CA-Based Initiator System for ROP of Caprolactone

8/13/2019 CA-Based Initiator System for ROP of Caprolactone

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A N ovel a nd Ver sati le Ca lcium-B a sed Init ia tor Sy stem for the

Ring-Opening P olymeriza tion of Cy clic Est ers

Zhiyuan Zhong, Pieter J . Dijkstra, Christin Birg, Matthias Westerhausen, andJ an Feijen*,

Depart m ent of Chemi cal T echnol ogy and I n st i t u t e f or B i omedi cal T echnol ogy, U ni versi t y of T went e,P . O. B ox 217, 7500 A E E nschede, T he Net herl ands, and Depart m ent Chemi e der L u d w i g - M a x i m i l i a n s - U n i v e r s i t a t , B u t e n a n d t st r . 9 ( H a u s D ) , D - 8 13 7 7 M u nchen, Germ any

Receiv ed N ovem ber 15, 2000

ABS TRACT: A novel a nd efficient calcium a lkoxide init iating sy stem, generat ed in si tu from bis(tetra -hydrofuran)calcium bis[bis(trimethylsilyl)amide] and an alcohol, for the ring-opening polymerization ofcyclic esters has been developed. The solution polymerization in THF using mild conditions is living,yielding polyesters of controlled molecular weight an d ta i lored m acromolecular architecture. Thepolymerizations initiated with the 2-propanol-Ca[N(SiMe3)2]2(THF)2 system are first-order in monomerwith no induction period. At high 2-propan ol/Ca [N(SiMe3)2]2(THF)2 ra tios, complete conversion of2-propan ol occurs due to fa st an d reversible tra nsfer between dorma nt an d a ctive species.

Introduction

B iodegrad a ble and biocompatible alipha tic polyesters

have received much interest for their medical, pharma-ceutical, and environmental applicat ions.1-3 M a n y o fthese polyesters can be synt hesized by t he ring-openingpolymeriza tion of cyclic esters, for w hich va rious effec-t ive init iat ing systems ha ve been developed.4-9

However, in practice, complete removal of the catalystresidues from th e polymer is not possible, an d t hereforea biocompatible catalyst should be used. Ca-, Fe-, andMg-ba sed ca ta lysts/initia tors a re the most fa vored, sincethese meta ls part icipate in t he human metabolism.10-12

Recently, the ring-opening polymerization of L-lactidea n d/or -c a prola c t on e wit h ca t a ly s t s ba s e d on t h e s emetals has been described. 13-17 However, racemizationis generally observed for L-lactide polymerization as a

result of the high temperature and long polymerizationtime necessary to reach high conversion. 18

In-situ generated yt trium alkoxides, based on fastexchange between yttrium 2,6-di-tert-butylphenoxidesand different a lcohols, ha ve unprecedented act ivity inthe ring-opening polymerization of lactides and lactonesunder very mild conditions, allowing excellent controlover t he polymerizat ion process.19,20 Very recently, thering-opening polymeriza tion of -caprolactone w ith [tris-(hexamet hyldisilyl)am ide]ytt rium in the presence of a nexcess of 2-propanol, which gave polymers with con-trolled molecular para meters, wa s a lso reported.21 Wedescribe here a novel a nd efficient calcium alkoxidein it ia t in g s y s t em, g e ne ra t e d in s i t u f ro m bis(t e t ra -hydrofuran)calcium bis[bis(trimethylsilyl)amide]and an

alcohol, for the ring-opening polymerization of cyclicesters.

Experimental Section

Materials. L-Lactide (Purac Biochem b.v., The Netherlands)was purified by recrystallization from dried toluene. -Capro-lactone (Merck-Schuchardt , D ar msta dt, Germa ny), 2-propan ol,

an d methan ol were dried over Ca H 2an d distilled prior to use.Poly(ethylene glycol) with Mn ) 2.0 103 g/mol (Sigma -

Aldrich, S teinheim, Germa ny) wa s purified by dissolution inC H C l3and precipitation from diethyl ether followed by dryingunder reduced pressure (8.0 mmHg) for more tha n 1 w eek.Bis(tetra hydrofura n)ca lcium bis[bis(trimethylsilyl)am ide][Ca-[N(SiMe3)2]2(THF)2] w as pr epar e d b y t he t r a nsm e t al at i on ofbis[bis(trimeth ylsilyl)a mido]tin(II) wit h calcium meta l in THFand crystal l ized from n-hexane at 0 C, as described previ-ously.22 Ca[N(SiMe3)2]2(THF)2is sensitive towar d moisture andai r and r e ad i ly sol ubl e i n c om m on or gani c sol vent s (e .g . ,toluene, benzene, THF). Toluene and benzene-d6 were driedby refluxing over a Na/K alloy. THF wa s dried by refluxinga n d d is t il la t i on ov er s od iu m w i r e. Al l g la s s w a r e f or t h epolymerization was dried in an oven before use.

Polymerizations. All polymerizations were carried out atroom temperat ure with THF as the solvent in a glovebox undera nitrogen a tmosphere. In a typical procedure, a THF (1.0 mL)

solution of Ca [N(SiMe3)2]2(THF)2 (0. 069 m m ol ) w a s ad d e dunder vigorous stirring to a mixture of L-lactide (1.0 g, 6.9mmol) and 2-propanol (0.138 mmol, added as 5 wt % stocksolution in THF) in THF (6.0 mL) ([M]0/[2-P rO H ]0/[Ca ]0 ) 100/2/1). After t he desir ed rea ction t ime (35 min), polymeriza tionwas terminated by introducing acetic acid. A sample was takenfor conversion determinat ion using 1H NM R . The pol y (L-lactide) was isolated by precipitation from excess methanolfollowed by fi l trat ion a nd drying a t 40 C in vacuo. Monomerconversion: 100%; yield: 0.91 g; Mn , G P C ) 6 .9 1 03, P D I )1.05. 1H N M R ( C D C l3): 0.05 (s, HN(Si(C H3)3)2), 1.24 (t,(C H3)2CHOC(O)-), 1.56 (d, -C(O)CH(C H3)O-), 2.66 (broad ,-C(O)CH(CH 3)OH), 4.34 (q, -C(O)C H(C H 3)OH), 5.06 (m,(C H 3)2C HOC(O)-), 5.16 (q, -C(O)C H(C H 3)O-). An Mn of 6.9103 was calculated based on the relative intensities of the1H NM R (C DC l3) s ig nal s a t 5.16 a nd 1.24. P olymerization

of -caprolactone (-CL) wa s performed a s described a bove toafford poly(-capr olact one). Monomer convers ion: 100%, Mn , G PC) 6.2 103, P D I ) 1.24. 1H NM R (C DC l3): 0.05 (s, HN(Si-(C H3)3)2), 1.22 (d, (C H3)2CHOC(O)-), 1.37 (m, -C(O)CH 2-C H 2C H2C H 2C H 2O-), 1.66 (m , -C(O)CH 2C H2C H 2C H2-C H 2O-), 2.30 (t , -C(O)CH2C H 2C H 2C H 2C H 2O-), 3.63 (t ,-C(O)CH 2C H 2C H 2C H 2C H2OH), 4.04 (t, -C(O)CH 2C H 2C H 2-C H 2C H2O-), 4.98 (m, (CH 3)2C HOC(O)-).

Synthesisof Poly(E-caprolactone)-b-(L-lactide). A livingpoly(-caprolactone) prepolymer w as prepar ed similarly asdescribed above. To a mixtur e of -CL (1.54 g, 13.5 mmol) and2-propanol (0.27 mmol, added as 5 wt %stock solution in THF)in THF (16.0 mL ) ([-CL]0/[2-P rO H ]0/[Ca ]0 ) 100 /2/1) w a s

University of Twente. Ludw ig-Ma ximilian s-Un iversit a t .* Corresponding aut hor. Fax +31-53-4893823, E-mail j.feijen@

ct.utwente.nl.

3863M acromolecul es2001, 34 , 3863-3868

10.1021/ma 0019510 CCC: $20.00 2001 American C hemical SocietyP ubl ish ed on Web 05/02/2001


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added a THF (1.0 mL) solution of Ca[N(SiMe 3)2]2(THF)2(0.135mmol) under vigorous stirr ing. After 6 min prepolymerization,part of the reaction mixture (ca. 2.0 mL) was removed, andthe polymerization was terminated by the addition of aceticacid. 1 H NMR analysis revealed complete monomer conversion.To the remaining m ixture conta ining th e l iving poly(-capro-lactone) prepolymer, L -LA (1.50 g, 10.4 m mol) in 8 m L of THFwas added. After another 80 min, the reaction was quenchedb y a d d i ng e xce ss ac e t i c ac id , a nd t he pol ym e r w as i sol at e dusing the procedures described above. L-LA conversion : 93%,Mn , G P C ) 12.6 1 03, P D I ) 1.18.

Synthesis of Poly(L-lactide)-b-(ethylene glycol)-b-(L-lactide). To a v igorously st irred THF solut ion (6.0 mL) of poly-(ethylene glycol) with Mn ) 2.0 103 g/mol (0.138 g, 0.069mmol) and l-LA (1.0 g, 6.9 mmol) was added a THF solution(1.0 m L ) of C a[ N(S i M e3)2]2(THF)2 (0.069 mmol). A rapidincrease in viscosity was observed. After 18 min, the reactionwas quenched by adding excess acetic acid, and the polymerw a s i sol at e d usi ng t he pr oc ed ur es d e sc ri b ed ab ove. l -L Aconversion: 100%, yield: 0.96 g, Mn , G P C ) 15.5 103, P D I )1.03. 1H NM R (C DC l3): 1.56 (d, -C(O)CH(C H3)O-), 2.68(broad, -OH), 3.65 (s, -OC H2C H2O-), 4.28-4.34 (m, -O C H -(CH 3)C(O)OCH2CH 2O- a nd -C(O)C H(CH 3)OH), 5.16 (q, -C(O)-C H(C H 3)O-).

Measurements. 1H (300 or 400 MHz) a nd 13C (75.26 MHz)

NMR spectra were recorded on a Varian Inova spectrometerw i t h c hem i cal shi ft s r e lat i ve t o t he solve nt pe ak. The G P Cm e asur em e nt s w e r e c ond uct e d w i t h a Wat e r s 6000A G P Cappara tus equipped with a series of sta ndar d Wat ers Styra gelHR columns and a H502 viscometer detector (Viscotek Corp.)for absolute molecular weight determinations. P olymers w eredissolved in chloroform (1.0 wt %), and elution w a s performedat 25 C at a f l ow r at e of 1.5 m L /m i n usi ng c hlor ofor m a seluent. Differential scanning calorimetry (DSC) was carriedout with a P erkin-Elmer DSC -7 appara tus calibrated with pureindium. The sample wa s heat ed from 20 to 185 C at a r at e of10 C/min, kept at 185 C for 2 min, a nd cooled to 20 C a t arat e of 40 C/min, and t hen a second heat ing scan a t a ra te of10 C /min w as recorded. The ma ximum of t he endothermicpeak w as t ake n a s t he m e l t ing t e m per at ur e .

Results and DiscussionAttempts to homopolymerize L-lactide (L-LA) or -

caprolactone (-CL) wit h C a[N(SiMe3)2]2(THF)2in THFat room temperature (18 C) revea led a slow L-LA bu tf a s t -CL polymerization (Table 1, entries 1-3). Thepoly(L -L A) is ola t e d h a d a n a rro w molecu la r we ig htdistribution. The molecular weight as determined byG P C de via t e d la rg ely f ro m t h e t h e ore t ica l v a lu e. B e -cause th e end groups could not be detected by 1H NMR,n o a c c u ra t e Mn value could be calculated. The -CLpolymerization afforded polymers of somewhat broaderpolydispersity index (PDI). Analogous observations havebeen reported for yttrium a nd sa ma rium a mides in -CLpolymerization.21,23,24

I n t h e p res en ce of Ca [N (SiM e3)2]2(THF)2 a n d 2-propanol, t he polymerizat ion of L -LA and -CL pro-ceeded smoothly to afford the corresponding polyesterwith a nar row molecular weight distribution (entries 4a n d 5). F or e xa m p le , w h e n a TH F s ol ut i on of C a -[N(SiMe3)2]2(THF)2 w a s a d ded t o a m ixt ur e o f 2 -propanol a nd L-LA at a molar rat io [L-LA]0/[2-P rOH ]0/[Ca]0of 100/2/1, th e convers ion w a s complet e w it hin 35min. The polyester isolat ed by precipita tion from meth a -n o l h a d a n Mn of 6.9 103 (entry 4), close to thetheoretical va lue (7.2 103) ca lcula ted fr om the m ono-mer-to-a lcohol molar ra tio. Moreover, th e polymer ha da low polydispersity index (PD I) of 1.05. The 1H N M Rspectrum as well as detailed peak assignments of theobta ined poly(L-L A) is s h own in F ig u re 1. Th e t wodoublets appearing as a triplet at 1.24 and t he qua rteta t 4.34, with an integral ra t io close to 6:1 within thelimits of the NMR experimental errors, were a ssignableto the methyl protons of the isopropoxycarbonyl endgroup and t he methine proton neighboring the hydr oxylend group, respectively. A tra ce signal a ppearing at 0.05 was at tributed to t he free HN(Si(C H3)3)2 residuesorig in a t in g f rom t h e a lc oh oly s is of Ca [N (SiM e3)2]2-(THF)2. The M n calculated from the relative intensities

Table 1. Polymerization ofL -LA and E-CL Initiated with Alcohol-Ca[N(SiMe3)2]2(THF)2 Systems ([M]0/[Ca]0 ) 100/1)a

Mn 10-3 P D I

en t r y m on R OH [M]0(m ol/L ) t im e (m in ) con vc(%) NMR d G P C e theof G P C e

1 L-L A 1.0 35 71 8.4 5.1 1.162b -C L 0.5 1 100 22.8 5.7 3.953 -C L 0.5 8 100 11.8 5.7 2.394 L-L A 2-P r OH 1.0 35 100 6.9 6.9 7.2 1.055 -C L 2-P r OH 0.8 6 100 6.2 6.2 5.7 1.246 L-L A P E G 2000 1.0 18 100 15.1 15.5 15.5 1.037 L-L A MeOH 1.0 18 97 10.3 12.7 7.0 1.07

8 -C L MeOH 0.8 10 100 8.5 9.0 5.7 1.29

a All polymerizat ions were carried out under N 2 a tmosphere at room temperature (1 8 C) w i t h TH F a s t h e s olv e nt . E n t r ie s 1-3without a lcohol, the others with [ROH]0/[Ca ]0 ) 2/1 (mola r ra tio). b Toluene as solvent. c Es t im a t e d f r om 1H NMR spectra (300 MHz,C D C l3) of the crude polymerizat ion mixtures. d Experimental values obtained from 1H N M R e n d g r ou p a n a ly s is ( 3 0 0 M H z , CD Cl 3).e Determined by GPC ana lysis. f Calculated based on the following formula: Mn,theor ) Mw, alcohol + Mw, monomer [M]0/[I ]0 conversion,[I]0 refers to [ROH]0 or 2[Ca]0 (in the absence of alcohol, i.e., entries 1-3).

Figure 1. The 300 MHz 1H NMR spectrum (CDCl3) of poly-(L-LA) obta ined w ith 2-P rOH-Ca[N(SiMe3)2]2(THF)2 (molarra tio: 2/1) (ent ry 4, Table 1).

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of signals a t 5.16 (ma in chain m ethine proton) a nd a t 1.24 (methyl protons of the isopropoxycarbonyl endgroup) wa s 6.9 103. The good a greement betw een thetheoretical va lue of M n a n d t h a t de t ermin ed by G P C o r1H N M R e n d g ro u p a n a ly s is u n a mbig u o u s ly s h o we dthat the 2-propanol groups and not the bis(trimethyl-silyl)amide ligands were incorporated during the initia-tion and that the polymerization proceeded exclusivelyb y a c yl-ox y ge n clea v a g e of t h e mon ome r. Simila rresults were also observed for the -CL polymeriza tion(entry 5), with isolated poly(-CL ) c h a in s bea rin g a nisopropoxycarbonyl group at one end and a hydroxyl

g r o u p a t t h e o t h e r e n d a s r e v e a l e d b y t h e 1H N M Ranalysis (Figure 2).

The ra tio of the degree of polymeriz a tion (DP ) of poly-(L-LA) and monomer conversion increased proportion-ally with the init ial monomer-to-alcohol ra t io (Figure3). Moreover, the molecula r w eight a lso followed a linearre la t io n sh ip in mon ome r con v ers ion , wi t h t h e P D Ibecoming lower dur ing t he polymeriza tion course (Fig-ure 4). The perfect control over molecular weight andlow P D I in dica t e t h a t t h e p oly meriza t ion h a s a l iv ingnature. This was further confirmed by the sequentialcopolymerization of -CL and L-LA. In the first stage, aTHF solution of Ca [N(SiMe3)2]2(THF)2 w a s a d d ed t o amixture of -CL and 2-propanol ([-CL]0/[2-P rO H ]0/[Ca ]0) 100/2/1, [-CL]

0) 0.8 mol/L), a ffording aft er 6 min

polymeriza tion 100%monomer conversion. To th is r eac-tion mixture, a solution of L-LA (44 equiv with respectto 2-propanol) in THF was added. The polymerizationof L-LA ensued to give at 93%conversion after 80 mina block copolymer w ith Mn ) 12.6 103 (Mn, theory )12.4 103) a n d P D I ) 1.18. The 1H NMR spectrum oft h e block cop oly mer is s h own in F ig u re 5. B e s ide sresonances from the main chain, the signals at 1.22(doublet) and 4.34 (qua rtet) chara cteristic of th e methy lprotons of the isopropyl ester end group and the lactylmethine proton neighboring the hydroxyl group, respec-tively, w ere clearly detected. The t riplet assigna ble toR-methy lene pr otons of hydr oxyl-capped poly(-CL) at 3.63 completely disappeared. These results indicate

a quantitative crossover from the living poly(-CL ) endto t he living poly(L-LA) end. 13C N M R a n a ly s is o f t h ecopolymers of -caprolactone and L-lactide affords dis-tinct information on the sequence distribution of -oxy-ca p r oy l a n d l a ct y l u n it s , w i t h t h e ca r b on y l s ig n a l sproven t o be the most sensitive to sequence effects.25-27

The absence of resonances between the two carbonyls ig n a ls a t 173.4 a nd 169.4, corresponding to poly(-CL) block a nd poly(L-LA) block, respectively, as shownin Figure 6, indicates tha t n o random sequences due totra nsesterificat ion were formed.25-27 I n c o n t r a s t , a t -tempts to prepare the block copolymer in the reverseorder or to synth esize ra ndom copolymers by simulta-neously polymerizing a n -CL a nd L-LA mixture failed,both yielding exclusively poly(L-LA) homopolymer. In-t e res t in g ly , t h e s a me p h en ome n a we re obs erv ed f ora n a l og ou s i ni ti a t or s ys t em s , s uch a s a l um in u malkoxides28 and yt trium alkoxides.19

The alcohol used determines the end functionalitiesa nd/or ma cromolecular a rchitectur es. To exemplify t his,poly(ethylene glycol) (Mn,NMR ) 2.0 103, P D I ) 1.03,P E G 2000) wa s u s ed in t h e p res en t s y s t em. A TH Fsolution of Ca[N(SiMe3)2]2(THF)2 w a s a d d ed t o a m i x-t u re o f P E G 2000 a n d L- L A a t a m o l a r r a t i o [L-LA]0/[OH]0/[Ca ]0 ) 100/2/1. The polym eriz a ti on proceeded to100%conversion wit hin 18 min, yielding poly(L-lactide)-

Figure 2. The 300 MHz 1H NMR spectrum (CDCl3) of poly-

(-CL) obtained with 2-PrOH-Ca[N(SiMe3)2]2(THF)2 (molarra tio: 2/1) (entr y 5, Ta ble 1).

Figure 3. Dependence of th e ra tio of degree of polymerization(DP) of poly(L-LA) and monomer conversion on t he init ia lmonomer/2-P rOH m olar ra tio. The DP wa s determined by 1HNMR end group an alysis. P olymerizat ion conditions: [2-P rOH]0/[Ca]0 ) 2/1, room tem pera tu re, THF . Con vers ion (%) is notedin parentheses.

Figure 4. Poly(

L

-LA) molecular weight and polydispersityindex (PDI) vs conversion with [M]0/[2-P rO H ]0/[Ca ]0 ) 150/2/1, room temperature, THF, [M]0 ) 0.8 mol /L.

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b-(eth ylen e glycol)-b-(L-lactide) triblock copolymer cappedwith hydroxyl groups at both ends and with a Mn a ndPDI of 15.5 103 a nd 1.03, respectively (entry 6).

The combina tion of C a [N(SiMe3)2]2(THF)2a n d me t h a -nol in th e homopolymerizat ions of L-LA or -CL yieldedp oly es t e rs h a v in g a mu ch h ig he r Mn tha n expected

(entries 7 an d 8). This ma y result fr om the a ggrega tionof in-situ genera ted calcium met hoxide and /or growin gspecies, since calcium alkoxides containing stericallycompact groups (-OMe, -OEt, etc.) are oligomeric orpolymeric.29,30 The a lcohol used in this ca ta lyst /initia torsystem apparently plays an important role. Stericallymore crowded alcohols, such as 2-propanol and poly-(ethylene gly col), can sufficiently suppress th e forma tionof coordinat ive aggrega tes a nd th us lead t o good controlover the polymerization.

In another experiment, polymerizat ion of L-LA w ascarried out w ith a lar ge excess of 2-propa nol relative toCa[N(SiMe3)2]2(THF)2 ([L-LA]0/[2-P rOH ]0/[Ca ]0 ) 192/8/1). After 1.5 h , a 1H N M R s p ect ru m of t h e c ru de

polymerizat ion mixture showed th at conversion w ascomplete and all 2-propanol molecules had taken partin t he polymerizat ion (Mn,NMR ) 3.9 103, Mn,theory )3.5 103, P D I ) 1.13). This implies tha t the a lcohol-Ca[N(SiMe3)2]2(THF)2 initiator system promotes livingring-opening polymerizat ion of cyclic esters w ith fastreversible transfer between dormant species and activespecies (immorta l polymerizat ion8,31). A 1H N MRspectrum of a 2-propanol-Ca[N(SiMe3)2]2(THF)2 mix-t ur e (10/1) in C 6D 6 at room temperature revealed thatthe isopropyl groups are in a single average environ-me n t , s u p p o rt in g t h e ra p id a n d re v e rs ible e x c h a n g ebetween coordinated alkoxides and free alcohols.

Another important issue for L-LA polymerizat ion is

the possible racemizat ion during the rea ction. 13C NMRspectroscopy ha s been esta blished a s a useful methodt o iden t i f y t h e s t e reos e q u en ce dis t r ibu t ion in p oly -(lactide).32-35 13C N MR spectra (Figure 7) of a ll poly(L-LA)s obtained in this study showed only three sharps ign a ls corre s pon din g t o t h e ca rbo n y l, me t h y l, a n dmethine car bons, respectively, indica ting t he format ionof isotactic poly(L-LA) and no base-promoted epimer-i za t i on of t h e L-LA monomer or poly(L-LA).34 Th eintroduction of stereochemical defects into poly(L-LA)chains as a result of racemizat ion would dramaticallyalt er the therma l behavior such as a decrease of meltingpoint and the degree of crystallinity.36,37 Therefore, thechara cterist ic therma l propert ies a re good indexes forthe str uctural perfectness. DS C of a poly(L-LA) sa mplere v e a le d a c ry s t a l l iza t io n e x o t h e rm a t 106 C a n d asingle melt ing pea k a t 165 C (Figur e 8). This is in closeagreement w ith t he melt ing behavior of optically purepoly(L-LA) reported by Prudhomme et al. 37

Kinetics of -CL polymerization in THF initiat ed witha low concentra t ion of C a[N(SiMe3)2]2(THF)2 w a s i n -v es t ig a t e d a t r oom t e mp er a t u r e a n d m on i t or ed b ymanual sampling followed by 1H NMR an alysis (CDC l3)to determine the monomer conversion. In the presenceof 2 equiv of 2-propanol with respect to Ca[N(SiMe3)2]2-(THF)2, the polymerization is first-order in monomer,a nd no induction period is observed (Figure 9). This isin s h a rp c o n t ra s t t o p o ly me riza t io n s wit h a lu min u malkoxides38,39 or commercial yt tr ium isopropoxides 40

Figure 5. The 300 MHz 1H NMR spectrum (CDCl3) of poly-

(-CL)-b-(L-LA) block copolymer prepared by sequential ring-opening polymeriza tion of -CL a nd L-LA employing 2-P rOH-Ca[N(SiMe3)2]2(THF)2 (mola r ra tio: 2/1).

Figure6. Carbonyl region of 13 C N MR spectrum (75.26 MHz,C D C l3) of poly(-CL)-b-(L-LA) block copolymer prepared bysequential ring-opening polymerizat ion of -C L a n d L-LAemploying 2-P rOH-Ca[N(SiMe3)2]2(THF)2 (mola r ra tio: 2/1).

Figure7. The 75.26 MHz 13C NMR spectrum (CDCl3) of poly-(L-LA) obta ined w ith 2-P rOH-Ca[N(SiMe3)2]2(THF)2 (molarra tio: 2/1) (ent ry 4, Table 1).



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wh e re a p ron ou n ce d in du ct ion t ime t o re a rra n g e t h eligands of the init iator thereby allowing the monomerto access the coordination sphere of the metal is present.Interest ingly, no retardat ion was observed for either-caprolactone or L-lact ide polymerizat ion w ith the in-situ yttrium isopropoxides generated from yttrium 2,6-di-tert-butylphenoxides and 2-propanol.20,40 I t a p pe a rsthat in-situ generated init iators have superior polym-erizat ion kinetics in that the polymerizat ion react ionstarts immediately upon mixing catalyst and monomer.These feat ures ar e in line with the a bsence of termina-t ion react ions a nd t he conclusion t ha t fa st excha nge ofthe free 2-propa nol with bis(trim ethylsilyl)amide liga ndsoccu r s a n d t h a t t h e i n i t ia t i on i s f a s t com pa r e d t opropaga tion. The a ppar ent propaga tion rat e consta nts(kpa pp), calculated according to ln([M]0/[M ]t) ) kpa pp[2-P r O H ]0t, a re 0.041 L mol-1 s-1 ([2-P rOH ]0 ) 2.0 mmol/L ) a n d 0. 33 L m ol-1 s-1([2-PrOH]0 ) 2.7 mm ol/L),respectively, w hich a re lower tha n t hat determined forthe yttrium isopropoxide polymerization of -CL usingC H 2C l2 a s t h e s o lv e n t 40 bu t comp a ra ble t o t h os e ofaluminum alkoxides in THF. 38,41,42 I n c on t ra s t , in t h eabsence of 2-propanol, the polymerizat ion appears top roce ed in t wo s t a g e s. A ra p id in it ia t ion a n d e a rlyp rop a g a t ion is f ol lowe d by a v ery s low f irst -orde rpropagation.

O n t h e ba s is o f t h e re su lt s a n d by a n a log y w it h t h emechanism s a ccepted for the r ing-opening polymeriza-

t ion of cy cl ic es t er s m ed ia t e d w i t h ot h er m et a lalkoxides,4,40,43 a n in i t ia t io n me c h a n is m in wh ic h t h ebis (t r ime t h y ls i ly l)a m ide l ig a n ds in Ca [N (SiM e3)2]2-(THF)2 ar e irreversibly excha nged for the alcohol andt h e in -s i t u f orme d ca lc iu m a lk ox ide s s u bse q u en t lypromote th e ring-opening polymeriza tion of cyclic estersthr ough exclusive acyl-oxygen cleava ge of the monomer

and insertion into the calcium-a lkoxide bond (Scheme1) is proposed. In the ca se of excess a lcohol wit h r egar dto bis(trimethylsilyl)am ide ligands, the act ive species(coordina ted a lkoxides a nd/or gr owing polymer ends)e xch a n g e r a p id l y a n d r ev er s ib ly w i t h t h e d or m a n tspecies (free a lcohol m olecules a nd/or h ydr oxyl-cappedp o ly me rs ) . T h is f e a t u re e n s u re s t h a t mo re t h a n t wopolymer cha ins can be produced by each Ca [N(SiMe3)2]2-(THF)2molecule. The living species can be hydrolyticallyd ea c t iv a t ed b y a d d i ng a n a c id , w h i ch l ea d s t o t h eforma tion of the hydroxyl end group.

Conclusions

Aggrega tion a nd/or insolubility of calcium a lkoxidederivat ives was circumvented by generat ing them insitu from Ca[N(SiMe3)2]2(THF)2 precursor and an ade-quate alcohol using THF as the solvent. In-situ formedc a lc iu m a lk o x ide s a re h ig h ly a c t iv e , in i t ia t in g a f a s tliving ring-opening polymerization of both -caprolac-tone and L-lactide under mild conditions. Polyesters andblock copolyesters of expected molecular weight an dtailored chain structure can be readily prepared. Thering-opening process involves selective a cyl-oxygenrupture of the monomer and insertion into the calcium-alkoxide bond initially obtained after the alcoholysis ofcalcium am ides. Kinetic profiles w ith first-order propa -g a t i on i n m on om er a n d n o i n du ct i on p er i od w e r eestablished for -caprolactone polymerizat ion with a2-PrOH-Ca[N(SiMe3)2]2(THF)2 in i t ia t in g s y s t e m. N o

Figure 8. DS C t he r m og r am (se c ond sc an) of a pol y (L-LA)sa mple recorded at a hea ting ra te of 10 C /min under N 2flow.

Figure 9. Kinetics of -CL ([-CL]0 ) 200 mmol/L) polymer-ization init iated with Ca[N(SiMe3)2]2(THF)2 in THF at roomt e m pe r at ur e : [C a]0 ) 1.0 mmol/L, in th e a bsence of a lcohol(0); [Ca ]0 ) 1.0 mm ol/L, [2-P rOH ]0 ) 2.0 m mol /L (b); [Ca]0 )1.35 m mol/L, [2-P rOH ]0 ) 2.70 m mol/L (2).

Scheme 1. Polymerization Reactions

M acromolecul es, Vol. 34, N o. 12, 2001 Ca -B a s ed I nit ia t or Sys t em for R OP of Cyclic Es t ers 3867


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racemizat ion wa s observed in L-LA polymerization, asrevealed by NMR a nd DS C a na lyses. The high cata lyt icactivity of the calcium-oxygen bond of alkoxide in thep oly meriza t ion of cy cl ic e st e r s u bst ra t e s a s de mon -s t ra t e d by t h e p re se n t s t u dy of f ers g rea t p ot e n t ia l o fcalcium-based initiators in the synthesis of biomedicaland pharmaceutical polyesters. Detailed mechanist icand kinetic investigat ions for L-lactide polymeriza tionas well as the development of structurally well-definedsingle-site calcium alkoxide w ith a formula Ln*-C a-OR (Ln* refers to a bulky ligand set) are currently inprogress.

Acknowledgment. This study w as f ina ncially sup-p o rt e d by t h e N e t h e rla n ds F o u n da t io n f o r Ch e mic a lResearch.

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