Utilization of Water-Soluble Aminoethylamino–β–Cyclodextrin in the Pfitzinger Reaction—Catalyzed to the Synthesis of Diversely Functionalized Quinaldine

Abstract

In this study we describe the use of an aminoethylamino-β-cyclodextrin (AEA-β-CD) as a supramolecular homogeneous catalyst for the synthesis of a series of diversely substituted quinaldine derivatives which are medicinally important, via Pfitzinger reaction. This supramolecular catalyst exhibited remarkable catalytic activity with high substrate scope to achieve the synthetic targets in good to excellent yield, 69-92%. The structural and morphological properties of the synthesized AEA-β-CD were determined through MALDI-TOF mass spectrometry, NMR, FT-IR, and SEM analysis. Possible reaction mechanisms were determined through molecular host-guest complexation and proposed based on 2D NMR (ROESY) spectroscopy, FT-IR, FE-SEM, and DSC.Polymers 2020, 12, 393 2 of 12 Supramolecular chemistry denotes the chemistry beyond the molecule involving noncovalent intermolecular forces and has a profound influence on the catalysis of a variety of organic reactions to attain higher selectivity mimicking biological phenomena. A major application of supramolecular chemistry is the design and understanding of catalysts and catalysis. Noncovalent interactions are extremely important in catalysis, binding reactants into conformations suitable for reaction and lowering the transition state energy of reaction. Among the various known supramolecular catalysts, β-cyclodextrin (β-CD) is most preferable due to its unique properties, and for economic reasons when compared with αand γ-cyclodextrins. Due to the hydrophobic cavity of β-CD, it allows "host-guest" inclusion complex formation with a wide variety of guest molecules through hydrophobic interaction, and the hydrophilic surface of β-CD makes the complex water-soluble. Modified β-CD provides novel derivatives with unique structures and functions to support the development of different research fields [12]. Additionally, amino-functionalized β-CD has been used as a catalyst in organic synthesis due to its powerful catalytic activity such as in multicomponent reaction (MCR) condensation, oxidation, and asymmetric synthesis [13][14][15].As part of our continuing interest in modified β-CD catalyzed organic synthesis [16,17], herein we report an efficient and eco-friendly procedure for the synthesis of quinaldine derivatives from isatin, 1,3-dicarbonyl, and alcohol in water via Pfitzinger reaction catalyzed by AEA-β-CD, a reusable homogeneous catalyst, at 60 • C (Scheme 1). To the best of our knowledge, the synthesis of diversely functionalized quinaldine, catalyzed by AEA-β-CD, has not been reported yet.

Single Step Upgradation of Isatin to Bioactive Fused Heterocycles via Ring Expansion Reactions

“…The substrate scope of the reaction was further investigated by a one‐pot reaction of isatin, acetylacetone, and propyl alcohol in the presence of TMSCl (Scheme 6). Similarly, Kim and his group [38] also concentrated on a Pfitzinger reaction of isatin 1, 1,3‐dicarbonyl compound 32 , and alcohol 33 via a homogeneous supramolecular catalyst, aminoethyl amino‐β‐cyclodextrin (AEA‐β‐CD). The catalyst was first synthesised from 1‐tosyl‐1 H ‐imidazole and ethane‐1,2‐diamine in the presence of a base and water through a two‐step process and characterised by spectroscopic techniques.…”