Of e-caprolactone

Ring opening of a lactone, e.g. of e-caprolactone with dihydroxy or trihydroxy initiators ... 

One variation in polyester intermediates that has roused some interest are those prepared by a ring-opening polymerisation of e-caprolactone and methyl-e-caprolactones with titanium catalysts and diol and triol initiators Figure 27.6). 

Poly(f -caprolactone) (PCL), the most representative member of this polyester family, is obtained by the ring-opening polymerization of e-caprolactone. It is a low-7 (60°C), low-Tg (—60°C) semicrystalline polyester that presents mechanical properties resembling those of low-density polyethylene (Table 2.10). 

A three-necked flask equipped with a condenser and stirrer was charged with the PET depolymerization product (0.05 mol of BHET and dimer in the ratio of 80 to 20 wt%), 0.05, 0.10, and 0.15 mol of e-caprolactone (in separate experiments), and 0.1 wt% of dibutyltin dilaurate. The reaction mixture was heated at 150°C for 2 h. The resulting co-oligomer (0.01 mol) was dissolved in 500 mL of tetrahydrofuran in a three-necked flask equipped with a condenser and a stirrer. After the temperature was raised to 67°C, a solution of 0.01 mL of hexamethylene diisocyanate in 50 mL of tetrahydrofuran was added dropwise. After heating and stirring the reaction mixture for 12 h, it was cooled and precipitated in ether. The polyurethane precipitate was collected by filtration and dried at 70°C for 12 h. 

Preparation and characteristics of ABA type polycaprolactone-b-polydimethyl-siloxane block copolymers have been recently reported 289). In this study, ring-opening polymerization of e-caprolactone was achieved in melt, using a hydroxybutyl terminated PSX as the initiator and a catalytic amount of stannous octoate. Reactions were completed in two steps as shown in Reaction Scheme XIX. 

The general subject of lactone polymerization has been reviewed (7, 19). Polymerization of e-caprolactone can be effected by at least four different mechanisms categorized as anionic, cationic, coordination, and radical. Each method has unique attributes, providing... 

FIGURE 1 Continuous process for the manufacture of e-caprolactone by oxidation of cyclohexanone with peracetic acid. 

The anionic method of polymerization is most useful for the synthesis of low molecular weight hydroxy-terminated oligomers and polymers that are to be further processed. For example, the treatment of hydroxy-terminated oligomers with isocyanates has been used to obtain polyester-urethanes (9,20), while triblock copolymers (PCL-PEG-PCL) are prepared by initiating the polymerization of e-caprolactone with the disodium alcoholate from polyethylene glycol (26). 

FIGURE 2 Anionic, cationic, and coordination mechanisms of polymerization of e-caprolactone and related lactones. 

FIGURE 14 Different skeletal structures of PCL and its copolymers derived from the polymerization of e-caprolactone using mono- and polyfunctional initiators. 

Alkyl sulfonates are very effective cationic initiators of e-caprolactone, although only the more reactive methyl triflate and methyl fluorosulfate result in a high conversion. The mechanism of polymerization in the presence of these initiators is believed to involve methylation of the exocyclic carbonyl oxygen, followed by partial ring opening of the activated lactone by the counteranion (Fig. 

The living nature of PCL obtained in the presence of Zn(OAl-(OPri)2)2 has been used to prepare both di- and triblock copolymers of e-caprolactone and lactic acid (42,43). Treatment of the initial living PCL with dilactide afforded a PCL-PLA diblock with M /Mn = 1.12, with each block length determined by the proportions of the reactants, i.e., the ratio of [monomer]/[Zn]. While the living diblock copolymer continued to initiate dilactide polymerization, it failed to initiate e-caprolactone polymerization. To obtain a PCL-PLA-PCL triblock, it was necessary to treat the living PCL-PLA-OAIR2 intermediate with ethylene oxide, then activate the hydroxy-terminated PCL-PLA-(OCH2CH2)nOH with a modified Teyssie catalyst (Fig. 5). 

Stannous octoate has the advantage of having been used to prepare polymers (Silastic, Capronor) for which substantial toxicological data are now available (6,48). Stannous octoate-initiated polymerization has been used to prepare copolymers of e-caprolactone with other lactones, including diglycolide, dilactide, 6-valerolactone, e-decalactone, and other alkyl-substituted e-caprolactones. Conducting... 

Initiation of stannous octoate-catalyzed copolymerization of e-caprolactone with glycerol was used to prepare a series of trifunctional hydroxy-end blocked oligomers, which were then treated with hexane-1,6-diisocyanate to form elastomeric polyesterurethanes with different crosslink densities (49). Initiation of e-caprolactone polymerization with a hydroxypropyl-terminated polydimethylsiloxane in the presence of dibutyl tin dilaurate has been used to prepare a polyester-siloxane block copolymer (Fig. 4) (50). 

Ring-opening polymerization of 2-methylene-l,3-dioxepane (Fig. 6) represents the single example of a free radical polymerization route to PCL (51). Initiation with AIBN at SO C afforded PCL with a of 42,000 in 59% yield. While this monomer is not commercially available, the advantage of this method is that it may be used to obtain otherwise inaccessible copolymers. As an example, copolymerization with vinyl monomers has afforded copolymers of e-caprolactone with styrene, 4-vinylanisole, methyl methacrylate, and vinyl acetate. 

FIGURE 8 Relationship between the glass transition temperature and the composition of copolymers of e-caprolactone and lactic acid. 

An analysis of partition coefficient data and drug solubilities in PCL and silicone rubber has been used to show how the relative permeabilities in PCL vary with the lipophilicity of the drug (58,59). The permeabilities of copolymers of e-caprolactone and dl-lactic acid have also been measured and found to be relatively invariant for compositions up to 50% lactic acid (67). The permeability then decreases rapidly to that of the homopolymer of dl-lactic acid, which is 10 times smaller than the value of PCL. These results have been discussed in terms of the polymer morphologies. 

The rate of release of levonorgestrel from films of block copolymers of e-caprolactone and dl-lactic acid (drug load 30%) was shown to be a function of the copolymer composition. The rate was unchanged for compositions of 100% and 88% e-capirolactone, but decreased thereafter as the e-caprolactone content decreased (42). 

Evidence of enzymatic degradation in vivo was first observed with a random copolymer of e-caprolactone and e-decalactone (93). 

FIGURE 21 Semilog plot of the in vitro rate of hydrolytic chain scission of various copolymers of e-caprolactone, measured under in vitro conditions. (From Ref. 95.)... 

More definitive evidence of enzymatic attack was obtained with 1 1 copolymers of e-caprolactone and 6-valerolactone crosslinked with varying amounts of a dilactone (98,99). The use of a 1 1 mixture of comonomers suppressed crystallization and, together with the crosslinks, resulted in a low-modulus elastomer. Under in vitro conditions, random hydrolytic chain cleavage, measured by the change in tensile properties, occurred throughout the bulk of the samples at a rate comparable to that experienced by the other polyesters no weight loss was observed. However, when these elastomers were implanted in rabbits, the bulk hydrolytic process was accompanied by very rapid surface erosion. Weight loss was continuous, confined to the... 

FIGURE 23 Rate of enzymatic surface erosion of a 1 1 copolymer of e-caprolactone and 6-valerolactone, crosslinked with a dilactone to form an elastomer. The effect of substitution of the e-caprolactone nucleus is also shown. (From Ref. 98). 

FIGURE 24 Rate of enz3nnatic surface erosion of e-caprolactone crosslinked with 12 mol % of the dilactone, 2,2-bis( e-caprolactone-4-yl)propane. (From Ref. 98.)... 

Ito, K., and Yamashita, Y., Propagation and depropagation rates in the anionic polymerization of e-caprolactone cyclic oligomers, Macromolecules. Ij., 68-72, 1978. 

J. P., Anionic pol3nnerization of lactones initiated by alkali graphitides. 1 Polymerization of e-caprolactone initiated by KC24, J. Polym. Sci.. Part A Polym. Chem.. 21. 923-936, 1983. 

Nobutoki, K., and Sumitomo, H., Preparation of block copolymer of e-caprolactone with living polystyrene. Bull. Chem. 

Yamashita, Y., Tsuda, T., Ishida, H., and Hasegawa, M., Polymerization and Copolymerization of e-Caprolactone, Koeyo Kagaku Zasshi, 71, 755-757, 1968. 

Song, C. X., and Feng, X. D., Synthesis of ABA triblock copolymers of e-caprolactone and DL-lactide, Macromolecules. 

Endo, M., Aida, T., and Inoue, S., Immortal polymerization of e-caprolactone initiated by aluminum porphyrin in the presence of alcohol. Macromolecules, 20, 2982-2988, 1987. 

Ester-thioester copolymers were enzymatically synthesized (Scheme 7). ° The lipase CA-catalyzed copolymerization of e-caprolactone with 11-mercaptoundecanoic acid or 3-mercaptopropionic acid under reduced pressure produced the polymer with molecular weight higher than 2 x 10". The thioester unit of the resulting polymer was lower than the feed ratio. The transesterification between poly(8-caprolactone) and 11-mercaptoundecanoic acid or 3-mercaptopropionic acid also took place by lipase CA catalyst. Recently, aliphatic polythioesters were synthesized by lipase CA-catalyzed polycondensation of diesters with 1,6-hexanedithiol. ... 

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