Identification of Aminopyrimidine Regioisomers via Line Broadening Effects in 1H and 13C NMR Spectroscopy
James Garner A , Tim Hill A , Luke Odell A , Paul Keller B , Jody Morgan B and Adam McCluskey A CA Chemistry, School of Environmental and Life Sciences, University of Newcastle, Callaghan NSW 2308, Australia.
B Department of Chemistry, University of Wollongong, Wollongong NSW 2522, Australia.
C Corresponding author: Email: Adam.McCluskey@newcastle.edu.au
Australian Journal of Chemistry 57(11) 1079-1083 https://doi.org/10.1071/CH03316
Submitted: 12 December 2003 Accepted: 8 June 2004 Published: 1 November 2004
Abstract
Substituted mono- and diamino-pyrimidines were synthesized as part of our medicinal chemistry programmes. Primary amines substituted at the 4-position exhibited room-temperature line broadening effects in both 1H and 13C NMR spectroscopy due to the presence of rotamers, but these effects were not observed for substituents in the 2-position. This provided a simple diagnostic tool for the identification of regioisomers, a determination which would otherwise have required two-dimensional experiments.
* We have previously reported the experimental details for compounds A–D, 1–3, 5–7, 20–25, 27–33, 39, and 40. The experimental details for all other compounds may be found in the Accessory Materials.
† Assignment of C2 or C4 substituents were confirmed by HMBC and HMQC experiments, and in all instances confirmed the above assignments based on line broadening effects.
‡ Coalescence temperature, for the purpose of qualitative analysis, is reported as the temperature at which coalescence is actually observed; that is, a very low, broad baseline hump is observed. Alternatively, Tc is estimated by extrapolating between the two measurements at which it occurred.
§ Compounds were geometry-optimized using the Møller–Plesset function at MP2 level of theory. Conformer distributions were calculated using molecular mechanics at the MMFF level of theory. Compounds were rotated by 30º increments for all available torsion points of the C(aryl)–N bond of the amine substituent. The program allowed for a maximum of 20000 conformations and a maximum ΔE of 100 kJ mol−1 difference. Conformations that had similar energies and van der Waals overlap were treated as identical by the programme, which reduced the set of ‘unique’ conformers reported. Each conformer can be regarded as representative of a number of conformations with the same energy and similar structural space.
Acknowledgments
This work was supported by the National Health and Medical Research Council. J.G. and L.O. also thank the University of Newcastle for financial support.
[1]
R. Marek,
A. Lycka,
Curr. Org. Chem. 2002, 6, 35.
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
