Thermal decomposition of 1,1-bis(methylthio)ethene, pyran-2-one Diels-Alder adducts: an unusual [1,5]-sulfenyl rearrangement

Andrew J Pratt,Phillip M Rendle,Christopher A Ramsden

doi:10.3998/ark.5550190.0007.317

Andrew J Pratt, Phillip M Rendle + Show 1 more

Open Access

https://doi.org/10.3998/ark.5550190.0007.317

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Abstract

The thermal decomposition of two Diels-Alder adducts derived from pyran-2-ones and bis(methylthio)ethene has been studied. A product obtained from the thermal decomposition of one of these Diels-Alder adducts (1), derives from a [1,5]-sulfenyl shift, the first welldocumented report of such a process occurring under non-polar conditions. The rearrangement in this case probably occurs via a radical pathway. No such rearrangement was observed on decarboxylation of a Diels-Alder adduct (7) derived from a benzopyranone. This latter thermolysis required more vigorous conditions as required for the application of this class of compounds as potential anti-cancer prodrugs.

Highlights

The bridged Diels-Alder adduct 1 can be prepared by reaction of methyl coumalate 2 with 1,1bis(methylthio)ethene 3, in refluxing toluene.4 This adduct was heated neat at 145 °C and the decomposition chemistry monitored by proton NMR
Functionalised polycyclic aromatic compounds have anti-tumour activity by virtue of their ability to intercalate between adjacent heterocyclic bases of DNA
Since thiol groups can be selectively released from appropriately substituted precursors at tumours2 we targeted pyran-2one-derived Diels-Alder adducts with thioether substituents as potential anti-tumour prodrugs where cleavage of a thioether linkage can lead to aromatisation of ring system (Figure 1)

Summary

Introduction

The bridged Diels-Alder adduct 1 can be prepared by reaction of methyl coumalate 2 with 1,1bis(methylthio)ethene 3, in refluxing toluene.4 This adduct was heated neat at 145 °C and the decomposition chemistry monitored by proton NMR. One product was methyl coumalate 2; resulting from a reversal of the cycloaddition reaction used to prepare the adduct; it is surprising that this retro-Diels-Alder reaction can successfully compete with decarboxylation. The conjugated diene 5 was formed if the Diels-Alder reaction of 2 with 3 was carried out over an extended period.

Results

Conclusion