Effect of Substituents on the Reactivity of Ninhydrin with Urea. Issue 4 (29th January 2018)

• Record Type: Journal Article
• Authors: Jong, Jacobus A. W.; Moret, Marc‐Etienne; Verhaar, Marianne C.; Hennink, Wim E.; Gerritsen, Karin G. F.; van Nostrum, Cornelus F.
• Is Part Of: ChemistrySelect. Volume 3:Issue 4(2018)
• Page Start: 1224
• Page End: 1229
• Publication Date: 2018-01-29
• Subjects: computational chemistry -- ninhydrin -- quantitative 13C -NMR -- substituent effects -- urea; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201800040
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Ninhydrin, i. e. the stable hydrate of the reactive species indanetrione, is a well‐known compound used for the quantification of ammonia and amino acids. However, substituent effects on the reactivity of ninhydrin with nucleophiles are not described. In this work, the kinetics of the reaction of C4‐ and C5‐ substituted ninhydrins with urea was studied and monitored by 13 C‐NMR. Surprisingly, the obtained results show that electron donating groups (EDGs) as well as electron withdrawing groups (EWGs) decrease the rate of the reaction. EDGs decrease the electrophilicity of indanetrione, resulting in slower overall kinetics than unsubstituted ninhydrin. The calculated Gibbs free energy differences for the dehydration of unsubstituted and substituted ninhydrins and the subsequent reaction with urea showed that the dehydration of the compounds is more sensitive to electronic effects than the subsequent reaction with urea. Therefore, although EWGs increase the electrophilicity of indanetrione, this is more than counterbalanced by an adverse shift of the hydration equilibrium towards the unreactive hydrate (i. e. ninhydrin), resulting in slower kinetics as well. Abstract : Substituent effects on the reaction of ninhydrin with urea show that electron donating groups (EDGs) and electron withdrawing groups (EWGs) decrease the rate of the reaction as compared to unsubstituted ninhydrin. Computational studies indicate that EDGs increase the rate of the dehydration of ninhydrin, but decrease the rate of the nucleophilic attack of urea on the central carbonyl of indanetrione and vice versa, resulting in slower kinetics for both EWGs and EDGs.