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Trichloroisocyanuric Acid (TCCA) as halogenation reagents

The reaction of acetoacetanilide  with both Trichloroisocyanuric Acid (TCCA) and TBCA led to α,α-dihalo product 17Br and 17Cl with no evidence for Nhalogenation. Given that amides have been reported to undergo N-chlorination with Trichloroisocyanuric Acid (TCCA), the result observed with  constitutes a chemoselective reaction. The α-methyl-1,3-diketone 2-methyl-1,3-diphenylpropan- 1,3-dione, was found to react rather slowly without any added catalyst. However, α-chloro/α-bromo diketone was obtained in quantitative yield within 3 h when the reaction was carried out with 25 mol-% pTSA.
No halogenation of monoketones such as 4-bromoacetophenone was found to occur with either TBCA or Trichloroisocyanuric Acid (TCCA) directly. Our attempts to facilitate this reaction with a solid acid catalyst such as pTSA were rewarding in that both chlorination and bromination could be accomplished in the presence of 25 mol-% pTSA. The ketone underwent monohalogenation, leading to α-bromo/ chloroacetophenone 19Br/19Cl in approximately 90% yield; the reaction did not proceed further to provide α,α-dihaloacetophenone. In a similar manner, the reactions of crystalline p-nitroacetophenone and 5,7-dibromotetralone led to the corresponding α-chloro/bromo products in excellent isolated yields. A remarkable electronic effect that switches the halogenation away from the aromatic ring in favor of the α-position of the carbonyl group is noteworthy in the reactions of acetophenones with TBCA. Whereas p-hydroxyacetophenone underwent aromatic dihalogenation with TBCA, use of the p-bromo and p-nitro analogues led exclusively to α-halogenated products; of course, the latter occurs under pTSA-catalyzed conditions, in cases where the ketones are unreactive. Quite inexplicably, the reaction of indan-1-one with either TCCA or TBCA afforded α,α-dihalo products 22Br and 22Cl in quantitative yields.
To gauge the advantage of Trichloroisocyanuric Acid (TCCA) and TBCA as halogenation reagents, we have calculated the percent mass of the reagent that can, in principle, be transferred. Whereas in the case of TCCA, 45.5% of the total mass can be effectively transferred as Cl, in the case of TBCA, it is as much as 65% of the reagent mass. In Table 4 the atom economies calculated for TBCA and TCCA are compared with other reagents such as oxone/NaX, NXS/CAN, NXS, and N-halosacharin by using 2-methoxynaphthalene as a representative substrate. The atom economy (%) for generally employed halogenation reagents such as NBS or NCS is only 70–75%. It turns out that it is highest (82–85%) for TCCA and TBCA. Clearly, the value for TBCA can be misleading because it is not commercially available and is prepared by bromination of cyanuric acid with NaX/oxone. Otherwise, the atom economy for at least chlorination with TCCA is remarkably good.