Synthesis and Crystal Structure of Two Nitro-Regioisomers of cis-4-(4-Methoxyphenyl)-3-Methyl-2-Phenyl-1,2,3,4-Tetrahydroquinoline

Teresa González,Vladimir V. Kouznetsov,Arnold Rafael Romero Bohórquez

doi:10.11144/javeriana.sc18-1.scsn

Abstract

Objectives. To synthesize two nitro-regioisomers of the cis-4-(4-methoxyphenyl)-3-methyl-2-phenyl-1,2,3,4-tetrahydroquinoline and carry out its complete structural characterization using single crystal X-ray diffraction technique and other spectroscopic methods. Materials and methods. The purity of the products and the composition of the reaction mixtures were monitored by thin layer chromatography over Silufol UV254 chromatoplates (0.25 mm). Products were isolated and purified by column chromatography (SiO2) using petroleum ether/ethyl acetate. Substances were identified using nuclear magnetic resonance (NMR) and mass spectrometry (MS). X-ray diffraction data for crystal characterization, were collected using a Bruker AFC7S Mercury diffractometer with Mo-Kα radiation (λ = 0.71073 Å) at room temperature. Results. Two nitro-regioisomers of the cis-4-(4-methoxyphenyl)-3-methyl-2-phenyl-1,2,3,4-tetrahydroquinoline have been synthesized via the “one pot” thee-component imino Diels-Alder reaction catalyzed by BF3.OEt2. The structures of these regioisomers was confirmed by 1H NMR and 13C NMR studies and the crystal structure was studies using single crystal X-ray diffraction technique. Conclusions. An easy and efficient synthetic route was employed for the preparation of two nitro-regioisomers of the tetrahydroquinoline derivatives. The spectroscopy analyses (NMR, GC-MS and X-ray diffraction) showed a complete characterization and permit to establish the correct stereochemistry for the tetrahydroquinoline ring. The molecular packing for the 5-nitro regioisomer 4 was resulted by combinations of intermolecular hydrogen bond and van der Waals interactions, while 7-nitro regioisomer 3 possesses only intermolecular van der Waals interactions and N—H··· π interactions also occur.

Highlights

A great number of natural and synthetic tetrahydroquinoline compounds are core structures in many important pharmaceutical agents (Katrizky et al 1996, Kouznetsov et al 1998)
Regioisomeric nitro-tetrahydroquinolines 3 and 4 were prepared via the protocol of a “one pot” three-component imino Diels-Alder reaction between in situ forming N-aryl aldimines and trans-anethole in the presence of BF3.OEt2, at 70oC in acetonitrile. These compounds were synthesized by cycloaddition reaction starting from the commercially available 3-nitroanilines 1, benzaldehyde 2, and trans-anethole, according to the literature procedure (Kouznetsov et al 2007, Kouznetsov et al 2008). e required products 3 and 4 were obtained in good yields after column chromatography puri cation on silica gel (Figure 1)
E crystal packing for the 5-nitro regioisomer 4 was the result of combinations of intermolecular hydrogen bonds of the N—H···O type and van der Waals interactions, which may lead to the supramolecular structure of the molecule

Summary

Introduction

A great number of natural and synthetic tetrahydroquinoline compounds are core structures in many important pharmaceutical agents (Katrizky et al 1996, Kouznetsov et al 1998). Cycloaddition reactions have proved to be the most powerful and successful reactions to construct these ring systems rapidly; while the acid-catalyzed imino Diels-Alder reaction (Povarov reaction) between 2-azadienes and electron-rich alkenes in its three-component version is one of the most powerful synthetic tools for the construction of nitrogen-containing six-membered heterocyclic compounds, including tetrahydroquinolines (Kouznetsov 2009, Glushkov et al 2008, Buonora et al 2001). This reaction enables the condensation of anilines, aldehydes, and electron-rich alkenes using acidic catalysts under mild conditions to obtain new substituted tetrahydroquinolines. We have determined the crystal structure of these compounds using X-ray techniques, confirming their spectral characterization and obtaining detailed information about their molecular conformation

Methods

Results

Discussion

Conclusion