Electrochemical and Quantum Chemical Study of Reactivity of Orthophthalaldehyde with Aliphatic Primary Amines

Abstract

The reactivity of orthophthalaldehyde (OPA) with primary amines is a base for broad application of OPA: in the determination of amino acids, in medicine as a disinfection agent and in organic synthesis, therefore the detailed knowledge of the mechanism is of interest. The electrochemical reducibility of OPA was utilized for the investigation of its reactivity with eight aliphatic primary amines which could be separated into four types. Based on the electrochemical monitoring, the apparent reaction rates were evaluated. It was found that the reaction rate essentially depends on the substitution at the α-carbon atom of the amine. The quantum chemical computations revealed that the reaction rate well corresponds with the Hirshfeld and NBO atomic charges on the α-carbon atom. Because of the strong hydration of OPA in aqueous solutions, the reaction was performed both in aqueous solutions (pH 9–10) as well as in diethyl ether. For the identification of intermediates and products, NMR, MS and X-ray crystal structure analyses have been used. Besides the expected isoindolin-1-one main products, the phthalimide derivative as a side product was observed and a new type of the conjugate product has been found and identified. The plausible reaction pathway was proposed.

Elucidating the Mechanism for the Reaction of o-Phthalaldehyde with Primary Amines in the Presence of Thiols

“…Aqueous solutions of OPA, DTT, and alanine were prepared in a 50 mM borate buffer, in the presence of 4.6 M NaCl, in order to closely replicate the experimental conditions and ionic strength for the droplet experiments reported by Jacobs et al The pH was adjusted by adding NaOH. No effect on the reaction kinetics in the presence of different buffers was observed, and we assume that the high ionic strength of our solutions does not substantially affect the overall reaction mechanism. All reagents were purchased from Sigma-Aldrich (OPA: P1378, ≥97%; l-alanine: 05129, ≥98.5%; DTT: D0632, ≥98%; boric acid: 0394, ≥99.5%; sodium tetraborate: 221,732, 99%; NaCl: S7653, ≥99.5%, NaOH: S5881, ≥98%).…”

“…There is an indication that it is the deprotonated primary amino group that reacts with OPA . This alanine protonation/deprotonation equilibrium is shown as step 1 in Table S1 and Figure .…”

“…There is an indication that it is the deprotonated primary amino group that reacts with OPA. 13 This alanine protonation/deprotonation equilibrium is shown as step 1 in Table S1 and Figure 2. The ratio of deprotonated/protonated species as a function of pH is calculated from the second pK a of alanine (9.69) using the Henderson−Hasselbach equation…”

“…As discussed previously, ,, potential reaction mechanisms reported in the literature are mainly based on the identification of products rather than on kinetic studies. Although product identification has provided valuable insight into the chemical nature of the fluorescent product, to date, it has not led to conclusive evidence for the actual reaction mechanism.…”

Theoretical study on the solvent‐free self‐catalyzed coupling mechanism of a chiral vicinal diamine and isobutyraldehyde mediated by the outgrowth H2O

“…Vicinal diamines, a class of structurally crucial scaffolds, display unique chemical and biological properties, and can be transformed to alkyl-substituted vicinal diamines and N-heterocyclic compounds by Mannich reactions. [1][2][3][4][5] Alkyl-substituted vicinal diamines have also been found in varied bioactive compounds, [6][7][8][9][10] and are privileged ligands for a wide variety of diastereo-and enantioselective organocatalysts. [11][12][13][14][15] Various platinum complexes with vicinal diamines are also efficient antitumor agents in chemotherapy.…”