6-methyl-e-caprolactone

Interestingly, enzymes are chiral catalysts and their potential for enantio-selective polymerization has been investigated [93]. Several examples are reported where a racemic mixture of lactones is polymerized by enzymatic polymerization to afford the corresponding optically active polyester [93]. For instance, lipase CA (Novozym 435) catalyses the ROP of racemic 4-methyl-s-caprolactone and 4-ethyl-s-caprolactone in bulk at 45 °C and 60 °C to afford (S )-eiuiched poly(4-methyl-e-caprolactone) and poly(4-ethyl- -caprolactone) with an enantiomeric purity higher than 95% [153]. 

By taking advantage of the simultaneous enzyme inhibition by nickel, the nickel-catalyzed ATRP, and the stereoselectivity of the enzyme, Peters et al. obtained chiral block copolymers by this method from 4-methyl-e-caprolactone (4-MeCL) by [27], The polymerization of racemic 4-MeCL showed good enantioselectivity and produced a chiral macroinitiator with ATRP endgroup by selectively polymerizing only the (5 )-4-MeCL. Macroinitiation was then started by adding the nickel catalyst and methyl methacrylate (MMA) to the reaction mixture, which simultaneously inhibited the enzyme and activated the ATRP process. Chiral poly[MMA-fe-(5 )-4-MeCL] was successfully obtained in this synthesis. 

Peeters et al. combined the enantioselective eROP of 4-methyl-e-caprolactone (4-MeCL) with controlled atom transfer radical polymerization (ATRP) of methyl methacrylate (Scheme 11.17) [58]. It was found that the addition of Ni(PPh3)4 inhibited Novozym 435 and at the same time catalyzed the ATRP reaction. On the other hand, Novozym 435 did not interfere with the ATRP of methyl methacrylate. As a result the sequence of the reaction was important first the enantioselective eROP of 4-MeCL was conducted at low temperature to have a high enantioselectivity until the conversion was around 50%. Then, Ni(PPh3)4 and MM A were added and the temperature was raised to 80 °C to start up the ATRP reaction of MM A. After precipitation of the polymer to remove the unreacted (R)-4-MeCL, the chiral block copolymer (Mn= llkgmoT1 and 17 kg mol 1) was... 

Scheme 11.17 Cascade approach to a chiral block copolymer combining enantioselective ROP of 4-methyl-e-caprolactone and ATRP of methyl methacrylate.

PoIy(A -isopropylaciylamide-Z>- 4-methyl-e-caprolactone) water 2010LE1... 

Scheme-2. Novozym-435 catalysed Enantioselective ring opening of 4-methyl-e-caprolactone and 4-ethyl-e-caprolactone.

Figure 5. Percent monomer conversion as a function of time for novozym-435 catalyzed ring-opening bulk polymerization of 4-ethyl-e-caprolactone at 60 °C (A), 4-methyl-e-caprolactone at 60 C ( ) and 4-methyl-e-caprolactone at45 C ( ).

Table 3. Lipase Novozym-435-Catalyzed Enantioelective Ring-Opening Polymerization of 4-Methyl-e-caprolactone at 60 °C ...

NMR Spectroscopy. H and C NMR spectra were recorded on a Bruker ARX-360 spectrometer at 360 and 90 MHz and a Bruker DPX-2S0 spectrometer at 250 and 62.9 MHz, respectively. H NMR chemical shifts (ppm) are reported downfield from 0.00 ppm using tetramethylsilane (TMS) as an internal standard. The concentrations used were -4% w/v in chloroform-d (CDCl,). C NMR spectral chemical shifts in (ppm) are referenced relative to the internal standard chloroform-d at 77.00 ppm. 4-Methyl-e-caprolactone monomer conversions were determined from the relative peak areas of H NMR signals corresponding to methyl (-CH3) protons in the polymer and the monomer at 0.93 and 0.99 ppm, respectively. 4-Ethyl-e-caprolactone monomer conversions were determined from the relative peak areas of H NMR signals corresponding to methylene (-... 

The ROP of lactones with various ring sizes (6- to 13- and the 16-membered ring) catalysed by CALB showed differences in their polymerisation rates. The Ku was more or less independent of the ring size, suggesting similar affinities of the lipase for all lactones, while no obvious trend could be discerned for Vmax [102]. The ROP of 4-substituted e-CL catalysed by the same lipase demonstrated dramatic differences in polymerisation rates and selectivity, depending on the size of the substituent. Quantification of the reaction rates showed that the polymerisation rate decreased by a factor of 2 upon the introduction of a methyl (Me) substituent at the 4-position. Moreover, 4-ethyl-e-caprolactone (4-EtCL) polymerised 5 times slower than 4-methyl-e-caprolactone (4-MeCL) and 4-propyl-e-caprolactone (4-PrCL) polymerised 70 times slower. The decrease in polymerisation rate is accompanied by a strong decrease in enantioselectivity [104]. 

Optically active polyesters were synthesized by lipase CA-catalyzed ring-opening polymerization of racemic 4-methyl or ethyl-e-caprolactone. The (5 )-isomer was enantioselectively polymerized to produce the polyester with >95% ee. Quantitative reactivity of 4-substituted e-caprolactone using lipase CA as catalyst was analyzed. The polymerization rate decreased by a factor of 2 upon the introduction of a methyl substitutent at the 4-position. Furthermore, 4-ethyl-8-caprolactone polymerized five times slower than the 4-methyl-8-caprolactone. This reactivity difference is strongly related to the enantioselectivity. Interestingly, lipase CA displayed 5 -selectivity for 4-methyl or ethyl-8-caprolactone, and the enantioselectivity was changed to the (f )-enantiomer in the case of 4-propyl-8-caprolactone. 

Various substituted lactones were used for enzymatic polyester synthesis via ROP ( )-a-methyl- 3-propiolactone [101], P-methyl-P-propiolactone [78], a-decenyl-P-propiolactone [27], a-dodecenyl-P-propiolactone [46],benzyl-P-D,L-malonolactonate [104], a-methyl-e-caprolactone [96], oc-methyl-8-valerolactone [96], l,4-dioxane-2-one [91], and others (see also Table 4.2). 

While the polymerization of optically inactive AA-BB and AB monomers under DKR conditions leads to chiral polyesters, these approaches always result in limited molecular weights since a condensation product is formed that needs to be effectively removed. A solution for this would be to use the eROP of lactones, where no condensation products are formed during polymerization. In principle, the eROP of lactones can lead to very high MW polyesters (>80kgmol 1) [57]. Addition of a methyl substituent at the ro-position of the lactone introduces a chiral center. Peeters et al. conducted a systematic study of substituted e-caprolactones which revealed that monomers with a methyl at the 3-, 4-, or 5-position could be polymerized enantioselectively while a methyl at the 6-position (a-methyl-e-caprolactone, 6-MeCL) could not [58]. The lack of reactivity of the latter monomer in a Novozym 435-catalyzed polymerization reaction was attributed to the formation of S-secondary alcohol end-groups. These cannot act as a nucleophile in the propagation reaction since the lipase-catalyzed transesterification is highly R-selective for secondary alcohols. 

Snbstitnted medium size lactones were polymerized by lipase catalyst. Ring-opening polymerization of Q -methyl-snbstituted six- and seven-membered lactones (a-methyl-3-valerolactone and a-methyl-e-caprolactone, respectively) proceeded using lipase CA catalyst in bnlk (159). As to (R)- and (S)-3-methyl-4-oxa-6-hexanolides (MOHELs), lipase PC indnced the polymerization of both isomers. The apparent initial rate of the S isomer was seven times larger than that of the R isomer, suggesting that the enantioselective polymerization of MOHEL took place through lipase catalysis (160). 

To determine the effects of optical purity of polyesters on their physical characteristics we carried out (33) synthesis of poly 4-ethyl-e-caprolactone (4-EtCL) and poly 4-methyl-E-captolactone (4-MeCL) of variable enantiopurities. From the enantioelective ring opening polymerization of the racemic 4-ethyl and... 

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. 

II. B polyethylene glycol, ethylene oxide, polystyrene, diisocyanates (urethanes), polyvinylchloride, chloroprene, THF, diglycolide, dilac-tide, <5-valerolactone, substituted e-caprolactones, 4-vinyl anisole, styrene, methyl methacrylate, and vinyl acetate. In addition to these species, many copolymers have been prepared from oligomers of PCL. In particular, a variety of polyester-urethanes have been synthesized from hydroxy-terminated PCL, some of which have achieved commercial status (9). Graft copolymers with acrylic acid, acrylonitrile, and styrene have been prepared using PCL as the backbone polymer (60). 

The relative rates of polymerization of a series of substituted e-caprolactones initiated by (246) demonstrate that methyl groups, particularly adjacent to the acyl oxygen, retard polymerization.757 In addition, the rate of polymerization of the parent unsubstituted CL at 25 °C was found to be 4 x 102 times greater than L-LA at 70 °C. The slower propagation of LA is usually attributed to coordination of the nearest inserted carbonyl of the polymer chain to the A1 center, leading to formation of a stable 5-membered chelate, which hinders monomer uptake.758... 

Various Ln amides have already been described in Sections 4.3.5 and 4.3.6 as catalysts for polymerisation of ethylene," I38,i4i i43 jjex-l-ene, isoprene,styrene, " methyl methacrylate or other polar monomers such as t-butyl acrylate or acrylonitrile, . 138,143,152,177 nng-opening polymerisation catalysts for e-caprolactone or... 

The 5,6,7,8-tetrahydro-2/7-l,2-oxazocine-3(4/7)-one was detected by gas chromatography-mass spectrometry (GC/ MS) in traces after a reaction sequence starting from e-caprolactone, which was sequentially transformed with HBr in AcOH and MeOH into the corresponding tu-bromo methyl ester, subsequent reaction with A -hydroxyphthalimide, removal of the protecting group with methylhydrazine, and final cyclization with AlMe3 <2003CJC937>. 

---