Nitration versus nitrosation chemistry of menthofuran: remarkable fragmentation and dimerization pathways and expeditious entry into dehydromenthofurolactone.
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.
Dipartimento di Chimica Organica e Biochimica, Università di Napoli Federico II, Via Cinthia 4, I-80126 Napoli, Italy.
Maria
M
De Lucia
Francesco
F
Mainieri
Luisella
L
Verotta
Massimo
M
Maffei
Lucia
L
Panzella
Orlando
O
Crescenzi
Alessandra
A
Napolitano
Vincenzo
V
Barone
Giovanni
G
Appendino
Marco
M
d'Ischia
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D019281:Dimerization; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008956:Models, Chemical; D015394:Molecular Structure; D039821:Monoterpenes / Q000138:chemical synthesis* / Q000737:chemistry*; D017942:Nitric Acid / Q000737:chemistry*; D015538:Nitrosation; D009608:Nitrous Acid / Q000737:chemistry*; D012015:Reference Standards; D013237:Stereoisomerism
D039821:Monoterpenes; C527462:dehydromenthofurolactone; D017942:Nitric Acid; C054487:menthofuran; D015107:4-Butyrolactone; D009608:Nitrous Acid