New Multi-1,2,3-Selenadiazole Aromatic Derivatives

The aromatic polyketones 3a-d are versatile compounds for the synthesis of the multi-1,2,3-selenadiazole aromatic derivatives 1a-d. The preparation starts with the reaction between the multi-bromomethylene benzene derivatives 2a-d and 4-hydroxy-acetophenone to give compounds 3a-d which are transformed through the reaction with semicarbazide hydrochloride or ethyl hydrazine carboxylate into the corresponding semicarbazones derivatives 4a-d or hydrazones 5a-d. The reaction with selenium dioxide leads to regiospecific ring closure of semicarbazones or hydrazones to give the multi-1,2,3-selenadiazole aromatic derivatives in high yield.


Introduction
Heterocyclic systems with multi-arm 1,2,3-thiadiazoles were recently prepared by Meier et. al [1][2] and heterocyclic systems containing two 1,2,3-selenadiazole rings were also recently prepared by Reddy et. al [3][4], but multi-arm 1,2,3-selenadiazoles are still unknown. Therefore depending on the previous experience of the principal investigator in synthesizing multi-arm 1,2,3-thiadiazoles, the analogous multi-arm selenadiazoles were prepared following the method that was first reported by Lalezari et. al [5][6][7], through reaction in the presence of acetic acid of selenium dioxide with αketomethylene semicarbazones or hydrazones which contain aminocarbonyl or ethoxycarbonyl groups as good leaving groups. NOE measurements showed that the (E)-configuration largely predominated around the CN double bond. This paper was retracted on 4 July 2007, see: Molecules 2007Molecules , 12, 1289; http://dx.doi.org/10.3390/12071289 RETRACTED Selenium containing heterocycles are of increasing interest because of their interesting chemical properties [8][9][10][11][12][13] and varied biological activities [14][15][16]. Remarkable differences are known to exist between Se-and S-containing compounds. Due to the larger size of the Se-atom, selenium compounds show an increased polarizability and therefore they are, in general, less stable than the corresponding S-analogues [17][18][19][20]. We report herein on our efforts to generate the multi-branched benzene derivatives 1a, 1b, 1c and 1d, in which the 1,2,3-selenadiazole rings are linked to the central benzene core via phenoxymethylene spacers.

Acknowledgements
We are grateful to the Deanship of Scientific Research of the Jordan University for Science and Technology for financial support. Also, we thank Prof. H. Meier from Mainz University-Germany for helpful discussions.

General
The solvents were purified by standard procedures. The melting points (m.p.) were determined on an Electrothermal digital melting point apparatus and are uncorrected. Infrared (IR) spectra of pure substances were recorded as KBr-pellets using a Nicolet 410 FT-IR spectrometer (ν in cm -1 ). The 1 Hand 13 C-NMR spectra were recorded on Bruker AM400 and AC200 spectrometers in CDCl 3 or DMSO-d 6 using TMS as internal standard. The spectral data are reported in delta (δ) units relative to
General Procedure for the Preparation of Multi-Ketones 3a-d [1] A mixture of 4-hydroxyacetophenone (1 equivalent) and 2a (0.14 equivalents), 2b (0.21 equivalents), 2c (0.3 equivalents) or 2d (0.45 equivalents), potassium carbonate (1 equivalent) and potassium iodide (in the same equivalent amount as the bromo compound used) plus a few drops of Aliquat 336 were refluxed in dry acetone (100 mL) for 48 hours. The reaction was followed by TLC (eluent: chloroform) till completion. After cooling, the reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (3 × 40 mL). The combined organic layers were dried over magnesium sulphate. The solvent was evaporated under vacuum and the residual solid was washed with diethyl ether. When necessary, a recrystalization from acetone or chloroform was performed.    General procedure for the preparation of multiple semicarbazones 4a-d A mixture of semicarbazide hydrochloride (1 equivalent) and sodium acetate (1 equivalent) was dissolved in absolute ethanol (40 mL). The mixture was heated for 15 min under reflux, then filtered while hot to remove precipitated sodium chloride. The filtrate was mixed with ketone 3a (0.14 equivalents), ketone 3b (0.21 equivalents), ketone 3c (0.30 equivalents) or ketone 3d (0.45 equivalents), respectively. The reaction mixture was heated to reflux then two drops of concentrated hydrochloric acid were added. The mixture was heated under reflux for overnight with continuously removal of generated water. After that the solvent was removed under vacuum and the residue was washed with diethyl ether.  General procedure for the preparation of multiple hydrazones 5a-d [1].

1-{4-[2,3,4,5,6-Penta(4-acetylphenoxymethyl)benzyloxy]phenyl}-1-ethanone (3a).
A solution of di-or tri-or tetra-or hexaketone 3a-d (1 equivalent), a few drops of concentrated hydrochloric acid and 6, 9, 12 or 18 equivalents of ethyl hydrazinecarboxylate in dry chloroform (50 mL) was heated under reflux overnight with continuously removal of generated water. The solution was concentrated and the residue was washed with diethyl ether and chloroform. [2,3,4,5,  General procedure for preparation of multiple 1,2,3-selenadiazoles 1a-d Hydrazone 5a (0.47 mmol) or 5b (0.59 mmol) or 5c (0.9 mmol) or 5d (0.27 mmol) was dissolved in glacial acetic acid (30 mL) with vigorous stirring and gentle heating to 40-45°C. The solution was treated with selenium dioxide powder (8.46 mmol, 7.08 mmol, 8.1 mmol or 0.81 mmol, respectively) and the mixture was kept under gentle heating with vigorous stirring. After 2 min, the color of the mixture becomes red. Monitoring of the reaction by TLC showed that the reaction was complete in two days. The mixture was filtered and the filtrate was poured into ice water and extracted with chloroform (3 × 50 mL). The combined organic layers were washed with saturated sodium hydrogen RETRACTED carbonate solution and dried using magnesium sulphate. The solvent was removed under vacuum. The crude product was purified by chromatography using methanol or ethyl acetate as eluents, followed by recrystallization from chloroform/hexane. [4-(1,2,3-