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25 May 2010

9-Methyl-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,8-diyl Diacetate

and
Chair and Department of Medical Chemistry, 1st Faculty of Medicine, Medical University of Warsaw, 3 Oczki Street, 02-007 Warsaw, Poland
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Author to whom correspondence should be addressed.
Molbank2010, 2010(2), M685;https://doi.org/10.3390/M685
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Abstract

9-Methyl-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,8-diyl diacetate was synthesized from 2-methylcyclohexane-1,3-dione and 1H-pyrrole-2,5-dione. The title compound was characterized by 1H NMR, 13C NMR, elemental analysis and MS.

1. Introduction

Cyclic imides are extensively used as analgesic [1] and antinociceptive agents [2], or as reactants for polymer synthesis [3]. An imide nucleus can be also found in a structure of anxiolytic [4], antimicrobial [5], anticancer and anti-inflammatory substances [6,7]. They are also the objects of quantum chemical studies [8]. Several techniques to produce cyclic imides were described. Thus, unsubstituted cyclic anhydrides are successfully subjected to the reaction with ammonia, urea, formamide, lithium nitride or ammonium carbonate under mild conditions [9,10,11]. Substituted polycyclic imide rings are usually prepared in the Diels-Alder reaction [12,13]. Currently, catalyzed syntheses conducted under microwave irradiation have been described [14]. This work describes a conventional method for the synthesis of the substituted 4-azatricyclo-[5.2.2.02,6]undecene derivative.
Molbank 2010 m685 sch001 550
Scheme 1. Synthesis of 9-methyl-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,8-diyl diacetate.

2. Experimental

2.1. General

All chemicals and solvents were purchased from Sigma-Aldrich (Vienna, Austria). Melting points were determined on an Electrothermal Digital Melting Point Apparatus (Essex, UK) and are uncorrected. The NMR spectra were recorded on a Bruker (Rheinstetten, Germany) spectrometer. The chemical shift values are expressed in ppm relative to TMS as an internal standard. Elemental analysis was recorded on a CHN model 2400 Perkin-Elmer (Hitachi, Tokyo, Japan). Mass spectra were performed on MARINER PE Biosystems instrument (Foster City, USA) with TOF detector. Methanol was used as a solvent. The spectra were performed in the positive ion mode with a declustering potential 140–300 V. TLC was carried out using silica gel 60 F254, layer thickness 0.25 mm (E. Merck, Darmstadt, Germany) and the results were visualized using UV lamp at 254 nm.

2.2. Synthesis of 9-methyl-3,5-dioxo-4-azatricyclo[5.2.2.02,6]undec-8-ene-1,8-diyl diacetate (3)

A mixture of 2-methylcyclohexane-1,3-dione (1) (5 g, 0.040 mol), 1H-pyrrole-2,5-dione (2) (4.62 g, 0.048 mol), and 4-methylbenzenesulfonic acid (0.05 g, 0.0003 mol) was dissolved in 15 mL of isopropenyl acetate and refluxed for 14 h. The solvent was evaporated. The crude product was crystallized from a hexane:ethyl acetate mixture (1:1 vol.) to afford a colourless solid.
Yield: 58%.
M.P. 161–162 °C.
1H NMR (400 MHz, DMSO-d6): δ = 11.18 (s, 1H, NH), 4.00 (d, J = 8.4 Hz, 1H, CH-C=O), 3.07 (dd, J1 = 2.8 Hz, J2 = 8.4 Hz, 1H, CH-C=O), 2.81 (d, J = 2.4 Hz, 1H, CH-C=C), 2.45 (m, 1H, CH2CH2), 2.14 (s, 3H, CH3-C=O), 2.09 (s, 3H, CH3-C=O), 1.73 (m, 2H, CH2CH2), 1.55 (s, 3H, CH3), 1.47 (dd, J1 = 4.4 Hz, J2 = 12.0 Hz, 1H, CH2CH2).
13C NMR (100 MHz, DMSO-d6): δ = 178.60 (C=O), 176.94 (C=O), 169.67 (C=O), 168.58 (C=O), 142.46 (C=C), 123.18 (C=C), 81.07 (C), 45.35 (CH), 44.41 (CH), 35.36 (CH), 27.64 (CH2), 23.18 (CH2), 21.87 (CH3), 21.16 (CH3), 9.45 (CH3).
HR ESI-MS: m/z [%]: 330.0954 [M + Na]+ 100.
Anal. Calcd. (found) for C15H17NO6 (307.30): C, 58.63 (58.68); H, 5.58 (5.62); N, 4.56 (4.58).

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3Supplementary File 4Supplementary File 5Supplementary File 6

References

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