Thiol-ene reaction
In
The reaction results in an
Mechanisms
Radical addition
Thiol-ene additions are known to proceed through two mechanisms:
Thiol-ene radical additions are advantageous for chemical synthesis because the step growth (propagation and chain-transfer steps) and chain growth (homopolymerization) processes can be effectively used to form homogeneous polymer networks. Photopolymerization is a useful radical-based reaction for applications within the nanotechnology, biomaterial, and material sciences, but these reactions are hindered by the inhibitory capabilities of
Michael addition
Thiol-ene reactions are known to proceed through a
Kinetics
Click chemistry reactions are known to be high efficiency and have fast reaction rates, yet there is considerable variability in the overall reaction rate depending on the functionality of the alkene. To better understand the
Due to the complex kinetics of this two-step cyclic reaction, the rate-determining step was difficult to delineate. Given that the rates of both steps must be equal, the concentration of the radical species is determined by the rate constant of the slower of the reaction steps. Thus the overall reaction rate (RP) can be modeled by the ratio of the propagation rate (kP) to the chain-transfer rate (kCT).The behavior of the reaction rate is outlined by the relationship below. In all cases the reaction is first order, when kP ≫ kCT [Eq. 1] the reaction rate is determined by the thiol concentration and the rate limiting step is chain-transfer, when kP ≪ kCT [Eq. 2] the reaction rate is determined by the alkene concentration and the rate limiting step is the propagation, and finally when kP ≈ kCT [Eq. 3] the reaction is half order with respect to both the alkene and thiol concentrations.
The functional groups on the thiol and alkene compounds can affect the reactivity of the radical species and their respective rate constants. The structure of the alkene determines whether the reaction will be propagation or chain-transfer limited, and therefore first order with respect to alkene or thiol concentration respectively. In the case of reactive alkenes, such as allyl ether, chain-transfer is the rate-limiting step, while in the case of less reactive alkenes, such as vinyl silazanes, propagation is the rate-limiting step. The thiol's hydrogen affinity also affects the rate-limiting step. Alkyl thiols have less abstractable protons and therefore the chain-transfer step has a lower reaction rate than the propagation step.[4]
Most time the quasi-first-order reaction yields a kinetic rate equation following the exponential decay function for the reactants and products.
- [normalized thiol-ene product] =
where k is an effective rate constant and t is time.
However, when the radical generation becomes the rate-limiting step, an induction period is often observed at the early stage of the reaction, for example, for photoinitiated reaction under weak light condition. The kinetic curve deviates from the exponential decay function for a common first-order reaction by having a slow growth period. The kinetic model has to include the radical generation step to explain this induction period (right figure). The final expression has a
- [normalized thiol-ene product] =
where k is an effective rate constant and t is time.
Synthetically useful thiol-ene reactions
Initiation of cascade cyclization
The thiol-ene reaction (and analogous
Intramolecular thiol-ene reactions
Intramolecular cyclization of thiyl and acyl thiyl radicals has been used to access alicyclic and heteorcyclic compounds, via anti-Markovnikov thiol-ene reactions on 1,6-dienes, under photochemical conditions.[15]
Cis–trans conversion of alkenes
Given the reversibility of the thiol-ene radical addition, the reaction can be used to facilitate
Potential applications
Dendrimer synthesis
A general strategy for the divergent synthesis of a
Polymer synthesis
Multifunctional thiols such as
Surface patterning
The thiol-ene functionalization of surface has been widely investigated in material science and biotechnology. The attachment of a molecule with a sterically accessible alkene or thiol group to a solid surface enables the construction of polymers on the surface through subsequent thiol-ene reactions.[2] Given that in aqueous solutions thiol-ene reactions can be initiated by UV light (wavelength 365–405 nm) or sunlight, the attachment of a given functional group to the exposed thiol or alkene can be controlled spatially through photomasking.[21] More specifically, a photomask, enables the selective exposure of a surface to a UV light source, controlling the location of a given thiol-ene reaction, whereas the identity of the attached molecule is determined by the composition of the aqueous phase placed above the surface at the time of UV exposure. Thus, the manipulation of the shape of the photomask and the composition of the aqueous layer results in the creation of heterogeneous surface, whose properties depend on identity of the attached molecule at a given location.[2]
Thiol-ene functionalization of a surface can be achieved with a high level of spatial specificity, allowing the production of photomasks.[21]
Organo-triethoxysilane molecules, either thiol or vinyl tailed, have been introduced in surface functionalization. Ethoxysilane and methoxysilane functional groups are commonly used to anchor organic molecules on a variety of oxides surfaces. The thiol-ene coupling can be achieved either in the bulk solution before molecular anchoring [8] or step-wise onto a substrate that enables photolithography.[22] The reaction can be done in five minutes under sunlight that has ~4% UV light that is useful for the thiol-ene reaction.[8]
Protein patterning on electron beam resist
Thiol-ene can also be used as an
See also
References
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