Ind. Eng. Chem. Res. 2005, 44, 8641-8643
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Polymerization of Lactides and Lactones by Metal-Free Initiators† Hong Li,‡ Jun Wu,‡ Sylvain Brunel,§ Christiane Monnet,§ Roselyne Baudry,# and Pierre Le Perchec*,§ The State Key Laboratory of Functional Polymeric Materials for Adsorption and Separation, Institute of Polymer Chemistry, Nankai University, 300071 Tianjin, People’s Republic of China, Laboratoire des Mate´ riaux Organiques a` Proprie´ te´ s Spe´ cifiques, UMR 5041, CNRS, BP 24, 69390 Vernaison, France, and D.C. Sherrington Laboratory, Strathclyde University, England
New metal-free and thermally stable initiators as hexaalkylguanidinium salt (HAGs) derivatives have been investigated for the polymerization of lactones. Polymerization occurs smoothly at low temperature (120 °C) in bulk and has been determined to be dependent on the nature of the anionic counterions. Among the various HAG salts investigated, the bromide derivative offers the highest activity (of the same order of magnitude as that of the tin(II) octanoate catalyst). By mixing HAG bromide (HAG,Br) and sodium carboxylate salts, the catalytic activity increased, likely because of improved solubilization of the catalyst in the polymeric medium. Although a weak molecular weight was obtained, the polymerization process was determined to be efficient, in term of the consumption of any lactone monomers, making the process promising. For example, (3S)-L-lactide polymerizes smoothly in the presence of a mixture of HAG,Br and sodium carboxylate with 65% enantioselective excess. Introduction
Scheme 1. Structure of Guanidinium Salts.
Biodegradable polyesters with improved properties are attracting increased interest for many applied fields.1-4 They are used as dispersing agents for pigments, as well as additives for high-impact thermoplastics and for low-temperature-adhesiveness materials. They have been widely investigated as medical implants and drug-delivery supports. Aliphatic polyesters are profitably obtained by ring opening polymerization (ROP) of sizable cyclic monomers, such as glycolide, -caprolactone, D,L-lactide, and the optically active (3S)cis-L-lactide. Such monomers are among the most attractive to produce the corresponding biodegradable materials. A large variety of initiators generate ROP reactions,5-13 and their activities were outlined on the basis of rate comsunption of the monomers and optical purity of the poly L-lactides. ROP processes have received attention in regard to the toxicity allowance of initiating agents. This represents a thorny question, which is yet to be solved in the case of the industrial production of polyesters. Kricheldorf claimed that Zn-lactate could be used as an alternative solution to provide a resorbable initiator.14,15 However, until now, the best compromise was observed with tin(II) alkylcarboxylate derivatives.12 These compounds have led to the production of polymers at low cost, as shown for the production of poly(Llactide), unless their toxic allowance was not regarded with deep care. † Dedicated to the 60th birthday of Professor D. C. Sherrington. * To whom correspondence should be addressed. E-mail:
[email protected]. ‡ The State Key Laboratory of Functional Polymeric Materials for Adsorption and Separation, Institute of Polymer Chemistry, Nankai University. § Laboratoire des Mate´riaux Organiques a` Proprie´te´s Spe´cifiques, CNRS. # D. C. Sherrington Laboratory, Strathclyde University (Postdoctoral fellowship, 2003-2004).
X- ) Cl-, Br-, SCN-; R1-R4 ) Me or n-Bu; and R5 and R6 ) n-Bu.
Discussion The search for new metal-free initiators with lower toxicity than that of tin(II) 2-ethylhexanoate (SnOct2) has led us to consider hexaalkyl guanidinium salts (HAGs) as candidates to solve this problem (Scheme 1). HAGs have long been considered to be thermally stable reactive compounds that can be readily prepared on a large scale from low-cost tetraalkylureas or from tetraalkylguanidines.16 They are loose lipophilic ion-pair compounds, the cation of which has a stability that results from positive charge delocalization over the three N atoms. For example, in case of hexabutylguanidinium chloride (HBG,Cl), the chloride anion displays an enhanced nucleophilic activity, as was claimed in the case of the decomposition of 2(S)-octyl chloroformate producing enantiomerically pure 2(R)-chloroctane.17 Various electrophilic reactions, such as acyl chloride production from carboxylic acids, esterification, epoxides ring opening, and acetal deprotection, have been described,18-20 and these reactions have outlined the high catalytic activity of HAGs. Until now, no such salts have been considered for use as initiators for the ROP of lactides and lactones. In the present work, the goal was reinforced by anticipating the innocuous character of HAGs. When the initiation step in the ROP process is anionic, its efficiency is dependent on the capacity of
10.1021/ie058022n CCC: $30.25 © 2005 American Chemical Society Published on Web 09/13/2005
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Ind. Eng. Chem. Res., Vol. 44, No. 23, 2005
Scheme 2
Table 1. Lactides and Lactones Polymerization with TMDBG,Br and Sodium Carboxylatea monomera D,L-lactide L-lactide L-lactide
-caprolactone glycolide G ) HBG or TMDBG; X ) Cl, Br, or SCN.
sodium salt
time (h)
Mn (g/mol)b
PDI
yield, Y (%)
n-octanoate n-octanoate L-lactate n-octanoate n-octanoate
72 138 96 336 72
21000 5400 5600 16600 1900
1.69 2.23 1.6 1.63 c
99 91 100 98.9 96.8
a Reaction conditions involved 0.25 mol % of the monomer. Obtained from 1H NMR in dimethyl sulfoxide (DMSO) at 360 K. c Insoluble in DMSO at 360 K. b
the initiator to promote the first ring opening and the ability of ions pair to ensure the propagating step of an intermediate alkoxide. Because of the nucleophilic enhanced character of the HAG anion and the peculiar structure of the guanidinium cation, it is anticipated that the polymerization will be efficient. To examine the ROP feasability of such a structure and the nature effect of the associated anion, three HAGs were prepared as described in the literature: hexabutyl guanidinium chloride (HBG,Cl),21,22 N,N,N′,N′tetramethyl, N′′,N′′-dibutyl guanidinium bromide (TMDBG,Br),22 and N,N,N′,N′-tetramethyl, N′′,N′′-dibutyl guanidinium thiocyanate (TMDBG,SCN) from an exchange reaction between KSCN and TMDBG,Br. To detect and compare the relative activity power of the various HBG salts, the polymerization of D,L-lactide was conducted in vacuum-sealed tubes at low temperature (120 °C) in the bulk fused phase of the monomer. Catalysts were introduced in a relative large amount (molar ratio of 1:200), and their activities were compared with that of SnOct2. Pure polymers were obtained from solubilization in acetone and precipitation in water, whereas nuclear magnetic resonance (1H NMR and 13C NMR) and infrared (IR) characterizations afford polymers that are identical to the literature descriptions (Scheme 2). Depending on the time scale of the reactions, the various HBG catalysts have presented similar behaviors, For HBG,Cl at residence time (rt) ) 260 h, the yield (Y) is 90%, the number-average molecular weight (Mn) is 5400 g/mol, and the polydispersity index (PDI) is 1.6. For HBG,Br at rt ) 130 h, Y ) 94%, Mn ) 6000 g/mol, and PDI ) 2.3. For HBG,SCN at rt ) 130 h, Y ) 93%, Mn ) 4000 g/mol, and PDI ) 3.2. (For reference, SnOct2, at rt ) 96 h, has the following values: Y ) 70%, Mn ) 7000 g/mol, and PDI ) 2.6.) As expected, the polymerization kinetics was slower with the chloride anion, whereas HGB,Br seems to be closely related to the tin(II) derivatives. The moderate yield obtained with SnOct2 was attributed to the viscosity polymer phase at 120 °C and, in contrast, the HBG salts display good solubilites, which allows the reaction to proceed to completion, because of the hydrophobic environment. In any case, the NMR analyses indicate that a high purity of the polymer phase was obtained, without side products. With SnOct2, the carboxylate anion is known to proceed via a coordination-insertion mechanism.12,23 In contrast, the ROP process of (3S)-cis-L-lactide, conducted at 120 °C with sodium alkylcarboxylate salts, affords lower molar masses, extended racemization, and chaintransfer reactions, whereas the zinc salt was determined to be much more efficient.14,24 Therefore, the possibility to improve the activity of such anions in the presence of HAGs counterions seems to be a topic of interest. In the case of D,L-lactide polymerization, an equimolar amount of sodium n-octanoate and TMDBG,Br improves
the catalytic activity, compared to TMDBG,Br alone (see Table 1); only traces of monomer were observed in a shorter time, and the polymer had better characteristics (Mn ) 21 300 g/mol and PDI ) 1.6). Poly -caprolactone and polyglycolide also were produced, in good yields, confirming the efficiency of the HAGs salts (see Table 1). TMDBG,Br and sodium octanoate association was also tested for ROP of (3S)-cis- L-lactide. Polymer was obtained with low molar mass, but the poly(L-lactide) was present in an optically active form, with an RD value of -112.2° (in CHCl3). Compared to data of pure poly(L-lactide), -173.5°,25 this accounts for a 65% enantiomeric excess, as confirmed from 13C NMR analysis of the carbonyl (δ ) 169.59 Hz) and methine (δ ) 68.99 Hz) signals. An in situ production of an active hydrophobic guanidinium octanoate was suggested to explain the enhancement and optical purity improvement, in comparison to sodium octanoate alone (PLLA RD ) -67°).24 Sodium L-lactate polymerization has confirmed the activity of the TMDBG,Br catalyst in ROP polymerization. Poly-L-lactide was isolated in pure form, with complete consumption of the monomer occurring after 96 h of reaction time at 120 °C (see Table 1). HAGs alone, or in association with an alkyl carboxylate sodium salt, are favorably compared to the tin(II) salt activity as the lactone and lactide ROP initiator. An interesting result is obtained from the catalytic activity of the TMDBG,Br and sodium carboxylate, unless partial racemization was observed for (3S)-Llactide polymerization. A nucleophilic enhancement of the HAG anions was established both experimentally and theoretically. Counterions associated with HAGs units previously have been considered to be powerful reagents for nucleophilic addition at the carbonyl group or as hydrogen abstraction alpha to the carbonyl compounds. Both mechanisms might initiate the polymerization, with HAGs carboxylate as the propagating ion pairs. Because the HAGs carboxylate ion pair is produced in a hydrophobic environment, the reaction occurs almost in completion and degradation products are limited, because of the absence of OH end-chain groups.26 Conclusion Hexaalkylguanidinium salts (HAGs) may represent a promising metal-free catalyst for the ring opening polymerization (ROP) processes of lactones. Polymers have been obtained under moderate conditions, whereas the initiators can easily be eliminated by water washing to produce pure materials. The stability, innocuity, and easy handling of guanidinium salts are favorable for developing new approaches for the manufacture of polylactones.
Ind. Eng. Chem. Res., Vol. 44, No. 23, 2005 8643
Experimental Section Hexabutylguanidinium chloride (HBG,Cl)13,21 was prepared from N,N,N′,N′-tetrabutylchloroformamidinium chloride (obtained from tetrabutylurea and oxalyl chloride) and dibutylamine; yield, 60%; mp, 142-144 °C (literature value: 143 °C). Elemental analysis: N, 9.7% (calc. 9.8%); Cl, 8.23% (calc. 8.39%). Main spectroscopic values: IR KBr, ν(CdN) ) 1540 cm-1; 1H NMR (CDCl3), ν(CH2-N) ) 3.2 ppm; 13C NMR (CDCl3), ν(CdN) ) 164.3 ppm. N,N,N′,N′-tetramethyl, N′′,N′′-dibutylguanidinium bromide (TMDBG,Br) was produced from N,N,N′,N′-tetramethylguanidine, 1-bromobutane, and anhydrous potassium carbonate in refluxed acetonitrile.22 It was isolated in 94% yield (mp
