Strong Intramolecular Hydrogen Research Articles

Strong intramolecular hydrogen bonding in confined amino acids

Intramolecular hydrogen bonding is evaluated in three different amino acids encapsulated in C60 fullerene in the context of electron density analysis. While conventional intramolecular hydrogen bonding in isolated amino acids are dominated by electrostatic character, it is shown that strong intramolecular hydrogen bonding can be formed in confined amino acids so that in two cases covalent intramolecular hydrogen bonding is appeared in the confined species. Also, results show that zwitterionic amino acids are stable in confined state, where no implicit or explicit solvation is applied. Covalent character for intramolecular hydrogen bonding in amino acids have not yet been reported.

Photophysical studies of organostannoxane supported hexafluorophore assemblies

The condensation reaction between n-butylstannoic acid and ArCOOH (Ar = 1-naphthyl-CH2 (1), 9-anthracenyl (2), 9-xanthenyl (3), 1-pyrenyl-(CH2)3 (4), 1-pyrenyl (5)) afforded hexameric organostannoxanes [n-BuSn(O)(O2CAr)]6 in high yield. The molecular structures of compounds 2 and 3 were confirmed by single crystal X-ray diffraction analysis. These compounds possess a drum-like structure and each molecule is attached with six fluorophores through carboxylate functionality. 119Sn NMR and MALDI-TOF analyses suggest that the compounds 1, 4, and 5 also belong to the family of organotin drum structure. There are also various intra- and intermolecular interaction between the fluorophores. In particular, compound 2 shows a strong intramolecular hydrogen bond (CH····π 2.489 Å) between two anthracene moieties. However, such interaction is weaker in 3. The absorption spectra of 1–5 indicate that λmax was very slightly red-shifted with respect to their fluorophore carboxylic acid. Fluorescence measurements reveal that these molecules are good blue emitters in solution state but red-shifted in the solid-state. Quantum yield calculation shows that emission efficiencies decreased for smaller spacers between fluorophore and stannoxane core. We have carried out thermal studies for all compounds. These suggest that the compounds are robust and stable until about 300 °C. Interestingly, we have demonstrated the synthesis of SnO2 from the hexameric organotin drum 3 by heating in the temperature range 600–1200 °C.

Maleate salts of bedaquiline.

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-meth-oxy-quinolin-3-yl)-3-hy-droxy-3-(naphthalen-1-yl)-4-phenyl-but-yl]di-methyl-aza-nium 3-carb-oxy-prop-2-enoate}, C32H32BrN2O2 +·C4H3O4 -, namely, a hemihydrate, a tetra-hydro-furan (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydro-maleate and a singly protonated bedaquilinium cation. The maleate exhibits the strong intra-molecular hydrogen bond typical for cis-di-carb-oxy-lic acid anions. The conformations of the cations and packing inter-actions in the maleate salts are compared to those of free base bedaquiline and other bedaquilinium salts.

Naphthalenediimides with High Fluorescence Quantum Yield: Bright-Red, Stable, and Responsive Fluorescent Dyes.

The naphthalenediimide (NDI) scaffold in contrast to its higher congeners possess low-fluorescence. In spite of elegant synthetic developments, a highly emissive NDI is quite rare to find, as well as, a green-light-emitting NDI is yet to be explored. Herein, we report a novel class of symmetric and asymmetric NH2 -substituted core-NDIs (1-5) with tunable fluorescence in the visible region and extending to the NIR frontier. Importantly, the bis-NH2 -substituted NDI 2 revealed quantum yield, of ≈81 and ≈68 % in toluene and DMSO, respectively, suggesting versatility of the fluorophore in a wide range of solvent polarity. The dye 1 is shown to be the first NDI-based green-light emitter. The donor piperidine group in 5 diminish the by 40-fold providing a lever to modulate the excited-state intramolecular proton transfer (ESIPT) process. Our synthetic protocol applies a Pd catalyst and a benign hydride source simplifying the non-trivial -NH2 group integration at the NDI-core. TD-DFT calculations predicted strong intramolecular hydrogen bonds in the excited state in the bulk nonpolar medium and responsiveness to solvent polarity. The maximization of the NDI emission outlined here would further boost the burgeoning repertoire of applications of the NDI scaffold.

Catalytic Conversion of Sugar-Derived Polyhydroxy Acid to Trimellitate

Biomass resources, especially carbohydrates derived from cellulose and hemicellulose, could be utilized as an alternative feedstock for the production of fuel and bulk chemicals. Here, we present a sustainable route for the synthesis of trimethyl trimellitate from 1,6-dimethyl galactarate, the diester of sugar-derived polyhydroxy galactaric acid. The process starts with the deoxydehydration reaction of 1,6-dimethyl galactarate to form dimethyl muconate with an 84% yield. Nuclear magnetic resonance (NMR) and density functional theory results show that the molecular structure of 1,6-dimethyl galactarate possesses strong intramolecular hydrogen bond networks and is endowed with chemical recalcitrance. ¹H NMR tests of variable catalyst concentrations reveal that the introduction of ammonium perrhenate could weaken the intramolecular hydrogen bond effect and activate the chemically inert molecules. The Diels–Alder reaction of muconate and acrylate is conducted efficiently to produce a substituted cyclohexene intermediate without any catalyst used, and a 72% yield of the target product, trimethyl trimellitate, is obtained via the dehydro-aromatization reaction of the cycloadduct. This new approach provides a template path for the synthesis of aromatic oxygenated compounds and would promote the development of green polymer materials.

NMR Structure Elucidation of Naphthoquinones from Quambalaria cyanescens.

Naphthoquinones isolated from Quambalaria cyanescens (quambalarines) are natural pigments possessing significant cytotoxic and antimicrobial properties. Determining the structure of naphthoquinone compounds is important for the understanding of their biological activities and the informed synthesis of related analogues. Identifying quambalarines is challenging, because they contain a hydroxylated naphthoquinone scaffold and have limited solubility. Here, we report a detailed structural study of quambalarine derivatives, which form strong intramolecular hydrogen bonds (IMHBs) that enable the formation of several tautomers; these tautomers may complicate structural investigation due to their fast interconversion. To investigate tautomeric equilibria and identify new quambalarines, we complemented the experimental NMR spectroscopy data with density functional theory (DFT) calculations.

Choline Hydrogen Dicarboxylate Ionic Liquids by X-ray Scattering, Vibrational Spectroscopy and Molecular Dynamics: H-Fumarate and H-Maleate and Their Conformations.

We explore the structure of two ionic liquids based on the choline cation and the monoanion of the maleic acid. We consider two isomers of the anion (H-maleate, the cis-isomer and H-fumarate, the trans-isomer) having different physical chemical properties. H-maleate assumes a closed structure and forms a strong intramolecular hydrogen bond whereas H-fumarate has an open structure. X-ray diffraction, infrared and Raman spectroscopy and molecular dynamics have been used to provide a reliable picture of the interactions which characterize the structure of the fluids. All calculations indicate that the choline cation prefers to connect mainly to the carboxylate group through OH⋯O interactions in both the compounds and orient the charged head N(CH3)3+ toward the negative portion of the anion. However, the different structure of the two anions affects the distribution of the ionic components in the fluid. The trans conformation of H-fumarate allows further interactions between anions through COOH and CO2− groups whereas intramolecular hydrogen bonding in H-maleate prevents this association. Our theoretical findings have been validated by comparing them with experimental X-ray data and infrared and Raman spectra.

Crystal, mol-ecular structure and Hirshheld surface analysis of 5-hy-droxy-3,6,7,8-tetra-meth-oxy-flavone.

The title compound (systematic name: 5-hydroxy-3,6,7,8-tetramethoxy-2-phenyl-4H-chromen-4-one), C19H18O7, is a flavone that was isolated from a butanol extract of the herb Scutellaria nepetoides M. Pop. The flavone mol-ecule is almost planar, with a dihedral angle between the planes of the benzo-pyran-4-one group and the attached phenyl ring of 6.4 (4)°. The 5-hy-droxy group forms a strong intra-molecular hydrogen bond with the carbonyl group, resulting in a six-membered hydrogen-bonded ring. The crystal structure has triclinic (P ) symmetry. In the crystal, the mol-ecules are linked by C-H⋯O hydrogen bonds into a two dimensional network parallel to the ab plane. The Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (53.9%) and H⋯O/O⋯H (20.9%) inter-actions.

Deducing the Conformational Properties of a Tyrosine Kinase Inhibitor in Solution by Optical Spectroscopy and Computational Chemistry.

Dacomitinib (PF-00299804) was recently approved by the Food and Drug Administration (FDA) as a tyrosine kinase inhibitor (TKI). Unfortunately, side effects and disease resistance eventually result from its use. Off-target effects in some kinase inhibitors have arisen from drug conformational plasticity; however, the conformational states of Dacomitinib in solution are presently unknown. To fill this gap, we have used computational chemistry to explore optimized molecular geometry, properties, and ultraviolet-visible (UV-Vis) absorption spectra of Dacomitinib in dimethyl sulfoxide (DMSO) solution. Potential energy scans led to the discovery of two planar and two twisted conformers of Dacomitinib. The simulated UV-Vis spectral signatures of the planar conformers reproduced the two experimental spectral bands at 275 and 343 nm in solution. It was further discovered that Dacomitinib forms conformers through its three flexible linkers of two C–NH–C bridges, which control the orientations of the 3-chloro-4-fluoroaniline ring (Ring C) and the quinazoline ring (Rings A and B) and the 4-piperidin-1-yl-buten-2-nal side chain, and one C–O–C local bridge which controls the methoxy group locally. When in isolation, these flexible linkers form close hexagon and pentagon loops through strong intramolecular hydrogen bonding so that the “planar” conformers Daco-P1 and Daco-P2 are more stable in isolation. Such flexibility of the ligand and its ability to dock and bind with protein also depend on their interaction with the environment, in addition to their energy and spectra in isolation. However, an accurate quantum mechanical study on drug/ligand conformers in isolation provides necessary reference information for the ability to form a complex with proteins.

Effect of intramolecular hydrogen-bond formation on the molecular conformation of amino\xa0acids

The molecular conformation of the carboxyl group can be crucial for its chemical properties and intermolecular interactions, especially in complex molecular environments such as polypeptides. Here, we study the conformational behaviour of the model amino acid N-acetylproline in solution at room temperature with two-dimensional infrared spectroscopy. We find that the carboxyl group of N-acetylproline adopts two distinct conformations, syn- and anti-. In the syn-conformer the O–H group is oriented at ~60∘ with respect to the C=O and in the anti-conformer the O–H is anti-parallel to the C=O. In hydrogen-bond accepting solvents such as dimethyl sulfoxide or water, we observe that, similar to simple carboxylic acids, around 20% of the -COOH groups adopt an anti-conformation. However, when N-acetylproline is dissolved in a weakly hydrogen-bond accepting solvent (acetonitrile), we observe the formation of a strong intramolecular hydrogen bond between the carboxyl group in the anti-conformation and the amide group, which stabilizes the anti-conformer, increasing its relative abundance to ~60%.

Study of p-(3-carboxy-1-adamantyl)-calix[4]arene with hydrogen bonds along the upper and lower rim by IR spectroscopy and DFT.

The IR spectra of p-(3-carboxy-1-adamantyl)-calix[4]arene (AdC4A) were studied. Using IR spectroscopy, it has been shown that in calixarene in dilute solution in CCl4, there was no free hydroxyl absorption band. The hydroxyl group band was characterized by a very low frequency, which indicates a strong intramolecular hydrogen bond on the lower rim of the calixarene molecules. On the upper rim of the calixarene, the carboxyl groups form cyclic dimer or tetramer complexes via intermolecular hydrogen bonds. The cone conformation persists, but there is a mutual influence of the hydrogen bonds along the top and bottom rims of the calixarene molecule. The structure with dimeric hydrogen bonds between the carboxyl groups is 16.5KJ/mol more preferable than the structure with tetrameric cyclic hydrogen bonds for AdC4A. The reactivity depends on the type of association on the upper rim, whether these are hydrogen-bonded dimers or cyclic tetrameric association. Graphical abstract .

Intramolecular hydrogen-bonding effects on structural and electronic properties of pyrrole-phenylene derivatives: a DFT study

Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations are employed to evaluate structural, electronic, charge-transport and optical properties of pyrrole-phenylene copolymer ((Py-co-Ph)4) and its derivatives. The distorted coplanar structure is found for the pristine pyrrole-phenylene copolymer, while the functionalized structures with –OCH3, –OH, and –F exhibit the highly coplanar structures due to larger π-orbital overlap along neighboring backbones and strong intramolecular hydrogen bonding interaction. A good linear correlation between HOMO and LUMO as a functional resonance effect is observed. A better hole transport behavior is obtained from –OCH3, –N(CH3)2, –OH, –CN, and –F functionalizations compared to the parent. According to the optical properties, –CN, –COOH, and –NO2 substitutions reveal the absorption peaks covering the solar region, which are characterized as the potential solar materials.

Polymyxins Bind to the Cell Surface of Unculturable Acinetobacter baumannii and Cause Unique Dependent Resistance.

Multidrug‐resistant Acinetobacter baumannii is a top‐priority pathogen globally and polymyxins are a last‐line therapy. Polymyxin dependence in A. baumannii (i.e., nonculturable on agar without polymyxins) is a unique and highly‐resistant phenotype with a significant potential to cause treatment failure in patients. The present study discovers that a polymyxin‐dependent A. baumannii strain possesses mutations in both lpxC (lipopolysaccharide biosynthesis) and katG (reactive oxygen species scavenging) genes. Correlative multiomics analyses show a significantly remodeled cell envelope and remarkably abundant phosphatidylglycerol in the outer membrane (OM). Molecular dynamics simulations and quantitative membrane lipidomics reveal that polymyxin‐dependent growth emerges only when the lipopolysaccharide‐deficient OM distinctively remodels with ≥ 35% phosphatidylglycerol, and with “patch” binding on the OM by the rigid polymyxin molecules containing strong intramolecular hydrogen bonding. Rather than damaging the OM, polymyxins bind to the phosphatidylglycerol‐rich OM and strengthen the membrane integrity, thereby protecting bacteria from external reactive oxygen species. Dependent growth is observed exclusively with polymyxin analogues, indicating a critical role of the specific amino acid sequence of polymyxins in forming unique structures for patch‐binding to bacterial OM. Polymyxin dependence is a novel antibiotic resistance mechanism and the current findings highlight the risk of ‘invisible’ polymyxin‐dependent isolates in the evolution of resistance.

Crystal structure, Hirshfeld surface analysis and computational study of a rhodamine B-salicyl-aldehyde Schiff base derivative.

The mol-ecular structure of the title compound {systematic name: 3',6'-bis(di-ethyl-amino)-2-[(2-hy-droxy-benzyl-idene)amino]-spiro-[isoindoline-1,9'-xan-then]-3-one}, C35H36N4O3 or RbSa, can be seen as being composed of two parts sharing a central quaternary carbon atom. Both the xanthene and iso-indole moieties are nearly planar: 14 atoms in the former moiety show an r.m.s. deviation of 0.0411 Å and eleven atoms in the latter moiety show an r.m.s. deviation of 0.0545 Å. These two planes are almost perpendicular to each other, the angle between the mean planes being 87.71 (2)°. The title compound appears to be in its enol form. The corresponding H atom was located and freely refined at a distance of 1.02 (3) Å from the O atom and 1.72 (2) Å from the N atom. The strong intra-molecular hydrogen bond O-H⋯N bridging the hydroxyl group and its neighboring nitro-gen atom forms an S(6) graph-set motif. Apart from the intra-molecular O-H⋯N hydrogen bond, C-H⋯O inter-actions are observed between two neighbouring RbSa mol-ecules related by an inversion center. The C-O donor-acceptor distance is 3.474 (2) Å. Moreover, C-H⋯π inter-actions are observed between the C-H bond of one of the ethyl groups and the centroid of the benzene ring of the iso-indole moiety. The C⋯centroid distance is 3.8191 (15) Å. No π-π inter-actions are observed in the crystal structure as the shortest distance between ring centroids is more than 4 Å. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H, C⋯H/H⋯C, O⋯H/H⋯O and N⋯H/H⋯N inter-actions. DFT calculations at the CAM-B3LYP/6-31 G(d) level were carried out to gain a better understanding of the relative energies and the tautomerization process between two possible conformers (keto and enol), as well as the transition state of the title compound.

A tetraphenylethylene-functionalized benzoxazine and copper(II) acetylacetonate form a high-performance polybenzoxazine

In this study, we synthesized TPE-BZ, a new tetraphenylethylene (TPE)-functionalized benzoxazine (BZ) monomer (1,1,2,2-tetrakis(3-phenyl-3,4-dihydro-2H-benzo[e] [1,3]oxazin-6-yl)ethane), through reduction of the Schiff base formed from TPE-4OH–CHO (1,1,2,2-tetra(3-formyl-4-hydroxyphenyl)ethylene) and aniline and subsequent reaction with paraformaldehyde. Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectrometry confirmed the structure of the TPE-BZ monomer. We used differential scanning calorimetry (DSC), FTIR spectroscopy, and thermogravimetric analysis (TGA) to investigate the thermal ring opening polymerization (ROP) and thermal stability of the TPE-BZ monomer after thermal treatment at various temperatures (from room temperature to 250 °C). The TGA profiles revealed that thermal treatment at 250 °C under a N2 atmosphere gave a poly(TPE-BZ) that possessed excellent thermal stability and a high char yield (435 °C, 64.3 wt%). Furthermore, water contact angle measurements of the poly(TPE-BZ) obtained at 210 °C for 2 h indicated a relatively low surface free energy (18.6 mJ m−2), presumably because of strong intramolecular hydrogen bonding between the phenolic OH groups and the N-Mannich bridge in the polybenzoxazine matrix. We also employed DSC, FTIR spectroscopy, and TGA to examine the specific interactions in TPE-BZ/Cu(acac)2 complexes. DSC analysis revealed that blending the TPE-BZ monomer with various weight ratios of Cu(acac)2 lowered the thermal curing temperature of TPE-BZ from 250 to 239 °C, accompanied by a lower curing temperature at 189 °C. Using the Kissinger method, the activation energy of the TPE-BZ/Cu(acac)2 complex (127 kJ mol−1) was lower than that of the TPE-BZ monomer (141 kJ mol−1), suggesting that Cu(acac)2 functioned as a catalyst that initiated ROP of the oxazine units, while providing a product that retained high thermal stability.

Strong Impact of Intramolecular Hydrogen Bonding on the Cathodic Path of [Re(3,3'-dihydroxy-2,2'-bipyridine)(CO)3Cl] and Catalytic Reduction of Carbon Dioxide.

Herein, we present the cathodic paths of the Group-7 metal complex [Re(3,3′-DHBPY)(CO)3Cl] (3,3′-DHBPY = 3,3′-dihydroxy-2,2′-bipyridine) producing a moderately active catalyst of electrochemical reduction of CO2 to CO. The combined techniques of cyclic voltammetry and IR/UV–vis spectroelectrochemistry have revealed significant differences in the chemistry of the electrochemically reduced parent complex compared to the previously published Re/4,4′-DHBPY congener. The initial irreversible cathodic step in weakly coordinating THF is shifted toward much less negative electrode potentials, reflecting facile reductive deprotonation of one hydroxyl group and strong intramolecular hydrogen bonding, O–H···O–. The latter process occurs spontaneously in basic dimethylformamide where Re/4,4′-DHBPY remains stable. The subsequent reduction of singly deprotonated [Re(3,3′-DHBPY-H+)(CO)3Cl]− under ambient conditions occurs at a cathodic potential close to that of the Re/4,4′-DHBPY-H+ derivative. However, for the stabilized 3,3′-DHBPY-H+ ligand, the latter process at the second cathodic wave is more complex and involves an overall transfer of three electrons. Rapid potential step electrolysis induces 1e–-reductive cleavage of the second O–H bond, triggering dissociation of the Cl– ligand from [Re(3,3′-DHBPY-2H+)(CO)3Cl]2–. The ultimate product of the second cathodic step in THF was identified as 5-coordinate [Re(3,3′-DHBPY-2H+)(CO)3]3–, the equivalent of classical 2e–-reduced [Re(BPY)(CO)3]−. Each reductive deprotonation of the DHBPY ligand results in a redshift of the IR ν(CO) absorption of the tricarbonyl complexes by ca. 10 cm–1, facilitating the product assignment based on comparison with the literature data for corresponding Re/BPY complexes. The Cl– dissociation from [Re(3,3′-DHBPY-2H+)(CO)3Cl]2– was proven in strongly coordinating butyronitrile. The latter dianion is stable at 223 K, converting at 258 K to 6-coordinate [Re(3,3′-DHBPY-2H+)(CO)3(PrCN)]3–. Useful reference data were obtained with substituted parent [Re(3,3′-DHBPY)(CO)3(PrCN)]+ that also smoothly deprotonates by the initial reduction to [Re(3,3′-DHBPY-H+)(CO)3(PrCN)]. The latter complex ultimately converts at the second cathodic wave to [Re(3,3′-DHBPY-2H+)(CO)3(PrCN)]3– via a counterintuitive ETC step generating the 1e– radical of the parent complex, viz., [Re(3,3′-DHBPY)(CO)3(PrCN)]. The same alternative reduction path is also followed by [Re(3,3′-DHBPY-H+)(CO)3Cl]− at the onset of the second cathodic wave, where the ETC step results in the intermediate [Re(3,3′-DHBPY)(CO)3Cl]•– further reducible to [Re(3,3′-DHBPY-2H+)(CO)3]3– as the CO2 catalyst.

Synthesis, Crystal Structure and Bioactivities of N-(5-(4-chlorobenzyl)-1,3,5-Triazinan-2-Ylidene)Nitramide

The compound N-(5-(4-chlorobenzyl)-1,3,5-triazinan-2-ylidene)nitramide (C10H12ClN5O2, M = 269.70) was synthesized and structurally confirmed by 1H NMR, 13C NMR, HRMS and single-crystal x-ray diffraction. The crystal belongs to the monoclinic system with space group P21/c. The title compound consisted of a benzene ring and a 1,3,5-triazine ring. All carbon atoms in the benzene ring were nearly coplanar with a dihedral (C6–C5–C10 and C7–C8–C9) angle of 1.71°and all non-hydrogen atoms of the 1,3,5-triazine ring were not planar, but exhibited a half-chair conformation. The crystal structure was stabilized by a strong intramolecular hydrogen bonding interaction N(3)–H(3)···O(2) and three intermolecular hydrogen bonding interactions, N(2)–H(2)···O(1), N(2)–H(2)···N(4) and N(3)–H(3)···Cl(1). The preliminary bioassay showed that the title compound showed not only aphicidal activity against Sitobion miscanthi (inhibition rate: 74.1%) and Schizaphis graminum (77.5%), but also antifungal activities against Pythium aphanidermatum (62.0%). These results provide valuable guidelines for the design and synthesis of novel aphid control agents and fungicides.

Harnessing aromaticity and intramolecular hydrogen bonding to tailor organosuperbases by using 2,4,6-cycloheptatriene-1-imine scaffold

The density functional theory (DFT) calculations at B3LYP/6-31 + G(d,p) level were performed for a series of new 2,4,6-cycloheptatriene-1-imine scaffolds which have potential to introduce as organosuperbases. In the present study, we have exploited the 2,4,6-cycloheptatriene-1-imines which strategically substituted at 2 and 7 positions by two potential anchoring arms having lone pair possessing atoms. The designed organic superbases were found to have the higher basicity than the benchmarked molecule, 1,8-bis(dimethylamino)-naphthalene. The proposed superbase B14 bearing guanidine and aniline groups possesses the highest proton affinity value as 1143.8 kJ mol−1. The protonation enthalpy, Gibbs free energy, harmonic oscillator model of aromaticity (HOMA), and nucleus-independent chemical shift (NICS) were used for the basicity comparison. After the protonation of the designed molecules, the positive charge on the conjugate acid is expected to be delocalized in the cycloheptatriene ring and led to its aromatization. The results indicate that the HOMA and NICS values of the ring in the conjugate acid are strongly elevated. On the other hand, very strong intramolecular hydrogen bonding is formed after protonation. These two factors enhance the stability of the conjugate acids and thereby increase the basicity of the designed molecules.

Interaction of triols with formaldehyde and acetone: Experimental and theoretical study

AbstractExperimental and theoretical aspects of the condensation of glycerol and its homologs (1,2,3‐ and 1,2,4‐butanetriols) with formaldehyde and acetone are studied under conditions of acid catalysis. Calculation of the thermodynamic parameters of the resulting products by the composite method CBS‐QB3 shows that the six‐membered heterocycles, the products of the interaction of triols with formaldehyde, are thermodynamically more stable than the five‐membered acetals, while the reaction of the same triols with acetone is preferable for the formation of the five‐membered acetals. This is due to the fact that the regioselectivity of the studied reactions is determined by the structural features and reactivity of the carbocations formed in a condensed medium during the course of the reaction. According to the theoretical data obtained experimentally, during the condensation of glycerol and 1,2,4‐butanetriol with formaldehyde in the most stable form of the six‐membered cyclic carbocation, intramolecular hydrogen bonding and anomeric stabilization due to the axially oriented hydroxyl group take place. As a result, cation 1b–1 is 1.2–1.6 kJ/mol more stable than its five‐membered isomers (1a–1 and 1b–2). It leads to the predominant formation of 1,3‐dioxane (3b). However, upon condensation of butanetriol‐1,2,3 with formaldehyde, the intermediate cation 4a–1 turns out to be significantly more stable than the other isomers due to the strong intramolecular hydrogen bond in the six‐membered ring with the participation of the hydroxyl group of the substituent and the hydroxyl group of the cationic center, leading to the predominant formation of the dioxolane 6a.

Synthesis, crystal structure and conformational analysis of an unexpected [1,5]dithiocine product of aminopyridine and thiovanillin.

The condensation reaction of 2-mercapto-3-methoxybenzaldehyde with 3-aminopyridine afforded an unexpected N-alkylated [1,5]dithiocine instead of the N-salicylideneaniline. The proposed mechanism for this condensation involves a strong intramolecular hydrogen bond between the thiol and the amine groups, leading to a second condensation. The corresponding product, i.e. 4,10-dimethoxy-13-(pyridin-3-yl)-6H,12H-6,12-epiminodibenzo[b,f][1,5]dithiocine methanol 0.463-solvate, C21H18N2O2S2·0.463CH3OH, was characterized by single-crystal X-ray diffraction analysis. The supramolecular structure shows π-π stacking and S...S interactions in the crystal packing. Within the asymmetric unit, two geometries of the N atom are observed. Although a planar geometry should be expected, a pyramidal one is observed due to the crystal packing. The presence of the two geometries was further supported by density functional theory (DFT) calculations that show an electronic energy difference of less than 2 kJ mol-1 between the two conformers.