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.     

The structure of ammonium pyrazolates in the solid state

The crystals obtained by mixing equimolar amounts of diethyl 1H-pyrazole-3,5-dicarboxylate and the primary amines phenethylamine and homoveratrylamine are ammonium pyrazolate salts as determined by 13C and 15N CPMAS NMR.     

Facile synthesis of hydantoins and thiohydantoins in aqueous solution

A series of hydantoins and thiohydantoins have been synthesized in water at room temperature from urea (or N-methylurea, or thiourea) and simple aldehydes (as glyoxal, and its simple derivatives) in the presence of phosphoric anhydride. The reaction time is 10 min using an equimolar amount of P₄O₁₀ with respect to the other reagents, but the reaction occurs also, even if with longer reaction times, with very small amounts of P₄O₁₀.In addition, this method provides a clean and ‘green’ approach to hydantoins, compounds of great interest in biological and pharmacological fields.     

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.     

Theoretical study of the kojic acid structure in gas phase and aqueous solution

Density functional calculations at the B3LYP/6‐311++G** level have been performed to determine the ground‐state conformational preference for kojic acid, a widely used skin‐whitening, antibrowning, and antibacterial agent. It is found that the gas phase consists almost entirely of the 5‐hydroxy‐2‐(hydroxymethyl)‐4H‐pyran‐4‐one tautomer, although several rotamers of this are prevalent. In aqueous solution, however, other tautomers are also present. The validity of the calculations is confirmed by the observed FTIR, NMR, and UV–vis spectra, which show good correspondence with the theoretical spectra. The electronic interactions are interpreted in terms of charge and bond order analysis as well as the composition of the HOMO and LUMO. The calculations show that kojic acid has partial aromatic character and is a good nucleophile. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

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 chemical shifts of 1-(2',4'-dinitrophenyl) and 1-(2',4',6'-trinitrophenyl) pyrazoles in the solid state and in solution

The (13)C and (15)N CPMAS NMR spectra of 18 pyrazoles substituted at position 1 by dinitrophenyl and trinitrophenyl (picryl) groups have been recorded. To help in the assignments, some of these compounds were studied in DMSO-d(6) solution. Phenomena such as the conformation of the N-aryl groups and broadening of splittings due to quadrupolar nuclei are discussed.     

Deuterium isotope effects on 15N chemical shifts of double Schiff bases in the solid state and solution

The proton transfer equilibrium in a series of double Schiff base derivatives of trans‐1,2‐diaminocyclohexane in solution and the solid state was studied by means of ¹⁵N NMR spectroscopy and analysis of the deuterium isotope effect on the chemical shifts Δ¹⁵N(D). The presence of a proton transfer equilibrium in the N‐2‐hydroxynaphthylidene moieties of the Schiff bases studied in the solid state at room temperature was evidenced. The results confirmed the interrelation of the two hydrogen bonds in double Schiff base derivatives of trans‐1,2‐diaminocyclohexane. Copyright © 2003 John Wiley & Sons, Ltd.     

The structure of 1-formyl-3-phenyl-Δ-pyrazoline in the gas phase (DFT calculations), in solution (NMR) and in the solid state (X-ray crystallography)

The molecular structure of 1-formyl-3-phenyl-Δ²-pyrazoline was determined by X-ray crystallography (triclinic, P-1). The geometry thus obtained was compared with that obtained by DFT calculations. The GIAO method was used to calculate absolute shieldings, which agree conveniently with those measured by ¹³C and ¹⁵N NMR. The title compound appears to be an essentially planar molecule.     

Multinuclear magnetic resonance study of the structure and tautomerism of azide and iminophosphorane derivatives of chloropyridazines

Some azido‐ and iminophosphorane derivatives of 3,6‐dichloro‐ and 3,4,5,6‐tetrachloropyridazine were synthesized and studied by means of NMR measurements. Based on multinuclear data (chemical shifts, coupling constants) for compounds containing the azide group, no potentially possible tetrazole–azide equilibrium can be observed, even under acidic conditions. An unusual substitution of a chlorine atom (in position 4) of tetrachloropyridazine in the reaction with hydrazine was demonstrated by NMR measurements of two newly synthesized compounds containing azido‐ and iminophosphorane groups. Using multinuclear magnetic resonance data, the sites of ethylation and protonation of azido‐ and iminophosphorane derivatives of chloropyridazines were established. In the case of the tetrazolopyridazines, ethylation occurs at the N1′ and N2′ atoms, whereas for monocyclic compounds it takes place at the N1 and/or N2 atoms of the pyridazine ring. Preferred sites of protonation are the N1′ atom of the tetrazole ring and the N1 atom of the pyridazine ring. Moreover, the structures of potassium salts of 6‐(3‐cyano‐1‐triazeno)tetrazolo[1,5‐b] pyridazine and its amido derivative were established using NMR data, especially ¹⁵N NMR chemical shifts. Copyright © 2002 John Wiley & Sons, Ltd.     

The structure of fosfomycin salts in solution and in the solid state by nuclear magnetic resonance spectroscopy and DFT calculations

Two samples of fosfomycin salts, the calcium and the disodium ones, were used to record their NMR spectra both in solution and in the solid state. The existence of fosfomycin in a neutral and two ionized structures (mono and dianion) was considered to interpret the spectra that were solved using the GIAO calculated chemical shifts of the minimum energy conformations. Although the starting materials were dianions, the spectra in solution show the presence of monoanions.     

Molecular structure of 2-(hydroxyimino)propanohydroxamic acid in solid state and DMSO solution

The 1H and 13C NMR spectra of 2-(hydroxyimino)propanohydroxamic acid (hpha) were measured in DMSO-d6 solution. The set of several monomeric structures along with the cluster of H-bonded hpha with three DMSO molecules were proposed to fit the experimental data. The calculated chemical shifts [B3LYP/6-311++G(d,p)] strongly suggested the formation of the cluster in which all the labile protons were H-bonded to the solvent molecules. The comparison between experimental and calculated Raman spectra of hpha in DMSO also suggested that in these conditions the investigated compound forms the proposed cluster rather than dimers. According to our calculations [B3LYP/6-31+G(d)] this cluster was energetically stabilized (84-106 kJ mol-1) compared to postulated dimeric structures. On the other hand, formation of dimers was proposed to be present for hpha in solid state. The comparison of the vibrational data (IR, RS) with the computed harmonic frequencies of three most probable dimers [B3LYP/6-31+G(d)] suggested that the dimer in which molecules adopted the zEe-keto form and were linked by two symmetric, almost linear H-bonds between the carbonyl oxygen atoms and the hydroxamic O-H protons was the predominant species of hpha in the solid state. Thus, the structures of hpha in solid state and DMSO solution appeared to be different.     

The structure of xenon hexafluoride in the solid state

According to single crystal X-ray diffraction, neutron powder diffraction, solid state MAS NMR data, and differential scanning calorimetry, XeF₆ exists in at least six different modifications. Three of them are formed at temperatures above room temperature, one exists at room temperature, while two have been found at low temperatures. In the high temperature modifications XeF₆ forms a non-symmetric tetramer, better described as a cyclic trimer with a weakly associated monomer. The normal temperature modification is the previously described cubic phase IV, having disordered tetrameric and hexameric units. The low temperature modifications are regular tetramers. Only in presence of HF symmetric dimers are formed.     

The behavior of Gliclazide in solution and in the solid state: a case of organic compound presenting a solid‐solution structure

The structure of the hypoglycemic agent Gliclazide has been studied by ¹H, ¹³C, and ¹⁵N NMR in solution (CDCl₃ and DMSO‐d₆) and in the solid state. In the solid state, the compound crystallizes as an EZ isomer without dynamic properties. In CDCl₃ solution, the structure is still EZ but with a slow nitrogen inversion about the pyrrolidine nitrogen: two invertomers have been observed and characterized. In DMSO‐d₆, the rate is faster and only averaged signals were observed. GIAO calculated absolute shieldings were used to confirm the nature of the observed species. In the solid state, Gliclazide presents the phenomenon of solid‐solution with two disordered conformations present in the crystal at a 90:10 ratio. Copyright © 2009 John Wiley & Sons, Ltd.     

The structure of glibenclamide in the solid state

The structure of glibenclamide, 5‐chloro‐N‐(2‐{4‐[(cyclohexylamino)carbonyl] aminosulfonyl}phenyl) ethyl)‐2‐methoxybenzamide, an important antidiabetic drug, has been studied both in solution and in the solid state by a combination of NMR spectroscopy and theoretical calculations. The possibility that glibenclamide suffers a tautomerization under melting to afford a desmotrope was rejected. Copyright © 2012 John Wiley & Sons, Ltd.     

The N and C solid state NMR study of intramolecular hydrogen bond in some Schiff bases

In present work set of eight Schiff bases derived from substituted salicylaldehydes and aliphatic and aromatic amines has been studied in the solid state by ¹⁵N and ¹³C CPMAS NMR methods. ¹⁵N CPMAS NMR measurement is especially useful for investigation of the tautomerism in the compounds considered, owing to the large difference in the nitrogen chemical shifts of OH and NH tautomers. In the solid state, four of the compounds examined were shown by ¹⁵N CPMAS NMR to exist as OH tautomeric forms, and the remaining four as the corresponding NH forms with different stage of proton transfer process, from oxygen to nitrogen site.

This was confirmed by ¹³C CPMAS. The results reported were compared with those obtained for only two compounds in CDCl₃ solutions (solubility problems).     

13C NMR spectra and the structure of dithizone

The structural characteristics of dithizone in the solid state and in solution were studied by a high-resolution¹³C NMR method. A highly symmetrical structure of dithizone was established in the crystalline state, and it was suggested that it exhibits dual behavior in complexation reactions with metal ions.V. I. Vernadskii Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, 117975 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 113–117, January, 1992.     

Protonation of leucoemeraldine in the solid state and in solution

The protonation of leucoemeraldine in power form and in N-methylpyrrolidinone (NMP) solution by HCIO₄ and HBF₄ has been studied by x-ray photoelectron spectroscopy (XPS), infrared (IR), and ultraviolet (UV)-visible absorption spectroscopy. In powder form, less than 25% of the amine nitrogens can be protonated in the absence of oxygen. The effects of oxygen on the degree of protonation and the distribution of amine and imine units upon deprotonation of the salt are investigated. The degree of protonation in leuccemeraldine can be increased to about 50% with 3 M HCIO₄, similar to that achievable with emeraldine base in powder form. In NMP solution, leucoemeraldine is easily oxidized by dissolved oxygen. Protonation of both leucoemeraldine and emeraldine base in NMP solutions results in metastable species which gradually undergo deprotonation. The resulting products are affected by the O₂ content of the solutions. © 1993 John Wiley & Sons, Inc.     

Acid-base properties of xanthosine 5'-monophosphate (XMP) and of some related nucleobase derivatives in aqueous solution: micro acidity constant evaluations of the (N1)H versus the (N3)H deprotonation ambiguity

The first acidity constant of fully protonated xanthosine 5'-monophosphate, that is, of H3(XMP)+, was estimated by means of a micro acidity constant scheme and the following three deprotonations of the H2(XMP)+/- (pKa=0.97), H(XMP)- (5.30), and XMP2- (6.45) species were determined by potentiometric pH titrations; further deprotonation of (XMP-H)3- is possible only with pKa>12. The most important results are that the xanthine residue is deprotonated before the P(O)2(OH)- group loses its final proton; that is, twofold negatively charged XMP carries one negative charge in the pyrimidine ring and one at the phosphate group. Micro acidity constant evaluations reveal that this latter mentioned species occurs with a formation degree of 88 %, whereas its tautomer with a neutral xanthine moiety and a PO3(2-) group is formed only to 12 %; this distinguishes XMP from its related nucleoside 5'-monophosphates, like guanosine 5'-monophosphate. At the physiological pH of about 7.5 mainly (XMP-H)3- exists. The question, which of the purine sites, (N1)H or (N3)H, is deprotonated in this species cannot be answered unequivocally, though it appears that the (N3)H site is more acidic. By application of several methylated xanthine species intrinsic micro acidity constants are calculated and it is shown that, for example, for 7-methylxanthine the N1-deprotonated tautomer occurs with a formation degree of about 5 %; a small but significant amount that, as is discussed, may possibly be enhanced by metal ion coordination to N7, which is known to occur preferably to this site.