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

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.

本研究以连有一个及两个双环胍基的吡啶类化合物作为潜在超强碱源展开探究。将2-{hpp}C5H4N（化合物I）与2,6-{hpp}2C5H3N（化合物II，其中hppH=1,3,4,6,7,8-六氢-2H-嘧啶并[1,2-a]嘧啶）采用三乙基铵四苯基硼酸盐([HNEt3][BPh4])进行质子化反应，分别得到[I-H][BPh4]（1a）、[II-H][BPh4]（2）及[II-H2][BPh4]2（3）。溶液态1H及15N核磁共振波谱表征显示，化合物2的阳离子具有对称结构，表明其在溶液中存在快速质子交换过程。固态15N核磁共振数据可区分两种胍基单元，证明其为胍/胍鎓混合结构。X射线衍射数据与亚胺氮原子位点的质子化结果相符，该结论已通过单晶中子衍射在化合物1a中得到验证。化合物1a的晶体结构表明，两个[I-H]+阳离子被包裹在[BPh4]-阴离子构成的笼状结构中。分别在气相与乙腈(MeCN)溶剂中开展的计算分析显示，[II-H]+中亚胺中心间的质子转移自由能垒，在乙腈溶剂中比气相环境低一个数量级。本研究结果证实，将hpp基团与吡啶环相连可稳定质子化中心，进而提升气相中的固有碱性；但庞大的取代基团会阻碍阳离子的有效溶剂化，导致其乙腈相中的pKa值降低。分光光度法测得的pKa值与计算结果高度吻合，同时验证了化合物I与II在溶液中属于超强碱。