Preparation of new N-( 6-methyl-2-nitrophenyl-1 , 2 , 3 , 4-tetrahydroquinolin-4-yl ) pyrrolidin-2-ones Simple preparation of new N-( 6-methyl-2-nitrophenyl-1 , 2 , 3 , 4-tetrahydroquinolin-4-yl ) pyrrolidin-2-ones and their spectroscopic analysis

Objectives. To prepare new N-(1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-one molecules and to characterize them by spectroscopic methods. Materials and methods. All reagents were purchased from Aldrich, commercial grade. 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). Product isolation and purification were performed by column chromatography (SiO2) using ethyl acetate. Results. Preparation of new N-(2nitrophenyl-1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-ones has been achieved via the one-pot synthesis, based on a BiCl3-catalyzed imino Diels-Alder cycloaddition reaction of toluidine, N-vinylpyrrolidin-2-one and 4-nitroor 3-nitrobenzaldehydes. The structure of the pyrrolidine derivatives was confirmed by H NMr and 13C NMr studies, in addition to inverse-detected 2D NMr experiments and monocrystal X-ray diffraction. Conclusions. An efficient, economic, and fast synthetic route (multi-component imino Diels-Alder reaction) was employed in the construction of several new tetrahydroquinoline derivatives, useful and attractive rigid skeleton with well-defined stereochemistry.


Introduction
Quinoline and tetrahydroquinoline structures are an essential feature of many natural products. These heterocycles play a key role in heterocyclic and medicinal chemistry. Their synthesis by various methodologies has been published extensively (1)(2)(3)(4). Polyfunctionalized tetrahydroquinolines (THQs) are molecules of great interest in organic synthesis since many natural products present this system in their structure, and because they exhibit diverse biological activities (5)(6)(7)(8)(9). Besides their notorious bioactivity, THQs are also important and reliable precursors in quinoline preparation, another group of heterocyclic molecules that has a great number of pharmacological properties (10). An efficient route in the preparation of THQs is the acid-catalyzed Povarov reaction that is classified as imino Diels-Alder cycloaddition (11)(12)(13) and permits the condensation of anilines, aldehydes, and electron-rich alkenes using acidic catalysts under mild conditions to achieve the obtainment of new substituted tetrahydroquinolines.
As a part of our research program in the DOS methodology towards the synthesis of bioactive substituted tetrahydroquinolines and quinolines, we are currently conducting research on the synthesis of small drug-like (tetrahydro)quinoline molecules containing a C-2 aryl fragment, whose synthesis could be accomplished via cycloaddition reactions. We want to report here the simple preparation of new N-(2-nitrophenyl-1,2,3,4tetrahydroquinolin-4-yl) pyrrolidin-2-ones using BiCl 3catalyzed three-component Povarov reaction among nitrobenzaldehydes, toluidine and N-vinylpyrrolidin-2-one, and their transformations into potentially bioactive 2-aryltetrahydroquinoline derivatives, N-amidyl substituted at the C-4 position.

Materials and methods
All reagents were purchased from Aldrich, commercial grade. The purity of the products and the composition of the reaction mixtures were monitored by thin layer chromatography over Silufol UV 254 0.25 mm-thick chromatoplates. The melting points (uncorrected) were determined on a Fisher-Johns melting point apparatus. The Ir spectra were recorded on an Infralum FT-02 spectrophotometer in KBr. 1 HNMr spectra were recorded on BrukerAM-400 or AC-300 spectrometers in CDCl 3 . Chemical shifts are reported in ppm. (A signal at 7.24 ppm of CHCl 3 in CDC l3 was used as reference for protons). A Hewlett Packard 5890a series II Gas Chromatograph interfaced to an HP 5972 Mass Selective Detector (MSD) with an HPMS Chemstation Data System was used for MS identification at 70 eV using a 60 m capillary column coated with HP-5 [5%-phenyl-poly(dimethyl-siloxane)]. X ray diffraction single-crystal technique with an AFC7S four circle diffractometer was used. The data acquisition was made to 293 K of temperature with MoKa (l = 0.71073 Å) radiation and a measurement range between 1 and 25º to theta (q). The structure elucidation and the refinement were made with the software Shelxs-97 and Shelxl-97, respectively. Elemental analyses were performed on a Perkin Elmer 2400 Series II analyzer and were within ± 0.4 of the theoretical values. The reaction progress was monitored using thin layer chromatography on a silufol UV 254 TLC aluminum sheet.
The structures of the C-2 substituted tetrahydroquinolines 5 and 6 were confirmed on the basis of analytical and spectral data and were supported by inverse-detected 2D NMr experiments. Ir spectrum characteristic absorption bands of the compound 5 were observed at 3394 and 1666 cm -1 , assignable to the amine and amide groups, respectively, and the nitro group signals at 1512 and 1342 cm -1 . Their mass spectrum showed a molecular ion m/z: 351 that coincided with the molecular weight (351 g/mol).  (Figure 3).
The nitro-isomer 6 has similar chemical behavior in the spectra data. The chemical structures of the obtained N-(tetrahydroquinolinyl) pyrrolodin-2-one molecules were strongly confirmed through Ir, 1 H and 13 C NMr analyses; however, having a possible mechanism of achieved multicomponent condensation, we could anticipate the various diastereomers, cis or trans configuration. For these reasons, further structural studies were carried out.

X-Ray Diffraction Single Crystal Study
Samples of both compounds 5 and 6 were grown by slow evaporation in ethanol; however, we could obtain suitable crystals only for the compound 5. The diffraction data of the compound 5 were collected at 273K using a CCD area detector with graphite-monochromatic Mo Kα radiation (l = 0.71073 Å). The data were computed using Bruker-AXS software. For the solution and refinement of the structure, Shelxs-97 (17) and Shelxl-97 (18) were used respectively. Molecular and crystal structures were obtained using Mercury software (19). The molecular structure for the compound is presented in the figure 4. A cis conformation of the C-2 and C-4 substitutes is evident, as well as a chair configuration adopted by the tetrahydroquinoline system.    The packing structure is shown in figure 5 and the powder profile simulated by the single crystal data is shown in figure 6.

Conclusions
We synthesized two nitro-isomers of N-(tetrahydroquinolinyl) pyrrolidin-2-ones using a versatile and simple methodology called the three component imino Diels-Alder cycloaddition.
The spectral analysis showed the 2-Haxial, 4-H axial configuration; therefore, the di-equatorial disposition of the C-2 and C-4 substitutes confirmed the formation of the endo-adduct during a Diels-Alder cycloaddition process. The