Experimental and Computational Studies of Microwave-Assisted, Facile Ring Opening of Epoxide with Less Reactive Aromatic Amines in Nitromethane

Sumit Kumar; Charu Upadhyay; Meenakshi Bansal; Maria Grishina; Bhupender S Chhikara; Vladimir Potemkin; Brijesh Rathi; Poonam

doi:10.1021/acsomega.0c01760

Experimental and Computational Studies of Microwave-Assisted, Facile Ring Opening of Epoxide with Less Reactive Aromatic Amines in Nitromethane

ACS Omega. 2020 Jul 21;5(30):18746-18757. doi: 10.1021/acsomega.0c01760. eCollection 2020 Aug 4.

Authors

Sumit Kumar¹, Charu Upadhyay¹, Meenakshi Bansal², Maria Grishina³, Bhupender S Chhikara⁴, Vladimir Potemkin³, Brijesh Rathi^{2

3}, Poonam^{1

3}

Affiliations

¹ Department of Chemistry, Miranda House, University of Delhi, Delhi 110007, India.
² Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College University Enclave, University of Delhi, Delhi 110007, India.
³ Laboratory of Computational Modelling of Drugs, South Ural State University, Chelyabinsk 454080, Russia.
⁴ Department of Chemistry, Aditi Mahavidyalaya, University of Delhi, Bawana, Delhi 110039, India.

Abstract

Nucleophilic ring opening reactions of epoxides with aromatic amines are in the forefront of the synthetic organic chemistry research to build new bioactive scaffolds. Here, convenient, green, and highly efficient regioselective ring opening reactions of sterically hindered (2R,3S)-3-(N-Boc-amino)-1-oxirane-4-phenylbutane with various poorly reactive aromatic amines are accomplished under microwave irradiation in nitromethane. All the reactions effectively implemented for various aromatic amines involve the reuse of nitromethane that supports its dual role as a solvent and catalyst. The corresponding new β-alcohol analogs of hydroxyethylamine (HEA) are isolated in 41-98% yields. The reactions proceed under mild conditions for a broad range of less reactive and sterically hindered aromatic amines. Proton NMR experiments suggest that the nucleophilicity of amines is influenced by nitromethane, which is substantiated by the extensive computational studies. Overall, this methodology elucidates the first-time use of nitromethane as a solvent for the ring opening reactions under microwave conditions involving an equimolar ratio of epoxide and aromatic amine without any catalyst, facile ring opening of complex epoxide by less reactive aromatic amines, low reaction time, less energy consumption, recycling of the solvent, and simple workup procedures.