(N-Arylaminomethyl)pyridine-N-oxides: Synthesis and characterization of potential ligand systems and the formation of their N,O-chelate aluminum complexes

Pyridine-N-oxide-2-carbaldehyde (4a) was converted to the corresponding imine (5a) by treatment with 2,6-diisopropylaniline. Subsequent reduction with a sodium borohydride gave the corresponding (N-arylaminomethyl)pyridine-N-oxide derivative (6a). A series of analogous compounds was prepared starting from the respective (aldimino)quinoline-N-oxide (4b) or (ketimino)pyridine-N-oxide (10) systems. Deprotonation of the (aminomethyl)pyridine-N-oxides resulted in a series of unexpected reactions, such as coupling, internal redox reactions or fragmentation. Eventually, the N,O-chelate aluminum complexes (22, 23) derived from the (aminoethyl)pyridine-N-oxide ligand systems could be obtained by treatment of the respective iminopyridine-N-oxides with trimethylaluminum. Many products were characterized by X-ray diffraction.     

α-Bromination of linear enals and cyclic enones

Facile α-bromination of cyclic enones and linear enals involving N-bromosuccinimide and 1-2 equiv of pyridine-N-oxide is reported herein. α-Bromination of linear enals was found to proceed with double bond geometry retention.     

Electrophilic substitutions and HOMOs in azines and purines

The low reactivity of pyridine, pyridazine, pyrazine, pyrimidine, and purine toward electrophilic substitution reactions can be explained assuming a frontier orbitals control of the reaction. DFT study of the molecular orbitals of these molecules shows that the HOMOs of these substrates are not π orbitals. Furthermore, the change in the reactivity observed in pyridine-N-oxide, in activated pyrimidines, and in activated purines can be explained considering that, in this case, the HOMOs are π orbitals.     

Multicomponent Hantzsch cyclocondensation as a route to highly functionalized 2- and 4-dihydropyridylalanines, 2- and 4-pyridylalanines, and their N-oxides: preparation via a polymer-assisted solution-phase approach

An improved and efficient entry to highly functionalized β-(2-pyridyl)- and β-(4-pyridyl)alanines and the corresponding 1,4-dihydro and N-oxide derivatives has been developed by one-pot thermal Hantzsch-type cyclocondensation of aldehyde-ketoester-enamine systems in which one of the reagents (aldehyde or ketoester) was carrying the unmasked but protected chiral glycinyl moiety. Thus coupling N-Boc-O-benzyl aspartate β-aldehyde, acetoacetate and aminocrotonate esters afforded tetrasubstituted β-(4-dihydropyridyl)alanines (75% yield). One of these products was almost quantitatively transformed into the β-(4-pyridyl)alanine derivative which in turn was oxidized to the corresponding N-oxide. Each of these enantiomerically pure (Mosher's amide analysis) heterocyclic α-amino acids was incorporated into a tripeptide by coupling with (S)-phenylalanine. In a similar way tetrasubstituted β-(2-dihydropyridyl)alanine, β-(2-pyridyl)alanine and β-(1-oxido-2-pyridyl)alanine were prepared via Hantzsch cyclocondensation reaction using benzaldehyde, aminocrotonate, and acetoacetate carrying the N-Boc-O-benzyl glycinate moiety. It was shown that the work up of the reaction mixtures derived from the cyclocondensation and oxidation reactions can be carried out by the use of polymer supported reagents and sequestrants thus allowing the isolation of the products in high purity without any chromatography.     

Peracid-induced ring opening of some hexahydro-2H-isoxazolo[2,3-a]pyridines to second-generation cyclic aldonitrones

A study of the stereo- and face selectivity of the cycloaddition reactions of several mono- and disubstituted alkenes with 4-hydroxymethyl-3,4,5,6-tetrahydropyridine 1-oxide has been carried out. The addition reactions have displayed a very high degree of face selectivity in the range 13-48:1. Use of dimethyl methylenemalonate as a protective group in nitrone cycloaddition reactions has been demonstrated. The invertomeric analysis revealed that the bicyclic cycloadducts remain predominantly as the cis-fused isomer, which leads to the formation of synthetically important second-generation cyclic aldonitrones via peracid oxidation. One interesting finding was that treatment of the cycloadducts with two equivalents of peracid afforded the cyclic N-hydroxy lactams, presumably via further oxidation of the aldonitrones. The piperidine ring has been elaborated by cycloaddition reaction of the second-generation nitrones with several alkenes, which in most cases gave the cycloadducts in a stereoselective manner.     

Thermooxidative decomposition of heterocyclic <Emphasis Type="Italic">N</Emphasis>-oxides

Thermooxidative decomposition of pyridine N-oxide, 4-(4-dimethylaminostyryl)pyridine N-oxide, 4-(4-methoxystyryl)pyridine N-oxide, quinoline N-oxide, 2-methylquinoline N-oxide, 4-chloroquinoline N-oxide, 2-styrylquinoline N-oxide, and 2-(4-dimethylaminostyryl)quinoline N-oxide was studied. The kinetic parameters of the thermooxidative processes were calculated according to three independent procedures. The relation between the nature of heterocyclic N-oxide and its stability to thermal oxidation was analyzed.     

C(3)-乙烯基的化学修饰与含氧基团取代的叶绿素-a衍生物的合成

以焦脱镁叶绿酸-a甲酯为起始原料, 通过加成和氧化反应将其3-位上的乙烯基转化为羟乙基、溴乙基、二羟乙基、二溴乙基和溴羟乙基, 再经过二甲亚砜/乙酸酐或者高钌酸四丙基铵(TPAP)/N-甲基吗啉-N-氧化物所组成的混合氧化剂的氧化反应, 得到多种C(3)-多酮基取代的二氢卟吩衍生物. 其单羟基作为离去基团与不同的活泼亚甲基化合物经过重排过程, 得到相应的酮基取代的二氢卟吩衍生物. 所得新叶绿素衍生物的化学结构均经UV, IR, ¹H NMR及元素分析得以证实, 并对相应的反应提出可能的反应机理.     

Directed H-bonding inhibition in molecular recognition: an NMR case study of the H-bonding of a dicarboxylic acid with a new mixed diamide receptor having one adjacent pyridine-N-oxide

The inhibition of hydrogen bond formation in the recognition of adipic acid by a new diamide receptor 1 having a pyridine-N-oxide and a simple pyridine ring adjacent to the amide moieties is observed. NMR studies show binding by the pyridine amide group in 1, which demonstrates the discrimination in hydrogen bonding between the carboxyls and an amide adjacent to pyridine versus another adjacent to the pyridine N-oxide. This specific inhibition of hydrogen bonding to a carboxyl group by the two different amides in 1 is corroborated by the NMR binding studies of 1 with propionic acid.     

Preparation of chiral bipyridine bis-N-oxides by oxidative dimerization of chiral pyridine N-oxides

The direct preparation of chiral 2,2′-bipyridine bis-N-oxides has been developed. The method involves two stages, first, the deprotonation of substituted chiral pyridine N-oxides and second, the oxidative dimerization of the resulting 2-lithiopyridine N-oxides. Optimization of the reaction conditions led to the selection of LiTMP in THF for the deprotonation and molecular iodine as the oxidant. The corresponding 2-iodopyridine N-oxide is invariably formed as a by-product. A series of 11 chiral pyridine N-oxides was prepared that bear substituents at the C(2) and C(5) positions. Oxidative dimerization of these mono-N-oxides proceeded in 33–77% yield. In all cases, the dimerization was highly diastereoselective for the formation of the P-configuration of the chiral axis.     

Extraction of metal ions by N-phenyl-, N-methyl-, and N-unsubstituted hydroxamic acid resins

Procedures are described for preparing macroreticular chelating resins with hydroxamic acid or N-methylhydroxamic acid functional groups. The chelating properties of the resins are compared with each other and with an N-phenylhydroxamic acid resin reported earlier. The extraction of 19 metal ions was studied as a function of pH for the N-methylhydroxamic acid resin. Several analytical applications of this resin have been demonstrated including the purification of chemical reagents, concentration of trace metal ions, and chromatographic separation of metal-ion mixtures.     

Kinetic and mechanistic investigations on the oxidation of N’-heteroaryl unsymmetrical formamidines by permanganate in aqueous alkaline medium

Kinetic studies on the oxidation of two substituted azinyl formamidines (Azn-Fs), namely N,N-dimethyl-N’-(pyrimidin-2-yl) formamidine (Pym-F) and N,N-dimethyl-N’-(pyridin-2-yl) formamidine (Py-F), by alkaline permanganate have been performed by spectrophotometry. The spectroscopic and kinetic evidence reveals the formation of 1:1 intermediate complexes between the oxidant and substrates. The influence of pH on the oxidation rates indicated that the reactions are base-catalyzed. The reactions show identical kinetics, being first order each in [MnO₄ ^?]₀ and [Azn-F]₀, but with a fractional first-order dependence on [OH^?]. The effect of temperature on the reaction rate has been studied. Increasing ionic strength has no significant effect on the rate. The final oxidation products of Pym-F and Py-F were identified as 2-aminopyrimidine and 2-aminopyridine, respectively, in addition to dimethyl amine and carbon dioxide. Under comparable experimental conditions, the oxidation rate of Py-F is higher than that of Pym-F. A reaction mechanism adequately describing the observed kinetic behavior is proposed, and the reaction constants involved in the different steps of the mechanism have been evaluated. The activation parameters with respect to the rate-limiting step of the reactions, along with thermodynamic quantities, are presented and discussed.     

Building hydrogen-bonded networks from metal complexes containing the heterotopic (N or O) ligand 4,4′-bipyridine-N-monoxide

The heterotopic ligand 4,4′-bipyridine-N-monoxide (BIPYMO) has a rigid, linear structure and contains both a pyridine N-donor and a pyridine-N-oxide O-donor which are capable of coordinating to a metal centre or alternatively acting as a hydrogen bond acceptor. The hydrogen bonding capacity of BIPYMO is first demonstrated by the formation of hydrogen-bonded networks with water and some simple dicarboxylic acids (fumaric = FUM, terephthalic = TPA). It is then shown that BIPYMO can coordinate through the pyridine N-donor to Pd(II) and through the pyridine-N-oxide O-donor to Fe(II), Co(II) and Mn(II). In each case, the peripheral, uncoordinated N- or O-atoms act as a hydrogen bond acceptors and interact with a metal-bound and hydrogen bond donor (H₂O, fumarate = FUM, malonate = MAL, isophthalate = IPA) to form a solid-state, network through a combination of metal–ligand coordination and hydrogen bonding. Single-crystal X-ray structures of {(BIPYMO)(H₂O)₂}_n, {(BIPYMO)(FUM)}_n, {(BIPYMO)(TPA)}_n, {[Pd(BIPYMO)₂(MAL)₂](H₂O)}_n, {[Pd(BIPYMO)₂(IPA)₂](H₂O)₂}_n and {[M(BIPYMO)₂(FUM)₂(H₂O)₂]}_n (M = Mn, Fe, Co), show how the individual building blocks are organised via hydrogen bonding through uncoordinated pyridine N-atoms or pyridine-N-oxide O-atoms to form supramolecular networks.     

A manganese(V)-oxo π-cation radical complex: influence of one-electron oxidation on oxygen-atom transfer

One-electron oxidation of Mn(V)-oxo corrolazine 2 affords 2(+), the first example of a Mn(V)(O) π-cation radical porphyrinoid complex, which was characterized by UV-vis, EPR, LDI-MS, and DFT methods. Access to 2 and 2(+) allowed for a direct comparison of their reactivities in oxygen-atom transfer (OAT) reactions. Both complexes are capable of OAT to PPh(3) and RSR substrates, and 2(+) was found to be a more potent oxidant than 2. Analysis of rate constants and activation parameters, together with DFT calculations, points to a concerted OAT mechanism for 2(+) and 2 and indicates that the greater electrophilicity of 2(+) likely plays a dominant role in enhancing its reactivity. These results are relevant to comparisons between Compound I and Compound II in heme enzymes.     

NH4I/1,10-phenanthroline catalyzed direct sulfenylation of N-heteroarenes with ethyl arylsulfinates

An efficient synthesis of N-heterocyclic aryl sulfides via NH₄I/1,10-phenanthroline-catalyzed direct sulfenylation reactions was reported. In this reaction, heteroarenes such as indoles, and pyrroles serve as nucleophiles by installing a arylthio group at the C3 and C2 position of heterocycles, respectively. With readily accessible and free of unpleasant odor ethyl arylsulfinates as sulfur reagents, the metal-free-catalyzed direct sulfenylation of N-heteroarenes has been developed. 3-Arylthio-indoles and 2-arylthio-pyrroles derivatives were obtained in moderate to excellent yields, even on gram scale. The reaction was general for a broad scope of substrates and demonstrated good tolerance to a variety of functional groups.     

Probing the reactivity of nebularine N1-oxide. A novel approach to C-6 C-substituted purine nucleosides

A novel approach to the synthesis of purine nucleoside analogues, featuring the reaction of the C6-N1-O⁻ aldonitrone moiety of 9-ribosyl-purine (nebularine) N1-oxide with some representative dipolarophiles, as well as Grignard reagents, is reported. Addition of Grignard reagents to the electrophilic C-6 carbon of the substrate allows a facile access to C-6 C-substituted purine nucleosides without using metal catalysts. 1,3-Dipolar cycloaddition processes lead to novel nucleoside analogues via opening, degradation or ring-enlargement of the pyrimidine ring of the base system of the first-formed isoxazoline or isoxazolidine cycloadduct.     

Reactions of anionic porphyrin with group 11 elements: a spectrophotometric and electrospray ionization mass spectrometry study

The reaction of 3,8,13,18-tetramethyl-21H,23H-porphine-2,7,12,17-tetrapropionic acid or coproporphyrin-I (CPI) with the elements of 11 group have been studied. CPI is an anionic porphyrin that slowly reacts with copper ion to form Cu^IICPI and with silver ions to form Ag^IICPI, Ag^IIICPI complexes and colloidal silver. Gold ions do not form complexes with CPI, but, in the main, colloidal gold and some CPI-N-oxide. The kinetics of the reactions with copper and silver were spectrophotometerically studied and the rate constants were calculated. The identification and characterization of this water-soluble anionic porphyrin and its metal complexes have been performed by electrospray mass spectrometry (ESI-MS) that proved to be an excellent method for these determinations. The multiple charged parent ions for metal free ligand and their metal complexes were identified.     

Molecular complexes of aryltellurium(IV) chlorides

The synthesis and spectroscopic study of molecular complexes of type [RTeCl₃ · L] and [RTeCl₃ · 2L], where R = phenyl, 4-phenoxyphenyl and L = pyridine, pyridine-N-oxide, tri-n-octylphosphine oxide, 1,10-phenanthroline and 2,2′-bipyridyl are reported. These compounds were characterised by their IR spectra, elemental analysis and conductivity data. The conductivities in acetonitrile shows the non-electrolytic behaviour of these hygroscopic compounds which are monomeric in boiling benzene.     

Application of N-halo reagents in organic synthesis

This review article summarizes published data on the application of N-halo reagents (such as N-halo amines, N-halo amides and/or imides, N-halo sulfonamides and/or imides, and etc.) in various organic functional group transformations such as: oxidation reactions, deprotection and protection of different functional groups, halogenation of saturated and unsaturated compounds, acylation of alcohols, phenols, amines or thiols, epoxidation of alkenes, aziridination and etc. The main purpose of writing this review is encouraging of active researchers interested to this field for the synthesis of new N-halo reagents specially with different halogens and applications of these new N-halo reagents in organic reactions or finding more and more applications of existing N-halo reagents in organic synthesis.     

Synthesis of chiral 2,2′-dipyridylamines and their use in the copper-catalyzed asymmetric allylic oxidation of cyclohexene

Chiral dipyridylamines have been synthesized by N-arylation reactions, and the applicability of those compounds to the copper-catalyzed asymmetric allylic oxidation of cyclohexene was demonstrated.     

A novel synthetic approach towards N-phenylsuccinimides from γ-lactam-2-carboxylic acid derivatives by reaction with CAN-NaBrO3

N-Arylsuccinimides have been synthesized by decarboxylative oxidation of N-aryl-γ-lactam-2-carboxylic acids with the dual oxidant CAN/NaBrO₃ in refluxing acetonitrile-water.