Multifaceted Synthetic Route to Functional Polyacrylates by

Article pubs.acs.org/Macromolecules

Multifaceted Synthetic Route to Functional Polyacrylates by Transesterification of Poly(pentafluorophenyl acrylates) Anindita Das and Patrick Theato* Institute for Technical and Macromolecular Chemistry, University of Hamburg, Bundesstrasse 45, 20146 Hamburg, Germany S Supporting Information *

ABSTRACT: Synthesis of functional polyacrylates by 4-dimethylaminopyridine (DMAP) catalyzed trans-esterification of poly(pentafluorophenyl acrylate) (polyPFPA) is reported. High fidelity and versatility of this strategy was exemplified by near quantitative conversion with diverse functional alcohols (primary, secondary as well as phenolic) featuring reactive groups like alkene, alkyne or acrylate, enabling further sequential functionalization using click chemistry. Co-integrating an equimolar mixture of allyl and propargyl alcohol produced an orthogonally clickable copolymer by thiol−ene and 1,3-cycloaddition reaction. Base catalyzed ester exchange allowed installation of acid labile Boc-L-serine to create amino acid pendent polymer keeping both NH2- and COOH-group free, thereby providing a facile route toward zwitterionic polymers. Reaction with 2-dimethylaminoethanol conferred dual pH and CO2 responsive polymers from the same reactive precursor. The synthetic strategy was further extended to attach alcohols obtained from natural resources such as geraniol, L-lactic acid or sesamol to engineer new renewable polymers. Even a graft copolymer with very high (93%) grafting density could be achieved utilizing PEG350−OH. The trans-esterification was found to be highly selective for primary alcohols over secondary alcohols and also to the activated PFP-ester over a normal ester such as poly(methyl acrylate). Using such selectivity, fluorescently tagged polymer could be synthesized by replacing only the PFP-ester of a poly(methyl acrylate-co-PFPA) with 1-pyrenemethanol. Further, PFPA was polymerized with 2.0 mol % diacrylate to produce a cross-linked gel network. The PFP-ester groups of the cross-linked gel could be quantitatively replaced with Boc-Lserine, which upon deprotection of the Boc group resulted in a novel zwitterionic hydrogel exhibiting pH-dependent swelling properties. Time-dependent FTIR experiment suggested fast kinetics of the reaction, making this synthetic route practically applicable for postpolymerization modification. Mechanistic investigation exposed involvement of both DMAP and the nucleophilic solvent N,N-dimethylformamide (DMF) in catalyzing the reaction. This also explains the reason as to why near quantitative conversion was achieved in DMF and not in the non-nucleophilic solvent 1,4-dioxane.

1. INTRODUCTION Functional polymers with well-defined architectures, molecular weight distribution, and precise location of the functional groups are of utmost importance in modern polymer research and neighboring disciplines. Despite the versatility and amplified tolerance to most functional monomers, controlled radical polymerization (CRP) techniques suffer from difficulties when it comes to creating a library of functional polymers with identical degree of polymerization and functional group distribution, highly essential for their structure−property relationship studies. Incompatibility of certain functionalities such as alkenes, alkynes, thiols, acrylates, and many others toward the polymerization conditions further add to their disadvantage. In this regard, postpolymerization modification1−4 offers a beneficial alternative approach for tailoring multifunctional macromolecules by introducing the dissenting functional group after the polymerization step. However, the success of this strategy is determined by the efficiency of the chemical handles employed for quantitative installation of functional moieties into the reactive precursor polymers. While there is a tremendous ongoing © XXXX American Chemical Society

research on polymer analogous reaction driven by selective and high yielding “click chemistry,”5−10 activated-ester amine chemistry4,11−16 still stands tall considering the effortless methods to synthesize the activated ester polymers, easy accessibility of functional amines, and mild reaction conditions. Nevertheless, in the process of installing a desired pendent functional group, it also changes the polymer backbone from ester to amide, which influences the intrinsic properties of the polymer chain such as Kuhn length, persistence length, solubility, and others, which may not be always desired. On the other hand trans-esterification of a polymeric-activated ester with functional alcohols will not only address this issue but also render additional advantages over its amine counterpart. For examples, unlike amines, alcohols can tolerate coexistence of many functional groups, such as acids, aldehydes and α,β-unsaturated carbonyl derivatives and thereby allows incorporation of alcohols featuring Received: October 19, 2015 Revised: November 23, 2015

A

DOI: 10.1021/acs.macromol.5b02293 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

catalytic amount (0.2 equiv) of p-toluenesulfonic acid (PTSA) in 1,4-dioxane for 15 h at 65 °C (Scheme 1, Table 1, entry 1).

those functionalities into the polymer side chain. Considering the biodegradability of esters and the abundant availability of functional alcohols from both natural and commercial sources, developing a generalized synthetic route for trans-esterification of activated ester polymers is an order of the day. Toward this line, although a few isolated examples have been reported, they reveal poor yield and offer limited opportunities in terms of structural diversity of the modified polymers.17−19 The synthetic challenge associated with this technique is the low conversion prevailing due to the backward reaction that has been partially addressed, though at the cost of using large excess of the reacting alcohol or removal of the released alcohol from time to time. Sawamoto and co-workers20,21 recently demonstrated an interesting possibility of transition metal catalyzed living radical gradient copolymerization in tandem with in situ transesterification of methyl methacrylate (MMA), but the methodology has not been expanded to be utilized as a generalized and versatile one for postpolymerization functionalization using functional alcohols. Even poly(pentafluorophenyl acrylate) (polyPFPA), the focus of the present work, has been attempted already and was found to be not suitable for transesterification.19,22 Nevertheless, considering multiple exciting properties of poly(PFPA) such as solubility in wide range of organic solvents, high reactivity toward amines, and availability of large number of controlled polymerization techniques for their preparation we envisaged it would be worth revisiting at the pros and cons of trans-esterification of polyPFPA with alcohols. In the present work, we establish, for the first time, a robust, versatile and comprehensive methodology for constructing multifunctional polyacrylates by 4-dimethylaminopyridine (DMAP) catalyzed trans-esterification of polyPFPA employing only stoichiometric amounts of the functional alcohols under mild reaction condition and elucidate mechanistic detail of the reaction pathway.

Table 1. Optimization of the Trans-Esterification of PolyPFPA with 3-Thiopheneethanol entry

catalyst

temp [°C]

solvent

time [h]

conversion from FTIR [%]

1 2 3 4 5

PTSA DMAP DMAP DMAP −

65 65 80 80 80

1,4-dioxane 1,4-dioxane 1,4-dioxane DMF DMF

15 15 15 15 15

negligible 52 75 quantitative 40

The progress of the polymer analogues reaction was monitored by following the disappearance of the signature carbonyl band of the PFP-ester at 1785 cm−1 using FTIR spectroscopy. This allowed us to separately identify the two ester bands with the progress of the reaction. For PTSA catalyst, the PFP-ester band intensity remained almost unchanged after the reaction carried for 15 h (Figure 1a). In addition, appearance of no new signal for the desired ester carbonyl illustrates the failure of acid mediated trans-esterification of polyPFPA. This prompted us to employ Lewis base catalyst, DMAP, utilized in acyl transfer of alcohols.28,29 Gratifyingly, a new band around 1732 cm−1 was identified in the FTIR spectrum due to formation of the desired ester polymer. However, strong signal appearing for PFP-ester suggested incomplete conversion (52%), which slightly improved (75%) by conducting the reaction at elevated temperature (Figure 1a and Table 1, entry 2 and 3). Interestingly, use of a more polar solvent DMF led to quantitative ester exchange as evident from the complete transfer of the ester band at 1785 cm−1 to 1732 cm−1. Nevertheless, in absence of DMAP under otherwise identical condition, very little conversion indicated the vital role of DMAP in the reaction. The newly formed polymer (P1) was purified by dialysis from THF and characterized by 1H NMR (Figure 1b). The chemical shifts (δ) for the thiophene protons at 7.27, 7.09, and 6.97 ppm in the substituted polymer closely matched with the aromatic protons of the 3-thiopheneethanol. In addition, the methylene protons (Ha) adjacent to the ester bond showed downfield shift (4.23 ppm) in comparison to Ha protons (3.70 ppm) of 3thiopheneethanol. Absence of characteristic bands for carboxylic acid around 1700 and 3500 cm−1 (broad) in the FTIR spectrum (Figure S1) of the purified polymer clearly eliminate the possibility for detectable concurrent side reaction due to hydrolysis. To test the general applicability of the present methodology, a library of functional polymers were synthesized from polyPFPA using structurally diverse alcohols. All the reactions were conducted at 80 °C in DMF for 15 h with 0.2 equiv of the catalyst. Table 2 illustrates successful installation of functionally diverse alcohols with very high efficiency. In most cases near quantitative conversion was achieved as calculated from FTIR measurements by comparing the area under the PFP-ester carbonyl peak before and after the reaction taken from the crude mixture. The integral of the peak at time (T = 0) was taken as 0% conversion. 2.2. Synthesis of Polymers with Clickable Side Chains. Polymers featuring “clickable” side groups are instrumental in the synthesis of more complex macromolecules with structural and functional diversity.9 However, synthesis of polymers with reactive pendent groups is often challenging due to incompat-

2. RESULTS AND DISCUSSION 2.1. Post-Polymerization Modification. To establish the reaction platform, the trans-esterification process was optimized with polyPFPA (1.0 equiv) and commercially available 3thiopheneethanol (1.2 equiv with respect to the repeat unit of polyPFPA). The synthetic route is depicted in Scheme 1. Scheme 1. Trans-Esterification of PolyPFPA with 3Thiopheneethanol

Conventionally, trans-esterification is achieved by an acid catalyzed pathway. The most common example includes synthesis of poly(ethylene terephthalate)23−25 a very important commercial polymeric material known for half a century. Even acid catalyzed transmethylation of fatty acid is popular in elucidating its composition in biolipids by gas chromatography.26,27 Therefore, we commenced our study by utilizing B


Article

Macromolecules

Figure 1. (a) IR spectra (selected region) of polyPFPA (black) and its postpolymerization modification with 3-thiopheneethanol at different conditions. (b) Proton NMR spectra of P1 (top) and 3-thiopheneethanol (bottom). ∗ denotes residual solvent peak from THF-d8.

in the proton NMR spectrum of P3 clearly demonstrated chemical inertness of the allyl group in the trans-esterification pathway. Similar to P3, direct polymerization of P4 from propargyl acrylate is difficult by radical pathway due to one of the possible side reactions31 such as (1) complexation of the alkyne group with Cu catalyst in ATRP, (2) homocoupling of alkynes during polymerization condition, and (3) uncontrolled chain termination by proton abstraction from the alkyne causing interference of the propagating radicals in cross-linked products formation and so forth. To overcome these side reactions, terminal alkyne is often protected with a trimethylsilyl group (TMS). Here lies the significance of our newly developed strategy that can produce P4 with quantitative yield avoiding any unwanted side reactions or additional steps due to deprotection. The peak at 2.6 ppm for He proton in the NMR spectrum of P4 confirms quantitative survival of the alkyne group during the postmodification of polyPFPA with the corresponding alcohol. Following our synthetic protocol, orthogonally clickable statistical copolymer32−35 P5 (Figure 2, topmost spectrum) could be successfully obtained using an equimolar (1:1) mixture

ibility of certain functionalities with the polymerization conditions. We developed a straightforward route to those polymers by integrating reactive alcohols featuring those functionalities (Scheme 2). For example, reaction with allyl and propargyl alcohols (Table 2, entries 3 and 4) produced P3 and P4 respectively, with almost quantitative yield as evident from FTIR spectra of the purified polymers (Figure S2). Both polymers were characterized by proton NMR spectroscopy (Figure 2). These two polymers featuring reactive side chains are interesting from a synthetic viewpoint as they can be readily subjected to a subsequent modification via thiol−ene or 1,3-dipolar cycloaddition reactions to synthesize tailor-made multifunctional polymeric architectures. Notably, direct radical polymerization of both allyl (meth)acrylate and propargyl (meth)acrylate often lead to an uncontrolled polymerization. Allyl groups are known to participate in cross-linking when the reaction approaches toward the end.30 In sharp contrast, the current synthetic approach offers synthesis of P3 from allyl alcohol without formation of any insoluble gel network. The alkenyl protons (Hb and Hc) detected between 5.0 and 6.0 ppm C


Article

Macromolecules

of allyl and progargyl alcohol. Formation of the copolymer was analyzed by comparing the 1H NMR spectrum of the copolymer with the individual homopolymers P3 and P4. Successful incorporation of both the allyl and propargyl alcohols in P5 was confirmed from the presence of all the characteristic signals attributed to the alkenyl (Ha, Hb, and Hc) and alkynyl (He) protons, and the two methylene protons of the allyl (Ha) and propargyl (Hd) ester bonds. Further comparing the integration of Hb:Hd [(Hd + Ha) − Hb)] protons revealed an incorporation ratio of 0.6:1 although the feed was 1:1. This can be attributed to either greater reactivity of propargyl alcohol for transesterification or lower boiling point of allyl alcohol might cause its little loss at elevated temperature causing incomplete conversion as also observed during the homopolymer synthesis. Competence of this strategy for constructing polymers with reactive side chains was further demonstrated by sequestering diolefinic geraniol, an active component of rose oil, into P6 that featured two allyl groups per side chain (Table 2, entry 6 Figure 3). Synthesis of such novel polymers with near quantitative conversion (95%) obtained from renewable sources36,37 might reveal exciting properties for new applications. The unique advantage of this methodology was further established by quantitative installation of 2-hydroxyethyl acrylate into polyPFPA producing P7 (Scheme 2) with pendent acrylate side chains. It is impossible to accomplish such linear polymer starting from a diacrylate monomer that would lead to crosslinked insoluble gel. No trace of PFP-ester peak in the FTIR spectrum of the purified polymer P7 suggested quantitative conversion (Figure S2). Unperturbed signals for the nonreacted acrylate protons (Hc, Hd, and He) along with considerable downfield shift of the Ha and Hb protons in the proton NMR spectrum of P7 ascertained the formation of the desired polymer (Figure 4b). It is noteworthy that the same reaction is impossible to conduct with 2-aminoethyl acrylates owing to the possible formation of the homocoupled Michael adduct between the amine and its own acrylate counterpart.38 Such polymers with pendent acrylate groups offer new avenues for designing multifunctional linear, graft or cross-linked polymers by thiol−ene click,39,40 Michael addition41 or nanocarriers by simply photo initiated cross-linking.42 To further demonstrate that, we conducted sequential functionalization43 of P7 with 1-hexanethiol by thiol−ene Michael addition to synthesize P7′(Figure 4c). Successful incorporation of 1hexanethiol in P7′ was evident from the nearly complete disappearance of the peaks for the olefinic protons (Hc, Hd, and He) and appearance of new signal for Hf, Hg, and Hh in addition to signals for alkyl chain protons between 1.6−0.72 ppm. 2.3. Synthesis of Stimuli Responsive and Amino Acid Functionalized Polymers. While all previous examples demonstrate the possibility of incorporating reactive alcohols, the present methodology also allows synthesis of stimuliresponsive polymers44−47 and amino acid pendent polymers48−51 by integrating alcohols featuring stimuli responsive functional moieties or hydroxyl functionalized amino acids (Scheme 3). Trans-esterification of polyPFPA with 2-dimethylaminoethanol produced P8 (Figure S3 and S4) with 95% conversion (Table 2, entry 8). P8 featuring tertiary amine groups that are sensitive to acid conditions are interesting for their pH responsive behavior.52 Recently, such polymers have also been projected as CO2 responsive polymers.53 Lewis base catalyzed ester exchange takes further advantage of incorporating acid labile alcohol, Boc-L-serine to produce amino

Table 2. Summary of Trans-Esterification of PolyPFPA with Various Functionalized Alcohols

D


Article

Macromolecules Scheme 2. Synthesis of Polymers with Pendent Reactive Side Groups

amino acid pendent polymers known in literature,50,51 either the COOH-group or the NH2− group is anchored to the polymer side chain. This strategy enables synthesis of polymers with both free amine and the acid functionality offering an facile approach to synthesize zwitterionic polymers,55,56 which in recent past have attracted great attention for their antifouling properties besides their other potential applicability in biomedical processing, ionic conductance, chemical separations, and so forth.57 2.4. Trans-Esterification with Secondary and Phenolic Alcohols. Besides primary alcohols, our methodology works equally efficiently with less nucleophilic secondary and phenolic alcohols (Scheme 4) with near quantitative conversions in most cases (Table 2). Reaction with cyclopentanol (1.5 equiv) resulted in polymer P10 with 97% conversion (Table 2, entry 10, Figure S5). Proton NMR spectra of P10 corroborated the attachment of the respective alcohol within the polymer chain (Figure S6). This prompted us to study the possibility of incorporating secondary alcohols from renewable sources. We next targeted naturally produced L-lactic acid, an carboxylic acid functionalized secondary alcohol largely employed in making polylactides, one of the most exploited biodegradable polymer in biomedical application besides their well-known contribution in other areas of research.58−60 Our methodology successfully demonstrated synthesis of novel lactic acid pendant polyacrylate P11 with complete conversion (Table 2, entry 11). The substituted polymer was fully characterized by both 1H NMR and FTIR spectroscopy (Figures S7 and S5). As earlier observed for P9, catalytic activity of DMAP was retained even in this case, manifesting again a unique example of acid group tolerance in the base catalyzed reaction. To expand the horizon of novel functional polymers obtained from sustainable resources, this time the reaction was carried out with sesamol, a phenolic alcohol produced from sesame oil seed. The synthesis of polymer P12 (Scheme 4 and Figure 6) again with quantitative conversion (Figure S5) employing inherently

Figure 2. 1H NMR spectra of P3, P4, and P5 in CDCl3. ∗ denotes a residual solvent peak.

acid pendent polymer (P9) (Scheme 3, Figure 5) with free C- as well as N-terminus. Appearance of an intense broad band in the FTIR spectrum of P9 between 1650 cm−1 to 1730 cm−1 indicates presence of all three types of carbonyl stretching contributed by the new ester, acid and amide of the serine derivative (Figure S4). Further, no trace of PFP-ester peak was observed, confirming quantitative conversion even with the same catalyst loading (0.2 equiv) illustrating no adverse effect of the carboxylic acid group on the catalytic activity of DMAP. The polymer was duly characterized by 1H NMR study (Figure 5). Ha proton of the polymer revealed downfield shift (4.43 ppm) on comparing with the free alcohol (3.82 ppm) and overlapped with the signal coming from Hb. Additionally, appearance of intense signal for the methyl protons of the Boc group at 1.45 ppm confirmed successful integration of Boc-L-serine within the polymer backbone. In the subsequent step, zwitterionic polymer54 could be engendered from P9 by N-Boc deprotection of the amine. For majority of E


Article

Macromolecules

Figure 3. Proton NMR spectrum of P6 in CDCl3. ∗denotes residual solvent peak.

Scheme 3. Synthesis of Stimuli Responsive and Amino Acid Functionalized Polymers

Figure 4. Proton NMR spectrum of P7 (b) plotted with the 2hydroxyethyl acrylate (a) in CD3OD and P7′ (c) in CDCl3. ∗ denotes residual solvent peak.

less nucleophilic aromatic alcohol illustrates the preponderance of this approach over all other methods earlier reported for transesterification of activated esters. While the current trend in polymer research is focused toward developing synthetic polymeric materials from renewable resources, a simple and straightforward strategy like ours for designing sustainable polymers such as P6, P11, and P12 from natural resources will be a substantial step toward this direction. Reactivity of polyPFPA toward both primary and secondary alcohols raised an interesting question regarding selectivity, if any, between them. To address this issue, we carried out the reaction of polyPFPA with equimolar mixture of two structurally similar, benzyl alcohol (1.2 equiv) and α-methylbenzyl alcohol (1.2 equiv) which individually showed quantitative and 88% conversion, respectively (Table 2, entry 2 and entry 13, Figure S8). Comparing the 1H NMR spectrum of the mixture (P14) with the individual polymers suggested predominant incorporation of the benzyl alcohol in P14 (Figure 7). However,

presence of very weak signal for Hc contributed by αmethylbenzyl alcohol revealed participartion of the secondary alcohol in trace amount. Further comparing the integration of Ha: Hc protons coming from the two alcohols showed an incorporation ratio of 0.12:1 illustrating reasonably high selectivity (89%) for the primary alcohol. 2.5. Synthesis of Water-Soluble Graft-co-polymer. Having successfully established trans-esterification of polyPFPA with small molecule alcohols, we extended this synthetic strategy to construct graft copolymer. To meet this target, polyethylene glycolmethyl ether (PEG350−OH) was treated with the polyPFPA following same procedure (Scheme 5). After 15 h, the reaction was 79% complete that could be raised to 93% by conducting the reaction at 100 °C for 42 h. The graft-co-polymer P15 was characterized by 1H NMR spectroscopy, GPC (Figure 8) and FTIR spectroscopy (Figure S9). The downfield shift of Ha F


Article

Macromolecules

Figure 5. Proton NMR spectrum of P9 (blue) compared with that of Boc-L-serine (black) in CD3OD. ‘*’denotes residual solvent peak.

Scheme 4. Trans-Esterification of PolyPFPA with Secondary and Phenolic Alcohols

protons (4.25 ppm) in the proton NMR spectrum of P15 along with appearance of signals from backbone protons clearly illustrate the incorporation of flexible PEG chain (Figure 8a). The GPC analysis (Figure 8b) revealed molecular weight (Mn) of the graft copolymer to be 19 400 g/mol in comparison to 12 600 g/mol of the parent polyPFPA indicating approximately 91% conversion as for full conversion the theoretically estimated molecular weight of P14 is 21 400 g/mol. In fact a conversion value of 91% corroborated nicely with that obtained from FTIR studies (93%). 2.6. Selectivity for Activated Ester. In the forgone discussion, we demonstrated postmodification of a homopolymer of PFPA with functional alcohols. We now illustrate selective trans-esterification of the PFP-ester in a statistical copolymer of poly(methyl acrylate-co-pentafluorophenyl acryl-

Figure 6. Proton NMR spectrum of P12 plotted with sesamol in CDCl3. ∗ denotes residual solvent peak.

G


Article

Macromolecules

Figure 7. 1H NMR spectra of P2, P13, and P14 in CDCl3. ∗ denotes residual solvent peak.

93%, which is very encouraging considering the steric factor contributed by the bulky pyrene moiety that would have a negative impact on the conversion. Comparing the UV/vis and photoluminescence spectra of P16 with the parent polymer revealed presence of characteristic absorption and excimer band of pyrene in P16, additionally confirming dye labeling into the polymer chain (Figure 9b). Appearance of excimer emission band61 around ∼490 nm further supported polymer aggregation by π-stacking leading to broadening of peaks in the NMR spectrum of P16. This strategy creates possibilities for engineering other fluorescently tagged polymers of biological significance by replacing methyl acrylate monomer with water-soluble PEG or N-(2-hydroxypropyl) methacrylamide (HPMA). To understand whether the postmodification can be achieved even in a confined environment such as a gel matrix, where the mobility of the PFP-ester is restricted, we made a cross-linked polymer gel (P17) of PFPA using 2 mol % of 1,6-hexanediol diacrylate. The gel was characterized by FTIR spectroscopy that showed a strong band at 1784 cm−1 for PFP-ester and a weak band at 1734 cm−1 for diacrylate cross-linker (Figure S11a). It was also interesting to monitor whether the gel remains intact even after trans-esterification. That would clearly suggest no participation of the diacrylate linker in the trans-esterification reaction, which would otherwise transform the gel to sol. To demonstrate that, we functionalized the gel with Boc-L-serine in

Scheme 5. Synthesis of Graft-co-polymer P15

ate), poly(MA-co-PFPA) with 1-pyrenemethanol to produce fluorescently tagged statistical copolymer P16 (Scheme 6). 1 H NMR studies revealed broad peak in the aromatic region (around 8.00 ppm) attributed to pyrene protons in concomitance with downfield shift (5.67 ppm) of the methylene proton (Ha) in P16 (Figure 9a, top spectrum) suggesting effective integration of the dye into the polymer chain. Comparative study with the parent polymer (Figure 9a, middle) showed preservation of intense signal for Hb protons (3.55 ppm) even after substitution, suggesting nonparticipation of inactive methyl acrylate ester in the trans-esterification process. Broad nature of the spectrum of P16 indicates possibility of polymer assembly due to π-stacking of the pendent pyrene moieties. Further from the FTIR spectra (Figure S10), conversion was calculated to be H


Article

Macromolecules % conversion = IT − II/IF − II × 100

(1)

where II, IF, and IT and are the initial, final and the intermediate intensity at time T, respectively. Figure 10a shows no isosbestic point between the product and the reactant ester peaks suggesting the PFP-ester may not be directly converted to the desired ester. This was even more evident from the data shown in Figure 10b. Notably, the rate at which the signal for PFP-ester disappeared was not the same as the rate at which the new ester was formed. It is apparent that the blue curve followed the black one until a certain point and then it takes a deviation and shows nonlinear increase with time. To understand the process in depth, the reaction was conducted again, this time with DMAP (0.2 equiv) in DMF without the alcohol. Surprising, the PFP-ester peak was fully consumed even in absence of the alcohol. In turn, a new peak originated at 1758 cm−1.that completely disappeared and transformed to the desired ester (1732 cm−1) peak upon addition of 3-thiopheneethanol in the same reaction mixture (Figure 11a). These observations clearly suggested that in absence of the alcohol, the PFP-ester is reacting either with DMAP or DMF or both. To elucidate that, we repeated the reaction without DMAP and found the PFP ester peak strongly retained (Figure 11a) in this recipe confirming the catalytic role of DMAP in driving the reaction forward. However, it was expected that 0.2 equiv of DMAP can only replace 0.2 equiv of the PFP ester. The fact that the PFP-ester was completely consumed suggested the participation of the nucleophilic solvent DMF during the course of the reaction. We demonstrated this hypothesis by conducting a control reaction of polyPFPA with DMAP in a non-nucleophilic solvent such as 1,4-dioxane in absence of the alcohol (Figure 11b). Under similar conditions, only partial consumption of the PFP-ester peak was noticed (Figure 11b) after 3 h of carrying the reaction. This is in sharp contrast to our previous observation in DMF (Figure 11a) that showed complete consumption of the activated ester. Interestingly, addition of stoichiometric amount of DMF (1.2 equiv) into the same reaction mixture in 1,4dioxane resulted in the disappearance of the PFP-ester signal and reappearance of the peak at 1758 cm−1 with time, which perfectly matched with the one detected when the reaction was conducted in DMF without the alcohol. This clearly demonstrates, along with DMAP, DMF also contributes in driving the reaction forward, which comes as no surprise, as there are reports where DMF forms adducts with reactive acid derivatives.63,64 A similar type of reaction might be happening in this case as well. It is perhaps the same reason as to why we observe quantitative transesterification in DMF but not in 1,4-dioxane. Putting together all these information we proposed a reaction mechanism (Scheme 7) for the trans-esterification pathway. Initially the activated polyPFPA reacts with nucleophilic catalyst, DMAP to form an Nacylpyridinium type adduct29,65 I-1, which delivers the desired final ester by two pathways. I-1, being a highly reactive acid derivative can either react directly with the alcohol or a second activated ester I-2 is formed by the reaction between I-1 and the nucleophilic solvent DMF, which ultimately produce the final ester by alcoholysis. Considering the large excess of DMF, used as solvent, the second possibility is more realistic. The proposed mechanism can now explain the behavior of the kinetic plot (Figure 10b) Upto ∼20%, blue and black curve overlapped each other probably suggesting initially 0.2 equiv of DMAP is fully consumed until that point and then possibilities of multiple types of carbonyls simultaneously come into the picture. The

Figure 8. (a) 1H NMR spectrum of the graft-co-polymer P15 (blue) plotted with PEG350−OH (black). NMR spectrum of the graft-copolymer P15. (b) GPC profile of P15 and polyPFPA in THF.

Scheme 6. Synthesis of Fluorescently Labeled Statistical Copolymer P16

DMF that has earlier shown quantitative trans-esterification in the linear PFPA polymer. Indeed the polyPFPA gel (P17) could be quantitatively functionalized as determined from the FTIR spectra of the modified gel that revealed complete disappearance of the PFP-ester band and appearance of a broad band for the carboxylic acid and the amide of the Boc-L-serine (Figure S11a). Interestingly, after the derivatization, the gel was still not soluble suggesting the network structure remained intact. Subsequent removal of the N-Boc group with TFA could be successfully achieved in THF as observed by FTIR spectroscopy. Swelling of the serine functionalized polymeric network in water by adjusting the pH between 2.5 and 3.562 conferred zwitterionic hydrogel (Figure S11b). This method provides a powerful tool to fabricate functional hydrogels with numerous biologically important hydroxyl derivatives without changing the cross-link density or any other parameters as demonstrated herein. 2.7. Mechanism Investigation. To elucidate mechanistic aspects, we monitored the kinetics of the reaction of polyPFPA with propargyl alcohol in the presence of DMAP (0.2 equiv) by time dependent FTIR measurements (Figure 10a). During the reaction, the intensity of the polyPFPA ester peak at 1785 cm−1 decreased with the appearance of a distinct peak at 1742 cm−1 for the newly formed ester. The conversion was measured from the peak intensity as a function of time following eq 1. I


Article

Macromolecules

Figure 9. (a) 1H NMR stack plot of P16 (topmost) with poly(MA-co-PFPA) (middle) and 1-pyrenemethanol (bottom) in CDCl3. *denotes residual solvent peak. (b) Absorption (solid) and the emission (dotted) spectra of P16 (blue) and poly(MA-co-PFPA) (black) in CDCl3.

extinction coefficient of those various possible carbonyls (both intermediates and product) together contribute to the intensity and thus it shows irregularity which eventually saturates when the reaction in complete.

the most versatile polymeric activated ester for postpolymerization via amide bond formation, while the current results shows that in coming days it can be equally employed for transesterification with structurally diverse alcohols like never before. Abundant access to wide variety of functional alcohols makes this simple and straightforward strategy more approachable, thereby opening new doors for plethora of novel functional polymers, which might instigate new exciting properties for various applications. Besides merely being an alternate pathway for postpolymerization modification, it has lot more to offer, as polyesters are less stable or in other words more degradable under biological conditions that makes this chemistry even more appealing. The tolerance for various reactive functional groups such as acid, alkene, alkyne offers opportunities for constructing clickable polymer featuring those reactive side groups that

3. CONCLUSION In conclusion, we have illustrated a facile synthetic route to structurally diverse polyacrylates by DMAP-catalyzed transesterification of polyPFPA. The present synthetic strategy comes as a boon as it avoids many hitches associated with transesterification such as use of excess alcohol, continuous removal of the released product from the polymerization mixture, and intolerance to acid sensitive functional groups yet gives near quantitative conversion with all tested primary, secondary, or phenolic alcohols. Until now polyPFPA has been celebrated as J


Article

Macromolecules

Figure 10. (a) Kinetics of the trans-esterification of polyPFPA with propargyl alcohol. (b) Plot showing rate of conversion as a function of time.

Figure 11. (a) Selected region of the FTIR spectra of the reaction of polyPFPA with (blue) and without (black) DMAP in DMF and after adding alcohol (green). (b) Time-dependent FTIR spectra illustrating formation of the intermediate I-2 in 1,4-dioxane with 1.2 equiv DMF in absence of the alcohol.

remains an ever challenging task to achieve by direct polymerization. Even successful incorporation of highly reactive acrylate based alcohols reveals the preponderance of this methodology over its amine counterpart. Such a modular approach even provides access to stimuli responsive polymers or amino acid pendent polymers from a single reactive homo polyPFPA. Integrating alcohols from renewable resources, like geraniol, Llactic acid, or sesamol, demonstrates its compliancy in synthesis of sustainable polymers some of those might unravel new possibilities for future application. Selectivity of this methodology for only PFP-ester further add to its future impact in synthetic polyester chemistry as it would allow precise positioning of functional groups at selective locations without disturbing the other nonreactive ester groups present within a polymer chain. This will help engineering both in polyester backbone and without. One even can think of employing the current strategy in new polyester synthesis by step growth polymerization utilizing an AB or AB2 type monomer featuring both alcohols and activated esters groups together. Efforts in this direction for fabricating functional linear or hyperbranched polyesters are underway in our laboratory.

Scheme 7. Schematic Representation of the Mechanism of DMAP-Catalyzed Trans-Esterification of PolyPFPA in DMF

K


Macromolecules

■

4. EXPERIMENTAL SECTION 4.1. Materials. All chemicals were purchased from commercial sources and used as received, unless otherwise mentioned. Anhydrous dimethylformamide (DMF) was purchased from Sigma-Aldrich and passed over dry molecular sieves prior to use. Pentafluorophenyl acrylate (PFPA) was prepared according to literature procedure. 19 2(dodecylthiocarbonothioylthio)-2-methylpropionic acid was purchased from Sigma-Aldrich. 1,6-Hexanediol diacrylate was perchased from Alfa Aesar and passed through basic alumina before use. Azobis(isobutyronitrile) (AIBN) was recrystallized from methanol prior to polymerization. Poly(ethylene glycol)methyl ether was dried using a Dean−Stark apparatus prior to use. All the alcohols used were dried over anhydrous molecular sieves. 4.2. Structural Characterization. 1H NMR spectroscopy was performed on a Bruker 300 MHz FT-NMR spectrometer with deuterated solvents. The chemical shifts are given in ppm relative to standard, tetramethylsilane (TMS). The molecular weight and corresponding molecular weight distribution (Mw/Mn) was determined by gel permeation chromatography (GPC) using polystyrene standards and the data were obtained from two setups. (A) The THF system was equipped with FLOM Intelligent Pump Al-12, SFD RI 2000 detector, Shodex KF-806L column, PLgel 10 μM guard column. (B) The DMF system was equipped with SpectraSystem P1000 pump, Merck LaChrom RT Detector L-7490, MZ-Gel SDplus linear 5 μM column and two guard columns, MZ-Gel SDplus linear 5 μM, 100 Å and MZ-Gel SDplus linear 5 μM, 50 Å. The measurement was conducted at room temperature using THF as eluent and at 60 °C with DMF as eluent with a flow rate of 1 mL min−1. Infrared spectroscopy was conducted on a Thermo Fisher Scientfic Nicolet iS10 using ATR unit. UV−vis spectroscopy was conducted in JASCO V-630 UV/vis Spectrophotometer. Emission spectroscopy was measured in Varian Cary Eclipse Fluorescence Spectrophotometer with slit width of 2.5 nm. 4.3. General Procedure for Postpolymerization Modifications with Alcohol. The trans-esterification of polyPFPA with alcohols was performed as follows: polyPFPA (0.42 mM, 1.0 equiv) was dissolved in 0.4 mL dry DMF and added with 1.2 equiv of the alcohol (1.5 equiv for secondary and phenolic alcohol) and 0.2 equiv of DMAP. The mixture was stirred for 15 h at 80 °C. Measured aliquot was taken from the crude mixture for FT-IR measurements. The conversion was calculated by integrating the area under the PFP ester carbonyl peak before and after the reaction. After removing the DMF, all the polymers were purified by either dialysis from THF/MeOH or precipitation from MeOH. P7, P9, and P11 were additionally washed with 1.0 N HCl to remove traces of DMAP. 4.4. Kinetic Measurements by FTIR. The kinetics of the transesterification process was investigated as follows: polyPFPA (0.42 mM, 1.0 equiv) was dissolved in dry DMF (0.4 mL) in a reaction vial. To this, propargyl alcohol (1.2 equiv) and DMAP (0.2 equiv) was added. The flask was immersed into an oil bath preheated to 80 °C. Each time 10 μL aliquot was taken out for the FTIR measurement. Time-dependent conversion was calculated by the decrease of the carbonyl band in the IR spectrum. The integration of the peak at 0 min was defined as 0% conversion. The method was followed for 15 h until the PFP-ester signal disappeared completely and the new ester peak intensity became saturated.

■

Article

AUTHOR INFORMATION

Corresponding Author

*(P.T.) E-mail: [email protected]. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS A.D. gratefully acknowledges the Alexander von Humboldt foundation for a postdoctoral fellowship.

■

REFERENCES

(1) Gauthier, M. A.; Gibson, M. I.; Klok, H.-A. Angew. Chem., Int. Ed. 2009, 48, 48−58. (2) Günay, K. A.; Theato, P.; Klok, H.-A. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 1−28. (3) Lutz, J.-F.; Sumerlin, B.; Matyjaszewski, K. Macromol. Rapid Commun. 2014, 35, 122. (4) Kakuchi, R.; Theato, P. Functional Polymers by Post-Polymerization Modification: Concepts, Guidelines and Applications, 1st ed.; Patrick, T., Klok, H.-A., Eds.; WILEY-VCH: Weinheim, Germany, 2013. (5) Goodall, G. W.; Hayes, W. Chem. Soc. Rev. 2006, 35, 280−312. (6) Lutz, J. F. Angew. Chem., Int. Ed. 2007, 46, 1018−1025. (7) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004−2021. (8) Lowe, A. B. Polym. Chem. 2010, 1, 17. (9) Iha, R. K.; Wooley, K. L.; Nyström, A. M.; Burke, D. J.; Kade, M. J.; Hawker, C. J. Chem. Rev. 2009, 109, 5620−5686. (10) Zhu, C.; Yang, B.; Zhao, Y.; Fu, C.; Tao, L.; Wei, Y. Polym. Chem. 2013, 4, 5395−5400. (11) Batz, H.-G.; Franzmann, G.; Ringsdorf, H. Angew. Chem., Int. Ed. Engl. 1972, 11, 1103−1104. (12) Ferruti, P.; Bettelli, A.; Feré, A. Polymer 1972, 13, 462−464. (13) Theato, P.; Kim, J.; Lee, J. Macromolecules 2004, 37, 5475−5478. (14) Mammen, M.; Dahmann, G.; Whitesides, G. M. J. Med. Chem. 1995, 38, 4179−4190. (15) Theato, P. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 6677− 6687. (16) Das, A.; Theato, P. Chem. Rev. 2015, DOI: 10.1021/ acs.chemrev.5b00291. (17) Vosloo, J. J.; Tonge, M. P.; Fellows, C. M.; D'Agosto, F.; Sanderson, R. D.; Gilbert, R. G. Macromolecules 2004, 37, 2371−2382. (18) Xu, J.; Lian, W.; Pispas, S.; Zhang, G. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2998−3003. (19) Eberhardt, M.; Mruk, R.; Zentel, R.; Théato, P. Eur. Polym. J. 2005, 41, 1569−1575. (20) Ogura, Y.; Terashima, T.; Sawamoto, M. ACS Macro Lett. 2013, 2, 985−989. (21) Nakatani, K.; Ogura, Y.; Koda, Y.; Terashima, T.; Sawamoto, M. J. Am. Chem. Soc. 2012, 134, 4373−4383. (22) Samanta, S. R.; Cai, R.; Percec, V. Polym. Chem. 2015, 6, 3259− 3270. (23) Mikhailov, G. D.; Shevchenko, V. V.; Polyakov, L. V.; Chegolya, A. S. Fibre Chem. 1980, 11, 359−361. (24) Saint-Loup, R.; Jeanmaire, T.; Robin, J.-J.; Boutevin, B. Polymer 2003, 44, 3437−3449. (25) Kim, S. H.; Kim, S. C. J. Appl. Polym. Sci. 2007, 103, 1262−1271. (26) Liu, K.-S. J. Am. Oil Chem. Soc. 1994, 71, 1179−1187. (27) Christie, W. W. Preparation of Ester Derivatives of Fatty Acids for Chromatographic Analysis; Christie, W. W., Ed.; Oily Press: Dundee, Scotland, 1993. (28) Höfle, G.; Steglich, W.; Vorbrüggen, H. Angew. Chem., Int. Ed. Engl. 1978, 17, 569−583. (29) Xu, S.; Held, I.; Kempf, B.; Mayr, H.; Steglich, W.; Zipse, H. Chem. - Eur. J. 2005, 11, 4751−4757. (30) Paris, R.; de la Fuente, J. L. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 2395−2406.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.5b02293. Experimental details of the synthesis of all the polymers and supplementary characterization data of the modified polymers, as well as additional FTIR and 1H NMR spectra and an image of the zwitterionic hydrogel (PDF) L


Article

Macromolecules (31) Mansfeld, U.; Pietsch, C.; Hoogenboom, R.; Becer, C. R.; Schubert, U. S. Polym. Chem. 2010, 1, 1560−1598. (32) Schaefer, M.; Hanik, N.; Kilbinger, A. F. M. Macromolecules 2012, 45, 6807−6818. (33) Nilles, K.; Theato, P. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 3683−3692. (34) Yilmaz, I. I.; Arslan, M.; Sanyal, A. Macromol. Rapid Commun. 2012, 33, 856−862. (35) Ghosh, S.; Basu, S.; Thayumanavan, S. Macromolecules 2006, 39, 5595−5597. (36) Schenzel, A.; Hufendiek, A.; Barner-Kowollik, C.; Meier, M. A. R. Green Chem. 2014, 16, 3266−3271. (37) Winkler, M.; Romain, C.; Meier, M. A. R.; Williams, C. K. Green Chem. 2015, 17, 300−306. (38) Mather, B. D.; Viswanathan, K.; Miller, K. M.; Long, T. E. Prog. Polym. Sci. 2006, 31, 487−531. (39) Dan, K.; Ghosh, S. Angew. Chem., Int. Ed. 2013, 52, 7300−7305. (40) He, L.; Szopinski, D.; Wu, Y.; Luinstra, G. A.; Theato, P. ACS Macro Lett. 2015, 4, 673−678. (41) González, G.; Fernández-Francos, X.; Serra, À .; Sangermano, M.; Ramis, X. Polym. Chem. 2015, 6, 6987. (42) Choi, W. Il; Tae, G.; Kim, Y. H. J. Mater. Chem. 2008, 18, 2769− 2774. (43) Malkoch, M.; Thibault, R. J.; Drockenmuller, E.; Messerschmidt, M.; Voit, B.; Russell, T. P.; Hawker, C. J. J. Am. Chem. Soc. 2005, 127, 14942−14949. (44) Stuart, M. a C.; Huck, W. T. S.; Genzer, J.; Müller, M.; Ober, C.; Stamm, M.; Sukhorukov, G. B.; Szleifer, I.; Tsukruk, V. V.; Urban, M.; Winnik, F.; Zauscher, S.; Luzinov, I.; Minko, S. Nat. Mater. 2010, 9, 101−113. (45) Zhai, L. Chem. Soc. Rev. 2013, 42, 7148−7160. (46) Theato, P.; Sumerlin, B. S.; O'Reilly, R. K.; Epps, T. H., III Chem. Soc. Rev. 2013, 42, 7055−7056. (47) Jochum, F. D.; Theato, P. Chem. Soc. Rev. 2013, 42, 7468−7483. (48) Wada, T.; Kano, A.; Shimada, N.; Maruyama, A. Macromol. Res. 2012, 20, 302−308. (49) Evans, A. C.; Skey, J.; Wright, M.; Qu, W.; Ondeck, C.; Longbottom, D. A.; O’Reilly, R. K. J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 6814−6826. (50) Roy, S. G.; De, P. J. Appl. Polym. Sci. 2014, 131, 41084−41095. (51) Mori, H.; Endo, T. Macromol. Rapid Commun. 2012, 33, 1090− 1107. (52) Blanazs, A.; Massignani, M.; Battaglia, G.; Armes, S. P.; Ryan, A. J. Adv. Funct. Mater. 2009, 19, 2906−2914. (53) Lin, S.; Theato, P. Macromol. Rapid Commun. 2013, 34, 1118− 1133. (54) Liu, Q.; Singh, A.; Liu, L. Biomacromolecules 2013, 14, 226−231. (55) Alswieleh, A. M.; Cheng, N.; Canton, I.; Ustbas, B.; Xue, X.; Ladmiral, V.; Xia, S.; Ducker, R. E.; El Zubir, O.; Cartron, M. L.; Hunter, C. N.; Leggett, G. J.; Armes, S. P. J. Am. Chem. Soc. 2014, 136, 9404− 9413. (56) Calvo, A.; Yameen, B.; Williams, F. J.; Soler-Illia, G. J. A. A.; Azzaroni, O. J. Am. Chem. Soc. 2009, 131, 10866−10868. (57) Xuan, F.; Liu, J. Polym. Int. 2009, 58, 1350−1361. (58) Dechy-Cabaret, O.; Martin-Vaca, B.; Bourissou, D. Chem. Rev. 2004, 104, 6147−6176. (59) Slomkowski, S.; Penczek, S.; Duda, A. Polym. Adv. Technol. 2014, 25, 436−447. (60) Molla, M. R.; Ghosh, S. Macromolecules 2012, 45, 8561−8570. (61) Birks, J. B.; Christophorou, L. G. Spectrochim. Acta 1963, 19, 401− 410. (62) Maji, T.; Banerjee, S.; Biswas, Y.; Mandal, T. K. Macromolecules 2015, 48, 4957−4966. (63) Koganty, R. R.; Shambhu, M. B.; Digenis, G. A. Tetrahedron Lett. 1973, 14, 4511−4514. (64) Martin, G. J.; Naulet, N. Tetrahedron Lett. 1976, 17, 357−360. (65) Lutz, V.; Glatthaar, J.; Würtele, C.; Serafin, M.; Hausmann, H.; Schreiner, P. R. Chem. - Eur. J. 2009, 15, 8548−8557.

M


Multifaceted Synthetic Route to Functional Polyacrylates by

Recommend Documents