Controlled bulk polymerization of L-lactide and lactones by dual activation with organo-catalytic systems

Abstract

The acid–base catalytic system based on N,N-dimethyl-4-aminopyridine (DMAP) and a protic acid that has already been revealed to be efficient for the ring-opening polymerization (ROP) of L-lactide in solution at room temperature was tested for the same polymerization in bulk at 100 °C. As observed in solution, the presence of the DMAP·HX (X = Cl, CH₃SO₃, CF₃SO₃) salt enhanced yields. Linear and star-like polylactides with 3 and 4 branches were prepared. Polylactides were thus easily prepared reaching high molar masses (up to 75 000 g mol⁻¹ for linear PLLA and 140 000 g mol⁻¹ for star-like PLLA) with good control in less than 1 h. In all cases, the appearance of transesterification reactions was shown to occur only at very high yield. The ROP of lactones (ε-caprolactone and δ-valerolactone) was also investigated with the same catalytic systems in bulk conditions. In contrast to lactide polymerization, only the DMAP/DMAP·HOTf allowed lactone polymerization with a slower rate. However, the control over the molar masses remained very good. Block copolymers were also synthesized.

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Introduction

Polyesters such as polylactides, polylactones and their copolymers have attracted a great deal of attention due to their biodegradable and biocompatible properties that could allow their extensive use in the biomedical field for a wide range of applications including controlled drug delivery, absorbable sutures, medical implants, and scaffolds for tissue engineering.^1–3 Their synthesis generally requires the use of organometallic catalysts^3–8 leaving unwanted metallic residues in the polymer. As an alternative, since more than 10 years and the description of the first organo-catalyst (4-dimethylamino pyridine) for the ring-opening polymerization (ROP) of lactide,⁹ organo-catalyzed polymerizations has become a very attractive and active field, the ROP being the most studied.^10–14 Enzymes were also heavily studied as possible non-metallic catalysts, but polymerization rate is generally slow and high loading of enzyme is required.^15–21 Therefore, the development of efficient organic catalysts that will enable the synthesis of well-defined functional polymeric materials received significant attention. As a consequence, many catalytic systems were described going from electrophilic to nucleophilic activation. For instance, the controlled ROP of several monomers could be catalyzed by weak to strong acids,^11,22–27 thioureas,^28,29 amido-based catalysts,^30,31 alcohols,³² phenols,^33–35 pyridines,^9,36–40 phosphines,⁴¹ N-heterocyclic carbenes,^42–48 guanidines^43,49–52 and quaternary ammoniums.⁵³ All these studies were conducted at room temperature in organic solvents like dichloromethane, toluene or even benzene that could be inappropriate for sustainable chemistry and industrial use. Moreover, the molar masses described were moderate (up to 20 000 g mol⁻¹) which should be too low for some applications. In order to circumvent these issues, we present herein the bulk polymerization of L-lactide and lactones (ε-caprolactone and δ-valerolactone) with a very simple catalytic system based on 4-dimethylaminopyridine (DMAP) associated to 0.5 equivalent of a protic acid, that already revealed efficient in solution at 25 °C.⁴⁰ The synthesis of block copolymers was also investigated in bulk as a preferable process for industry. Several studies have already investigated organo-catalyzed bulk polymerization of lactide, but polymerizations were generally performed above 130 °C (up to 185 °C);^41,54–59 only one example at lower temperature was described, namely 100 °C with imidazole as the catalyst, leading to macrocycles.⁶⁰ For organo-catalyzed lactones polymerization in bulk, far more examples were described in the literature.^61–70

Experimental part

Materials

L-Lactide (98%, L-LA), p-phenylbenzyl alcohol (98%, p-PhBnOH), benzyl alcohol (98%, BnOH), trimethylolpropane (98%, TMP), pentaerythritol (99%, PeOH) and N,N-dimethyl-4-aminopyridine (99%, DMAP) were purchased from Aldrich. ε-Caprolactone (99%, ε-CL) and δ-valerolactone (98% δ-VL) were purchased from Alfa Aesar. Hydrochloric acid (37% in water solution) was purchased from Prochilab. Methanesulfonic acid (HOMs, 99.5%, Aldrich) and trifluoromethanesulfonic acid (HOTf, 98%, Acros organics) were used as received. Toluene, tetrahydrofuran and dichloromethane (stabilized with amylene) were purchased from Atlantic Labo. CH₂Cl₂ and CD₂Cl₂ were distilled from CaH₂ prior to use. THF and toluene were dried over sodium/benzophenone. L-Lactide was recrystallized three times from toluene and stored under nitrogen. ε-Caprolactone and δ-valerolactone were dried over CaH₂ and cryo-distilled before use. p-PhBnOH was recrystallized from dichloromethane and stored under nitrogen. DMAP was dried under vacuum before use. Other alcohols were used as received.

Characterization

¹H-NMR spectra were recorded on a Bruker Avance 400 apparatus at 400 MHz at 25 °C in CDCl₃. Polymer molar masses and dispersities were measured by size exclusion chromatography (SEC) on a PL-GPC50 Plus apparatus equipped with Tosoh G4000HXL, G3000HXL and G2000HXL columns (Eluent: THF, flow rate 1.0 mL min⁻¹, temperature: 40 °C), either with RI and UV detectors and a polystyrene standards calibration or with triple detection (RI, Light Scattering and viscosimetry) with dn/dc = 0.058 mL g⁻¹ for PLA. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed using a Voyager-DE STR (Applied Biosystems) spectrometer equipped with a nitrogen laser (337 nm), a delay extraction, and a reflector. The MALDI-TOF mass spectra represent averages over 100 laser shots. This instrument operated at an accelerating potential of 20 kV. Polymer (2 μL) and matrix (20 μL, dithranol) solutions in CH₂Cl₂ (10 g L⁻¹) were mixed with 2 μL of a sodium iodide solution (10 g L⁻¹ in methanol), which favors ionization. The final solution (1 μL) was deposited onto the sample target and dried in air at room temperature. Differential scanning calorimetry (DSC) measurements were performed on a TA instruments DSC Q100 from −100 to 180 °C at a heating rate of 10°C min⁻¹.

DMAP·HX synthesis

DMAP·HCl, DMAP·HOMs and DMAP·HOTf were prepared following our previously published synthetic protocol.⁴⁰ General procedure: DMAP (10 mmol, 1.22 g) is stirred with a stoichiometric amount of HX (HCl 37% in water solution, 1 mL; HOMs 0.96 g; HOTf, 1.50 g) in THF (20 mL) at room temperature for 1 hour to give a white precipitate. The salts were filtrated, dried under vacuum and stored under nitrogen to be used as is.

Ring-opening polymerization of L-lactide in bulk conditions

General procedure: a 10 mL Schlenck was flame-dried under vacuum and initiator (p-phenyl benzyl alcohol, 1.35 mg, 0.0069 mmol), DMAP (0.84 mg, 0.0069 mmol), DMAP·HOTf (1.88 mg, 0.0069 mmol) and L-LA (100 mg, 0.69 mmol) were successively added. The mixture was stirred under nitrogen at 100 °C. At the end, the reaction mixture was dissolved in 1 mL of CH₂Cl₂ and then the solution was poured into 30 mL of cold methanol to give white solid that was dried under vacuum. Monomer conversions were estimated by ¹H-NMR before precipitation, while molar masses and polydispersities were determined by size exclusion chromatography.

Ring-opening polymerization of ε-caprolactone and δ-valerolactone in bulk conditions

General procedure: a 10 mL Schlenck flask was flame-dried under vacuum and initiator (p-phenyl benzyl alcohol, 7.83 mg, 0.04 mmol), DMAP (4.87 mg, 0.04 mmol), DMAP·HOTf (10.89 mg, 0.04 mmol) and the corresponding cyclic ester (4 mmol) were successively added. The mixture was stirred under nitrogen at 100 °C until almost quantitative conversion was reached (>95%). Monomer conversion was estimated by ¹H NMR, while molar masses and polydispersities were determined by size exclusion chromatography.

ε-Caprolactone and δ-valerolactone ring-opening polymerization kinetics in bulk conditions

Kinetic studies of ε-caprolactone and δ-valerolactone polymerizations catalyzed by DMAP/DMAP·HX were monitored by ¹H NMR spectroscopy. General procedure: a 10 mL Schlenck flask was flame-dried under vacuum. Initiator (p-phenyl benzyl alcohol, 6.35 mg, 0.0345 mmol), DMAP (4.21 mg, 0.0345 mmol), DMAP·HOSO₂CF₃ (9.39 mg, 0.0345 mmol), and either ε-caprolactone (78.8 mg, 0.69 mmol) or δ-valerolactone (69.1 mg, 0.69 mmol) were then successively added. The reaction medium was then stirred under nitrogen at the desired temperature. Aliquots were periodically taken from the Schlenk tube and analyzed by ¹H NMR and SEC.

Synthesis of block copolymers in bulk conditions

A 10 mL Schlenk flask was flame-dried under vacuum and charged with the freshly distilled lactone (ε-CL or δ-VL, 4.0 mmol), DMAP (4.87 mg, 0.04 mmol), DMAP·HOTf (10.89 mg, 0.04 mmol), and the initiator (p-PhBnOH, 7.36 mg, 0.04 mmol). The flask was then immersed into an oil bath preheated at 100 °C and stirred magnetically for the desired time. After polymerization completion, an aliquot was taken off in order to characterize the first block by ¹H NMR and SEC. L-Lactide (576.0 mg, 4 mmol) was then added and after 1 h reaction at 100 °C, the copolymer was dissolved in dichloromethane and precipitated into pentane. The precipitated copolymer was then filtered, dried under vacuum at room temperature for 15 h, and characterized by ¹H and ¹³C NMR spectroscopy, SEC and DSC.

Results and discussion

Bulk ring-opening polymerization of L-lactide catalyzed by DMAP + DMAP·HX

Bulk polymerization of L-lactide was first investigated at 100 °C with DMAP + DMAP·HX (X = Cl, OMs, OTf) as the catalytic system using p-phenylbenzyl alcohol as the initiator (Scheme 1).

Scheme 1 Polymerization of L-lactide.

Results are summarized in Table 1. It was first checked that without any catalyst, ring-opening polymerization did not occur at such a high temperature (run 1, Table 1). The catalyst-to-initiator molar ratio was varied from 1/1 to 1/5, as well as the monomer-to-initiator ratio which was varied from 20/1 to 100/1. When 5 mol% of alcohol was used, polymerization was fast and high conversions were observed in 1 h with all the catalytic systems, even with DMAP alone (runs 2 to 6). No real beneficial effect of DMAP·HX was observed as already reported for polymerization in dichloromethane. When a larger molar mass was targeted (2 mol% of alcohol), DMAP as a unique catalyst was less efficient. Nevertheless, this compound was still quite effective alone in these conditions as 52% conversion was reached after 1 h reaction. The presence of the corresponding salt increased significantly the polymerization rate. For example, with the DMAP/DMAP·HOTf catalytic system, polymerization was almost quantitative in 1 h. This effect was even more pronounced for higher monomer-to-initiator ratio (run 16 vs. run 13, Table 1). The molar masses measured by ¹H NMR were in good agreement with the theoretical values. In addition, dispersities were fairly narrow (Đ < 1.2). Concerning the activation mechanism, one could expect a dual activation of both the chain-end by DMAP and the monomer by DMAP·HX as it is the case in solution and for other catalytic systems.^{28,40,71–75} Besides, the linear relationship between the molar mass and the conversion in agreement with theoretical molar masses (see ESI, Fig. S2†) and the low Đ suggested a well-controlled polymerization with fast initiation and minimal termination reactions.

Table 1 Bulk L-lactide polymerization catalyzed by DMAP + DMAP·HX with p-phenylbenzyl alcohol as the initiator at 100 °C^a

Run	DMAP (mol%)	DMAP·HX		Initiator (mol%)	Conversion^b (%)	Mnth^c (g mol^−1)	Mn NMR^d (g mol^−1)	Đ^e
		X	mol%
a L-LA: 100 mg; t = 1 h.b Conversion of monomer by ^1H NMR by comparing the integration of the methine peak of the monomer at 5.2 ppm to that of the polymer at 5.4 ppm.c Theoretical molar mass: Mnth = [LA]/[I] × MLA × yield + Minitiator.d Experimental molar mass determined by ^1H NMR by comparing the integration of the methine (CH) peaks of the polymer at 5.4 ppm and that of the aromatic protons of the initiator at 7.1–7.7 ppm (see Fig. S1 in ESI).e Dispersity determined by size exclusion chromatography in THF at 40 °C.
1	—	—	—	5	0	—	—	—
2	2	—	—	5	88	2700	2900	1.10
3	1	—	—	5	81	2500	2700	1.12
4	1	Cl	1	5	96	2900	2900	1.09
5	1	OMs	1	5	98	3000	2900	1.11
6	1	OTf	1	5	100	3100	3200	1.10
7	2	—	—	2	64	4800	4700	1.08
8	1	—	—	2	52	4000	4100	1.07
9	1	Cl	1	2	84	6200	6700	1.10
10	1	OMs	1	2	89	6600	6700	1.15
11	1	OTf	1	2	98	7200	7000	1.10
12	2	—	—	1	48	7100	6100	1.07
13	1	—	—	1	30	4500	4600	1.10
14	1	Cl	1	1	81	11 900	11 000	1.14
15	1	OMs	1	1	84	12 300	12 000	1.10
16	1	OTf	1	1	95	13 900	13 900	1.16

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To further evaluate the control of the polymerization, the reaction was monitored by MALDI-TOF mass spectrometry (Fig. 1). DMAP/DMAP·HOTf was the catalytic system and p-PhBnOH was the initiator. Aliquots were removed from the reaction mixture after 5, 10, 20, 40 and 60 minutes. Mass spectra clearly indicated that no transesterification occurred when conversions were less than 90%, meanwhile at higher conversions, transesterified lactide was present (minor peaks at 72 g mol⁻¹ interval). So, this side reaction only occurred when monomer was almost consumed.

Fig. 1 MALDI-TOF mass spectra of polylactide after 5, 10, 20, 40 and 60 min of reaction (polymerization conditions: p-PhBnOH 5 mol%; DMAP/DMAP·HOTf 5/5 mol%; 100 °C).

DSC measurements were also performed on the different samples (see ESI, Fig. S3†). Whatever the catalytic system, typical expected results for a PLLA of low molar masses were observed, i.e. a glass transition temperature around 50 °C and a melting temperature in the range of 130 °C.

Synthesis of poly L-lactic acids with larger molar mass and branched structures

The synthesis of polylactide with larger molar mass and/or branched structures was investigated. For this purpose, mono- or multi-alcohols (Scheme 2) were used as initiators under the same conditions (100 °C, 1 h), only with DMAP/DMAP·HOTf which appeared as the most active catalytic system. Results are summarized in Table 2. Under these conditions, at very high targeted molar masses (0.1 mol% of initiator, runs 20, 24 and 28), the conversion followed the number of branches (51, 78 and 95%, respectively) as the reaction rate was dependent on the concentration of hydroxyl groups. For the other cases, conversions were almost quantitative showing the efficiency of the catalytic system.

Scheme 2 Alcohols used as initiators for L-lactide polymerization.

Table 2 Bulk L-lactide polymerization catalysed by DMAP/DMAP·HOTf at 100 °C^a

Run	Initiator		OH group (mol%)	[M]/[I]	Conversion^b (%)	Mnth^c (g mol^−1)	Mn NMR^d (g mol^−1)	Mw SEC LS^e (g mol^−1)	Đ^f
	Alcohol	mol%
a L-LA: 720 mg; t = 1 h.b Conversion of monomer determined by NMR by comparing the ^1H NMR integration of the monomer methine (CH) peaks at 5.2 with those in the polymer at 5.4 ppm.c Theoretical molar mass: Mnth = [LA]/[I] × MLA × yield + Minitiator.d Experimental molar mass determined by ^1H NMR by comparing the integration of the methine (CH) peaks of the polymer at 5.4 ppm and that of the aromatic protons of the initiator at 7.2–7.5 ppm or the methine proton of the other chain-end(s) at 4.3 ppm (see for examples: Fig. S4–S6 in ESI).e Experimental molar mass determined by size exclusion chromatography in THF at 40 °C with Light Scattering detector (dn/dc = 0.058 mL g^−1).f Dispersity determined by size exclusion chromatography in THF at 40 °C.g Not determined.
17	BnOH	1	1	100	96	13 900	13 800	nd^g	1.23
18	BnOH	0.5	0.5	200	90	26 000	24 700	nd^g	1.25
19	BnOH	0.2	0.2	500	75	54 100	nd^g	nd^g	1.20
20	BnOH	0.1	0.1	1000	51	73 500	nd^g	nd^g	1.18
21	TMP	1	3	100	100	14 500	14 800	nd^g	1.10
22	TMP	0.5	1.5	200	97	28 000	28 200	nd^g	1.10
23	TMP	0.2	0.6	500	84	60 600	66 200	47 500	1.12
24	TMP	0.1	0.3	1000	78	112 400	nd^g	86 900	1.13
25	PeOH	1	4	100	98	14 200	15 300	nd^g	1.16
26	PeOH	0.5	2	200	99	28 600	29 500	23 300	1.16
27	PeOH	0.2	0.8	500	95	68 500	67 600	53 600	1.15
28	PeOH	0.1	0.4	1000	95	137 000	136 700	142 400	1.12

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Molar masses were evaluated by ¹H NMR and/or SEC with a light scattering detector. It could be observed a fairly good agreement between measured and theoretical molar masses. Moreover, the dispersities remained quite low (Đ < 1.3) indicating a good control of the polymerization. Polylactide with a wide range of molar mass and branched structures can be thus easily prepared. Again, the possible occurrence of transesterification reactions during the polymerization reaction was checked by MALDI-TOF mass spectrometry. PeOH was selected as the initiator (1 mol%). Aliquots were removed from the reaction mixture after several reaction times. Results are presented on Fig. S7 in ESI.† After 20 min of reaction corresponding to 84% conversion and a molar mass of 13 000 g mol⁻¹ (see ESI, Fig. S8†), molar masses were too high and no signal was observed by Maldi-Tof spectrometry. For shorter reaction times (up to at least 50% conversion), no side transesterification reactions was observed showing a good control of the polymerization. The polylactides thus obtained were also studied by DSC (see ESI, Fig. S9†). In all cases a glass transition temperature was observed around 50 °C, but a melting temperature around 130 °C is only observed for linear PLA.

In order to check further the control/livingness of the polymerization, extra monomer was added to the reaction mixture after almost quantitative consumption of the previous feed. As seen on Fig. 2, molar mass increased after each monomer feed and the dispersity remained low (Đ = 1.07–1.14), showing thus a very good control of the polymerization. Polylactide could also be used as a macroinitiator (Fig. 3).

Fig. 2 SEC chromatograms of PLLA after several monomer feedings (PLLA-1: first step, [M]/[I] = 100; PLLA-2: after first addition of monomer, [M]_total/[I] = 200, PLLA-3: after second addition of monomer, [M]_total/[I] = 500).

Fig. 3 Polymerization of L-lactide initiated by 4-arms star polylactide (PLLA-4).

Bulk ring-opening polymerization of lactones catalyzed by DMAP + DMAP·HX

The ROP of ε-caprolactone and δ-valerolactone was carried out in the presence of DMAP/DMAP·HX catalytic system and p-PhBnOH as the initiator in bulk at 100 °C (Scheme 3). In contrast to L-lactide, only the DMAP/DMAP·HOTf was able to catalyze the ROP of lactones. So the following study focused on this latter system.

Scheme 3 ROP of ε-caprolactone and δ-valerolactone catalyzed by DMAP/DMAP·HOTf with p-PhBnOH as the initiator.

Bulk ROP of ε-CL was then first investigated varying the polymerization conditions. Results are summarized in Table 3. The catalyst efficiency was substantially dependent on the catalyst loading. DMAP alone was considerably less efficient than when associated to DMAP·HOTf (runs 37 and 38 vs. run 36). It can also be noticed that the polymerization rate was much slower than in the case of LA, as more than 5 days were needed to reach almost completion and a polycaprolactone exhibiting a molar mass of 10 000 g mol⁻¹ (run 31) with a high catalyst loading. Nevertheless, this catalytic system was more efficient than other non-protic catalysts like thioureas/DBU for example. Besides, molar masses evaluated by ¹H NMR were in fairly good agreement with the theoretical ones, at least for low conversion, and dispersities remained quite low (<1.20). For higher conversion, agreement was lower and dispersities increased, probably due to the presence of side reactions for such long reaction times. Nevertheless, the polymerization control was further demonstrated by the linear fit of a plot of the molar mass with the conversion, with again an increase of the dispersities for high conversions (see ESI, Fig. S11†).

Table 3 Bulk ε-caprolactone polymerization catalyzed by DMAP/DMAP·HOtf with p-phenylbenzyl alcohol as the initiator at 100 °C^a

Run	DMAP (mol%)	DMAP·HOTf (mol%)	p-PhBnOH (mol%)	Time (h)	Conversion^b (%)	Mnth^c (g mol^−1)	Mn NMR^d (g mol^−1)	Đ^e
a ε-CL: 4 mmol.b Conversion of monomer determined by NMR by comparing the ^1H NMR integration of the monomer methylene (CH2) peak at 4.2 with that of the polymer at 4.05 ppm.c Theoretical molar mass: Mnth = [CL]/[I] × MCL × yield + Minitiator.d Experimental molar mass determined by ^1H NMR by comparing the integration of the methylene (CH2) peaks of the polymer at 4.05 ppm and that of the aromatic protons of the initiator at 7.2–7.5 ppm or the methylene proton of the other chain-end(s) at 3.65 ppm (see Fig. S10 in ESI).e Dispersity determined by size exclusion chromatography in THF at 40 °C.
29	5	5	5	66	95	2340	2080	1.20
30	5	5	1	15	10	1300	1290	1.12
31	5	5	1	135	92	10 400	10 800	1.45
32	10	10	1	16	18	2160	1820	1.06
33	10	10	1	40	29	3400	2950	1.09
34	10	10	1	113	73	8110	7000	1.34
35	10	10	1	136	83	9120	7690	1.38
36	2	—	2	213	26	1760	1870	1.25
37	2	2	2	210	71	4000	2860	1.36
38	2	2	2	243	90	5280	3280	1.36

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In order to get better insight into the polymerization control and more precisely the chain-end fidelity, MALDI-TOF mass spectrometry was performed on different samples (see ESI, Fig. S12 and S13†). In addition to the expected chain-ends, several other chain-ends were observed. Chains bearing DMAP moieties were probably obtained through nucleophilic attack of DMAP onto the monomer (side initiation) or a polymeric chain (transesterification reaction at the end of the polymerization as these chains were mainly observed at low molar mass). Some chains bearing carboxylic acid chain-ends were also observed.

They were probably obtained through side initiation or transesterification reaction by residual water at high conversion as they were only observed at low molar mass.

Polymerization of δ-valerolactone was also carried out in bulk conditions at 100 °C (Table 4). The catalyst-to-initiator molar ratio and the monomer-to-initiator ratio were varied. Polymerizations were much faster than for ε-CL but still slower than for LA as 48 h were needed to reach almost complete conversion, as expected for non-protic organo-catalysts. Polymers with controlled molar masses up to 9000 g mol⁻¹ and low dispersities were obtained, indicating fast initiation and minimal transesterification reactions.

Table 4 Bulk δ-valerolactone polymerization catalyzed by DMAP/DMAP·HOTf with p-phenylbenzyl alcohol as the initiator at 100 °C^a

Run	DMAP (mol%)	DMAP·HOTf (mol%)	p-PhBnOH (mol%)	Time (h)	Conversion^b (%)	Mnth^c (g mol^−1)	Mn NMR^d (g mol^−1)	Đ^e
a δ-VL: 4 mmol.b Conversion of monomer determined by NMR by comparing the ^1H NMR integration of the monomer methylene (CH2) peak at 4.3 with that of the polymer at 4.05 ppm.c Theoretical molar mass: Mnth = [VL]/[I] × MVL × yield + Minitiator.d Experimental molar mass determined by ^1H NMR by comparing the integration of the methylene (CH2) peaks of the polymer at 4.05 ppm and that of the aromatic protons of the initiator at 7.2–7.5 ppm or the methylene proton of the other chain-end(s) at 3.65 ppm (see Fig. S14 in ESI).e Dispersity determined by size exclusion chromatography in THF at 40 °C.
39	5	5	5	29	90	1990	1760	1.18
40	5	5	1	24	62	6340	6940	1.15
41	5	5	1	47	82	8370	8600	1.27
42	2.5	2.5	1	31	58	6030	5840	1.27

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This was further confirmed by the linear increase of the molar mass with the conversion, in agreement with theoretical molar masses (see Fig. S15 in ESI†). In order to get better insight into the polymerization control and more precisely the chain-end fidelity, MALDI-TOF mass spectrometry was performed (see ESI, Fig. S16†). It was observed mainly the expected chain-ends, but also few chains bearing carboxylic acid chain-ends that could be obtained through side initiation or transesterification reaction by water at high conversion as they were essentially observed at low molar mass.

Synthesis of block copolymers (poly(lactone-b-LLA))

In order to take advantage and to further show the controlled/living character of the active polymer chain end, the synthesis of diblock copolymers (poly(lactone-b-LLA)) was investigated (Scheme 4).

Scheme 4 Block copolymer synthesis of ε-caprolactone or δ-valerolactone with L-lactide catalyzed by DMAP/DMAP·HOTf with p-PhBnOH as the initiator.

As the rate of polymerization is by far slower for the lactones, it was decided to first polymerize the lactone for extended time (2 days for δ-VL and 5 days for ε-CL) and then to add LLA and let the polymerization run for 1 h. It should thus prevent the occurrence of transesterification reaction of the polylactide block. Moreover, for many other catalytic systems allowing the block copolymer synthesis of lactones and lactide, it was preferred to perform first the polymerization of the lactone block as the reinitiation of the lactide block from a primary alcohol was easier than the reinitiation of the lactone from a secondary alcohol. SEC traces showed unimodal distributions for both the first block and the block copolymer with an expected shift toward the higher molar masses for the block copolymers showing a good initiation of the lactide block from the polylactone block (Fig. 4). The block copolymers were further characterized through ¹H and ¹³C NMR spectrometry (see ESI, Fig. S17 and S18†). The formation of diblock copolymers was thus confirmed by ¹H NMR analysis with the disappearance of the signal at 3.60 ppm corresponding to the original PCL or PVL macroinitiator chain-end to the profit of a signal located at 4.35 ppm, corresponding to PLLA chain-end. Further evidence of the formation of block copolymers was provided by ¹³C NMR analysis as the carbonyl region exhibited only two peaks around 173 ppm and 169 ppm assigned to the carbonyl group of PCL or PVL and the carbonyl group of PLLA, respectively. The absence of additional peaks between these 2 peaks indicated that mixed sequences were not present, as it would be expected if transesterification reactions occurred.

Fig. 4 SEC chromatograms of block copolymers.

Block like structure of the copolymer was additionally confirmed by DSC analysis. In the case of PCL-b-PLLA, two melting peaks appeared clearly on the thermograms, each melting temperature corresponding to the melting temperature of both homopolymers (51 °C for the PCL block and 138 °C for the PLLA block, see ESI, Fig. S19†). In addition, glass transition temperature of the PCL block was observed at −53 °C. On the contrary, it was not possible to observe the T_g of the PLLA block as it overlaps with the melting temperature of the PCL block. For the PVL-b-PLLA, the thermograms exhibited a glass transition temperature at −25 °C above that of the PVL block that should around −50 °C (see ESI, Fig. S20†). An exothermic transition at 20–40 °C due to cold crystallization was also observed followed up by the melting peak of the PVL block at 49 °C. A broad melting peak for the PLLA block was also observed at 110 °C.

Conclusions

In this study, it was shown that very simple organocatalytic systems based on DMAP associated to a protic acid were able to catalyze the controlled ROP of L-lactide and lactones without any organic solvents. Precise polymerization of L-lactide could indeed be performed in bulk at 100 °C to give access to polylactide with high molar masses (up to 140 000 g mol⁻¹) and/or star-like structures in less than 1 h. Nevertheless, it was also shown that at very high yield, transesterification could occur. For lactone (ε-caprolactone and δ-valerolactone) polymerizations, longer reaction times were needed (several days) but the polymerization remained controlled with conversion up to 95%. Block copolymers were also successfully synthesized through sequential polymerization of the lactone and L-lactide.

Acknowledgements

The Agence Nationale de la Recherche (ANR) and the Chimie des Procédés et du Développement Durable Program (ANR-07-CP2D-15) are gratefully acknowledged for funding (J.K. and D.P. Fellowships). The authors would also like to thank Christelle Absalon and Christiane Vitry, from Bordeaux 1 University, for MALDI-TOF experiments.

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Footnotes

† Electronic supplementary information (ESI) available: ¹H and ¹³C NMR spectra, Maldi-Tof spectra, DSC thermograms, molar mass vs. conversion curves. See DOI: 10.1039/c4ra01239a

‡ Current address: Masaryk University, Department of Chemistry, Kamenice 5, Brno 62500, Czech Republic.

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