Picolinic N-oxide Research Articles

Impact of added ligand oxides in the sulfoxidation of phenylmercaptoacetic acids with oxovanadium(IV)‐salen complexes

AbstractThe mechanistic aspects covering the effect of added ligand oxides, picoline N‐oxide (PicNO), pyridine N‐oxide (PyNO), and triphenyl phosphine oxide (TPPO) on the selective sulfoxidation of phenylmercaptoacetic acids to PSAA by H2O2 catalyzed by oxovanadium(IV)‐salen complexes have been studied spectrophotometrically in 100% acetonitrile medium. Hydroperoxovanadium(V)‐salen is the reactive species in this sulfoxidation. The rate of sulfoxidation is found to be enhanced significantly by increasing the concentrations of PMAA, salen, and H2O2. The ascertained order of reactivity among the oxovanadium(IV)‐salen complexes is 5,5′‐dimethyl > unsubstituted salen > 5,5′‐dichloro. The reaction is found to be impeded by the addition of ligand oxide and introduction of substituents in PMAA. The observed order of rate retardation among ligand oxides is TPPO < PyNO < PicNO. Downward Hammett plot obtained has been rationalized by change in rate‐determining step from coordination of PMAA to active species for electron‐withdrawing substituents to transfer of oxygen to PMAA for electron‐donating substituents within the same mechanism.

Chemoselective Ru-Catalyzed Oxidative Lactamization vs Hydroamination of Alkynylamines: Insights from Experimental and Density Functional Theory Studies.

The Ru-catalyzed intramolecular oxidative amidation (lactamization) of aromatic alkynylamines with 4-picoline N-oxide as an external oxidant has been developed. This chemoselective process is very efficient to achieve medium-sized ε- and ζ-lactams (seven- and eight-membered rings) but not for the formation of common δ-lactams (six-membered rings). DFT studies unveiled the capital role of the chain length between the amine and the alkyne functionalities: the longer the connector, the more favored the lactamization process vs hydroamination.

Ruthenium-Catalyzed Oxidative Amidation of Alkynes to Amides.

Complex CpRuCl(PPh3)2 catalyzes reactions of terminal alkynes with 4-picoline N-oxide and primary and secondary amines to afford the corresponding amides. The reactions occur in chlorinated solvent and aqueous medium, showing applications in peptide chemistry. Stoichiometric studies reveal that the true catalysts of the processes are the vinylidene cations [CpRu(═C═CHR)(PPh3)2]+ which are oxidized to the Ru(η2-CO)-ketenes by the N-oxide. Finally, nucleophilic additions of primary and secondary amines to the free ketenes yield the corresponding amides.

Halogen and Sulfur Oxidation of Germanium and Tin Dications.

Herein we present the oxidation of base-stabilized tetrelII dications [LM][OTf]2 [L = BIMEt3 = tris(1-ethyl-benzoimidazol-2-ylmethyl)amine and M = Ge, Sn] with PCl5, SeCl4, Br2, and I2 to access dicationic dihalides [LMX2][OTf]2. The addition of oxygen-rich donor molecules (picoline N-oxide, OPEt3) to dications [LM][OTf]2 yielded donor-acceptor complexes bearing a tetrel(II) dication adjacent to a pnictogen(V) moiety. The addition of elemental sulfur to [LGe][OTf]2 yielded [(LGeS)2][OTf]4 containing a dimeric tetracation.

Efficient solution-processed yellow/orange phosphorescent OLEDs based on heteroleptic Ir(Ⅲ) complexes with 2-(9,9-diethylfluorene-2-yl)pyridine main ligand and various ancillary ligands

Abstract Efficient solution-processible yellow/orange emissive phosphors are highly required in solution-processed phosphorescent organic light-emitting diodes (s-PhOLEDs). With respect to phenyl pyridine (ppy)-type Ir(III) complexes, 2-(9,9-diethylfluoren-2-yl)pyridine (Flpy)-type Ir(III) complexes have huge potential in yellow/orange s-PhOLEDs due to their extended conjugation and excellent solubility in common organic solvents. Herein, a new series of phosphorescent Ir(III) complexes, i.e. Ir(Flpy)2pic-N O, Ir(Flpy-CF3)2pic-N O, Ir(Flpy-CF3)2dbm and Ir(Flpy-CF3)2acac, based on Flpy main ligand and picolinic N-oxide (pic-N O), acetylacetone (acac), and dibenzoyl methane (dbm) ancillary ligands are synthesized. The photophysical, electrochemical, and electroluminescent (EL) properties of these phosphorescent Ir(III) complexes are investigated in details. By introducing the CF3 group in Flpy ligand and varying the ancillary ligands, the emission spectra of these phosphorescent complexes are tuned in a large range with EL emission peaks from 544 nm to 588 nm. The s-PhOLEDs employing these phosphors show promising EL performance with maximum external quantum efficiency (EQE) from 15.4% to 23.7% and high power efficiency from 61.9 l m W−1 to 80.4 l m W−1. These highly efficient phosphorescent Ir(III) complexes may serve as ideal chromaticity components in solution-processed full-color displays and lighting devices.

Protonation of Pyridine Monocarboxylate‐N‐Oxides – Determination of Thermodynamic, Absorbance and Ion Interaction Parameters

AbstractThe thermodynamic parameters (pKa, ΔH, ΔG, ΔS) for the protonation of three isomeric pyridine monocarboxylate‐N‐oxides (PCNO) namely picolinate‐N‐oxide (PANO) nicotinate‐N‐oxide (NANO) isonicotinate‐N‐oxide (IANO) were determined in the present study. The pKa determined by potentiometry follow the order: PANO > IANO > NANO at all ionic strengths. The calorimetric results revealed that the PANO protonation was endothermic and the other are exothermic, indicating the entropy driven protonation of PANO while the other two has minor contribution of enthalpy as well. The ion interaction parameters for PCNOs are obtained by determining the pKa for the same at various ionic strengths (I=0.1 −3.0 M) and the data is extrapolated to find pKa0 (pKa at I=0) by specific ion interaction theory (SIT). The pKa / pKa0 determined by absorption spectra are also in line with potentiometric results. The energetics and variations in charge densities on individual atoms on protonation were calculated theoretically. PCNOs protonation are compared with its base moieties: pyridine monocarboxylates to interpret the effect of the N‐oxide moiety on the protonation thermodynamics.

Modulation of catalytic activity by ligand oxides in the sulfoxidation of phenylmercaptoacetic acids by oxo(salen)chromium(V) complexes

Mechanism of sulfoxidation of eleven para-substituted phenyl mercaptoacetic acids (PMAAs) by three oxo(salen)chromium(V)+ PF6− complexes in the presence of different ligand oxides (LOs) such as triphenylphosphine oxide, pyridine N-oxide and 4-picoline N-oxide have been studied spectrophotometrically in 100% acetonitrile medium. Spectral and kinetic profiles establish the formation of adduct, OCr(V)(salen)+-LO as the reactive intermediate in the catalytic cycle. The rate of sulfoxidation is found to be enhanced significantly by the addition of LOs and introduction of substituent in PMAA and salen complex. Both electron releasing and electron withdrawing substituents in the substrate and oxidant facilitate the rate of sulfoxidation. Correlation with Hammett constants yields a non-linear concave upward curve. Based on the experimental results and substituent effects two different mechanisms, a direct oxygen atom transfer (DOT) for PMAAs with electron withdrawing substituents and a single electron transfer for PMAAs with electron donating substituents have been postulated.

Electrophilic and nucleophilic pathways in ligand oxide mediated reactions of phenylsulfinylacetic acids with oxo(salen)chromium(V) complexes

The mechanism of oxidative decarboxylation of phenylsulfinylacetic acids (PSAA) by oxo(salen)Cr(V)+ ion in the presence of ligand oxides has been studied spectrophotometrically in acetonitrile medium. Addition of ligand oxides (LO) causes a red shift in the λmax values of oxo(salen) complexes and an increase in absorbance with the concentration of LO along with a clear isobestic point. The reaction shows first-order dependence on oxo(salen)-chromium(V)+ ion and fractional-order dependence on PSAA and ligand oxide. Michaelis–Menten kinetics without kinetic saturation was observed for the reaction. The order of reactivity among the ligand oxides is picoline N-oxide>pyridine N-oxide>triphenylphosphine oxide. The low catalytic activity of TPPO was rationalized. Both electron-withdrawing and electron-donating substituents in the phenyl ring of PSAA facilitate the reaction rate. The Hammett plots are non-linear upward type with negative ρ value for electron-donating substituents, (ρ−=−0.740 to −4.10) and positive ρ value for electron-withdrawing substituents (ρ+=+0.057 to +0.886). Non-linear Hammett plot is explained by two possible mechanistic scenarios, electrophilic and nucleophilic attack of oxo(salen)chromium(V)+-LO adduct on PSAA as the substituent in PSAA is changed from electron-donating to electron-withdrawing. The linearity in the logk vs. Eox plot confirms single-electron transfer (SET) mechanism for PSAAs with electron-donating substituents.

ChemInform Abstract: Rhodium‐Catalyzed Oxygenative [2 + 2] Cycloaddition of Terminal Alkynes and Imines for the Synthesis of β‐Lactams.

A rhodium-catalyzed oxygenative [2 + 2] cycloaddition of terminal alkynes and imines has been developed, which gives β-lactams as products with high trans diastereoselectivity. In the presence of a Rh(I) catalyst and 4-picoline N-oxide, a terminal alkyne is converted to a rhodium ketene species via oxidation of a vinylidene complex and subsequently undergoes a [2 + 2] cycloaddition with an imine to give rise to the 2-azetidinone ring system. Mechanistic studies suggest that the reaction proceeds through a metalloketene rather than free ketene intermediate. The new method taking advantage of catalytic generation of a ketene species directly from a terminal alkyne provides a novel and efficient entry to the Staudinger synthesis of β-lactams under mild conditions.

Rhodium-Catalyzed Oxygenative [2 + 2] Cycloaddition of Terminal Alkynes and Imines for the Synthesis of β-Lactams

A rhodium-catalyzed oxygenative [2 + 2] cycloaddition of terminal alkynes and imines has been developed, which gives β-lactams as products with high trans diastereoselectivity. In the presence of a Rh(I) catalyst and 4-picoline N-oxide, a terminal alkyne is converted to a rhodium ketene species via oxidation of a vinylidene complex and subsequently undergoes a [2 + 2] cycloaddition with an imine to give rise to the 2-azetidinone ring system. Mechanistic studies suggest that the reaction proceeds through a metalloketene rather than free ketene intermediate. The new method taking advantage of catalytic generation of a ketene species directly from a terminal alkyne provides a novel and efficient entry to the Staudinger synthesis of β-lactams under mild conditions.

Tolerance of various biological species to triorganotins

Several triphenyltin chloride picoline N-oxide adducts were synthesized. X-ray studies of triphenyltin chloride 4- picoline N-oxide indicate that the adduct has a distorted trigonal bipyramid (TBP) configuration with the phenyl groups in the equatorial positions and the axial positions being occupied by the 4-picoline N-oxide ligand and chlorine atom. Structures of the other adducts are assumed to be similar based on the IR spectra. Multinuclear NMR studies indicated that the TBP configuration is lost in solution. Screening results of the adducts against Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) indicate that the E. coli were more tolerant to the adducts. In addition to the adducts, three other series of triorganotins that incorporated various modified fragments of pyrethroids were also tested against B. subtilis and E. coli. No common order of toxicity was observed for these compounds based on the organic group attached to the tin atom. In addition to the evaluation of the triphenyltin chloride adducts and modified triorganotins against the two bacteria, 12 commercial triorganotins were evaluated against a freshwater snail, Biomphalaria glabrata (B. glabrata). The screening results indicated that the bacteria are more tolerant to the triorganotins than B. glabrata.

Rhodium‐Catalyzed Oxygenative Addition to Terminal Alkynes for the Synthesis of Esters, Amides, and Carboxylic Acids

A gem of a couple: The title reaction of terminal alkynes with O and N nucleophiles proceeds in the presence of [{Rh(cod)Cl}2], P(4-FC6H4)3, and 4-picoline N-oxide. Alcohols, amines, and water add to the terminal alkynes to give esters, amides, and carboxylic acids, respectively. The reaction involves formation of a rhodium vinylidene, oxidation to a ketene by oxygen transfer, and nucleophilic addition.

The first crystal structures of two 2-D lead(II)-coordination polymers with picolinic acid N-oxide and pseudohalides extended to 3-D networks by intermolecular interactions

Two-dimensional lead(II)-azido and -thiocyanato coordination polymers with picolinate N-oxide (PNO), [Pb(PNO)(NCS)]n (1) and [Pb(PNO)(N3)]n (2) were synthesized and characterized by elemental and thermal analyses, IR and 1H NMR spectroscopy, and X-ray crystallography. Compound 1 crystallized in the chiral space group P212121 , whereas 2 adopts the centrosymmetric P21/c space group. Multiple weak C–HO and C–HN interactions assemble the polymeric layers into 3-D supramolecular networks.

ChemInform Abstract: Potential Mechanism-Based Tyrosine Kinase Inhibitors. Part 1. Phosphorylation Chemistry of Pyridine N-Oxides.

Phosphorylated derivatives of 4-picoline N-oxide have been observed on treatment with both phos-phorylating and phosphitylating agents. These intermediates were trapped by external nucleophiles. Propane-1-thiol reacted preferentially at carbon to yield a propylsulfanylpyridine whereas propylamine reacted preferentially at phosphorus. This chemistry carries implications for the design of mechanism-based tyrosine kinase inhibitors.

Hydrothermal Synthesis, Crystal Structure and Electrochemical Property of Two Inorganic–Organic Hybrid Frameworks via Hydrogen Bonding

Two inorganic–organic hybrid frameworks, namely [Cu2(pdca)2(bibp)(H2O)2]·H2O (1) and [Fe(pdca)(pyco)(H2O)]·H2O (2) (H2pdca = pyridine-2,6-dicarboxylic acid, bibp = 4,4′-bisimidazolylbiphenyl, pyco = picolinate N-oxide) were synthesized via hydrothermal reactions. Both compounds have been characterized by elemental analysis, spectroscopic analysis, thermogravimetric analysis (TGA) and the single crystal diffraction. Complex 1 is dinuclear and five-coordinated copper(II) complex, while complex 2 displays mono-nuclear and six-coordinated iron(III) complex. In the crystal structures of both complexes, the coordinated and crystalline water molecules and H2pdca ligands contribute to the formation of O–H···O and C–H···O hydrogen bonds, which link the molecules into layers parallel. Cyclic voltammetry (CV) analysis shows one reversible reduction potential at 0.14 V (Epc) in complex 1, whereas in complex 2 shows a reduction potential at 0.15 V (Epc) in the cathodic region.

Aqua(picolinatoN-oxide-κ2O1,O2)(pyridine-2,6-dicarboxylato-κ3O,N,O′)iron(III) monohydrate

In the title compound, [Fe(C6H4NO3)(C7H3NO4)(H2O)]·H2O, the FeIII ion is coordinated by two O and one N atoms from a pyridine-2,6-dicarboxyl­ate ligand, by two O atoms from a picolinate N-oxide ligand and by one water O atom in a distorted octa­hedral geometry [Fe—O = 1.940 (3)–2.033 (3) Å and Fe—N = 2.057 (4) Å]. In the crystal structure, the coordinated and solvent water mol­ecules contribute to the formation of O—H⋯O hydrogen bonds, which link the mol­ecules into layers parallel to the ab plane.

Versatility of p-sulfonatocalix[5]arene in building up multicomponent bilayers

The ability of pyridine N-oxide molecules to form host–guest complexes with p-sulfonatocalix-[5]arene was probed and resulted in the formation of europium complexes incorporating 2- or 4-picoline N-oxide, and 4,4′-dipyridine N,N′-dioxide. Relative to lanthanide complexes of p-sulfonatocalix[5]arene incorporating pyridine N-oxide, the presence of a methyl group on the aromatic ring for the picoline N-oxides, or a larger dipyridine dioxide guest dramatically alters the self-assembly, resulting in the formation of three new supramolecular motifs for the calixarene.

Amide−N-Oxide Heterosynthon and Amide Dimer Homosynthon in Cocrystals of Carboxamide Drugs and Pyridine N-Oxides

The carboxamide-pyridine N-oxide heterosynthon is sustained by syn(amide)N-H...O-(oxide) hydrogen bond and auxiliary (N-oxide)C-H...O(amide) interaction (Reddy, L. S.; Babu, N. J.; Nangia, A. Chem. Commun. 2006, 1369). We evaluate the scope and utility of this heterosynthon in amide-containing molecules and drugs (active pharmaceutical ingredients, APIs) with pyridine N-oxide cocrystal former molecules (CCFs). Out of 10 cocrystals in this study and 7 complexes from previous work, amide-N-oxide heterosynthon is present in 12 structures and amide dimer homosynthon occurs in 5 structures. The amide dimer is favored over amide-N-oxide synthon in cocrystals when there is competition from another H-bonding functional group, e.g., 4-hydroxybenzamide, or because of steric factors, as in carbamazepine API. The molecular organization in carbamazepine.quinoxaline N,N'-dioxide 1:1 cocrystal structure is directed by amide homodimer and anti(amide)N-H...O-(oxide) hydrogen bond. Its X-ray crystal structure matches with the third lowest energy frame calculated in Polymorph Predictor (Cerius(2), COMPASS force field). Apart from generating new and diverse supramolecular structures, hydration is controlled in one substance. 4-Picoline N-oxide deliquesces within a day, but its cocrystal with barbital does not absorb moisture at 50% RH and 30 degrees C up to four weeks. Amide-N-oxide heterosynthon has potential utility in both amide and N-oxide type drug molecules with complementary CCFs. Its occurrence probability in the Cambridge Structural Database is 87% among 27 structures without competing acceptors and 78% in 41 structures containing OH, NH, H(2)O functional groups.

A comparative study of the reactivity of Zr(IV), Hf(IV) and Th(IV) metallocene complexes: Thorium is not a Group IV metal after all

Thorium(IV) is often considered to show similar chemistry to Group IV transition metals. However, studies in our laboratory have shown that this generalization is incorrect. This report presents direct comparisons where the Th(IV) metallocene complexes (C 5Me 5) 2ThR 2 (R = CH 3, Ph, CH 2Ph) undergo unique chemical reactivity with pyridine, 2-picoline, pyridine N-oxide, 2-picoline N-oxide, and benzonitrile, while the Group IV metal analogues (C 5R 5) 2M(CH 3) 2 (R = H, CH 3; M = Zr, Hf) do not. We also report revised high-yield syntheses for the zirconium and hafnium starting materials, (C 5H 5) 2MR 2 (M = Zr, Hf; R = CH 3, Ph, CH 2Ph), using Grignard reagents for alkylation in addition to the X-ray crystal structures of (C 5H 5) 2Hf(Ph) 2 and (C 5H 5) 2Hf(CH 2Ph) 2.

(Nitrato-κO)(1,10-phenanthroline-κ2N,N′)(picolinatoN-oxide-κ2O,O′)copper(II)

The coordination environment of copper(II) in the title compound, [Cu(C6H4NO3)(NO3)(C12H8N2)], is square pyramidal; the basal plane comprises the two N atoms of 1,10-phenanthroline and the two O atoms of picolinate N-oxide, with the apical position occupied by a nitrate O atom.