Trichloroisocyanuric acid and NaNO2 mediated nitration of indoles under acid-free and Vilsmeier–Haack conditions: synthesis and kinetic study

Abstract

This study deals with the synthetic and kinetic aspects of trichloroisocyanuric acid (TCCA) and NaNO 2 mediated nitration of indoles in aqueous acetonitrile media under acid-free and Vilsmeier-Haack conditions (using N,N′-dimethyl amides) conditions. Nitration of indoles revealed second order kinetics, with a first order dependence on [indole] and [nitrating agent] ([TCCA]/[NaNO 2 ], [(TCCA-DMF)]/[NaNO 2 ] or [(TCCA-DMA)]/[NaNO 2 ], in which [NaNO 2 ] far excess over other reagents). Reactions followed overall second order kinetics with first order in [reagent] and [indole] under the experimental conditions. Isokinetic temperature (β) values were obtained from Leffler's equation for different kinetic protocols (β = 303 K (TCCA-NaNO 2 ); 303 K (TCCA-DMF)/NaNO 2 ; and 244 K (TCCA-DMA)/NaNO 2 ). These values are the experimental temperature range (303-323 K) indicating that the entropy factors are probably more important in controlling the reaction.

Trichloroisocyanuric acid (TCCA) and carboxamide interactions in TCCA/NaNO2 triggered nitration of pyrrole and indole in aqueous aprotic media: A kinetic correlation of solvent properties with reactivity

“…The method of isolation of nitration products is also similar to that reported in our earlier publication. 21,22 After ensuring the completion of reaction (by TLC), the reaction mixture was treated with sodium bicarbonate (NaHCO 3 ) in the first step, followed by the addition of ethylacetate. An organic layer separated by using a separating funnel and dried with anhydrous MgSO 4 .…”

“…20 More recently, we have reported the kinetics of TCCA/NaNO 2 and TCCA-carboxyl amide adducts/NaNO 2 -triggered nitration of aromatic and heteroaromatic compounds in acid-free reaction media. 21,22 The mechanism of the TCCA/NaNO 2 -triggered nitration was explained due to the in situ generation of the nitronium ion (NO 2 + ), which reacts with organic compounds (aromatic hydrocarbons, phenols, and indoles) as shown in Scheme 1. TCCA upon hydrolysis afforded hypochlorous acid (HOCl), which in turn affords nitryl chloride (NO 2 Cl) due to the reaction with sodium nitrite (NaNO 2 ).…”