Trihaloisocyanuric Acids as Atom‐Economic Reagents for Halogenation of Aromatics and Carbonyl Compounds in the Solid State by Ball Milling

Abstract

It is shown that both tribromoisocyanuric acid (TBCA) and trichloroisocyanuric acid (TCCA) are excellent reagents for direct halogenation of electron‐rich aromatics under solvent‐free, ball‐milling conditions. The results are remarkable in light of the fact that chlorination of aromatics without any acid catalyst is heretofore unknown. The procedure is operationally simple, and the reactions occur within a few hours, affording high yields of halogenated products. Similarly, crystalline β‐keto dicarbonyl compounds are shown to undergo direct α,α‐dihalogenation with TBCA and TCCA with ball milling. Whereas monoketones are found to be unreactive with TBCA/TCCA, addition of 25 mol‐% of p‐toluenesulfonic acid as a solid catalyst catalyzes the reaction, leading to the formation of α‐chloro/bromo ketones in very good isolated yields. The fact that each of the reagents, in principle, serves as a source of three halogen atoms should render solvent‐free halogenation of aromatics and carbonyl compounds with TBCA/TCCA an invaluable synthetic protocol.

Trichloroisocyanuric Acid: a Versatile and Efficient Chlorinating and Oxidizing Reagent

“…Another example of direct chlorination of electron‐rich aromatic rings carried out by the use of TCCA was reported by Moorthy . The reaction proceeds with solid aromatic compounds under solvent‐free and ball‐milling conditions, within a few hours affording high yields of mono‐halogenated products (Scheme ).…”

“…Recently a halogenation of carbonyl compounds in the solid state carried out by the use of TCCA, as a halogen source, in the solid state by ball milling was reported . Crystalline 1,3‐diketones are shown to undergo direct α,α‐dichlorination with 0.7 equiv.…”

Mechanochemical synthesis of small organic molecules

“…The reactions were found to have yields above 80% for most of the cases but with poor selectivity in mono- or polybrominations ( Scheme 26 ). They have also explored halogenations of 1,3-dicarbonyl compounds to obtain dihalo derivatives in excellent yield [ 100 ].…”

In Situ Formed IIII‐Based Reagent for the Electrophilic ortho‐Chlorination of Phenols and Phenol Ethers: The Use of PIFA‐AlCl3 System

“…The following compound was obtained according to the general procedure for chlorination by using 3-methoxy-2-napthol in 59 [50] …”