Superbasicity of a Bis-guanidino Compound with a Flexible Linker: A Theoretical and Experimental Study

Abstract

The bis-guanidino compound H(2)C{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...N=" hydrogen bonding to form an eight-membered C(3)N(4)H heterocycle. Solid-state CPMAS (15)N 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.

Exceptional Superbasicity of Bis(guanidine) Proton Sponges Imposed by the Bis(secododecahedrane) Molecular Scaffold: A Computational Study

“…Partial protonation is indicated again in the neutral guanidine moiety of 18H + (ΔЈ CN = 0.034 Å). Finally, the larger ρ value [15,29] for the protonated guanidine group is consistent with more efficient delocalization (97.6 %, i.e. the C=N bond length is equal to 97.6 % of the average C-NR 2 bond length; in fully symmetrical guanidinium cations ρ = 1.00).…”

“…In the bis(secododecahedrane) proton sponges studied, relatively strong IMHB is present (for published diamines, the IMHB contribution to the APA is within the values of 10-27 kcal mol -1 ). [15,13] This fact is corroborated by effective stabilization upon protonation, which is associated with the linearity of their IMHB [i.e. α(N-H + ···N) angles].…”

“…The Δ CN value of the second, formally neutral guanidino group in 18H + is also smaller than that of the fully localized system 18 (Δ CN = 0.091), which is consistent with some degree of delocalization attributed to the partial protonation of this moiety. The ΔЈ CN value [15] (contribution of the lone pairs of the imidazolidinylidene N 1 and N 3 atoms to the overall bonding) for the protonated guanidine group of 18H + (ΔЈ CN = 0.015 Å) indicates a relatively low degree of lone-pair delocalization from the tertiary nitrogen atom. The ΔЈ CN value is reduced for both guanidine moieties, as compared to neutral 18 (0.052 Å).…”

“…A less effective proton sponge was found to be bis(triazabicyclo[4.4.0]dec-1-ene) compound 17 (PA = 270.6 kcal mol -1 , obtained by the B3LYP/6-311+G**// B3LYP/6-31G* model). [15] The aim of this computational study was to design novel bis(guanidine) superbase systems with enhanced basicity. For this purpose, we examined the basicity properties of a series of bis(guanidines) 18-46 possessing a bis(secododecahedrane) molecular framework, substituted at 3-syn,13-syn-positions with a (1,3-dimethylimidazolin-2-ylidene)-amino group (Scheme 3).…”

Proton Affinities of Organocatalysts Derived from Pyridine N-oxide

“…One can either conceive molecules with a potential of very efficient delocalization of the positive charge over a large molecular scaffold or alternatively, molecules with more than one highly basic functions cooperating in binding of the proton can be considered. As an example of the first approach, the phenylene bis-guanidines developed by Z. Maksić and coworkers [6][7][8][9][10][11] can be mentioned. A prototypical representative of the second group is N,N,N′,N′-tetramethyl-1,8-naphthalenediamine, conveniently denoted as proton sponge.…”