Why is guanidine such a strong base



Summary:
Proton sponges are neutral organic bases with a chelating proton acceptor function. The classic example of this is 1,8-bis (dimethylamino) naphthalene (DMAN), first used by Alder et al. presented. DMAN has a pKBH + (MeCN) value of 18.2. In the course of time, new and innovative proton sponges based on Alder's concept were synthesized and characterized, which show both a significantly higher thermodynamic basicity and better kinetic activity. In our working group, 1,8-bis- (tetramethylguanidino) naphthalene (TMGN), 1,8-bis- (dimethylethylene guanidino) naphthalene (DMEGN) and 1,8-bis- (hexamethyliminophosphoranyl) naphthalene (HMPN) were synthesized and characterized. The aim of this work was to increase the thermodynamic basicity of naphthalene-1,8-diyl-based proton sponges and to search for new fields of application. This was achieved, among other things, by synthesizing a new proton sponge (DIAN) from the group of 1,8-bis (guanidino) naphthalenes. The structural and spectroscopic data of this perfect “chelate or pincer ligand” for a proton were discussed. The thermodynamic basicity was determined and the hydrolysis behavior and the nucleophilic properties towards ethyl iodide were experimentally investigated and discussed. In addition, the kinetic barrier of the proton self-exchange reaction of DIAN and [DIAN-H] PF6 was determined by NMR line shape analysis using the Eyring equation to be 49.6 kJ / mol. The pKBH + value of the DIAN was determined by means of the 1H-NMR titration method with TMGN as the reference base. Compared to TMGN (pKBH + (MeCN) = 25.1) and DMEGN (pKBH + (MeCN) = 23.0 (theoretical)), DIAN has a higher pKBH + value of approx. 26.4 in acetonitrile. The higher basicity of DIAN compared to TMGN or DMEGN is essentially due to the higher polarity of the exocyclic C-N bond due to the stabilization of the carbenium center + CN3 in the aromatic imidazolium system. Another goal was to increase the thermodynamic basicity of bisphosphazene proton sponges. Different synthesis strategies for the construction of 1,8-disubstituted naphthalenes and sterically demanding phosphorus compounds of the types PR3, R3P = NH and X- + PR3 (R = NMe2, NMeR, N = C (NMe2) 2 etc.) were tested. In order to realize this, different derivatives of the P-electrophiles, the P-nucleophiles and the N-nucleophiles were presented. The Staudinger variant turned out to be the most promising route. Although it has not been possible to isolate the superbasic phosphorus (III) guanidine to date, despite the efforts of other groups, the reaction of 1,8-diazidonaphthalene with the phosphorus (III) amide provided a new route via the bisphosphazide to the well-known HMPN . Among other things, bis (triazenido) phosphoranylnaphthalene could be isolated and characterized. Finally, the Staudinger reaction with the Verkade azaphosphatran produces the new 1,8-bis (azaphosphatranyl) naphthalene (APAN). According to DFT calculations by Maksić et al. 1,8-bis (azaphosphatranyl) naphthalene has a proton affinity of 278.0 kcal / mol in the gas phase. This value is higher than for HMPN (274.0 kcal / mol), so that APAN should have a higher pKBH + value than HMPN (pKBH + (MeCN) = 29.9). The free base APAN was protonated with the acid (CF3SO2) 2NH and the conjugate acid of APAN was thus represented. Not only proton sponges based on iminophosphorane pincer ligands, but also those based on sulfoximines became the focus of interest. Bolm et al. have synthesized 1,8-bis ((S) -S-methyl-S-phenylsulfoximinyl) naphthalene ((S, S) -MPSIN) by means of a double cross-coupling reaction. In a cooperation with the AG Bolm, the basicity, the hydrolysis behavior and the nucleophilicity of (S, S) -MPSIN towards ethyl iodide were experimentally investigated and discussed. Single crystals of (S, S) -MPSIN and its corresponding acid [(S, S) -MPSIN-H] BF4 were obtained and their structure was elucidated. It turned out that the thermodynamic basicity of (S, S) -MPSIN is, as expected, significantly lower than that of the guanidine proton sponges. The basicity of (S, S) -MPSIN lies between that of triflate and water, with water being able to deprotonate [(S, S) -MPSIN-H] +. Although (S, S) -MPSIN is structurally related to the guanidine proton sponges, (S, S) -MPSIN is not a particularly good base, [(S, S) -MPSIN-H] + is rather a moderately strong acid, clearly more acidic than, for example, the ammonium cation. The activation energy for the proton self-exchange as a measure of the kinetic activity of (S, S) -MPSIN was also determined by means of NMR line shape analysis according to the Eyring equation to be 39.5 kJ / mol. In the second part of this work an attempt was made to find new fields of application for proton sponges in organic and organometallic chemistry. When characterizing the proton sponges, the nucleophilic reactivity towards ethyl iodide was determined experimentally. Despite their high thermodynamic basicity, they show a relatively low nucleophilicity. In contrast to ethyl iodide, CH2X2 (X = Cl, Br) are inert. The proton sponges show no conversion with dichloromethane at 25 ° C, but HMPN in particular is reactive with dibromomethane. There is competition between the acid-base reaction with HBr elimination and the activation of dibromomethane in the sense of a double nucleophilic substitution reaction. The activation product arises in a ratio of two to one to the conjugate acid of HMPN. With regard to the nucleophilic substitution at CH2Br2, the guanidine proton sponges TMGN and DIAN are largely inert. The guanidine and iminophosphorane proton sponges are perfect proton acceptor ligands. So far, however, little was known about possible ligand properties towards Lewis acids. To investigate the donor properties, TMGN was used as a representative of the class of guanidine proton sponges; BeCl2 was initially selected as the Lewis acid. The coordination of BeCl2 to the chelating ligand TMGN creates a tetrahedral beryllium complex. [(TMGN) BeCl2] is the first beryllium complex with a guanidine ligand regime. The preparation of a unique, resonance-stabilized, cationic, trigonal-planar beryllium complex [(TMGN) BeCl] + by chloride abstraction was not successful. Recent work by Himmel et al. show that TMGN is able to coordinate Pd (II) and Pt (II) cations. These complexes have found their application as catalysts in Heck reactions. Since the Buchwald-Hartwig reaction was used as an example of a C-N cross-coupling reaction in this work, it was obvious to replace the common diamine ligands with bisguanidine ligands in amidation reactions of iodobenzene according to Buchwald. In this context, the Cu (I) -halogenido complexes were characterized by TMGN. In addition to complexes of other ligands such as DIAN, HMPN, 1,2-bis- (1,1,3,3-tetramethylguanidino) ethane (TMGE) and 1,2-bis- (1,3-diisopropylguanidino) ethane (IGE), these complexes tested as catalysts in the CN coupling. It has been shown that the guanidine-copper (I) complexes can catalyze such an amidation reaction of aryl halides. But the hope that TMGN could lead to a significantly higher activity than special diamine ligands such as N, N’-dimethylethylenediamine, was not fulfilled. The guanidine ligand IGE showed the best activity. Another application is the protolysis of molecular hydrogen observed for the first time in this work with the guanidine proton sponges 1,8-bis (dimethylethylene guanidine) naphthalene DMEGN or TMGN in the presence of tris (pentafluorophenyl) borane BCF. [TMGN-H] [H-BCF] and [DMEGN-H] [H-BCF] (58) could be isolated and fully characterized. The less basic classic proton sponge DMAN is not able to split molecular hydrogen under the same conditions. HMPN and DIAN, which have a higher basicity than DMEGN and TMGN, enter into unselective reactions with BCF even in the absence of hydrogen. This work enriched the class of superbasic proton sponges with two new representatives, APAN and DIAN; the third, (S, S) -MPSIN, based on sulfoximine tweezers turned out to be slightly basic. The heterolytic cleavage of molecular hydrogen by proton sponges opens up interesting perspectives for future work.

Summary:
Proton sponges are neutral organic bases showing a chelating proton-binding site. The classical example of a proton sponge is 1,8-bis- (dimethylamino) naphthalene (DMAN) first introduced by Alder et al. The pKBH + value of DMAN in acetonitrile is 18.2. Over the years new and innovative proton sponges on the basis of Alders proton sponge concept were synthesized and characterized. These new proton sponges show a higher basicity as well as a higher kinetic activity than DMAN. In our work group the new-generation proton sponges 1,8-bis- (tetramethylguanidino) naphthalenes (TMGN), 1,8-bis- (dimethylethylene guanidino) -naphthalenes (DMEGN) and 1,8-bis- (hexamethyliminophosphoranyl) naphthalenes ( HMPN) were synthesized and fully characterized. The intention of this work was to increase the thermodynamic basicity of proton sponges with the naphthalene skeleton and to evaluate new potential applications in chemistry. This was achieved by the successful synthesis of a new proton sponge from the group of 1,8-bis (guanidino) naphthalenes. This third guanidine-based proton sponge is called 1,8-bis (1,3-dimethyl-1,3-imidazol-2-ylidenamino) naphthalene (DIAN). Its structural and spectroscopic data were discussed, showing the properties of a perfect pincer ligand for a proton. The thermodynamic basicity was determined using NMR titration. In addition, the hydrolysis and the nucleophilic properties of DIAN towards ethyl iodide have been studied. The kinetic activation was investigated using the proton self exchange reaction of DIAN with [DIAN] PF6 via NMR line shape analysis. The resultant energy barrier is 49.6 kJ / mol. The pKBH + value of DIAN was determined using the 1H-NMR titration with a reference base like TMGN. Compared to TMGN (pKBH + (MeCN) = 25.1) and DMEGN (pKBH + (MeCN) = 23.00 (calculated)) DIAN had a higher pKBH + value of 26.4 in acetonitrile. The stronger basicity of DIAN compared to TMGN or DMEGN is based on the higher polarity of the exocyclic C-N bond, which corresponds to the stabilization of the carbenium center in the heteroaromatic imidazolium moiety. Another goal was to enhance the thermodynamic basicity of bisphosphazene-based proton sponges. Three synthetic strategies for building 1,8-disubstituted naphthalenes and sterically demanding phosphorous compounds of the types PR3, R3P = NH and X- + PR3 (R = NMe2, NMeR, N = C (NMe2) 2 and soon) were tested. This work also engages in studies on the synthesis of P-electrophiles, P-nucleophiles and N-nucleophiles. The Staudinger reaction proved to be the most promising route. Although to date the superbasie phosphorus (III) -guanidine could not be isolated, the reaction of 1,8-diazidonaphthalene with the phosphorus (III) -amide provided a new path to HMPN via the bisphosphazide. In this work could be among other things bis- (triazenido) - phosphoranylnaphthaline isolated and characterized. The Staudinger reaction with the Verkade azaphosphatrane derivate produces a new proton sponge called 1,8-bis- (azaphosphatranyl) naphthalene (APAN). According to DFT calculations of Maksić et al. 1,8-bis- (azaphosphatranyl) naphthalene has a proton affinity in the gas phase of 278.0 kcal / mol. This value is higher than that of HMPN (274.0 kcal / mol), so that APAN should have a higher pKBH + -value than HMPN (pKBH + (MeCN) = 29.9). The free base (APAN) was protonated with the acid (CF3SO2) 2NH and thus formed into its conjugate acid. In addition to proton sponges based on iminophosphorane pincer ligands, sulfoximine ligands moved into the center of our attention. Bolm et al. synthesized 1,8-bis - ((S) -S-methyl-S-phenylsulfoximino) naphthalenes ((S, S) -MPSIN) using a double cross coupling reaction. In this work, the basicity, the hydrolysis and the nucleophilic behavior (S, S) -MPSIN towards ethyliodide are experimentally investigated and discussed. Single crystal structure of (S, S) -MPSIN and its corresponding acid [(S, S) -MPSIN-H] BF4 were obtained and discussed. It turned out that the thermodynamic basicity of (S, S) -MPSIN is significantly lower than that of the guanidine proton sponges. The basicity of (S, S) -MPSIN ranges between triflate and water, which is able to deprotonate [(S, S) -MPSIN-H] +. Although (S, S) -MPSIN is structurally comparable with the guanidine proton sponges, it is not a good base. In fact the corresponding acid of (S, S) -MPSIN is a moderate acid, as it clearly is a stronger acid than the ammonium cation. The investigation of the kinetic activation was achieved using the proton self exchange reaction of (S, S) -MPSIN with [(S, S) -MPSIN-H] + via NMR line shape analysis according to the Eyring equation. The resultant energy barrier is 39.5 kJ / mol. In the second part of this work efforts have been made to find new applications for proton sponges in organic and organometallic chemistry. The nucleophilic reactivity of proton sponges towards ethyl iodide has been determined experimentally. Despite the high basicity of the proton sponges they show a relatively low nucleophilicity. In contrast to ethyl iodide dihalomethanes CH2X2 (X = Cl, Br) are inert towards the proton sponges. No reaction occurs with dichloromethane at 25 ° C. The first bisiminophosphorane proton sponge HMPN shows conversion with dibromomethane at 25 ° C. In addition to an acid-base reaction between HMPN and dibromomethane was observed a nucleophilic reaction competitor. The activation product of nucleophilic reaction is formed in the ratio of two to one in comparison to the conjugate acid of HMPN. In contrast to HMPN both the guanidine proton sponges (DIAN, TMGN) are unreactive towards CH2Br2. The guanidine and iminophosphorane proton sponges are perfect proton acceptor ligands. The properties of these ligands towards Lewis acids were hardly known. For the investigation of the donor properties, TMGN has been used to represent the class of guanidine-proton sponges, as a Lewis acid BeCl2 was selected. By coordinating BeCl2 to the chelating ligand TMGN a tetrahedral beryllium complex was formed. [(TMGN) BeCl2] is the first complex of beryllium with a guanidine ligand. The preparation of a stable, cationic, trigonal planar beryllium complex [(TMGN) BeCl] + by chloride abstraction failed. Recent works by Himmel et al. show that TMGN is able to coordinate Pd (II) and Pt (II) cations. These catalysts were used in a Heck reaction. In this work the Buchwald-Hartwig reaction was tested as an example for a C-N cross coupling reaction. The amidation of iodobenzene was chosen, which is usually performed with a copper (I) salt and a bidentate diamine ligand. In this work the diamine ligand was replaced by a bisguanidine ligand. In this context the complexes of copper (I) halides with TMGN were prepared. These and other complexes with the ligands DIAN, HMPN, 1,2-bis- (1,1,3,3-tetramethylguanidino) ethane (TMGE) and 1,2-bis- (1,3-diisopropylguanidino) ethane (IGE) were tested in a CN cross coupling reaction. It was shown that guanidine-copper (I) complexes can catalyze such an amidation reaction of aryl halides. Guanidine ligands shows a lower activity compared to diamine ligands such as N, N-dimethylethylenediamine. The highest activity of the tested gunidine ligands shows IGE. Another potential application is the in this study for the first time observed protolysis of molecular hydrogen with the guanidine proton sponges 1,8-bis- (dimethylethylenguanidino) -naphthalene (DMEGN) and TMGN in the presence of tris (pentafluorophenyl) borane BCF. The salts [TMGN-H] [H-BCF] and [DMEGN-H] [H-BCF] were isolated and completely characterized. It is interesting to note that the less basic “classical” proton sponge DMAN do not react under the same conditions with molecular hydrogen. Other proton sponges like HMPN and DIAN are stronger bases than TMGN and DMEGN. They react nonselectively with BCF even in the absence of molecular hydrogen. This work expanded the class of proton sponges by the two new representatives APAN and DIAN. The third “proton sponge” (S, S) MPSIN based on a sulfoximine. It turned out to be slightly alkaline. The heterolytis splitting of molecular hydrogen by proton sponges opens interesting perspectives for future work.