A simple one-pot synthesis of new 9-aroyl-3,4,6,7,9,10-hexahydro-1,8(2 H ,5 H )-acridinediones

A series of new acridinedione derivatives have been synthesized via one-pot three-component reactions of cyclohexane-1,3-dione, ammonium acetate and arylglyoxals in the presence of alginic acid as a bio-polymeric catalyst in ethanol at room temperature or under reflux conditions. The products were characterized by their spectroscopic data and microanalyses.


Introduction
Acridinedione derivatives are a class of nitrogen-containing heterocyclic compounds with significant synthetic potential.The 1,8-acridinediones and their derivatives are known to exhibit a wide range of biological and pharmaceutical properties such as antibacterial, 1 antimicrobial, 2 anticancer, [3][4][5] antitumor, [6][7] antifungal, 8 antimalarial, 9 antiviral, 10 larvicidal 11 and hypertensive 12 activities.Electroluminescent devices based on decahydroacridinedione (DAD) derivatives exhibit good efficiencies and excellent color purity. 13][16][17][18][19][20] Alginic acid is a naturally occurring polysaccharide that can also be produced by a microbial fermentation.It has many carboxylic acid and hydroxyl groups in its backbone. 21,22Alginic acid can activate the reaction components not only via its Brønsted acid centers but also by hydrogen bonding, as a heterogeneous catalyst. 23,24n continuation of our research interests in the synthesis of heterocyclic compounds using arylglyoxals as valuable sources, [25][26][27][28][29][30][31][32][33] here, we report the synthesis of a series of new 9-aroyl-1,8acridinediones by a one-pot three-component reaction of cyclohexane-1,3-dione, arylglyoxals and ammonium acetate in the presence of alginic acid as a catalyst in ethanol at room temperature or under reflux conditions.

Results and Discussion
The reaction of cyclohexane-1,3-dione (1) arylglyoxals as hydrates 2a-h and ammonium acetate (3) in the presence of alginic acid as a catalyst in ethanol at room temperature or under reflux conditions gave a series of new 9-aroyl-1,8-acridinediones 4a-h by a one-pot, three-component reaction as shown on Scheme 1.The proposed mechanism of reaction is shown in Scheme 2. The first step involves the attack of the enol form of cyclohexane-1,3-dione (1) on arylglyoxal 2a-h catalyzed by alginic acid to form the corresponding condensation intermediate 5a-h by loss of a molecule of water.Reaction of this intermediate, protonated by alginic acid, with a second molecule of cyclohexane-1,3dione (1) in its enol form gives the corresponding intermediate 6a-h.This intermediate 6a-h is also activated through proton transfer from alginic acid to react with ammonium acetate to form an imine intermediate 7a-h, which by subsequent tautomerisation through a proton transfer to alginate anion forms the corresponding enamine 8a-h.In the next step, alginic acid activates the remaining ketone group for ring closure by amino group of the enamine moiety, followed by final elimination of another molecule of water catalyzed by alginic acid to afford the desired products 4a-h.
Owing to the extreme insolubility of products 4a-h, their 1 H and 13 C-NMR spectra could not be measured in CDCl3, except for compound 4f, which showed a singlet at δ = 3.81 ppm for the hydrogen next to aroyl group (H-9) in its keto form (A). The 1 H and 13 C-NMR spectra of all products 4a-h were measured in DMSO-d6, showing singlets for hydroxyl groups at δ = 11.32-11.83 in the enol form (B), which were exchanged by D2O addition.It seems that the products exist as enol form (B) in more polar solvent (DMSO-d6) and as keto form in a less polar solvent (CDCl3) as shown on Scheme 1.The C=O absorptions in FT-IR spectra was observed at 1606-1618 cm -1 .
The reaction conditions, yields and melting points for the synthesis of 9-aroyl-1,8acridinedione derivatives are shown in Table 1.

Experimental Section
General.The chemicals used in this work were purchased from Acros Organics or from Merck, and were used without purification.Melting points were measured on a Philip Harris C4954718 apparatus. 1H and 13 C NMR spectra were recorded on a Bruker Avance AQS 300 MHz spectrometer at 300 and 75.5 MHz, respectively.Chemical shifts were measured in DMSO-d6 as solvent relative to TMS as the internal standard.Infrared spectra were recorded on a Thermo-Nicolet Nexus 670 FT-IR instrument using KBr discs.Elemental analyses were performed using a Leco Analyzer 932.

Scheme 2 .
Scheme 2. The proposed mechanism for the one-pot three-component reaction.