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Superbasicity of a Bis-guanidino Compound with a Flexible Linker: A Theoretical and Experimental Study
journal contribution
posted on 2023-06-08, 08:04 authored by Martyn P Coles, Pedro J Aragon-Saez, Sarah H Oakley, Peter B Hitchcock, Matthew G Davidson, Zvonimir B Maksic, Robert Vianello, Ivo Leito, Ivari Kaljurand, David C ApperleyThe bis-guanidino compound H2C{hpp}(2) (I; hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) has been converted to the monocation [I-H](+) and isolated as the chloride and tetraphenylborate salts. Solution-state spectroscopic data do not differentiate the protonated guanidinium from the neutral guanidino group but suggest intramolecular "-N-H center dot center dot center dot N=" hydrogen bonding to form an eight-membered C3N4H heterocycle. Solid-state CPMAS N-15 NMR spectroscopy confirms protonation at one of the imine nitrogens, although line broadening is consistent with solid-state proton transfer between guanidine functionalities. X-ray diffraction data have been recorded over the temperature range 50-273 K. Examination of the carbon-nitrogen bond lengths suggests a degree of "partial protonation" of the neutral guanidino group at higher temperatures, with greater localization of the proton at one nitrogen position as the temperature is lowered. Difference electron density maps generated from high-resolution X-ray diffraction studies at 110 K give the first direct experimental evidence for proton transfer in a poly(guanidino) system. Computational analysis of I and its conjugate acid [I-H](+) indicate strong cationic resonance stabilization of the guanidinium group, with the nonprotonated group also stabilized, albeit to a lesser extent. The maximum barrier to proton transfer calculated using the Boese-Martin for kinetics method was 2.8 kcal mol(-1), with hydrogen-bond compression evident in the transition state; addition of zero-point vibrational energy values leads to the conclusion that the proton transfer is barrierless, implying that the proton shuttles freely between the two nitrogen atoms. Calculations determining the gas-phase proton affinity and the pK(a) in acetonitrile both indicate that compound I should behave as a superbase. This has been confirmed by spectrophotometric titrations in MeCN using polyphosphazene references, which give an average pK(a) of 28.98 +/- 0.05. Triadic analysis indicates that the dominant term causing the high basicity is the relaxation energy.
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- Published
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Journal of the American Chemical SocietyISSN
0002-7863Publisher
American Chemical SocietyExternal DOI
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6Volume
131Page range
16858-16868Department affiliated with
- Chemistry Publications
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- No
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- Yes
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2012-02-06Usage metrics
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