A Throughway to Functional Poly(disubstituted acetylenes): Combination of Activated Ester Strategy with Click Reaction

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Introduction
3][4][5][6][7][8][9] Nowadays, the research work focuses on poly(disubstituted acetylenes) (PDSAs), owing to their improved stability and high fluorescent efficiency, in comparison with their poly(monosubstituted acetylenes) (PMSAs) counterparts. 10,11Yet, the polymerization condition of disubstituted acetylenes is harsh, the catalysts are very sensitive to moisture and oxygen.Furthermore, the polar groups (such as amide, amine, hydroxyl, and thiol) on the disubstituted acetylene monomers can poison the catalyst systems and lead to null polymerization. 4,12Considering these troubles, the preparation and application of functional PDSAs are greatly limited.
To break through the existing limitations, researchers are continously trying to find alternative strategies to the direct polymerization of the functionalized disubstituted acetylene monomers.Post-polymerization modification has been proved to be a promising strategy. 13A representative instance is the adaption of Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between azides and alkynes (CuAAC), which is referred to as "click chemistry, 14 in the post-polymerization modification.Click chemical reactions enjoy the unique benefits of high efficiency, quantitative yield, and mild reaction conditions.A precursor PDSA can be obtained by the polymerization of a disubstituted acetylene monomers bearing a protected end alkyne group.Free end-alkynes groups are released after the deprotection procedure, and finally expected functionalities are modified to the precursor PDSA through highly efficient reaction with functional azides. 15Or in contrary, using the azide-functionalized PDSA as precursor polymer, the target PDSA is derived from the "click" reaction between azide pendents and functionalized alkynes. 16[23][24][25] These existing works have shown the possibility of this strategy to serve as a platform for the construction of functional PDSAs.Herein, we report our recent works on expanding the platform by combining activated ester strategy with alkyne-azide click reaction, introducing more 60 functional groups into the modified PDSAs.

Results and Discussion
Attempt to directly polymerize disubstituted acetylene monomer containing alkyne.It is highly useful to attach alkyne onto the side chains of a precursor PDSA, then prepare 65 functionalized PDSAs via reaction with differently functionalized azides.But this route has been proved to be obstructed.As shown in Scheme 1, the direct polymerization of alkyne-containing disubstituted acetylene monomer M1 (the synthetic route and characterization data of M1 are shown in Scheme S1 and Fig. S1 70 to S4, Electronic Supplementary Information or ESI) in the presence of WCl 6 -Ph 4 Sn catalyst system, which is commonly used in the polymerization of disubstituted acetylene monomers, leads to the unexpected PMSA, rather than the expected PDSA (P1).This is easy to be identified by the colour of the resultant mixture.For most PDSAs, the solution appears a yellow colour, while for PMSAs, the colour is usually dark orange to red.The generation of PMSA has been confirmed by infrared and 1 H and 13 C NMR spectral data (see Experimental Section and Fig. S5 and S6 in ESI).To obtain the expected PDSA, the end alkyne must be 5 protected with a bulky and hydrophobic trialkylsilane unit.In our previous attempt, thimethylsilane was used as the capping reagent to prevent the reaction of the alkyne functional group.But this route requires a protection-deprotection procedure, which results in low reaction efficiency and low yield.Introducing alkyne into PDSA by activated ester strategy.The problems are dissolved by aid of the activated ester strategy.

20
As shown in Scheme 2, the end alkyne functional group can be attached onto the side chains of PDSA through the replacement of pentafluoro-phenol with propargylamine.The precursor PDSA (P0) was prepared according to the procedures described elsewhere. 15The average molecular weight was 14.5 kDa and poly-25 dispersion index (PDI) was 1.79, as estimated by GPC technique using monodisperse polystyrene samples as internal calibration.Fig. 1. 19 F NMR spectra of (A) the precursor PDSA (P0) and (B) the propargylamine modified PDSA (P2).

30
After the modification reaction, the resultant polymer has an average molecular weight of 10.6 kDa and a PDI of 1.38.The replacement reaction took place at room temperature in very high efficiency and the yield was approximate to the theoretical value (99%).Comparing the 19 F NMR spectra of precursor (P0) and the 35 resultant PDSA (P2), it is found that resonant peaks for F atoms, which are clearly recognized at -152.35, -157.45, and -162.17ppm all disappeared in the spectrum of P2, indicating the fully disengagement of the pentafluoro-phenol in P0.The successful replacement of activated ester (pentafluorophenol) group by propargylamine was also confirmed by the Fourier transition infrared (FTIR) spectra of P0 and P2.For FTIR 45 spectrum of P0 (Fig. 2A), the absorption band peaked at 3060 cm - 1 is assigned to the stretching vibration of C−H bond on phenyl.
Concomitantly, the absorption bands at around 1605, 1520, 844 and 690 cm -1 (not marked) provide the proofs of the existence of phenyl group, and the latter two bands are fingerpints of 1,4-50 disubstituted and mono-substituted phenyl groups.These bands show up in all of the PDSAs' spectra in this work (Fig. 2, S1 and S4).The absoprtion band at 1766 cm -1 origins from the carbonyl in the ester group, which comes along with the absorption bands at around 1250 and 1050 cm -1 , indicating the presence of 55 aromatic ester group.For the spectrum of P2, the absorption band of the stretching mode of carbonyl appears at 1644 cm -1 , indicating the transition of ester to amide group.The absorption band at 1294 cm -1 is a side proof of the amide group.Different from spectrum A, some new bands show up.The band with a 60 peak at 3294 cm -1 is assigned to the stretching vibration of C−H bond on alkyne.In principle, this band should be sharp one.The broadening observed here is ascribed to the overlapping with the stretching mode of N−H bond in amide group.The weak but obvious band at around 2120 cm -1 can be assigned to the anti-65 symmetric vibration of the C≡C bond.In addition to the absorption bands for amide and alkyne groups, new bands also appear at 2926∼2850 cm -1 , which are assigned to the antisymmetric and symmetric stretching vibrations of C−H bond of methylene group.Incidentally, the band for bending mode of C−H bonds in the methylene group appears at around 1492 cm -1 .
The simultaneous appearance of these bands clearly prove the presence of propargyl-groups in P2 and the transformation of the ester to the amine group.It is worthy of note that the absorption band of C−F bond at around 1010 cm -1 , which is shown clearly in spectrum A, totally disappears in spectrum B. This change suggests the complete replacement of pentafluoro-phenol by amine groups.The average molecular weight Mw and PDI of P3 were masured to be 9.6 kDa and 1.23, respectively.The lowered molecular weight does not mean the polymer degradation induced by postpolymerization modification.Because, on one hand, the chemical structure and solubility of P0, P2, P3 are distinct, the same 40 polymerization degree cannot be counted on by using the same polystyrene (PS) calibration.The adjactive phenyl goups on the pendents of P3 may have stronger interation with PS and result in longer retention time.On the other hand, from chemcial view of point, the CuAAC reaction proceeded in a mild condition that is 45 harmless to polymer structure.The transformation of P2 to P3 has also been confirmed by 1 H NMR spectroscopic evidence.For P2, the chemical shifts of the proton on propagyl appears at 3.09 ppm, corresponding to H a in Fig. 3B.After modification reaction, this peak totally disappears and a new peak appears at around 7.95 50 ppm, which corresponds to the transition from a proton on alkyne to the one on triazole ring (H e in Fig. 3C).The magnetic shielding effect and electron-deficient nature of the triazole moiety allow the resonance of the proton to come forth at much lower field.The chemical shift for the methylene protons on propargyl group 55 of P2 is about 4.04 ppm; it shifts to about 4.45 ppm in P3.This low-field shift is ascribed to the electron-withdrawing effect of the triazole moiety.The chemical shift at about 5.56 ppm comes from the methylene protons contributed by benzyl azide.It appears at relative lower field if compared with the protons on 60 normal methylene groups because of the mutual interaction of the triazole and phenyl rings.
The transition from P2 to P3 has been also confirmed by the changes in their FTIR spectra (Fig. 2, spectra B and C).For P2, the broad band ranging from 3400 to 3000 cm -1 with a sharp peak 65 at around 3294 cm -1 corresponds to the overlapping of the stretching vibration of C−H bond on alkyne and the stretching band of N−H bond on imide group.For P3, the sharp peak becomes obtuse and the broad band becomes weaker, indicating that the alkyne group has been exhausted while the amide group 70 is retained.Due to the contribution from the benzyl, the absorption band of methylene becomes evident stronger in P3 than that in P2.Meanwhile, the band splits into two groups of sub-bands because the methylene groups are in two different chemical atmospheres, one lies between amide and triazole and 75 the other between triazole and phenyl groups.Afterwards, the triazole moieties are grafted onto the P0 from the primary amine functionalized triazole intermediate via activated ester strategy.The average molecular weight of Mw and PDI are 10.2 kDa and 1.36 respctively, which are comparable with the resultant P3 derived from Scheme 2. The 1 H NMR spectrum is 5 quite similar to that recorded for the resultant P3 from Scheme 2 (Fig. S8), indicating the same polymer derived from different synthetic routes.
In summary, we have shown an improved preparation method of functional PDSAs through the synthetic route of combining 10 activated ester and CuAAC click reaction.The structures of the derived PDSAs have been characterized by multiple spectroscopic techniques including GPC, FTIR, 1 H NMR, and 19 F NMR.The characterization data confirmed the validity of the expected polymer structures, thus confirmed the accessability of the pre-15 designed synthetic route.In comparison with the widely used activated ester strategy, the combination with CuAAC reaction offers the possibility of modification the precursor PDSA with azide-containing compounds, thus expands the platform of functional PDSAs.In comparison with the previously reported 20 route, which used the end-alkyne-containing PDSA as precursor, the protection-deprotection steps have been omitted, thus the efficiency has been evidently improved.With the rapid development of azide-and alkyne-chemistry, more and more functional agents containing azide and alkyne groups will be Instruments 1 H and 19 F NMR spectra were measured on a Bruker ARX 500 NMR spectrometer using tetramethylsilane (TMS; δ = 0 ppm) as 45 internal standard.FTIR spectrum was measured on a Perkin Elmer 16 PC FT-IR spectrophotometer.High-resolution mass spectra (HRMS) were taken on a GCT premier CAB048 mass spectrometer operating in a MALDI-TOF mode.Molecular weights (M w and M n ) and polydispersity indexes (PDI, M w /M n ) of 50 the polymers were estimated in THF by a Waters gel permeation chromatography (GPC) system.A set of monodisperse polystyrene standards covering molecular weight range of 10 3 -10 7 were used for molecular weight calibration.

Fig. 3 .
Fig. 3. 1 H NMR spectra of (A) the matrix polymer, (B) the alkyne modified and (C) the triazole functionalized PDSAs.The solvent peaks are marked as asterisks.1 H NMR spectra provide further evidences to support the transformation of P0 to P2 (Fig.3).For P0, only resonant peaks in the range of 7.24 to 7.60 ppm are observed, which are contributed by two phenyl groups in the polymer skeleton.For P2, the characteristic resonant peaks at 3.09 and 4.04 ppm are assigned to the protons on the alkyne and methylene, repsectively.Together with the19 F NMR and FTIR spectra, all of the spectral data sufficiently prove the achievement of alkyne-functionalized 25

Scheme 3
Scheme 3 Synthetic route to the triazole functionalized PDSA (P3) from P0 through post-polymerization modification via activated ester strategy.Post-polymerization modification of PDSA by alkyne-azide80 25 designed and prepared, and we expect the combination strategy demonstrated in the present work to be helpful to fabricate novel and useful PDSAs.before use.Tetrahydrofuran (THF) was distilled under normal pressure from sodium benzophenone ketyl under nitrogen immediately prior to use.Triethylamine (Et 3 N) was distilled and dried over potassium hydroxide.WCl 6 and Cu (PPh 3 ) 3 Br were bought from Aldrich.Ph 4 Sn was bought from 35 ABCR.Propagylamine and benzil azide were perchased from Acros.DMAP, TsOH was bought from Alfa.Other solvents, including N,N-dimethylformamide (DMF), chloroform, methanol, ethyl acetate, chloroform (CHCl 3 ), dichloromethane (DCM), hexane and petroleum ether (PE, b. p. 60∼90 o C) were purchased 40 from Sinopharm Co. Ltd.They were in analytical grade and directly used as received without further purification.
Preparation of P3 from an alternative route.The synthetic route is shown in Scheme 3. Into a round-bottom flask was added 15 37 mg (0.04 mmol) Cu (PPh 3 ) 3 Br under N 2 atmosphere.266 mg (2 mmol) benzyl azide was dissolved in 15 mL distilled THF and was injected into the flask.110 mg (2 mmol) propargylamine dissolved in another 15 mL distilled THF was injected into the flask.The mixture solution was stirred at 60 o C for 12 hours. 20 Preparation of P3. 52 mg (0.2 mmol) P2 was added into a Schlenk tube.The tube was flushed with N 2 in glove box and 3.7 mg (0.004 mmol) Cu (PPh 3 ) 3 Br was added.26.6 mg (0.2 mmol) benzyl azide was dissolved in 3 mL distilled THF and was injected into the Schlenk tube.The mixture was heated to 60 o C and reacted for 12 hours.After precipitation treatment and drying in vacuum oven at 60 o C over night, 65 mg yellowish-green solid (P3) was gotten and the yield was 82.9%.
Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.E-mail: sunjz@zju.edu.cn;Fax: +86-571-87953734; Tel: +86-571-87953734 b Guangdong Innovative Research Team, State Key Laboratory of Luminescent Materials and Devices, South China University of Department of Chemistry, Jockey Club Institute for Advanced Study, Institute of Molecular Functional Materials, State Key Laboratory of Molecular Neuroscience, and Division of Biomedical Engineering, The Hong Kong University of Science & Technology, Clear Water Bay, c