Trihaloisocyanuric Acids / NaX : an Environmentaly Friendly System for Vicinal Dihalogenation of Alkenes without using Molecular Halogen

The great synthetic potential of organic halides puts them in a unique position within organic chemistry. They can be efficiently converted into other functionality by well-known methodologies, such as halogen-metal exchange, palladium-catalyed reaction for new C-C bond formation, conversion into radicals, nucleophilic substitution etc. Furthermore, several marine organic halides have been discovered in the last years with interesting biological activity. Although several reagents have been used to introduce halogen atoms in organic substrates, the typical route to prepare vicinal dihalo compounds is the electrophilic molecular halogen (X 2 ) addition to alkenes. Molecular chlorine (Cl 2 ) is a very toxic gas that presents a potential hazard and its quantitative utilization is generally problematical. Molecular bromine (Br 2 ) is a toxic and lowboiling lachrymatory liquid which causes severe burns on contact with skin. Moreover, both halogens are corrosive, difficult to handle and strong oxidants. In addition, traditional halogenations of alkenes are performed in polychlorinated solvents, such as CHCl 3 or CCl 4 which are being considered “villains” from the green chemistry point of view. Furthermore, in chlorinated solvents, free radical reaction can compete to electrophilic process and some by products are usually obtained. Based on the above considerations, the search for new methodologies that avoid the utilization of molecular halogen is of great interest and attractive. Unfortunately, some alternative reagents used for dihalogenation of alkenes are very hazardous, toxic, not readily available or need to be freshly prepared. Trichloroisocyanuric acid (TCCA) is a stable and inexpensive solid frequently used for swimming-pool disinfection and easily available in pool supply and some hardware stores. Tribromoisocyanuric acid (TBCA), an analogue of TCCA, is easily and safely prepared from cyanuric acid, KBr and oxone. We have shown that these trihaloisocyanuric acids are very interesting from Green Chemistry point of view, once they are easily handled stable solids and efficient source of electrophilic halenium ions (X) that can halogenate organic compounds without using X 2 . They also present a very good atom economy, once they can transfer most part of their mass to the substrate. For example, TBCA can transfer up to 65% of its mass to the substrate. Furthermore, in these reactions, cyanuric acid precipates as by-product, which can be recovered by filtration and reused to prepare more TBCA (Scheme 1). Herein we communicate our results on the utilization of trihaloisocyanuric acids to perform the vicinal dihalogenation of alkenes.


Introduction
The great synthetic potential of organic halides puts them in a unique position within organic chemistry.They can be efficiently converted into other functionality by well-known methodologies, such as halogen-metal exchange, palladium-catalyed reaction for new C-C bond formation, conversion into radicals, nucleophilic substitution etc. 1 Furthermore, several marine organic halides have been discovered in the last years with interesting biological activity. 2lthough several reagents have been used to introduce halogen atoms in organic substrates, the typical route to prepare vicinal dihalo compounds is the electrophilic molecular halogen (X 2 ) addition to alkenes. 3 Molecular chlorine (Cl 2 ) is a very toxic gas that presents a potential hazard and its quantitative utilization is generally problematical.Molecular bromine (Br 2 ) is a toxic and lowboiling lachrymatory liquid which causes severe burns on contact with skin.Moreover, both halogens are corrosive, difficult to handle and strong oxidants. 4In addition, traditional halogenations of alkenes are performed in polychlorinated solvents, such as CHCl 3 or CCl 4 which are being considered "villains" from the green chemistry point of view. 5Furthermore, in chlorinated solvents, free radical reaction can compete to electrophilic process and some by products are usually obtained. 6ased on the above considerations, the search for new methodologies that avoid the utilization of molecular halogen is of great interest and attractive.Unfortunately, some alternative reagents used for dihalogenation of alkenes are very hazardous, toxic, not readily available or need to be freshly prepared. 7richloroisocyanuric acid (TCCA) is a stable and inexpensive solid frequently used for swimming-pool disinfection and easily available in pool supply and some hardware stores. 8Tribromoisocyanuric acid (TBCA), an analogue of TCCA, is easily and safely prepared from cyanuric acid, KBr and oxone. 9We have shown that these trihaloisocyanuric acids are very interesting from Green Chemistry point of view, once they are easily handled stable solids and efficient source of electrophilic halenium ions (X + ) that can halogenate organic compounds without using X 2 . 10hey also present a very good atom economy, once they can transfer most part of their mass to the substrate.For example, TBCA can transfer up to 65% of its mass to the substrate.Furthermore, in these reactions, cyanuric acid precipates as by-product, which can be recovered by filtration and reused to prepare more TBCA (Scheme 1).
Herein we communicate our results on the utilization of trihaloisocyanuric acids to perform the vicinal dihalogenation of alkenes.

Results and Discussion
The reactions of alkenes with TCCA in the presence of chloride ion or with TBCA in the presence of bromide ion produced the vicinal dihaloalkanes.The reactions were carried out stirring together 10 mmol of the alkene (cyclohexene, 1-methylcyclohexene, styrene, α-methyl-Trihaloisocyanuric Acids/NaX: an Environmentaly Friendly System J. Braz.Chem.Soc. styrene, or 1-octene,) with 3.4 mmol of the corresponding trihaloisocyanuric acid and 5 mmol of the halide in aqueous acetone at room temperature. 11The end of the reactions were determined when an aliquot did not produce a color change in a wet iodide-starch test paper.After work up, cyanuric acid was filtered off and the corresponding vicinal dihaloalkanes were obtained in moderate to excellent yields.The products were characterized by GCMS, physical constants and coinjection with authentic samples in HRGC.Table 1 summarizes the obtained results.
In the investigation of the actual halogenating reagent, we studied the reaction of cyclohexene with TCCA / Br - and TBCA / Cl -and obtained a mixture of several products, among of them trans-1-bromo-2-chlorocyclohexane.
Control experiments with styrene and both systems TCCA/ Br -and TBCA / Cl -produced diverse products and in both reactions 2-bromo-1-chloro-1-phenylethane is formed.These results suggests the in situ formation of BrCl as the halogenation agent for both reactions. 12owever, based on the works of Ross and coworkers 13 Shao and Shi, 6 the formation of a complex halogenating reagent formed between the trihaloisocyanuric acid and the halide ion could not be discarded.

Conclusions
In summary, we have found a very convenient method for the vicinal dihalogenation of alkenes in the absence of molecular halogen and polyhalogenated solvents.Furthermore, the reagents are safe and of easy handling, and the by-product for both reactions is cyanuric acid that can be recycled.Due to environmental problems involved in the manipulation of hazardous, toxic and corrosive halogens as well as the not readily available alternative reagents used in such transformation, our methodology becomes very attractive and consistent with green chemistry principles.