Keto–Enol Tautomerism of Phenindione and Its Derivatives: An NMR and Density Functional Theory (DFT) Reinvestigation

Keto–enol tautomerism of phenindione (2-phenyl-1,3-indandione) and of its 4-phenyl-substituted derivatives was reinvestigated by NMR, supported by density functional theory (DFT) quantum-mechanical calculations. The calculated data quantitatively confirmed the stabilization in DMSO solution of the enol form by a strong hydrogen bond. The symmetry of the NMR spectra of the enol forms was explained by a fast proton transfer between carbonyl oxygen atoms, which is facilitated by the formation of a strong ionic complex of the enol form and an anion. It was shown that keto–enol tautomerization also proceeds with the participation of a similar complex between an anion and the diketo form of 2-phenyl-1,3-indandione

C_Ar–H···O Hydrogen Bonds in Substituted Isobenzofuranone Derivatives: Geometric, Topological, and NMR Characterization

Substituted isobenzofuranone derivatives <b>1a</b>–<b>3a</b> and bindone <b>4</b> are characterized by the presence of an intramolecular C_Ar–H···O hydrogen bond in the crystal (X-ray), solution (¹H NMR and specific and nonspecific IEF-PCM solvation model combined with MP2 and B3LYP methods), and gas (MP2 and B3LYP) phases. According to geometric and AIM criteria, the C_Ar–H···O interaction weakens in <b>1a</b>–<b>3a</b> (independent of substituent nature) and in <b>4</b> with the change in media in the following order: gas phase > CHCl₃ solution > DMSO solution > crystal. The maximum value of hydrogen bond energy is 4.6 kcal/mol for <b>1a</b>–<b>3a</b> and 5.6 kcal/mol for <b>4</b>. Both in crystals and in solutions, hydrogen bond strength increases in the order <b>1a</b> < <b>2a</b> < <b>3a</b> with the rising electronegativity of the ring substituents (H < OMe < Cl). The best method for calculating ¹H NMR chemical shifts (δ^calcd – δ^expl < 0.7 ppm) of hydrogen bonded and nonbonded protons in <b>1a</b>–<b>3a</b> and <b>1b</b>–<b>3b</b> (isomers without hydrogen bonds) is the GIAO method at the B3LYP level with the 6-31G** and 6-311G** basis sets. For the C–H moiety involved in the hydrogen bond, the increase of the spin–spin coupling constant ¹<i>J</i>(¹³C–¹H) by about 7.5 Hz is in good agreement with calculations for C–H bond shortening and for blue shifts of C–H stretching vibrations (by 55–75 cm^–1)

C_Ar–H···O Hydrogen Bonds in Substituted Isobenzofuranone Derivatives: Geometric, Topological, and NMR Characterization

Substituted isobenzofuranone derivatives <b>1a</b>–<b>3a</b> and bindone <b>4</b> are characterized by the presence of an intramolecular C_Ar–H···O hydrogen bond in the crystal (X-ray), solution (¹H NMR and specific and nonspecific IEF-PCM solvation model combined with MP2 and B3LYP methods), and gas (MP2 and B3LYP) phases. According to geometric and AIM criteria, the C_Ar–H···O interaction weakens in <b>1a</b>–<b>3a</b> (independent of substituent nature) and in <b>4</b> with the change in media in the following order: gas phase > CHCl₃ solution > DMSO solution > crystal. The maximum value of hydrogen bond energy is 4.6 kcal/mol for <b>1a</b>–<b>3a</b> and 5.6 kcal/mol for <b>4</b>. Both in crystals and in solutions, hydrogen bond strength increases in the order <b>1a</b> < <b>2a</b> < <b>3a</b> with the rising electronegativity of the ring substituents (H < OMe < Cl). The best method for calculating ¹H NMR chemical shifts (δ^calcd – δ^expl < 0.7 ppm) of hydrogen bonded and nonbonded protons in <b>1a</b>–<b>3a</b> and <b>1b</b>–<b>3b</b> (isomers without hydrogen bonds) is the GIAO method at the B3LYP level with the 6-31G** and 6-311G** basis sets. For the C–H moiety involved in the hydrogen bond, the increase of the spin–spin coupling constant ¹<i>J</i>(¹³C–¹H) by about 7.5 Hz is in good agreement with calculations for C–H bond shortening and for blue shifts of C–H stretching vibrations (by 55–75 cm^–1)

C_Ar–H···O Hydrogen Bonds in Substituted Isobenzofuranone Derivatives: Geometric, Topological, and NMR Characterization

Substituted isobenzofuranone derivatives <b>1a</b>–<b>3a</b> and bindone <b>4</b> are characterized by the presence of an intramolecular C_Ar–H···O hydrogen bond in the crystal (X-ray), solution (¹H NMR and specific and nonspecific IEF-PCM solvation model combined with MP2 and B3LYP methods), and gas (MP2 and B3LYP) phases. According to geometric and AIM criteria, the C_Ar–H···O interaction weakens in <b>1a</b>–<b>3a</b> (independent of substituent nature) and in <b>4</b> with the change in media in the following order: gas phase > CHCl₃ solution > DMSO solution > crystal. The maximum value of hydrogen bond energy is 4.6 kcal/mol for <b>1a</b>–<b>3a</b> and 5.6 kcal/mol for <b>4</b>. Both in crystals and in solutions, hydrogen bond strength increases in the order <b>1a</b> < <b>2a</b> < <b>3a</b> with the rising electronegativity of the ring substituents (H < OMe < Cl). The best method for calculating ¹H NMR chemical shifts (δ^calcd – δ^expl < 0.7 ppm) of hydrogen bonded and nonbonded protons in <b>1a</b>–<b>3a</b> and <b>1b</b>–<b>3b</b> (isomers without hydrogen bonds) is the GIAO method at the B3LYP level with the 6-31G** and 6-311G** basis sets. For the C–H moiety involved in the hydrogen bond, the increase of the spin–spin coupling constant ¹<i>J</i>(¹³C–¹H) by about 7.5 Hz is in good agreement with calculations for C–H bond shortening and for blue shifts of C–H stretching vibrations (by 55–75 cm^–1)

Hydrogen Bonding in Bis(6-amino-1,3-dimethyluracil-5-yl)-methane Derivatives: Dynamic NMR and DFT Evaluation

Three bis­(6-amino-1,3-dimethyluracil-5-yl)-methane derivatives were studied experimentally by variable-temperature ¹H NMR in polar aprotic solutions (CD₂Cl₂, C₅D₅N, C₂D₂Cl₄) and computationally by DFT. The unusual for diarylmethanes coplanar conformation of dimethyluracil rings of each molecule is held by a pair of unequal intramolecular N–H···O hydrogen bonds. We show the presence of two dynamic processes involving breakage/formation of these bonds. First, it is two independent NH₂ group rotations, each coupled to nitrogen inversion. Second, it is uracil ring rotations (ring flips). The thermodynamic parameters (Δ<i>H</i>^‡, Δ<i>S</i>^‡, and Δ<i>G</i>^‡) of both processes were estimated by the full line shape analysis of NMR signals and also by DFT calculations. We demonstrate that, though the ring flips exchange pairs of NH protons, the two processes are not coupled: during the ring flip NH₂ groups do not rotate, and during the NH₂ rotation the rings do not necessarily rotate. Unlike in many other diarylmethanes, the ring flips in the studied compounds are happening stepwise; i.e., the configuration when both rings are “in flight” at the same time is energetically unfavorable (small degree of “cog wheel effect”). The signs of the Δ<i>S</i>^‡ values indicate that the molecular flexibility increases during the NH₂ rotations, but decreases during the ring flips

2<i>H</i>‑Indazole Tautomers Stabilized by Intra- and Intermolecular Hydrogen Bonds

2-[(2H-Indazol-3-yl)­methylene]-1H-indene-1,3­(2H)-dione 6 and (E)-2-[(2H-indazol-3-yl)­methylene]-2,3-dihydro-1H-inden-1-one 7 have been synthesized. In the crystal, the NH hydrogen atom of 6 is disordered between the N(1) and N(2) atoms with the population ratio of 0.69:0.31. Molecule 7 crystallizes in two tautomeric polymorphs: 7-1H tautomer (yellow) and 7-2H tautomer (red). Both 6 and 7 form centrosymmetric dimers in the crystal with the monomeric units linked by CO···H···N bifurcated hydrogen bonds in 6 and N–H···N hydrogen bonds in 7. According to 1H and 13C NMR data, in DMSO-d6 solution, the 6-1H tautomer predominates, whereas in less polar CDCl3 or CD2Cl2, the 6-2H tautomer is stabilized by a strong N–H···OC intramolecular hydrogen bond. Compound 7 in dimethyl sulfoxide (DMSO) or ethanol solutions exists in the form of 7-1H and 7-2H tautomers. On the example of the 7-2H tautomer, it was shown for the first time that the 2H tautomers of 3-substituted indazoles can be stabilized by an intermolecular hydrogen bond and may remain in aprotic solvents almost indefinitely. However, in the open air or in water, fast 2H → 1H tautomerization occurs. As follows from density functional theory calculations, the high stability of the 2H form in solution is due to the formation of centrosymmetric dimers, which are more stable than the corresponding dimers of the 1H tautomer

2<i>H</i>‑Indazole Tautomers Stabilized by Intra- and Intermolecular Hydrogen Bonds

2-[(2H-Indazol-3-yl)­methylene]-1H-indene-1,3­(2H)-dione 6 and (E)-2-[(2H-indazol-3-yl)­methylene]-2,3-dihydro-1H-inden-1-one 7 have been synthesized. In the crystal, the NH hydrogen atom of 6 is disordered between the N(1) and N(2) atoms with the population ratio of 0.69:0.31. Molecule 7 crystallizes in two tautomeric polymorphs: 7-1H tautomer (yellow) and 7-2H tautomer (red). Both 6 and 7 form centrosymmetric dimers in the crystal with the monomeric units linked by CO···H···N bifurcated hydrogen bonds in 6 and N–H···N hydrogen bonds in 7. According to 1H and 13C NMR data, in DMSO-d6 solution, the 6-1H tautomer predominates, whereas in less polar CDCl3 or CD2Cl2, the 6-2H tautomer is stabilized by a strong N–H···OC intramolecular hydrogen bond. Compound 7 in dimethyl sulfoxide (DMSO) or ethanol solutions exists in the form of 7-1H and 7-2H tautomers. On the example of the 7-2H tautomer, it was shown for the first time that the 2H tautomers of 3-substituted indazoles can be stabilized by an intermolecular hydrogen bond and may remain in aprotic solvents almost indefinitely. However, in the open air or in water, fast 2H → 1H tautomerization occurs. As follows from density functional theory calculations, the high stability of the 2H form in solution is due to the formation of centrosymmetric dimers, which are more stable than the corresponding dimers of the 1H tautomer

2<i>H</i>‑Indazole Tautomers Stabilized by Intra- and Intermolecular Hydrogen Bonds

2-[(2H-Indazol-3-yl)­methylene]-1H-indene-1,3­(2H)-dione 6 and (E)-2-[(2H-indazol-3-yl)­methylene]-2,3-dihydro-1H-inden-1-one 7 have been synthesized. In the crystal, the NH hydrogen atom of 6 is disordered between the N(1) and N(2) atoms with the population ratio of 0.69:0.31. Molecule 7 crystallizes in two tautomeric polymorphs: 7-1H tautomer (yellow) and 7-2H tautomer (red). Both 6 and 7 form centrosymmetric dimers in the crystal with the monomeric units linked by CO···H···N bifurcated hydrogen bonds in 6 and N–H···N hydrogen bonds in 7. According to 1H and 13C NMR data, in DMSO-d6 solution, the 6-1H tautomer predominates, whereas in less polar CDCl3 or CD2Cl2, the 6-2H tautomer is stabilized by a strong N–H···OC intramolecular hydrogen bond. Compound 7 in dimethyl sulfoxide (DMSO) or ethanol solutions exists in the form of 7-1H and 7-2H tautomers. On the example of the 7-2H tautomer, it was shown for the first time that the 2H tautomers of 3-substituted indazoles can be stabilized by an intermolecular hydrogen bond and may remain in aprotic solvents almost indefinitely. However, in the open air or in water, fast 2H → 1H tautomerization occurs. As follows from density functional theory calculations, the high stability of the 2H form in solution is due to the formation of centrosymmetric dimers, which are more stable than the corresponding dimers of the 1H tautomer

Intra- and Intermolecular Hydrogen Bonds in Pyrrolylindandione Derivatives and Their Interaction with Fluoride and Acetate: Possible Anion Sensing Properties

The series of push–pull compounds containing the pyrrole ring as a donor and the 1,3-indandione derived moieties as the acceptor unit were synthesized, and strong intramolecular hydrogen bonding in their molecules was studied. In the presence of fluoride and acetate anions their solutions undergo color changes. It was shown by NMR, UV–vis, and quantum chemical calculations including AIM analysis that all these compounds undergo solvent-assisted rupture of the intramolecular hydrogen bond followed by the formation of a strong intermolecular hydrogen bond with fluoride and acetate anions which finally abstract a proton from the pyrrole ring. The insensitivity of the studied compounds to other anions (Cl, Br, HSO₄, PF₆) is consequence of the instability of the corresponding hydrogen-bonded complexes