Sergeja Bombek

ZrCl4-promoted halogen migration during an electrophilic amination of halogenated phenolsElectronic supplementary information (ESI) available: spectroscopic data (1H NMR,13C NMR, IR, MS), mp and elemental analysis (or HRMS) for the products 3 and 4. See http://www.rsc.org/suppdata/cc/b2/b203622c/Dedicated to Professor Waldemar Adam, University of Würzburg, Germany, on the occasion of his 65th birthday.

An electrophilic amination of halogenated phenols with diisopropyl diazenedicarboxylate in the presence of ZrCl4 as a Lewis acid, accompanied by a halogen migration, was demonstrated for the first time; the fluorine, chlorine, bromine, or iodine atom migrated during the amination process under mild reaction conditions.

Methyl 2-(2-chloroethylaminocarbonyl)diazenecarboxylate SB-166 inhibits the growth of different tumour cell lines, including drug-resistant sublines

Recently we synthesized new drugs, diazenecarboxamides (shortly diazenes), that were cytotoxic for several tumour cell lines. Because the solubility and biological activity of these drugs was relatively low, new compounds have been synthesized. In the present study we examined the cytotoxic effect of nine compounds: an imidazolidin-2-one (SB-282: methyl 5-benzoyl-3-(2-chloroethyl)-2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-ylcarbamate), two diazenecarboxamides (UP-140: N-phenyl-2-(2-quinolinyl)diazenecarboxamide; JK-1090: N-(4-iodophenyl)-2-(2-pyridinyl)diazenecarboxamide), two aminocarbonyl substituted diazenecarboxylates (SB-178: methyl 2-[(cyclohexylamino)carbonyl]diazenecarboxylate; SB-166: methyl 2-[[(2-chloroethyl)amino]carbonyl]diazenecarboxylate) and four diazenedicarboxamides (SB-410: N(1)-(2-chloroethyl)-N(2)-(2-pyridinylmethyl)-1,2-diazenedicarboxamide; SB-472: N(1)-(2-chloroethyl)-N(2)-(4-isopropylphenyl)-1,2-diazenedicarboxamide; SB-503: N(1)-(4-sec-butylphenyl)-N(2)-(2-chloroethyl)-1,2-diazenedicarboxamide; SB-474: N(1)-(4-tert-butylphenyl)-N(2)-(2-chloroethyl)-1,2-diazenedicarboxamide). Using a modified colorimetric MTT assay, their cytotoxicity was determined on eight human cell lines: laryngeal carcinoma parental and two drug-resistant cell lines, glioblastoma parental and drug-resistant cell lines, cervical carcinoma parental and drug-resistant cell lines and breast adenocarcinoma cells. Results show that diazene SB-166 was very effective, reducing significantly the cell survival of all eight examined cell lines, including four drug-resistant cell lines. Compound SB-410 was cytotoxic for all examined cell lines, but mostly only in the highest concentration. Other compounds were not significantly cytotoxic to any of the treated cell lines. Our results, especially those obtained on drug-resistant cells, encourage further research on compound SB-166 as a potential anticancer drug.

A simple and efficient synthesis of 2-imidazolin-2-ones

We report on the reactions of diazenes 1 and 2 with 1,3-dicarbonyl compounds. The first step involves a regioselective attack of the diazene on the active methylene group, giving the Michael adducts 3 or 4, and can be performed either in the presence of sodium acetate or DBN (1,5-diazabicyclo[4.3.0]non-5-ene). The Michael adducts underwent ring-closure leading to 2-imidazolidinones 5 or 6 which were isolated in some cases. We found that 5 or 6 easily eliminated water in the presence of an acid to give imidazolin-2-ones 7 or 8 as the final products. The rate-determining step of this last mentioned process depends on the stereochemistry at C4 and C5 of the initial 2-imidazolidinone. A one-pot procedure to produce 7 or 8 directly from the diazene and the appropriate dicarbonyl partner is also described.