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Download fileExperimental and Theoretical Analyses of Azulene Synthesis from Tropones and Active Methylene Compounds: Reaction of 2-Methoxytropone and Malononitrile
journal contribution
posted on 2012-06-15, 00:00 authored by Takahisa Machiguchi, Toshio Hasegawa, Shinichi Yamabe, Tsutomu Minato, Shoko Yamazaki, Tetsuo NozoeA representative azulene formation from an active troponoid
precursor
(2-methoxytropone) and an active methylene compound (malononitrile)
has been analyzed both experimentally and theoretically. 2H-Tracer experiments using 2-methoxy[3,5,7-2H3]tropone (2-d3) and malononitrile
anion give 2-amino-1,3-dicyano[4,6,8-2H3]azulene
(1-d3) in quantitative yield.
New and stable 2H-incorporated reaction intermediates have
been isolated, and main intermediates have been detected by careful
low-temperature NMR measurements. The detection has been guided by
mechanistic considerations and B3LYP/6-31(+)G(d) calculations. The
facile and quantitative one-pot formation of azulene 1 has been found to consist of a number of consecutive elementary
processes: (a) The troponoid substrate, 2-methoxytropone (2), is subject to a nucleophilic substitution by the attack of malononitrile
anion (HC(CN)2–) to form a Meisenheimer-type
complex 3, which is rapidly converted to 2-troponylmalononitrile
anion (5). (b) The anion 5 is converted
to an isolable intermediate, 2-imino-2H-cyclohepta[b]furan-3-carbonitrile (6), by the first ring
closure in the reaction. (c) A nucleophilic addition of the second
HC(CN)2– toward the imine 6 at the C-8a position produces the second Meisenheimer-type adduct 7. (d) The second ring closure leads to 1-carbamoyl-1,3-dicyano-2-imino-2,3-dihydroazulene
(11). A base attacks the imine 11, which
results in generation of a conjugate base 12 of the final
product, azulene 1.