Communication Cite This: Organometallics XXXX, XXX, XXX−XXX
Biodegradable PHB from rac-β‑Butyrolactone: Highly Controlled ROP Mediated by a Pentacoordinated Aluminum Complex Francisco M. García-Valle,† Vanessa Tabernero,† Tomás Cuenca,† Marta E. G. Mosquera,*,† Jesús Cano,*,† and Stefano Milione*,‡ †
Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación en Química “Andrés M. del Río” (IQAR), Universidad de Alcalá, Campus Universitario, 28871 Alcalá de Henares, Spain ‡ Dipartimento di Chimica e Biologia “Adolfo Zambelli″/DCB, Università degli Studi di Salerno, via Giovanni Paolo II, 132 Fisciano, I-84084 Salerno, Italy S Supporting Information *
ABSTRACT: The diphenoxyimine five-coordinated aluminum complex [AlMeL2] (1), (L = N-(2,6-diisopropylphenyl)phenoxyimine), has been synthesized and fully characterized. The mononuclear structure observed in the solid state by Xray diffraction analysis is maintained in solution, as shown by diffusion-ordered NMR spectroscopy (DOSY). Complex 1 is an active ROP catalyst able to provide well-controlled living ring-opening polymerization of rac-BBL at 100 °C, with PDI = 1.03, in the presence of BnOH to give the biodegrable polyester poly(hydroxybutyrate) (PHB). The suggested active species of this catalytic process, the aluminum complex [Al(OBn)L2] (2), has been synthesized and fully characterized. DFT calculations have been carried out to study the influence of the catalytic active species pocket over the polymer molecular weight control. Moreover, 1 is also active in the copolymerization of rac-β-butyrolactone and L-lactide to provide random copolymers. ROP of lactides and lactones,12 including β-butyrolactone,13 providing living catalytic processes in some cases. Nevertheless, none of the compounds described so far have given good performances in the ROP of β-butyrolactone in terms of activity and/or control over the polymerization process.13,14 Within phenoxyimine aluminum compounds, we are interested in five-coordinated aluminum complexes featuring two phenoxyimine ligands, [AlRL2]. These derivatives have a coordination environment similar to that imposed by tetradentate ONNO ligands, such as salen, but the absence of the bridge linking the two phenoxyimine units could induce a more flexible and labile coordination geometry15 around the metal center. In this way, a good balance between the appropriate steric hindrance and the accessibility to the metal can be met and unexpected catalytic performances can be achieved. Surprisingly, these complexes have been scarcely investigated in the ROP of cyclic esters. Herein, we describe the synthesis and characterization of a mononuclear diphenoxyimine aluminum complex, [AlMeL2] (1), (L = N-(2,6diisopropylphenyl)phenoxyimine), and its application in the ROP of β-butyrolactone, where it has been proven to be very active. The suggested active species of this catalytic process, the aluminum complex [Al(OBn)L2] (2), has also been synthesized and fully characterized.
P
oly(hydroxybutyrate) (PHB) is a naturally polyester produced by microorganisms under unbalanced growth conditions as intracellular carbon and energy reserves. Differently from the starch-derived plastics which are moisture sensitive, the highly isotactic PHB produced by bacteria is a thermoplastic material with good resistance to ultraviolet light and hydrolytic degradation. However, a broader range of applications1 for this polymer is limited by its high production costs and by the fact that only a highly isotactic microstructure is produced by microorganisms.2 An attractive synthetic pathway for the preparation of aliphatic polyesters is the ring-opening polymerization (ROP) of cyclic esters. This process has the advantage of allowing an effective control over the properties of the produced polymer.3 Hence, an interesting path to give PHB would be the ROP of rac-β-butyrolactone. However, because of the relative inertness of β-butyrolactone (BBL), to date, few examples of efficient catalysts in the ROP of BBL have been reported, and even fewer are those able to produce stereoregular polymers.4−6 In this sense, aluminum compounds bearing different tetradentate ONNO-type ligands have also been successfully employed in the ROP of cyclic esters.7 Notably, aluminum complexes with salen,8,9 dialkoxy-diimino,9 salan,10 or salalen11 ligands allow achieving polylactide (PLAs) with a wide range of iso-/heterotacticities. However, aluminum complexes with bidentate ON-type ligands have been less explored, although phenoxyimine aluminum complexes, [AlR2L], can initiate the © XXXX American Chemical Society
Received: November 23, 2017
A
DOI: 10.1021/acs.organomet.7b00843 Organometallics XXXX, XXX, XXX−XXX
Communication
Organometallics
the base, while the methyl group C(1) constitutes the top vertex of the pyramid. The Al−Cmethyl distances, 1.965(9) and 1.936(9) Å, are within the values reported for half-salen monoalkyl derivatives (1.925−1.995 Å range).16 As well, the Al−O and Al−N bond lengths are in agreement with the reported literature data; however, the Al−O distances (1.749(5)−1.787(6) Å) are within the shorter distances reported (1.75−1.85 Å range), while the Al−N distances (2.107(6), 2.123(6) Å) are within the longer ones described (1.95−2.15 Å range). This structural feature could indicate a certain lability of the Al−N bonds. The nuclearity of 1 was also investigated in solution through a Diffusion Ordered NMR SpectroscopY (DOSY) experiment (Table S1 and Figure S6 in the SI).17 The result showed that the mononuclear structure observed in the solid state is retained in solution. Polymerization Studies. Complex 1 was assessed as an initiator for the ring-opening polymerization of rac-βbutyrolactone (BBL) in toluene solution at 100 °C in the presence of 1 equiv of benzyl alcohol (BnOH) as cocatalyst. Representative results are reported in Table 1. Almost quantitative conversions of 100 equiv of BBL were achieved within 5 h (run 1, Table 1). The turnover frequency (TOF) was 18.0 h−1. The activity displayed by 1 compares well with those of the most active Al complexes in the ROP of BBL (Table S5 in the SI). A solvent-free experiment (run 2, Table 1) was carried out to prove the stability of the aluminum system under industrial conditions, and the activity was higher than when using toluene as solvent. For a more in-depth investigation of the polymerization process, the reaction was tracked by analyzing the product mixtures sampled from the reactor at given reaction times. The plot of ln([BBL]0/[BBL]t) versus time was linear, indicating that the polymerization process is first order in monomer concentration with instantaneous initiation. The apparent propagation rate constant, kapp, was 0.018 ± 0.001 min−1 (Figure 2a). GPC analysis of the isolated polymer shows that experimental number-average molecular weights (Mn(exptl)) increase linearly with monomer conversion. The values obtained are in optimal agreement with the theoretical values, assuming the growth of one macromolecular chain per added alcohol equivalent (Figure 2b). This, together with the nearly constant PDI values, is in accordance with a controlled ROP process. At lower polymerization temperature (80 °C), the complex was still active, although the activity decreased and satisfactory
Complex 1 was readily prepared through the classical alkane elimination route with trimethylaluminum in hexane (Scheme 1). Scheme 1
The formation of the aluminum derivative was evidenced by H and 13C NMR (Figures S1−S3 in the SI) and elemental analysis. Low-temperature 1H NMR experiments showed four signals for the isopropyl methyl groups, indicating that in this case the rotation around the N−C bond is restricted. Nevertheless, at room temperature, only one broad signal is observed, instead of the two expected signals under free rotation of the C−N bond. This spectroscopic observation agrees with a fluxional behavior in solution according to a decoordination−coordination process of the Al−N bonds (Figures S4 and S5 in the SI). Single crystals suitable for X-ray diffraction analysis were obtained. The molecular structure is shown in Figure 1, and 1
Figure 1. ORTEP plot for 1 showing thermal ellipsoids plots (30% probability). Hydrogen atoms and methyl substituents of the iPr groups are omitted for clarity.
selected bond distances and angles are given in Table S3 in the SI. The geometry around the aluminum center is a distorted square-based pyramid, where the oxygen atoms and the nitrogen atoms of the ligands are nearly coplanar and form Table 1. ROP of rac-β-Butyrolactone Initiated by 1/BnOH runa
BBL:1:BnOH
time (min)
conversiond (%)
Mn(theor)e
Mn(exptl)f
PDIf
1 2b 3c 4 5 6 7 8
100:1:1 100:1:1 100:1:1 100:1:2 100:1:5 100:1:10 200:1:1 400:1:1
300 150 510 180 150 120 840 2880
90 95 75 96 94 97 97 93
7.8 8.2 6.5 4.2 1.7 0.9 16.8 32.1
7.4 6.4 6.1 4.7 1.9 1.1 15.6 25.7
1.03 1.06 1.08 1.07 1.08 1.15 1.09 1.07
All reactions, unless noted otherwise, were carried out in 2.0 mL of toluene, with [1] = 10 mM and [BBL] = 1 M at 100 °C. bIn bulk. Polymerization temperature 80 °C. dMolecular conversion determined by 1H NMR spectroscopy (CDCl3, 298 K). eCalculated molecular weight using Mn(theor) (kg mol−1) = 86.09 × ([BBL]0/[ROH]0) × BBL conversion. fExperimental molecular weight Mn and polydispersity (PDI) determined by SEC in THF using polystyrene standards and corrected using the factor 0.54. a c
B
DOI: 10.1021/acs.organomet.7b00843 Organometallics XXXX, XXX, XXX−XXX
Communication
Organometallics
Figure 2. (a) Pseudo-first-order kinetic plot for ROP of rac-βbutyrolactone by 1 (kapp = 0.018 ± 0.001 min−1, R2 = 0.978). (b) Plot of number-averaged molecular weights (■, Mn(exptl)) and the corresponding theoretical values (○, Mn(theor)) versus monomer conversion using 1 for rac-β-butyrolactone polymerization. Conditions: [1]0 = 10.0 mM, [BBL]0:[I]0:[BnOH]0 = 100:1:1, 100 °C, toluene as solvent.
Figure 3. Steric maps and percent buried volume (%Vbur) of the model of the active species formed by 1/BnOH. The isocontour curves are given in Å.
reactions that generally depress the control exerted by the catalytic system over the polymerization process. It is worth noting that the catalytic pocket of the salen Al complex featuring the N,N′-bis(3-adamantyl-5-methylsalicylidene)-2,2dimethyl-1,3-propanediamine ligand, one of the most active Al catalysts but one having scarce control over the polymerization process,14c is substantially more open with a Vbur value of 65.7% (Figure S11 in the SI). Aluminum complexes that are effective in both homopolymerization and copolymerization of β-butyrolactone with Llactide remain scarce.4f,21 As a proof of principle, a copolymerization experiment was carried out by using 100 equiv of both monomers in toluene solution at 100 °C. After about 24 h, near-complete conversion of both monomers was achieved; the isolated polymeric product featured a monomodal molecular weight distributions with a moderate dispersity (Mw/Mn = 1.95). 1H NMR analysis indicated that the mole fractions of BBL and LA in the polymer were similar to those in the feed. Thus, complex 1 in combination with BnOH is an effective catalyst for the synthesis of rac-β-butyrolactone/L-lactide copolymers. The chain microstructure was further investigated by 13C NMR spectroscopy. All peaks due to the different monomer sequences were observed (Figures S18−S20 in the SI). In particular, the resonances for the lactide-butyrolactone heterodiad (at 68.7 and 19.6 ppm) were clearly detected and confirmed that both monomers are enchained in the same macromolecule. Thermal analysis by differential scanning calorimetry (DSC) revealed that the copolymer is amorphous, displaying a single glass transition temperature at 31 °C (Figure S22 in the SI). The microstructure disclosed by 13C NMR analysis and the thermal DSC studies is very close to that of a random copolymer:22 i.e., the two monomers are randomly distributed along the polymer chain. In conclusion, the diphenoxyimine five-coordinated aluminum complex [AlMeL2] (1), (L = N-(2,6-diisopropylphenyl)phenoxyimine) promotes the controlled ring-opening polymerization of rac-BBL in the presence of 1 equiv of BnOH with PDIs between 1.03 and 1.09. The high steric hindrance around the metal center would be responsible for this highly controlled polymerization behavior, hampering transesterification reactions (Figure 3). The end group analysis of the polymer products and the protonation reaction of 1 with BnOH suggests that the polymerization proceeds through the classical coordination/insertion mechanism with a ring-opening via acyl oxygen bond cleavage. BnOH acts as a chain transfer agent with the metal catalyst leading to the rapid immortal ROP of racBBL. This complex is also active in the copolymerization of rac-
monomer conversion was achieved after 8 h (run 3, Table 1). In the presence of additional amounts of BnOH (runs 4−6, Table 1), the activities increased; as such, with the [Al]/ [BnOH] molar ratio 1:10, near-complete monomer conversion was reached in 2 h. A similar behavior was already observed in amino(ether)phenolate tin(II) complexes.18 As well in those cases, the experimental number average molecular weights matched with the theoretical values. This behavior is indicative of fast and reversible chain transfer between growing and dormant macroalcohols during the polymerization process and proves that effective conditions for “immortal” polymerizations were attained.19 However, higher monomer loading led to a diminution of control over the polymerization process, as indicated by the discrepancy between the experimental and expected molecular weights at a monomer to initiator ratio of 400:1 in the feed. In this case, high Mn could be achieved. To get a better knowledge of the active species in this process, a stoichiometric reaction of 1 and 1 equiv of BnOH was performed in benzene-d6. The reaction was monitored by 1 H NMR, and the CH4 evolution is evident. This alkane elimination afforded the benzyloxy aluminum complex with two phenoxyimine ligands [Al(OBn)L2] (2), which would correspond to the active species. The higher steric demand imposed by the benzyloxy moiety with respect to the methyl group would slow down the rotation of the diisopropylphenyl groups around the N−C bond, as shown by the 1H NMR spectrum of 2, where those groups appear as four independent signals. Complex 2 was isolated and fully characterized (Figures S8− S10 in the SI). In order to gain further insight into the characteristics of the title catalytic system, we computed the Gibbs free energy profile of the propagation step with the aid of DFT calculations, and the calculated activation barriers are consistent with the temperature needed experimentally to achieve high conversions (Figure S23 in the SI). To obtain a better understanding of the steric environment determined by the two phenoxyimine ligands, we determined the steric map reporting the altimetry isocontour lines that delimitate the encumbered zones of the ligands in the proximity of the active site.20 In this map the metal atom is placed at the center and the complex is oriented with the nitrogen atoms in the axial positions (Figure 3). As can be inferred from the deep groove in the equatorial belt of the map, the catalytic pocket of active species is compressed by the aryl rings on the iminic nitrogen. The percent of buried volume (%Vbur) is 71.8. Two phenoxyimine ligands close the access to the metal center, inhibiting the secondary intra- and interchain transesterification C
DOI: 10.1021/acs.organomet.7b00843 Organometallics XXXX, XXX, XXX−XXX
Communication
Organometallics β-butyrolactone and L-lactide, affording copolymers with a random microstructure.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.7b00843. Additional text, figures, and a table giving experimental details, X-ray crystallographic data, and additional data (PDF) Accession Codes
CCDC 1585562 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Authors
*E-mail for M.E.G.M.:
[email protected]. *E-mail for J.C.:
[email protected]. *E-mail for S.M.:
[email protected]. ORCID
Jesús Cano: 0000-0002-6643-7534 Stefano Milione: 0000-0002-3473-1480 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We acknowledge the MICINN (I3 program SPI1752XV0), UAH (CCG08-UAH/PPQ-4203 and UAH-AE-2017-2), and MINECO (CTQ201458270-R) projects for financial support. F.M.G.-V. acknowledges the UAH for a fellowship.
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DOI: 10.1021/acs.organomet.7b00843 Organometallics XXXX, XXX, XXX−XXX
