NMR studies of the tautomerism of cyclo-tris(4-R-2,6-pyridylformamidine) in solution and in the solid state

Two novel cyclo-tris(4-R-2,6-pyridylformamidine)s (R = H, CH(3)) have been studied by solution- and solid-state NMR. Both compounds show fast exchange of NH protons in dimethyl sulfoxide at room temperature. The E-syn configuration of the formamidine group with the NH protons in the outer ring position could be proved by low-temperature (1)H NMR experiments. The influence of deuteration of the NH group on the exchange rate has been demonstrated qualitatively. Proton exchange at the formamidine groups results in both a symmetric (S) and an asymmetric (A) isomer which could be spectroscopically identified and characterized at 193 K. Whereas two degenerate forms exist for S, six degenerate A forms can be distinguished. Prototropic tautomerism at one formamidine group results in exchange from S into A, whereas A is transformed to a degenerate A form or to S. It could be shown that some transitions between substructures are impossible by a single -NH-CH=N-/-N=CH-NH- exchange. The S isomer with three equivalent formamidine groups is the preferred isomer in solution as indicated by the S/A ratio at 193 K. From this result we conclude that in polyformamidines, ordered sequences of formamidine tautomers are also formed at low temperatures. Prototropic exchange was not observed in the solid state, neither by (13)C nor by (15)N solid-state NMR. For one trimer (R = CH(3)), three molecules dimethyl sulfoxide per trimer molecule are within the lattice as could be proved by (13)C CPMAS NMR.     

Structure and tautomerism of 4-substituted 3(5)-aminopyrazoles in solution and in the solid state: NMR study and Ab initio calculations

Annular tautomerism of 3(5)-aminopyrazoles containing a cyano, thiocyanato, or aryl substituent in the 4-position has been studied by ¹H and ¹³C NMR in solution, cross-polarization and magic-angle spinning ¹³C NMR in the solid state, and ab initio quantum chemical calculations (B3LYP/6-31G**). The title compounds in the solid state exist as 3-amino tautomers. A rare case of slow (on the NMR time scale) annular prototropic tautomerism has been observed in DMSO-d ₆: signals of particular tautomers (3- and 5-aminopyrazoles) have been detected in the NMR spectra. 4-Cyano and 4-thiocyanato derivatives exist preferentially as 5-amino tautomers, whereas 4-methoxy analog is represented mainly by the 3-amino tautomers. Ab initio calculations (B3LYP/6-31G**) for the gas phase and DMSO solution (in terms of the polarizable continuum model) have shown increase of the relative stability of more polar 5-amino tautomer in going to DMSO.     

Solvent effects on valence tautomerism: A comparison between the interconversion in solution and solid state

A detailed comparative study of the valence tautomeric interconversion of complexes 1–3 in three different environments is reported. The three environments are solid state (both crystalline and amorphous materials), solution and embedded into a polymeric matrix. The VT behavior of the three complexes strongly differs from one to the other, though no systematization can be established. In solution, different solvatational parameters seem to affect the equilibrium. However, such solvate effect cannot be translated either into the solid state or polymeric matrix, where the equilibrium is controlled by the vibrational relaxation of the network.     

Template-controlled face-to-face stacking of olefinic and aromatic carboxylic acids in the solid state

A rigid 1,8-dipyridylnaphthalene template for supramolecular organization of unsaturated dicarboxylic acids in the solid state has been developed. Self-assembly of the template and aromatic dicarboxylic acids generates nondistorted paracyclophane and pyridinophane architectures with perfectly superimposed pi-systems. The dipyridyl template can be used to promote stereoselective solid-state dimerization of olefinic dicarboxylic acids.     

Vibrational spectra of isomeric pyridinic carboxylic acids in solid state and in solution and their SERS studies in silver sol

Raman spectroscopic studies of three isomeric pyridinic carboxylic acids, viz. picolinic, nicotinic and iso-nicotinic acid in solid state, in aqueous solution and in silver hydrosol, in the frequency range 900–1750 cm⁻¹, have been made. Assignments of the observed bands have been proposed in relation to the molecular forms present in solid state and in solution. Different degrees of intensity enhancements of the Raman bands in surface-enhanced Raman scattering (SERS) have been observed in all the three isomeric molecules. In iso-nicotinic acid, the intensity enhancement has been found to be minimum. Comparisons of Raman spectra in aqueous solution with those due to SERS in silver sol indicate that picolinic and nicotinic acid adsorb perpendicularly to the sol surface whereas in iso-nicotinic acid it occurs via donation of a π-electron of the aromatic ring, i.e. the plane of the ring lies parallel to the surface of the sol.     

A 13C NMR spectroscopic study of the phase transitions of alkane dicarboxylic acids in the solid state

¹³C NMR spectra of a few odd-member alkane dicarboxylic acids such as glutaric and pimelic acids have been studied across their phase transitions. The spectra provide clear evidence for the structural changes accompanying the transitions. In the case of malonic acid, the study establishes that the two carboxyl units are equivalent in the high-temperature phase unlike in the other odd-member dicarboxylic acids where they are non-equivalent.     

Structure of N,N'-bis(amino acids) in the solid state and in solution. A 13C and 15N CPMAS NMR study

Three bis(amino acids) linked by the amino groups have been prepared and structurally characterized. We have named them Gly-Gly, Ala-Ala and Gly-Ala (or Ala-Gly). These compounds have been characterized by NMR both in solution and in the solid state. They exist as zwitterions with the ammonium group proximal to the carboxylate anion. In the case of Gly-Ala, a dynamic situation is observed by CPMAS NMR ((13)C and (15)N) corresponding to a double proton migration between two proximal tautomers.     

The tautomerism of Omeprazole in solution: a 1H and 13C NMR study

The tautomerism of 5(6)-methoxy-2-([(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl] sulfinyl)-1H-benzimidazole (omeprazole) was determined in solution, K(T) = 0.59 in THF at 195 K, in favor of the 6-methoxy tautomer. The assignment of the signals was made by comparison with its two N-methyl derivatives in acetone-d6 and through theoretical calculations of the absolute shieldings (GIAO/DFT/6-311++G**).     

13C and 15N NMR spectra of aminobenzimidazoles in solution and in the solid state

The ¹³C [hexadeutero‐dimethylsulfoxide (DMSO‐d₆), hexamethyl‐phosphoramide (HMPA)‐d₁₈and solid‐state] and ¹⁵N (solid‐state) NMR spectra of six C‐aminobenzimidazoles have been recorded. The tautomerism of 4(7)‐aminobenzimidazoles and 5(6)‐aminobenzimidazoles has been determined and compared with B3LYP/6‐311 + + G(d,p) calculations confirming the clear predominance of the 4‐amino tautomer and the slight preference for the 6‐amino tautomer. GIAO‐calculated absolute shieldings compare well with experimental chemical shifts. Copyright © 2008 John Wiley & Sons, Ltd.     

A 13C NMR study of tautomerism in phenoxymethylisoxazol-5-ones

A ¹³C NMR study of new isoxazol-5-ones has been carried out in different solvents. Mathematical analysis of the tautomeric ring proton exchange in pyridine solvent indicates that the relative contributions of the NH, CH and OH tautomers are respectively 10 ± 5, 15 ± 3, 10 ± 8%, while the anionic form represents the remaining 65 ± 8%.     

A 1H, 13C and 15N NMR study in solution and in the solid state of six N-substituted pyrazoles and indazoles

Three N-substituted pyrazoles and three N-substituted indazoles [1-(4-nitrophenyl)-3,5-dimethylpyrazole (1), 1-(2,4-dinitrophenyl)-3,5-dimethylpyrazole (2), 1-tosyl-pyrazole (3), 1-p-chlorobenzoylindazole (4), 1-tosylinda-zole (5) and 2-(2-hydroxy-2-phenylethyl)-indazole (6)] have been studied by NMR spectroscopy in solution (1H, 13C, 15N) and in the solid state (13C, 15N). The chemical shifts have been compared with GIAO/DFT calculated absolute shieldings. Some discrepancies have been analyzed.     

The effects of tautomerism on the nature of molecules in the solid state

Tautomerism is a phenomenon well know to most chemists but frequently forgotten when chemistry leaves the bench and enters the computational realm. Through the examination of several examples from the crystallographic literature it can be clearly demonstrated that the tautomeric state of a molecules can strongly affect its nature.     

The tautomerism of 1H-pyrazole-3(5)-(N-tert-butyl)carboxamide in the solid state and in solution

The X-ray crystal structure of 1H-pyrazole-3-(N-tert-butyl)-carboxamide was determined. In the solid state, the 13C and 15N CP/MAS NMR spectra correspond to this tautomer. In solution, both tautomers are present in a ratio that depends on the temperature (at 293 K, 90% 3-substituted/10% 5-substituted). Some unusual 1H, 1H couplings involving the NH proton were observed. DFT (GIAO) calculations were carried out.     

Low-temperature NMR studies of Zn tautomerism and hindered rotations in solid zincocene derivatives

Using a combination of NMR methods we have detected and studied fluxional motions in the slip-sandwich structure of solid decamethylzincocene (I, [(eta5-C5Me5)Zn(eta1-C5Me5)]). For comparison, we have also studied the solid iminoacyl derivative [(eta5-C5Me5)Zn(eta1-C(NXyl)C5Me5)] (II). The variable temperature 13C CPMAS NMR spectra of I indicate fast rotations of both Cp* rings in the molecule down to 156 K as well as the presence of an order-disorder phase transition around 210 K. The disorder is shown to be dynamic arising from a fast combined Zn tautomerism and eta1/eta5 reorganization of the Cp* rings between two degenerate states A and B related by a molecular inversion. In the ordered phase, the degeneracy of A and B is lifted; that is, the two rings X and Y are inequivalent, where X exhibits a larger fraction of time in the eta5 state than Y. However, the interconversion is still fast and characterized by a reaction enthalpy of DeltaH = 2.4 kJ mol-1 and a reaction entropy of DeltaS = 4.9 J K-1 mol-1. In order to obtain quantitative kinetic information, variable temperature 2H NMR experiments were performed on static samples of I-d6 and II-d6 between 300 and 100 K, where in each ring one CH3 is replaced by one CD3 group. For II-d6, the 2H NMR line shapes indicate fast CD3 group rotations and a fast "eta5 rotation", corresponding to 72 degrees rotational jumps of the eta5 coordinated Cp* ring. The latter motion becomes slow around 130 K. By line shape analysis, an activation energy of the eta5 rotation of about 21 kJ mol-1 was obtained. 2H NMR line shapes analysis of I-d6 indicates fast CD3 group rotations at all temperatures. Moreover, between 100 and 150 K, a transition from the slow to the fast exchange regime is observed for the 5-fold rotational jumps of both Cp* rings, exhibiting an activation energy of 18 kJ mol-1. This value was corroborated by 2H NMR relaxometry from which additionally the activation energies 6.3 kJ mol-1 and 11.2 kJ mol-1 for the CD3 rotation and the molecular inversion process were determined.     

A N NMR study of tautomerism in dimethyl dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate

Dimethyl dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate can exist either in 1,2- or 1,4-dihydro tautomeric forms. The ¹⁵N NMR spectra of dimethyl dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate were measured at the ¹⁵N natural abundance level as well as in ¹⁵N doubly labelled selectively and in ¹⁵N completely labelled compounds (20% ¹⁵N). The J(¹⁵N,¹⁵N) value was determined in ¹⁵N completely labelled compounds (20% ¹⁵N) using 1D ¹⁵N INADEQUATE and was found to be 12.2 ± 0.2 Hz in deuteriochloroform, acetonitrile-d₃, DMSO-d₆ and CD₃OH. Very similar ¹⁵N chemical shifts and ¹J(¹⁵N,¹H) values were also observed in all the solvents. This indicates that compound 1 exists completely in the 1,4-dihydro tautomeric form (i.e., as dimethyl 1,4-dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate) in all the solvents tested.     

A 1H NMR study of tautomerism in some 1-arylamino-3-aryliminopropenes

¹H n.m.r. spectra at ambient temperatures reveal that an equilibrium exists between the ‘all-trans’ and ‘all-cis’ isomers of some of the 1-arylamino-3-aryliminopropenes. The ‘all-cis’ isomer predominates in nonpolar solvents, whereas the ‘all-trans’ isomer is favoured in hydrogen bonding solvents. From a consideration of the magnitudes of the ³J coupling constants, it is reported that the ‘cis-trans’ isomer is the most stable form of the 4-nitrophenyl derivative in dimethyl sulphoxide.     

Structural and vibrational study of the tautomerism of histamine free-base in solution

Infrared and Raman spectroscopy in H(2)O and D(2)O and quantum Density Functional calculations were used to determine the structure of histamine free-base in aqueous solution. A quantum mechanical study of the tautomeric equilibrium of histamine free-base in solution was performed at the 6-311G level. Electronic correlation energies were included by using the hybrid functional B3LYP. The solvent was simulated as a continuum characterized by a dielectric constant, and the quantum system (solute) was placed in an ellipsoidal cavity. Solute-solvent electrostatic interaction was calculated by means a multipolar moment expansion introduced in the Hamiltonian. Four relevant histamine conformations were optimized by allowing all the geometrical parameters to vary independently, which involved both the gauche-trans and the N3H-N1H tautomerisms. The calculated free energies predicted N3H-gauche as the most stable one of histamine free-base in solution. The order of stability is here completely altered with respect to previous results in gas phase, which presented the N1H-gauche conformer as the most stable structure. Our results also differ from previous Monte Carlo simulations, which obtained the N3H-trans conformer as the most stable in solution, although in this case, the histamine structures were kept frozen to the gas-phase geometry. Vibrational spectroscopy results support theoretical ones. Quadratic force fields for the four histamine conformers were achieved under the same calculation methodology. Previously, a general assignment of the infrared and Raman spectra of histamine free-base was proposed for solutions in both natural and heavy water. This allowed us to compare the experimental set of both wavenumbers and infrared intensities with the calculated ones. The lowest quadratic mean wavenumber deviation was obtained for the N3H-gauche conformer, in agreement with the free-energy calculations. Calculated infrared intensities were also compared to the experimental intensities, supporting this conformer as the relevant structure of histamine free-base in solution. It was then selected for a complete vibrational dynamics calculation, starting with a low-level scaling procedure to fit the set of calculated wavenumbers to the experimental values. The results were presented in terms of quadratic force constants, potential energy distribution, and normal modes.