Pyrazolium-sulfonates. Mesomeric betaines possessing iminium-sulfonate partial structures

Pyrazolium-3-sulfonates and pyrazolium-4-sulfonates possessing the iminiomethanesulfonate and the 3-iminio-pro-1-ene-2-sulfonate partial structure are prepared. Formally, they represent sulfur analogs of cross-conjugated (CCMB) and pseudo-cross-conjugated heterocyclic mesomeric betaines (PCCMB) and sulfur trioxide adducts of abnormal N-heterocyclic carbenes ( a NHC) and N-heterocyclic carbenes (NHC), respectively. The theoretical as well as experimental vibrational spectra of these two classes are compared. Results of calculations of HOMO/LUMO profiles and an X-ray single crystal structure analysis are presented


Introduction
The iminiomethanesulfonate group I and the 3-iminio-prop-1-ene-2-sulfonate group II (Figure 1) are partial structures of hitherto almost overlooked classes of heterocyclic mesomeric betaines.Formally, they represent sulfurtrioxide adducts of N-heterocyclic carbenes (NHC), remote N-heterocyclic carbenes (rNHC), or abnormal N-heterocyclic carbenes (aNHC), respectively, which possess the partial structures III and IV in heterocyclic rings. 1 Figure 2 shows N-heterocyclic carbenes of imidazole and pyrazole.Imidazol-2-ylidene is an NHC, whereas imidazol-4-ylidene -which cannot be represented by an electron sextet structureis a member of the class of aNHC. 2 Pyrazol-3-ylidene has been isolated as metal complexes, 3 trapped with heterocumulenes, 4 examined mass-spectrometrically, 5 and rearranged to 4aminoquinolines. 6It belongs to the class of NHCs whereas its isomer, pyrazol-4-ylidene has been described as remote N-heterocyclic carbene, 7 cyclic allene 8 or aromatic zwitterion. 9The correct representation of this structure has been discussed controversely. 10The carbon dioxide analogs of the sulfonates presented here are well known in heterocyclic as well as N-heterocyclic carbene chemistry.Thus, the partial structure V (Figure 3) can be identified in pseudo-cross-conjugated mesomeric betaines (PCCMB) 11 such as pyrazolium-3carboxylates, imidazolium-2-carboxylates, and 1-methylpyridinium-2-carboxylates which are indeed precursors of N-heterocyclic carbenes. 12They are formed on cleavage of the union bond between positive and negative portions of the molecule.Partial structure VI is characteristic for cross-conjugated mesomeric betaines (CCMB) such as pyrazolium-4-carboxylates, imidazolium-4-carboxylates, and 1-methylpyridinium-3-carboxylates which are more stable toward decarboxylations than PCCMBs. 13However, it was shown that imidazol-4-ylidenes, formed in situ from imidazolium-4-carboxylates, can be trapped with isocyanates.Some examples of iminium-sulfonates have been described in the literature.Thus, N,N´dimethylaminoiminiummethane sulfonate 3 is a representative of an open-chain molecule with partial structure I (Figure 1).It has been identified as metabolite of the biologically active thiocarbamide dimethylthiourea 1, and it is formed via the corresponding sulfenic and sulfinic acids before it is converted into sulfate and dimethylurea.X-ray analyses prove the formation of zwitterionic forms in the solid state, similar to the isomeric N,N-dimethyl derivative. 14Thus, in 2 the negative charge is delocalized in the pyramidal O-S-O group.Three-center four-electron πinteractions of the two filled pπ orbitals of the nitrogen atoms and a vacant carbon pπ orbital explain the very short C-N bonds of 130.3(3) pm and 130.4(3) pm.The C-S bond is nearly 10 pm longer than expected [188.8(2)pm], when the sum of the covalent radii of C and S is taken into consideration [179 pm]. 15The sulfonate 3 is much more stable than the sulfinate 2. Similarly, the Csp 2 -N bonds are shortened.The S-O bonds of the sulfonate group are nearly equivalent, and the C-S bond is shorter than that of 2 [182.0(3)pm], but longer than a normal C-S bond. 16heme 1. Open-chain iminium-sulfinate 2 and -sulfonate 3.
Imidazolium-2-sulfonate 7 is an example of a cyclic mesomeric betaine possessing partial structure I (Scheme 2).Seemingly, this compound cannot be formed by reaction of imidazol-2ylidene 5 with SO3 due to reduction of the sulfur atom. 17It was prepared by reaction of imidazol-2-ylidene 5 with sulfurylchloride to 2-chloroimidazolium 6 which was then treated with aqueous potassium cyanide to give the betaine 7 as colorless crystals. 18The C-S bond distance in 7 was determined by X-ray crystallography to be 182.2(2)pm.Protonation can be accomplished with HBF4 diethyletherate and HF/SbF5, respectively. 19heme 2. Synthesis of imidazolium-2-sulfonate.
Benzimidazolium-2-sulfonates 8 have been obtained on reaction of the corresponding thiones with MeNCl2 and subsequent oxidation with HClO4, 20 or starting from benzimidazoline-2-ones and POCl3 and subsequent treatment with sulfites or bisulfites 21 (Scheme 3).Some derivatives have been described as dyes. 22As oxidation of benzimidazoline-2-thiones with hydroperoxide resulted in the formation of benzimidazolium sulfate, the intermediate formation of benzimidazolium-2-ylidene was proposed which is trapped by protons. 23Indazolium-3sulfonates 9 played a role in dye chemistry. 24Pyridinium-2-sulfonates 10 have been used as fluorescent probes for DNA labeling, 25 polymers, 26 and antibiotics. 27They were also used in polymer synthesis 28 and dye chemistry. 29N-Fluoropyridinium-2-sulfonates are known to be highly selective fluorinating agents. 30The compounds 11 31 and 12 have partial structure II.N-Methylpyridinium-3-sulfonate 12 has been isolated from gorgonian octocorals found in the Caribbean Sea 32 and has been employed in a continuous flow process. 33Pyridinium-3-sulfonate is by far the most common building block of more complex structures 34 including dyes. 35To the best of our knowledge, no example of a five-membered representative has been described to date.The salt pyrazolo[1,2-a]pyrazolium-6-sulfonic acid, however, is mentioned in the literature. 36heme 3. Sulfonates possessing partial structures I and II.
In continuation of our work in mesomeric betaine chemistry, 37 N-heterocyclic carbenes in heterocyclic synthesis 38 and catalysis, 39 and vibrational spectroscopy for the characterization of these classes of compounds 40 we wish to report here the syntheses and characterizations of pyrazolium-3-sulfonates and pyrazolium-4-sulfonates.We performed X-ray crystallography, vibrational spectroscopy, and calculations to characterize these new mesomeric betaines.
Pyrazoles, which are unsubstituted in position 4, can also be converted into pyrazolium-4sulfonates on treatment with dialkylsulfates.The yields, however, are quite low and strongly depend on the concentration of the dialkylsulfate.Thus, reaction of 5-methyl-1-phenylpyrazole 16a with one equivalent of dimethylsulfate gave 12% yield of the pyrazolium-4-sulfonate 18a, whereas ten equivalents gave 41% yield.Reaction of 3,5-dimethyl-1-phenylpyrazole 16b gave only 19% of the corresponding pyrazolium-sulfonate 18b.Correspondingly, sulfonations of the pyrazoles 16c,d were accomplished.Pyrazolium methylsulfates 19 were obtained as by-products in all reactions.

Classifications
Mesomeric betaines are defined as conjugated molecules which can exclusively be represented by dipolar canonical formulae which delocalize the positive as well as negative charge within a common π-electron system.11a A closer inspection of the canonical formulae of pyrazolium-3sulfonates and pyrazolium-4-sulfonates shows differences with respect to the delocalization of the charges.Thus, in pyrazolium-3-sulfonates common atoms for either charge exist, when electron sextet structures are formulated as shown.In this case, the positive charge is formally localized on the oxygen atoms of the sulfonate group.This mesomeric structure, although without any physical consequence, is characteristic of pseudo-cross-conjugated mesomeric betaines (PCCMB).In addition, the characteristic dipole of PCCMBs can be dissected from the mesomeric structures.To compare the two types of mesomeric betaines mass spectrometrically, we sprayed samples of 15a and 18a from methanol and observed base peaks at m/z = 275.0 and additional peaks at 253.1 in the ESI mass spectra at 0 V fragmentor voltage.These peaks can be assigned to the pyrazolium-sulfonates plus Na + and H + , respectively.For the case of 18a, at 100 V fragmentor voltage the pyrazolium cation, formed by loss of SO3 from 18a and trapping of the resulting pyrazol-4-ylidene by a proton, gives the base peak at m/z = 173.1.
The HOMO/LUMO profiles of the two pyrazolium sulfonates are displayed in Fig. 7.They show that the sulfur atom is always a nodal position of the HOMOs, whereas the LUMOs are essentially located in the cationic moieties.However, a subtle difference is seen: the LUMO in pyrazolium-3-sulfonate is somewhat extended over the sulfonate group and more specifically over the C-S bond (here the union bond).This result is related with the ability of the positive and negative charges to delocalize on the sulfonate group, as aforementioned, which is characteristic of PCCMB.We also calculated the electrostatic surface potentials of the two types of sulfonates, which are shown in Fig. 8 together with the permanent dipole moments for the ground state.As is observed, the change in the sulfonate position, from 15a (PCCMB) to 18a (CCMB), gives rise to a 15% of dipole moment increase, namely from 20.51 to 23.62 D. This fact is accompanied by a relocation of the electric charge.Thus, the partial charge over the sulfonate groups changes from -0.535 (PCCMB) to -0.545 a.u.(CCMB), while that located on the pyrazolium moiety goes from +0.915 to +0.946 a.u.respectively.Interestingly, the positive charge specifically hosted over the five atoms of the pyrazolium skeleton grows up more than for the whole moiety, namely from +0.599 to +0.773 a.u.This is largely caused by a general increase of the positive charge on all the atoms except the sulfur-attached carbon, whose negative charge is dramatically increased, namely from -0.375 to -1.110 a.u. on going from 3sulfonate to 4-sulfonate.
The optimized bond lengths and calculated stretching force constants of the more relevant bonds are presented in Table 1.The calculated distance for the union bond, C-S, is greater in 3sulfonate than in 4-sulfonate.We would like to emphasize how the force constants are more sensitive than the bond lengths to the cross conjugation phenomenon.Taking the C-S stretching vibration as reference, the relative variation of its force constant is noticeably higher (8.9%) than the optimized bond lengths (1.1%).This fact allows us to detect a subtle difference in the S-O bonds of these molecules, whose averaged force constants are 8.74 and 8.42 mdyn/Å, respectively, while similar bond lengths are predicted.The rest of bonds exhibits very low deviations, being always more relevant the variations in force constant than in bond distances.In order to achieve an experimental support to the theoretical results we have recorded the infrared spectra of both molecules from solid samples.Wavenumbers of the more relevant bands are listed in Table 2. a Wavenumbers in cm -1 .b s = strong, m = medium, w = weak, v = very.c ν = stretching, δ = bending, r = methyl rocking; bz = benzene; py = pyrazolium The most outstanding result is the opposite behaviour recorded for the bands of aromatic and sulfonate moieties.Most of the bands assigned to stretching vibrations of benzene and pyrazolium rings upshift when going from 3-sulfonate (PCCMB) to 4-sulfonate (CCMB).This is an interesting result as, in spite of the positive charge of the pyrazolium ring is smaller in the PCCMB, the electronic density in the CCMB is more effectively localized over the inter-atomic regions, giving as a consequence stronger skeletal bonds.On the contrary, the two SO3stretching bands of 3-sulfonate, which were clearly assignable to the infrared bands at 1261 and 1239 cm -1 , are measured at 1234 and 1222 cm -1 in 4-sulfonate, as accurately predicted by the calculated force constants (Table 1).Strong infrared bands are related with the stretching vibration of the union bond, namely at 1097 and 1096 cm -1 for 3-and 4-sulfonate, respectively.Although this deviation is in agreement with the force constants, it is too small to fully describe the different strength between the two bonds, which indicates that other vibrational coordinates contribute to the corresponding normal mode.

Experimental Section
General.Flash-chromatography was performed with silica gel 60 (0.040-0.063 mm).Nuclear magnetic resonance (NMR) spectra were obtained with a Bruker Avance 400 NMR spectrometer. 1 H NMR spectra were recorded at 400 MHz and 13 C NMR spectra at 100 MHz, with the solvent peak or tetramethylsilane used as the internal reference.Multiplicities are described by using the following abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, sept = septet and m = multiplet.FT-IR spectra of all compounds except for 15a and 18a were obtained on a Bruker Vector 22 in the range of 400 to 4000 cm -1 .All substances were measured as pellets (2.5%) in KBr.Infrared spectra of 15a and 18a at room temperature were recorded from pure solid samples, dispersed into a KBr pellet, using a Bruker VERTEX 70 Fouriertransform (FT) spectrometer purged with dry nitrogen.The KBr used was dried following the usual routine for infrared measurements (110°C, at least 24 h).Typically, 500 scans at a resolution better than 4 cm -1 were accumulated to optimize the signal-to-noise ratio.Individual scans were examined by the recording routine before averaging, being automatically discarded when the mean intensity deviations were greater than 10% over the full interferogram length.The mass spectra were measured with a Varian 320 MS Triple Quad GC/MS/MS with a Varian 450-GC.The ESI mass spectra were measured with an Agilent LCMSD Series HP1100 with APIES.Samples were sprayed from methanol.Melting points are uncorrected and were determined in an apparatus according to Dr. Tottoli (Büchi).All yields are isolated yields.They are not optimized.The Gaussian'09 package of programs 45 was used for DFT quantum chemical calculations.The Becke's three parameter (B3) gradient-corrected exchange functional was used, and the nonlocal correlation was provided by the Perdew-Wang'91 (PW91) expressions. 46,47To simulate a polar environment, a polarizable continuum model (PCM) was employed. 48,49This model places the solute molecule into a size-adapted cavity formed from overlapping atom-centered van der Waals spheres, while the solvent is assimilated to a continuum characterized by its dielectric constant (78.4 for water).Ground state electronic properties and vibrational features were obtained using the split-valence 6-311+G(2d,p) basis set. 50,51It includes diffuse functions on heavy atoms and polarization on all the atoms, which allows for a suitable description of molecules with charge separation as zwitterions or betaines.The minimum energy structures were achieved by permitting all the geometrical parameters to vary independently, Harmonic force constants, in Cartesian coordinates, were evaluated at the ground state optimized geometry using analytical second derivatives.The Cartesian force constants were transformed into a set of non-redundant locally symmetrized internal coordinates accordingly to the Pulay methodology. 52n X-ray crystallographic analysis of C12H14Cl2N2O4S was performed at 223(2) K by using a STOE IPDS II diffractometer with Mo-K radiation ( = 0.71073 Å) and a graphite monochromator.Crystal system: triclinic, SG P1 (No.The crystal structures were dissolved by direct methods using SHELXS-97 53 and refined using alternating cycles of least squares refinements against F 2 (SHELXL-97) 53 .All non H atoms were found in difference Fourier maps and were refined with anisotropic displacement parameters.The H positions were determined by final difference Fourier syntheses.The refinement converged to a final wR2 = 0.0770 and R1 = 0.0424 for 2656 unique reflections and 246 refined parameters with a goodness-of-fit of 1.053.Further details of the crystal structure investigations have been deposited with the Cambridge Crystallographic Data Centre, CCDC 827948.Copies of this information may be obtained free of charge on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (Fax: +44(1223)-336 033; e-mail: fileserv@ccdc.ac.uk or http://www.ccdc.cam.ac.uk).

5-Methyl-1-phenylpyrazole-4-sulfonic acid (17).
A sample of 475 mg (3.0 mmol) of 5-methyl-1-phenylpyrazole 54 was first dissolved in 2 mL of anhydrous CHCl3 and then treated with 0.4 mL (6.0 mmol) of chlorosulfonic acid.The resulting mixture was then heated at reflux temperature over a period of 2 h.After cooling, the mixture was concentrated in vacuo and poured on 100 mL of ice.After neutralization with aqueous NaOH, the solution was evaporated to dryness in vacuo.The resulting residue was extracted with 120 mL of EtOH and filtered over a small column.