About Us

Appel Reaction of Carboxylic Acids with Trichloroisocyanuric Acid (TCCA): a Mild and Acid-Free Preparation of Esters and Amides

Trihaloisocyanuric acids(TCCA) [1,3,5-trihalo-1,3,5-triazine-2,4,6-(1H,3H,5H)-triones] (Figure 1) are safe, stable and easily handled solids used as electrophilic halogenating reagents. Even though diverse trihaloisocyanuric acids are known, the most widely used is the inexpensive and commercially available trichloroisocyanuric acid (TCCA; X = Cl). While not yet commercially available, tribromoisocyanuric acid (TBCA; Figure 1, X = Br) can be easily prepared from inexpensive materials (cyanuric acid, KBr and oxone). Recently, some researcher showed an efficient Appel conversion of alcohols into the corresponding alkyl bromides using tribromoisocyanuric acid/triphenylphosphine system, being a bromophosphonium salt (1), formed by reaction of triphenylphosphine with TBCA, the key reactive species for such transformation.
Herein we report the preparation of esters and amides by reaction of carboxylic acids with alcohols and amines, respectively, in the presence of the tribromoisocyanuric acid(TCCA)/triphenylphosphine system. The reactions were carried out at room temperature by stirring together the carboxylic acid (1 mmol), tribromoisocyanuric acid (0.37 mmol) and triphenylphosphine (1 mmol) in dichloromethane. The progress of the reaction was followed by gas chromatography with mass spectrometer (GC-MS) and after complete substrate conversion to the acyl bromide (confirmed by MS), an alcohol (1 mmol) or an amine (excess) was added to the reaction media. The reactions gave, respectively, esters and amides (along with triphenylphosphine oxide and cyanuric acid), that were isolated by column chromatography and characterized by their melting points (amides) and spectroscopic techniques. 
Interestingly, although tribromoisocyanuric acid(TCCA) is known to be a powerful alcohol oxidant20 and electrophilic brominating reagent for alkenes21 and arenes,22 no brominated or oxidation products were detected by the analytical techniques employed in the crude reaction, indicating a fast formation of bromotriphenylphosphonium salt from the reaction of TBCA with triphenylphosphine. In summary, we have developed a new and convenient route for the preparation of esters and amides from carboxylic acids under neutral conditions. The reaction is easily reproducible, the conditions are mild and the reagents are easily available.