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Nitriles with exceptionally high proton affinity due to a C–N bond formation upon protonation
In this review, the principles of gas-phase proton basicity measurements and theoretical calculations are recalled as a reminder of how the basicity PA/GB scale, based on Brønsted–Lowry theory, was constructed in the gas-phase (PA—proton affinity and/or GB—gas-phase basicity in the enthalpy and Gibbs energy scale, respectively). The origins of exceptionally strong gas-phase basicity of some organic nitrogen bases containing N-sp3 (amines), N-sp2 (imines, amidines, guanidines, polyguanides, phosphazenes), and N-sp (nitriles) are rationalized. In particular, the role of push–pull nitrogen bases in the development of the gas-phase basicity in the superbasicity region is emphasized. Some reasons for the difficulties in measurements for poly-functional nitrogen bases are highlighted. Various structural phenomena being in relation with gas-phase acid–base equilibria that should be considered in quantum-chemical calculations of PA/GB parameters are discussed. The preparation methods for strong organic push–pull bases containing a N-sp2 site of protonation are briefly reviewed. Finally, recent trends in research on neutral organic superbases, leaning toward catalytic and other remarkable applications, are underlined.
This work extends our earlier quantum chemical studies on the gas-phase basicity of very strong N-bases to two series of nitriles containing the methylenecyclopropene and cyclopropenimine scaffolds with dissymmetrical substitution by one or two electron-donating substituents such as Me, NR2, N=C (NR2)2, and N=P (NR2)3, the last three being strong donors. For a proper prediction of their gas-phase base properties, all potential isomeric phenomena and reasonable potential protonation sites are considered to avoid possible inconsistencies when evaluating the energetic parameters and associated protonation or deprotonation equilibria B + H+ = BH+. More than 250 new isomeric structures for neutral and protonated forms are analyzed. The stable structures are selected and the favored ones identified. The microscopic (kinetic) gas-phase basicity parameters (PA and GB) corresponding to N sites (cyano and imino in the cyclopropenimine or in the substituents) in each isomer are calculated. The macroscopic (thermodynamic) PAs and GBs, referring to the isomeric mixtures of favored isomers, are also estimated. The total (pushing) substituent effects are analyzed for monosubstituted and disubstituted derivatives containing two identical or two different substituents. Electron delocalization is examined in the two π–π conjugated transmitters, the methylenecyclopropene and cyclopropenimine scaffolds. The aromatic character of the three-membered ring is also discussed.
Ionization of organic compounds with different structural and energetic properties including benzene derivatives, polycyclic aromatic hydrocarbons (PAHs), ketones, and polyenes was studied using a commercial atmospheric pressure corona discharge (APCI) ion source on a drift tube ion mobility-quadrupole-time-of-flight mass spectrometer (IM-QTOFMS). It was found that the studied cohort of compounds can be experimentally ionized via protonation, charge transfer, and hydride abstraction leading to formation of [M + H]+, [M]+•, and [M - H]+ species, respectively. By experimentally monitoring the product ions and comparing the thermodynamic data for different ionization paths, it was proposed that NO+ is one of the main reactant ions (RIs) in the ion source used. Of particular focus in this work were theoretical and experimental studies of the effect of solvents frequently used for analytical applications with this ion source (acetonitrile, methanol, and chloroform) on the ionization mechanisms. In methanol, the studied compounds were observed to be ionized mainly via proton transfer while acetonitrile suppressed the protonation of compounds and enhanced their ionization via charge transfer and hydride abstraction. Use of chloroform as a solvent led to formation of CHCl2+ as an alternative reactant ion (RI) to ionize the analytes via electrophilic substitution. Density functional theory (DFT) was used to study the different paths of ionization. The theoretical and experimental results showed that by using only the absolute thermodynamic data, the real ionization path cannot be determined and the energies of all competing processes such as charge transfer, protonation, and hydride abstraction need to be compared.
The gas-phase basicity of nitriles can be enhanced by a push–pull effect. The role of the intercalated scaffold between the pushing group (electron-donor) and the pulling (electron-acceptor) nitrile group is crucial in the basicity enhancement, simultaneously having a transmission function and an intrinsic contribution to the basicity. In this study, we examine the methylenecyclopropene and the N-analog, cyclopropenimine, as the smallest cyclic π systems that can be considered for resonance propagation in a push–pull system, as well as their derivatives possessing two strong pushing groups (X) attached symmetrically to the cyclopropene scaffold. For basicity and push–pull effect investigations, we apply theoretical methods (DFT and G2). The effects of geometrical and rotational isomerism on the basicity are explored. We establish that the protonation of the cyano group is always favored. The push–pull effect of strong electron donor X substituents is very similar and the two π-systems appear to be good relays for this effect. The effects of groups in the two cyclopropene series are found to be proportional to the effects in the directly substituted nitrile series X–C≡N. In parallel to the basicity, changes in electron delocalization caused by protonation are also assessed on the basis of aromaticity indices. The calculated proton affinities of the nitrile series reported in this study enrich the gas-phase basicity scale of nitriles to around 1000 kJ mol−1.
Substituted tetrahedranes offer exceptional carbon bases with the gas‐phase proton affinities (PAs) up to 356 kcal mol⁻¹, due to the strain‐induced ring opening upon protonation. Additional tetrahedrane moieties exert a dramatic basicity amplification to PAs reaching 600 kcal mol⁻¹, being the strongest organic superbases reported, clearly surpassing the proposed limit of achievable basicities (Angew. Chem. Int. Ed. 2015, 54, 9262). However, because protonation/deprotonation of these compounds is not reversible, PAs of the opened‐cage isomers were calculated which were lower than the basiciy limit.
Density functional theory (DFT) is a widely used methodology for the computation of molecular and electronic structure, and we confirm that B3LYP and the high-level ab initio G3B3 method are in excellent agreement for the lowest-energy isomers of the 16 glucose epimers. Density-functional tight-binding (DFTB) is an approximate version of DFT with typically comparable accuracy that is 2 to 3 orders of magnitude faster, therefore generally very suitable for processing large numbers of complex structures. Conformational isomerism in sugars is well known to give rise to a large number of isomer structures. On the basis of a comprehensive study of glucose epimers in vacuo and aqueous solution, we found that the performance of DFTB is on par to B3LYP in terms of geometrical parameters excluding hydrogen bonds and isomer energies. However, DFTB underestimates both hydrogen bonding interactions as well as torsional barriers associated with rotations of the hydroxy groups, resulting in a counterintuitive overemphasis of hydrogen bonding in both gas phase as well as in water. Although the associated root mean squared deviation from B3LYP within epimer isomer groups is only on the order of 1 kcal/mol, this deviation affects the correct assignment of major isomer ordering, which span less than 10 kcal/mol. Both second- as well as third-order DFTB methods are exhibiting similar deviations from B3LYP. Even after the inclusion of empirical dispersion corrections in vacuum, these deviations remain for a large majority of isomer energies and geometries when compared to dispersion-corrected B3LYP.
Effects of the pushing groups (electron donors) for nitriles increase as follows: H2N < H2N-N=N < H2N-CH=CH < H2N-CH=N < (H2N)(2)C=CH < (H2N)(2)C=N < (H2N)(3)P=N. The G2(MP2)-calculated PA(N-cyano) for (H2N)(2)C=N-C equivalent to N and (H2N)(3)P=N-C equivalent to N are larger than that of HC equivalent to N by 186 and 250 kJ mol(-1), respectively. The hypothesis of protonation in the gas phase at the N-imino and N-amino atoms, corresponding respectively to PAs weaker by 30 and 70 kJ mol(-1) than that of the N-cyano site, can be rejected.
The basicity of Verkade's superbase (12) in MeCN solution is considered by a quite accurate theoretical model. It is shown that the corresponding pKa value is 29.0. Hence, its basicity is comparable or higher than that of some other P1 phosphazenes, but it is lower than the basicity of P2 phosphazenes. Structural characteristics of Verkade's superbase and its conjugate acid, as well as the origin of its pronounced basicity, are briefly discussed. Extended Verkade's superbase 13 and some Janus-type phosphazenes are examined too. It is shown that they are very good candidates for even stronger neutral organic superbases. A very useful by-product of the present study are quite accurate estimates of the gas phase proton affinities of some P1, P2, P3 and P4 polyaminophosphazenes obtained by the B3LYP/6-311+G(2df,p)//B3LYP/6-31G* scheme. The latter was successfully tested against G2 results on small molecules. This is of importance, because the experimentally measured gas phase values for phosphazenes are not available, implying that the theoretical data fill this gap with reliable information.
Seventeen superbasic phosphazenes and two Verkade's bases were used to supplement and extend the experimental gas-phase basicity scale in the superbasic region. For 19 strong bases the gas-phase basicity values (GB) were determined for the first time. Among them are such well-known bases as BEMP (1071.2 kJ/mol), Verkade's Me-substituted base (1083.8 kJ/mol), Et-N=P(NMe2)2-N=P(NMe2)3 (Et-P2 phosphazene, 1106.9 kJ/mol), and t-Bu-N=P(NMe2)3 (t-Bu-P1 phosphazene, 1058.0 kJ/mol). For the first time experimental GB values were determined for P2 phosphazenes. Together with our previous results self-consistent experimental gas-phase basicity scale between 1020 and 1107 kJ/mol is now established. This way an important region of the gas-phase basicity scale, which was earlier dominated by metal hydroxide bases, is now covered also with organic bases making it more accessible for further studies. The GB values for several superbases were calculated using density functional theory at the B3LYP/6-311+G** level. For the phosphazene family the standard deviation of the correlation between the experimental and theoretical values was 6.5 kJ/mol.
Proton affinities (PA) and gas phase basicities (GB) of novel structure of non-ionic organic superbases on the basis of guanidine embedded imidazole framework, were computed at B3LYP/6-311+G(d,p) level of theory. The used logic for designing these structures is synergistic effect of guanidine-imidazole twin in order to aromatization and subsequent stabilization of imidazole ring upon protonation which is strengthen with push-pull effect of variety electron-donating groups on the five-membered ring. This strategy caused to the design of organobases with considerable basicity in the range of 985.39–1177.68 kJ mol⁻¹. Majority of the designed structures show the PA values more than 1028 kJ mo1⁻¹, as the threshold of superbasicity. The HOMA/HOMED, and NICS(1)zz analyses were used for each structure and its conjugated acid in order to better understand and discuss the basicity values.
The organic superbase catalyst t-Bu-P4 achieves nucleophilic aromatic substitution of methoxyarenes with alkanenitrile pronucleophiles. A variety of functional groups [cyano, nitro, (non)enolizable ketone, chloride, and amide moieties] are allowed on methoxyarenes. Moreover, an array of alkanenitriles with/without an aryl moiety at the nitrile α-position can be employed. The system also features no requirement of a stoichiometric base, MeOH (not salt waste) formation as a byproduct, and the production of congested quaternary carbon centers.
There are several classes of organic superbases whose basicity increases because of the formation of intramolecular hydrogen bond or/and of enhancement of electron delocalization in their protonated structures. In this work, effects of these two factors on the basicity of π-π and n-π conjugated nitrogen bases (mainly imines) are studied theoretically using the B3LYP/6-311++G(d,p) method. Comparison of proton affinities (PA) and gas phase basicities (GB) of investigated bases shows that change of electron delocalization after protonation in one ring enhances PA even by 30-40 kcal mol⁻¹. Comparison of PAs of some proton sponges and “proton sponge-like” structures reveals that formation of a single hydrogen bond enhances PA by about 10 kcal mol⁻¹. During this work, a large number of new superbases were designed and their basicities were assessed in the gas phase (with PA between 270 and 295 kcal mol⁻¹) and acetonitrile (with pKa between 30 and 40).
With the synthesis of N,N',N″,N‴-tetrakis(3-(dimethylamino)propyl)triaminophosphazene (TDMPP, 1), we present the first phosphazene superbase with enhanced basicity through the effect of multiple intramolecular hydrogen bonding (IHB). Due to intramolecular solvation of four NH protons, the proton affinity is even higher than that of second-order phosphazene (dma)P2-tBu. X-ray structural proof, NMR titration experiments, and computational investigations provide a more detailed quantitative description of the IHB influence on the superbasicity of 1 in solid-state, solution, and the gas-phase.
We describe the catalytic amination of β-(hetero)arylethyl ethers with amines using the organic superbase t-Bu-P4 to obtain β-(hetero)arylethylamines. The reaction has a broad substrate scope and allows the transformations of electron-deficient and electron-neutral β-(hetero)arylethyl ethers with various amines including pyrrole, N-alkylaniline, diphenylamine, aniline, indole, and indoline derivatives. Mechanistic studies indicate a two-reaction pathway of MeOH elimination from the substrate to form a (hetero)arylalkene followed by the hydroamination of the alkene.
Proton affinities (PA) and gas phase basicities (GB) of epoxide and episulfide derivatives with 2–6 carbon atoms were computed at the B3LYP/6-311++G(d,p) level of theory. These simple derivatives did not undergo ring opening upon protonation and their PAs were lower than 880 kJ mol⁻¹. The PAs of the episulfides were higher than those of the corresponding epoxides. By substitution of strong electron donating groups such as phosphazene and guanidine, we stimulated ring opening upon protonation. This strategy led in designing of compounds with exceptional superbasicity of oxygen and sulfur sites. The calculated PAs were in the range of 1000–1200 kJ mol⁻¹.
Proton sponges are polyamines with high proton affinity that enable gentle deprotonation of even mildly acidic compounds. In this study, the concept of proton sponges as signal enhancing dopants for electrospray ionisation is presented for the first time. 1,8-Bis(dimethylamino)naphthalene (DMAN) and 1,8-bis(tetramethylguanidino)naphthalene (TMGN) were chosen as dopants, using methanol and acetonitrile/methanol as solvents. Individual standard compounds, compound mixtures and a diesel fuel as a complex sample matrix were investigated. Both proton sponges enhanced signal intensities in electrospray ionisation negative mode, but TMGN decomposed rapidly in methanolic solution. Significantly higher signals were only achieved using the acetonitrile/methanol mixture. On average a more than 10-fold higher signal intensity was measured with 10(-3 )mol l(-1) DMAN concentration. A stronger signal increase of alcohol functionalities was observed compared to acid functionalities. All compound classes which were detected in the diesel fuel (CH- and CHOx-class) received roughly 100-fold higher signal intensities when using DMAN as a dopant. Furthermore, the number of detected compounds as well as the double bond equivalent of the detected compounds increased. The compound class distribution shifted when adding DMAN and the formerly dominant CHO2-, CHO3-, and CHO4- classes received similar relative intensities as formerly less accessible classes. The findings depict DMAN as a promising additive for electrospray ionisation negative analysis of at least mildly acidic compounds, even within complex sample material.
A new class of superbases was designed using cycloheptatriene derivatives and their basicities were assessed theoretically by B3LYP/6-311++G(d,p) method in gas phase. The superbasicity of these compounds is due to formation of an aromatic 7-membered ring upon protonation which stabilizes the protonated structure. Other fragments such as guanidine and phosphazene groups were also added to these compounds to enhance their basicities. The computed proton affinities (PA) for these superbases were 245-288 kcal/mol. Cycloheptatriene was also used in the design of some proton sponges to increase their basicities. The computed PAs of the proton sponges were 256-279 kcal/mol.
Nitrogen bases containing one or more pushing amino-group(s) directly linked to a pulling cyano, imino, or phosphoimino group, as well as those in which the pushing and pulling moieties are separated by a conjugated spacer (C═X)n, where X is CH or N, display an exceptionally strong basicity. The n-π conjugation between the pushing and pulling groups in such systems lowers the basicity of the pushing amino-group(s) and increases the basicity of the pulling cyano, imino, or phosphoimino group. In the gas phase, most of the so-called push-pull nitrogen bases exhibit a very high basicity. This paper presents an analysis of the exceptional gas-phase basicity, mostly in terms of experimental data, in relation with structure and conjugation of various subfamilies of push-pull nitrogen bases: nitriles, azoles, azines, amidines, guanidines, vinamidines, biguanides, and phosphazenes. The strong basicity of biomolecules containing a push-pull nitrogen substructure, such as bioamines, amino acids, and peptides containing push-pull side chains, nucleobases, and their nucleosides and nucleotides, is also analyzed. Progress and perspectives of experimental determinations of GBs and PAs of highly basic compounds, termed as "superbases", are presented and benchmarked on the basis of theoretical calculations on existing or hypothetical molecules.
The basicity of cyclopropenimines (CPIs) and cyclopropenimino-based proton sponges is investigated by means of densityfunctional theory (DFT) calculations and for the first time directly compared with the basicity of phosphazenes. It is foundthat CPIs are more basic than the corresponding phosphazenes in the gas phase. Proton sponges based on CPI as pincer li-gands also possess higher or at least the same gas-phase proton affinity as proton sponges based on phosphazenes. How-ever, in comparison with phosphazenes, CPI-based pincer ligands possess greater conformational flexibility, which enablesalmost complete avoidance of nitrogen lone pairs. This leads to the substantially smaller destabilization of neutral base inCPI proton sponges. Utilizing homodesmotic reactions, we have shown that significant contribution to the proton affinityof CPI proton sponges is an electron-donating effect of the second CPI substituent, whereas only a smaller portion of the sta-bilization energy should be attributed to intramolecular hydrogen bond. Further, it was shown that tetrasubstituted CPInaphthalenes possess very low ionization potential, which qualifies them as very strong electron donors. Finally, utilizingcyclopropenimino substituents, it was found that theoretical gas basicity limit of 370kcal mol1recently calculated by Leitoand coworkers could be extended beyond 370kcal mol1in a case of cyclopropenimino phosphorus carbenes andcylopropenimino phosphorus ylides
Cyclopropenimine as pincer ligand and strong electron donor in proton sponges: Cyclopropenimine as Pincer Ligand and Strong Electron Donor in Proton Sponges. Available from: https://www.researchgate.net/publication/303373506_Cyclopropenimine_as_pincer_ligand_and_strong_electron_donor_in_proton_sponges_Cyclopropenimine_as_Pincer_Ligand_and_Strong_Electron_Donor_in_Proton_Sponges [accessed Jun 25, 2016].
Experimental gas-phase superbasicity scale spanning 20 orders of magnitude and ranging from bicyclic guanidine 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene to triguanidinophosphazenes and P3 phosphazenes is presented together with solution basicity data in acetonitrile and tetrahydrofuran. The most basic compound in the scale-triguanidinophosphazene Et-N═P[N═C(NMe2)2]3-has the highest experimental gas-phase basicity of an organic base ever reported: 273.9 kcal mol(-1). The scale includes besides the higher homologues of classical superbasic phosphazenes and several guanidino-substituted phosphazenes also a number of recently introduced bisphosphazene and bis-guanidino proton sponges. This advancement was made possible by a newly designed Fourier transform ion cyclotron resonance (ICR) mass spectrometry setup with the unique ability to generate and control in the ICR cell sufficient vapor pressures of two delicate compounds having low volatility, which enables determining their basicity difference. The obtained experimental gas-phase and solution basicity data are analyzed in terms of structural and solvent effects and compared with data from theoretical calculations.
DFT calculations have been performed for a series of push-pull nitriles [(R2N)n(X=Y)iCN, where i = 0, 1, or 2, n = 1, 2, or 3, R2N = H2N, Me2N, or C4H8N]. The possible protonation N-sites (N-cyano, N-imino, and N-amino) have been examined and their proton affinities (PA) estimated. For all compounds in the series, even for those containing the guanidino, phosphazeno, and diphosphazeno pushing groups, the N-cyano atom is the favored site of protonation. The n-π conjugation strongly decreases the PA value of the pushing amino group in favor of the pulling cyano one. Nitriles with the phosphazeno groups [(R2N)3P=NP(R2N)2=N and (R2N)3P=N] exhibit the strongest basicity in the series. Some of them (with PA > 1000 kJ mol-1) are stronger bases than DMAN, the so called "Proton Sponge". Nitriles bearing the guanidino group [(R2N)2C=N] are less basic than those with the phosphazeno group [(R2N)3P=N] but more basic than those with the formamidino group (R2NCH=N) containing the same substituent R. The N-imino atoms, present in the transmitter group (X=N), display PA values lower than those of the N-cyano site by more than 30 kJ mol-1. When proceeding from the unsubstituted derivatives (R = H) to the methylated ones (R = Me), the Me groups at the N-amino atom increase the PA value of the N-cyano site for Me2NX=YCN by ca. 30-60 kJ mol-1. For the guanidino and phosphazeno derivatives containing two and three amino groups, respectively, this effect is not additive. The four Me groups for (Me2N)2C=NCN and the six Me groups for (Me2N)3P=NCN increase the PA(N-cyano) values by only 30-50 kJ mol-1. The CN bond lengths of the neutral forms are well correlated with the PA(N-cyano) values.
The potential limits of superbasicity achievable with different families of neutral bases by expanding the molecular framework are explored using DFT computations. A number of different core structures of non-ionic organosuperbases are considered (such as phosphazenes, guanidinophosphazenes, guanidino phosphorus ylides). A simple model for describing the dependence of basicity on the extent of the molecular framework is proposed, validated, and used for quantitatively predicting the ultimate basicities of different compound families and the rates of substituent effect saturation. Some of the considered bases (guanidino phosphorus carbenes) are expected to reach gas-phase basicity around 370 kcal mol(-1) , thus being the most basic neutral bases ever reported. Also, the classical substituted alkylphosphazenes were predicted to reach pKa values of around 50 in acetonitrile, which is significantly higher than previously expected.
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New structural motives for organosuperbases, that are easy to prepare and highly basic are urgently required in many areas of chemistry. The synthesis of N,N'-bis(imidazolyl)guanidine bases (BIG bases) is reported. Their pKα values are determined as 26.1-29.3 in THF. They are thus probably the strongest known phosphorous-free organic bases both in solution and in the gas phase. Calculations help to determine the structural and electronic factors giving rise to the high basicity.
The available data on gas phase basicities and proton affinities of molecules are compiled and evaluated. Tables giving the molecules ordered (1) according to proton affinity and (2) according to empirical formula, sorted alphabetically are provided. The heats of formation of the molecules and the corresponding protonated species are also listed.
Systematic studies of very strong neutral acids and very strong neutral bases have been performed in the gas phase during the last decade. In the case of organic systems, the current upper limit of the basicity scale is now not very far from the current lower limit of the acidity scale. The gap between the proton affinity (PA) of the strongest organic suberbase and the deprotonation enthalpy (DPE) of the strongest organic superacid is only ca. 100 kJ mol-1. The PA predicted for phosphazenes fills up this gap between the two scales. Inorganic oxides and mineral acids have also PAs and DPEs in this range. Therefore, a spontaneous proton transfer in the gas phase between neutral superacids and neutral superbases may be envisioned.
The basicities of a large number of organic bases and superbases, including nitrogen basic centers in various chemical environments occurring in phosphazenes, amidines, amines, anilines and pyridines, have been studied in acetonitrile by the isodensity polarized continuum model employing two DFT computational schemes differing in the basis sets for final single-point calculations. It turned out that the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) method serves the purpose giving good agreement for basicities with experiment for both gas phase and acetonitrile solutions treating widely different bonding situations of basic nitrogen atoms on an equal footing. An attempt is made to correlate the experimental pKa(MeCN) values with the proton affinities (PA) in MeCN. The results are less accurate than those achieved by using basicities in acetonitrile. In particular, the PA(MeCN)s frequently failed in reproducing the pKa(MeCN) values in systems possessing multiple intramolecular hydrogen (IMH) bonds formed via corona effects. In such cases the use of basicities is mandatory instead. A useful corollary of these calculations on systems with multiple IMH bonds is that comparison of the theoretical and experimental pKa values can provide an insight into the structure of the most stable conformations in solutions.
The available data on gas-phase basicities and proton affinities of approximately 1700 molecular, radical and atomic neutral species are evaluated and compiled. Tables of the data are sorted (1) according to empirical formula and (2) according to evaluated gas basicity. This publication constitutes an update of a similar evaluation published in 1984.
We describe several improvements to the reaction field model for the ab initio determination of solvation effects. First, the simple spherical cavity model is expanded to include higher-order electrostatic interactions. Second, two new and efficient implementations of the polarizable continuum model (PCM) are described, which allow a more realistic specification of the solute cavity as well as infinite-order electrostatics. Electron correlation effects are evaluated using the B3LYP density functional and Möller−Plesset perturbation theory to second order. An assessment of the importance of these various factors is made by comparing theoretical results to the experimentally known conformational equilibrium between syn and anti forms of furfuraldehyde and the C−C rotational barrier of (2-nitrovinyl)amine. Comparisons are also made with calculations that employ an ellipsoidal cavity with sixth-order electrostatics. Optimization using a simple Onsager model appears to be sufficient to evaluate the important geometry changes in solution. Energies obtained from the spherical and ellipsoidal cavity models often exhibit poor convergence in the truncated electrostatic series. Correlation to experiment is much improved when an infinite-order PCM method is used.
A density functional theory (B3LYP/6-311+G**), ab initio (HF/3-21G*), and semiempirical (PM3) study of intrinsic basicities, protonation energies, or protonation enthalpies of organic phosphorus imine (iminophosphorane) including phosphazene, phosphorus ylide (phosphorane), and phosphine superbases has been performed. The study shows that representatives of the first two classes of the above-mentioned organic superbases can reach the basicity level of the strongest inorganic superbases such as alkali-metal hydroxides, hydrides, and oxides. The strongest organic phosphazene imine superbases are predicted to reach the gas-phase basicity level of ca. 300 kcal/mol (number of phosphorus atoms in the system n ≥ 7), whereas the strongest organic phosphazene ylide superbases are estimated to have (at n ≥ 5) gas-phase basicities around or beyond 310−320 kcal/mol. The phosphine superbases, including the Verkade's bicyclic phosphines (proazaphosphatranes) are predicted to have a basicity comparable to P2 phosphazenes or P1 phosphorus ylides, whereas the respective proazaphosphatrane imines and ylides are expected to be the strongest organic superbases which contain only a single phosphorus atom. Extremely high expected basicity values and handling preferences over inorganic superbases make representatives of novel organic superbases possible partners for observing the spontaneous gas-phase proton transfer between neutral Brønsted superacids and -bases. For the comparison, the basicities of some alkali-metal substituted ammonia, phosphine, phosphorus, and nitrogen ylides and imines have been also calculated.
The gas-phase basicities of N-methyl substituted 1,8-diaminonaphthalenes and several related compounds were determined by measurement of proton transfer equilibria (1), B1 H+ + B2 = B1 + B2H+, with a high-pressure mass spectrometer. The gas-phase basicity ladder obtained through continuous equilibria (1) extends over a 30 kcal/mol interval from methylamine to 1,8-bis(dimethylamino)naphtha!ene. The results indicated that ring protonation in m-phenylenediamine and 1-aminonaphthalene leads to a more stable ion than N-protonation. The 1,8-diaminonaphthalenes are N-protonated. The gas-phase basicity results are in agreement with the previously postulated reason for the unusually high basicity of 1,8-bis(dimethylamino)naphthalene, namely, that steric strain in the neutral base is relieved by protonation. It is found that the methyl substituent effects on the basicity of the 1,8-diaminonaphthalenes are strongly attenuated in solution, as expected since N-methylated ions are less well solvated. The proton-induced relief of strain in the fully methylated base produces nearly the same energy change in the gas phase and in solution, as expected since this change should not affect the solvation of the ion. The neutral base 1,2-bis(dimethylamino)benzene is not strained and therefore is of considerably lower basicity.
A study was conducted to demonstrate advancements in determining the absolute proton affinities of neutral organic molecules in the gas phase (GP) and their interpretation. The study provided information about some of the main achievements and advancements in theoretical and computational studies of proton affinities, avoiding a taxonomic account of the literature. It focused on the results obtained by computational chemistry in studying the GP acid/base facets of predominantly organic compounds in their ground states (GS). Significant advancements were made in these areas due to advancements in powerful computer hardware and the development of new methods of quantum mechanics for tackling many-body problems, implemented as efficient algorithms in versatile software. Computational natural sciences also eliminated the distinctions between traditional disciplines of physics, chemistry, and molecular biology, providing an important link between rigorous theory and experiment.
By building a relative basicity ladder, the current basicity scale (Lias et al., J. Phys. Chem. Ref. Data, 17 Suppl. No. 1 (1988)) has been reexamined in its upper part, and extended for organic compounds (amenable to proton transfer measurements) up to proton affinity, PA = 1050 kJ mol−1. Structural effects involved in superbasicities are briefly discussed and routes to further extension of the gas-phase basicity scale for organic compounds are proposed.
The gas-phase acidities and basicities for 49 acids and 32 bases, calculated using B3LYP hybrid DFT method and 6-31G∗, 6-31+G∗, 6-311+G∗∗, and 6-311+G(3df,3pd) basis sets are compared with corresponding experimental values. The best results were obtained with 6-311+G(3df,3pd) basis set; the average absolute errors were below 2.5 kcal/mol both for basicities and acidities. Good results for both acidities and basicities (the average absolute errors were ⩽3 kcal/mol) were also obtained using the 6-311+G∗∗ basis set and even with a moderate 6-31+G∗ basis set (mean absolute errors were <4.6 kcal/mol). The obtained results can be further improved by applying empirical corrections.
A series of stable organosuperbases, N-alkyl- and N-aryl-1,3-dialkyl-4,5-dimethylimidazol-2-ylidene amines, were efficiently synthesized from N,N'-dialkylthioureas and 3-hydroxy-2-butanone and their basicities were measured in acetonitrile. The derivatives with tert-alkyl groups on the imino nitrogen were found to be more basic than the tBuP(1) (pyrr) phosphazene base in acetonitrile. The origin of the high basicity of these compounds is discussed. In acetonitrile and in the gas phase, the basicity of the alkylimino derivatives depends on the size of the substituent at the imino group, which influences the degree of aromatization of the imidazole ring, as measured by (13)C NMR chemical shifts or by the calculated ΔNICS(1) aromaticity parameters, as well as on solvation effects. If a wider range of imino-substituents, including electron-acceptor substituents, is treated in the analysis then the influence of aromatization is less predominant and the gas-phase basicity becomes more dependent on the field-inductive effect, polarizability, and resonance effects of the substituent.
Benchmark quantum calculations of proton affinities and gas-phase basicities of molecules relevant to biochemical processes, particularly acid/base catalysis, are presented and compared for a variety of multilevel and density functional quantum models. Included are nucleic acid bases in both keto and enol tautomeric forms, ribose in B-form and A-form sugar pucker conformations, amino acid side chains and backbone molecules, and various phosphates and phosphoranes, including thio substitutions. This work presents a high-level thermodynamic characterization of biologically relevant protonation states and provides a benchmark database for development of next-generation semiempirical and approximate density functional quantum models and parametrization of methods to predict pK(a) values and relative solvation energies.
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.
The gas-phase basicity (GB) of tetra-tert-butyltetrahedrane (tBu4THD) was determined by FT-ICR mass spectrometry and comparison with reference compounds of known basicity. Its GB, 1035+/-10 kJ x mol(-1), makes tetra-tert-butyltetrahedrane one of the strongest bases reported so far. Ab initio calculations [B3LYP/6-31G(d) and B3LYP/6-311 + G(d,p)//6-31G(d)] have been carried out in order to compare the high experimental basicity of tBu4THD with that estimated theoretically. Both B3LYP/6-31G(d) and QCISD(T) calculations were used to determine the reaction path which connects the initial tetrahedrane-ammonium complex with the final products, protonated cyclobutadiene (CBDH+) and ammonia.
The spatial and electronic structure of the very strong neutral organic bases bis(tetramethylguanidino)naphthalene (TMGN), 4,5-bis(tetramethylguanidino)fluorene (TMGF) and some related compounds are explored by ab initio computational methods. Their affinity towards the proton is scrutinized both in the gas phase and in solution in acetonitrile. The protonation at the most basic center (the imine nitrogen) yields asymmetric and relatively strong intramolecular hydrogen bonds (IHB). It is found that the angular strain effect and steric repulsion practically vanish in TMGN which implies that its high absolute proton affinity (APA) has its origin in the inherent basicity of the guanidine fragment and a relatively strong IHB in [TMGN]H(+). The nonbonded repulsions in TMGF are higher than in TMGN, which in conjunction with a slightly stronger IHB in the corresponding conjugate acid makes it more basic: APA(TMGF)>APA(TMGN). An interesting new phenomenon is observed in both TMGN and TMGF: the proton triggers the resonance stabilization not only in the directly bonded guanidine moiety, but also in the other guanidine fragment which is more distant from the proton, albeit in a less pronounced manner. The latter feature is termed a partial protonation. This supports the hydrogen bonding and contributes to the IHB stabilization. Convincing evidence is presented that the solvent effect in acetonitrile is determined by two antagonistic factors: 1) the intrinsic (gas phase) proton affinity and 2) the size effect which is given by the ratio between the positive charge in molecular cation (conjugate acid) and the magnitude of the molecular surface. The resulting pK(a) values are given by an interplay of these factors.
1,8-Bis(tetramethylguanidino)naphthalene (TMGN, 1) is a new, readily accessible, and stable "proton sponge" with an experimental pK(BH(+)) value of 25.1 in MeCN, which is nearly seven orders of magnitude higher in basicity than the classical proton sponge 1,8-bis(dimethylamino)-naphthalene (DMAN). Because of the sterically less crowded character of the proton-accepting sp(2)-nitrogen atoms, TMGN also has a higher kinetic basicity than DMAN, which is shown by time-resolved proton self-exchange reactions. TMGN is more resistant to hydrolysis and is a weaker nucleophile towards the alkylating agent EtI in comparison to the commercially available guanidine 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD). Crystal structures of the free base, of the mono- and bisprotonated base were determined. The dynamic behavior of all three species in solution was investigated by variable-temperature (1)H NMR experiments. DeltaG (++) values obtained by spectra simulation reveal a concerted mechanism of rotation about the C-N bonds of the protonated forms of TMGN.
It is shown that a combination of Schwesinger's phosphazene base concept and the idea of the disubstituted 1,8-naphthalene spacer, first introduced by Alder in paradigmatic 1,8-bis(dimethylamino)naphthalene (DMAN), yields a new superbase, HMPN, which represents the up to date most basic representative of this class of "proton sponges", as evidenced by the theoretically estimated proton affinity PA = 274 kcal/mol and the measured pK(BH+) (MeCN) 29.9 +/- 0.2. HMPN is by nearly 12 orders of magnitude more basic than Alder's classical 1,8-bis(dimethylamino)naphthalene (DMAN). The title compound, HMPN, is prepared and fully characterized. The spatial structure of HMPN and its conjugate acid is determined by X-ray technique and theoretical DFT calculations. It is found that monoprotonated HMPN has an unsymmetrical intramolecular hydrogen bridge (IHB). This cooperative proton chelating effect renders the bisphosphazene more basic than Schwesinger's set of "monodentate" P1 phosphazene bases. The density functional calculations are in good accordance with the experimental results, providing some complementary information. They conclusively show that the high basicity of HMPN is a consequence of the high energy content of the base in its initial neutral state and the intramolecular hydrogen bonding in the resulting conjugate acid with contributions to proton affinity of 14.1 and 9.5 kcal/mol, respectively.
Detailed studies have been made using different source gases and solvents in a Micromass Quattro mass spectrometer under positive ion atmospheric pressure chemical ionization conditions. The major background ions from nitrogen, air, or carbon dioxide were investigated by tandem mass spectrometry, followed by similar studies on solvents commonly employed in normal- and reversed-phase high-performance liquid chromatography, namely, water-acetonitrile, acetonitrile, and dichloromethane, with nitrogen, air, or carbon dioxide; hydrocarbon solvents were studied using nitrogen. Spectra were interpreted in terms of the gases, solvents, and their impurities. The acetonitrile spectra provided clear evidence for both charge exchange and proton transfer, the former being facilitated by the introduction of some air into a flow of nitrogen. Radical cations of acetonitrile dimers, trimers, and tetramers were observed, as were protonated dimer and trimer species. Examination of the analytical response of four polycyclic aromatic hydrocarbons in various hydrocarbon solvents, with nitrogen gas, showed that the sensitivity of detection for an analyte and its ionization mechanism are dependent on both the analyte structure and the solvent, with pyrene showing the highest sensitivity, phenanthrene and fluorene being intermediate, and naphthalene having the lowest sensitivity. The degree of protonation followed the same trend. Signal intensity and degree of protonation were dependent on the alkane solvent used, with isooctane providing the best overall sensitivity for the sum of protonated molecules and molecular ions. The ions observed in these studies appeared to be the most stable ions formed under equilibrium conditions in the source.