New Views on the Reaction of Primary Amine and Aldehyde from DFT Study

Abstract

A general theoretical investigation on the reaction of primary amine with aldehyde was carried out by density functional theory. The calculation systems involve three kinds of primary amines (methylamine, vinylamine, and phenylamine) and three kinds of aldehydes (formaldehyde, acetaldehyde, and acrylaldehyde). The steric and electronic inductive effects on the reaction mechanism were studied. Results reveal that the nucleophilic attack of primary amine on aldehyde under neutral conditions leads to carbinolamines, rather than Schiff bases. The nucleophilic attack on the protonated aldehyde produces the protonated Schiff base. The steric hindrance of the aldehyde slows down the nucleophilic attack but allows enough time to abstract a H; consequently, the formation of the protonated Schiff base is preferred. During the carbinolamine protonation, the H(+) preferably locates on the amine nitrogen and then is abstracted by the hydroxyl oxygen over an energy barrier, leaving protonated Schiff base after timely water liberation. The formation of a prereaction potential energy well obviously softens the steric and electronic inductive effects on the active barrier for different reactants.

Internal Hydrogen Bond Influences the Formation of [2+2] Schiff Base Macrocycle: Open‐Chain Vs. Hemiaminal and Macrocycle Forms

“…[40,41,44,46] The energy barrier of 34.6-32.4 kcal mol -1 for the hemiaminal formation step resembles the values calculated for the reaction between ammonia and formaldehyde (34.2 kcal mol -1 B3LYP/6-311++G(d,p), [44] 33.5 kcal mol -1 G3B3 composite method [46] ) or between acetone and methylamine (32.7 kcal mol -1 ), [41] formaldehyde and phenylamine (31.8 kcal mol -1 B3LYP/6-311++G(2d,2p)), [45] but is higher than for the reaction between formaldehyde and methylamine or vinylamine (24.8 kcal mol -1 and 24.4 kcal mol -1 , respectively). [40,41,44,46] The energy barrier of 34.6-32.4 kcal mol -1 for the hemiaminal formation step resembles the values calculated for the reaction between ammonia and formaldehyde (34.2 kcal mol -1 B3LYP/6-311++G(d,p), [44] 33.5 kcal mol -1 G3B3 composite method [46] ) or between acetone and methylamine (32.7 kcal mol -1 ), [41] formaldehyde and phenylamine (31.8 kcal mol -1 B3LYP/6-311++G(2d,2p)), [45] but is higher than for the reaction between formaldehyde and methylamine or vinylamine (24.8 kcal mol -1 and 24.4 kcal mol -1 , respectively).…”

“…What arouse controversy in literature is the order of the elementary chemical events along the reaction paths and their occurrence with respect to a pertaining transition state. [45] In general, however, contrary to ELF results, establishing covalent bond evolution on the basis on interatomic distances only is difficult or sometimes vague. Recently, the discussion has been broadened as quantum chemical topology methods such as Electron Localization Function (ELF) [47,48] and Atoms in Molecules [49] analyses have been employed to study bond evolution along the reaction paths for the reaction of benzaldehyde with 4-amine-4H-1,2,4-triazole [42,43] and ammonia with formaldehyde.…”

“…[44] Such an order can be also concluded from bond lengths reported for the reactions between formaldehyde and ammonia [40] and between primary amines and variety of aldehydes. [45] In general, however, contrary to ELF results, establishing covalent bond evolution on the basis on interatomic distances only is difficult or sometimes vague.…”

“…[23][24][25][26][27][28][29][30][31][32][33][34][35][36] It should be emphasized that the 1,2-cycloalkyldiamines (especially trans-1,2-diaminocyclohexane) were studied in detail in the formation of ([2+2]) imine macrocycles scrutinizing the role of chirality of conformational preorganization. [37][38][39] The mechanism of the imine formation has been recently extensively studied theoretically, [40][41][42][43][44][45][46] but it has not been fully understood yet. What does not raise doubts are three stages of the reaction, i.e.…”

Characterisation of the reaction mechanism between ammonia and formaldehyde from the topological analysis of ELF and catastrophe theory perspective

“…The latter also determined the infinitepressure Rice-Rampsperger-Kassel-Marcus unimolecular decomposition rate for aminomethanol water elimination. Similar study has been performed by Ding et al [11] who investigated three different types of reactions between primary amines and variety of aldehydes (including formaldehyde) in order to describe steric and electronic inductive effects on the reaction mechanism. Erdtman et al [12] studied reaction of methylamine with formaldehyde at the G2(MP2,SVP) level of theory.…”