Towards Functional Fluorous Surfactants. Synthesis and Spectroscopic Features of Systematically Modified Sugar-Substituted Fluorous 1,2,3-Triazoles

Highlights

• Synthesis of 30 new fluorous glycosidyl triazoles comprising 10 sets of compounds each with systematically varied substituents.

• Determination of spectroscopic features that can be related to changes in molecular structure, including rarely assigned sugar (galactosyl) and polyfluoroalkyl resonances.

• Significant new understanding of the role of varying polyfluoroalkyl substitution and arrangement and types of triazole substituents in influencing spectroscopic properties.

• Establishment of a valuable resource with information for fluorous chemists and sugar chemists based on new polyfluoroalkyl-substituted 1-b-D-glucosyl and 6-D-galactosyl 1,2,3-triazoles.

• Provision of model compounds for study as fluorous surfactants.

ABSTRACT

A library of 10 series of homologous compounds making up a total of 30 new, fluorous 1-substituted 1,2,3-triazol-4-ylmethyl(and ethyl) ether surfactant candidates, with highly systematic variations in substituent position and type, have been synthesised in consistently good yields by processes involving copper(I)-accelerated Huisgen-Meldal dipolar cycloaddition reactions. Each series contains a perfluorobutylethyl, perfluorohexylethyl or perfluorooctylethyl substituents at triazole position N(1) or attached through the triazole ether oxygen, and either a 1-β-D-glucosyl or 6-α-D-galactosyl substituent at the alternative triazole position. Half the library was prepared directly with the sugar components in a protected form (peracetylated glucose derivatives and 1,2:3,4-bisacetonide galactose derivatives) while the other series with unprotected sugars were obtained following a secondary deprotection step by trans-esterification using sodium methoxide or acid catalysed acetal solvation.

All the triazoles are candidates for study as fluorous surfactants that are switchable between amphiphilic partner states, hydrophobic in the case of protected sugars and hydrophilic in unprotected sugars. As a prelude to surfactant studies, the NMR spectroscopic characteristics of the newly establish library of compounds were examined. Data were compared and contrasted within and between each series with reference to related literature analogues. Analysis of unprotected 6-galactosyl derivatives was complicated by the well known generation of inseparable, epimeric mixtures of hemiacetal pyranose and furanose products and the general paucity in the literature of NMR spectroscopic data assignments of signals from 1-β-hydroxygalactopyranose compounds. These matters have been addressed in this paper and the comparisons include analyses of unprotected 1'-α- and 1'-β-hydroxy-pyranose derivatives.

Introduction

There has been widespread interest in polymeric and other, hybrid fluorous compounds because of the unique surface activity and physical and biological properties of materials derived from them [[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]]. Implicit in many reports has also been the potential of the compounds for the carriage of added functionality [11]. Fluorous modifications of small molecules derived from heterocycles have received less systematic attention as surfactants [[11], [12], [13], [14], [15], [16], [17], [18], [19]], although many innovative applications of fluorous tagged molecules have appeared [20], especially in terms of separation strategies [21] and recyclable catalysts [[22], [23], [24]]. We have outlined the potential of small fluorous heterocycles as surfactants and participants in self-assembly [25], and have described the synthesis of 1,2,3-triazoles [25,26] and tetrazoles [26] with one perfluoroalkyl substituent and one n-alkyl substituent, as examples of such compounds. A study of the influence of members of this library of heterocycles at various concentrations on the surface tension of m-xylene [27], revealed considerable surface activity, but indicated some anomalies in the expected behaviour [25,26]. Similar anomalies of unpredictable behaviour had been reported by others for solutions of polyfluorocarbon-hydrocarbon hybrid molecules in vaseline oil [28]. In this case, it was suggested that the discrepancies were possibly attributable to issues of viscosity. We chose to examine the possibility that the unpredictable surface tension behaviour was due to the combination of two hydrophobic components, one fluorophilic and the other lipophilic, of the two quite different sets of heterocyclic and non-heterocyclic compounds. Our interest therefore turned to analogues of the fluorous heterocyclic molecules in which the partner group was more hydrophilic [29].

This paper describes the synthesis of fluorous 1,2,3-triazole analogues in which a polyfluoroalkyl group is retained and is paired with a sugar substituent. We also present our qualitative analyses of their NMR spectroscopic properties and report on effects such as: (a) the relative positions of the polyfluoroalkyl and sugar substituents on the triazole, (b) the length and nature of any spacer/tethering group, (c) the type of sugar and the point of attachment of the triazole on the sugar, and (d) the influence of sugar protecting groups on the physical properties of the molecules. This is the first such study of its kind and the second of only two sugar-based libraries of fluorous triazoles [30] to be reported with such systematic variations although isolated, fluorinated and polyfluoroalkylated carbohydrates have been described over the past two decades (for informative reviews, see [[31], [32], [33]]; for other relevant articles, see [[34], [35], [36], [37], [38], [39], [40], [41]]). In addition to generally useful applications such as formation of ordered membranes and liquid crystalline phases (see [1,31,32]), a contemporary application of carbohydrate-based amphiphiles with perfluoroalkyl chains has been their use as tools to handle membrane proteins in aqueous media [41]. It should be stressed that the strength of our findings lies in the range of compounds from which they are derived rather than detailed quantitative measures of individual examples, and the extent to which spectra have been unambiguously assigned and can therefore be compared.