- New description of substituent effect on electronic spectra by means of substituent constants-VI. Ultraviolet spectra of 4-substituted pyridine N-oxides and blue shifted iodine bands of their EDA complexes with iodine
-
Electronic spectra of 4-substituted pyridine N-oxides and their EDA complexes with iodine were studied.The substituent effect on the near u.v. 1A1 intramolecular CT bands of the N-oxides and on the blue shifted iodine bands caused by CT complex formation are discussed in terms of a general equation, theoretically derived in order to describe the substituent effect on electronic spectra by means of substituent constants.The results are quite successful and supported by semi-empirical SCFMO-Cl calculations.Based on the results mentioned above, the character of n-? type N-oxide-iodine CT complexes is also examined.The complex formation constants(log K) and pKa values of the N-oxides correlate especially well, indicating that the CT interaction mechanism cannot be neglected in proton addition reactions such as hydrogen bonding and pKa values.
- Uno, Bunji,Kano, Kenji,Kaida, Naoki,Kubota, Tanekazu
-
-
Read Online
- Identical acyl transfer reactions between pyridine N-oxides and their N-acylonium salts
-
28 identical acyl exchange reactions R-CO-Nu+, X- + Nu between pyridine N-oxides in acetonitrile were studied. Here, X- = BPh 4 - and R = methyl, N,N-dimethylamino, N,N-diethylamino, 4-morpholino, 1-piperidino, N-methyl, N-phenylamino, or N,N-diphenylamino group. The IR and NMR spectroscopic characteristics of acyloxypyridinium salts were determined, and the quantum-chemical parameters of all reagents calculated. The results were subjected to correlation analysis. It was found that the rate of identical acyl transfer reactions was controlled by the interaction of frontier orbitals in the transition state.
- Rybachenko,Shroeder,Chotii,Kovalenko,Red'Ko,Gierzyk
-
-
Read Online
- A general synthesis of bis(o-azaheteroaryl)methane derivatives from N-oxides of azines and azoles
-
A general method of preparation of derivatives of bis(o-azaheteroaryl)methanes from aromatic N-oxides is reported, the key step of which is a 1,3-dipolar cycloaddition between N-oxides of azines or azoles and in situ generated terminal difluoroalkenes containing an o-azaheteroaryl substituent at the double bond. Selected products were applied for the preparation of two novel unsymmetrical analogues of BODIPY fluorescent dyes, containing both an imidazole and a quinoline or isoquinoline unit.
- Szpunar, Magdalena,Loska, Rafa?
-
-
Read Online
- Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation
-
Preclinical evidence in support of the potential utility of mGlu5 NAMs for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. Despite some promising results from clinical studies, no small molecule mGlu5 NAM has yet to reach market. Here we present the discovery and evaluation of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, VU0424238), a compound selected for clinical evaluation. Compound 27 is more than 900-fold selective for mGlu5 versus the other mGlu receptors, and binding studies established a Ki value of 4.4 nM at a known allosteric binding site. Compound 27 had a clearance of 19.3 and 15.5 mL/min/kg in rats and cynomolgus monkeys, respectively. Imaging studies using a known mGlu5 PET ligand demonstrated 50% receptor occupancy at an oral dose of 0.8 mg/kg in rats and an intravenous dose of 0.06 mg/kg in baboons.
- Felts, Andrew S.,Rodriguez, Alice L.,Blobaum, Anna L.,Morrison, Ryan D.,Bates, Brittney S.,Thompson Gray, Analisa,Rook, Jerri M.,Tantawy, Mohammed N.,Byers, Frank W.,Chang, Sichen,Venable, Daryl F.,Luscombe, Vincent B.,Tamagnan, Gilles D.,Niswender, Colleen M.,Daniels, J. Scott,Jones, Carrie K.,Conn, P. Jeffrey,Lindsley, Craig W.,Emmitte, Kyle A.
-
supporting information
p. 5072 - 5085
(2017/06/28)
-
- Iodine/TBHP-Promoted One-Pot Deoxygenation and Direct 2-Sulfonylation of Quinoline N-Oxides with Sodium Sulfinates: Facile and Regioselective Synthesis of 2-Sulfonylquinolines
-
A highly efficient iodine/TBHP-mediated one-pot deoxygenative and regioselective 2-sulfonylation of quinoline N-oxides with sodium sulfinate salts has been developed. This metal-, base-, and phosphorus-free protocol employs readily accessible and easy-to-handle reagents and can be conveniently carried out at room temperature under mild conditions, providing an alternative access to a series of 2-sulfonylquinolines and other related heteroaryl sulfone products in moderate-to-excellent yields within a short reaction time.
- Sumunnee, Ladawan,Buathongjan, Chonchanok,Pimpasri, Chaleena,Yotphan, Sirilata
-
supporting information
p. 1025 - 1032
(2017/02/15)
-
- Amines vs. N-Oxides as Organocatalysts for Acylation, Sulfonylation and Silylation of Alcohols: 1-Methylimidazole N-Oxide as an Efficient Catalyst for Silylation of Tertiary Alcohols
-
A comparison of the relative catalytic efficiencies of Lewis-basic amines vs. N-oxides for the acylation, sulfonylation and silylation of primary, secondary and tertiary alcohols is reported. Whilst the amines are generally superior to the N-oxides for acylation, the N-oxides are superior for sulfonylation and silylation. In particular, 1-methylimidazole N-oxide (NMI-O) is found to be a highly efficient catalyst for sulfonylation and silylation reactions. To the best of our knowledge, NMI-O is the first amine or N-oxide Lewis basic organocatalyst capable of promoting the efficient silylation of tert-alcohols in high yield with low catalyst loading under mild reaction conditions.
- Murray, James I.,Spivey, Alan C.
-
supporting information
p. 3825 - 3830
(2016/01/25)
-
- Highly efficient and selective phosphorylation of amino acid derivatives and polyols catalysed by 2-aryl-4-(dimethylamino)pyridine-N-oxides-towards kinase-like reactivity
-
The chemoselective phosphorylation of hydroxyl containing amino acid derivatives and polyols by phosphoryl chlorides catalyzed by 2-aryl-4-(dimethylamino)pyridine-N-oxides is described.
- Murray, James I.,Woscholski, Rudiger,Spivey, Alan C.
-
supporting information
p. 13608 - 13611
(2015/01/09)
-
- Grafting of a rhenium-oxo complex on Schiff base functionalized graphene oxide: An efficient catalyst for the oxidation of amines
-
A rhenium-oxo complex such as methyltrioxorhenium (MTO) has been homogeneously immobilized on a Schiff base modified graphene oxide (GrO) support via covalent bonding. The loading of MTO on GrO nanosheets was monitored by FTIR, TG-DTA, and elemental analyses. The developed heterogeneous catalyst is found to be efficient for the oxidation of various amines to the corresponding N-oxides using hydrogen peroxide as an oxidant in high to excellent yields. At the end of the reaction, the catalyst is readily recovered by filtration and reused for subsequent runs. After the third run, the catalyst showed a marginal decrease in catalytic activity owing to the leaching of the MTO complex from the support. This journal is the Partner Organisations 2014.
- Khatri, Praveen K.,Choudhary, Shivani,Singh, Raghuvir,Jain, Suman L.,Khatri, Om P.
-
p. 8054 - 8061
(2014/05/20)
-
- Equilibrium of acyl transfer between pyridine N-oxides and their acylonium salts
-
Transfer of acyl groups from N-acyloxypyridinium salts to pyridine N-oxides in acetonitrile was studied. The equilibrium constants of acyl exchange were determined. These quantities vary in the range covering eight orders of magnitude, depending on the st
- Rubachenko,Schroeder,Chotii,Kovalenko,Red'ko,Lenska
-
p. 1241 - 1246
(2008/12/22)
-
- Molecular complexes of 4-nitropyridine and 4-nitroquinoline N-oxides with boron trifluoride and hydrogen chloride as intermediates in SNAr reactions
-
Complexation of 4-nitropyridine N-oxides with ν- (BF3, HCl) and π-acceptors (tetracyanoethylene, chloranil, 2,3-dichloro-5,6-dicyano-1,4- benzoquinone, 7,7,8,8-tetracyanoquinodimethane) activates the nitro group to nucleophilic replacement by chlorine. Adducts formed by 4-nitropyridine and 4-nitroquinoline N-oxides with boron trifluoride and hydrogen chloride were studied by IR spectroscopy. It was shown that these complexes belong to the n,ν type and that the donor-acceptor interaction therein involves the oxygen atom of the N-oxide group.
- Nizhnik,Andreev,Belashev
-
scheme or table
p. 1824 - 1830
(2009/09/06)
-
- Rate and equilibrium constants of benzoyl group transfer between pyridine N-oxides
-
Kinetic characteristics of 19 transfer reactions of benzoyl group from N-benzoyloxypyridinium salts to pyridine N-oxides and 4-dimethylaminopyridine were studied in acetonitrile by the stopped-flow method. The rate of an identical reaction for 4-methoxypyridine was measured by dynamic NMR spectroscopy. For 5 other identical reactions the rates were estimated from Bronsted correlations. Equilibrium constants were estimated with the use of UV spectrophotometry (6), IR spectroscopy (2), from kinetic data (K ij = k ij /k ji ) (2), and in one case as logK i-j = logK i-x - logK j-x . The second order rate constants (k ij ) varied in the range 102-105 l mol -1 s-1, the equilibrium constants (K ij ) in the range 102-10-2; the activation parameters (ΔH ≠) were within 15-50 kJ mol-1, (-ΔS ≠) -20-110 J mol-1 K-1. The reactions under study occur in a single stage following the concerted SN2 mechanism through an early associative transition state. The benzoyl groups exchange rate and equilibrium are well described by simplified Marcus equation (omitting the quadratic term). 2005 Pleiades Publishing, Inc.
- Rybachenko,Schroeder,Chotii,Lenska,Red'Ko,Kovalenko
-
p. 774 - 778
(2007/10/03)
-
- Rate and Equilibrium Constants of Dimethylcarbamoyl Transfer between Pyridine N-Oxides
-
Dimethylcarbamoyl transfer from N-acyloxypyridinium salts to pyridine N-oxides in acetonitrile occurs in one stage by the forced concerted SN2 mechanism. The rate and equilibrium of the reaction are fairly described by the Bronsted equation. The Marcus equation provides a much higher quality of reactivity predictions.
- Schroeder,Rybachenko,Chotii,Kovalenko,Grebenyuk,Lenska,Eitner
-
p. 455 - 462
(2007/10/03)
-
- Equilibrium of acetyl transfer between pyridine N-Oxides and their acetylonium salts
-
The equilibrium constants of acetyl transfer between O-acetylonium salts of a series of pyridine N-oxides and 4-(4-dimethylaminostyryl)pyridine N-oxide in acetonitrile and methylene chloride were determined. The equilibrium constants correlate with the ac
- Rybachenko,Chotii,Kovalenko,Schroeder
-
p. 786 - 788
(2007/10/03)
-
- Acetyl exchange between pyridine N-oxides in acetonitrile solutions: An attempt to apply the Marcus equation to acetyl transfer
-
Forty-three (including eight identical) reactions of acetyl transfer from N-acetyloxypyridinium salts to pyridine N-oxides in acetonitrile solutions were studied. The rate constants k2 vary in the range 107-10-1 1 mol-1 s-1; the equilibrium constants K, in the range 107-10-7; the activation enthalpy ΔH≠, in the range 17-30 kJ mol-1; the activation entropy -ΔS≠, in the range 60-85 J mol-1 K-1; and the heat of reaction -ΔH0, within ±50 kJ mol-1. All reactions occur in a single stage by the concerted SN2 mechanism with a low degree of bond cleavage in the transition state. The rate and equilibrium of the acetyl exchange are satisfactorily described by the Bronsted equation. The quality of predicting the reactivity is substantially improved by introducing into the correlation equation a second parameter, the rates of identical reactions.
- Rybachenko,Schroeder,Chotii,Titov,Kovalenko,Leska,Grebenyuk
-
p. 1608 - 1615
(2007/10/03)
-
- A simple and efficient method for the preparation of N- heteroaromatic N-oxides
-
Urea-hydrogen peroxide/formic acid system has shown utility for mild and safe N-oxidation of N-heteroaromatic compounds.
- Balicki, Roman,Golinski, Jerzy
-
p. 1529 - 1534
(2007/10/03)
-
- Oxidation of N-heterocycles by H2O2 catalyzed by a Mn-porphyrin: An easy access to N-oxides under mild conditions
-
A variety of N-heteroaromatic compounds were converted into their corresponding N-oxides with good yields and with high chemoselectivity in tile presence of hydrogen peroxide as oxygen donor and a catalytic amount of Mn-porphyrin. The scope and limitation of this method are discussed.
- Thellend,Battioni,Sanderson,Mansuy
-
p. 1387 - 1388
(2007/10/03)
-
- Antipruritic composition
-
An antipruritic composition for an oral medicine, injection, and external medicine, comprising an effective amount of a chelated zinc (e.g., zinc picolinate) as an antipruritic agent.
- -
-
-
- The Equilibrium in the Formation of N-acetoxypyridinium Salts
-
The interaction of pyridine N-oxides with acetyl chloride and acetyl bromide has been investigated in chloroform, methylene chloride, and acetonitrile.The equilibrium constants and the thermodynamic characteristics of the formation of N-acetoxypyridinium salts have been obtained.
- Rybachenko, V. I.,Chotii, K. Yu.,Kozhevina, L. I.,Titov, E. V.
-
p. 813 - 816
(2007/10/02)
-
- Studies on 1,3-Benzoxazines. I. Synthesis of Primary 2-Amino-pyridines via the Reaction of Imidoyl Chlorides of 1,3-Benzoxazines with Pyridine N-Oxides
-
A new synthetic method for primary 2-aminopyridine derivatives is described.Treatment of the imidoyl chlorides of 1,3-benzoxazines (1a-i) with pyridine N-oxides resulted in the introduction of an oxazine moiety into the α-position of the pyridine ring through rearrangement of the initially formed reaction adduct.Acid hydrolysis of the rearrangement products afforded 2-aminopyridine derivatives in excellent yields.When methoxypyridine N-oxides were used, products of a different type (10 and 14) were obtained.
- Wachi, Kazuyuki,Terada, Atsusuke
-
p. 465 - 472
(2007/10/02)
-