The reaction chemistry of menthofuran (
1), a toxic furan terpenoid from various mint oils, with nitricacid and nitrous acid has been investigated. Treatment of
1 with nitric acid afforded a 1:1 mixture of thebisfuran derivatives
5 and
6, resulting from the unexpected cleavage of the furan into two carbonylfragments (3-methylcyclohexanone and hydroxyacetone) and their subsequent trapping by unreacted
1.Under conditions of high dilution, the nitrofuran derivative
7 was formed instead as the major reactionproduct. During investigation of this chemistry, it was found that oxidation of
1 with DDQ led to theimportant fragrant monoterpenoid
4 [dehydromenthofurolactone (anhydro Woodward-Eastman lactone)]in 44% yield. Exposure of
1 to nitrite ions at pH 3 afforded a completely different type of products,encompassing the known lactone
14, the lactam
15, and the remarkable dimer
16, bearing a
N-hydroxy-2-pyrrolinone moiety linked to a nitrooximinofuran unit by an oxygen bridge. By using a combinedspectroscopic and DFT approach, the constitution and configuration of
16 could be determined. Theseresults fill a gap in the chemistry of furan compounds and describe routes to menthofuran-derived scaffoldsof potential synthetic and biomedical relevance.
