N-alkylpyridinium Salts Research Articles

Visible-Light-Mediated Aerobic Oxidation of N-Alkylpyridinium Salts under Organic Photocatalysis.

Quinolones and isoquinolones exhibit diverse biological and pharmaceutical activities, and their synthesis is highly desirable under mild conditions. Here, a highly efficient and environmentally friendly visible light-mediated aerobic oxidation of readily available N-alkylpyridinium salts has been developed with Eosin Y as the organic photocatalyst and air as the terminal oxidant, and the reaction provided quinolones and isoquinolones in good yields. The method shows numerous advantages including mild and environmentally friendly conditions, high efficiency, tolerance of wide functional groups and low cost. Furthermore, 4-desoxylonimide with important pharmaceutical activities was effectively prepared by using our method. Therefore, the present method should provide a novel and useful strategy for synthesis and modification of N-heterocycles.

Nucleophilic Dearomatization of Pyridines under Enamine Catalysis: Regio-, Diastereo-, and Enantioselective Addition of Aldehydes to Activated N-Alkylpyridinium Salts.

Catalytic addition of chiral enamines to azinium salts is a powerful tool for the synthesis of enantioenriched heterocycles. An unprecedented asymmetric dearomative addition of aldehydes to activated N-alkylpyridinium salts is presented. The process exhibits complete C-4 regioselectivity along with high levels of diastereo- and enantiocontrol, achieving a high-yielding synthesis of a broad range of optically active 1,4-dihydropyridines. Moreover, the presented methodology enables the synthesis of functionalized octahydropyrrolo[2,3-c]pyridines, the core structure of anticancer peptidomimetics.

Organocatalyzed One-Step Synthesis of Functionalized N-Alkyl-Pyridinium Salts from Biomass Derived 5-Hydroxymethylfurfural.

An efficient and scalable method has been developed for the synthesis of N-alkylpyridinium salts from biomass derived 5-hydroxymethylfurfural and alkyl amines using a catalytic amount of formic acid. This protocol is also extended to various diamines providing the exclusive formation of mono-N-alkylpyridinium salts. In addition, the mechanism for the formation of pyridinium salts was studied by DFT and using H2(18)O isotope labeled experiments showing no incorporation of (18)O in the product.

Enamine Rearrangement of Pyridinium Salts to Indole Ring: A Combined Experimental and Molecular Modeling Study

N-Alkyl pyridinium (II) and N-alkyl isoquinolinium salts V undergo cyclization reaction when heated with sodium bicarbonate to give the corresponding indolizine derivatives III and VIa, VIb, VIc, VId, VIe, respectively, which undergo ring opening and recyclization reactions when heated with aqueous sodium hydroxide to give the corresponding indole derivatives IV and IXa, IXb, IXc, IXd, IXe, respectively. Molecular modeling tools including Molecular Mechanics using Augmented MM3 parameters followed by geometry optimization calculations in MO-G using PM3 parameters were performed to gain better understanding and more insights on the thermodynamic properties of the recyclization reactions of compounds IIa, IIb, IIc, IId, IIe, IIf, IIg to the corresponding IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg and IIIa, IIIb, IIIc, IIId, IIIe, IIIf, IIIg to the corresponding IVa, IVb, IVc, IVd, IVe, IVf, IVg. The results were in excellent agreement with the experimental data and hence were proven to be a good tool in explaining different yields % because of the steric and electronic effects of electron-withdrawing groups on the reactivity of the pyridine ring for nucleophilic attack.

Synthetic studies towards the Lycopodium alkaloid paniculatine

Two bridging tetracyclic products have been observed while attempting to construct the final C-ring of the Lycopodium alkaloid, paniculatine, by an intramolecular addition of enolates to unactivated N-alkyl pyridinium salts.

ChemInform Abstract: Reaction of N-Alkylpyridinium Salts with Hydroxylamine.

ChemInform Abstract: Reaction of N-Alkylpyridinium Salts with Hydroxylamine.

7-alkyl-1,3,7-triazapyrenium salts: Rare event of oxidative hydroxylation under the conditions of acid catalysis

The transformation of N-alkylpyridinium salts into the corresponding N-alkylpyridones under the treatment with an alkaline solution of K3[Fe(CN)6] discovered by Decker to the end of XIX century [1] became a standard preparation procedure for N-alkylpyridones [2]. This reaction was later extended to numerous other heteroaromatic cations [3, 4]. The potassium ferrocyanide remains the classic oxidant in this reaction, more seldom oxygen [5] and other oxidants [6] are employed. The general condition of the reaction is the alkaline water medium. We formerly reported on the synthesis and oxidative hydroxylation of 1and 7-alkyl-1,3,7-triazapyrenium salts [7]. In the system KOH–K3[Fe(CN)6]–H2O they formed 2and 6-oxoderivatives respectively. We report here on an uncommon reaction of oxidative hydroxylation of 7-alkyl-1,3,7-triazapyrenium salts Ia–Ic under acid catalysis. It was found that at the addition of K3[Fe(CN)6] to the solution of salts Ia–Ic in 60% sulfuric acid the reaction readily proceeded at room temperature yielding the products of oxidative hydroxylation IIa–IIc. The probable mechanism of this reaction involves the protonation of salt I, the nucleophilic attack on dication A of a water molecule, and the subsequent oxidation of the product of the covalent hydration, cation of pseudobase B (or of the pseudobase itself). In such reactions occurring in alkaline medium the anion of the pseudobase

Synthesis and Biological Activity of Some 3‐Imidazo[1,2‐a]pyridin‐2‐yl‐chromen‐2‐one and 3‐Indolizin‐2‐yl‐chromen‐2‐one.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The ammonia-free partial reduction of substituted pyridinium salts

This paper reports a study into the partial reduction of N-alkylpyridinium salts together with subsequent elaboration of the intermediates thus produced. Activation of a pyridinium salt by placing an ester group at C-2, allows the addition of two electrons to give a synthetically versatile enolate intermediate which can be trapped with a variety of electrophiles. Furthermore, the presence of a 4-methoxy substituent on the pyridine nucleus enhances the stability of the enolate reaction products, and hydrolysis in situ gives stable dihydropyridone derivatives in good yields. These versatile compounds are prepared in just three steps from picolinic acid and can be derivatised at any position on the ring, including nitrogen when a p-methoxybenzyl group is used as the N-activating group on the pyridinium salt. This publication describes our exploration of the optimum reducing conditions, the most appropriate N-alkyl protecting group, as well as the best position on the ring for the methoxy group. Electrochemical techniques which mimic the synthetic reducing conditions are utilised and they give clear support for our proposed mechanism of reduction in which there is a stepwise addition of two electrons to the heterocycle, mediated by di-tert-butylbiphenyl (DBB). Moreover, there is a correlation between the viability of reduction of a given heterocycle under synthetic conditions and its electrochemical response; this offers the potential for use of electrochemistry in predicting the outcome of such reactions.

1,4-Dihydropicolinic acid derivatives: novel NADH analogues with an altered connectivity pattern

Sodium dithionite reduction of α-substituted N-alkylpyridinium salts (derived from picolinic acid derivatives) afforded the corresponding 1,4-dihydropyridines with a new substitution pattern, in which the electron-withdrawing group is at the α-position. These compounds promote biomimetic reductions and are hence considered functional NADH analogues.

Simple synthesis of a weak nucleophilic base (4-ethyl-2,6-diisopropyl-3,5-dimethylpyridine) evidencing a double Janus group effect.

By analogy with 2,6-di-tert-butylpyridine and its 4-methyl-substituted derivatives, which are nonnucleophilic bases, 4-ethyl-2,6-diisopropyl-3,5-dimethylpyridine (4) is also such a base. The isopropyl groups (Janus-like groups) are forced by the neighboring methyl groups to turn their "tert-butyl-analogue face" toward the heteroatom, thereby protecting it sterically against electrophilic attack. The synthesis proceeds in two stages via the corresponding pyrylium salt 3 that is obtained by alkene diacylation. X-ray data for 4, its picrate, and the hexafluorophosphate of 3 confirm that the ground-state conformation agrees with the Janus effect prediction. The chemical behavior of 4 indicates that it is indeed a weak nucleophilic base, which is able to substitute the nonnucleophilic bases in organic syntheses. The compound 3 reacts at normal pressure with methylamine or ethylamine, forming N-alkylpyridinium salts. The cationic polymerization of isobutene in the presence of 4 was also investigated.

Asymmetric synthesis of tetracyclic substructures of Strychnos indole alkaloids

The addition of the enolate of methyl 1-methyl-2-indoleacetate 1 and lithium 2-(lithiomethyl)indole-1-carboxylate 5 to pyridines and N-alkylpyridinium salts bearing a chiral auxiliary at the 3-position (tolylsulfinyl, acyl iron complexes, bornane-10,2-sultam), with subsequent acid cyclization of the resulting dihydropyridines, is investigated.

Selective Complexation of N-Alkylpyridinium Salts: Recognition of NAD+ in Water

A molecular clip made of two naphthalene side walls and bisphosphonate arms selectively binds to N-alkylpyridinium ions in water. Through the unique potential of this clip to combine π–cation and electrostatic interactions with the hydrophobic effect, the host molecule is able to complex NAD+ (nicotinamide adenine dinucleotide; see picture) efficiently in aqueous solution.

Reactions of 3-substituted 1,2-epoxypropanes with pyridinium salts. N-alkylpyridinium salts and their synthetic potential

1-Chloro-2,3-epoxypropane and 2,3-epoxypropyl carboxylates react with pyridinium carboxylates and phosphonates, yielding N-alkylated pyridinium salts.

Addition of organocopper reagents to N-alkylpyridinium salts. A flexible access to polysubstituted dihydropyridines

The addition of a series of organocopper (alkyl, vinyl, allyl, and ethynyl) reagents to 3-acyl- N-alkylpyridinium salts, followed by acylation of the intermediate 1,4- or 1,2-dihydropyridines with trichloroacetic anhydride has been studied.

Synthesis of 3,5-diacyl-4-phenyl-1,4-dihydropyridines

3,5-Diacyl-4-phenyl-1,4-dihydropyridines have been synthesized via a regio- and chemoselective addition of Ph 2Cu(CN)Li 2 to β-substituted N-alkylpyridinium salts, followed by acylation of the intermediate 1,4-dihydropyridines with trichloroacetic anhydride and subsequent haloform-type reaction. A similar sequence using an N-silylpyridinium salt and PhMgBr allows the preparation of the corresponding N-unsubstituted dihydropyridines.

Synthesis, Structure, and Thermotropic Mesomorphism of Layered N-Alkylpyridinium Tetrahalopalladate(II) Salts

Two homologous series of N-alkylpyridinium salts, [Cn-Py]2[PdX4] (n = 12, 14, 16, 18; X = Cl, Br), have been synthesized, and their thermal behavior has been studied by differential scanning calorimetry and hot-stage polarizing optical microscopy. Except for the substances with n = 12, all the materials show thermotropic polymorphism. The crystal structures of [C12-Py]2[PdCl4], [C16-Py]2[PdCl4], and [C16-Py]2[PdBr4] have been solved. All three complex salts crystallize in the triclinic space group P1̄. Crystal packing reveals layered structures with alternating polar and apolar sublayers, where each [PdX4]2- anion is sandwiched between two antiparallel pyridinium cations. Alkyl chains are highly interdigitated and tilted with respect to the layer normal. The structural characterization of the [Cn-Py]2[PdX4] (n = 16, 18; X = Cl, Br) salts has been achieved also through variable-temperature powder X-ray diffraction. The [PdCl4]2- salts undergo transitions to a second crystalline phase and then to an ordered and a disordered smectic phase. The latter are assigned to single-layered smectic-E and partially bilayered smectic-Ad phases, respectively. On warming, the [PdBr4]2- analogues only show the smectic-Ad phase, preceded by a crystalline phase very similar to the room-temperature solid phase. The relative importance of hydrogen bonding throughout the sequence of structural changes is briefly addressed.

Synthesis, Characterization, and Electrochemistry of Some Acridine-1,8-dione Dyes

The synthesis, characterization, and electrochemical behavior of some acridinedione derivatives are reported. Cyclic voltammetric studies show that all the dyes undergo irreversible oxidation irrespective of the substitution on the nitrogen. The product formed on oxidation is the aromatic derivative in the case of N-H compounds and the acridinium salt in the case of the N-substituted compounds, which have been isolated and characterized. Formation of an intermediate carbon-centered radical is observed as evidenced by ESR spin-trapping experiments. A mechanistic scheme for the electrochemical oxidation is proposed. On carrying out reduction after oxidation, different products are formed depending on the substitution on the nitrogen. There is no reduction of the oxidized product in the case of N-H compounds, and compounds with substitution on nitrogen undergo reduction consistent with the observation in N-alkylpyridinium salts.

A General Method for the Synthesis of Bridged Indole Alkaloids. Addition of Carbon Nucleophiles to N-Alkylpyridinium Salts

The methodology based on the nucleophilic addition of stabilized carbon nucleophiles to N-alkylpyridinium salts constitutes a powerful tool for the synthesis of bridged indole alkaloids belonging to a variety of structural types, either tetracyclic (as vinoxine and ervitsine) or pentacyclic, in the latter case after closure of the tryptamine chain by cyclization upon the indole ring.

Gas chromatographic analysis of reduction products of paraquat, diquat and the related compounds: reductive cleavage in the pyridine ring on N-alkylpyridinium derivatives with NaBH4-NiCl2 reduction system, and inhibition of the cleavage

When N-alkylpyridinium derivatives were reduced with sodium borohydride-nickel (II) chloride reduction system, reductive cleavage occurred at the C-N bond in the pyridine ring of N-alkylpyridinium derivatives to give a small amount of reductive cleavage product along with the major perhydrogenated product. It was presumed in the previous report that this reductive cleavage in the pyridine ring proceeded through a complex of nickel ion and 1,2,3,6-tetrahydropyridine derivatives produced with NaBH4 alone reduction. The abundances of these reductive cleavage products arising from N-alkylpyridinium derivatives, i.e., paraquat, diquat and so on, are capable of giving a bad effect on the accuracy of gas chromatographic analysis. For the purpose of inhibition of the reductive cleavage in this reduction system, a suitable catalyst was examined. In addition, we pursued whether borane-1,2,3,6-tetrahydropyridine derivative complexes arose from N-alkylpyridinium derivatives by NaBH4 alone reduction or not, and whether these borane-amine complexes were the precursors of reductive cleavage products or not. N-Alkyl-1,2,3,6-tetrahydropyridine derivatives (III-I, IV-I, VI-I, VII-I and VIII-I) and the corresponding borane-amine complexes (III-II, IV-II, VI-II, VII-II and VIII-II) were synthesized by NaBH4 reduction in aqueous solution of N-alkylpyridinium salts, i.e. I, II, 1,4-dimethylpyridinium iodide (III), 1-dodecylpyridinium chloride (IV), 1,1'-diethyl-4,4'-dipyridinium dichloride (V), 1-methyl-4-phenylpyridinium iodide (VI), 1-n-propylpyridinium iodide (VII) and 1-n-butylpyridinium iodide (VIII). The structure of the borane-amine complexes were proved by the Mass spectrometry and 1H- and 13C-NMR analysis. The NiCl2-NaBH4 reduction of the borane-amine complexes gave the perhydrogenated products alone, but not reductive cleavage products. In conclusion, it was recognized that the precursors of reductive cleavage products were not borane-amine complexes, but 1,2,3,6-tetrahydropyridine. Furthermore, it was found the reductive cleavage at the C-N bond in the pyridine ring of these 1,2,3,6-tetrahydropyridine derivatives was hindered by applying Amberlite-Ni2B, NaBH4 reduction system.