polymerization, macrolactones were also formed by intramolecular reaction. Two aromatic hydroxyesters did not react under these conditions. For the ring-opening polymerization of lactones the reaction of ?-caprolactone with methanol as the preferred nucleophile, was studied. Polyesters with a DP of up to 35 were obtained in n-hexane at temperatures between 25 and 40°C. The degrees of polymerization of the polyesters were determined by comparative analyses of the end groups in the ¹H-NMR spectra and by determination of molecular weights either by vapor phase osmometry, gel permeation chromatography, or intrinsic viscosity. © 1993 John Wiley & Sons, Inc.     

Novel ring-opening polymerization of lactide by lipase

Six-membered D,L-, L,L- and D,D-lactides were polymerized by lipase over a temperature range of 80 to 130 °C to yield the polylactide with a molecular weight (M_w) of greater than 270000. Among the lipases tested, lipase PS gave the greatest molecular weight of polylactide. The polymerization of D,L-lactide by lipase was better than that of L,L- and D,D-lactides. The polymerization of lactide by lipase showed the characteristic features, such as induction period for the initiation of polymerization, formation of oligomer and subsequent formation of high molecular weight polylactide, which may imply the characteristic polymerization by lipase. Immobilization of lipase on celite significantly enhanced the polymerization of lactide particularly with respect to the low concentration of the enzyme and the M_w of the resultant polymer. It was found that there is no clear relationship between enzymatic polymerizability and enzymatic degradability with respect to the enzyme origin and the stereochemistry of lactide.     

Microspheres by dispersion polymerization of lactides and ϵ-caprolactone

Polyester microspheres were synthesized by the ring-opening polymerization of lactides (racemate or optically active L,L-isomer) and ϵ-caprolactone. Polymerizations were carried out in the 1,4-dioxane-heptane mixed solvents in the presence of poly(dodecyl acrylate)-g-poly(ϵ-caprolactone) (poly(DA-CL)) used as surface-active agent. Polymerizations were initiated with tin(II) 2-ethylhexanoate (lactides), diethylaluminum ethoxide or sodium trimethylsilanolate (ϵ-caprolactone). In the studies of the polymerization of lactides, relations were determined between diameters, the distribution of diameters of synthesized microspheres, and the structure of poly(DA-CL). It was found that it is possible, depending on thermal treatment of microspheres after synthesis, to obtain polylactide microspheres differing in the degree of crystallinity. Kinetics of the dispersion pseudoanionic and anionic polymerizations of ϵ-caprolactone were also investigated and the results of these studies were compared with the data for the corresponding polymerizations of ϵ-caprolactone in solution.     

Synthesis and characterization of biodegradable homopolymers and block copolymers based on adipic anhydride

Homopolymers of adipic anhydride (AA) and block copolymers of ϵ-caprolactone (ϵ-CL) and AA have been synthesized with aluminum triisopropoxide as an initiator. Homopolymerization was studied at 20°C in toluene and methylene chloride (CH₂Cl₂). The end-group analysis agrees with a coordination insertion mechanism based on the acyl-oxygen cleavage of the AA ring. Living poly(ϵ-caprolactone) (PCL) chains are very efficient macro-initiators for the polymerization of AA, with formation of diblock copolymers of a narrow molecular weight distribution. At our best knowledge, low molecular weight ω-aluminum alkoxide PCL macroinitiators (M_n < 1000) allow the first valuable synthesis of PAA with a molecular weight as high as 58,000 and a quite narrow polydispersity (M_w/M_n = 1.2). Size-exclusion chromatography (SEC) and ¹³C NMR confirm the blocky structure of the copolymers, in agreement with DSC that shows two melting endotherms and two glass transitions characteristic of the crystalline and amorphous phases of PCL and PAA, respectively. Block copolymers of ϵ-CL and AA are also sensitive to hydrolysis, which makes them possible candidates for biomedical applications. Initiation of the AA polymerization in bulk with aluminum triisopropoxide in the presence of various ligands is also discussed. © 1997 John Wiley & Sons, Inc.     

The anionic ring-opening polymerization and copolymerization of cyclic carbonates

Cyclic carbonates are eligible to ring-opening polymerization using a wide variety of initiators such as carbanionic or alcoholate species as well as initiators known to be effective for the ring-opening polymerization of lactones and for the group transfer polymerization of vinyl monomers. Depending on the catalyst, high molecular weight polymers may be obtained in high yields (kinetically controlled regime) or a ring-chain equilibrium is observed upon end-biting, back-biting and transesterification reactions (thermodynamically controlled regime). The polymerizability of the cyclic carbonates is strongly dependent on their structure. Five-membered cycles generally cannot be polymerized, whereas six-membered cycles can be polymerized and copolymerized in an ideal manner. The polymerizability of higher cyclics, in particular when containing aromatic ring systems, is highly dependent on the substitution pattern of the aromatics. Since the active species in the polymerization of aliphatic cyclic carbonates was disclosed to be of alcoholate type, a copolymerization with ϵ-caprolactone is easily achieved, the reactivity of the cyclic carbonate, however, being by far larger than that of the lactone. On the other hand, the copolymerization with pivalolactone exerts a different behaviour, since the active species of the growing pivalolactone chain after a few steps assumes the character of a carboxylate anion which is unable to promote the ring-opening polymerization of cyclic carbonates. Since carbanionic species may be used as initiators for the ring-opening polymerization of cyclic carbonates, polystyryl, polybutadienyl, and polyisoprenyl anions may be used as initiators to achieve the corresponding block copolymers. To obtain block copolymers with poly(methyl methacrylate) blocks a group transfer polymerization of the respective acrylate has to be performed, followed by the polymerization of the cyclic carbonate. The latter, however, rather proceeds by a metal- free anionic process than by a group transfer process. The ring-opening polymerization and copolymerization of cyclic carbonates allows the preparation of a broad variety of new polymers with remarkable properties.     

The features of cationic polymerization of lactones under the action of onium salts

Results on the kinetics of polymerization of ϵ -caprolactone (ϵ -CL) under the action of quaternary onium salts with complex counterions are reported. The structure and molecular weight distribution (MWD) of polymerization products, and of the catalysts and active propagating centers were studied by gel permeation and gas chromatography, IR and UV spectroscopy, chemical and X-ray analysis. The role of photochemical transformations at ϵ -CL polymerization in the presence of onium salts with counterion FeCl₄ was revealed. The mechanism of polymerization is discussed.     

The use of d-mannitol-derived C2-symmetric trienes in tandem metathesis reactions towards valuable lactones

Chiral lactones were synthesized from d-mannitol. C₂-symmetric triene precursors were constructed with a central relay-olefin allowing the key domino ring-closing metathesis to be achieved. It led to the symmetrical cleavage of the substrate and to the formation of 2 mol of the desired 5- or 6-membered lactone. Attempts to form 7-membered lactones thus far only led to 14-membered macrodiolides instead.     

Low-temperature polymerization of lactams by using as catalyst the salt derived from NaAlEt4 and monomer and with several compounds as initiator

Low-temperature polymerization of α-pyrrolidone, α-piperidone, and ?-caprolactam was examined by using the salts derived from NaAlEt₄ and monomer, sodium lactamates, or the salt derived from AlEt₃ and monomer as catalyst and with N-acetyl lactams, ethyl acetate, or lactones as initiator. Sodium lactamate catalyst gave unsatisfactory results in the cases of ethyl acetate or lactones initiators, and gave the following order for the relative efficiency of initiators: N-acetyl lactam > ?-caprolactone ≥ ethyl acetate > β-propiolactone. The polymerization results obtained by the salt from NaAlEt₄ catalyst–ethyl acetate initiator system were nearly the same as those with N-acetyl lactam. The increases in the degree of polymerization and in the yield of polymer were observed in case of the salt from NaAlEt₄ catalyst-lactone initiator system, particularly in the cases of α-piperidone and ?-caprolactam. Also an incorporation of initiator into polymer chain was observed.     

Effect of the remaining lanthanide catalysts on the hydrolytic and enzymatic degradation of poly-(ϵ-caprolactone)

Poly-(ϵ-caprolactone) is a biodegradable polymer, which can be used for both medical and environmental applications. Due to its multiple applications the synthesis of such a polymer has been attracting an increasing attention in the past few decades. In our work, the polymers were synthesised by bulk polymerisation, using different lanthanide halides as initiators. The lanthanide derivatives are known as very active catalysts in the ring-opening polymerisation of cyclic esters. Moreover, they are not toxic in comparison of catalysts, which are usually used for this synthesis. In this paper, the influence of the lanthanides on both the hydrolytic and enzymatic degradation of the PCL obtained by ring-opening polymerization of ϵ-caprolactone with different lanthanide-based catalysts such as: lanthane chloride (LaCl₃), ytterbium chloride (YbCl₃) and samarium chloride (SmCl₃) was assessed. Samarium seems to slightly accelerate the hydrolytic degradation of the polymer and to slow down or inhibit its enzymatic degradation, mainly when the molecular weight of the polymer is high. The behaviour of PCL containing another lanthanide like lanthane is dependent on the nature of the metallic ion. Complete degradation, by the Lipase PS from Pseudomonas cepacia, is achieved only with Ytterbium.     

RING-OPENING POLYMERIZATION OF ε-CAPROLACTONE BY LANTHANOCENE CATALYSIS*

Ring-opening polymerization of ε-caprolactone (CL) catalyzed bylanthanocenes, O(C_2H_4C_5H_3CH_3)_2YCl (Cat-YCl) and Me_2Si[(CH_3)_3SiC_5H_3]_2NdCl(Cat-NdCl) has been carried out for the first time. It has been found that both yttroceneand neodymocene are very efficient to catalyze the polymerization of CL, giving high molec-ular weight poly (ε-caprolactone) (PCL ). The effects of [cat] / [ε- CL] molar ratio, polymeriza-tion temperature and time, as well as solvents were investigated and polymerization tem-perature is found to be the most important factor affecting the polymerization. The bulkpolymerization gives higher molecular weight PCL and higher conversion than that in solu-tion polymerization. NaBPh_4 was found to promote the polymerization of ε-caprolactone,and thus to increase both the polymerization conversion and MW of poly (ε- caprolactone ).     

A novel intramolecular reversible reaction between the hydroxyl group and isobutenylene chain in a cyclophane-type macrocycle

A novel Hg²⁺ ion induced reversible ring contraction was achieved employing the intramolecular reaction of isobutylene with an aromatic hydroxyl group of cyclophane; reversibility of the reaction was facilitated by excess addition of NaBH₄ which also resulted in complexation. The ring contraction and expansion was monitored by UV-VIS absorption, and by fluorescence and ¹H NMR spectra. Switchable fluorescence behavior (on—off—on) was observed when the ring-size was tuned from a 19-membered ring to an 18-membered and vice versa. This fine tuning has the potential to be applied in the construction of new supramolecular devices.     

Regioselective ring-opening anionic polymerization of β-lactones

New aspects of anionic polymerization of 4-membered lactones are presented, attention being paid to regioselectivity of ß-lactones ring-opening reactions. It has been demonstrated that supramolecular complexes of alkali metal alkoxides used as initiators enable control of lactones polymerization, and due to anion activation yield polymers with specific molecular architecture. Synthesis of the analogue of natural polymer poly(3-hydroxybutyrate) via anionic polymerization of ß-butyrolactone is discussed.     

New functionalized polyesters to achieve controlled architectures

Following our continued interest in the production of bioerodible and biodegradable functional polymers for biomedical applications, we synthesized and characterized new unsaturated polyesters. The presence of functional groups in the polymer backbone provided sites for chemical modification, and through a variation in the structure, the physical properties, such as the hydrophilicity and solubility, could be affected. With 1,1-di-n-butyl-stanna-2,7-dioxacyclo-4-heptene as the initiator in the ring-opening polymerization of polyesters, a new set of functionalized polyesters was created. The polymerization of ϵ-caprolactone resulted in poly(ϵ-caprolactone) with a double bond incorporated into the structure. The polymers were obtained in a controlled manner with low molecular dispersities. The double bond was previously incorporated into L -lactide polymers, and the two reactions were compared in this study. The conversion of ϵ-caprolactone, with a degree of polymerization of 50, was completed within 140 min, whereas for L -lactide, only a 45% conversion took place in the same period of time. The dispersities were somewhat higher with ϵ-caprolactone because of the higher reaction rate and, therefore, lower selectivity. The incorporated CC double bond in the polyesters provided a variety of opportunities for further modifications. In this case, the double bond of the L -lactide macromonomers was oxidized into epoxides. Epoxidation was carried out with m-chloroperoxybenzoic acid as a chemical reagent. The conversion of the double bonds into epoxides was completed, and the obtained yields were good (>95%). As a result of the mild reaction conditions, the epoxidation of the double bond was carried out quantitatively without any side reactions. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 444–452, 2004