End-functionalized polystyrene by ATRP: A facile approach to primary amino and carboxylic acid terminal groups

End-Functionalized Polystyrene by ATRP: A Facile Approachto Primary Amino and Carboxylic Acid Terminal Groups

JAN HEGEWALD, JURGEN PIONTECK, LIANE HAUßLER, HARTMUT KOMBER, BRIGITTE VOIT

Department Polymer Reactions and Blends, Leibniz Institute of Polymer Research Dresden,Hohe Straße 6, D-01069 Dresden, Germany

Received 17 December 2008; accepted 27 March 2009DOI: 10.1002/pola.23451Published online in Wiley InterScience (www.interscience.wiley.com).

ABSTRACT: Monoamino-terminated and monocarboxylic acid-terminated polystyrenescontaining active halogenated end groups were prepared by atom transfer radical po-lymerization (ATRP) using the so-called initiator method and protective group chem-istry. a-Chloropropionates were synthesized and utilized as initiators containing thetert-butoxycarbonyl (t-BOC)-protected amino and the tert-butyl (t-Bu)-protected car-boxylic acid function, respectively. Optimum polymerization conditions were attainedusing CuCl/N,N,N0,N00,N00-pentamethyldiethylenetriamine (PMDETA) as catalyst and10 vol % n-butanol as homogenizing agent at 110 �C. However, targeting larger quan-tities an alternative route was established employing 50 vol % N,N-dimethylforma-mide (DMF). Subsequent hydrolysis of the x-tert-butoxycarbonyl polystyrenesafforded well-defined polymers with quantitative deprotection of the functionalgroups. Comparatively, thermolytic cleavage of the protective sites was studied. 1HNMR verified the quantitative removal of the t-BOC-protecting groups. Furthermore,the resulting a-amino-x-chloro polystyrenes were reacted with Sanger reagent toconfirm the existence of the thereby converted primary amino groups. VVC 2009 Wiley

Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3845–3859, 2009

Keywords: amino and carboxylic terminal groups; atom transfer radicalpolymerization (ATRP); functionalization of polymers; polystyrene; tert-butoxycarbonylprotecting group (t-BOC)

INTRODUCTION

The properties and applications of polymersdepend upon molecular weight, molecular weightdistribution, and molecular structure (composi-tion, topology, and functionality).1,2 Consequently,synthetic methods allowing control over these pa-rameters are desirable.

On account of this, Sawamoto and coworkers3,4

and Matyjaszewski et al.5 reported first on theatom transfer radical addition (ATRA), also called

Kharasch addition,6,7 to control radical polymer-ization of vinyl monomers. This approach wascoined atom transfer radical polymerization(ATRP) by Matyjaszewski. These polymerizationsare based on a transition-metal complex to controlthe dynamic equilibrium between active propa-gating radicals and a larger amount of dormantspecies by reversible redox reaction involving theexchange of a radically transferable atom orgroup, for example, a halogen. Provided that ini-tiation is complete and exchange between reactivespecies is fast so that termination reactions canbe suppressed, one can adjust the final molecularweight of the polymer by the initial monomer-to-initiator ratio and the functionalities (a- andx-end) by the structure of the initiator while

Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 47, 3845–3859 (2009)VVC 2009 Wiley Periodicals, Inc.

Correspondence to: J. Pionteck (E-mail: [email protected])

3845

maintaining a narrow molecular weight distribu-tion. Furthermore, one has control over the chem-istry since ATRP shows great tolerance towardmonomers and functional groups, which is onlylimited by molecules and functionalities that docoordinate to the catalyst system.8 By using afunctional initiator functionalities such ashydroxyl,9–11 epoxide,12 cyano,13 and allyl14

groups have been incorporated at one chain endwhile the other chain end remained a halide,which can be reactivated to create block copoly-mers, end-capped, for example, via dehydrohalo-genation to give vinylic chain ends, or trans-formed in a postpolymerization step to other func-tionalities using nucleophilic substitution orelectrophilic (cyclo-)addition reactions.15

Aiming primary amino functionalities severalstrategies may be envisaged. It appears that aro-matic amines are compatible with ATRP.16–18

However, the low reactivity of aromatic amineslimits their utility. Also, attempts to synthesize ali-phatic a-primary aminofunctionalized x-halogen-ated polymers directly by ATRP were undertaken,but side reactions of the amino groups with thehalogen end of the initiator molecules or the grow-ing chains and interactions with the ligand weredisadvantageous.19 Consequently, ATRP requiresthat aliphatic primary amino groups are incorpo-rated in some latent form to be converted to thedesired functionality in a postpolymerization step.Postma et al. explored the synthesis of primaryamino end-functional polystyrenes through inter-mediary phthalimido end groups according theGabriel/Ing-Manske procedure.20 However, theirstrategy necessitates the removal of the bromineend to avoid interactions with hydrazine duringthe deprotection step. Coessens et al. and Matyjas-zewski et al. described the chemoselective dis-placement of the x-halo-functionality to the corre-sponding x-azido-functional groups resulting inprimary amino functions after subsequent reduc-tion.21–23 Also the approach chosen by Sadhu et al.utilizing the tert-butoxycarbonyl (t-BOC) group toprotect the free amino function during ATRP didnot result in a-amino x-halogenated polymers.24,25

They described that hydrogen transfer from excessligand resulted in polymers devoid of halogen. Fur-thermore, terminating side reactions like dehydro-halogenation and disproportionation occurringfrom the beginning of the polymerization led to aloss of control, hence, halogen-free polymers withrather broad polydispersities were obtained.

Besides aminoterminal groups, which canserve as anchor groups for a variety of interesting

biological and nonbiological applications in bothorganic and aqueous solutions,17,26,27 carboxylicacid functionalities are of particular interest.They can also be utilized for the aforementionedpurposes. Furthermore, carboxylic acid groupscan be transformed into other useful functional-ities or can be used to prepare block copolymers,for example, by using ring-opening polymeriza-tion28 or by reactive blending26,29 forming in situcompatibilizing agents in immiscible blends. Atfirst, a-halocarboxylic acids were used as initiatorin ATRP but they exhibited low efficiencies.28,30

Therefore, Zhang and Matyjaszewski developedan approach using carboxylic acid initiators withremote halogen. Albeit they observed ‘‘catalystpoisoning’’ in the manner that carboxylic acidgroups coordinate to the transition-metal catalyst,the carboxy function remote to the initiation sitedoes obviously not interfere the ATRP process andleads to well-defined polystyrenes with terminalcarboxylic acid groups.28 In addition, protectivegroup chemistry was applied.26,28 Protection ofthe carboxylic acid group by trimethylsilyl, tert-butyldimethylsilyl or tert-butyl group led toimproved initiator efficiencies but required anadditional step, the hydrolysis to deprotect thefunctionality.

Herein, the utilization of protective group chem-istry is extended to the synthesis of well-definedpolystyrenes carrying a primary amino or carbox-ylic acid functionality at the a-end while retainingthe active halogen initiator site at the x-end(Scheme 1). The retained functionality at bothends makes the resulting polymers interestingand viable for numerous ideas and applications,for example, their utilization as macroinitia-tor,31,32 postpolymerization reaction to modify oneor both ends,13,15 and so forth. Furthermore, theinfluence of polymerization parameters on theATRP process will be discussed. As ATRP is quitecomplex, these influences are further examinedwith regard to the synthesis of larger quantities inthe 80-g scale, making the synthesized well-defined functionalized polymers accessible forpotential applications in different technologicalareas like surface modification, adhesion, drugdelivery, polymeric catalysis, or for compatibiliza-tion in polymer blends. In this regard, we haveinvestigated the deprotection by both acidolysisand thermolysis. The former we have studied tofacilitate the removal of copper catalyst simultane-ously with the postpolymerization hydrolysis step.

Anticipatory, the ATRP accompanied by protec-tive group strategy provides a facile approach

3846 HEGEWALD ET AL.

Journal of Polymer Science: Part A: Polymer ChemistryDOI 10.1002/pola

toward primary amino and carboxylic acid-func-tionalized polymers with well-controlled molecu-lar structure.

EXPERIMENTAL

Materials

Unless otherwise stated, all materials were pur-chased from commercial sources and used withoutfurther purification: Copper(I) chloride (CuCl,Aldrich, 99.995þ%), copper(I) bromide (CuBr,Aldrich, 99.999%), N,N,N0,N00,N00-pentamethyldie-thylenetriamine (PMDETA, Aldrich, 99%), 2,20-bipyridine (bpy, Lancaster, 99þ%), tris(2-amino-ethyl)amine (TREN, Aldrich, 96%), 2-chloropro-

pionyl chloride (CPC, Aldrich, 95þ%), 2-bromo-propionyl bromide (BPB, Aldrich, 97%), di-tert-butyl dicarbonate (BOC anhydride, Fluka, 98þ%),alumina (aluminum oxide 90 active neutral,Merck). Styrene (St, Aldrich) was dried over cal-cium hydride and distilled under reduced pres-sure. Solvents were distilled prior to use.

Characterization

NMR spectra were recorded on a DRX 500 NMRspectrometer (Bruker) operating at 500.13 MHzfor 1H and 125.77 MHz for 13C. CDCl3 was usedas solvent, lock, and internal standard (d(1H)¼ 7.26 ppm, d(13C) ¼ 77.0 ppm). The atom num-bering corresponds to those given in Scheme 2.

Scheme 1. Illustration of the processing steps toward mono-primary amino andmonocarboxylic acid-terminated polystyrene via (i) ATRP and subsequent (ii) hydrolysis.

Scheme 2. Synthesis of t-Bu and t-BOC-protected ATRP initiators: Route I formonocarboxy-terminated polymers and route II for monoamino-terminated polymers;Route III–IV: Synthesis of primary amine-containing initiator.

END-FUNCTIONALIZED POLYSTYRENE BY ATRP 3847


GPC measurements were carried out using aJasco 880 PU pump equipped with three Styragelcolumns (106 A, 105 A, 104 A, linear, and guard) inseries with a Waters 2410 RI detector. Calibrationwas based on narrow molecular weight polysty-rene standards. For Sanger tests, GPC was con-ducted with a Polymer Laboratories PL-GPC 50Plus system equipped with an RI and a UV detec-tor (set at a wavelength of 380 nm), and a Resi-pore column (PL 1113-6300, Varian), using THFas eluant at a flow rate of 1 mL min�1. The ma-trix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS)experiments were performed on a Biflex IV sys-tem (Bruker Daltonics) with delayed extractionoption. Desorption or ionization was performed bya pulsed N2 laser. The mass spectra were obtainedfrom 19-kV acceleration voltages in the reflectionmode. An external calibration was used (PEG5000 standard, Polymer Laboratories, Amherst,MA). The matrix used was 1,3,9-trihydroxyan-thracene (Dithranol, Sigma-Aldrich) with Ag saltas a cationizing agent. Solutions of analyte andmatrix were prepared with a concentration of 10 gL�1 in THF and mixed in a molar ratio of 1:10.The measurements were carried out with positivepolarity. Atom absorption spectroscopy was per-formed utilizing a SpektrAA 10 (Varian) withgraphite furnace GTA96 (Varian) and a copper-hollow cathode (LOT) at a resonance line of324.8 nm.

Synthesis of tert-Butyl-2-chloropropionate (1)

Several papers deal with the synthesis of tert-butyl-2-chloropropionate.33,34 We have chosen thefollowing approach (I, Scheme 2): CH2Cl2 (100mL), t-butanol (14.8 g, 0.2 mol), and TEA (30.3 g,0.3 mol) were placed in a 250-mL round bottomflask and cooled down to 0 �C. A solution of CPC(25.38 g, 0.2 mol) in CH2Cl2 (50 mL) was addedvery slowly to the stirred and with ice-bath cooledsolution and left for additional 12 h at RT. Themixture was washed thoroughly with water toremove excess t-butanol and triethylammoniumchloride. The organic phase was extracted, driedover MgSO4, and distilled. To avoid decompositionof the product, the distillation was carried out atreduced pressure of 50 mbar. The product wasreceived as third fraction between 72 and 74 �Cwith a yield of 67% (22.1 g).

1H NMR (CDCl3, d in ppm): 4.28 (q, 1H, H1),1.65 (d, 3H, H2), 1.48 (s, 9H, H3).

Synthesis of [2-[(2-Chloro-propionylamino)-ethyl]-carbamic Acid tert-Butyl Ester (3)

Compound 3 was synthesized in two steps as out-lined in II, Scheme 2.

a. The synthesis described by Vo et al.35

was optimized and utilized for the firststep. A solution of di-tert-butyldicarbonate[(BOC)2O, 26.2 g, 0.12 mol] in 1,4-dioxane(300 mL) was added for more than 4 h to avigorous stirred solution of ethylenedia-mine (55.7 g, 0.93 mol) in 1,4-dioxane(300 mL) at RT. After 20 h of stirring atRT, a white slurry of bis(N,N0-tert-butyloxy-carbonyl)-1,2-diaminoethane was removedby filtration. The filtrate was concentratedby vacuum evaporation to remove excess ofsolvent and unreacted ethylenediamine.The subsequent dropwise addition of500 mL water precipitated bis(N,N0-tert-butyloxycarbonyl)-1,2-diaminoethane, whichwas filtered off. The resulting aqueous solu-tion was saturated with sodium chlorideand extracted with dichloromethane. The or-ganic phase was collected, dried over mag-nesium sulfate, and evaporated to give18.6 g (97% yield) of tert-butyl-N-(2-amino-ethyl)carbonate (2) as a yellowish oil.

b. The esterification of 2 with 1-halogenopro-pionate halide proceeded as follows: 5.46 g(0.034 mol) of 2 were dissolved in dryCH2Cl2 (50 mL), the flask was poured withargon and sealed with a rubber septum.The solution was cooled down to 0 �C andfreshly distilled triethylamine (TEA, 4.8mL, 0.034 mol) was added. The solutionwas left in an ice bath, and CPC (3.3 mL,0.034 mol) was added dropwise via a sy-ringe over a period of 10 min. The reactionmixture was left for additional 30 min inan ice bath and was then stirred for 48 hat room temperature. After two days, hex-ane (250 mL) was added slowly. The pre-cipitated white crystals were separated byfiltration and washed with cold hexane.The crystals were recrystallized from hex-ane and dried in vacuum at 40 �C to give8.2 g (96% yield).

1H NMR (CDCl3, d in ppm): 7.13 (br, 1H, NH3),4.84 (br, 1H, NH6), 4.41 (q, 1H, H1), 3.40 (q, 2H,H4), 3.33 (q, 2H, H5), 1.74 (d, 3H, H2), 1.46 (s, 9H,H7).



Aminolysis of CPC with Ethylenediamine

The reaction proceeded under nitrogen atmos-phere. Ethylenediamine (30.05 g, 27.05 mL,0.5 mol) was dissolved in 1,4-dioxane (300 mL).The solution was cooled to 0 �C and CPC (6.35 g,8.3 mL, 0.05 mol) diluted in dioxane (200 mL) wasadded dropwise into the ice-bath cooled solutionwithin 12 h. The reaction mixture was stirred foradditional 24 h at RT, the formed solid was fil-tered off, and the solution was concentrated toremove excess of dioxane and unreacted ethylene-diamine. The liquid residue was treated withwater, which was subsequently dropped intothe stirred solution. A white solid was precipi-tated, and the residual solution was saturatedwith NaCl and extracted with dichloromethane.The organic phase was collected, dried overMgSO4, and the solvent was evaporated. Despiteextremely mild conditions and the 10-foldexcess of diamine, 1H NMR revealed that theproduct received corresponds to the two diaster-eoisomers of the diamide of ethylenediamine (5,III, Scheme 2).

1H NMR (CDCl3, d in ppm): 7.00 (s, 2H, NH3),4.42 and 4.40 (two q, 2H, H1), 3.48 (m, 4H, H4),1.74 (d, 6H, H2).

N-(2-Aminoethyl)-2-chloropropionamide (4)by Deprotection of 3

The propionamide (3, 0.08 g, 0.32 mmol) was dis-solved in dichloromethane (9 mL) and a fivefoldmolar excess of trifluoroacetic acid (TFA, 0.12 mL,1.6 mmol) was added dropwise. The reaction wasleft to proceed for 24 h at RT to give the TFA saltof N-(2-aminoethyl)-2-chloropropionate (6). TEA(0.22 mL, 1.6 mmol) was added to the stirred solu-tion. After additional 30 min, water was addedand the solution was extracted with dichlorome-thane. The organic phase was collected, driedover magnesium sulfate, and evaporated to give0.36 g (75%) of the product 4. It is important tonote that the product tends to polymerize athigher temperatures (60 �C) and/or base-cata-lyzed by polycondensation under elimination ofhydrochloric acid to form polyamide (7), as indi-cated in IV, Scheme 2.

6: 1H NMR (CDCl3/TFA-d 1:1, d in ppm): 4.51(q, 1H, H1), 3.80 and 3.70 (m, 2H, H3), 3.46 (m,2H, H4), 1.74 (d, 3H, H2).

4: 1H NMR (CDCl3, d in ppm): 7.02 (br, 1H,NH3), 4.39 (q, 2H, H1), 3.31 (m, 2H, H3), 2.85 (t,2H, H4), 1.72 (d, 3H, H2).

General Polymerization Procedure

A Schlenk flask was equipped with a magneticstirring bar and tightly sealed with a rubber sep-tum. To remove any oxygen the predried flask wasthen cycled three times between vacuum andnitrogen. Solids were added in a reverse flow ofnitrogen and liquids using a nitrogen-rinsed sy-ringe. At first, CuI salt was added, and the flaskwas again cycled three times between vacuum andnitrogen. Ligand and solvent were added subse-quently, and the system was stirred until itbecame homogeneous, hence the catalyst couldform. After the addition of monomer, the initiatorwas added. Three ‘‘freeze–pump–thaw’’ cycleswere performed to remove any left oxygen. Finally,the flask was purged with nitrogen and immersedin an oil bath preheated to the desired tempera-ture �2 �C (Table 1). Conversion and molecularweight over time were determined from aliquotstaken from the reaction mixture by 1H NMR andGPC, respectively. The reaction was stoppedimmersing the Schlenk flask in liquid nitrogenand diluting the solution with THF. The polymerwas precipitated in a 10-fold excess of methanol.

When alcohol was employed as homogenizingagent (10 vol %), the procedure follows thedescription except the fact that the alcohol wasadded prior to the ligand.

Characteristic NMR signals of the end groupsof 8 and 11 (Scheme 3):

8: 1H NMR (CDCl3, d in ppm): 5.3–5.6(HNAC¼¼O), 4.55–4.8 (HNAC(O)O), 4.25–4.55(CHCl), 2.6–3.3 (HNACH2ACH2ANH), 1.43 and1.45 (C(CH3)3), 0.8–1.05 (CHACH3).

13C NMR(CDCl3, d in ppm): 176.4 and 177.1 (HNAC¼¼O),156.5 (HNAC(O)O), 79.4 (C(CH3)3), 60.9 and 61.8(CHCl), 28.4 (C(CH3)3), 16.7–18.8 (CHACH3).

11: 1H NMR (CDCl3, d in ppm): 4.3–4.5 (CHCl),1.28–1.4 (several singlets, C(CH3)3), 0.8–1.05(CHACH3).

13C NMR (CDCl3, d in ppm): 175.8–176.1 (C(O)O), 79.5 and 79.6 (C(CH3)3), 60.9 and61.8 (CHCl), 37.8–38.2 (CHACH3), 27.9 and 28.0(C(CH3)3), 16.2–18.4 (CHACH3).

Deprotection of the t-BOC and t-Bu-ProtectedPolymers by Acidolysis (Scheme 3)

In a typical experiment, the protected polymer(100 mg, 4 lmol) was dissolved in dry THF(5 mL). TFA (0.02 mL, 320 lmol) was added drop-wise to the polymer solution, and the mixture wasstirred at 55 �C under an inert atmosphere ofnitrogen for two days. Then the solvent was



partially removed by rotary evaporation, and thedeprotected polymer was precipitated in coldmethanol. To obtain primary aminofunctionalizedpolystyrene, the polymer was redissolved in THF(5 mL), and TEA (4 lL, 32 lmol) was added forneutralization. The solvent was removed, and thepolymer was again precipitated in cold methanoland dried at 60 �C in a vacuum oven.

Characteristic NMR signals of the end groupsof 10 and 12 (Scheme 3):

10. 1H NMR (CDCl3, d in ppm): 5.1–5.5(HNAC¼¼O), 4.25–4.55 (CHCl), 2.5–3.4 (HNACH2ACH2ANH), 0.8–1.05 (CHACH3).

12. 1H NMR (CDCl3, d in ppm): 4.3–4.5 (CHCl),0.8–1.1 (CHACH3).

13C NMR (CDCl3, d in ppm):180.3 and 180.6 (C(O)OH), 60.9 and 61.9 (CHCl),36.4 and 36.9 (CHACH3), 15.8–18.2 (CHACH3).

RESULTS AND DISCUSSION

Initiator Synthesis

A variety of ATRP initiators are commerciallyavailable. However, for our purposes to utilize t-BOC and t-Bu groups for the protection of pri-mary amino and carboxylic acid functions during

Table 1. Experimental Conditions and Properties of t-BOC-Protected Polystyrenes Prepared by ATRP withInitiator 3 (Mn ¼ 250.7 g/mol) and 1 (Mn ¼ 164.6 g/mol) (Scheme 3), [I]0/[CuCl]0/[Ligand]0 ¼ 1/1/1and [M]0/[I]0 ¼ 240, Targeting 25,000 g/mol: Effect of Ligand, Solvent, and Temperature

Entry Initiator LigandSolvent(vol %)

Temp.(�C)

Time(h) Mn,GPC

Mn,tha

(g/mol) PDIGPC

Yield(%)

1b 3 bpy – 100 5 57,000 13,999 2.09 552 3 Me6TREN – 100 2.5 49,000 11,749 1.67 463 3 PMDETA – 100 7 25,000 12,749 1.26 504 3 PMDETA – 100 24 38,000 17,498 1.30 695 3 PMDETA – 115 9 30,000 16,748 1.25 666 3 PMDETA – 130 3 41,000 22,747 1.30 907b 3 bpy DMF, 25 100 7 46,000 10,249 1.99 408 3 PMDETA DMF, 25 100 7 17,000 13,999 1.23 559 3 PMDETA DMF, 25 100 24 34,000 15,998 1.18 63

10 3 PMDETA DMF, 50 100 24 27,600 18,498 1.28 7311 3 PMDETA DMF, 25 115 20 45,000 20,248 1.49 8012 3 PMDETA DMF, 50 115 20 38,000 18,998 1.62 7513 3 PMDETA MeOH, 10 110 6 29,000 12,249 1.13 4814 3 PMDETA BuOH, 10 110 9 26,500 22,997 1.11 9115c 3 PMDETA BuOH, 20 110 2 5,300 3,500 1.11 6516c 3 PMDETA MeOH, 10 110 2 8,000 4,500 1.15 8517c 1 PMDETA MeOH, 10 110 2 7,400 4,114 1.20 7918c 1 PMDETA – 115 2.5 5,800 4,064 1.42 78

aMn,th ¼ conversion (Minitiator þ (Mstyrene � [M]0/[I]0)).b [I]0/[CuCl]0/[bpy]0 ¼ 1/1/3.c [M]0/[I]0 ¼ 48, targeting 5000 g/mol.

Scheme 3. Synthetic route to derive (i) monoamino-terminated polystyrene from t-BOC-protected polystyrene and (ii) monocarboxylic acid-terminated polystyrene fromt-Bu-protected polystyrene by acidolysis, respectively.



the course of polymerization, respectively, novelfunctional initiators have been successfully syn-thesized. The choice of initiator structure wasbased on previous reports. Sadhu et al. employeda-bromobutyrate containing the t-BOC-protectedamino group as initiator for the synthesis ofmonoamino-terminated PMMA by ATRP.24 Themolecular weight of the products they obtainedwas consistently higher than the theoretical one,and the molecular weight distribution was rela-tively broad (2.2–2.9). They concluded from thesefindings that terminating side reactions, halogenexchange, disproportionation, and dehydrohaloge-nation, occurred from the beginning of the poly-merization.

It is known that tertiary alkyl halides, thoughelectronically similar to propagating species, areless active in ATRP because of smaller back straineffect.8,36,37 This is not observed for secondarystructures. Besides, it was found that chlorineend groups are not as sensitive toward side reac-tions with amines as bromine end groups.19

Thereupon, we synthesized 2-chloropropionatederivatives for initiation. The straightforwardreaction of a-halogenoalkonate halide with tert-butanol yielded initiator (1) with a yield of 67% (I,Scheme 2), which is similar to other reports.33,34

The propionamide initiator (3) was obtained inhigh yield after reaction of ethylenediamine anddi-tert-butyldicarbonate followed by esterificationwith the appropriate a-halogenoalkonate halide(II, Scheme 2).

Although it is controversially discussedwhether primary aliphatic amines hinder theATRP process by interfering with the metal–ligand catalyst,19,38 we have carried out attemptsto synthesize N-(2-aminoethyl)-2-chloropropiona-mide as ATRP initiator carrying a free primaryamino group. The conversion of ethylenediaminewith CPC (III, Scheme 2) invariably yielded thediamide (5), even if the diamine was used in a 10-fold molar excess and the reaction kinetic wasdecelerated by cooling with ice bath andextremely slow addition of CPC. However, thedeprotection of 3 with TFA and subsequent neu-tralization (IV, Scheme 2) resulted in the desiredinitiator 4 carrying a free amino group at one endand a chloropropionamide group as active initia-tor site at the other end. The cyclization to 3-methyl-piperazin-2-one as possible side reactionin the presence of a base was not observed. Butunfortunately ensuing experiments revealed thatN-(2-aminoethyl)-2-chloropropionate (4) tends toalkylate at higher temperatures of 60 �C forming

polyaminoamide under release of hydrochloricacid. Therefore, the initiator (4) cannot be utilizedfor the ATRP of polystyrene at temperatures ofaround 100 �C. Otherwise, ATRP was already con-ducted at ambient temperatures.39,40 Further-more, one can imagine the usage of the proto-nated form (6) as initiator for ATRP in aqueoussolution41 or in the presence of minor amounts ofpolar solvent.1,41,42

ATRP Process

In the following, we focus on the use of t-Bu and t-BOC-protected initiators for ATRP. Thus, the hal-oester (1) and the halopropionamide (3) wereemployed for the polymerization step (i, Scheme1) to yield, after postpolymerization deprotection(ii, Scheme 1), carboxylic acid and primary amino-terminated polystyrene, respectively. A represen-tative selection of polymerization conditions andanalytical data of the obtained polymers is sum-marized in Table 1. The molecular weight Mn andthe molecular weight distribution (Mw/Mn ¼ PDI)were determined by GPC. The yield was deter-mined gravimetrically and used to estimate thetheoretical molecular weight (Mn,th). Gravimetryis an easy and common method for conversionmeasurement, but it may implicate some experi-mental error.

The ligand tunes the electronic, steric, and sol-ubility properties of ATRP catalyst;43 hence, itforces the catalyst to complex and participate inthe electron transfer, a mechanistic requirementto preserve the controlled radical character ofATRP.44 Based on previous reports,22,45–47 firsttrials were conducted in bulk employing bpy asligand. However, the obtained polystyrene wasdistinguished by a higher molecular weight thancalculated and a rather broad polydispersity(entry 1, Table 1). This is likely due to high radi-cal concentration as result of low catalytic systemefficiency leading to bimolecular termination reac-tion and poor temperature control caused by thehighly exothermic free radical polymerizationcharacter at the beginning. Adams and Young48

found similar effects when employing amide-based initiators with a CuCl/bpy catalyst for theATRP of methacrylics. Therefore, we employedstronger ligands keeping other polymerization pa-rameter constant. Although Me6TREN (entry 2)gave similar results as bpy, the utilization ofPMDETA resulted in polystyrene with the tar-geted molecular weight of 25,000 g/mol and a PDIof 1.26 (entry 3). However, this value was



obtained at 50% conversion, that is, the theoreti-cal molecular weight should be half of it. Longerpolymerization times (entry 4) gave higher yield,but also a higher molecular weight and anincreased PDI. To improve the control, the poly-merization temperature was raised from 100 to115 �C and further to 130 �C (entries 5 and 6),keeping other polymerization conditions constant.It is known that elevated polymerization tempera-tures increase the rate of polymerization becauseof an increased rate of propagation. As result, theratio between propagation and termination reac-tion is higher, and better control may be observedat higher temperatures.44 Additionally, the solu-bility of catalyst increases at higher temperature,making the metal–ligand complex more effective.Indeed, in our studies, an increase in temperatureled to faster conversion and higher yield, but thiswas accompanied by an increase in the molecularweight and molecular weight distribution, prob-ably as result of chain transfer and other sidereactions, which also become more pronounced athigher temperatures.

Another possibility to improve the control dur-ing ATRP is an appropriate solvent. It reduces thelocal concentration of radicals and might posi-tively influence the solubility and complexation ofthe catalyst; hence, the electron transfer reactioncatalyzing the ATRP. For example, Pascual et al.achieved homogeneous ATRP of styrene withCuBr(bpy)3 using 10 vol % N,N-dimethylforma-mide (DMF).49 In a similar approach using 25 vol% DMF and CuCl(bpy)3 (entry 7), poorly con-

trolled polystyrene was obtained in our case.Employing 25 vol % DMF with CuCl/PMDETA(entry 9), the PDI was reduced from 1.30 in bulk(entry 4) to 1.18, and only the yield was slightlydiminished from 69% to 63%. However, the molec-ular weight was still higher than the calculatedone. Therefore, the amount of DMF was furtherincreased to 50 vol % (entry 10), and polystyrenewith the desired molecular weight and a PDI of1.28 was reached in 73% yield. The polymeriza-tion proceeds in a controlled way, and the molecu-lar weight (determined by GPC) grows linearlywith conversion (determined by 1H NMR, Fig. 1).

To reduce the amount of solvent but maintain-ing its homogenizing effect more polar and proticsolvents, 10 vol % methanol (entry 13) and, asconsequence of its low boiling point, 10 vol % n-butanol (entry 14) were used. Hereby, it is impor-tant to emphasize that only good results wereobtained adding the alcohol prior the ligand.Employing n-butanol, the molecular weightincreases according the perceptions of a controlled‘‘living" polymerization monotonically with con-version (Fig. 1) and reaches the desired molecularweight, narrowly distributed (PDI ¼ 1.11), in 91%yield. Thus, the initiator efficiency is increasedfrom 0.66 with 50 vol % DMF at 100 �C polymer-ization temperature (entry 10) to 0.86 with only10 vol % of n-butanol at 110 �C (entry 14).

Figure 2 depicts GPC traces appendant to thedata points presented in Figures 1 and 3. Thesemilogarithmic representation in Figure 3confirms the first-order kinetics of the polymeriza-tion with respect to monomer concentration.

Figure 1. Evolution of molecular weight (filled sym-bols) and polydispersity (hollow symbols) versusmonomer conversion for the polymerization of styreneusing initiator 3 at 100 �C with 50 vol % DMF (entry10, Table 1) and at 110 �C with 10 vol % n-butanol(entry 14, Table 1).

Figure 2. GPC traces of polystyrene polymerizedwith initiator 3 at 110 �C with 10 vol % n-butanolrecorded from samples at the specified time. Conver-sion was determined by 1H NMR, Mn and PDI weredetermined by GPC.



Furthermore, it gets evident that the rate of poly-merization is dramatically faster with 10 vol % n-butanol at only slightly more elevated tempera-tures of 110 �C (entry 14) than with 50 vol %DMF at 100 �C (entry 10). An acceleration ofATRP in polar solvents has already beenreported.41,42 Moreover, the use of polar additives,such as butylamines38 or water,50,51 in a way thata homogeneous reaction mixture is retained,enhances the controlled radical polymerization ofhydrophobic monomers, in these particular stud-ies of methacrylates. Matyjaszewski et al.52

pointed out that solvent-assisted side reactions,such as elimination of HX from polystyryl halides,are more pronounced in polar solvent and recom-mends the use of nonpolar solvent for the ATRP ofstyrene. To assay these findings, polystyrene witha lower molecular weight of 5000 g/mol was syn-thesized for NMR studies. The polymerizationconditions were derived from previous experi-ments; 10 vol % methanol at 110 �C were appliedemploying both initiators, the haloester (1) andthe halopropionamide (3). The obtained polysty-renes carrying the protected functionality, eithercarboxylic acid (entry 17) or amino group (entry16), were obtained in good yield with the desiredlow molecular weight. The proton spectrumshown in Figure 4(a) corresponds to the desired t-BOC-protected amino-terminated polystyrene (8,Scheme 3) containing the chloromethine endgroup. No distinct peaks indicating unsaturatedchain ends (between 6.05 and 6.20 ppm53) arevisible, so the amount of unsaturated end groupsis negligible (\2%). The presence of the t-BOCgroup gets evident by the strong signals of its

methyl groups overlapping the methylene protonsignal of the polystyrene backbone with two peaksat 1.43 and 1.45 ppm. The characteristic signal ofthe chloromethine end group appears between4.25 and 4.55 ppm. The peak assignments wereestablished by combination of 1D and 2D NMRmethods. The NMR spectrum of t-Bu-protectedcarboxylic acid-terminated polystyrene (11,Scheme 3) also evidences the presence of the pro-tecting group and the retained chloromethine endgroup (not shown).

Deprotection by Acidolysis to Releasethe Desired Functionality

After successful ATRP, the obtained well-defineda-tert-butoxycarbonyl-x-chloride-terminated poly-mers (8 and 11) were deprotected under classicalconditions with TFA as the reagent of choice.54–56

The removal of the t-Bu group yielded straightfor-ward and quantitatively the carboxylic acid-func-tionalized polystyrene. The expected structurewas fully verified by 1H and 13C NMR spectros-copy (Experimental section).

In the following, the deprotection of the t-BOCgroup resulting in the terminal primary aminoend group-functionalized polystyrene is presentedin detail. The treatment with TFA causes the lib-eration of isobutylene and carbon dioxide andleads to the protonated ammonium salt form ofthe polymer (9, Scheme 3). Its proton NMR spec-trum [Fig. 4(b)] depicts the distinct resonance at

Figure 3. Kinetics of the polymerization of styreneusing initiator 3 at 100 �C with 50 vol % DMF (entry10, Table 1) and at 110 �C with 10 vol % n-butanol(entry 14, Table 1).

Figure 4. 1H NMR spectrum of t-BOC protectedpolystyrene with retained chloride end group. Insetsshow signals of the initiating group and the methineproton of the terminal group: (a) of the t-BOC pro-tected polystyrene, (b) after deprotection in the am-monium salt form, and (c) in the amino form (cf.Scheme 3).



4.25–4.55 ppm of the chloromethine terminalgroup. The signals of the carbamate hydrogenbetween 4.55 and 4.8 ppm disappear in conse-quence of its removal. Furthermore, the amidichydrogen signals located between 5.3 and 5.6 ppmshift to 5.8 and 6.3 ppm. After neutralization of 9with TEA to yield the final product, a-amino-x-chloro polystyrene (10, Scheme 3), the amidic pro-ton resonances shift backwards to 5.1–5.5 ppm[Fig. 4(c)]. The signal corresponding to the protonof the chloromethine end group is retained at4.25–4.55 ppm. The integral ratio of the two sig-nal regions is 1:1 and coincides perfectly with theexpected structure (10). Moreover, no signals indi-cating unsaturated chain ends are visible.

To further examine the end groups, MALDI-TOF MS analysis was performed in the reflectionmode. Figure 5 shows the obtained MALDI-TOFMS spectra of the protected polymer and of thepolymer after 2 and 24 h of hydrolization followedby neutralization. In all spectra, two series of sig-nals with a peak-to-peak distance of 104.15 Da(mass of polystyrene repeat unit) are detectable.The major peak series in the spectrum of the pro-tected polymer, the asterisk denotes the peakwith a molar mass of 7540 Da, corresponds to theparent product (8, Scheme 3) distinguished by thechlorine end group. The prior minor peaksincrease with hydrolization time, whereas thepeaks reflecting the t-BOC-protected chlorine con-taining polystyrene decrease. Unfortunately, thesignals of this peak series cannot clearly be

assigned, thus the structure of the hydrolyzedproduct cannot be unambiguously verified byMALDI-TOF MS. Indeed, it has been describedpreviously that MALDI-TOF MS is beset bypotential polymer end group fragmentation dur-ing the ionization process.38,57 However, the exis-tence of a-amino end groups was confirmed byconversion of the polymer with 1-fluoro-2,4-di-nitrobenzene (Sanger reagent) resulting in anintense yellow chromophore. The latter was effec-tively observed when a-amino polystyrene wasstirred in the presence of Sanger reagent in pureTHF. However, such visual test should not beoverinterpreted. To ascertain the nucleophilic aro-matic substitution between the primary aminogroup and the Sanger reagent, the yellowish poly-mer was characterized by GPC measurementsutilizing an RI and supplementary a UV detectorset to a wavelength of 380 nm. For comparison,also the a-t-BOC-protected polymer was convertedwith Sanger reagent and characterized by GPCwith RI and UV detection. The elugrams of bothdetectors are presented in Figure 6. Whereas boththe converted protected and deprotected polymersare detected at 6.8 mL with the RI detector the a-t-BOC-protected polymer gives no signal, andonly the converted a-amino polystyrene wasdetected with the UV-detector. This clearly

Figure 5. MALDI-TOF mass spectra of t-BOC-pro-tected polystyrene (entry 16, Table 1): protected(bold), after 2 h and 24 h of hydrolization with TFAand subsequent neutralization. [Color figure can beviewed in the online issue, which is available atwww.interscience.wiley.com.]

Figure 6. Primary amino test using 1-fluoro-2,4-dinitrobenzene (Sanger reagent): GPC elugramsmeasured for protected a-amino polystyrene, a-aminopolystyrene deprotected by acidolysis (Mn � 27,600 g/mol), and a-amino polystyrene deprotected by ther-molysis (Mn � 14,600 g/mol) after reaction withSanger reagent. GPC elugrams were recorded in THFwith RI detector and UV detector set at a wavelengthof 380 nm.



indicates that the dinitrobenzene is covalentlybound to the polymer, hence the existence of reac-tive primary amino groups at the end of the poly-mer chains.

Upscaling of the ATRP Process

To explore the full potential of the presentedapproach toward well-defined primary amino andcarboxylic acid end-functionalized polystyrenes,an additional objective of our work was to makethis ATRP process viable on a larger scale; in par-ticular by (i) an upscaling of the ATRP process,(ii) easing the copper-catalyst removal, and (iii)facilitating the deprotection step.

With regard to the first point (i), we enhancedthe quantity of monomer to batches up to 80 g.First experiments were carried out employingthe explored optimized conditions of entry 10 inTable 1. Well-defined a-tert-butoxycarbonyl-x-chloride polystyrenes exhibiting the proposedstructural features were obtained. The molecularweights are in the desired range, and just the poly-dispersities are slightly increased (Table 2). Apossible explanation is that the homogeneitycould not be fully maintained at upscaling. How-ever, 44 g of well-defined end-functionalized poly-styrene were successfully synthesized in onebatch. Also, the upscaling in the presence of n-bu-tanol (conditions of entry 14) resulted in polymerswith the desired molecular weight and weight dis-tributions Mw/Mn of about 1.2, but the reproduci-bility is still under investigation.

As a drawback of ATRP, the final product con-tains a significant amount of copper catalyst,which may be hazardous or may impede specificapplications. Several strategies for catalyst re-moval have been developed.58–62 Based on previ-ous publications, methanol was used to precipi-tate the polymer and simultaneously to remove

the copper catalyst partially.60,61 The methanolsolution turned blue indicating the copper uptakeand the copper concentration of the resultingpolymer equates to 461 ppm, measured by atomabsorption spectroscopy. The concentration of cop-per was reduced to 6 ppm when the polymer (1 g)was subsequently dissolved in THF and passedthrough a column filled with alumina (0.3 g). As itis intricate and time consuming to pass largerquantities (e.g., 50 g) of polymer through a col-umn, other approaches were considered to evencombine the catalyst removal with the requireddeprotection step. The alumina (0.3 g) was addedduring the treatment of the polymer (1 g) withTFA in THF and removed by subsequent filtrationprior precipitating the polymer in methanol. Theresidual copper content of the resulting polymerwas below the detection limit of 2 ppm. Further-more, the (recovery) yield related to the postpoly-merization steps (deprotection and copper catalystremoval) is increased to 92% compared to 84%when the polymer was passed through a column.Supplementary, the copper concentration of thepolymer precipitated twice in methanol, after po-lymerization and after treatment with TFA, equa-tes 17 ppm. To sum up, best catalyst removal effi-ciency was achieved stirring the polymer solutionwith alumina. Besides, the advantage that lesssolvent is required compared to passing the poly-mer through a column, the recovery yield isgreater, the product contains less copper, and thecatalyst removal can be accompanied with thedeprotection saving an additional step.

With regard to objective (iii), to facilitate thedeprotection, thermolysis offers the possibility toremove the t-BOC group cleanly and in quantita-tive yield.56,63 Thermolysis of t-BOC has been suc-cessfully utilized in the chemical amplification ofphotoactive materials for microelectronics and ingeneral to release desired functionalities in poly-meric films for a variety of applications.63–65

Although the thermal removal can be catalyzed,that is, the thermolysis temperature can be low-ered by acids (e.g., HSbF6 or HAsF6),

63,66 firstthermogravimetric experiments were carried outwithout catalyzing agents under nitrogen atmos-phere with a heating rate of 10 K/min. The experi-ments were performed using a TGA-Q5000 (TA-Instruments) coupled with online Fourier trans-form infrared spectroscopy (FTIR, Nicolet 380,Thermo Fisher Scientific), making it possible toassign volatile components under investigation tothe decomposition stages detected by TGA (TGA-FTIR). The thermogram recorded from t-BOC-

Table 2. Upscaling of the ATRP of Styrene withInitiator 3 Utilizing 50 vol % DMF at 100 �C,Targeting 25,000 g/mol

m0

(Styrene) (g)Time(h)

Mn,GPC

(g/mol) PDIGPC

Yield(%)

6 24 27,600 1.28 7320 21 29,000 1.33 5540 21 30,000 1.38 7280 21 27,400 1.40 55

[M]0/[I]0 ¼ 240.



protected amino-terminated polystyrene (Mn,GPC

¼ 14,600 g/mol) is presented in Figure 7(a) andindicates a two-stage decomposition behavior. Agood correlation exists between the derivative ofthe TGA curve and the maxima of the Gram-Schmidt curve, the summation of the intensitiesof the characteristic band lines over the entirespectral range, as a function of temperature [Fig.7(b)]. Figure 7(c) illustrates chemigrams of theband intensities as function of time correspondingto the temperatures shown in Figure 7(a,b). Thedashed, dash-dotted, and solid curves representthe band intensities of the distinct bands at 889,2363, and 775 cm�1 characteristic for isobutene(d(¼¼CH2)), carbon dioxide (m(O¼¼C¼¼O)), and sty-rene (d(¼¼CH)), respectively. Thus, from couplingFTIR with TGA it gets clear that the weight lossat 260 �C (after 23 min) is only attributed to thedegradation of t-BOC units to carbon dioxide andisobutene. This decomposition stage assigned tothe deprotection of the primary amino functional-ities is followed by a plateau, where no volatilecomponents are released, indicating that the ther-mally modified polymer is stable up to muchhigher temperatures. The second decompositionstage starts at 340 �C (30 min) and shows themaxima in the derivative of the TGA and in the

Gram-Schmidt curve at 420 �C (38 min); it is dis-tinguished by absorption spectra correlating withthe library absorption spectrum of styrene.

For structural investigations of the thermallydeprotected polymers, the t-BOC-protectedamino-terminated polystyrenes were exposed toTGA and either heated to 280 �C with 10 K/minand instantly cooled down with the same rate, orheated up to 240 �C with 10 K/min, left for 10 minat the specified temperature, and cooled downwith 10 K/min to ambient temperatures. Bothproducts were characterized by GPC and 1H NMRand showed the same characteristics. The molarmass of the deprotected polymers did not varyfrom the former protected polymer. 1H NMR evi-denced the quantitative removal of the t-BOCgroup. Furthermore, the characteristic signal ofthe chloromethine end group between 4.25 and4.55 ppm disappeared, whereas new peaksbetween 6.05 and 6.2 ppm arose. Hence, dehydro-halogenation, occurred during the solid-statethermolysis leading to unsaturated chain ends.Unfortunately, the primary amino function at thea-chain end could not be confirmed unambigu-ously. Comparing the proton spectrum of thethermolytic deprotected polystyrene with theproton spectrum of a-amino-x-chloro polystyrene

Figure 7. TGA-FTIR of t-BOC-protected amino-terminated polystyrene: (a) weight,(b) derivative weight and Gram-Schmidt curve in dependence on the temperature,and (c) chemigrams of the FTIR band intensities of evolving gases at 889, 2363, and775 cm�1 as function of time during thermogravimetric analysis representing therelease of isobutene, carbon dioxide, and styrene, respectively.



resulting from acidolysis [Fig. 4(c)], the amidicproton resonances between 5.1 and 5.5 ppm arenot pronounced. However, signals correspondingto the ethylene spacer at 2.9–3.6 ppm are evidentand show pH sensitivity. A possible explanationfor the disappearance of the characteristic amidicproton signals is that the thermal deprotection oft-BOC is accompanied by the evolution of ammo-nia resulting in the neutral tautomeric N-ethyli-dene-propionamide and N-vinyl-propionamideend groups. However, neither 1H NMR evidencesthe corresponding peaks nor the characteristicbands for ammonia, especially at 967 cm�1, weredetected by TGA-FTIR during the thermal treat-ment. Furthermore, the thermally modified poly-styrene was converted with Sanger reagent, com-paratively to polystyrene deprotected via acidoly-sis, and resulted in a deep yellow colored powder,which was additionally measured by GPC utiliz-ing an RI and supplementary a UV detector(Fig. 6). Besides the intense yellow color the peaksin the RI and UV detector appearing at the sameelution volume of 8.3 mL indicates the presenceand reactivity of primary amino groups after ther-mal t-BOC elimination.

Comparing acidolysis and thermolysis for thedeprotection of t-BOC end groups to obtain thedesired a-amino-x-chloro polystyrene, both meth-ods can be utilized to remove the protective groupquantitatively. Although the chloride end isretained after acidolysis, the thermal treatment ofthe polymer up to temperatures of 240 �C leads todehydrohalogenation and the formation of x-unsaturated chain ends. As outlined in the litera-ture, the thermolysis temperature can be loweredemploying catalyzing acids for the solid-statethermolysis. This might prevent dehydrohalo-genation. Thus, thermolysis opens a facile approachfor the deprotection of t-BOC groups without theneed of additional chemical treatment.

CONCLUSIONS

Novel a-chloropropionamides and a-chloropropio-nates were synthesized and successfully used asinitiator for the ATRP to obtain primary aminoand carboxylic acid end-functionalized polysty-renes, respectively. Optimum polymerization con-ditions were found utilizing CuCl/PMDETA ascatalyst and a polar solvent such as n-butanol topromote the homogeneity of the polymerizationsystem. Well-defined polymers distinguished bythe desired molecular weight, narrow polydisper-

sities, and the desired functionality at the a-endwere obtained in small scale (�1 g) and largescale (�44 g). Moreover, the halogen end wasretained during ATRP. Thus, the polymer con-tains not only a primary amino or carboxylic acidsite but also the active initiator site at the x-end.Consequently, both sites may be modified accord-ing the requirements of a possible application.

The catalyst removal from the polymer withregard to the upscaling was facilitated by stirringthe polymer solution with alumina yielding a re-sidual copper concentration in the polymer of lessthan 2 ppm. In this manner, the catalyst removalcan be accompanied with the hydrolysis of theprotection group, carried out in THF under classi-cal conditions with TFA as the reagent of choice.The deprotection by acidolysis afforded well-defined polymers with quantitative conversion ofthe functionalities retaining the chloride end forproposed postpolymerization steps. Compara-tively, the t-BOC protecting group could also beremoved quantitatively by solid-state thermolysis.However, the thermally modified product is dis-tinguished by x-unsaturated chain ends.

The synthetic strategy reported in this articlecan be potentially considered as a ‘‘universal’’route toward large quantities of well-defined carb-oxylic acid and primary amino-functionalizedpolymers, respectively. According to the presentedroutes for catalyst removal and deprotection, onecan adjust the strategy with respect to the struc-tural features and purity requirements on theproduct.

Financial support by the Deutsche Forschungsgemein-schaft (DFG) under grants of SFB 287 is acknowledged.The authors thank D. Kuckling, R. Schulze, K. Arnhold,M. Kipping (Technische Universitat Dresden), and J.Stadermann and S. Boye for the help in matrix-assistedlaser desorption-ionization time-of-flight mass spec-trometry (MALDI-TOF MS), AAS, TGA, GPC, andGPC-UV, respectively. S. Mendrek is acknowledged forpreliminary synthetic studies.

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End-functionalized polystyrene by ATRP: A facile approach to primary amino and carboxylic acid terminal groups