Nucleophile-Initiated Thiol-Michael Reactions: Effect of Organocatalyst, Thiol, and Ene

Abstract

A detailed evaluation of the kinetics of the thiol-Michael reaction between hexanethiol and hexyl acrylate is described. It is shown that primary amines are more effective catalysts than either secondary or tertiary amines with, for example, quantitative conversion being achieved within 500 s in the case of hexylamine with an apparent rate constant of 53.4 mol L−1 s−1 at a catalyst loading of 0.057 mol %. Certain tertiary phosphines, and especially tri-n-propylphosphine and dimethylphenylphosphine, are shown to be even more effective species even at concentrations 2 orders of magnitude lower than employed for hexylamine and performed in solution with quantitative conversions reached within ca. 100 s for both species and apparent rate constants of 1810 and 431 mol L−1 s−1, respectively. The nature of the thiol is also demonstrated to be an important consideration with mercaptoglycolate and mercaptopropionate esters being significantly more reactive than hexanethiol with reactivity mirroring the pK a of the thiols. Likewise, it is shown that the structure of the activated ene is also crucial with the degree of activation and ene-substitution pattern being important features in determining reactivity. In terms of reaction with hexanethiol in the presence of hexylamine as catalyst, it is shown that propylmaleimide > diethyl fumarate > diethyl maleate > dimethylacrylamide > acrylonitrile > ethyl crotonate > ethyl cinnamate > ethyl methacrylate.

Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications

“…The gels with shorter gelation time can serve to encapsulate cells inside the matrix and can be used as injectable scaffold for target specific applications. 34,35 It is well known in literature that gelation time is dependent on the PEG's molecular architecture; that 4arm PEGs have shorter gelation time than 8armPEGs. 36 Please do not adjust margins Please do not adjust margins Our observations were also similar and we demonstrated the in vitro prospects of it in our subsequent sections.…”

“…38,39 Adjustment of pH (≈ 8-8.2), generated thiolate anions and promoted faster nucleophilic attack on MAC to form stable hydrogels in short tenure compared to formulations without the catalyst (pH 6.6 ͌ 6-8). [34][35]40 Fig. S1A depicts the in situ gelation kinetics of 4 arm PEG thiol with and without catalyst Triethanolamine (TEOA) (M4A2 and M4A2.1 formulations).…”

“…Addition of 0.05M TEOA to the formulation accelerated the gelation at room temperature to generate crosslinked hydrogel in 2.5-3h subsequently longer gelation time > 8 hours had been observed without the addition of catalyst. At basic pH the electrostatic attraction between the intermolecular collagen fibrils increases along with acceleration of gelation yielding in higher stiffness of the hydrogels 35 therefore TEOA was added as a catalyst to all the formulations to evaluate mechanical properties that has been discussed in next section. Likewise, we have also modified the collagen with acrylates and compared the in situ gelation kinetics of acrylated collagen (AC) versus MAC.…”

Synthesis of Programmable Main-chain Liquid-crystalline Elastomers Using a Two-stage Thiol-acrylate Reaction

“…Ultimately, the polymerization rate can be tuned by the catalyst concentration. 34 One of the advantages this methodology offers is that the resulting intermediate polydomain LCE network is uniform and stable, such that the secondstage reaction can be delayed indefinitely. This can enable the synthesis and programming steps to be performed in separate laboratories.…”

Development of optimized autonomous self-healing systems for epoxy materials based on maleimide chemistry

“…[50] As can be seen in Figure 1, the reaction proceeds rather slowly, reaching 15 % of maleimide conversion in 120 minutes. However, the use of a tertiary amine catalyst (NEt 3 ) dramatically increases the reaction rate [51] and 100% conversion is reached in less than 10 minutes.…”