facile synthesis and characterization of hyperbranched poly(ether amide)s generated from michael...

Facile Synthesis and Characterization of HyperbranchedPoly(ether amide)s Generated from Michael AdditionPolymerization of In Situ Created AB2 Monomers

YING LIN,1,2 ZHONG-MING DONG,1,2 XIAO-HUI LIU,1 YUE-SHENG LI1

1State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry,Chinese Academy of Sciences, Changchun 130022, China

2Graduate School of the Chinese Academy of Sciences, Changchun 130022, China

Received 23 March 2007; accepted 18 April 2007DOI: 10.1002/pola.22175Published online in Wiley InterScience (www.interscience.wiley.com).

ABSTRACT: A new straightforward strategy for synthesis of novel hyperbranched poly(ether amide)s from readily available monomers has been developed. By optimizingthe reaction conditions, the AB2-type monomers were formed dominantly during theinitial reaction stage. Without any purification, the AB2 intermediate was subjectedto further polymerization in the presence (or absence) of an initiator, to prepare thehyperbranched polymer-bearing multihydroxyl end-groups. The influence of mono-mer, initiator, and solvent on polymerization and the molecular weight (MW) of theresultant polymers was studied thoroughly. The MALDI–TOF MS of the polymersindicated that the polymerization proceeded in the proposed way. Analyses of 1HNMR and 13C NMR spectra revealed the branched structures of the polymersobtained. These polymers exhibit high-moderate MWs and broad MW distributionsdetermined by gel permeation chromatography (GPC) in combination with tripledetectors, including refractive index, light scattering, and viscosity detectors. In addi-tion, the examination of the solution behavior of these polymers showed that the val-ues of intrinsic viscosity [g] and the Mark–Houwink exponent a were remarkablylower compared with their linear analogs, because of their branched nature. VVC 2007

Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4309–4321, 2007

Keywords: gel permeation chromatography (GPC); hyperbranched; MALDI;Michael addition polymerization; poly(ether aimide)s

INTRODUCTION

Dendrimers and hyperbranched polymers (HBP),together classified as dendritic polymers, haveattracted considerable and increasing attentionin recent years.1 In contrast to dendrimers, HBPhave imperfectly branched structures.2 However,they still inherit the desirable properties similarto dendrimers, such as three-dimensional globu-

lar architecture, low viscosity, good solubility,and abundance of terminal groups. Furthermore,they can be prepared conveniently and cost-effec-tively on a large scale in a one-pot procedure.3

Therefore, HBP can be used as alternatives todendrimers for emerging industrial applications.In last decade, a wide range of HBP have beensynthesized by diverse synthetic strategies, suchas self-polycondensation,4 ring opening polymer-ization,5 self-condensation vinyl polymerization,6

atom transfer radical polymerization,7 reversibleaddition fragmentation chain transfer polymer-ization,8 and other approaches.9

Correspondence to: Y.-S. Li (E-mail: [email protected])

Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 45, 4309–4321 (2007)VVC 2007 Wiley Periodicals, Inc.

4309

Michael addition reaction, which is also com-monly termed as conjugate addition, has re-cently gained widespread attention as a polymersynthesis strategy for tailored macromoleculararchitectures.10 Benefiting from mild reactionconditions, high functional group tolerance, alarge host of polymerizable monomers and func-tional precursors as well as high conversionsand favorable reaction rates,11 Michael additionreaction is widely applied in numerous emergingtechnologies especially for biomedical applica-tions such as drug delivery and gene delivery.12

In fact, the first dendrimer, poly(amido amine)(PAMAM), was synthesized using Michael addi-tion reactions by Tomalia et al. as early as1985.13 The high conversion and facile nature ofMichael addition led to nearly monodisperseindividual dendrimer molecules.2(a) The secondcommon dendrimer, poly(propylene imine) (PPI),is also accessed through the Michael addition ofprimary diamines with acrylonitrile.14 Neverthe-less, the availability of dendritic systems is lim-ited to the two aforementioned dendrimersPAMAM and PPI. Although HBP contain linearunits as insufficient branching, many propertiesof dendritic macromolecules are generally inher-ited. Therefore, HBP synthesized from Michaeladdition are receiving increasing interests espe-cially in biomaterials application.15–19

Usually, Michael addition reactions wereapplied to the ABx strategies for hyperbranchedpolymer synthesis.15 However, most of ABx

monomers are not commercially available andare prepared by several steps. The limited avail-ability of functionally asymmetrical ABx mono-mers has prevented many industrial applica-tions, and more facile synthetic methods are de-sirable for further exploration of HBP. Recently,hyperbranched poly(aspartamide)s were synthe-sized from bismaleimides and aromatic tri-amines using the A2 þ B3 methodology. The A2

and B3 monomers are more readily availablethan ABx monomer, enabling a much widerrange of monomers and polymers.16 Despite thisfact, these reactions are difficult to be controlled;stringent polymerization conditions are neededto avoid gelation, for example, low monomerconcentrations, slow addition rates, and strictlycontrolled monomer conversion.17 Hence, it isnot easy to obtain fully soluble products withhigh molecular weight (MW). A further develop-ment is the use of multifunctional monomerswith suitable unequal reactivity. Several fami-lies of HBP were prepared based on this meth-

odology. Yan reported the synthesis of poly(esteramine)s by the direct Michael addition of di-amines (BB02) to diacrylates (A2), in which eachdiamine contained a secondary amino group anda primary amino group.18 More recently, Liuand his coworkers developed the A2 (or A3) þBB0B@ approach to obtain hyperbranched poly(amino ester)s by the Michael addition polymer-ization of diacrylate (A2) or triacrylate (A3) with1-(2-aminoethyl)piperazine (BB0B@), where thetrifunctional amines have reactivity sequence asfollows: 28 amine (original) > 18 amine > 28amine (formed).19 Because of the suitable reac-tivity difference, crosslinking can be avoidedand the HBP can be prepared even at high con-versions.

To date, only limited families of HBP havebeen prepared through the methods mentionedabove. Our recent efforts have also focused onthe facile synthesis of more types of novel HBPwith various structures.20 To our best knowl-edge, it has not been reported that the hyper-branched poly(ether amide)s were prepared viaMiachael addition polymerization. In this arti-cle, hyperbranched poly(ether amide)s weredesigned from commercially available CB2 typemonomer, secondary amine with two hydroxyls,and AD type monomer, double bond and acryloylchloride group. As shown in Scheme 1, theamino group (C) is more reactive than thehydroxyl (B) towards the acryloyl chloride,which results in the predominant formation of

Scheme 1. Synthetic strategy for novel hyper-branched poly(ether amide)s.

4310 LIN ET AL.

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

amide intermediate. The intermediate can beregarded as a new AB2 type monomer, since thehydroxyl group (B) can add onto the activateddouble bond (A) of acrylic compound followingthe mechanism of Michael addition reaction.Without any purification, the intermediate wassubjected to further polymerization in the pres-ence of catalyst or initiator. The polymerizationmechanism was investigated with respect toelectronic and steric effect. The NMR experi-ment coupled with triple detectors SEC analysisoffers a detailed picture of the branched archi-tecture, MW, and solution properties of theresulted hyperbranched poly(ether amide)s. Thepolymers obtained were water-soluble and hadabundance of terminal hydroxy groups, whichmake them promising functional materials.

EXPERIMENTAL

Materials

Diisopropanolamine (DPAM) and diethanolamine(DEAM) were purchased from ACROS and puri-fied by reduced pressure distillation before use.Sodium hydride (NaH, 35 wt % dispersion in min-eral oil) was obtained from Aldrich and the min-eral oil was removed by three extractions with drytetrahydrofuran (THF). Dry THF, CH2Cl2, andCHCl3 were prepared from solvent purificationsystem (MBRAUN, Germany) prior to use; thecontent of H2O was less than 0.2 ppm. Triethyl-amine (Et3N) was distilled over calcium hydrideafter refluxing for 12 h. Acryloyl chloride (AC),methacryloyl chloride (MAC), potassium tert-butoxide (t-BuOK), 18-crown-6, triphenylphos-phine (PPh3), hydroquinone, and other reagentswere used as received.

Characterization

1H NMR spectra were recorded on a Bruker AV300 MHz spectrometer with CDCl3 or DMSO-d6

as the solvent. 13C NMR spectra were recordedon a Varian Unity 400 spectrometer operatingat 100.0 MHz. To check the quantitative accu-racy of these spectra, the samples were ana-lyzed against with NOE (Nuclear OverhauserEnhancements) effects by inverse gated decou-pling and with a pulse interval of 10.5 s to allowcomplete recovery of all carbons. At least 5000acquisitions were collected for each spectrum.Glass transition temperatures (Tg) were mea-

sured by differential scanning calorimetry (DSC)on a Perkin–Elmer Pyris 1 DSC with the heat-ing/cooling rates of 10 8C/min, and taken as themidpoint of the inflection tangent, upon thethird or subsequent heating scan. Thermogravi-metric analytic (TGA) measurements were per-formed with a Perkin–Elmer Pyris 1 Thermogra-vimetric analyzer with a heating rate of 20 8C/min in nitrogen. The inherent viscosities weremeasured with an Ubbelohde viscometer ther-mostated at 25 8C with c ¼ 0.5 g/dL in THF. GCwas conducted on GC-14C gas chromatograph(SHIMADZU, Japan). ESI-MS was measured byLCQ ion trap instrument (Finnigan MAT, SanJose, CA) with an electrospray source in positiveion mode. Electrospray voltage was 5.0 kV andcapillary temperature was set as 260 8C.

Gel permeation chromatography (GPC) wasperformed on a Waters 1525 separation module(Waters Corp.) connected with M302 triple de-tector array (Viscotek Corp., Houston, TX), acombination of refractive index, light scattering(LS angle, 78 and 908; laser wavelength, k ¼ 670nm), and viscosity detector. Two mixed bed GPCcolumns (GMHHR-M, GMHHR-H, Viscotek Corp.)were used. THF was used as mobile phase at aflow rate of 1.0 mL/min and an operatingtemperature of 30 8C. Data were collected andanalyzed using OminSEC software version 4.1(Viscotek Corp.). Weight–average molecularweights (Mw) were calculated based on absolutemeasurements using light scattering detector.

MALDI–TOF MS (matrix-assisted laser de-sorption/ionization-time-of-flight mass spectrom-etry) was carried out using an Applied Biosys-tems Voyager-DE-STR Biospectrometry (AppliedBiosystems, Framingham, MA) equipped withdelayed extraction. A 337 nm UV nitrogen laserproducing 3 ns pulses was used and the massspectra were obtained in the linear and reflectormode using 2,5-dihydroxybenzoic acid as matrixand methanol as solvent for matrix and sample.

Model Reaction of Synthesis of Intermediates

N,N-Bis(2-hydroxyethyl)acrylamide, 1

To a solution of DEAM (2.00 g, 19 mmol) andEt3N (9.30 mL, 67 mmol) in CH2Cl2 (100 mL),AC (1.72 g, 19 mmol) was added in drops undera nitrogen atmosphere at �20 8C. After beingstirred at �20 8C for 5 h, solvent was removedby rotary evaporation. The residue was then dis-solved with THF (100 mL), and the insoluble

HYPERBRANCHED POLY(ETHER AMIDE)S 4311


triethylamine hydrochloride salt (Et3NHCl) wasremoved by filtration. The filtrate was evapo-rated at reduced pressure and afforded theproduct (2.87 g, 95%) as colorless oil. GC–MSindicated that the purity was 95%.

1H NMR (CDCl3): d 6.66 (1H, dd, J ¼ 10.5,17.0 Hz, CH2¼¼CH), 6.29 (1H, dd, J ¼ 2.0, 17.0Hz, trans CHH¼¼CH), 5.71 (1H, dd, J ¼ 2.0,10.5 Hz, cis CHH¼¼CH), 4.90–4.05 (2H, br, OH),3.80 (4H, dt, CH2OH), 3.61–3.54 (4H, m, NCH2).13C NMR (CDCl3): d 168.3, 128.3, 127.9, 60.8,60.6, 52.1, 50.9. ESI–MS: found 159.9 (M þ H)þ

(calcd 160.09).

N,N-Bis(2-hydroxyethyl)methacrylamide, 2

The synthesis procedure was the same as thatof 1. Yield: 93%. GC-MS indicated that the pu-rity was 95%.

1H NMR (CDCl3): d 5.29 (1H, d, J ¼ 10.0 Hz,trans CHH¼¼CCH3), 5.12 (1H, d, J ¼ 10.0Hz, cisCHH¼¼CCH3), 4.85–4.67 (2H, br, OH), 3.80 (4H,dt, CH2OH), 3.61–3.54 (4H, m, NCH2), 1.86 (3H,s, CH3).

13C-NMR (CDCl3): d 174.5, 140.6, 115.8,60.0, 52.5, 48.5, 20.3. ESI–MS: found 173.8 (Mþ H)þ (calcd 174.11).

N,N-Bis(2-hydroxypropyl)acrylamide, 3

To a solution of DPAM (2.53 g, 19 mmol) andEt3N (9.3 mL, 67 mmol) in THF (100 mL) wasadded AC (1.72 g, 19 mmol) in drops under anitrogen atmosphere at 0 8C. After being stirredat 0 8C for 5 h, the precipitate (Et3NHCl) wasremoved by filtration. The filtrate was evapo-rated at reduced pressure and afforded theproduct (3.38 g, 95%) as colorless oil. GC-MSindicated that the purity was 93%.

1H NMR (CDCl3): d 6.55 (1H, dd, J ¼ 10.5,17.0 Hz, CH2¼¼CH), 6.28 (1H, dd, J ¼ 2.0, 17.0Hz, trans CHH¼¼CH), 5.61 (1H, dd, J ¼ 2.0,10.5 Hz, cis CHH¼¼CH), 4.14–3.95 (2H, m,CH2CH(CH3)OH), 3.68–3.58 (2H, br, OH), 3.54–3.13 (4H, m, NCH2CH), 1.12 (6H, d, CH3).

13C-NMR (CDCl3): d 168.8, 129.0, 128.0, 66.6, 57.5,21.1; ESI–MS: found 188.0 (M þ H)þ (calcd188.13).

N,N-Bis(2-hydroxypropyl)methacrylamide, 4

The synthesis procedure is the same as that of3. Yield: 92%. GC-MS indicated that the puritywas 96%.

1H NMR (CDCl3): d 5.19 (1H, d, J ¼ 10.0 Hz,trans CH2¼¼CCH3), 5.11 (1H, d, J ¼ 44.0 Hz, cisCH2¼¼CCH3), 4.75–4.51 (2H, br, OH), 4.27–3.97(2H, m, CH2CH(CH3)OH), 3.63–3.09 (4H, m,NCH2CH), 1.96 (3H, s, CH2¼¼CCH3), 1.17 (6H,d, CH3(CH)OH). 13C-NMR (CDCl3): d 174.1,140.6, 115.9, 65.7, 57.0, 53.4, 20.7, 19.7. ESI–MS: found 201.9 (M þ H)þ (calcd 202.14).

Polymerization Procedure

Typical polymerization procedures are as follows:P1 (Table 2, run 1): DEAM (2.00 g, 19 mmol),

Et3N (9.30 mL, 67 mmol), and 100 mL ofCH2Cl2 were placed in a flask immersed intoice-CaCl2�6H2O bath. After the DEAM was com-pletely dissolved, AC (1.72 g, 19 mmol) in 50 mLof CH2Cl2 was dropped slowly into the flask andthe reaction mixture was stirred at �20 8C for5 h to form intermediate. The Et3NHCl wasremoved as precipitate by adding excess THF.The solvent was distilled off and then 16 mL ofwater was added to the residue as polymeriza-tion solvent. About 0.05 g hydroquinone wasemployed as free radical inhibitor to preventradical polymerization. The polymerization wasconducted under stirring at 40 8C for 24 h. Dur-ing the polymerization, the system became moreand more viscous. The purification of the poly-mer was done via precipitation from THF solu-tion by adding excess hexane three times. Theresultant polymer was dried at 60 8C undervacuum for 24 h to give 2.72 g (yield 90%)yellow rubber-like solid.

P4 (Table 2, run 11): DPAM (2.53 g, 19mmol), Et3N (9.30 mL, 67 mmol), and 100 mL ofTHFwere placed in a flask immersed into ice-water bath. After the DPAM was completely dis-solved, MAC (1.99 g, 19 mmol) in 50 mL of THFwas dropped slowly into the flask and then thesuspension was stirred at 0 8C for 5 h to formthe intermediate. The white precipitate ofEt3NHCl salt was filtered off. After the filtratewas concentrated to 20 mL under reduced pres-sure, t-BuOK (0.106 g, 0.95mmol) and 18-crown-6 (0.278 g, 0.95 mmol) was added as initiatorand phase transfer catalyst, respectively. About0.05 g hydroquinone was employed as free radi-cal inhibitor to prevent radical polymerization.The polymerization was conducted under stir-ring at 60 8C for 36 h. During the polymeriza-tion, the system became more and more viscous.The purification of the polymer was done viareprecipitation three times from THF solution

4312 LIN ET AL.


by adding excess hexane. The resultant polymerwas dried at 60 8C under vacuum for 24 h togive 3.48 g (yield 91%) yellow honey-like solid.

RESULTS AND DISCUSSION

Molecular Design and Exploration of AB2

Intermediates in High Yields

It is reasonable to speculate that the in situMichael addition polymerization of AD þ CB2

monomers can be described by Scheme 1 onaccount of the sufficient reactivity differencebetween amine and hydroxyl functionality to-ward (meth)AC. Amine will react faster with(meth)AC than hydroxyls to selectively form am-ide-derived AB2 type intermediates, and thenthe intermediates are subjected to Michael addi-tion polymerization to generate hyperbranchedpoly(ether amide)s. In our work, it is vitally im-portant to find out the suitable reaction condi-tions to synthesize soluble HBP with high MWand without gel. To make sure the polymeriza-tions proceeded successfully, the model reactionsof preparing AB2 intermediates were explored,and GC, ESI–MS experiments were carried outto demonstrate the formation of targeted mole-

cule. Besides, slow addition of AD to CB2 solu-tion was carried out to enable a good control ofintermediates yields.

Take the reaction of DEAM with AC for anexample, possible products are shown in Scheme2. Compound AB2 is the targeted molecule. Theside products A2B and A3 are reactive to AB2

monomer and will, if formed, have influence onthe subsequent polymerization. Therefore, opti-mum conditions which allowed high yield of AB2

intermediate are desirable. For the system ofDEAM and equimolar AC, when the reactiontemperature was 0 8C, byproducts A2B and A3

coexisted with AB2 and the yield of AB2 wasonly 33%. The byproducts A2B and A3, contain-ing two or more than two double bonds, willmake the reaction system unstable and easilylead to gel even at room temperature. As aresult, at 0 8C the soluble HBP with high MWcould not be obtained. However, when the reac-tion temperature was decreased to �20 8C,about 95% AB2 product can be easily obtained,as indicated from the GC results. Figure 1 dis-plays the corresponding mass spectrum of theresultant products. The peak of m/z ¼ 150.9was assigned to the ion peak of AB2 monomercoupled with a proton. The byproducts wereobserved at m/z ¼ 105.9 and 213.8, which areattributed to the residual DEAM and the A2Bintermediate, respectively. The minor A2Bbyproduct could further react with AB2 mono-mer to form A2B2 intermediate (Scheme 2), withtwo double bonds and two hydroxyl groups. TheA2B2 intermediate is prone to form the intermo-lecular loop, which limits the development ofMW.4(e,f) In a word, analysis of GC and mass

Scheme 2. Possible products of the reactionbetween acryloyl chloride and diethanolamine.

Figure 1. ESI mass spectrum of intermediate 1 [Mþ H]þ taken from the reaction system at �20 8C afterremoving insoluble Et3NHCl salt.



spectra demonstrated that an AB2-type interme-diate did form dominantly at low temperature.

The above-mentioned temperature depend-ence can be explained by the fact that at lowtemperature, the reactivity difference betweenamine and hydroxyl groups to AC was enlarged,which favored the dominant formation of AB2

type intermediate. If monomer MAC, instead ofAC, is used to react with DPAM, instead ofDEAM, the same result can be obtained from itsmass spectrum (Fig. 2). The reaction conditionsand the results of the AB2 intermediate prepara-tion were listed in Table 1. The data in Table 1indicate that the selectivity of the reaction alsoexhibits monomer dependence. At the same tem-perature of 0 8C, the yields of intermediate 3and 4 were 93 and 96%, respectively, muchhigher than those of 1 and 2. It can be attrib-uted to that with the introduction of methyl inDPAM, the reactivity of adjacent OH isdecreased because of steric hindrance, and thusthe selectivity of the reaction is increased.

In Situ Polymerization to HBP

Based on the model reaction, the optimal tem-perature that leads to high yield of AB2 interme-diate was selected and then in situ polymeriza-tion of AD þ CB2 monomers was carried out.For instance, P1 was synthesized through thereaction of DEAM with AC at �20 8C in CH2Cl2for 5 h to form AB2 intermediate, and thenMichael addition polymerization at 40 8C inH2O for 24 h was carried out. No gelation wasobserved throughout the polymerization process.1H NMR experiments were used to monitor thepolymerization. Figure 3 described the develop-ment of the 1H NMR spectrum with the reac-tion. As reflected in Figure 3(b), peaks a and bwere shifted downfield and the peaks at 5.5–6.5ppm ascribed to double bond appeared, whichindicates that the predicted AB2 intermediatedid form dominantly during the initial reactionstage. With the polymerization proceeding, thepeaks ascribed to double bond were markedlyweakened and finally undetectable after 20 h,which showed that polymer was obtained inhigh conversion. Moreover, the signals of themethylene protons were overlapped and not dis-tinguishable from each other in Figure 3(d),indicating complex microenvironments resultedfrom various architectures in polymer. In addi-tion, pure AB2 monomer 1 obtained from columnchromatography separation was also subjectedto Michael addition polymerization under thesame conditions for comparison purpose. The re-sultant polymer displayed nearly the same prop-erties as that from in situ polymerization, excepta lightly higher MW (see Table 2, run 2). Thisresult indicates that the occurrence of minorside products has no determined influence onthe formation of hyperbranched polymer.

Figure 2. ESI mass spectrum of intermediate 4 [Mþ H]þ taken from the reaction system at 0 8C afterremoving insoluble Et3NHCl salt.

Table 1. Reaction Conditions and Conversions for the Synthesis of AB2 Monomersa

Run AD CB2 SolventTemperature

(8C) IntermediateSelectivity

(%)bYield(%)c

1 AC DEAM CH2Cl2 0 1 50 332 AC DEAM CH2Cl2 �20 1 96 953 MAC DEAM CH2Cl2 0 2 66 514 MAC DEAM CH2Cl2 �20 2 96 955 AC DPAM THF 0 3 98 936 MAC DPAM THF 0 4 98 96

aThe initial molar ratio of AD to CB2 was set at 1/1 and the reaction time was 2 h.bDetermined using ESI–MS.c Isolated yield based on GC.

4314 LIN ET AL.


Likewise, in situ polymerization was also suc-cessfully carried out for intermediate 3. The cor-responding 1H NMR spectrum was shown inFigure 4. Compared with intermediate 1, thepolymer obtained displayed relatively smallerMW, as reflected by the double bond thatremained in 1H NMR spectrum and the value inTable 2. However, for intermediates 2 and 4, theconversions were very low under similar condi-tions even after several days. The reason is that

the introduction of methyl group to double bondsignificantly decreases reactivity of Michaeladdition polymerization. More discussions aboutit will be addressed in next section. To improvethe reaction rate and get high MW hyper-branched poly(ether amide)s, some Lewis basessuch as NaH, t-BuOK, and PPh3 were used asthe initiator, and the polymerization was per-formed in THF at 60 8C. In most cases, reactionswere allowed to proceed for 36 h to ensure com-plete conversion. The conditions and results ofthe polymerizations with different initiatorswere summarized in Table 2. The data in Table2 show that the initiator considerably affects theMichael addition polymerization. The MWs ofthe resulting HBP are at the sequence of NaH> t-BuOK > PPh3, in consistent with thesequence of base strength. In addition, the MWsof the resultant polymers also depend on thesolubility of the initiator used. The use of phasetransfer agent 18-crown-6 increases the solubil-ity of t-BuOK in THF, accordingly, the MW isgreatly increased.

The MWs of the polymers were determinedby MALDI–TOF MS together with GPC. As atypical example, the MALDI–TOF MS spectra ofP1 (Run 4 in Table 2) and P4 (Run 11 in Table2) were shown in Figures 5 and 6, respectively.As with P1, the number–averaged MW mea-sured by MALDI–TOF MS (Mn;MS ¼ 2900) wasremarkably smaller than the value obtained

Figure 3. Comparison of the 1H NMR spectrarecorded in situ for polymerization of intermediate 1(a) DEAM in CDCl3, (b) intermediate 1 in CDCl3, (c)polymerization for 8 h in D2O, and (d) polymerizationfor 20 h in D2O.

Table 2. Reaction Conditions and Polymerization Results of Various Monomers

Run Intermediate Initiator SolventTemperature

(8C)Mn;LS

(kDa) PDI[g]

(dL/g) aaRh

b

(nm) g0c DBdTg

(8C)T10%d

(8C)

1 1 –e H2O 40 38.5 5.91 0.147 0.25 8.49 0.16 0.66 15.5 305

2 1f –e H2O 40 40.7 5.95 0.150 0.24 8.52 0.16 0.66 16.0 308

3 1 –e MeOH 40 34.8 4.76 0.135 0.32 7.56 0.18 0.63 8.3 298

4 1 –e THF 40 15.9 2.53 0.106 0.36 5.87 0.36 0.62 3.6 274

5 2 t-BuOK/18-Crown-6

THF 60 17.3 3.36 0.117 0.35 6.30 0.32 0.61 0.8 278

6 2 NaH THF 60 14.6 2.47 0.096 0.40 6.42 0.37 0.61 �0.2 267

7 2 t-BuOK THF 60 10.3 2.15 0.085 0.41 3.59 0.44 0.60 �2.0 255

8 2 Ph3P THF 60 8.2 1.89 0.064 0.47 2.15 0.58 0.57 �2.9 236

9 3 –f H2O 40 28.7 4.37 0.128 0.33 7.43 0.21 0.63 4.6 293

10 3 –f MeOH 40 23.1 3.60 0.124 0.37 6.59 0.27 0.62 3.1 285

11 4 t-BuOK/18-Crown-6

THF 60 8.6 2.05 0.068 0.51 2.66 0.60 0.57 �3.4 239

aMark–Houwink value.bHydrodynamic radius.c Branching factor.d Calculated by quantitive 13C NMR spectrum.eNo initiator was used.f The monomer was purified by column chromatography.



from GPC (Mn;LS ¼ 15,900). The same phenom-enon was observed for P4. As we know, the tri-ple detector system used on GPC instrument isdescribed as yielding absolute MW, regardless ofthe architecture of the macromolecule.21 Thus, itmust be MALDI–TOF MS which underestimatedthe molar mass of the polymers. In general,branched polymers are often too complex to beanalyzed with MALDI–TOF MS because ofbroad mass distributions and differences in end-group functionality.22 The MALDI–TOF MS canonly get accurate MWs of the polymers whichhave narrow MW distributions (MWD), whereasfor polydisperse polymers it fails to yield reliablevalues, and can only detect a low MW frac-

tion.20(d),22 However, MALDI–TOF MS can beused for analysis of chemical composition includ-ing end group identity, repeating units and evenside reactions.18(d),23 As shown in Figure 5, sev-eral series of structurally related homologousoligomers can be discerned from the MALDI–TOF MS. The labeled peaks at m/z 1136, 1295,1454, 1613, 1772, and so forth in the insertmatch exactly the molar mass of the cationizedoligomers combined with Na [M þ Na]þ. Hence,MALDI–TOF MS demonstrated that the poly-merization proceeded as the proposed way.

It is worth mentioning that the Michael addi-tion of hydroxyl group to (meth)acrylate usuallyfailed to obtain high MW. For instance, Gibas etal. have studied the Michael addition polymer-ization of hydroxyethyl (meth)acrylate to synthe-size linear polymers.24 In their studies, anoligomer with MW about 1000 was obtained andsome side reactions were observed. A similarresult was also obtained in Kadokawa’s work ofsynthesis of hypebranched polymers via protontransfer polymerization of acrylate monomercontaining two hydroxyl groups.15(d) In the pres-ent work, high MW up to 38,500 (Mn;LS) wassuccessfully obtained. The reason can beexplained by the following. Firstly, the mono-mers we used for polymerization are (meth)acry-lamide and what they used were (meth)acrylate.As we know, the electron-withdrawing tendencyof the amide group (��CONRR) is stronger thanthat of ester group (��COOR). Therefore, thereactivity of acrylamide towards Michael addi-tion is higher than acrylate. Secondly, the choiceof suitable initiator is also important for the

Figure 5. MALDI–TOF mass spectrum of hyper-branched polymer P1. The major peaks in the insetcorrespond to the [M þ Na]þ for the heptamer, octa-mer, nonamer, decamer, and undecamer.

Figure 6. MALDI–TOF mass spectrum of hyper-branched polymer P4. The major peaks in the insetcorrespond to the [M þ Na]þ for the hexamer, hep-tamer, octamer, and nonamer.

Figure 4. Comparison of the 1H NMR spectrarecorded in situ for the polymerization of intermedi-ate 3 (a) DPAM (b) intermediate 3 (c) polymerizationfor 20 h, the solvent CDCl3 was not shown.

4316 LIN ET AL.


successful synthesis of some hyperbranched poly(ether amide)s with high MW. Data in Table 2also indicate that the MWD broaden withincreasing number-average MW of the polymer.The polymers with broad MWD were reasonablefor the AB2-type monomers, which was pre-dicted by Flory as early as 1950s.4(a)

Mechanism of Michael Addition Polymerizationand Its Monomer and Solvent Effect

The Michael addition involves the addition of anucleophile, also called a ‘Michael donor,’ to anactivated electrophilic double bond, a ‘Michaelacceptor’, resulting in a ‘Michael adduct’. Scheme3 outlined the mechanism of Michael additionpolymerization of the AB2 intermediates, analo-gous to that published by Kadokawa et al.15(d)

The chain propagating species is an anionicgroup, which is produced by the proton-transferfrom hydroxy group to a carbanion formed viaMichael-type addition. The hydroxy groups ofthe monomers, therefore, are conceived as alatent propagating species, enabling the prepa-ration of hyperbranched materials.

In Michael addition, the reactivity of anacceptor toward nucleophilic attack is directlycorrelated with the electron-withdrawing tend-ency of the group linked to the double bond. Thecommonly accepted explanation for this correla-tion is based on the ability of the electron-with-drawing group to stabilize the negative chargeformed on the carbon adjacent to the site ofnucleophilic attack.25 As a result, the reactivityof the acceptor will decrease if the substituent is

electron rich, such as methyl at the double bondin intermediates 2 and 4. As mentioned above,the reactivity of intermediates 2 and 4 waslower than the corresponding intermediates 1and 3, respectively, and thus the additionalnucleophile is necessary for successful Michaeladdition polymerization of intermediates 2 and4. It is noteworthy that, in addition to the elec-tronic effect, the steric hindrance is also an im-portant factor. For intermediates 1 and 3, thereactivity of acceptor is the same; nevertheless,the polymer obtained from intermediate 3 dis-played relatively smaller MW than that from in-termediate 1. This is attributed to the steric hin-drance that resulted from the methyl substitu-tion at the carbon atom adjacent to the OHgroups. In addition, the polymerization reactiv-ity of 3 was higher than that of 2. This resultdemonstrated that the electronic effect plays amore important role than the steric hindrancein determining the reactivity of monomer inMichael addition polymerization.

Typical solvents for the Michael reactioninclude water, methanol, ethanol, THF, dioxane,and mixtures of these solvents. Usually, proticsolvents were desirable in the Michael reaction topromote rapid proton transfer and to stabilizecharged intermediates.26 The evolution of MW indifferent solvents for polymer P1 was observedby determining inherent viscosity of periodicsamples. As shown in Figure 7, the inherent vis-cosity increased rapidly in H2O and MeOH, andreached its plateau within 24 h. However, itincreased relatively slowly at THF and reachedits plateau within 36 h. The sequence of its pla-teau value was H2O > MeOH > THF, which is

Scheme 3. Mechanistic depiction of the Michaeladdition reaction for the AB2 intermediate, Nu refersto the nucleophile.

Figure 7. The inherent viscosity versus time duringpolymerizations for P1 in different solvents.



consistent with the MW value in Table 2. There-fore, the high protic solvent is responsible for thehigh rate of the Michael addition polymerizationand high MW of the polymer.

Branched Structure and Properties

The degree of branching (DB) is one of the mostimportant molecular parameters of HBP becauseit characterizes the difference in molecularstructure from their linear analogue. Since the1H NMR spectra of the polymers could not beapparently assigned because of the overlap ofthe protons, their DB was calculated on thebasis of quantitive 13C NMR (inverse gated de-coupling technique) using the definition put for-ward by Frechet and coworkers27 for the HBPfrom potential AB2 type monomers. Dendritic, lin-ear, and terminal units are defined as in Scheme1, and DB could be obtained on the basis of eq 1:

DB ¼ Dþ Tð Þ= Dþ T þ Lð Þ

where D and T stand for the amount of the den-tritic and terminal units, respectively, and L isthe amount of linear units. Take the quantitive13C NMR of the hyperbranched P1 as a typicalexample. The chemical shifts of ester moieties ofdendritic, linear, and terminal units were clearlyobserved. DB was calculated by eq 2:

DB ¼ Ic þ Ic2ð Þ= Ic þ Ic1 þ Ic2ð Þ

where Ic, Ic1, and Ic2 are the integral intensitiesof the peak c, c1, and c2 as indicated in Figure 8,

respectively. According to eq 2, DB value for P1obtained from H2O should be 0.66. The DBs ofother polymers calculated with the same methodwere also listed in Table 2.

HBP are well known to exhibit unusual solu-tion behavior, such as intrinsic viscosity [g] andthe value of the Mark–Houwink exponent a,are remarkably different from their linear ana-logues because of the compact character of thebranched structure.28 To further support theformation of hyperbranched structure in thissynthetic procedure, viscosity behavior of theresulting polymers was studied. The depend-ence of intrinsic viscosity on MW was deter-mined by GPC equipped with triple detectorarray: refractive index, viscosity, and light scat-tering (two angles 78 and 908) detectors. A typi-cal multidetector outputs for the hyper-branched P1 recovered from the THF–hexanepurification system was shown in Figure 9where the polymer peak has multimodal andbroad shape, suggesting branched structure.Figure 10 showed the corresponding double log-arithm plots of intrinsic viscosity ([g]) againstMW, which is often described by the empiricalMark–Houwink equation [–] ¼ KMa.29 For com-parison purpose, linear poly(ether amide)s weresynthesized via Michael addition polymeriza-tions from the corresponding monomers con-taining one hydroxyl group. Obviously, theintrinsic viscosity of the branched products islower than that of the linear reference, sug-gesting a denser and compacter structure forthe former. Most importantly, the compactbranched structure is confirmed by the Mark–Houwink exponent a value, which is signifi-

Figure 8. The enlarged 13C NMR spectra for hyper-branched polymer 1.

Figure 9. Typical triple detector outputs for hyper-branched P1.

4318 LIN ET AL.


cantly depressed (0.32) relative to that of linearreference (0.66). The Mark–Houwink exponenta has characteristic value and is typically below0.5 for HBP.30 Table 2 also gives the weight-av-erage Mark–Houwink exponent a for the finalproducts of various polymerization systems.The a values of branched polymers are small,from 0.25 to 0.51, within the typical range forhighly branched polymers.

The effect of architectural branching is alsoexpressed by Zimm branching factor g0, alsocalled geometric factor or contracting factor,which is defined as28(a):

g0 ¼ g½ �b þ g½ �lwhere [g]b and [g]l are the intrinsic viscosity ofbranched polymer and their linear analog withequal mass, respectively. For a linear polymer,the Zimm branching factor g0 ¼ 1, and for agiven molar mass polymer, the higher DB, thesmaller is g0. The parameter g0 is generallyaccepted as a good qualitative indicator of thedegree of chain branching.31 The results listedin Table 2 showed that the g0 decreases as theMW increases, which was consistent with theresult obtained from quantitive 13C NMR.

The resulted hyperbranched poly(ether amide)spossess abundant OH terminal groups; accord-ingly, they have good solubility in polar solventssuch as water, ethanol, methanol, acetone, DMF,DMSO, chloroform, and THF.

The results of DSC and TGA measurementsare also listed in Table 2. The polymers exhib-

ited glass transition temperatures (Tg) at therange of �3.4 to 15.5 8C, which indicates thatthe polymer is in the rubber-like viscous state atroom temperature. The lower Tg of the polymersP2 and P4 in comparison with other polymerscan be attributed to their smaller MWs and theintroduction of methyl groups in segment chain.No melting and crystallization peaks wereobserved, indicating their amorphous state,which is typical for highly branched polymers.TGA analysis showed that the 10% weight-loss temperatures were up to 300 8C, demon-strating the reasonable thermal stability ofthese polymers.

CONCLUSIONS

A series of novel hyperbranched poly(etheramide)s is successfully prepared from in situcreated AB2 monomers in a high-yield, straight-forward strategy following the mechanism ofMichael addition polymerization. By optimizingthe reaction conditions, AB2 intermediates weredominantly formed in high yield at the initialstage, which was demonstrated by GC andESI–MS. The polymerization of AB2 intermedi-ates was carried out with/without an initiatorat 40–60 8C in solution. It was found that thereactivity of monomers for Michael additionstrongly depended on the electronic and sterichindrance effect, in which the former plays amore important role in the polymerization. Inaddition, protic solvent and initiator with morenucleophilic characteristic are in favor of therate of polymerization and high MW. Remark-ably, the high MW up to 38,500 (Mn;LS) of theresulting HBP was accessed, attributing to thehigh yield of AB2 intermediates as well as theproper choice of initiator and solvent. 13C NMRcharacterization together with triple detectorGPC measurement evidenced that the resultantpolymers are characteristic of hyperbranchedstructure. The low values of Mark–Houwink ex-ponential a and intrinsic viscosity [g] are con-sistent with a highly branched architecture. Thetemperatures of 10 wt % mass loss (T10

d ) were inthe range of 239–305 8C, and Tgs were in therange of �3.4 to 15.5 8C, depending on themonomers used. Because of the water solubilityand the abundant terminal groups attached,these hyperbranched poly(ether amide)s areattractive materials for various functional ap-plications.

Figure 10. Mark–Houwink plot for hyperbranchedpolymer P1 and its linear analogue. The slope of theline indicates the value of a.



The authors are grateful for subsidy by the NationalNatural Science Foundation of China (Nos. 50473027and 50525312).

REFERENCES AND NOTES

1. (a) Newkome, G. R.; Moorefield, C. N.; Vogtle, F.Dendrimers and Dendrons-Concepts, Syntheses,Applications; Wiley-VCH: Weinheim, Germany,2001; (b) Frechet, J. M. J.; Tomalia, D. A. Den-drimers and Other Dendritic Polymers; Wiley:Chichester, England, 2002; (c) Hawker, C. J.;Wooley, K. L. Science 2005, 309, 1200.

2. (a) Tomalia, D. A.; Naylor, A. M.; Goddard W. A.,III. Angew Chem Int Ed Engl 1990, 29, 138; (b)Frechet, J. M. J. Science 1994, 263, 1710; (c)Frechet, J. M. J. J Polym Sci Part A: PolymChem 2003, 41, 3713; (d) Hawker, C. J Adv PolymSci 1999, 147, 113.

3. (a) Jikei, M.; Kakimoto, M. J Polym Sci Part A:Polym Chem 2004, 42, 1293; (b) Froehling, P.J Polym Sci Part A: Polym Chem 2004, 42, 3110;(c) Gao, C.; Yan, D. Prog Polym Sci 2004, 29, 183;(d) Voit, B. J Polym Sci Part A: Polym Chem2005, 43, 2679.

4. (a) Flory, P. J. J Am Chem Soc 1952, 74, 2718; (b)Kim, Y. H.; Webster, O. W. J Am Chem Soc 1992,114, 4947; (c) Hawker, C. J.; Chu, F.; Pomery, P. J.;Hill, D. J. T. Macromolecules 1996, 29, 3831; (d)Li, Z. X.; Liu, J. H.; Yang, S. Y.; Huang, S. H.;Lu, J. D.; Pu, J. L. J Polym Sci Part A: PolymChem 2006, 44, 5729; (e) Hahn, S. W.; Yun, Y. K.;Jin, J.; Han, O. H. Macromolecules 1998, 31,6417; (f) Kudo, H.; Maruyama, K.; Shindo, S.;Nishikubo, T.; Nishimura, I. J Polym Sci Part A:Polym Chem 2006, 44, 3640.

5. (a) Gottschalk, C.; Frey, H. Macromolecules 2006,39, 1719; (b) Ye, L.; Feng, Z. G.; Zhao, Y. M.; Wu,F.; Chen, S.; Wang, G. Q. J Polym Sci Part A:Polym Chem 2006, 44, 3650.

6. (a) Uhrich, K. E.; Hawker, C. J.; Frechet, J. M. J.;Turner, S. R. Macromolecules 1992, 25, 4583; (b)Frechet, J. M. J.; Henmi, H.; Gitsov, I.; Aoshima,S.; Leduc, M. R.; Grubbs, R. B. Science 1995, 269,1080.

7. (a) Matyjaszewski, K.; Gaynor, S. G. Macromole-cules 1997, 30, 7042; (b) Weimer, M. W.; Frechet,J. M. J.; Gitsov, I. J Polym Sci Part A: PolymChem 1998, 36, 955; (c) Cheng, C.; Wooley, K. L.;Khoshdel, E. J Polym Sci Part A: Polym Chem2005, 43, 4754; (d) Powell, K. T.; Cheng, C.;Wooley, K. L.; Singh, A.; Urban, M. W. J PolymSci Part A: Polym Chem 2006, 44, 4782.

8. (a) Wang, Z.; He, J.; Tao, Y.; Yang, L.; Jiang, H.;Yang, Y. Macromolecules 2003, 36, 7446; (b) Liu,B.; Kazlauciunas, A.; Guthrie, J. T.; Perrier, S.Polymer 2005, 46, 6293; (c) Lin, Y.; Liu, X. H.; Li,

X. R.; Zhan, J.; Li, Y. S. J Polym Sci Part A:Polym Chem 2007, 45, 26.

9. (a) Liu, J. H.; Ren, C.; Yang, Z.; Shi, W. F.J Polym Sci Part A: Polym Chem 2007, 45, 699;(b) Jia, Z. F.; Yan, D. Y. J Polym Sci Part A:Polym Chem 2005, 43, 3502.

10. Mather, B. D.; Viswanathan, K.; Miller, K. M.;Long, T. E. Prog Polym Sci 2006, 31, 487.

11. Vernon, B.; Tirelli, N.; Bachi, T.; Haldimann, D.;Hubbell, J. J Biomed Mater Res A 2003, 64, 447.

12. (a) Lynn, D. M.; Langer, R. J Am Chem Soc 2000,122, 10761; (b) Richardson, S. C. W.; Pattrick, N.G.; Stella Man, Y. K.; Ferruti, P.; Duncan, R. Bio-macromolecules 2001, 2, 1023; (c) Zhong, Z. Y.;Song, Y.; Engbersen, J. F. J.; Lok, M. C.; Hen-nink, W. E.; Feijen, J. J Controlled Release 2005,109, 317.

13. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.;Kallos, G.; Martin, S. Macromolecules 1986, 19,2466.

14. Maraval, V.; Laurent, R.; Donnadieu, B.; Mauzac,M.; Caminade, A. M.; Majoral, J. P. J Am ChemSoc 2000, 122, 2499.

15. (a) Trumbo, D. L. Polym Bull 1991, 26, 265; (b)Hobson, L. J.; Kenwright, A. M.; Feast, W. J.Chem Commun 1997, 14, 1877; (c) Hobson, L. J.;Feast, W. J. Polymer 1999, 40, 1279; (d) Kado-kawa, J.; Kaneko, Y.; Yamada, S.; Ikuma, K.;Tagaya, H.; Chiba, K. Macromol Rapid Commun2000, 21, 362.

16. Liu, Y. L.; Tsai, S. H.; Wu, C. S.; Jeng, R. J.J Polym Sci Part A: Polym Chem 2004, 42, 5921.

17. (a) Fang, J. H.; Kita, H.; Okamoto, K. Macromole-cules 2000, 33, 4639; (b) Unal, S.; Lin, Q.;Mourey, T. H.; Long, T. E. Macromolecules 2005,38, 3246.

18. (a) Gao, C.; Tang, W.; Yan, D. Y. J Polym Sci Part A:Polym Chem 2002, 40, 2340; (d) Gao, C.; Xu, Y.; Yan,D. Y.; Chen, W. Biomacromolecules 2003, 4, 704.

19. (a) Wu, D. C; Liu, Y.; He, C. B; Chung, T. S.; Goh,S. H. Macromolecules 2004, 37, 6763; (b) Wu, D.C.; Liu, Y.; Chen, L.; He, C. B.; Chung, T. S.; Goh,S. H. Macromolecules 2005, 38, 5519; (c) Wang,D.; Liu, Y.; Hong, C. Y.; Pan, C. Y. J Polym SciPart A: Polym Chem 2005, 43, 5127; (d) Wang,D.; Zheng, Z. J.; Hong, C. Y.; Liu, Y.; Pan, C. Y.J Polym Sci Part A: Polym Chem 2006, 44, 6226.

20. (a) Li, X. R.; Zhan, J.; Li, Y. S. Macromolecules2004, 37, 7584; (b) Li, X. R.; Zhan, J.; Lin, Y.; Li, Y.S. Macromolecules 2005, 38, 8235; (c) Li, X. R.; Su,Y. L.; Chen, Q. Y.; Lin, Y.; Tong, Y. J.; Li, Y. S. Bio-macromolecules 2005, 6, 3181; (d) Li, X. R.; Lu, X.F.; Lin, Y.; Zhan, J.; Li, Y. S.; Liu, Z. Q.; Chen, X. S.;Liu, S. Y. Macromolecules 2006, 39, 7889.

21. (a) Saunders, G.; Cormack, P. A. G.; Graham, S.;Sherrington, D. C. Macromolecules 2005, 38,6418; (b) Farinato, R. S.; Calbick, J.; Sorci, G. A.;Florenzano, F. H.; Reed, W. F. Macromolecules2005, 38, 1148.

4320 LIN ET AL.


22. (a) Montaudo, G.; Garozzo, D.; Montaudo, M. S.;Puglisi, C.; Samperi F. Macromolecules 1995, 28,7983; (b) Van Renterghem, L. M.; Feng, X.; Taton,D.; Gnanou, Y.; Du Prez, F. E. Macromolecules2005, 38, 10609.

23. (a) Nielen, M. W. F. Mass Spectrom Rev 1999, 18,309; (b) Koster, S.; Duursma, M. C.; Boon, J. J.;Heeren, R. M. A.; Ingemann, S.; van Benthem, R.A. T. M.; de Koster, C. G. J Am Soc Mass Spec-trom 2003, 14, 332.

24. (a) Gibas, M.; Korytkowska, A. K. Polymer 2003,44, 3811; (b) Gibas, M.; Korytkowska, A. K. PolymBull 2003, 51, 17.

25. Carroll, M. T.; Cheeseman, J. R.; Osman, R.;Weinstein, H. J Phys Chem 1989, 93, 5120.

26. (a) Connor, R.; McClellan, W. R. J Org Chem1938, 3, 570; (b) Danusso, F.; Ferruti, P. Polymer1970, 11, 88.

27. Hawker, C. J.; Lee, R.; Frechet, J. M. J. J AmChem Soc 1991, 113, 4583.

28. (a) Zimm, B. H.; Stockmayer, W. H. J Chem Phys;(b) Mourey, T. H.; Turner, S. R.; Rubinstein, M.;Frechet, J. M. J.; Hawker, C. J.; Wooley, K. L.Macromolecules 1992, 25, 2401.

29. Kurata, M.; Tsunashima, Y. In Polymer Hand-book, 4th ed.; Brandrup, J.; Immergut, E. H.;Grulke, E. A.; Abe, A.; Bloch, D. R., Eds.; Wiley:New York, 1999; Section VII, p 2.

30. (a) Appelhans, D.; Komber, H.; Voigt, D.; Hauss-ler, L.; Voit, B. I. Macromolecules 2000, 33, 9494;(b) Simon, P. F. W.; Muller, A. H. E.; Pakula, T.Macromolecules 2001, 34, 1677.

31. Graessley, W. W. In Characterisation of Macromo-lecular Structure; McIntyre, D., Ed.; U.S. NationalAcademy of Sciences: Washington, DC, 1968; Publ.No. 1573, pp 371–388.



facile synthesis and characterization of hyperbranched poly(ether amide)s generated from michael...

Documents