4175-73-9Relevant academic research and scientific papers
New Methods for the Introduction of Substituents into Thiazoles
Begtrup, Mikael,Hansen, Lars Bo L.
, p. 372 - 383 (2007/10/02)
New methods for the regioselective introduction of substituents into thiazoles have been developed using thiazole, 2-phenylthiazole and 4,5-dimethylthiazole as representative thiazoles.Improved halogenation methods, displacement of hydroxy groups in combination with dehalogenation at C-5 yield all eight possible 2-phenyl-4-halo-, 5-halo and 4,5-dihalo-thiazoles in which halogen is chlorine and bromine.Peracid oxidation of the thiazoles gives the corresponding thiazole 3-oxides.These are not activated towards halogenation but are deprotonated with sodium hydride.The anion formed react with electrophiles such as paraformaldehyde, 2,2-dimethylpropanal, 2,2-dimethylpropanoyl chloride, hexachloroethane, tetrabromomethane, and dimethyl disulfide leading to the introduction of carbon substituents, halogen, and methylthio groups.In these reactions, the reactivity of the thiazole ring positions decreases in the order 2 than 5 than 4.Monoselectivity is low when halogen and methylthio groups are introduced since these substituents enhance the acidity of adjacent ring protons. 2-Phenyl-4,5-dihalothiazole 3-oxides lose the 5-halogen when treated with sulfite ion.Trimethyloxonium tetrafluoroborate O-methylates thiazole 3-oxides.Thiazole N-oxides also react with acetyl chloride and phosphorus oxychloride to afford chlorothiazoles in a non-selective manner.Phosphorus trichloride deoxygenates thiazole 3-oxides.
