Preparation of Oligo(ethylene glycol)-Terminated Icosanedisulfides

Abstract

This paper describes the synthesis of hexa(ethylene glycol) and carboxymethylhexa(ethylene glycol)-terminated alkanedisulfides 4 and 7, respectively, in which the alkylene chains are twenty-methylenes-long. The key twenty-carbon synthon, 20-bromoicos-1-ene (1), was prepared by homologation of 8-bromooct-1-ene, which was achieved via Cu(II)-catalyzed coupling of the corresponding Grignard reagent with 1,12-dibromododecane. Compounds 4 and 7 are expected to yield self-assembled monolayers (SAMs) that are more stable and well-ordered than those formed by their traditional undecane homologues.Alkanethiols terminated by oligo(ethylene glycol) (OEG) groups have emerged as important reagents for forming biofunctionalized self-assembled monolayers (SAMs) on metal surfaces. 1 In a SAM, OEGs provide resistance to the nonspecific adsorption of proteins, while the alkylene chains tether the OEGs to the sulfur atoms and confer stability and order to the SAM through favorable interchain van der Waals contacts. The alkylene chains in these compounds are typically eleven-methylenes-long, owing to the commercial availability of the required eleven-carbon synthons, 11-haloundec-1-enes. 2 Despite the important role played by these groups, few studies have addressed the preparation of OEG-terminated thiols having alkylene chains that are longer than eleven methylenes. 3,4 Here, we describe the synthesis of hexa(ethylene glycol)-and (carboxymethyl)hexa(ethylene glycol)-terminated disulfides having alkylene chains that are twenty-methylenes-long ( Figure 1; compounds 4 and 7, respectively.) Figure 1 OEG-terminated icosanedisulfides prepared in this study.We chose to prepare 4 and 7 as symmetrical disulfides rather than as free thiols for two reasons. First, like free thiols, disulfides are known to be efficient and selective reagents for forming SAMs on metals such as gold. 4-6 Second, previous work by others has shown that oxidation of carboxyl-terminated alkanethiols to disulfides provides effective protection for the thiol group prior to transforming the carboxyl function. 5,6 An important result of these features is that carboxyl-terminated alkanedisulfides can be derivatized by amidation either before or after SAM formation. 6Our preparation of OEG-terminated icosanedisulfides (Scheme 1) is a modification of the method of Whitesides and co-workers for the synthesis of OEG-terminated undecanethiols, which employs the aforementioned commercially available 11-haloundec-1-enes. 2 Accordingly, we began by preparing the corresponding twenty-carbon synthon, 20-bromoicos-1-ene (1), by coupling octenyl magnesium bromide with 1,12-dibromododecane in THF using Li 2 CuCl 4 as catalyst. 7 Following multiple rounds of flash chromatography, we obtained 1 in modest yield (42%). Reaction of 1 with aqueous NaOH and ten equivalents of hexa(ethylene glycol) in refluxing THF and using tetrabutylammonium hydrogensulfate (TBAH) as phase-transfer catalyst afforded the monoether 2 in 72% yield. We note that this last reaction is an adaptation of the meth...

A mitochondria-targeted derivative of ascorbate: MitoC

“…However, as initial attempts to isolate long chain TPP thiol compounds from the hydrolysis reaction gave significant disulfide formation, we used an initial basic pH to hydrolyze the TPP thioacetate and then rapidly decreased the pH. The bromoalkene precursors [23] , [24] for the C17 and C21 compounds were prepared by haloalkylation of the Grignard reagent prepared from 11-bromoundecene [25] . Details of the synthetic chemistry are given in the Supplemental Materials.…”

The preparation of three new partially deuterated hexadecanethiols for applications in surface chemistry

“…Johnson 11 demonstrated that in the presence of Li 2 CuCl 4 , alkyl Grignard reagents couple with only one bromide of an alkyl dibromide, with formation of the dicoupled product possible at higher temperatures and longer reaction time. Based on this and other precedents, [12][13][14] the Grignard reagent of commercially available perdeuterated bromooctane (4) was prepared and coupled to dibromooctane as the starting point for 9,9,10,10, 11,11,12,12,13,13,14,14,15,15,16,16,16-(heptadecyldeuterio)hexadecanethiol-d 17 (1, Scheme 1).…”