?Click? Chemistry as a Promising Tool for Side-Chain

?Click? Chemistry as a Promising Tool for Side-Chain

(Parte 1 de 3)

“Click” Chemistry as a Promising Tool for Side-Chain Functionalization of Polyurethanes

David Fournier and Filip Du Prez*

Department of Organic Chemistry, Polymer Chemistry Research Group, Ghent UniVersity, Krijgslaan 281, S4-bis, B-9000 Ghent, Belgium

ReceiVed January 26, 2008; ReVised Manuscript ReceiVed May 1, 2008

ABSTRACT: Linearpolyurethanes(PUs) havingalkynegroupslocatedalong the backbonehave been synthesized by reacting two different alkyne-functionalized diols with a diisocyanate compound. 1H NMR and FTIR proved the presence of these functional groups and the ability for the introduction of an elevated and controllable amount of functional groups that do not interfere with the PU chemistry. TGA measurements demonstrated that the incorporated alkyne diol in the PU materials strongly improves the final char yield. In the second part of the work, the copper catalyzed Huisgen 1,3-dipolar cycloaddition was undertaken between the alkyne-functionalized PUs and a variety of azide compounds such as benzyl azide and different fluorinated azide compounds, resulting in side-chain functionalized PUs with varying degree of functionalization. 1H NMR spectra clearly indicated the quantitative yields of the “click” reaction.


Since polyurethanes (PUs) have been discovered by Bayer in the 40s,1 many academic and industrial research groups from all over the world have enlarged this field. PUs2 are mostly, but not only, based on the reaction between diisocyanatates, diols and polyols. The wide range of starting compounds leads to the synthesisof materialswith differentand unique properties. The targeted applications are numerous such as in the field of automobile, medicine, comfort, buildings, paintings, coatings, adhesives and packaging.3 Additionally, the chemistry of polyurethanes allows for the synthesis of foams (flexible and rigid) or thermoplastic polymers, depending on their synthetic conditions.Nowadays,thermoplasticPUs have found a growing interest since the mechanical, thermal and chemical properties can be tailored by the choice and composition of the starting compounds. Actually, much research is focused on the degradability and the recycling of such materials due to their intense production.4 More recently, much attention is shown for the development of functional polyurethanes because it is expected that they lead to applications that are outside of the PU market, thus giving rise to additional functionality to the end materials.

To introduce functionalities within the PU materials, few possibilities can be considered. One route to obtain functional polyurethanesis the use of monofunctionalcompounds (alcohol or isocyanate), which lead to polymer chain terminations with the functionalgroup at the chain end and to a reduced molecular weight. The end-chain modification of the PU can also be performed after its formation. For instance, hydroxyethyl (meth)acrylate has been employed for the modification of a NCO-functionalized polyurethane leading to UV-cross-linkable polyurethane (meth)acrylate (PUA).5,6 The UV-cured PUA coatings received considerable attention for their resistance to accelerated weathering or exposure to light for instance.7,8 A similar strategy led to the elaboration of amino-functionalized PUs starting from the reaction between an excess of hexamethylene diisocyanate (HDI) and propylene glycol.9 The isocyanate functions in the PU, located at the end-chains, were successively hydrolyzed with triphenylsilanol and water. These so-obtained amino-functionalized PUs may be afterward used for coatings, adhesives, sealants.9 Surface modification of isocyanate-functionalized PUs was also reported in order to incorporate different functional groups such as sulfonate or amine.10

Second,the functionalgroupcan be directlyintroducedduring the process (one-pot procedure) by using a functional building block. Nevertheless, careful attention should be paid toward the inertness of the introduced functional groups during the polyurethane process to avoid secondary reactions, making the materials unusable for the desired final applications. For instance, the introduction of amino groups into PU requires protection/deprotection steps. Recently, the preparation of PUs bearing pendant amino groups starting from HDI, poly( - caprolactone) (PCL), and a modified poly(ethylene glycol) (PEG) has been described.1 The approach consists in the reaction of dihydroxyl PEG with NH2-protected aspartic acid (Asp) leading to a prepolymer PEG-Asp-PEG. Then, the consequentreactionbetweenHDI, PCL and the amino-protected PEG-Asp-PEG allowed for the formation of PU with a low loading of pendant amino groups after an ultimate deprotection step. At the same time, Endo et al.12 prepared PU bearing hydroxyl groups in the side chain (PHUs) by reacting a bifunctional cyclic carbonate with a diamine, after which the hydroxyl groups were converted into functionalized urethane groups with the help of functionalized isocyanates. In medicine, functional PUs are widely studied since it was established that PU shows relatively good in Vitro blood compatibility in comparison to other polymeric films.13 For example, Kim et al.14 synthesized heparin-immobilized polyetherurethanes containing pendant ester groups from a NCO-prepolymer and diethyl bis(hydroxymethyl)malonate. The obtained ester-functionalized PU was then chemically modified to obtain either heparin or PEG-heparin as side groups. Another way that was largely explored consists of the functionalization of PUs by hydrogen removal of the urethane group (i.e., NH) of the material using for example, a drastic treatment based on sodium hydride (NaH).15–19 In general, the chemical modification of such functional polymers can also suffer of a certain lack of efficiency since the reactivity of functional groups may be affected by the structure of the polymer and also by the efficiencyof the chemicalreactionsused. For the past few years, this efficiency was intensively studied in the area of polymer chemistrysince, in 2001, Sharplessand co-workers20 introduced innovative approaches, named “click” chemistry, allowing quantitative reactions. Among the listed reactions, Huisgen 1,3-* Corresponding author. E-mail: filip.duprez@ugent.be.

10.1021/ma800189z C: $40.75 2008 American Chemical Society Published on Web 06/14/2008

dipolar cycloadditions between an azide and an alkyne compound have been widely explored due to, among others, its efficiency, versatility and inertness toward other functional groups. The use of a copper catalyst leads to a tremendous acceleration of the reaction at room temperature.21,2 Since the first report of “click” chemistry in polymer chemistry by Hawker, Sharpless and co-workers,23 the construction of welldefined and complex macromolecular architectures Via “click” chemistry has been a strongly growing field of research.24–27 Relating to the PU field, Qin et al.28 very recently reported the elaboration of polyurethanes using the combination of 2,4- toluene diisocyanate (TDI) and chromophore-functionalized diols. Nevertheless, the authors first synthesized these diols by the 1,3-dipolar azide-alkyne cycloaddition prior to their incorporationin the PU. These polymerswere studiedas organic second-order nonlinear materials for their further application in the field of high-speed electro-optic devices.

The aim of the present work was to develop an efficient way for the elaborationof alkyne-containingPUs by the introduction of alkyne diols during the PU process. Because of the resistance of the alkyne group toward the usual reaction conditions and functional groups during the PU synthesis, it was foreseen that an universal class of functionalized PU materials could be prepared. The ultimate step is the functionalization of the PUs Via “click” chemistry with the help of functional azide compounds, leading to a wide range of properties starting from the same compounds. To achieve this goal, two different alkynecontaining diols have first been synthesized. Then, alkynefunctionalized linear PUs with controllable alkyne loadings and variable molecular weight have been prepared. Finally, the postmodification has been done using the Huisgen 1,3-dipolar cycloadditions with several azide compounds in order to obtain new PU materials with properties that are directed Via the azide compound.

Experimental Section

Materials. Sodium azide (9%, Acros), copper(I) bromide

ylenetriamine (PMDETA, 9+%, Fluka), butane-1,4-diol (BDO, 9+%, Acros), Zonyl FSO-100 (Aldrich), hexamethylene diisocyanate (HDI, 98%, Aldrich), dibutyltin dilaureate (95%, Fluka), methane sulfonyl chloride (9.5%, Acros), hydrazine monohydrate (98%, Acros), dimethylformamide(DMF, HPLC grade, Fisher) and dimethyl sulfoxide (DMSO, HPLC grade, Acros) were used as received. The compounds benzyl azide (BzN3),29 3,5-bis(hydroxymethyl)-1-propargyloxybenzene(PBM),301,1,1,2,2,3,3,4,4,5,5,6,6- tridecafluoro-8-azidooctane,31 and 2,2-di(prop-2-ynyl)propane-1,3- diol (DPPD)32 were synthesized according to the literature. Triethylamine(HPLCgrade,Aldrich),tetrahydrofuran(THF,HPLC grade, Aldrich) and ethyl acetate (EtOAc, HPLC grade, Aldrich) were distilled prior to use.

Instrumentation.1H NMR spectra were recorded at 25 °C, with a Bruker Avance 300 spectrometer. Thermogravimetric analysis (TGA) was performed with a Mettler Toledo TGA/SDTA851e instrument under air atmosphere at a heating rate of 20 °C/min between25 and 800 °C. Infraredspectrawere obtainedwith ReactIR 4000 instrument (Mettler Toledo AutoChem ReactIRTM) using a silicone probe (SiComp, optical range ) 40-650 cm-1). Molecular masses and molecular mass distributions were measured using gel permeation chromatography (GPC) using N,N-dimethylacetamide (DMA) as solvent and LiBr (0.42 g/L) with a flow rate fixed at 1 mL/min and a temperature of 50 °C (with poly(methyl methacrylate) standards).

Synthesis of N-2-(Azidoethyl)phthalimide (PHT-N3). N-2- (Bromoethyl)phthalimide(10 g, 40.97 mmol) in a mixture of DMF/ water (120 mL, 9/1 v/v) was charged in a round-bottomflask. Then, 1.5 equivalent of sodium azide (59 mmol, 3.84 g) was introduced and the reaction mixture was allowed to stir at 60 °C for 1 day. The mixture was then cooled to room temperature and a minimum of 5 extractions against ether was done. The combined ether layers were dried with magnesium sulfate and the solvent removed in vacuum, yielding a yellowish powder that was further dried under

Synthesisof Zonyl-N3. Zonyl-N3 was synthesizedin two steps from hydroxyl chain terminatedfluorinatedsurfactantZonyl-FSO- flask, Zonyl (20 g, 1 equiv) was dissolved in freshly distilled THF (100 mL). Then, freshly distilled triethylamine(4.2 mL, 1.1 equiv) was added and the temperature fixed at 0 °C. Methane sulfonyl chloride was introduced dropwise (3.65 g, 1.15 equiv). After the addition, the reaction mixture was allowed to stir at room temperature overnight. Triethylamine salt was filtered off and the filtrate was evaporated under vacuum. This intermediate compound was not further purified and in a second step, it was dissolved in ethanol (100 mL) containing sodium azide (2.69 g, 1.5 equiv). The reaction was stirred overnight at reflux. Then, solvent was removed and both ether and water were added to the mixture allowing extractions. The combined organic layers were dried with magnesium sulfate and the solvent removed in vacuum, yielding a brown

Typical Synthesis of Linear Alkyne-Containing

Polyurethane. In a round-bottom flask were introduced 1 equiv of HDI, 1 equiv of a diol (or a predetermined mixture of two diols), and freshly distilled EtOAc. The mixture was degassed by bubbling nitrogen for 15 min and heated at 50 °C in a preheated oil bath. Then, dibutyltin dilaureate (approximately 20-30 µL) was added, and the reaction was allowed to stir under inert atmosphere for 2 h. During its formation,the PU slowly precipitatesin the medium, and the obtained polymer was then filtered off and extensively washed with EtOAc and acetone to remove all unreacted compounds.The synthesizedmaterialwas driedundervacuumovernight prior to further characterizations such as GPC or NMR.

Typical Huisgen 1,3-Dipolar Cycloaddition onto Linear

Polyurethane. In a round-bottom flask, the alkyne-functionalized PU (1 equiv of alkyne functions) was charged with the azide compound (2 equiv), the solvent (DMSO or DMF) and the copper catalyst based on either CuBr/PMDETA (0.1 equivalent each according to the alkyne content) or CuSO4,5 H2O/Naasc. (0.05 and 0.1 equiv, respectively). The reaction was performed overnight under nitrogenatmosphereat 50 °C. The resultingmodified material was precipitated in diethyl ether and dried under vacuum overnight prior to further characterizations.

Deprotection of Phthalimide-Functionalized PU. In a roundbottom flask, the phthalimide-functionalized PU (1 eq.) was dissolved in DMF. A solution of hydrazine monohydrate in DMF was slowly added to the reaction mixture. Then, the temperature was fixed at 70 °C for 4 h. The reaction mixture was cooled down to room temperature and the PU was precipitated into diethyl ether. The polymer was filtered off and dried under vacuum prior to characterizations.

Results and Discussion

Synthesis of Alkyne-Functionalized Polyurethanes. Since their discovery, the functionalization of PU materials has been a challengein order to elaboratenew highly interestingmaterials that are finding their applications in various fields. In this study, linear alkyne-functionalized PUs have been synthesized and characterized by conventional characterization techniques, after which they are modified Via “click” chemistry. The described strategy consists in incorporating alkyne functions in the PU by the introduction of alkyne-functionalized diols in the feed

Macromolecules, Vol. 41, No. 13, 2008 “Click” Chemistry as a Promising Tool 4623

of the polycondensation.For this purpose, one monoalkynediol, 3,5-bis(hydroxymethyl)-1-propargyloxybenzene (PBM) and a dialkynediol,2,2-di(prop-2-ynyl)propane-1,3-diol(DPPD),were synthesized according to the literature30,32 (Chart 1).

First, the monoalkyne diol (PBM) was mixed with hexamethylene diisocyanate (HDI) in ethyl acetate. According to the desired PBM loading, a predetermined amount of butane-1,4- diol (BDO) is added to the mixture. Then, the temperature was fixed at 50 °C and one drop of tin catalyst was added. As a result of the use of ethyl acetate as solvent, the PU polymer is precipitating during its formation after few minutes, leading to macromolecules having a low molecular weight, which facilitates the characterization by 1H NMR. Table 1 summarizes the results of the synthesized PUs with varying amounts of PBM (50, 25, and 8 mol %, entries 1-3, Table 1) and also a blank PU (0 mol % of PBM) synthesized from HDI and BDO (entry 4, Table 1).

Figure 1 shows a typical 1H NMR spectrum obtained from

PU-PBM-25. The typical resonance of the alkyne proton appears at 3.5 ppm proving that the functionalized diol has been incorporated in the polymer without any side reaction. Moreover, the peak at 7.2-7.3 ppm corresponds to hydrogens linked to the nitrogen atoms from the urethane groups. It clearly indicates that all expected peaks are present, either from the BDO, the PBM, or the diisocyanate. Moreover, by taking into account the integration of peaks at 4.75 ppm (2H, -CH2 from PBM), 3.9 ppm (4H, -O-CH2 from BDO) and 2.9 ppm (4H,

-NH-CH2 from HDI),the molarratiobetweenBDO and PBM could be determined.

The elaborated PUs were also characterized by FT-IR spectroscopy to further prove the incorporation of the functionalized alkyne diol in the materials. In Figure 2, the IR spectra display the overlay of the starting alkyne diol PBM and the synthesized PU-PBM-25.

The spectrum corresponding to the PU-PBM-25 (upper spectrum, Figure 2) shows typical bands, on one hand at 1737 cm-1 corresponding to the carbonyl function from the urethane groups and, on the other hand at 2220 cm-1 (CtC) and 3290 cm-1 (CtC-H) relatingto the terminalalkynefunctionspresent in the material. The thermal stability of the synthesized functionalized PU was studied by thermogravimetric analysis (TGA) measurements.

As shown in Figure 3 (top), all synthesized PUs are stable up to 300 °C. The initial decomposition temperature, defined as 5% weight loss (data in Table 1), are similar, showing that the incorporation of PBM in the material does not affect the thermal behavior at the early stage of the thermal decomposition process. However, it can be observed from the overlay that for a higher PBM content in the PU, the overall final char yield is increasing up to 25%. Thus, PBM may act at the same time as a stabilizer agent as already reported elsewhere. Indeed, alkyne groups are known to act as a cross-linker upon heating by creation of reticulated alkenes and can participate in a reaction of cyclotrimerization making the materials flame-retardant.35,36 This is ascribed to the formation of char on the upper part of the material,whichpreventsthe formationof volatilecompounds from the inner part. In addition, terminal alkynes have also been used to elaborate high-performancepolymers and composites.37 When final char yields were plotted against the amount of incorporated PBM (Figure 3, bottom), a linear relationship was surprisingly observed, meaning that a structure-property relationshipmay exist that can justify the above-mentionedexplanation about the thermal stability of alkyne-functionalized materials. Moreover, the stability of the materials has been studied after heatingthem at 200 °C for 30 min. 1H NMR measurements (data not shown) after this degradation study showed no change meaning that the PUs are stable in these conditions and especially that the alkyne functions are still available for further reactions.

The same strategy has been employed to incorporate in the

PU a diol bearing two alkyne functions per repeating unit (Scheme 1).

The reactivity of DPPD was examined by elaborating a soluble PU starting from DPPD and HDI (entry 1, Table 2) as shown in Scheme 1. Then, BDO was introduced in the feed of the polycondensation to obtain a PU with 15 mol% of DPPD (entries 2 and 3, Table 2).

Figure 4 shows the overlay of the starting diol DPPD and the PU-DPPD-15.

The IR spectrum of DPPD (upper spectrum) indicates the presence of the alkyne function due to the low intense band at 2120 cm-1 (CtC) and the shoulderat approximately3270 cm-1 (CtC-H) next to the intense OH stretching. Additionally, the spectrum corresponding to the PU-DPPD-15 shows the appearance of three intense bands at 1700 cm-1 from amide I

Chart 1. Diols Involved during the PU Process and Azide Compounds Used for the Copper-Catalyzed Huisgen 1,3-Dipolar Cycloaddition

Table 1. Synthesis of Linear PUs Starting from HDI and the Building Block PBM entry referencea composition

(mol %)bPBM/BDO/HDI

Mn c

(g/mol) PDIc char yieldf (%) a Indicated values relate to the amount of incorporated PBM (mol %) in the final material. b Final composition determined by 1H NMR in

DMSO-d6. c Determined by GPC calibrated with PMMA standards. d The resulting trace is out of the calibration window, and only the peak weight

(Mp) could be determined. e Not soluble in GPC solvent. f Temperature at 5% weight loss and final char yield, as determined by TGA. Heating ramp:

20 °C/min under air from 25 to 800 °C.

4624 Fournier and Du Prez Macromolecules, Vol. 41, No. 13, 2008

(CdO stretching vibrations) of the urethane, at 1540 cm-1 from the amide I (C-N stretching vibrations) and at 1258 cm-1 belonging to the amide I (C-N deformation).

The thermal stability of such materials was also examined by TGA. It reveals that all synthesized PU-DPPD are stable up to 250 °C or higher. In contrast to the previous series (PU-PBM), at the early stage of the degradation process (250-350 °C), the incorporation of DPPD makes the material more sensitive to the heating as observed in Figure 5.

(Parte 1 de 3)