SYNTHESIS AND REARRANGEMENT OF SUBSTITUTED S-(1-BENZOFURAN-2(3H)-ONE-3-YL) ISOTHIURONIUM-BROMIDES

Substituted S-(1-benzofuran-2 (3H)-one-3-yl) isothiuronium bromides are derived from cyclic lactame coumaran-2-one, which are prepared by dehydratation of (2-hydroxyphenyl)acetic acid. Thus prepared lactam is further brominated to position 3, where a good leaving group is needed. In next step 3-bromocoumaran-2-one reacts with different substituded thioureas  in the meaning of nucleophilic substitution of atom bromine to atom sulfur and give substituted S-(1-benzofuran-2 (3H)-one-3-yl) isothiuronium bromide, which was obtained as a solid in good yield. These relatively unstable salts were characterized by 1H and 13C NMR spectra, melting point and elemental analysis. Isothiuronium salts are transformed in base conditions and give substituted 5 - (2-hydroxyphenyl)-2-imino-1 ,3-thiazolidine -4-ones. In this rearrangement is applied acid-base catalysis under very mild conditions. The rearrangement proceeds even at physiological pH, which may have potential importance in the use of these compounds as prodrugs. Next, the kinetics and the mechanism of the rearrangement of N-(4-methoxyphenyl)-S‑(2-oxo-2,3-dihydro-1-benzofurane-3‑yl) isothiuronium bromide to 5‑(2‑hydroxyphenyl)-2-[(4-methoxyphenyl)imino]-1,3-thiazolidin-4-on is studied in aqueous buffers at 25 °C and ionic strength  I = 1 mol×l–1 under pseudo-first order conditions.