Controlled room temperature ROP of L-lactide by ICl₃: a simple halogen-bonding catalyst

Abstract

Halogen-bonding ROPactivation of L-lactide monomer by ICl₃ at room temperature leads to well-controlled poly(L-lactide)s of predictable molecular weights and narrow molecular weight distributions.

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Halogen bonding (XB) is commonly defined as a charge-transfer interaction involving halogens as electrophilic sites.¹ The attractive nature of XB is highly selective and directional, which makes them new and reliable items in the array of weak interactions. Thus, the deliberate crystal engineering relying on halogen bonded molecular units has demonstrated a remarkable ability in the elaboration of complicated supramolecular structures.² Furthermore, recent studies have reported the design of halogen bonded functional materials with applications in solid state synthesis, non linear optics, liquid crystals, imprinted polymers and very recently, XB has been also considered as a rational approach in drug design.³

Even if iodine-based structures have been used to promote polymerization of styrene and vinylether derivatives, (tetrahydro)furans and several cyclophanes,⁴ to the best of our knowledge, very limited interest has been devoted to use of halogens as catalysts in polymerization reactions. As far as the self-assembling process is concerned, the formation of supramolecular complexes supported by X⋯O=C halogen bonds is not a common feature⁵ and ring-opening polymerization (ROP) of (di)lactones has been attempted.

Herein, we demonstrate the possibility of using iodine trichloride (ICl₃) to promote the ROP of L-lactide (LA) in a selective and controlled manner at room temperature. Quite interestingly, the simple commercial ICl₃ proved to activate both the monomer and the alcohol initiator, presenting a simplicity that some of the recent non-organocatalytic systems do not have due to the use of co-catalysts or their simple non-commercially availability.⁶ Electrophilic activation of carbonyl groups with Lewis acids is a well-established method for enhancing their reactivity and selectivity toward nucleophilic addition.⁷ Here the halogen bonding capability of the ICl₃catalyst was first assessed by infra-red spectroscopy. The monitoring of a CHCl₃ solution of LA under ICl₃ addition results in a continuous shift of the ν_C=O maximum frequency band from ca. 1759 to 1772 cm⁻¹, consistent with an electron donation from the carbonyl group toward the iodine (Fig. 1).⁸ The C=O vibrational signal shifts mainly during the initial titration step with a maximum displacement observed for a catalyst-to-LA molar ratio of ∼3. This result suggests that the carbonyloxygen atoms may interact with at least one ICl₃viaXB when an excess of ICl₃ is used. As shown by ¹³C NMR (Fig. 2), the addition of one molar equivalent of ICl₃ with respect to LA monomer results in a clear downfield shift split of the carbonyl group present at 168.49 ppm (Δ ≈ 1.8 ppm). Methyl and methine carbons signals are also split and shifted to lower field, attesting for the strong XB interaction between the iodine and oxygen atoms. Since two sets of signals (α, β, γ and α′, β′, γ′) are present at r.t., we might expect a really slow interaction exchange between both LA and ICl₃ at room temperature.

Fig. 1 FT-IR wavenumber shifts observed by titration of LA with ICl₃ (carbonyl absorption, solvent = CHCl₃).

Fig. 2 ¹³C NMR spectrum of a LA/ICl₃ mixture (1/1) in CDCl₃.

Since alcohols are used as nucleophilic intiatiors in ROP of lactides, a possible interaction between ICl₃ and a representative alkyl primary alcohol (11-bromo-1-undecanol, 11-BU) was subsequently investigated by using ¹H NMR spectroscopy. When 11-BU was added to 1 molar equivalent of ICl₃, the hydroxylproton (Hγ) was significantly affected as indicated by a large downfield shift of the OH resonance (Δ ≈ 7.4 ppm), consistent with OH⋯Clhydrogen bonds (HB). This strong electron-withdrawing effect was also observed for methyleneprotons in α (Hϕ) and β-positions (Hε) of the OHgroup as characterized by shifts of 0.25 and 0.2 ppm, respectively (Fig. 3).

Fig. 3 ¹H NMR spectra of 11-BU (bottom) and an 11-BU/ICl₃ mixture (1/1) (top) in CDCl₃.

Combined multinuclear NMR and FT-IR spectroscopy results suggest that both monomer and initiator interact with the ICl₃catalyst through strong intermolecular XB and HB interactions, respectively. For that reason, ICl₃ was used as a possible catalyst for the ROP of LA using 11-BU as the initiator (Scheme 1).

Scheme 1

The polymerization of LA was carried out in CHCl₃ at r.t. using 11-BU as initiator for different monomer-to-initiator-to-catalyst ratios ([LA]₀ = 2.3 M, Table 1).

Table 1 Molecular characterizations of poly(L-lactide)s as obtained using 11-BU (I) and ICl₃ (C) as initiator and catalyst, respectively.^a

Entry	[LA]0/[I]0/[C]0	Time/h	Conv (%)^b	Mnth/g mol^−1	Mnexp^c/g mol^−1	PDI^c
a Conditions: [M]0 = 2.3 M, solvent: CHCl3, r.t. b Determined by ^1H NMR spectroscopy and/or gravimetry. c Molecular weight and polydispersity index as determined by gel permeation chromatography in THF after appropriate Mark-Houwink-Sakurada parameters application.
1	50/1/1	23	26	1900	1300	1.1
2	50/1/1	71	35	2500	2500	1.3
3	174/1/3	66	22	5500	4800	1.4
4	174/1/10	23	36	9000	9800	1.2
5	174/1/10	44	64	16000	14000	1.3
6	174/1/15	44	86	21600	21300	1.4

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Due to the slow intermolecular exchange between ICl₃ and LA (cf.Fig. 2), the polymerization occurs slowly at room temperature when an equimolar quantity of ICl₃ is used regarding the initiator (Table 1, entries 1 and 2). If 71 h are required to lead to poly(L-lactide) (PLA) chains with a polymerization degree (DP) of 18, excess of catalyst gradually increases the propagation kinetics and molecular weights up to 21 kg mol⁻¹ are obtained within 44 h (entry 6). Comparison between the PLA molecular weights (M_nexp) and those calculated gives a linear fit up to 21,000 g mol⁻¹, consistent with a controlled polymerization. Gel permeation chromatograms show a Gaussian distribution of molecular weights for each sample, with polydispersity indexes (PDIs) varying from 1.1 to 1.4.

A plausible polymerization pathway is through a double activation of both initiator and monomer mechanism in which initiation occurs when a pronounced nucleophilic alcohol reacts with a LA-ICl₃ complex to form the mono-adduct, and the α-chain end of the growing PLA bears an ester functionality derived from the alcohol (eqn (1)).⁹

Polymerization proceeds when the terminal ω-hydroxylgroup (activated by ICl₃) acts as a nucleophile to facilitate further chain extension. It is important to note that the number of ICl₃ molecules necessary to activate both monomer and the alcohol initiator is not known precisely and either one or at least two molecules might be involved into the activation process.

While ¹H NMR analysis of PLA consistently identifies both expected end-groups (Fig. 4), electrospray ionization mass spectrometry measurement (ESI-MS) shows almost exclusively peaks corresponding to the BrC₁₁H₂₂O(C(O)CH(CH₃)O)_nH population doped with Na⁺ (Fig. 5). Simply and doubly charged most intensive population signals agree perfectly well with the expected macromolecular structures and GPC data of a representative PLA (Table 1, entry 1, M_nexp = 1300 g mol⁻¹). In Fig. 6, one of the signals from the Fig. 5 population, namely BrC₁₁H₂₂O(C(O)CH(CH₃)O)₁₆H, Na⁺, is expanded. The computed isotopic distribution for the same signal reproduces the experimental signal almost perfectly.

Fig. 4 ¹H NMR analysis of a poly(L-lactide) as obtained by LA ROP from 11-BU and ICl₃ as initiator and catalyst, respectively.

Fig. 5 ESI mass spectrum of PLA (Table 1, entry 1) simply (○) and doubly (●) charged (observed charges: Na⁺).

Fig. 6 Comparison of the 1425–1431 m/z fragment of the ESI-MSspectrum in Fig. 5 (bottom) with the isotopic distribution computed for the following species: BrC₁₁H₂₂O(C(O)CH(CH₃)O)₁₆H, Na⁺ (top).

In conclusion, the ability of ICl₃ to activate electrophilic substrates through halogen bonding was demonstrated by NMR and FT-IR spectroscopies. The catalytic activity of the XB donor towards ROP produced narrowly dispersed PLA of predictable molecular weights. Elevated temperature experiments are currently under study to evaluate a possible kinetic improvement and will be the topic of a forthcoming paper.

Experimental part

Materials

L-Lactide (GALACTIC, Belgium) was recrystallized from dried toluene and stored in a glove box under dry nitrogen atmosphere before use. 11-Bromo-1-undecanol (Aldrich, 99%) was dried by three successive azeotropic distillation by addition of tetrahydrofuran and stored in a glove box under dry nitrogen atmosphere before use. Iodine trichloride (Aldrich, 95%) was used without any purification. Tetrahydrofuran (THF) and chloroform (CHCl₃) solvents were dried using a MBraun SolventPurification System (model MB-SPS 800) equipped with alumina drying columns.

Characterizations

FT-IR analyses were performed in a solid state by using a Fourier Transform Infra-Red Bruker Tensor 27 Spectrometer (6000–600 cm⁻¹) equipped with a Miracle micro-ATR from Pike. Lactide-ICl₃ mixtures were prepared by dissolving LA and ICl₃ in chloroform. The solution was slowly evaporated and the fine mixture analyzed after 5 min. ¹H and ¹³C NMR spectra were recorded using both a Bruker AMX-300 and Bruker AMX-500 apparatus at r.t. in CDCl₃ (30 mg/0.6 ml). The molecular mass measurements as well as the end-group determinations were performed on a Waters QToF2 mass spectrometer equipped with an orthogonal electrospray (ESI) source (Z-spray) operated in positive ion mode. PLA was dissolved in acetonitrile in order to approximately achieve 10⁻⁴ M concentrations, as estimated from the molar mass determined by GPC analysis. The solution was infused into the ESI source at a rate of 5 μl min⁻¹ with a Harvard syringe pump. Typical ESI conditions were: capillary voltage: 3.1 kV; cone voltage: 80 V; source temperature: 80 °C and desolvation temperature: 120 °C. Dry nitrogen was used as the ESI gas. The quadrupole was set to pass ions from 100 to 3000 Th and all ions were transmitted into the pusher region of the time-of-flight analyzer where they were mass-analyzed with a 1 s integration time. Data were acquired in continuum mode until acceptable averaged data were obtained. Size exclusion chromatography (SEC/GPC) was performed in THF at 35 °C using a Polymer Laboratories liquid chromatograph equipped with a PL-DG802 degasser, an isocratic HPLCpumpLC 1120 (flow rate = 1ml min⁻¹), a triple detector: refractive index (ERMA 7517), capillary viscometry and light scattering RALS (Viscotek T-60) (Polymer Laboratories GPC-RI/CV/RALS), an automatic injector (Polymer Laboratories GPC-RI/UV) and four columns: a PL gel 10 μm guard column and three PL gel Mixed-B 10μm columns. PS standards were used for calibration.

General polymerization procedure

All polymerizations were performed in an inert atmosphere glovebox using previously dried vials. As an illustrative example: LA (200 mg, 1.4 mmol), and ICl₃ (30 mg, 0.13 mmol) were dissolved in CHCl₃ (0.3 g). The mixture was allowed to dissolved for 30 s in a screwed capped vial before the addition of 11-BU (2 mg, 0.008 mmol). The polymerization was stopped after 44 h by addition of few drops of acetone, precipitated in cold methanol, analyzed by ¹H NMR and SEC.

Acknowledgements

This work was partially supported by the Belgian Federal Science Policy Office (PAI6/27). O.C. is a Research Associate of the Belgian National Fund for Scientific Research (FRS-FNRS). Dr P. Gerbaux is gratefully thanked for the ESI-MS measurements.

Notes and references

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8. The concomittant presence of a minimum frequency band relative to the νC=O of the lactide free of interaction is always present at ∼1756 cm⁻¹ for a [ICl₃]₀/[LA]₀ < 2.
9. It is still not clear if more than one ICl₃ is required for the O-acyl cleavage of the LA monomer.

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