Migrating 1H NMR peaks in the benzylation of adenine reveal the disruptive Kornblum oxidation in DMSO

dc.contributor.authorBuyens, Dominique Marie-Jeanne Solange
dc.contributor.authorPilcher, Lynne A.
dc.contributor.emaillynne.pilcher@up.ac.zaen_US
dc.date.accessioned2024-03-25T06:29:45Z
dc.date.available2024-03-25T06:29:45Z
dc.date.issued2023-10
dc.descriptionDATA AVAILABILITY STATEMENT : The data that support the findings of this study are available from the corresponding author upon reasonable request.en_US
dc.description.abstractThe alkylation of adenine using alkyl halides under basic conditions in dimethyl sulfoxide (DMSO), a common reaction to achieve N9-alkylated adenine derivatives, is often low yielding with unreacted adenine and complicated reaction mixtures. Herein, we report the reaction monitoring of the alkylation of adenine in DMSO in the presence of NaH using benzylic halides via realtime 1H NMR spectroscopy. NMR analysis revealed that under these generally used reaction conditions, the adeninate anion starting material is protonated as the anionic nucleophile abstracts a labile proton from an alkoxy sulfonium ion intermediate formed via the Kornblum oxidation reaction. To prevent the protonation of the adeninate anion, the reaction was performed in the presence of a mop-up base DBU. Simultaneously increasing the concentration of the alkyl halide and the mop-up base in a 1:1 ratio resulted in a complete reaction; however, increasing the temperature of the reaction promoted depletion of the starting material by protonation and hence reduced conversion to products. This result implies that heating of such electrophiles in DMSO should be avoided. The addition of a mop-up base can help resolve the complication of protonation arising from the Kornblum oxidation reaction in alkylation reactions under similar conditions.en_US
dc.description.departmentChemistryen_US
dc.description.librarianam2024en_US
dc.description.sdgNoneen_US
dc.description.sponsorshipThe National Research Foundation of South Africa and the Scarce Skills Doctoral Scholarship.en_US
dc.description.urihttps://onlinelibrary.wiley.com/journal/19435193en_US
dc.identifier.citationBuyens, D.M.S. & Pilcher, L.A. 2023, 'Migrating 1H NMR peaks in the benzylation of adenine reveal the disruptive Kornblum oxidation in DMSO', Journal of Heterocyclic Chemistry, vol. 60, no. 10, pp. 1760-1767, doi : 10.1002/jhet.4718.en_US
dc.identifier.issn0022-152X (print)
dc.identifier.issn1943-5193 (online)
dc.identifier.other10.1002/jhet.4718
dc.identifier.urihttp://hdl.handle.net/2263/95328
dc.language.isoenen_US
dc.publisherWileyen_US
dc.rights© 2023 The Authors. Journal of Heterocyclic Chemistry published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License.en_US
dc.subjectKornblum oxidationen_US
dc.subjectDimethyl sulfoxide (DMSO)en_US
dc.subject1H NMR spectroscopyen_US
dc.subject1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)en_US
dc.subjectNuclear magnetic resonance (NMR)en_US
dc.titleMigrating 1H NMR peaks in the benzylation of adenine reveal the disruptive Kornblum oxidation in DMSOen_US
dc.typeArticleen_US

Files

Original bundle

Now showing 1 - 2 of 2
Loading...
Thumbnail Image
Name:
Buyens_Migrating_2023.pdf
Size:
3.94 MB
Format:
Adobe Portable Document Format
Description:
Article
Loading...
Thumbnail Image
Name:
Buyens_MigratingSuppInfo_2023.pdf
Size:
588.68 KB
Format:
Adobe Portable Document Format
Description:
Supporting Information

License bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description: