Mechanistic investigations on Pinnick oxidation: a density functional theory study

Aqeel A Hussein; Azzam A M Al-Hadedi; Alaa J Mahrath; Gamal A I Moustafa; Faisal A Almalki; Alaa Alqahtani; Sergey Shityakov; Moaed E Algazally

doi:10.1098/rsos.191568

Mechanistic investigations on Pinnick oxidation: a density functional theory study

R Soc Open Sci. 2020 Feb 5;7(2):191568. doi: 10.1098/rsos.191568. eCollection 2020 Feb.

Authors

Aqeel A Hussein^{1

2}, Azzam A M Al-Hadedi³, Alaa J Mahrath⁴, Gamal A I Moustafa^{2

5}, Faisal A Almalki⁶, Alaa Alqahtani⁶, Sergey Shityakov⁷, Moaed E Algazally¹

Affiliations

¹ Faculty of Dentistry, University of Al-Ameed, Karbala PO Box 198, Iraq.
² Department of Chemistry, University of Southampton, Southampton, Hampshire SO17 1BJ, UK.
³ Department of Chemistry, Faculty of Science, University of Mosul, Mosul, Iraq.
⁴ Department of Chemistry and Biochemistry, College of Medicine, University of Babylon, Babylon, Iraq.
⁵ Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
⁶ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
⁷ Department of Anesthesia and Critical Care, University of Würzburg, 97080 Würzburg, Germany.

Abstract

A computational study on Pinnick oxidation of aldehydes into carboxylic acids using density functional theory (DFT) calculations has been evaluated with the (SMD)-M06-2X/aug-pVDZ level of theory, leading to an important understanding of the reaction mechanism that agrees with the experimental observations and explaining the substantial role of acid in driving the reaction. The DFT results elucidated that the first reaction step (FRS) proceeds in a manner where chlorous acid reacts with the aldehyde group through a distorted six-membered ring transition state to give a hydroxyallyl chlorite intermediate that undergoes a pericyclic fragmentation to release the carboxylic acid as a second reaction step (SRS). ¹H NMR experiments and simulations showed that hydrogen bonding between carbonyl and t-butanol is unlikely to occur. Additionally, it was found that the FRS is a rate-determining and thermoneutral step, whereas SRS is highly exergonic with a low energetic barrier due to the Cl(III) → Cl(II) reduction. Frontier molecular orbital analysis, intrinsic reaction coordinate, molecular dynamics and distortion/interaction analysis further supported the proposed mechanism.

Keywords: Pinnick oxidation; density functional theory simulations; molecular dynamics; molecular orbital theory; oxidation; transition state.

Associated data

figshare/10.6084/m9.figshare.c.4829211