9-Methyl-3,5-dioxo-4-azatricyclo[5.2.2.0^2,6]undec-8-ene-1,8-diyl Diacetate

Abstract

9-Methyl-3,5-dioxo-4-azatricyclo[5.2.2.0^2,6]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-[5.2.2.0^2,6]undecene derivative.

Scheme 1. Synthesis of 9-methyl-3,5-dioxo-4-azatricyclo[5.2.2.0^2,6]undec-8-ene-1,8-diyl diacetate.

Scheme 1. Synthesis of 9-methyl-3,5-dioxo-4-azatricyclo[5.2.2.0^2,6]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[5.2.2.0^2,6]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).