Conversion of Diols to Dithiols Via a Dehydration Polycondensation with a Dicarboxylic Acid Containing a Disulfide and Subsequent Reduction
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Polymer Journal (2010) 42, 956–959 & The Society of Polymer Science, Japan (SPSJ) All rights reserved 0032-3896/10 $32.00 www.nature.com/pj RAPID COMMUNICATION Conversion of diols to dithiols via a dehydration polycondensation with a dicarboxylic acid containing a disulfide and subsequent reduction Polymer Journal (2010) 42, 956–959; doi:10.1038/pj.2010.100; published online 27 October 2010 Derivatization of compounds often trans- thiol-ene and thiol-yne click reactions11–13 nesulfonate catalysts that afforded aliphatic forms the targeted functional group; however, have been useful. Application of thiol-related polyesters with number-average-molecular 4 most of these processes require severe reac- chemistry to polymer synthesis promises to weights (Mns) 41.0Â10 (refs 16–24). This tion conditions and/or excessive amounts of open a new frontier in material design, but polycondensation system made it possible to reagents.1 These drawbacks frequently occur first, methods that readily afford a thiol on use thermally unstable monomers that con- when transformations of polymer termini are deprotection must be developed. Martinelle tained a carbon–carbon double bond,17 a attempted. If we could derivatize the terminal and co-workers14 described a one-step end- bromine substituent18 and/or a hydroxyl functional groups of polymers easily, we functionalization of poly(e-caprolactone) by substituent.21,23 could design new types of polymers with a ring-opening polymerization that was cat- The aforementioned studies, including our predetermined properties. Transformations alyzed by Candida antarctica lipase B and own, prompted us to investigate the possibi- of polymer termini have been reported by used mercaptoethanol as the initiator. A lity that the terminal hydroxyl groups of a several groups. A method that uses anionic transformation of polycaprolactone (PCL) polymer could be replaced by thiols by a living polymerization was described by diol to PCL dithiol was reported by Leroux process that included a step polymerization. Szwarc.2 Cationic living polymerization has and co-workers,15 in which PCL diol was Such a method would overcome the limita- also been used to functionalize polymer condensed with an excess of a dicarboxylic tions of the current methods. First, we temini.3–5 Mu¨ller and co-workers5 showed acid that contained a disulfide bond by dicy- performed dehydration polycondensations that the thiophene-end-capped termini of a clohexylcarbodiimide coupling and subse- with various diols and the carboxylic acid, polyisobutylene chain could be transformed. quent reduction. 3,3¢-dithiodipropanoic acid (DTDPA), which Guillaneuf et al.6 functionalized the ends of We have directly polycondensed diols and contains a disulfide, using scandium(III) polystyrenes that had been obtained by living dicarboxylic acids at moderate temperatures trifluoromethanesulfonate (Sc(OTf)3)asthe radical polymerization techniques, that is, in the presence of rare-earth trifluorometha- catalyst. Then we cleaved the disulfides in the atom transfer radical polymerization or rever- sible addition and fragmentation transfer. These studies used living polymerizations O OH SOH that required stringent reaction conditions, + HO S HO for example, a very low temperature, a nitro- O gen atmosphere, a highly reduced pressure, a Sc(OTf) Dehydration polycondensation dry environment and ultrapure reagents. 3 7,8 Recently, Kilbinger and co-workers O reported a new method (involving ‘sacrificial S OH O O S n-1 synthesis’) to replace a functional group at S O HO S O the end of a polymer produced by ring-open- O ing metathesis. Although this method is revolutionary and therefore interesting, it 9,10 PBu Cleavage of disulfide bond suffers from low atom economy. 3 Much attention has been paid to thiol O compounds as reactants because they are O SH O (n-1) + 2 readily available and usually very reactive; HS O HS OH they are often used in addition reactions, O nucleophilic reactions, radical reactions and n>>2 thiol-disulfide coupled reactions; thiol oxida- Figure 1 Derivatization of diols by a dehydration polycondenstation with a disulfide-containing tion and disulfide reduction. In particular, dicarboxylic acid and subsequent reduction with tributylphosphine. Rapid Communication 957 1 4 resulting polyesters with tributylphosphine to products were confirmed by H-nuclear poly(DTDPA-alt-PCL) (Mn¼0.94Â10 , Mw/ afford the original compounds modified with magnetic resonance (NMR) spectroscopy, Mn¼1.3, run 9). Although the Mns were 3 dithiols that substituted for the hydroxyls and the MnsandMw/Mns were evaluated by B1.0Â10 higher than the prepolymer by with atom economy. Finally, starting with the size exclusion chromatography. The low the change of the hydrodynamic volume polyesterdithiol, and diisocianate, we synthe- yields are ascribed to purification procedure ascribed to terminal transformation from sized the corresponding polythiourethanes (reprecipitation). –OH to –OCOCH2CH2SH, after reduction (Figure 1). As an example of these reactions, of the disulfides the terminal substituents 3-methyl-1,5-pentanediol was reacted with were characterized by matrix-assisted laser RESULTS AND DISCUSSION DTDPA at 80 1C for 6 h under reduced pres- desorption/ionization–time of flight spectro- We performed dehydration polycondensa- sure in the presence of 0.5 mol% of Sc(OTf)3, scopy (Supplementary Figure S2), which con- 3 tions that used commercially available and the product had an Mn of 8.4Â10 and firmed that the product was the desired PCL 3 low-molecular-weight diols or polymeric an Mw/Mn of 1.9. The latter value agreed with dithiol (Mn¼3.0Â10 , Mw/Mn¼1.3) and did diols and DTDPA to produce products that that calculated using Flory’s theory,25 which not show peaks ascribed to monofunctinal could be converted into dithiols (Details of suggested that the reaction proceeded by step compounds. By integrating the 3.65– experimental procedure and some spectra are polymerization. After reduction of the disul- 3.73 p.p.m. (alcohol) and 2.69–2.92 p.p.m. described in Supplementary Information). fides with tributylphosphine, the product, (thiol) peak areas in the 1H-NMR spectrum The properties of the polyesters produced which was the expected dithiol (Mn¼0.76Â of PCL dithiol, the extent of derivatization 3 by dehydration polycondensation are shown 10 , Mw/Mn¼1.1), was precipitated twice from was found to be 93% (Figure 2). The poly- 1 in Table 1; the polydispersities of the CHCl3 with n-hexane. According to the H- dispersity of PCL dithiol is narrower than polyesters are those predicted by Flory’s the- NMR spectrum of the product (solvent, that of PCL diol, which may be because PCL 25,26 ory, which suggests that they were formed CDCl3), 95% of the hydroxyl groups had dithiols of low-molecular weights were not by step polymerization. The dehydration been converted to the corresponding thiols. recovered upon reprecipitation. polycondensations that used low-molecular- For higher conversion, control the polyester Polylactidediol (PLA diol, runs 11 and 12) weight diols were carried out at 80 1Cfor end group was performed by polycondensa- was prepared by a ring-opening polymeriza- 6 h under reduced pressure (0.3–3 mm Hg) tionswith1.05equivofDTDPAwascarried tion that was Sc(OTf)3 catalyzed in toluene at in the presence of 0.1–0.5 mol% of Sc(OTf)3 out at 80 1C to yield polyester having carboxyl 80 1C. For the two polymerizations, the Mns (runs 1–6). After the compounds were end groups based on widely accepted stoichio- of the PLA diols were 1.4Â103 and 2.8Â103 25 dissolved in chloroform (5 ml) and then metric principles of polycondensation. and their Mw/Mns were 1.3 as measured by precipitated using diethyl ether (100 ml), Subsequent reduction showed the higher func- size exclusion chromatography with CHCl3 as hydrogenetic reduction of the polyesters tionalities (rums 2, 4, 5, 6, 8 and 10). the eluent. The 1H-NMR spectrum of PLA 3 was carried out using 8-equiv tributylpho- The reaction of PCL diol (Mn¼1.6Â10 , diol (run 11) in CDCl3 is shown in Supple- sphine in CHCl3 at room temperature Mw/Mn¼1.8, run 9) with DTDPA and mentary Figure S1. To prepare the polyesters, for 24 h. The structures of the dithiol 0.5 mol% Sc(OTf)3 as the catalyst gave an equimolar amount of DTDPA was added Table 1 Derivatization of diols by hydration polycondensation with disulfide-containing dicarboxylic acida and subsequent reduction using TBPb Diol Polyester Dithiol Functionalitye c À3 d À4 d À3 Run Mn Â10 Mw/Mn Temp. (1C) Time (h) Yield (%) Mn Â10 Mw/Mn Yield (%) Mn Â10 Mw/Mn (%) 1 MPD 0.29 — 80 6 86 0.84 1.9 13 0.76 1.1 95 2 1,5-PDf 0.28 — 80 6 92 0.63 2.0 31 1.7g —99 3 1,6-HexD 0.29 — 80 6 95 1.4 2.3 29 1.9 — 91 4 1,7-HepDf 0.31 — 80 6 84 0.67 2.0 11 1.8g —94 5 1,8-ODf 0.32 — 80 6 86 0.90 2.0 16 1.1g —92 6 1,9-NDf 0.34 — 80 6 83 1.0 2.0 12 1.0g —92 7 TEG 0.35 — 100 14 78 1.1 1.5 14 1.3 1.2 99 8PCLdiolf 0.9 1.6 80 12/4 90 1.1 1.9 34 2.2 1.4 93 9 PCL diol 1.6 1.8 80 6 70 0.94 1.3 51 3.0 1.3 93 10 PCL diolf 3.4 1.8 80 12/4 79 1.6 1.7 85 4.7 1.4 99 11 PLA diol 1.4 1.3 100/120 12/23 22 1.6 1.2 40 3.6 1.3 499 12 PLA diol 2.8 1.3 100/120 12/23 44 1.1 1.3 89 4.2 1.3 499 13 PEG 4.2 1.1 100/120 77/13 99 1.2 1.8 89 6.0 1.4 45 Abbreviations: MPD, 3-methyl-1,5-pentanediol; PCL, polycaprolactone; PEG, polyethylene glycol; PLA, polylactide; SEC, size exclusion chromatography; TBP, tributylphosphine.