Title:Efficient Monoalkylation of Anilines with Chalcones using Microwave-Assisted aza-Michael Addition
Volume: 19
Issue: 8
Author(s): Hirokazu Iida*, Mitsuki Okawa, Siriwat Leeanansaksiri and Kie Takahashi
Affiliation:
- Department of Biosciences, Kanto Gakuin University College of Science and Technology, Mutsuura-higashi, Kanazawa-
ku, Yokohama, Kanagawa 236-8501, Japan
Keywords:
aza-Michael addition, microwave irradiation, monoalkylation, β-aminocarbonyl compounds, aniline, chalcone.
Abstract: The aza-Michael addition is an attractive methodology for synthetic organic chemistry because
the resulting β-aminocarbonyl compounds are valuable building blocks for the synthesis of
pharmaceutically useful compounds. However, monoalkylation of aniline and its derivatives is quite
difficult because anilines are poor nucleophiles compared to monoalkylated ones. Since the publication
of pioneering articles in 1986, the development of microwave-assisted organic synthesis has been remarkable.
Therefore, we began by investigating the monoalkylation of aniline and its derivatives under
microwave irradiation. Because of the ready formation of bisalkylated products, the monoalkylation
reaction between anilines and Michael acceptors is quite difficult. To overcome the difficulty, we investigated
the effect of microwave irradiation for the alkylation of anilines with chalcones as Michael
acceptors. Microwave-assisted aza-Michael addition proceeded smoothly to obtain mainly the monoalkylated
Michael adduct. The substitution effects of both chalcone and aniline concerning the yield were
also studied. We supposed that dimer formation by two monoalkylated compounds produces a bulky
environment around the amino group, which prevents monoalkylated compounds from undergoing a
second alkylation. We confirmed a highly efficient and rapid method for preparing monoalkylated anilines
using microwave-assisted aza-Michael addition between anilines and chalcones.
