N-Protonation vs O-Protonation in Strained Amides:  Ab Initio Study

Abstract

Protonation plays an important catalytic role in amide bond hydrolysis. Although the protonation site of an amide is still debatable, O-protonation is generally preferred to N-protonation in ordinary amides. However, N-protonation can be favored in strained molecular systems. To investigate this strain effect systematically, we studied formamide, strained N-formylazetidine, and highly strained N-formylaziridine using ab initio calculations. The electron correlation effect is found to be important in determining the protonation sites of strained amides, since it contributes to stabilize N-protonation somewhat more than O-protonation. Although O-protonation is highly favored in N-formylazetidine as well as in formamide, N-protonation is favored in N-formylaziridine in both aqueous and gas phases. In case of O-protonation, the geometries become planar even for highly strained amides. The presence of polar solvents contributes to stabilize N-protonation more than O-protonation. The planarity found in O-protonated strained amides and the nonplanarity in N-protonated strained amides would have an important bearing in enzymatic reactions as well as in asymmetric syntheses.

Infrared spectra analysis of OH on aggregate structure formation of oleamide in sulfuric acid solution

“…The oxygen of C@O in DMF can interact with H atom in sulfuric acid and form hydrogen bond. Also the formation of hydrogen bond leads to C@O being elongated to CAO and CAN being shortened to C@N, which is consistent with Cho's result [27]. Therefore, the possible interaction in the sulfuric acid-oleamide system is shown in Fig.…”

“…1 is the dominant one which is also proved by 13 C NMR spectrum [24]. Cho et al [27] used ab initio calculation to figure out the protonation sites of amide. It is accepted that O-protonation lengthens the CAO bond (by 0.07-09 Å) and shortens the CAN bond (by 0.06-0.11 Å), where CAO shows the properties of single bond and CAN shows the properties of double bond.…”

Chemistry of Bridged Lactams and Related Heterocycles

“…Non-planar amides have been frequently employed to investigate fundamental properties of amide bonds, such as proton exchange, 70–72 bonding, 128–131 rotational barriers, 76–77 chemical reactivity. 67–69 The effect of amide distortion has been leveraged to control chemical transformations 132–140 including hydrolysis, 61–66 acylation, 132–134 desymmetrization 135 and kinetic resolution 136,137 of alcohols.…”

Vapor‐Phase Beckmann Rearrangement of Oxime Molecules over H‐Faujasite Zeolite

“…[27,62] It is obvious that the change of the CÀO and CÀN bond lengths is mainly the result of the mesomeric effects resulting from the donation of the lone pair of electrons from the nitrogen atom that passes through the p-bond of the C=O bond to give the different resonance of protonated amide. The desorption energy of these products is calculated to be À50.6, À69.2, 43.4 and À60.1 kcal mol À1 , for the H 2 C=NOH, Z-MeHC=NOH, E-MeHC=NOH and Me 2 C=NOH systems, respectively.…”