Pyridine Hydrogen Research Articles

Investigation of axial ligand effects on catalytic activity of manganese porphyrin, evidence for the importance of hydrogen bonding in cytochrome-P450 model reactions

Various nitrogenous bases, such as imidazoles, pyridines and amines were employed as axial ligands in epoxidation reaction of cyclooctene bytetra-n-butylammonium hydrogen monopersulfate (n- Bu 4 NHSO 5), in the presence of Mn ( III )-tetrakis(2,3-dimethoxyphenyl)porphyrin-acetate ( T (2,3- OMeP ) PorMnOAc ). T (2,3- OMeP ) PorMnOAc is a fairly stable catalyst, with the ability of producing hydrogen bonding. High epoxidation yield of 85 ± 6% was obtained in the presence of imidazole axial ligand with 100% selectivity in 30 min. Higher conversion of around 100% was obtained by pyridine axial base, while selectivity was reduced to 69%. Further epoxidation reactions were also performed using Mn ( III )-Tetrakis(2,3-dihydroxyphenyl)porphyrin-acetate ( T (2,3- OHP ) PorMnOAc ) as catalyst. In addition to the usual electronic and steric effects, it is proposed that the catalytic activity depends on the existence and kind of hydrogen bonding between the axial base and the ortho-methoxy or hydroxy groups on the phenyl rings of manganese porphyrin. The cis to trans ratio of cis-stilbene oxide formed by imidazole and pyridine axial bases were obtained as 7.5 and 2.5 respectively. In addition GC-Ms and UV-vis studies were employed to find the nature of active species and product formation. Our DFT calculations disclosed that pyridine hydrogen bonding with moiety of the macrocycle rings strongly affects the relative energies of S/Q spin states in [ T (2,3- OMeP ) PorMn V ( O )( Py )]+, in that it results in the longer Mn – O bond and reactivity toward substrates.

Poly(4-vinylpyridinium)hydrogensulfate as an efficient and convenient catalyst for a three-component synthesis of 7-methyl-10-aryl-10H-5,8-dioxa-benzo[b]fluoren-9,11-diones

A simple and facile synthesis of 7-methyl-10-aryl-10H-5,8-dioxa-benzo[b]fluoren-9,11-dione derivatives was accomplished via a one-pot condensation of aldehydes, 4-hydroxy-6-methylpyran-2-one, and 2H-indene-1,3-dione at 80 °C under solvent-free conditions in the presence of poly(4-vinyl)pyridinium hydrogen sulfate as a solid acid catalyst. This method has several advantages including high yield of products, shorter reaction times, simple work-up, and cleaner reaction profile.

Structure and thermodynamics of a multimeric cavitand assembly

A set of COOH⋯N(pyridine) hydrogen bonds have been utilized in the targeted synthesis of a cavitand-based assembly. A cavitand appended with four pyridyl groups was synthesized from a Suzuki coupling of a tetrabromocavitand and 3-pyridyl boronic acid. The product resulting from the reaction between the tetra-pyridyl cavitand and 4-nitrobenzoic acid was investigated in solution using isothermal titration calorimetry (ITC) under equilibrium conditions, and in the solid state through single-crystal X-ray diffraction and infrared spectroscopy. The results show that the targeted pentameric hydrogen-bonded architecture was isolated in the solid-state, and the infrared spectroscopy confirm the presence of COOH⋯N(py) interactions. The same assembly, with a 1 : 4 cavitand : acid stoichiometry, is also present in solution in acetonitrile and the enthalpy of binding for this reaction is approximately −45 kJ mol−1.

Proton location in acid⋯pyridine hydrogen bonds of multi-component crystals

Role of local crystal environment on proton location was modelled using DFT calculations. Alteration in the strength of the hydrogen bonding can convert a system from a salt to a co-crystal.

Systematics in NH+···N-Bonded Monosalts of 4,4′-Bipyridine (44′biPy) with Mineral Acids

Despite significantly different crystal symmetry and packing, the crystal structures of NH+···N hydrogen-bonded salts of 4,4′-bipyridine (44′biPy) with mineral acids HA = HCl, HBr, HI, HClO4, HBF4 and H2SiF6 exhibit close analogies in the hydration, aggregation of the cations and their twisted conformation, as well as proton disordering. All monosalts have been synthesized and, at normal conditions, form crystals of general formula [44′biPyH]+A–·xH2O (x = 0.5, 1, or 2), and [44′biPyH]+2SiF62–·5H2O. In the structures, the 44′biPyH+ cations are NH+···N bonded into linear chains, and in most [44′biPyH]+A–·xH2O crystals the protons are disordered, similarly as in anisotropic relaxors 1,4-diazabicyclo[2.2.2]octane hydroiodide and hydrobromide (dabcoHI and dabcoHBr, respectively). The proton disorder implies generation of point defects of neutral 44′biPy molecules and [44′biPyH2]2+ dications in all these structures. In all [44′biPyH]+A– structures investigated, the acid anions are hydrogen bonded to water molecules and interact with pyridine hydrogen atoms. Two polymorphs of [44′biPyH]+I–·H2O differ in color: the orthorhombic polymorph α is yellow, and the triclinic polymorph β is orange.

Polymorphic Co-crystals from Polymorphic Co-crystal Formers: Competition between Carboxylic Acid···Pyridine and Phenol···Pyridine Hydrogen Bonds

The recent literature has shown an increase in the number of co-crystals reported to be polymorphic, with at least 45 such systems identified thus far. The question of whether co-crystals, defined as any multicomponent neutral molecular complex that forms a crystalline solid, are inherently less prone to polymorphism than the individual components is shown to be untrue in four sets of polymorphic co-crystals. The co-crystal formers in this study, acridine, nicotinamide, 3-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, malonic acid, and pimelic acid, are all polymorphic in their unimolecular states and are shown to be dimorphic in the following combinations: (3-hydroxybenzoic acid)·(acridine) [1(I) and 1(II)], (2,4-dihydroxybenzoic acid)·(nicotinamide) [4(I) and 4(II)], (malonic acid)·(nicotinamide) [5(I) and 5(II)], and (pimelic acid)·(nicotinamide) [6(I) and 6(II)]. These co-crystals are assembled primarily using carboxylic acid and phenol hydrogen bond donors that hydrogen bond to pyridine N or amide carbonyl acceptors. Two different combinations of donors and acceptors are primarily responsible for the formation of polymorphs in 1 and 4, whereas conformational differences within the malonic and pimelic acid molecules lead to different packing arrangements using the same combination of hydrogen bonded interactions in 5 and 6. The 1:2 co-crystal of (3-hydroxybenzoic acid)·(acridine)2 (2) displays both the phenol O–H···N hydrogen bond observed in 1(I) and the carboxylic acid O–H···N hydrogen bond observed in 1(II). In addition, a methanol solvate of (2,4-dihydroxybenzoic acid)·(nicotinamide) (3) is reported. DFT calculations show that the carboxylic acid···pyridine hydrogen bond is strongest and one of co-crystallization’s most useful interactions.

(Pyridin-4-yl)methylN′-(3-phenylallylidene)hydrazinecarbodithioate

In the title compound, C16H15N3S2, the central C2N2S2 residue is planar (r.m.s. deviation = 0.045 Å) and the pyridyl and benzene rings are inclined and approximately coplanar to this plane, respectively [dihedral angles = 72.85 (9) and 10.73 (9)°], so that, overall, the mol­ecule adopts an L-shape. The conformation about each of the N=C [1.290 (3) Å] and C=C [1.340 (3) Å] bonds is E. Supra­molecular chains along [1-10] are stabilized by N—H⋯N(pyridine) hydrogen bonding and these are connected into a double layer that stacks along the c-axis direction by C—H⋯π(pyridine) inter­actions.

Preparation and characterization of hydrogen-bonded P4VP-bisazobenzene complexes

Photoresponsive supramolecular complexes contain 4-hydroxyethyloxy-4′-(4-nitrophenylazo)azobenzene(BisAzo) molecule as a hydrogen bonding donor and poly(4-vinylpyridine) (P4VP) as a hydrogen bonding acceptor, and strong phenol pyridine hydrogen bonding is formed between them. FT-IR spectrum verifies the hydrogen bonding has formed between the phenol hydroxyl of BisAzo and pyridine ring of P4VP. The glass- transition temperature (Tg) is determined with differential-scanning calorimetry(DSC) and a decrease of complexes compared with pure P4VP is observed due to the attachment of BisAzo onto the backbone of P4VP. Polarized optical microscopy (POM) is performed to study the structure of supramolecular complexes,with a different texture observed which is different from both constituents alone. X-ray diffraction patterns are investigated with the same films already used for POM observation, indicating a lamellar structure with a periodic thickness of 4.1 nm. The supramolecular complexes P4VP/(BisAzo)x are prepared with the molar ratio of BisAzo to the pyridine group varied at x = 0.25, 0.5, 0.75 and 1.0, no mass aggregation is observed even at a high concentration of chromophore.

4-(3-Fluoroanilino)thieno[2,3-b]pyridine-6-carboxylic acid

In the title compound, C14H9FN2O2S, the thieno[2,3-b]pyridine residue is almost planar (r.m.s. deviation = 0.0194 Å), with the carb­oxy­lic acid group [dihedral angle = 11.9 (3)°] and the benzene ring [71.1 (4)°] being twisted out of this plane to different extents. An intra­molecular N—H⋯O(carbon­yl) hydrogen bond closes an S(6) ring. Supra­molecular chains along [01-1] mediated by O—H⋯N(pyridine) hydrogen bonds feature in the crystal. A three-dimensional architecture is completed by π–π inter­actions occurring between the benzene ring and the two rings of the thieno[2,3-b]pyridine residue [centroid–centroid distances = 3.6963 (13) and 3.3812 (13) Å]. The F atom is disordered over the two meta sites in a near statistical ratio [0.545 (5):0.455 (5)].

N-(4-Chloro-phen-yl)-5-(4,5-dihydro-1H-imidazol-2-yl)thieno[2,3-b]pyridin-4-amine.

In the title compound, C16H13ClN4S, the thienopyridine fused-ring system is nearly planar (r.m.s. deviation = 0.0333 Å) and forms a dihedral angle of 4.4 (3)° with the attached dihydro­imidazole ring (r.m.s. deviation = 0.0429 Å) allowing for the formation of an intra­molecular (exocyclic amine)N—H⋯N(imine) hydrogen bond. The benzene rings of the disordered (50:50) –N(H)—C6H4Cl residue form dihedral angles of 59.1 (3) and 50.59 (15)° with the fused ring system. In the crystal, (imidazole amine)N—H⋯N(pyridine) hydrogen bonds lead to a supra­molecular helical chain along the b axis. The chains assemble into layers (ab plane) with inter-digitation of the chloro­benzene rings which results in weak C—H⋯Cl inter­actions in the c-axis direction.

5,6-Dimethyl-4-(thio-phen-2-yl)-1H-pyrazolo-[3,4-b]pyridin-3-amine.

In the title mol­ecule, C12H12N4S, the thio­phene ring is disordered over two orientations with a refined site-occupancy ratio of 0.777 (4):0.223 (4). The pyrazolo­pyridine ring system is essentially planar with an r.m.s. deviation of 0.0069 (3) Å and makes dihedral angles of 82.8 (2) and 72.6 (5)°, respectively, with the major and minor components of the thio­phene ring. In the crystal, mol­ecules are linked into a chain along the a axis by a pair of N—H⋯N(pyrazole) hydrogen bonds and a pair of N—H⋯N(pyridine) hydrogen bonds, both having a centrosymmetric R 2 2(8) graph-set motif. A C—H⋯π inter­action is also present.

Adventures in co-crystal land: high Z′, stoichiometric variations, polymorphism and phase transitions in the co-crystals of four liquid and solid cyclic carboxylic acids with the supramolecular reagent isonicotinamide

The supramolecular reagent isonicotinamide (isonico) was used to co-crystallize with three liquid carboxylic acids, cyclopropanecarboxylic acid (C3A), cyclobutanecarboxylic acid (C4A) and cyclopentanecarboxylic acid (C5A), and a solid carboxylic acid, cyclohexanecarboxylic acid (C6A). A total of six co-crystal structures resulted, which are an illustration of the co-crystal space observed in the ever-expanding research on co-crystallization of multiple molecular components. Co-crystal 1, (C3A)·(isonico), has a crystal structure with one of the highest reported Z′ values. 12 acid and 12 isonico molecules combine in the asymmetric unit to give a Z′ = 12, all forming 1-D ribbons. Co-crystals 2a and 2b, both having a formula of (C4A)2·(isonico), having, respectively, a Z′ of 1 and 2, illustrate both stoichiometric variation as well as polymorphism, resulting in different packing architectures. Co-crystals (C5A)·(isonico) 3 and (C6A)·(isonico) 4 have isostructural structures at low temperature, and both show phase transitions above room temperature. For (C6A)·(isonico), we determined the structure of both the low temperature phase, 4a, as well as a high temperature phase, 4b, by single crystal X-ray diffraction, and monitored the transition of 3 by variable temperature powder X-ray diffraction. In all of the compounds reported here, synthesized from two components that are not necessarily solids at ambient conditions and which we have called co-crystals, the primary hydrogen bonded interaction is the carboxylic acid⋯pyridine hydrogen bond.

Covalent assistance to supramolecular synthesis: modifying the drug functionality of the antituberculosis API isoniazidin situ during co-crystallization with GRAS and API compounds

The anti-tuberculosis molecule isonicotinic acid hydrazide (isoniazid) is a promising molecule in the supramolecular synthesis of multi-component molecular complexes and also allows for its biological activity to be improved and modified by a simple covalent reaction. The low temperature crystal structures of both isoniazid (1) and the related N′-(propan-2-ylidene)isonicotinohydrazide molecule (2), the latter known to be a more effective agent against Mycobacterium tuberculosis, are reported. In addition, these two molecules were then co-crystallized with the same three Generally Regarded As Safe (GRAS) molecules, succinic acid, 4-hydroxybenzoic acid and 2-hydroxybenzoic acid, to produce the following pharmaceutical co-crystals: (isonicotinic acid hydrazide)2·(succinic acid) 3, (N′-(propan-2-ylidene)isonicotinohydrazide)2·(succinic acid) 4, (isonicotinic acid hydrazide)·(4-hydroxybenzoic acid) 6, (N′-(propan-2-ylidene)isonicotinohydrazide)·(4-hydroxybenzoic acid) 7, (isonicotinic acid hydrazide)·(2-hydroxybenzoic acid) 8, and (N′-(propan-2-ylidene)isonicotinohydrazide)·(2-hydroxybenzoic acid) 9. In addition, a co-crystal using 2-butanone as a modifier is also reported, (N′-(butan-2-ylidene)isonicotinohydrazide)2·(succinic acid) 5. Drug–drug co-crystals were also made with the anti-HIV compound 2-chloro-4-nitrobenzoic acid: (isonicotinic acid hydrazide)·(2-chloro-4-nitrobenzoic acid) 10, and (N′-(propan-2-ylidene)isonicotinohydrazide)·(2-chloro-4-nitrobenzoic acid) 11. All the co-crystals use the carboxylic acid⋯pyridine hydrogen bond to connect the GRAS or drug molecule to the pyridine ring. In general, the co-crystals with the modified isoniazid feature the C(4) homosynthon, and those with the original isoniazid a variety of homo- and heterosynthons. By comparing the melting points of the co-crystals that use isoniazid and those that use the modified isoniazid, a reduction in melting point is observed.

Ordering of the Water Molecule in the Crystal Structure of 2-[3-Methyl-4-(2,2,2-Trifluoroethoxy)-2-Pyridinyl]Methylthio-1H-Benzimidazole Hydrate (Lansoprazole Sulphide Hydrate)

Lansoprazole sulphide (2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole) hydrate crystallizes in the triclinic space group P-1 with two molecules in the asymmetric part of the unit cell. The molecules are almost identical, the normal probability plots show that the differences between them are of statistical nature. The crystal structure is determined mainly by the O–H···N and N–H···O hydrogen bonds; and both symmetry independent molecules create the hydrogen-bonded structures on their own. The common motif is the C 2 2 (6) chain of molecules along x (A) or y (B), but the interactions between the chains are different: chains of molecules A are joined by O–H···N(pyridine) hydrogen bonds while those of molecules B– by relatively strong O–H···S hydrogen bonds. Additionally, in both cases there are also C–H···S, C–H···π and π–π interactions between the neighbouring molecules. The different intermolecular interactions might be connected with the observed disorder of water molecules in the B-chains. At room temperature the s.o.f.’s of two alternative positions refined at 0.760(17) and 0.240(17). The less-occupied water molecule does not take part in the O–H···S hydrogen bonding. When temperature decreases the importance of this interaction grows, the occupancy of less occupied position becomes smaller and finally, around 150 K the structure becomes fully ordered. [One of the water molecule is disordered at room temperature, but when temperature decreases the structure becomes fully ordered around 150 K.]

Hydration structure of pyridine molecule studied by neutron diffraction with isotopic substitution method

Neutron diffraction measurements were carried out at 25 °C for aqueous 10 mol% pyridine heavy water solutions, (C 5 ∗H 5 ∗N) 0.1(D 2O) 0.9, in which the isotopic compositions 14N/ 15N and H Py/D Py (H Py: Pyridine hydrogen atom), were changed. The hydration structure of pyridine molecule was derived from the least squares fitting analysis of observed intermolecular first-order difference functions, Δ N inter( Q) and Δ H inter( Q). It was revealed that a pyridine molecule forms hydrogen bonds of the N⋯D W1 O W D W2 type (D W1, D W2: deuterium atoms in D 2O, O W: oxygen atom in D 2O) with 2.5(2) water molecules ( r N⋯DW1 = 1.95(1) Å, ∠N⋯D W1 O W = 174(11)°). The average number of water molecules around the hydrogen atom of the pyridine molecule was determined to be 1.2(1) with the average intermolecular H Py⋯D 2O distance of 2.82(1) Å.

Packing incentives and a reliable N–H⋯N–pyridine synthon in co-crystallization of bipyridines with two agrochemical actives

The co-crystallization of agrochemical actives thiophanate-methyl and thiophanate-ethyl with 2,2′-bipyridine, 4,4′-bipyridine and 1,2-bis(4-pyridyl)ethane was investigated with conventional crystallization, the slurry method and liquid-assisted grinding. Co-crystals of both thiophanates with all bipyridines were found and the structures solved with single crystal X-ray diffraction. Whereas the 2,2′-bipyridine co-crystals seem to form because of a combination of weak interactions, and in the case of the thiophanate-methyl, partly because of close packing incentives, the 4,4′-bipyridine and 1,2-bis(4-pyridyl)ethane co-crystals form mainly because of a favourable N–H⋯N–pyridine hydrogen bonding synthon.

Structures and conformational analysis of a 3 × 3 isomer grid of nine N-(fluorophenyl)pyridinecarboxamides

A 3 × 3 isomer grid of N-(fluorophenyl)pyridinecarboxamides is reported and integrating crystal structure analyses, ab initio optimisation calculations (gas phase and solvated forms in CH2Cl2, H2O) and conformational analyses. The nine NxxF isomers (x = 4-, 3- or 2-substitution on N and F) are investigated and compared to determine and correlate factors underpinning (a) the roles of the F/N atom substituents on molecular conformation and overall supramolecular aggregation, (b) competition between intermolecular amide⋯amide (in NppF) or intra-/intermolecular amide⋯pyridine hydrogen bond formation and (c) structural and physico-chemical properties. Crystal structure analyses of the NxxF isomers reveal different primary aggregation processes as either N–H⋯N or N–H⋯OC and with NmpF forming an unusual cyclic N–H⋯N hydrogen bonded tetrameric assembly [as a R44(24) ring]. Compounds NpmF and NpoF are isomorphous and the latter is also disordered. Conformational analysis of the NxxF molecular structures from DFT calculations differs from the crystal structure results for several isomers and highlighting the co-operative effects of intra-/intermolecular interactions in the solid state.

Pharmaceutical Co-crystals with Isonicotinamide—Vitamin B3, Clofibric Acid, and Diclofenac—and Two Isonicotinamide Hydrates

The co-crystals of three industrially important pharmaceutical molecules, the Vitamin B group member nicotinamide (1), the antihyperlipidemic drug clofibric acid (2), and the nonsteroidal anti-inflammatory drug diclofenac (3), are synthesized with the co-crystal former isonicotinamide and characterized by thermal analysis and single crystal X-ray diffraction. Two dimorphic hydrates of isonicotinamide were obtained during the course of these experiments: hydrate 4 (form I) has been reported recently, and hydrate 5 (form II) is new. Both are monohydrates but differ in the number of independent molecules in the asymmetric unit, Z′ = 2 and 8, respectively. Form II is metastable compared to I and converts to form I in the solid state. In all three pharmaceutical co-crystals, it is the pyridine N atom of either the nicotinamide molecule in 1 or the N atom of the isonicotinamide molecule in 2 and 3 that is used in connecting the different molecules together, as a hydrogen bond acceptor from the amine of the isonicotinamide in 1 and the carboxylic acid protons in 2 and 3. The carboxylic acid···pyridine hydrogen bond is an often used supramolecular synthon. A survey of relevant structures in the Cambridge Structural Database of isonicotinamide and nicotinamide co-crystals is given for completeness, and the co-crystal former ability of isonicotinamide and nicotinamide was investigated by performing density functional theory calculations.

Bistable or Oscillating State Depending on Station and Temperature in Three‐Station Glycorotaxane Molecular Machines

High-yield, straightforward synthesis of two- and three-station [2]rotaxane molecular machines based on an anilinium, a triazolium, and a mono- or disubstituted pyridinium amide station is reported. In the case of the pH-sensitive two-station molecular machines, large-amplitude movement of the macrocycle occurred. However, the presence of an intermediate third station led, after deprotonation of the anilinium station, and depending on the substitution of the pyridinium amide, either to exclusive localization of the macrocycle around the triazolium station or to oscillatory shuttling of the macrocycle between the triazolium and monosubstituted pyridinium amide station. Variable-temperature (1)H NMR investigation of the oscillating system was performed in CD(2)Cl(2). The exchange between the two stations proved to be fast on the NMR timescale for all considered temperatures (298-193 K). Interestingly, decreasing the temperature displaced the equilibrium between the two translational isomers until a unique location of the macrocycle around the monosubstituted pyridinium amide station was reached. Thermodynamic constants K were evaluated at each temperature: the thermodynamic parameters DeltaH and DeltaS were extracted from a Van't Hoff plot, and provided the Gibbs energy DeltaG. Arrhenius and Eyring plots afforded kinetic parameters, namely, energies of activation E(a), enthalpies of activation DeltaH( not equal), and entropies of activation DeltaS( not equal). The DeltaG values deduced from kinetic parameters match very well with the DeltaG values determined from thermodynamic parameters. In addition, whereas signal coalescence of pyridinium hydrogen atoms located next to the amide bond was observed at 205 K in the oscillating rotaxane and at 203 K in the two-station rotaxane with a unique location of the macrocycle around the pyridinium amide, no separation of (1)H NMR signals of the considered hydrogen atoms was seen in the corresponding nonencapsulated thread. It is suggested that the macrocycle acts as a molecular brake for the rotation of the pyridinium-amide bond when it interacts by hydrogen bonding with both the amide NH and the pyridinium hydrogen atoms at the same time.

Structural Characterization of Zinc and Iron (II/III) Complexes of a Porphyrin Bearing Two Built-in Nitrogen Bases. An Example of High-Spin Diaqua-Iron(III) Bromo Complex

A bis-strapped porphyrin with two intramolecular nitrogen bases was synthesized, and its zinc(II), iron(II), and iron(III) complexes have been structurally characterized. Whereas the zinc(II) complex is square pyramidal five-coordinate and the iron(II) complex is six-coordinate despite a significant distortion of the macrocycle induced by the rigidity of the straps, the iron(III) complex exhibits a peculiar bis-aqua structure in which no intramolecular axial base is bound to the iron atom in the porphyrin. Furthermore, on one side, the bromide counteranion of the iron is bound inside the cycle formed by a strap and establishes a hydrogen bond with an axially bound water molecule. On the other side, a residual HBr molecule protonates one pyridine base leading to the formation of an intermolecular pyridinium-pyridine hydrogen bond. The large ionic radius of the high-spin iron(III) cation is accommodated in the macrocycle with no displacement of the metal out of the mean porphyrinic plane, with an average Fe-Np bond distance of 2.057 A, and the axial Fe-Ow(aqua) bond distance measured at 2.090 A. As a result, this high-spin iron(III) bis-aqua complex is only lightly distorted.