Cyclic Polylactides Research Articles

Cyclic poly(l-lactide)s via simultaneous ROP and polycondensation (ROPPOC) catalyzed by dibutyltin phenoxides

Starting from dibutyltin oxide, four catalysts were synthesized, namely the dibutyltin bisphenoxides of phenol (SnPh), 4-chlorophenol (SnCP), 4-hydroxybenzonitrile (SnCN) and pentafluorophenol (SnOPF). With the first three catalysts polymerizations of l-lactide at 160 °C in bulk yielded large fraction of linear chains having phenylester end groups at short reaction times. At longer times the fraction of cycles considerably increased at the expense of the linear chains, when SnCN was used as catalyst. With SnOPF only cyclic polylactides were obtained at low Lac/Cat ratios (<400) with weight average molecular weights (Mw) up to 90 000 Da, whereas for high Lac/Cat ratios mixtures of cyclic and linear chains were found. Polymerizations in solution enabled variation of the molecular weight. Polymerizations of meso-lactide at temperatures down to 60 °C mainly yielded even-numbered linear chains supporting the postulated ROPPOC mechanism.

Stereoselective zwitterionic ring-opening polymerization of rac-lactide

Stereoselective zwitterionic ring-opening polymerization (ZROP) poses a potentially great challenge in polymer chemistry because of its unique ion-pairing catalysis mechanism. Herein, a stereoselective ZROP of rac-lactide (rac-LA) was explored for synthesis of isotactic cyclic polylactides by using commercially available N-heterocyclic carbene (NHC) catalysts at low temperature in tetrahydrofuran. The epimerization of lactide during ZROP can be inhibited at low temperature. The best isoselectivity can reach to a high value of Pm = 0.91 associated with a high melting point (Tm) of 193 °C. The resulting polylactides exhibit narrow molecular weight distributions (Mw/Mn < 1.2) and inhibited transesterification as evidenced by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The resulting polylactide is predominantly cyclic as evidenced by 1H NMR and MALDI-TOF MS analyses.

About formation of cycles in Sn(II) octanoate‐catalyzed polymerizations of lactides

ABSTRACTAt first, formation of cycles in commercial poly(l‐lactide)s is discussed and compared with benzyl alcohol‐initiated polymerizations performed in this work. This comparison was extended to polymerizations initiated with 4‐cyanophenol and pentafluorothiophenol which yielded cyclic polylactides via end‐biting. The initiator/catalyst ratio and the acidity of the initiator were found to be decisive for the extent of cyclization. Further polymerizations of l‐lactide were performed with various diphenols as initiators/co‐catalysts. With most diphenols, cyclic polylactides were the main reaction products. Yet, only catechols yielded even‐numbered cycles as main reaction products, a result which proves that their combination with SnOct2 catalyzed a ring‐expansion polymerization (REP). The influence of temperature, time, co‐catalyst, and catalyst concentrations was studied. Four different transesterification reactions yielding cycles were identified. For the cyclic poly(l‐lactide)s weight average molecular weights (Mw's) up to 120,000 were obtained, but 1H NMR end group analyses indicated that the extent of cyclization was slightly below 100%. The influence of various parameters like structure of initiator and catalyst and temperature on the formation of cyclic poly(l‐lactide)s has been investigated. Depending on the chosen conditions, the course of the polymerization can be varied from a process yielding exclusively linear polylactides to mainly cyclic polylactides. Three different reaction pathways for cyclization reactions have been identified. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1915–1925

Organocatalytic Stereoselective Cyclic Polylactide Synthesis in Supercritical Carbon Dioxide under Plasticizing Conditions.

Cyclic polylactide (cPLA) is a structural isomer of linear polylactide (PLA) although it possesses unique functionalities in comparison to its linear counterpart. Hitherto, the control of stereochemical purity in conventional cPLA synthesis has not been achieved. In this study, highly stereochemically pure cPLA was synthesized in the absence of a metal catalyst and organic solvent, which required high consumption of the residual monomer. The synthesis was conducted in supercritical carbon dioxide under CO2 plasticizing polymerization conditions in the presence of an organocatalyst and thiourea additives. In comparison with the stereocomplexes synthesized through conventional methods, cPLA from l-lactide (cPLLA) and cPLA from d-lactide (cPDLA) were synthesized with higher stereochemical purity and improved thermal stability. Moreover, the method presented herein is environmentally friendly and thus, applicable on an industrial level.

High molar mass cyclic poly(l-lactide) via ring-expansion polymerization with cyclic dibutyltin bisphenoxides

Two new catalysts (SnNa and SnBi) were prepared from dibutyltin oxide and 2,2′-dihydroxybiphenyl or 2,2′dihydroxy(1,1′-binaphtyl). These catalysts enabled rapid polymerizations of l-lactide at 160 or 180 °C in bulk, whereby almost exclusively cyclic polylactides were formed. These polymerizations were free of racemization and yielded pol(l-lactide)s having weight average molecular weights (Mw's) up to 140 000 g mol−1. The Mw's varied little with the Lac/Cat ratio as expected for a ring expansion polymerization (REP). Polymerizations performed in bulk at 140, 120 and 102 °C yielded cyclic polylactides with lower molecular weights. At 102 °C a strong predominance of even-numbered cycles was found with SnNa as catalyst. SnNa can also catalyze alcohol-initiated ROPs yielding linear poly(l-lactide) free of cyclics.

Sterically Bulky NHC Adducts of GaMe3 and InMe3 for H2 Activation and Lactide Polymerization

The sterically bulky Ga(III) and In(III) (IPr*)MMe3 adducts (1 and 2) and (SItBu)MMe3 adducts (3 and 4) (M = Ga, In; IPr* = 1,3-bis{2,6-bis(diphenylmethyl)-4-methylphenyl}-1,3-dihydro- imidazol-2-ylidene; SItBu = 1,3-bis(1,1-dimethylethyl)-imidazolidin-2-ylidene) were prepared and structurally characterized, allowing an estimation of the steric hindrance of such Lewis pairs (yields in 1–4: 92%, 90%, 73%, and 42%, respectively). While the IPr* adducts 1 and 2 are robust species, the more severely congested SItBu adducts 3 and 4 are more reactive and exhibit a limited stability in solution. Adduct (SItBu)GaMe3 (3) reacts quickly with H2 at room temperature to afford the corresponding aminal product, 1,3-di-tert-butylimidazolidine (5), along with free GaMe3. Such Frustrated Lewis Pair (FLP) reactivity constitutes the first instance of a H2 activation involving a simple trialkyl GaR3 species. Adduct 3 also mediates the ring-opening polymerization (ROP) of rac-lactide at room temperature to afford cyclic polylactide (PLA).

Ring-Opening Polymerization of l-Lactide to Cyclic Poly(Lactide) by Zeolitic Imidazole Framework ZIF-8 Catalyst.

The catalytic activity of ZIF-8 in the ring-opening polymerization of l-lactide without solvents or cocatalysts is presented for the first time. Two different synthetic strategies have been applied for synthesizing ZIF-8, either under solvothermal condition or by spray-drying procedure. Their catalytic activities are found to be correlating with the presence of open active sites in ZIF-8 structure. The structural defects that afford active acid and basic sites are supposed to cooperatively catalyze the reaction. ZIF-8 assembled by spray-drying technique, displays a superior catalytic activity at temperature of 160 °C, leading to the formation of high molecular weight cyclic polylactide. The ZIF-8 catalysts could be recycled and reused without any significant loss of catalytic activity.

Cyclic polylactides via simultaneous ring‐opening polymerization and polycondensation catalyzed by dibutyltin mercaptides

ABSTRACTl‐Lactide is polymerized in bulk at 160 °C either with dibutyltin bis(benzylmercaptide) (SnSBzl), dibutyltin bis(benzothiazole 2‐mercaptide) (SnMBT), or with dibutyltin bis(pentafluorothiophenolate) (SnSPF) as catalysts. SnSBzl yields linear polylactides having benzylthio‐ester end groups in addition to cyclic polylactides, whereas SnMBT and SnSPF mainly or exclusively yield cyclic polylactides. This finding, together with model reactions, indicates that the SnS catalysts promote a combined ring‐opening polymerization and polycondensation process including end‐to‐end cyclization. SnMBT caused slight racemization (3%–5%), when used at 160 °C. With SnSPF optically pure cyclic poly(l‐lactide)s with high‐molecular weights can be prepared at 160 °C. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3767–3775

Cyclic poly(l-lactide)s via ring-expansion polymerizations catalysed by 2,2-dibutyl-2-stanna-1,3-dithiolane

l-Lactide was polymerized in bulk at 120 or 160 °C with a cyclic dibutyltin catalyst derived from 1,2-dimercaptoethane.

Synthesis of cyclic polyesters: effects of alkoxy side chains in salicylaldiminato tin(II) complexes.

A new class of salicylaldiminato tin(II) catalysts having different alkoxy side chains has been developed. The ligands were modified to have different lengths and flexibilities such as –(CH2)2– (2a), –(CH2)3– (2b), –(ortho-C6H4)CH2– (2c) and –(CH2)2–O–(CH2)2– (2d). Complexes 2a, b were characterized crystallographically revealing a more constrained environment around the metal in complex 2a. These catalysts are active for the solvent-free polymerization of L-lactide and ε-caprolactone. Complex 2a having a shorter side chain was shown to better promote intramolecular transesterification affording cyclic polylactides and cyclic poly(ε-caprolactone). Complexes 2b and 2d having longer side chains produced cyclic poly(ε-caprolactone) as a major product but failed to give cyclic polylactides.

A tandem mass spectrometry-based method to assess the architectural purity of synthetic polymers: a case of a cyclic polylactide obtained by click chemistry

A tandem mass spectrometry-based method is developed to determine the degree of purity achieved in the cyclization of a linear poly(l-lactide).

Zwitterionic Ring Opening Polymerization with Isothioureas.

Bicyclic isothioureas 1 and 2 mediate controlled ring opening polymerizations (ROP) of lactides in the absence of protic initiators to afford high molecular weight polylactides (PLA) with narrow polydispersities. The cyclic structure of the resulting PLA was determined by dilute solution viscosity measurement and MALDI-TOF mass spectrometry. Compared to DBU initiator, isothioureas are more selective for producing cyclic PLA without appreciable linear contaminants. Mechanistic studies involving acyl amidinium support our hypothesis that DBU-initiated ZROP generates linear chains from a ketene aminal intermediate.

Characterization of polylactides with different stereoregularity using electrospray ionization ion mobility mass spectrometry.

We investigated the effect of stereoregularity on the gas-phase conformations of linear and cyclic polylactides (PLA) using electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) combined with molecular dynamics simulations. IM-MS analysis of PLA ions shows intriguing difference between the collision cross section (ΩD) value of poly-L-lactide (PLLA) and poly-LD-lactide (PLDLA) ions with respect to their chain architecture and stereoregularity. In the singly sodiated linear PLA (l-PLA∙Na(+)) case, both l-PLLA and l-PLDLA up to 11mer have very similar ΩD values, but the ΩD values of l-PLLA are greater than that of l-PLDLA ions for larger ions. In the case of cyclic PLA (c-PLA), c-PLLA∙Na(+) is more compact than c-PLDLA∙Na(+) for short PLA ions. However, c-PLLA exhibits larger ΩD value than c-PLDLA for PLA ions longer than 13mer. The origin of difference in the ΩD values was investigated using theoretical investigation of PLAs in the gas phase. The gas-phase conformation of PLA ions is influenced by Na(+)-oxygen coordination and the weak intramolecular hydrogen bond interaction, which are more effectively formed in more flexible chains. Therefore, the less flexible PLLA has a larger ΩD value than PLDLA. However, for short c-PLA, concomitant maximization of both Na(+)-oxygen coordination and hydrogen bond interaction is difficult due to the constricted chain freedom, which makes the ΩD value of PLAs in this range show a different trend compared with other PLA ions. Our study facilitates the understanding of correlation between stereoregularity of PLAs and their structure, providing potential utility of IM-MS to characterize stereoisomers of polymers.

Synthesis of Orientationally Isomeric Cyclic Stereoblock Polylactides with Head-to-Head and Head-to-Tail Linkages of the Enantiomeric Segments

A pair of orientationally isomeric cyclic stereoblock polylactides (PLAs) possessing head-to-head (HH) and head-to-tail (HT) linkages between the poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA) segments was synthesized through click chemistry and ring-closing metathesis (RCM) of three asymmetrically functionalized telechelic precursors. Thus, α-ethenyl-ω-azido-PLLA (2a) was reacted with α-ethenyl-ω-ethynyl-PDLA (2b) and α-ethynyl-ω-ethenyl-PDLA (2c) via click chemistry to form ethenyl telechelic stereoblock PLAs with HH and HT orientations (3a and 3b), respectively. The subsequent RCM produced cyclic stereoblock PLAs with the corresponding linking manners (4a and 4b). The effect of the topology on the melting temperature of the series of isomeric linear and cyclic PLAs having the contrastive linking orientations was systematically investigated.

Synthesis of cyclic polylactide catalysed by bis(salicylaldiminato)tin(ii) complexes

Eight bis(salicylaldiminato)tin(II) complexes have been synthesized from the reaction of Sn[N(SiMe(3))(2)](2) and 2 equiv of the corresponding ligands at room temperature. The ligands, synthesized from salicylaldehyde and amines, were designed to have different electronic and steric properties using different amines to synthesize the tin(II) complexes as aniline (2a), 2,6-dimethylaniline (2b), 2,6-diisopropylaniline (2c), 4-methoxyaniline (2d), 4-trifluoromethylaniline (2e), methylamine (2g), and tert-butylamine (2h). Ligand variation at the salicyl group synthesized from 4-bromosalicylaldehyde and 2,6-diisopropylaniline was used to form complex 2f. Complex 2c was characterized crystallographically. All catalysts were active for the neat polymerization of L-lactide at 115 °C. At a lactide : Sn molar ratio of 10 : 1, cyclic polylactide (PLA) was obtained as demonstrated by (1)H NMR and mass spectrometry. Addition of 1 equiv of benzyl alcohol in the polymerization produced linear PLA. At a higher lactide : Sn molar ratio of 200 : 1, high molecular weight PLAs with M(n) up to 132,200 Daltons were obtained. Results from GPC coupled with light scattering detector and viscometer suggested that they are cyclic PLA. The order of reactivity based on conversion was determined to be 2c < 2b < 2a in accordance with lower steric hindrance. For electronic contribution, the order of 2e < 2a < 2d was observed in agreement with the increasing electron donation of the ligands. Complex 2g having the smallest substituents was found to be the most active catalyst.

Synthesis, characterization and catalytic activity of Salen–(sodium) 2 and (Salen) 2–lanthanum–sodium complexes

Salen–Na 2( 1) and (Salen) 2–La–Na( 2) complexes have been prepared and structurally characterized [Salen = N, N′-bis (3,5-di- tert-butylsalicylidene)-1,3-propanediamine]. Experimental results show that the two complexes are efficient catalysts for the ring-opening polymerization (ROP) of l-lactide. According to the data of 1H NMR and electrospray-ionization (+ESI) mass spectrum, it is suggested that the obtained polymer is mainly cyclic polylactide (PLA) for a short PLA chain, but a mixture of cyclic and linear PLA for a long PLA chain. Structure–activity analysis of the two complexes is also done. We investigated why Salen–Na 2 complex is more active (Salen) 2–La–Na complex as the catalyst in the ROP of l-lactide and why the PLA catalyzed by complex 2 has lower PDIs than that catalyzed by complex 1.

Zwitterionic Polymerization: A Kinetic Strategy for the Controlled Synthesis of Cyclic Polylactide

The zwitterionic ring-opening polymerization of lactide initiated by N-heterocyclic carbenes generates cyclic polylactides with well-defined molecular weights between M(n) = 5000 and 30,000 g/mol with narrow polydispersities (M(w)/M(n) < or = 1.31). These zwitterionic polymerizations are extremely rapid (k(p) = 48.7 M(-1) s(-1)), but also exhibit exceptional control of molecular weight and molecular weight distribution. The unusual kinetic features of these zwitterionic polymerizations are illuminated with kinetic and mechanistic investigations, which implicate a mechanism that involves a slow initiation step (second order in [M]), a propagation step (first order in [M]) that is much faster than initiation (k(i) = 0.274 M(-2) s(-1)), cyclization (k(c) = 0.0575 s(-1)), and depropagation (k(d) = 0.208 s(-1)). Numerical and stochastic simulations of the kinetic data provide a kinetic rationale for the evolution of molecular weight with monomer conversion: the molecular weights increase with increasing monomer conversion, exhibit a nonzero intercept near 0% monomer conversion, and are relatively insensitive to the initial monomer-to-initiator ratio. The observed narrow molecular weight distributions are due to a high rate of propagation relative to cyclization and chain transfer. Kinetic simulations define the kinetic criteria under which the active zwitterions remain in solution; these simulations were substantiated by chain-extension experiments, which provide experimental evidence for chain extension of the zwitterions and reinitiation by the N-heterocyclic carbenes liberated upon macrocyclization. The kinetic model rationalizes some of the unique features of zwitterionic ring-opening polymerization and provides a useful mechanistic framework to optimize these polymerizations as a strategy to generate well-defined cyclic polyesters.

Cyclic Polylactides by Imidazole-Catalyzed Polymerization of l-Lactide

Heating of l-lactide with imidazole to 98−100 °C resulted in complete polymerization within 48 h. Even-numbered cycles resulting from end-to-end cyclization were the only reaction products after 4 h, but the polymerization process was accompanied by intensive racemization. Longer reaction times favored equilibration reactions with formation of odd-numbered cycles. Variation of the monomer−initiator ratio at 120 °C had little influence on the molecular weight. After 8 h at 150 °C, equal quantities of odd- and even-numbered cycles were found, indicating complete equilibration. Other protic heterocycles such as 1,2,4-triazole, benzimidazolyl acetonitrile, uracile, or hypoxanthine were not active as initiators/catalysts at 120 °C. However, the tertiary amine N-methylimidazole also catalyzes the formation of cyclic polylactides together with several byproducts. The reaction mechanisms are discussed.