Modular synthesis of block copolymers via cycloaddition of terminal azide and alkyne functionalized polymers {
Joost A.Opsteen and Jan C.M.van Hest *
Received (in Cambridge,UK)23rd August 2004,Accepted 21st October 2004First published as an Advance Article on the web 25th November 2004DOI:10.1039/b412930j
Polymeric building blocks containing terminal azide and alkyne functionalities are prepared via atom transfer radical polymer-ization (ATRP)and ud to modularly synthesize block copolymers via 1,3-dipolar cycloaddition reactions,which are quantitative according to SEC measurements.
Recently,Sharpless et al.have optimized Huisgen’s 1,3-dipolar cycloaddition of azides and terminal alkynes via copper(I )catalysis.1This type of ‘‘click’’reaction can be characterized as highly efficient and specific,with the starting materials being very stable to other functional groups.2
This ‘‘click’’chemistry has nowadays also been introduced in dendrimer and polymer synthesis 3and utilized to cross-link block copolymer vesicles.4The great potential of this coupling procedure for the construction of well defined (functional)polymer architectures has been quickly recognized,and is the s
ubject of intensive rearch.One of the until now still unexplored possibilities is to u this method to modularly synthesize block copolymers.
Nowadays,a wide range of ‘‘living’’or controlled polymeriza-tion techniques is available to prepare block copolymers of various architectures,solubility and functionality,via concutive polymerization of different monomers.The polymerization techniques compri ‘‘living’’ionic 5and ‘‘living’’radical polymer-izations.6–8Various techniques can also be combined to synthesize a myriad of block copolymer structures.9The disadvantages of this so-called macroinitiation approach are that complete formation of block copolymers is hard to asss and characterization of the individual blocks is very difficult.
The problems can be circumvented by applying a modular approach for the synthesis of block copolymers.Polymeric blocks bearing functional end groups are prepared parately and are linked covalently via their end groups.This approach enables full analysis (lecular weight distribution)of the parate blocks prior to coupling.A major disadvantage however of this method is that in order to have a high yield coupling reaction,reactive end groups have to be ud that therefore are prone to undergo side reactions,which limits the scope of the modular approach.
Here we report a novel modular strategy for the preparation of block copolymers by applying stable alkyne and azide end groups that are activated during the coupling process,circumventing the problem of loss of functionality.Additionally,in ATRP,end
group functionality can be introduced either by utilizing functionalized initiators 10or a post-polymerization end group modification.11The first procedure ensures complete functionali-zation of all polymer chains.In the latter ca there is a chance of incomplete functionalization due to the prence of dead chain ends,which can however be suppresd in controlled polymeriza-tions,such as atom transfer radical polymerization (ATRP).
Alkyne functionality was introduced in a ries of poly(methyl methacrylate)(PMMA)2a–c with different molecular weights and polystyrene (PS)3via ATRP,utilizing functionalized initiator 1,as depicted in Scheme 1.The alkyne functionality of this initiator was protected with a trimethylsilyl group in order to circumvent complexation with the copper catalyst during polymerization.This protective group was removed quantitatively according to 1H NMR using tetrabutylammonium fluoride (TBAF)(Scheme 1).All polymerizations proceeded via first order kinetics,indicating good control over the polymerization process,and,as a conquence,polydispersity indices (PDI’s)were low (Table 1).As aforementioned,functionality can also be introduced by post-polymerization end gro
up modification.This method was ud for the preparation of azide mono-and bifunctionalized PS (Scheme 2).The bromide end groups which were prent after performing ATRP were replaced by azides using azidotrimethyl-silane and tetrabutylammonium fluoride (TBAF).12Completion of the substitution reactions was confirmed by a shift of the methine protons adjacent to the end groups in 1H NMR spectra (d 4.48–3.91ppm)and the appearance of azide signals in FTIR-ATR spectra (2090cm 21).
As a third polymer,commercially available poly(ethylene glycol)methyl ether (PEG)was ud.The hydroxyl group was
{Electronic supplementary information (ESI)available:Experimental procedures and details.Semilogarithmic plots of all performed polymer-izations.SEC traces of all performed cycloaddition reactions.See www.rsc/suppdata/cc/b4/b412930j/
*j.vanhest@science.ru.nl
Scheme 1Introduction of terminal alkyne functionality in polymers utilizing functionalized ATRP initiator 1.
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quantitatively converted into an azide or alkyne functionality according to 1H NMR,as depicted in Scheme 3.The azide end group was introduced by tosylation of the hydroxyl functionality and subquent substitution with sodium azide.Terminal alkynes were introduced directly via a carbodiimide mediated coupling of 4-pentynoic acid.
The thus obtained polymer building blocks were coupled via 1,3-dipolar cycloaddition reactions between the azide and alkyne
end groups using CuI and 1,8-diaza[5.4.0]bicycloundec-7-ene (DBU),13hence forming block copolymers (Scheme 4),as summarized in Table 1.In the ca of block copolymers containing PEG blocks,a slight excess of PEG was ud (1.2equivalents)in order to drive the click reactions to completion.This excess of PEG was easily removed after the reaction via a washing step with metha
nol.In the ca of PMMA-b -PS,an excess of alkyne functionalized PMMA was ud (1.2equivalents).Becau in this ca the small excess could not be removed by washing,the excess of alkyne functionalized PMMA was successfully scavenged by a click reaction onto azide functionalized polystyrene resin (Scheme 4).14In all cas no residual starting material was obrved in SEC traces of the block copolymers (Fig.1)
Completion of the reaction was determined by the disappear-ance of the azide signals in FTIR spectra.Furthermore,for all performed click reactions a shift in the SEC trace was obrved towards higher molecular weight,indicating block copolymer formation (Fig.1).Moreover,no increa of the PDI was obrved upon block copolymer formation which implies that the coupling reactions went to completion.
Table 1Results of the polymerizations and subquent cycloaddition reactions
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Polymer M n,th a /kg mol 21M n,SEC b /kg mol 21PDI a PMMA–M [2a ]7.087.85 1.14b PMMA–M [2b ]18.1421.28 1.13c PMMA–M [2c ]15.4113.49 1.16d PS–M [3] 5.17 4.82 1.23e PS–N 3[4] 4.15 3.52 1.15f N 3–PS–N 3[5]12.8511.69 1.14g PEG–M [6] 2.08 2.72 1.04h PEG–N 3[7]
2.02
3.18 1.04i PMMA-b -PEG [2a-b -7]9.1011.77 1.12j PMMA-b -PEG [2b-b -7]20.1625.32 1.08k PS-b -PEG [3-b -7]
种牙过程
征婚7.197.53 1.17l PEG-b -PS-b -PEG [6-b -5-b -6]17.0117.69 1.13m
PMMA-b -PS [2c-b -4]
19.56
17.78
1.13
a
Theoretical M n bad on conversion measured by GC.b
SEC measurements were conducted in THF.PMMA and PS standards were ud for
笛曲
calibration.
Scheme 2Incorporation of azide end groups in polystyrene via an end group modification
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procedure.
Scheme 3Preparation of azide and alkyne functionalized poly(ethylene
glycol).
Scheme 4Two examples of the modular formation of block copolymers via a 1,3-dipolar cycloaddition of azide and alkyne functionalized polymers.(a)PMMA-b -PEG 2a-b -7.(b)PMMA-b -PS
2c-b -4using an azidomethyl polystyrene resin to scavenge the excess of alkyne function-alized
PMMA.
Fig.1SEC traces of alkyne functionalized PMMA 2a ,azide functiona-lized PEG 7and the coupled diblock copolymer 2a-b -7.
58|Chem.Commun.,2005,57–59This journal is ßThe Royal Society of Chemistry 2005
In conclusion,we have demonstrated a modular approach for the synthesis of block copolymers via a Huisgen1,3-dipolar cycloaddtion of terminal alkynes and azides.Terminal alkyne and azide functionalities were conveniently introduced via ATRP using functionalized initiators,or via a post-polymerization end group modification.SEC measurements of the subquent cycloaddition reactions demonstrated that block copolymers were formed quantitatively and that residual polymer precursors could be removed successfully from the reaction mixture.We are currently extending this procedure to bio-related block copolymers.
Joost A.Opsteen and Jan C.M.van Hest*
Organic Chemistry,Institute for Molecules and Materials,Radboud University Nijmegen,Toernooiveld1,6525ED Nijmegen,
引文
干重和鲜重什么意思The Netherlands.E-mail:j.vanhest@science.ru.nl
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黑胡椒牛肉意面
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