Thiol-epoxy reaction

Keywords Amphipathic polymers Bifunctionalized homopolymers Dual-func-timial polymers Poly(glycidyl methacrylate) Post-polymerization modification Sequential reactions siRNA delivery Thiol-epoxy reaction... 

Scheme 2 Thiol-epoxy reaction under basic conditions. The reaction is most likely to proceed by an mechanism. Therefore, the step-wise depiction is meant only to simplify the process for better understanding...

Scheme 3 Two possible regio-isomers expected from a thiol-epoxy reaction...

The thiol-epoxy reaction has proved to be an important synthetic tool in the preparation of a variety of pharmaceutical and natural products [55-64]. As mentioned above, this reaction can be performed using an acid or a base as a catalyst. The acid catalysts include boron trifluoride etherate [57], lanthanide chlorides [65], lithium perchlorate [60], cobalt chloride [66], and neutral alumina [67]. The basic catalysts can be organic or inorganic and include, among others, triethylamine, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), tetra-n-butylammonium fluoride (TBAF), and LiOH [61-64, 68, 69]. In the literature on small molecules, it is important to note that this reaction is complete in a few minutes to a few hours of reaction time, with quantitative yields and with high regioselectivity. In the case of LiOH and TBAF, quantitative conversion of the epoxide to a desired thio-ether compound is observed within minutes and with 100% regioselectivity (isomer I) [68, 69]. 

An important feature of this study [26] was determination of the regiochemistry of the polymer repeat unit after the thiol-epoxy reaction. This was accomplished through a careful model compound study, which suggested that the attack of the thiolate anion occurs at the least hindered carbon atom of the pendant glycidyl unit of the polymer chain and that regio-isomer I (Scheme 3) forms exclusively during thiol-epoxy functionalization. 

Other curatives, which react through addition mechanisms are phenolic resins, particularly if the hydroxyl/epoxy reaction is catalysed using a tertiary amine (usually accomplished at elevated temperatures), thiols, polysulphides and mercaptans (can be formulated to give very rapid cures), polyetheramines (relatively slow cures, which can be accelerated with nonyl phenol), polyamides (less reactive than their amine counterparts) and amidoamines (characterized as having very long pot lives). 

A fuUy biobased epoxy resin from vegetable oils From the synthesis of the precursors by thiol-ene reaction to the study of the final material. Journal of Polymer Science Part A Polymer Chemistry, 49(11) 2434—2444. 

Thiol groups can react with many chemical species with high yields under benign conditions and thus many thiol-related reactions, such as thiol-ene, thiol-yne, thiol-epoxy, thiol-isocyanate and thiol-halogen reactions, are considered to be chck-type reactions [63]. 

Sequential Thiol-Epoxy and Esterification Reactions A Facile Route to Bifunctional Homopolymer Sequences... 

Scheme 6 Use of sterically demanding substituents to prepare water-soluble and functionalized bottlebrush copolymers through sequential thiol-epoxy and esterification reactions...

Stuparu MC, Khan A (2014) Sequential thiol-epoxy and esterification reactions a facile route to bifunctional homopolymer sequences. Adv Polym Sci. doi 10.1007/12 2014 299... 

Scheme 1.13 Base catalyzed thiol-epoxy ring-opening click reaction.

In a typical procedure, the thiol-epoxy click reaction near quantitative yields can be employed as a polymerization reaction for preparing linear polymer chains substituted with free hydroxyl groups. Khan et al. [16] reported that the linear polymer can be easily constructed by step-growth polymerization of the commercially available diepoxide (AA-type) and bis-sulfur (BB-type) monomers using lithium hydroxide (base catalysts) as the polymerization catalyst. (Figure 8.3)... 

Here, it should be pointed out that the thiol-epoxy click reaction is a feasibility implemented in many important biosynthetic and biomedical applications because the base-catalyzed reactions can be easily carried out in water and in solvent-free conditions with high yield. 

Figure 7.18 Amine-containing dendrimers can be activated with epibromohydrin to result in the formation of reactive epoxy groups on the dendrimer surface. This reactive intermediate then can be used to conjugate with thiol-containing proteins, such as thiolated alkaline phosphatase. The reaction results in the formation of a thioether bond.

The epoxy-activated dendrimer may be conjugated to thiol-containing proteins by reaction in 50 mM sodium phosphate, pH 7.2. The reaction can be done at 4°C or at room temperature for 8-16 hours to form thioether linkages. 

The reaction of the epoxide with a thiol group yields a thioether linkage, whereas reaction with a hydroxyl gives an ether and reaction with an amine results in a secondary amine bond. The relative reactivity of an epoxy group is thiol > amine > hydroxyl, and this is reflected by... 

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