Premium
Synthesis and Structures of Se Analogues of the Antithyroid Drug 6‐ n ‐Propyl‐2‐thiouracil and Its Alkyl Derivatives: Formation of Dimeric Se–Se Compounds and Deselenation Reactions of Charge‐Transfer Adducts of Diiodine
Author(s) -
Antoniadis Constantinos D.,
Hadjikakou Sotiris K.,
Hadjiliadis Nick,
Papakyriakou Athanasios,
Baril Martin,
Butler Ian S.
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200501455
Subject(s) - chemistry , dichloromethane , acetonitrile , chloroform , thiouracil , medicinal chemistry , recrystallization (geology) , isopropyl , acetone , raman spectroscopy , organic chemistry , solvent , paleontology , physics , medicine , biology , thyroid , optics
Four selenium analogues of the antithyroid drug 6‐ n ‐propyl‐2‐thiouracil (PTU), of formulae RSeU, (R = methyl (Me) ( 1 ), ethyl (Et) ( 2 ), n ‐propyl ( n Pr) ( 3 ), and isopropyl ( i Pr) 4 ), have been synthesized. Reaction of 1 – 4 with diiodine in a 1:1 molar ratio in dichloromethane results in the formation of [(RSeU)I 2 ] (R = methyl ( 5 ), ethyl ( 6 ), n ‐propyl ( 7 ) and isopropyl ( 8 )). All compounds have been characterized by elemental analysis, FT‐Raman, FT‐IR, UV/Vis, 1 H–, 13 C–, 77 Se–1D and ‐2D NMR spectroscopy, and ESI‐MS spectrometric techniques. Recrystallization of 4 from dichloromethane afforded ( 4 ⋅CH 2 Cl 2 ). Crystals of [( n PrSeU)I 2 ] ( 7 ), a charge‐transfer complex, were obtained from chloroform solutions, while crystallization of 6 and 7 from acetone afforded the diselenides [ N ‐(6‐Et‐4‐pyrimidone)(6‐EtSeU) 2 ] ( 9 ⋅2 H 2 O) and [ N ‐(6‐ n Pr‐4‐pyrimidone)(6‐ n PrSeU) 2 ] ( 10 ) as oxidation products. Recrystallization of 7 from methanol/acetonitrile solutions led to deselenation with the formation of 6‐ n ‐propyl‐2‐uracil ( n PrU) ( 11 ). [( n PrSeU)I 2 ] ( 7 ) was found to be a charge‐transfer complex with a SeI bond. These results are discussed in relation to the mechanism of action of antithyroid drugs.