Kinetic Study of Living Ring-Opening Metathesis Polymerization with

Communication pubs.acs.org/JACS

Kinetic Study of Living Ring-Opening Metathesis Polymerization with Third-Generation Grubbs Catalysts Dylan J. Walsh,†,‡ Sii Hong Lau,†,‡ Michael G. Hyatt,§ and Damien Guironnet*,† †

Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States § Department of Chemistry, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States S Supporting Information *

complexes remains relatively unexplored in comparison to the depth of knowledge gained over the years for olefin metathesis reactions catalyzed by five-coordinate ruthenium-based olefin metathesis catalysts.7,10−17 Here, we report an in-depth analysis of the kinetics of living ROMP catalyzed by Grubbs third-generation catalysts. Our study led us to develop a rate law for the living ROMP initiated by G3 that includes an inverse-order dependency in pyridine. Furthermore, we demonstrate that in solution G3 is primarily a monopyridine adduct. Both results combine to validate the unexpected zero-order dependency of initiator under standard polymerization conditions. We started our kinetic study of G3 catalyzed ROMP by determining the polymerization order in monomer and catalyst. A series of polymerizations of N-hexyl-exo-norbornene-5,6dicarboximide (NB1) was performed at constant initial monomer concentration (0.05 mol/L) with varying amounts of 1 in CH2Cl2 at 25 °C (Scheme 1). The rate of monomer

ABSTRACT: The rate of living ring-opening metathesis polymerization (ROMP) of N-hexyl-exo-norbornene-5,6dicarboximide initiated by Grubbs third-generation catalyst precursors [(H 2 IMes)(py) 2 (Cl) 2 RuCHPh] and [(H2IMes)(3-Br-py)2(Cl)2RuCHPh] is measured to be independent of catalyst concentration. This result led to the development of a rate law describing living ROMP initiated by a Grubbs third-generation catalyst that includes an inverse first-order dependency in pyridine. Additionally, it is demonstrated that one of the two pyridines coordinated to the solid catalyst is fully dissociated in solution. The monopyridine adduct formation is confirmed in solution by 1H DOSY (diffusion-ordered NMR spectroscopy), and a Van’t Hoff analysis of the equilibrium between mono- and dipyridine adducts (extrapolated Keq,0 ∼ 0.5 at 25 °C). Finally, the difference in polymerization rates between two catalyst precursors is demonstrated to correspond to the difference in coordination strength between the two pyridines, suggesting that the catalytic species involved in the polymerization’s rate-determining step is not coordinated to pyridine.

Scheme 1. Ring-Opening Metathesis Polymerization of NHexyl-exo-norbornene-5,6-dicarboximide Initiated by a Grubbs Third-Generation Catalyst

L

iving polymerizations are powerful synthetic tools that have enabled the access to a wide variety of well-defined macromolecules with varying length, composition, and architectures.1,2 The precision of these synthetic methods relies exclusively on controlling the rates of each elementary polymerization step (initiation, propagation, transfer, and termination).2 Within these techniques, ring-opening metathesis polymerization (ROMP) of high ring strain cyclic monomers by Grubbs third-generation (G3) catalysts offers a rare combination of narrow molecular weight distributions at very high monomer conversions, fast polymerization rates, and good functional group tolerance.3−6 The precision of this method is a result of the fast and quantitative initiation step, enabled by the lability of the pyridine ligand coordinated to the ruthenium center, and the absence of any undesired chain transfer/termination reactions.3,7−9 ROMP catalyzed by G3 has been widely implemented for the synthesis of a multitude of polymer architectures that have found applications in drug delivery, self-assembly materials, and sequence controlled polymers.4−6 Despite this ubiquity, the polymerization pathway of ROMP initiated by six-coordinate third-generation Grubbs © 2017 American Chemical Society

conversion was monitored over time for each polymerization by H NMR spectroscopy, and the final polymers were characterized by gel permeation chromatography (GPC). The living character of the polymerizations was confirmed by the first-order monomer consumption (illustrated by a linear plot of ln([NB1]/[NB1]o) vs time, see Supporting Information Figure S8), the molecular weight of the polymer increasing with decreasing catalyst concentration, and the narrow molecular weight distribution (Table 1). To our surprise, however, all the polymerizations appear to occur at the same rate (Table 1, kobs: slope of ln([NB1]/[NB1]o) vs time plot), i.e., the rate is independent of catalyst concentration. The same trend was also 1

Received: July 29, 2017 Published: September 25, 2017 13644

DOI: 10.1021/jacs.7b08010 J. Am. Chem. Soc. 2017, 139, 13644−13647

Communication

Journal of the American Chemical Society

were monitored in situ by 1H NMR spectroscopy. The rate of monomer consumption remained first-order, and the rates of polymerization decreased with lower loadings of 1 (Figure 1a). Analysis of the ln−ln plot of kobs versus [1] revealed that under flooded pyridine conditions, ROMP is first-order in [1] (Figure 1b). Finally, the pyridine dependency for ROMP was determined by performing a series of polymerizations at constant catalyst and initial monomer concentrations with various pyridine loadings. In order to ensure pseudo-first order conditions, these polymerizations were performed in the presence of a large excess of pyridine (from 20 to 80 equiv vs [1]) (Figure 1c). Under these flooding conditions, the rate of polymerization shows a clear inverse first-order dependency of pyridine resulting in a rate law of the polymerization shown in eq 1. A series of polymerizations were performed at lower pyridine loadings to probe the limits of the pyridine flooding regime. In order to plot this set of data, it is necessary to consider the pyridine released in solution by the catalyst precursor (potentially 0 to 2 equiv pyridine per ruthenium).11 The combination of the zero-order dependency in catalyst observed in absence of any additional pyridine, the first-order in ruthenium and the inverse first-order pyridine dependency under flooding conditions are consistent only in the case where one equivalent of pyridine is released from the starting dipyridine complex. This dissociation would yield an equal concentration of ruthenium catalyst and free pyridine in solution, resulting in the apparent zero-order dependency of G3 (in the absence of extra pyridine) as the concentration terms cancel each other out in the rate law. Under this assumption, the rate of polymerization of 1, in the absence of any additional pyridine, falls on the linear regression obtained under flooding conditions (Figure 1c). This implies that under polymerization conditions ([Ru]0 = 0.0018 mol/L) 1 obeys eq 1 and also that during the polymerization, the ruthenium center is a singly coordinated pyridine species independent of any additional pyridine (within the concentrations studied).

Table 1. Polymerization of NB1 at Different [NB1]o/[1] Ratios in Absence of Any Additional Pyridinea entry

DP

[1] (mM)

Mn (theo)b

Mn (exp)b,c

Đc

kobsd

1 2 3 4

50 100 200 400

1.00 0.500 0.250 0.125

12,400 24,700 49,400 98,900

14,500 26,100 48,900 70,200

1.05 1.04 1.07 1.15

1.17 1.19 1.20 1.17

Polymerizations were carried out with [NB1]o = 0.05 M at 25 °C in CH2Cl2. bg/mol. cDetermined by GPC in THF at 40 °C versus polystyrene standards. dMeasured by monitoring the relative integration of the polymer and monomer olefin peaks using 1H NMR spectroscopy, (1/min). a

observed in toluene, THF and with catalyst 2 (see Supporting Information, Figures S9, S10, S11). This result is inconsistent with traditional living polymerization kinetics, in which the rate shows a first-order dependency on the monomer and the initiator.2 Therefore, we concluded that ROMP of norbornenetype monomers initiated by G3 must follow a different rate law or include additional terms. A previous case of zero-order kinetics has been reported for the living ROMP of norbornene. In this example, the polymerization initiated by a titanacyclobutane was zero-order in monomer due to an intramolecular rate-determining step.18 This unexpected zero-order dependency in G3 motivated us to consider the polymerization mechanism. For a polymerization to proceed, at least one of the two pyridines ligated to G3 must dissociate from the ruthenium center to enable the coordination of a monomer.4−7,13 Pyridine and monomer are then expected to compete for this coordination site throughout the polymerization. Studies on Grubbs first- and secondgeneration catalysts established that the rate of olefin metathesis is inversely proportional to the concentration of unbound phosphine.19,20 By analogy, we hypothesized that the polymerization rate law should have an inverse dependency on pyridine concentration. Data already present in the literature hints at the validity of our hypothesis in two ways. First, the addition of pyridine to ROMP catalyzed by G3 was shown to slow down the polymerization, and second, the addition of a strong acid to scavenge pyridine results in increased rates of polymerization.12,21−24 To probe this hypothesis, we performed a series of polymerizations to determine the order of catalyst in the presence of excess pyridine (50 equiv). The polymerizations

Rp = −

[Ru]o × [NB1] d[NB1] = k papp dt [pyr(x)]

(1)

The presence of a monopyridine ruthenium center in solution was initially counterintuitive as G3-type complexes are traditionally synthesized as dipyridine complexes.8 However, the monopyridine complex has been shown to form upon applying high vacuum to solid samples of 1.8 We isolated the

Figure 1. (a) Plot of ln([M]/[M]o) versus time for the ROMP of NB1 (CH2Cl2, 25 °C, [NB1] = 0.15 M, 50 equiv pyridine), linear regressions can be found in the Supporting Information (Table S4). (b) Plot of ln(kobs) versus ln ([1]) for the ROMP of NB1 (CH2Cl2, 25 °C, [NB1] = 0.15 M, 50 equiv. pyridine). (c) Plot of ln(kobs) versus ln[py] for the ROMP of NB1 (CH2Cl2, 25 °C, [NB1] = 0.15 M). Red dot corresponds to the rate of 1 in absence of extra pyridine. 13645

DOI: 10.1021/jacs.7b08010 J. Am. Chem. Soc. 2017, 139, 13644−13647

Communication

Journal of the American Chemical Society monopyridine in high yield by performing multiple sublimation cycles in benzene. The chemical structures of complex 1 and 2 in solution were studied by NMR spectroscopy. Both 1 and 2 exhibit two independent sets of pyridine signals by 1H NMR spectroscopy and in both cases, one of the two pyridines has the same chemical shifts as the corresponding free pyridine (see Supporting Information, Figures S1 and S2). A 1H DOSY experiment performed on 1 showed that the two pyridines have different diffusivities, which are larger than the diffusivity of the rest of the ruthenium complex (NHC and benzylidene), see Supporting Information Figure S13. Moreover, the pyridine with the chemical shift identical to free pyridine has the largest diffusivity. This can be rationalized by the presence of a free pyridine in solution that exchanges with the coordinated pyridine of G3. The 1H DOSY of complex 2 is similar to complex 1 in that bromopyridine had a higher diffusivity than the ruthenium complex; however, both bromopyridine molecules have the same diffusivities (see Supporting Information Figure S15). This suggests that the bromopyridines are exchanging faster than the DOSY NMR time scale and that the measured diffusivity is an average between a bromopyridine with a small diffusivity (coordinated) and one with a large diffusivity (free). Overall, these results are consistent with the hypothesis that G3 exists as the monopyridine adduct in solution at 25 °C. The final evidence supporting the formation of the monopyridine complex in solution at room temperature was obtained by studying complex 1 in CD2Cl2 at low temperature. At −88 °C, spiking a solution of 1 with additional pyridine resulted in the emergence of new pyridine signals (see Supporting Information, Figure S16), suggesting that the dipyridine complex was present in solution. Additionally, the 1 H NMR of a mixture of the mono- and dipyridine complexes at −88 °C showed two alkylidene signals. These alkylidene peaks coalesce into a single peak upon heating (coaslescence at −60 °C). The chemical shift of this peak (which represents the weighted average between mono- and dipyridine adducts) was used to determine an equilibrium constant at various temperatures (from −20 °C to +15 °C with 5 °C increments). These equilibrium constants were used to generate a Van’t Hoff plot, which is used to determine the enthalpy of equilibrium (39.9 kJ/mol), entropy of equilibrium (118 J/(mol K)), and the equilibrium constant at room temperature, Keq,0 ∼ 0.5 (Scheme 2, Figure 2). This implies that under the polymer-

Figure 2. Van’t Hoff plot for the equilibrium between mono- and dipyridine complexes in solution.

representing the thermodynamic equilibrium (K(x) eq ) between the coordination of pyridine and monomer, and a second term for propagation (kp) to give the rate law in eq 3 (Scheme 3a). Scheme 3. (a) Simplified Representation of the ROMP Mechanism Initiated by G3; (b) Equilibrium Reaction between Bromopyridine and Pyridine Coordination for the Formation of the Corresponding Pentacoordinated Ruthenium Center

Under this model, the ratio of the rates of polymerization by 1 and 2, in the presence of an equal concentration of catalyst, monomer, and their corresponding pyridine, should be equal to the equilibrium constant between pyridine and bromopyridine coordination to the ruthenium center (Scheme 3b, eq 4). (x) k papp = k pKeq = kp

Scheme 2. Equilibrium Reaction between Mono Pyridine and Dipyridine Complexes

[RuNB] × [pyr(x)] [Rupyr(x)] × [NB1]

(2)

R (px) = −

[Ru(x)]o × [NB1] d[NB1] = k pKeq(x) dt [pyr(x)]

R p(Br)

Keq(Br) × [Ru Br ]o × [pyr(H)]

R p(H )

=

Keq(H ) × [Ru H ]o × [pyr(Br)]

=

(Br ) Keq (H ) Keq

(3)

= K pyr (4)

First, 2 was found to polymerize NB1 4.8 times faster than 1 in the presence of 50 equiv of their respective pyridine, i.e., Rp(Br)/Rp(H) = 4.8. Second, pyridine was determined to coordinate 4.8 times more strongly than bromopyridine, i.e., Kpyr = 4.8 (see Supporting Information, Figure S23). The agreement between these two values suggests that the difference in rates between the two catalyst precursors, 1 and 2, can be solely attributed to the relative coordination strength of the pyridines.7 This result also implies that the catalyst species involved in the rate-determining step of the polymer-

ization conditions used here ([Ru]0 = 0.001 mol/L), at least 99% of the ruthenium complex in solution is coordinated to a single pyridine molecule. Finally, the comparison of the rates of polymerization measured for 1 and 2 provides another insight into the polymerization mechanism. Assuming that the equilibrium between pyridine and norbornene coordination is reversible, then the rate constant of the polymerization kapp p from eq 1 can be broken up into two terms (eq 2). With the first term 13646

DOI: 10.1021/jacs.7b08010 J. Am. Chem. Soc. 2017, 139, 13644−13647

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(5) Leitgeb, A.; Wappel, J.; Slugovc, C. Polymer 2010, 51, 2927− 2946. (6) Sutthasupa, S.; Shiotsuki, M.; Sanda, F. Polym. J. 2010, 42, 905− 915. (7) Love, J. A.; Morgan, J. P.; Trnka, T. M.; Grubbs, R. H. Angew. Chem., Int. Ed. 2002, 41, 4035−4037. (8) Sanford, M. S.; Love, J. A.; Grubbs, R. H. Organometallics 2001, 20, 5314−5318. (9) Black, G.; Maher, D.; Risse, W. In Handbook of Metathesis; Grubbs, R. H., Ed.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2002; Vol. 124, pp 2−71. (10) Ż ukowska, K.; Szadkowska, A.; Trzaskowski, B.; Pazio, A.; Pączek, Ł.; Woźniak, K.; Grela, K. Organometallics 2013, 32, 2192− 2198. (11) Trzaskowski, B.; Grela, K. Organometallics 2013, 32, 3625− 3630. (12) Dunbar, M.; Balof, S.; LaBeaud, L.; Yu, B.; Lowe, A.; Valente, E.; Schanz, H.-J. Chem. - Eur. J. 2009, 15, 12435−12446. (13) Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746−1787. (14) Camm, K. D.; Martinez Castro, N.; Liu, Y.; Czechura, P.; Snelgrove, J. L.; Fogg, D. E. J. Am. Chem. Soc. 2007, 129, 4168−4169. (15) Higman, C. S.; Lummiss, J. A. M.; Fogg, D. E. Angew. Chem., Int. Ed. 2016, 55, 3552−3565. (16) Sanford, M. S.; Love, J. A. In Handbook of Metathesis; Grubbs, R. H., Ed.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2002; Vol. 124, pp 112−131. (17) Song, J.-A.; Choi, T.-L. Macromolecules 2017, 50, 2724−2735. (18) Gilliom, L. R.; Grubbs, R. H. J. Am. Chem. Soc. 1986, 108, 733− 742. (19) Sanford, M. S.; Ulman, M.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 749−750. (20) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543−6554. (21) Radzinski, S. C.; Foster, J. C.; Matson, J. B. Macromol. Rapid Commun. 2016, 37, 616−621. (22) Radzinski, S. C.; Foster, J. C.; Chapleski, R. C.; Troya, D.; Matson, J. B. J. Am. Chem. Soc. 2016, 138, 6998−7004. (23) Slugovc, C.; Demel, S.; Stelzer, F. Chem. Commun. 2002, 34, 2572−2573. (24) P’Pool, S. J.; Schanz, H. J. J. Am. Chem. Soc. 2007, 129, 14200− 14212. (25) The rate determining step of the ROMP and the chemical structure of the complex involved with it (potentially a 14-electron ruthenium center or a 16-electron ruthenium norbornene complex) cannot be identified from these experiments. This is the focus of ongoing research in the group. (26) Lin, T.-P.; Chang, A. B.; Chen, H.-Y.; Liberman-Martin, A. L.; Bates, C. M.; Voegtle, M. J.; Bauer, C. A.; Grubbs, R. H. J. Am. Chem. Soc. 2017, 139, 3896−3903. (27) Moatsou, D.; Hansell, C. F.; O’Reilly, R. K. Chem. Sci. 2014, 5, 2246−2250.

ization contains no pyridine, even though pyridine is involved in the pre-equilibrium step.25 In conclusion, kinetic and thermodynamic evidence establishes key mechanistic features for the highly active G3 catalysts. First, in solution the precatalysts (H 2IMes)(Rpy)2(Cl)2RuCHPh are fully dissociated to the pentacoordinate monopyridine derivatives (H 2 IMes)(Rpy)(Cl)2Ru=CHPh resulting in the release of an equivalent of pyridine per molecule of precatalyst. This gives rise to polymerizations with an apparent zero-order rate dependence of G3, because [pyr] and [Ru]o cancel out in the rate law. Experimentally, this means that at constant initial monomer concentration, polymers with any degree of polymerizations can be synthesized in the same amount of time. Second, the ratio of the polymerization rates with complexes 1 and 2 corresponds to the difference in coordination strength between pyridine and bromopyridine. This result implies that both ruthenium complexes are the precursor to the same ruthenium catalyst involved in the rate-determining step of the polymerization. The development of this rate law allows for the determination of the apparent rate constant of propagation for any monomer, which is critical for the synthesis of precise polymeric architectures.22,26,27

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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/jacs.7b08010. NMR spectra, polymerization procedures, polymer characterization, and rate studies (PDF) CIF file for the mono pyridine complex (CIF)

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AUTHOR INFORMATION

Corresponding Author

*[email protected] ORCID

Damien Guironnet: 0000-0002-0356-6697 Author Contributions ‡

These authors contributed equally.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank Materia Inc. for the generous gift of Grubbs catalysts, the Department of Chemical and Biomolecular Engineering at the University of Illinois at Urbana−Champaign for start-up funds, and Danielle Gray with the George L. Clark X-ray facility for her assistance with X-ray diffraction. Major funding for the 500 MHz Bruker CryoProbe was provided by the Roy J. Carver Charitable Trust (Muscatine, Iowa; Grant #15-4521) to the School of Chemical Sciences NMR Lab.

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REFERENCES

(1) Polymeropoulos, G.; Zapsas, G.; Ntetsikas, K.; Bilalis, P.; Gnanou, Y.; Hadjichristidis, N. Macromolecules 2017, 50, 1253−1290. (2) Müller, A. H. E.; Matyjaszewski, K. In Controlled and Living Polymerizations; Müller, A. H. E., Matyjaszewski, K., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2009. (3) Choi, T.-L.; Grubbs, R. H. Angew. Chem., Int. Ed. 2003, 42, 1743−1746. (4) Bielawski, C. W.; Grubbs, R. H. Prog. Polym. Sci. 2007, 32, 1−29. 13647

DOI: 10.1021/jacs.7b08010 J. Am. Chem. Soc. 2017, 139, 13644−13647