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15N NMR Spectroscopy, X-ray and Neutron Diffraction, Quantum-Chemical Calculations, and UV/vis-Spectrophotometric Titrations as Complementary Techniques for the Analysis of Pyridine-Supported Bicyclic Guanidine Superbases

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School of Chemical and Physical Sciences, Victoria University of Wellington, P.O. Box 600, Wellington 6012, New Zealand
Computational Organic Chemistry and Biochemistry Group, Ruder Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
§ Departamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, 28040 Madrid, Spain
Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain
Institute of Chemistry, University of Tartu, 14a Ravila Street, 50411, Tartu, Estonia
# Department of Chemistry, University of Canterbury, Christchurch 8041, New Zealand
Bragg Institute, Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2234, Australia
Cite this: J. Org. Chem. 2016, 81, 17, 7612–7625
Publication Date (Web):August 5, 2016
https://doi.org/10.1021/acs.joc.6b01330
Copyright © 2016 American Chemical Society

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    Abstract

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    Pyridine substituted with one and two bicyclic guanidine groups has been studied as a potential source of superbases. 2-{hpp}C5H4N (I) and 2,6-{hpp}2C5H3N (II) (hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) were protonated using [HNEt3][BPh4] to afford [I-H][BPh4] (1a), [II-H][BPh4] (2), and [II-H2][BPh4]2 (3). Solution-state 1H and 15N NMR spectroscopy shows a symmetrical cation in 2, indicating a facile proton-exchange process in solution. Solid-state 15N NMR data differentiates between the two groups, indicating a mixed guanidine/guanidinium. X-ray diffraction data are consistent with protonation at the imine nitrogen, confirmed for 1a by single-crystal neutron diffraction. The crystal structure of 1a shows association of two [I-H]+ cations within a cage of [BPh4] anions. Computational analysis performed in the gas phase and in MeCN solution shows that the free energy barrier to transfer a proton between imino centers in [II-H]+ is 1 order of magnitude lower in MeCN than in the gas phase. The results provide evidence that linking hpp groups with the pyridyl group stabilizes the protonation center, thereby increasing the intrinsic basicity in the gas phase, while the bulk prevents efficient cation solvation, resulting in diminished pKa(MeCN) values. Spectrophotometrically measured pKa values are in excellent agreement with calculated values and confirm that I and II are superbases in solution.

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    The Supporting Information is available free of charge on the ACS Publications Web site at DOI: XXXXXX. 1H, 13C, and 15N NMR spectra; computational details and atomic coordinates; a crystallographic information file (cif) containing X-ray diffraction data for 1a, 1b, 2, 3 and neutron diffraction data for 1a The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.6b01330.

    • 1H, 13C, and 15N NMR spectra; computational details and atomic coordinates; neutron diffraction data for 1a (PDF)

    • X-ray diffraction data for 1a,b, 2, and 3 (CIF)

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