Nitration vs. nitrosation chemistry of menthofuran: remarkable fragmentation and dimerization pathways and expeditious entry into dehydromenthofurolactone

The reaction chem. of menthofuran (I), a toxic furan terpenoid from various mint oils, with nitric acid and nitrous acid has been investigated. Treatment of 1 with nitric acid afforded a 1:1 mixt. of the bisfuran derivs. II and III, resulting from the unexpected cleavage of the furan into two carbonyl fragments (3-methylcyclohexanone and hydroxyacetone) and their subsequent trapping by unreacted I. Under conditions of high diln., the nitrofuran deriv. IV was formed instead as the major reaction product. During investigation of this chem., it was found that oxidn. of I with DDQ led to the important fragrant monoterpenoid V [dehydromenthofurolactone (anhydro Woodward-Eastman lactone)] in 44% yield. Exposure of I to nitrite ions at pH 3 afforded a completely different type of products, encompassing the known lactone VI, the lactam VII, and the remarkable dimer VIII, bearing a N-hydroxy-2-pyrrolinone moiety linked to a nitrooximinofuran unit by an oxygen bridge. By using a combined spectroscopic and DFT approach, the constitution and configuration of VIII could be detd. These results fill a gap in the chem. of furan compds. and describe routes to menthofuran-derived scaffolds of potential synthetic and biomedical relevance.