TY - JOUR
T1 - Nitration versus nitrosation chemistry of menthofuran
T2 - Remarkable fragmentation and dimerization pathways and expeditious entry into dehydromenthofurolactone
AU - De Lucia, Maria
AU - Mainieri, Francesco
AU - Verotta, Luisella
AU - Maffei, Massimo
AU - Panzella, Lucia
AU - Crescenzi, Orlando
AU - Napolitano, Alessandra
AU - Barone, Vincenzo
AU - Appendino, Giovanni
AU - D'Ischia, Marco
PY - 2007/12/21
Y1 - 2007/12/21
N2 - (Chemical Equation Presented) The reaction chemistry of menthofuran (1), 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 mixture of the bisfuran derivatives 5 and 6, resulting from the unexpected cleavage of the furan into two carbonyl fragments (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 reaction product. During investigation of this chemistry, it was found that oxidation of 1 with DDQ led to the important 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 combined spectroscopic and DFT approach, the constitution and configuration of 16 could be determined. These results fill a gap in the chemistry of furan compounds and describe routes to menthofuran-derived scaffolds of potential synthetic and biomedical relevance.
AB - (Chemical Equation Presented) The reaction chemistry of menthofuran (1), 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 mixture of the bisfuran derivatives 5 and 6, resulting from the unexpected cleavage of the furan into two carbonyl fragments (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 reaction product. During investigation of this chemistry, it was found that oxidation of 1 with DDQ led to the important 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 combined spectroscopic and DFT approach, the constitution and configuration of 16 could be determined. These results fill a gap in the chemistry of furan compounds and describe routes to menthofuran-derived scaffolds of potential synthetic and biomedical relevance.
UR - http://www.scopus.com/inward/record.url?scp=84961983727&partnerID=8YFLogxK
U2 - 10.1021/jo701992r
DO - 10.1021/jo701992r
M3 - Article
SN - 0022-3263
VL - 72
SP - 10123
EP - 10129
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 26
ER -