The attachment and cleavage of phenols from solid supports and their single bead mass spectral analysis
Section snippets
Phenol attachment to resin
The attachment of phenols to chloromethyl resin (resin used was 1.6 meq. 250–300 μm chloromethyl polystyrene) using the conditions reported by Merrifield,4 proceeds very well using three equivalents of phenol in dimethylacetamide (DMA) at 50°C with sodium methoxide as base, as judged by chlorine analysis of the resin (there is negligible competition from methoxide). Typical phenols used are the alkyl phenols shown in Scheme 1. The use of a high boiling point solvent like DMA allows the reaction
Cleavage of phenols from resin
The effectiveness of the TFA cleavage conditions usually used for the cleavage of the Wang linker was initially investigated using a solution phase model compound (1, Scheme 2) constructed by simple benzylation of 4-amylphenol. When this compound was stirred in TFA, starting material was consumed within an hour at room temperature, and as judged by TLC the phenol was apparently released. Upon closer inspection, the product of the reaction was in fact the rearranged product 2 (which gave the
Phenol identification
High resolution mass spectrometry was used to identify the cleaved phenols unambiguously. Phenols, and in particular alkyl phenols, do not fly well under electrospray ionisation conditions. Consequently they were derivatised to their dansylates, which fly very well owing to the ease of protonation of the nitrogen atom. A rapid biphasic procedure was developed for the derivatisation (to form 4, Scheme 3), which is simpler than has previously been reported.11 This method is sensitive enough to be
Acknowledgements
We thank Zeneca Pharmaceuticals for a studentship (to M.H.T.). C.A. also acknowledges funds from Iberdrola, Spain (Visiting Professorship).
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