Ring-Opening Polymerisation of rac-Lactide Using a Calix [ 4 ] arene-Based Titanium ( IV ) Complex

1 Department of Chemistry “Ugo Schiff”, University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy 2 Laboratoire de Chimie Inorganique Moléculaire et Catalyse, UMR 7177 CNRS, Université de Strasbourg, 1 rue Blaise Pascal, 67008 Strasbourg Cedex, France 3 Laboratory of Peptide & Protein Chemistry & Biology, Scientific and Technological Park, University of Florence, 50019 Sesto Fiorentino, Italy


Introduction
Poly(lactic acids) (PLAs) are biocompatible and biodegradable materials with potential applications in medicine and agriculture, as well as packaging materials.The most efficient method for the synthesis of PLAs is the ring opening polymerisation (ROP) of lactide (LA), which possesses two chiral centers [1][2][3][4].The stereochemistry of the polymer formed determines its physical and mechanical properties, as well as its rate of degradation, and it is therefore important to ensure stereocontrol of the polymerisation process [5][6][7][8].
Calix [4]arenes are macrocyclic molecules made of four phenol units linked via methylene bridges connected to the ortho positions of the phenol rings.The presence of four oxygen atoms at the lower rim of these conical molecules provides a valuable platform for the synthesis of poly(phenoxy) metal complexes.Recently, we have reported on a calix [4]arene titanium complex that was found to be active in the ROP of L-LA [21].In this complex, the calix [4]arenyl moiety behaves as a small oxo surface, which confers a high thermal stability to the corresponding complexes [22][23][24][25].
under microwave irradiation, which is an emerging field of research in polymer chemistry [26][27][28][29][30][31][32][33][34][35] (see Scheme 1).standard to calibrate the system [37].The samples were prepared by dissolving 0.005-0.006g of polymer in 2 mL of chloroform (corresponding to ca. 3 g•L −1 ).The WAXD analyses were done using a D8 Advance (Bruker) with a Solx solid state detector, using a Bragg-Brentano Geometry.All the samples were preventively heated at 120-130 • for three days before analysis.The samples were exposed to a Cu Kα X-ray source with a wave length (λ) of 1.541 Å.The angle of incidence was varied from 4

Results and Discussion
As reported recently, the polymerisation of L-lactide with 1 under microwave conditions leads to isotactic PLLA (see Scheme 2).
Size exclusion chromatography analysis of the polymers formed revealed that, as expected, the molecular Table 1: Thermally induced polymerisation of L,D-LA using complex (1) (a) .weight (M w ) increased with increasing [L,D-LA]/[Ti] ratio (Figure 2), the highest M w determined value being 43 × 10 3 g•mol −1 (Table 1, entry 4).However, the M w values were much lower than expected.As already suggested for PLLA, this may be rationalized in terms of intramolecular transesterification during the propagation process [21,28].The occurence of this phenomenon was confirmed by the presence in the MALDI-TOF spectra of peaks separated by intervals corresponding to half of the molecular weight of the monomer.Despite the observed transesterification process, the polymers obtained displayed molar mass distribution (MWD) indexes in the restricted range of 1.2-1.3,which indicates that the polymerisation process was relatively well controlled.
The DSC thermograms of the PLDA revealed only one glass transition temperature (T g ) for each sample.This temperature decreased from 53.0 to 41.7 • C when the size of the polymer chain increased (M w increased) (Table 1, entries 1 to 4).Furthermore, the 1 H-NMR spectrum of each sample revealed an unexpected microstructure (see an example in Figure 3).The spectrum shows two well-resolved peaks, of equal normalized intensity, at ca. 5.21 and 5.22 ppm representing hexad stereosequences of isisi and iiisi, respectively.According to pairwise Bernoullian statistics, an equal probability for isisi and iiisi stereosequences implies that the polymerisation process is random [38][39][40][41].Considering that the calixarene complex becomes chiral after insertion of the first incoming lactide (be it L or D), it may be anticipated that for the following step a preferential insertion of one of the monomers (L-LA or D-LA) takes place.In fact, careful analysis of the 1 H NMR spectrum revealed a higher intensity for the iii sequence (almost 4 times than each other peak).In keeping with the studies of Coates et al. [15,16], this observation may be assigned to a partial isotacticstereoblock structure.The relatively high proportion of isisi    sequences may be interpreted in terms of a concomitant transesterification process.It is important to note that whatever the [L,D-LA]/[Ti] ratio applied, the polymerisation experiments led to PLDAs with similar microstructures, as revealed by the corresponding 1 H NMR spectra.These observations suggest that the stereochemistry of the step is mainly controlled by a chain-end mechanism.As a next step, the polymerisation reactions were carried out using microwave irradiation (MW).For these runs, summarized in Table 2, a [L,D-LA]/[Ti] ratio of 200 was used.As expected, the conversion increased with increasing reaction time, the conversion reaching 88% after 80 minutes (Table 2, entry 4).The maximum activity was obtained after 60 minutes (Table 2, entry 3), longer polymerisation time leading to some polymer decomposition (a brown colour and smell of aldehyde could be noticed).Careful analysis of the conversion versus time diagram (Figure 4) revealed that the polymerisation requires an activation time of about 20 minutes.Interestingly, we observed that in these polymerisation reactions carried out under MW conditions, lower M w and M n values were obtained than those obtained using the standard heating technique.

Conclusions
In conclusion, we have presented for the first time the use of a calixarene complex in the ring-opening polymerisation of L,D-LA using thermal or microwave heating.By comparison with experiments carried out with conventional thermal heating, the use of microwaves energy induced an increase of the polymerisation rate, the thermal method leading to a slightly better control of the molecular weight and molecular weight distribution.The most striking feature of the polymers formed is their partial isotactic-stereobloc microstructure, which is likely controlled by a chain end mechanism.Further studies are in progress which will concentrate on modified versions of the titanium complex with the aim of improving the activity as well as the stereochemical control of the polymerisation reaction.
Scheme 2: Ring opening polymerisation of L-lactide under microwave irradiations.

Figure 1 :
Figure 1: Variation of the activity as a function of the monomer/ catalyst ratio.

Figure 2 :
Figure 2: Variation of the molecular weight (M w ) of PLDA as a function of the monomer/catalyst ratio.

Figure 4 :
Figure 4: Conversion for L,D-LA against polymerisation time.
The temperature scale was calibrated with an indium reference sample (melting transition of indium 156.1 • C).Aluminum pans were filled with 0.010 g of the polymer sample.The thermal history of the polymers was eliminated by heating the specimen at a rate of 20 • C•min −1 to 200 • C and, by keeping the sample at this temperature for one minute, then by cooling at 20 • C•min −1 to 0 • C. The second and third scans were then recorded from 0 • C to 200 • C. The weight average molecular weight (M w ) and molecular weight distribution (M w /M n ) of the polymers were evaluated by size exclusion chromatography (HPLC-SEC) using a Perkin-Elmer type Series 2000 apparatus equipped with a Rheodyne 7010 injector (injection loop 200 μL, refraction index detector type LC-30 with two PL GEL columns (length: 30 cm; diameter: 5 μm; Polymer Labs)).The analyses were performed at 30 • C using chloroform as solvent, with a flow rate of 1.0 mL•min −1 using polymethylmetacrylate (PMMA)