Thiol-ene Polymerization

The thiol-ene reaction has been known for over 100 years.1 Yet, only recently it has gained noticeable attention, probably because Sharpless and coworkers drew attention to this highly efficient click reaction.2 Radical thiol-ene reactions, like many other 'click' chemistries, allow for the efficient synthesis of many novel polymers and dendrimers as well as for small molecule modifications of polymers such as side-chain and end-group functionalization. However, they are generally not efficient for coupling two polymers to an AB diblock copolymer or for more advanced polymer architectures such as star and comb polymers, even when one component is used in excess.3 Thiol-ene reactions have also been utilized to prepare new thioether-based monomers that can be (co)polymerized by a range of established methods.3

The reaction mechanism of a thermally and photolytically initiated thiol-ene reaction is similar to that of a thiol-Michael addition with radicals in place of anions. The reaction starts with a suitable initiator that generates a thiyl radical (RS*), either by direct abstraction of hydrogen from a thiol or indirectly, by addition to a double bond and subsequent abstraction of a hydrogen from a thiol. The formed thiyl radical adds to an alkene forming an intermediate radical, which then abstracts a hydrogen from another thiol to generate a new thiyl radical so that the cycle repeats itself until all double bonds are consumed (see cycle on the left in scheme below).4-6

The formed thiolether radicals can also radically add to other vinyl monomers, i.e. they can start a free-radical chain growth (see cycle on the right in above scheme). Which of these reaction paths dominates, depends on the type of vinyl monomer. For example, when methacrylates are polymerized with thioles, the methacrylate has a strong tendency to homopolymerize resulting in a pseudo two-stage polymerization where the first stage is dominated by vinyl homopolymerization and chain transfer and the second stage is dominated by a traditional thiol-ene polymerization. In this case, the thiol-ene moieties function as a solvent and chain transfer agent during the early stages of the polymerization, resulting in an overall lower stress buildup.4

Besides alkenes and (meth)acrylates, thiols can radically add to many other unsaturated compounds including norbornene, triallyl isocyanurate, allyl ethers, maleimides, maleates, vinyl ethers, vinyl esters, fatty acid monomers and alkynes. The latter reaction is typically referred to as thiol-yne reaction.7 For most of these ene compounds, the polymerization proceeds mainly by a step-growth addition mechanism, and for ternary thiol-ene polymerizations such as methacrylate-thiol-ene, the propagation mechanism includes a carbon radical propagation step in addition to the thiyl radical propagation and chain transfer steps.4,5 Thus, these systems undergo a combination of step-growth and chain-growth polymerization; their relative contributions depend on the composition and the relative kinetics of each step in the polymerization.
It is important to note that in the absence of a free-radical chain growth step, high molecular weight polymers can only be synthesized if both comonomers are bifunctional or multifunctional. An example of a free radical step-growth polymerization that produces linear polymer chains in this way is the reaction of an alkanediol diacrylate with an alkane dithiol (A-A + B-B) such as 1,6-hexanedioldiacrylate and 1,6-hexanedithiol.

The reaction rate depends on the type of ene and decreases with decreasing electron density of the carbon-carbon double bond, in other words, thiol-ene reactions favor electron rich enes.6,8 Thus, the reaction rate decreases in the order vinyl ether > alkene ≈ vinyl ester > allyl ether > allyl triazine ≈ allylisocyanurate > acrylate > unsaturated ester > N-substituted maleimides > acrylonitrile ≈ methacrylate > styrene > conjugated diene.6

The step growth mechanism of the thiol-ene polymerization shows some unique features and several advantages over traditional vinyl polymerization. For example, the viscosity of the reaction media does not much increase until high conversions are reached, resulting in a more uniform consumption of low molecular weight species and a more homogeneous crosslinked polymer.4 Unlike many other radical-mediated reactions, thiol-ene polymerizations are not significantly inhibited by oxygen and therefore do not produce an uncured tacky layer at surfaces exposed to air.4,5 Furthermore, thiol-ene reactions can be conducted under mild reaction conditions at high reaction rates and with high yield.5,6,8,9 Thiol-ene reactions also show very little volume shrinkage and residual stress in the final crosslinked polymer product due to the step growth mechanism and the late gel point conversion which means that most of the shrinkage occurs prior to gelation.4

References & Notes

  1. T. Posner, Berichte der deutschen chemischen Gesellschaft, Vol. 38(1), 646-657 (1905)

  2. H.C. Kolb, M.G. Finn, K.B. Sharpless, Angew. Chem. Int. Ed., 40, 2005 - 2021 (2001)

  3. A.B. Lowe, Polym. Chem., 5, 4820-4870 (2014)

  4. N.B. Cramer, C.L. Couch, K.M. Schreck, J.A. Carioscia, J.E. Boulden, J.W. Stansbury, C.N. Bowman, Dent Mater., 26 (1): 21-28 (2010)

  5. N.B. Cramer, J.P. Scott, C.N. Bowman, Macromolecules, 35, 14, 5361-5365 (2002)

  6. C.E. Hoyle, T.Y. Lee, T. Roper, J. Polym. Sci., Part A: Polym. Chem., 42, 5301-5338 (2004)

  7. Despite a similar mechanisms, thiol-yne reactions typically are slower than thiol-ene reactions.

  8. B.D. Fairbanks, D.M. Love, and C.N. Bowman, Macromol. Chem. Phys. 218, 1700073 (2017)

  9. F. Deubel, V. Bretzler, R. Holzner, T. Helbich, O. Nuyken, B. Rieger, R. Jordan, Macromol. Rapid Commun., Vol. 34(12), pp. 1020-1025 (2013)

April 15, 2020

  • Summary

    Thiol-ene Reaction

    also called alkene hydrothiolation, is an organic addition reaction between a thiol and an alkene to form a thioether.

  • The reaction mechanism of the thiol-ene click addition is similar to that of a Michael addition with radicals in place of anions.

  • The thiol-ene photopolymerization can be initiated without the use of any photoinitiator molecule.5

  • Free radical thiol-ene addition reactions, like many other ‘click’ chemistries, are highly efficient for both small molecule modifications and for coupling and modifying preformed polymers.

Read More

  • Thiol monomers are shown to copolymerize with a variety of monomers including vinyl ethers, vinyl esters, allyl ethers, acrylates, methacrylates, acrylonitriles and vinylbenzene monomers.

  • The Thiol-ene addition is a very versatile reaction in organic chemistry and finds many applications that vary from synthesis of novel polymers and dendrimers to in-situ polymer modifications in biological systems.