A REP-FAMSEC method as a tool in explaining reaction mechanisms : a nucleophilic substitution of 2-phenylquinoxaline as a DFT case study

dc.contributor.authorMdhluli, Brian Kamogelo
dc.contributor.authorNxumalo, Winston
dc.contributor.authorCukrowski, Ignacy
dc.contributor.emailignacy.cukrowski@up.ac.zaen_US
dc.date.accessioned2022-09-20T04:32:11Z
dc.date.available2022-09-20T04:32:11Z
dc.date.issued2021-03-12
dc.descriptionThe Supporting Information is available free of charge as Cartesian XYZ coordinates of molecular systems and their energies; selected geometric data; net atomic charges; inter‑fragment interaction energies; reaction energy profiles.en_US
dc.description.abstractIn search for the cause leading to low reaction yields, each step along the reaction energy profile computed for the assumed oxidative nucleophilic substitution of hydrogen (ONSH) reaction between 2‑phenylquinoxaline and lithium phenylacetylide was modelled computationally. Intermolecular and intramolecular interaction energies and their changes between consecutive steps of ONSH were quantified for molecular fragments playing leading roles in driving the reaction to completion. This revealed that the two reactants have a strong affinity for each other, driven by the strong attractive interactions between Li and two N‑atoms, leading to four possible reaction pathways (RP‑C2, RP‑C3, RP‑C5, and RP‑C10). Four comparable in energy and stabilizing molecular system adducts were formed, each well prepared for the subsequent formation of a C–C bond at either one of the four identified sites. However, as the reaction proceeded through the TS to form the intermediates (5a–d), very high energy barriers were observed for RP‑C5 and RP‑C10. The data obtained at the nucleophilic addition stage indicated that RP‑C3 was both kinetically and thermodynamically favored over RP‑C2. However, the energy barriers observed at this stage were very comparable for both RPs, indicating that they both can progress to form intermediates 5a and 5b. Interestingly, the phenyl substituent (Ph1) on the quinoxaline guided the nucleophile towards both RP‑C2 and RP‑C3, indicating that the preferred RP cannot be attributed to the steric hindrance caused by Ph1. Upon the introduction of H2O to the system, both RPs were nearly spontaneous towards their respective hydrolysis products (8a and 8b), although only 8b can proceed to the final oxidation stage of the ONSH reaction mechanism. The results suggest that RP‑C2 competes with RP‑C3, which may lead to a possible mixture of their respective products. Furthermore, an alternative, viable, and irreversible reaction path was discovered for the RP‑C2 that might lead to substantial waste. Finally, the modified experimental protocol is suggested to increase the yield of the desired product.en_US
dc.description.departmentChemistryen_US
dc.description.librarianam2022en_US
dc.description.sponsorshipThe National Research Foundation of South Africa.en_US
dc.description.urihttps://www.mdpi.com/journal/moleculesen_US
dc.identifier.citationMdhluli, B.K.; Nxumalo, W.; Cukrowski, I. A REP‑FAMSEC Method as a Tool in Explaining Reaction Mechanisms: A Nucleophilic Substitution of 2‑Phenylquinoxaline as a DFT Case Study. Molecules 2021, 26, 1570. https://DOI.org/10.3390/molecules26061570.en_US
dc.identifier.issn1420-3049 (online)
dc.identifier.other10.3390/molecules26061570
dc.identifier.urihttps://repository.up.ac.za/handle/2263/87223
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rights© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.en_US
dc.subjectREP‑FAMSECen_US
dc.subjectONSHen_US
dc.subjectQuinoxalineen_US
dc.subjectNucleophilic additionen_US
dc.subjectHydrolysisen_US
dc.subjectOxidative nucleophilic substitution of hydrogen (ONSH)en_US
dc.titleA REP-FAMSEC method as a tool in explaining reaction mechanisms : a nucleophilic substitution of 2-phenylquinoxaline as a DFT case studyen_US
dc.typeArticleen_US

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