dc.contributor.author	Sheehy, Kevin
dc.contributor.author	Bateman, Lorraine M.
dc.contributor.author	Flosbach, Niko T.
dc.contributor.author	Breugst, Martin
dc.contributor.author	Byrne, Peter A.
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	Irish Research Council	en
dc.contributor.funder	Verband der Chemischen Industrie	en
dc.date.accessioned	2020-08-05T14:23:54Z
dc.date.available	2020-08-05T14:23:54Z
dc.date.issued	2020-07-23
dc.date.updated	2020-08-04T01:03:32Z
dc.description.abstract	The preferred site of alkylation of diazine N-oxides by representative hard and soft alkylating agents was established conclusively using the 1H-15N HMBC NMR technique in combination with other NMR spectroscopic methods. Alkylation of pyrazine N-oxides (1 and 2) occurs preferentially on nitrogen regardless of the alkylating agent employed, while O-methylation of pyrimidine N-oxide (3) is favoured in its reaction with MeOTf. As these outcomes cannot be explained in the context of the hard/soft acid/base (HSAB) principle, we have instead turned to Marcus theory to rationalise these results. Marcus intrinsic barriers (∆G0‡) and ∆rG° values were calculated at the DLPNO-CCSD(T)/def2-TZVPPD/SMD//M06-2X-D3/6-311+G(d,p)/SMD level of theory for methylation reactions of 1 and 3 by MeI and MeOTf, and used to derive Gibbs energies of activation (∆G‡) for the processes of N- and O-methylation, respectively. These values, as well as those derived directly from the DFT calculations, closely reproduce the observed experimental N vs O selectivities for methylation reactions of 1 and 3, indicating that Marcus theory can be used in a semi-quantitative manner to understand how the activation barriers for these reactions are constructed. It was found that N-alkylation of 1 is favoured due to the dominant contribution of ∆rG° to the activation barrier in this case, while O-alkylation of 3 is favoured due to the dominant contribution of the intrinsic barrier (∆G0‡) for this process. These results are of profound significance in understanding the outcomes of reactions of ambident reactants in general.	en
dc.description.sponsorship	Irish Research Council (GOIPG Scholarship (IRC GOIPG/2018/1517)); Verband der Chemischen Industrie (Fonds der Chemischen Industrie (Liebig scholarship))	en
dc.description.status	Peer reviewed	en
dc.description.version	Accepted Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Sheehy, K., Bateman, L. M., Flosbach, N. T., Breugst, M. and Byrne, P. (2020) 'Competition Between N and O: Use of Diazine N-Oxides as a Test Case for the Marcus Theory Rationale for Ambident Reactivity', Chemical Science, doi: 10.1039/D0SC02834G	en
dc.identifier.doi	10.1039/D0SC02834G	en
dc.identifier.eissn	2041-6539
dc.identifier.endpage	136	en
dc.identifier.issn	2041-6520
dc.identifier.issn	x
dc.identifier.journaltitle	Chemical Science	en
dc.identifier.startpage	1	en
dc.identifier.uri	https://hdl.handle.net/10468/10357
dc.language.iso	en	en
dc.publisher	Royal Society of Chemistry	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Infrastructure Programme/15/RI/3221/IE/Process Flow Spectroscopy (ProSpect); Advanced Reaction Understanding using Flow Nuclear Magnetic Resonance (NMR) and Infrared (IR) Spectroscopies, with On-Line Ultra-Performance Liquid Chromatography (UPLC) and Mass Spectrometry (MS)/	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/	en
dc.relation.uri	https://pubs.rsc.org/en/Content/ArticleLanding/2020/SC/D0SC02834G
dc.rights	© The Royal Society of Chemistry 2020. Open Access. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.	en
dc.rights.uri	https://creativecommons.org/licenses/by/3.0/	en
dc.subject	Diazine N-oxides	en
dc.subject	Marcus theory	en
dc.subject	Alkylation	en
dc.title	Competition between N and O: use of diazine N-oxides as a test case for the Marcus theory rationale for ambident reactivity	en
dc.type	Article (peer-reviewed)	en

Competition between N and O: use of diazine N-oxides as a test case for the Marcus theory rationale for ambident reactivity

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