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Preparation of Halogenated Derivatives of Thiazolo[5,4-d]thiazole via Direct Electrophilic Aromatic Substitution
Journal of Heterocyclic Chemistry
  • Vladimir Benin, University of Dayton
  • Alan T. Yeates, Air Force Research Laboratory
  • Douglas Dudis, Air Force Research Laboratory
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Chlorination and bromination reactions of thiazolo[5,4-d]thiazole led to the generation of its mono- and dihalogenated derivatives. These are the first instances of successful direct electrophilic aromatic substitution in the thiazolo[5,4-d]thiazole ring system. X-ray analysis demonstrates that both 2-bromothiazolo[5,4-d]-thiazole and 2,5-dibromothiazolo[5,4-d]thiazole are planar structures, with strongly manifested π-stacking in the solid state. Theoretical analysis of the pyridine-catalyzed halogenation (MP2/6-31+G(d) and B3LYP/6-31+G(d)calculations) reveals that introduction of one halogen actually leads to a slightly enhanced reactivity towards further halogenation. Several halogenation mechanisms have been investigated: 1) The direct C-halogenation with N-halopyridine as electrophile; 2) C-halogenation viaintermediate N-halogenation, and 3) C-halogenation following an addition - elimination pathway, with intermediate formation of a cyclic halonium ion. The theoretical studies suggest that the direct C-halogenation is the favored mechanism.

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John Wiley & Sons
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Vladimir Benin, Alan T. Yeates and Douglas Dudis. "Preparation of Halogenated Derivatives of Thiazolo[5,4-d]thiazole via Direct Electrophilic Aromatic Substitution" Journal of Heterocyclic Chemistry Vol. 45 Iss. 3 (2008)
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