Microwave-assisted synthesis of mono- and disubstituted 4-hydroxyacetophenone derivatives via Mannich reaction: synthesis, XRD and HS-analysis

• Main Authors: Aljohani, Ghadah, Said, Musa A., Lentz, Dieter, Basar, Norazah, Albar, Arwa, Alraqa, Shaya Y., Al-Sheikh Ali, Adeeb
• Format: Article
• Language: English
• Published: MDPI AG 2019
• Subjects: QD Chemistry
• Online Access: http://eprints.utm.my/id/eprint/89372/1/GhadahAljohani2019_MicrowaveAssistedSynthesisofMonoandDisubstituted.pdf; http://eprints.utm.my/id/eprint/89372/; http://dx.doi.org/10.3390/molecules24030590
• Institution: Universiti Teknologi Malaysia

An efficient microwave-assisted one-step synthetic route toward Mannich bases is developed from 4-hydroxyacetophenone and different secondary amines in quantitative yields, via a regioselective substitution reaction. The reaction takes a short time and is non-catalyzed and reproducible on a gram scale. The environmentally benign methodology provides a novel alternative, to the conventional methodologies, for the synthesis of mono- and disubstituted Mannich bases of 4-hydroxyacetophenone. All compounds were well-characterized by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The structures of 1-{4-hydroxy-3-[(morpholin-4-yl)methyl]phenyl}ethan-1-one (2a) and 1-{4-hydroxy-3-[(pyrrolidin-1-yl)methyl]phenyl}ethan-1-one (3a) were determined by single crystal X-ray crystallography. Compound 2a and 3a crystallize in monoclinic, P21/n, and orthorhombic, Pbca, respectively. The most characteristic features of the molecular structure of 2a is that the morpholine fragment adopts a chair conformation with strong intramolecular hydrogen bonding. Compound 3a exhibits intermolecular hydrogen bonding, too. Furthermore, the computed Hirshfeld surface analysis confirms H-bonds and π–π stack interactions obtained by XRD packing analyses.