Mieczysław Mąkosza

Vicarious nucleophilic substitution of hydrogen. Mechanism and orientation

Hydrogens located at activated positions in electrophilic arenes, e.g. ortho and para hydrogens in nitrobenzenes, can be replaced with a nucleophile moiety provided there is at least one nucleofuge X connected to the nucleophilic centre. As the group really leaving in this hydrogen substitution process is not the hydride anion but X, the reaction has been named vicarious nucleophilic substitution of hydrogen (VNS). The concepts on the mechanism of the reaction and their experimental background are presented. Reactivity and orientation—the fundamental questions concerning synthetical applications of VNS—are discussed in light of the supposed mechanistic picture.

Reactions of Nucleophiles with Nitroarenes: Multifacial and Versatile Electrophiles

In this overview, it is shown that there are many initial reactions between nitroarenes and nucleophiles: addition to the electron-deficient ring at positions occupied by halogen and hydrogen atoms, addition to the nitro group, single-electron transfer (SET), and other types of initial reactions. The resulting intermediates react further in a variety of ways to form products of nucleophilic substitution of a halogen atom (SN Ar), a hydrogen atom (SN ArH), and others. Many variants of these processes are briefly discussed, particularly in relation of rates of the initial reactions and further transformations.

Catalysis in Two-Phase Systems: Phase Transfer and Related Phenomena

Publisher Summary This chapter focuses on catalysis in two-phase systems, and discusses the nature of this type of catalysis. A catalyst is a substance (chemical entity) which accelerates a chemical reaction (without being consumed) via a decrease of its activation energy. There are many types of catalysis for which this definition can be applied; some difficulties are encountered, however, in the case of the phase-transfer catalysis (PTC) and catalytic two-phase (CTP) systems. The main function of the catalyst is introduction of the reacting species into the site where the reaction partner is located and where the reaction proceeds. So using formal terms of activation energy one can perhaps consider that the main function of the PTC and CTP catalysts is to decrease the activation energy of the transfer of the reacting species to the reaction site. The PTC and CTP reactions usually do not require any organic solvents (when one of the reactants is a liquid), or require them only in small amounts, just sufficient to dissolve organic reactants. The PTC and CTP methodologies mimic to some extent the high-dilution technique, because in the organic phase the concentration of the reacting species can be only a fraction of that of the catalyst. The two-phase procedures are not only simpler and more convenient than traditional methods, but they usually give better yields of desired products of higher purity, whereas side reactions are

Substituent Effects on the Electrophilic Activity of Nitroarenes in Reactions with Carbanions

The effect on electrophilic activity of substituents located para, ortho, and meta to the nitro group of nitrobenzenes was determined by using vicarious nucleophilic substitution of hydrogen (VNS) with the carbanion of chloromethyl phenyl sulfone (1) as the model process. Values for the relative activities of substituted nitroarenes are given relative to nitrobenzene, which was taken as the standard. This process was chosen as a model reaction because it meets key criteria, such as the wide range of substituents that can be present on the nitrobenzene ring, a low sensitivity to steric hindrance, and in particular the possibility of ensuring conditions in which the overall relative rates of reaction in competitive experiments are equal to the relative rates of nucleophilic addition. The values of relative rates of addition, which were taken to be a measure of electrophilic activity, were determined by competitive experiments in which pairs of nitroarenes competed for the VNS reaction with carbanion of 1. A comprehensive set of data for effects of substituents on the electrophilic activity of nitroarenes is presented for the first time.

Alkylation of nitroarenes with Grignard reagents via oxidative nucleophilic substitution of hydrogen

Abstract Alkylation of nitroarenes with Grignard reagents via oxidative nucleophilic substitution of hydrogen (ONSH) can be efficiently executed with potasium permanganate in liquid ammonia as an oxidative system for the σ H adducts. The addition of RMgX to ArNO 2 of stoichiometry 1:1 is accompanied with a redox process apparently of stoichiometry 2:1. Because of that, real stoichiometry of the reaction between nitroarenes and Grignard reagents is ca. 1:1.5.

Reactions of Nitroheteroarenes with Carbanions : Bridging Aromatic, Heteroaromatic, and Vinylic Electrophilicity

The relative rate constants for the vicarious nucleophilic substitution (VNS) of the anion of chloromethyl phenyl sulfone (1-) with a variety of nitroheteroarenes, for example, nitropyridines, nitropyrroles, nitroimidazoles, 2-nitrothiophene, and 4-nitropyrazole, have been determined by competition experiments. It was shown that nitropyridines are approximately four orders of magnitude more reactive than nitrobenzene. Among the five-membered heterocycles 2-nitrothiophene is the most active followed by nitroimidazoles and 4-nitropyrazole. Nitropyrroles are the least electrophilic nitroheteroarenes with reactivities comparable to nitrobenzene. Quantum chemically calculated methyl anion affinities (B3LYP/6-311G(d,p)//B3LYP/6-31G(d)) of the nitroarenes correlated only moderately with the partial relative rate constants. The correlation of these activities with the LUMO energies of nitroarenes is even worse. By measuring the second-order rate constants of the addition of 1- to nitroarenes and to diethyl arylidenemalonates 10, it was possible to link the electrophilic reactivities of nitroheteroarenes with the comprehensive electrophilicity scale based on the linear-free-energy-relationship log k(20 degrees C)=s(N+E).

New synthesis of 2-heteroarylperfluoropropionic acids derivatives by reaction of azine N-oxides with hexafluoropropene.

Hexafluoropropene reacts with aromatic azine N-oxides under mild conditions to produce fluorides of 2-heteroarylperfluoropropionic acids. The reaction proceeds as 1,3-dipolar cycloaddition followed by spontaneous scission of the N--O bond in the isoxazolidine ring and elimination of HF. When the reaction is carried out in the presence of alcohols or N-alkyl anilines, the in situ formed acyl fluorides give the corresponding esters and amides. They can be also treated separately with nucleophiles to produce the respective acylation products, whereas their hydrolysis leads to unstable carboxylic acids that undergo spontaneous decarboxylation to 1-aryl-1,2,2,2-tetrafluoroethanes. This new reaction provides a simple and general method of synthesizing 2-heteroarylperfluoropropionic acid derivatives that were previously unknown and unavailable.

Remarks on the mechanism of phase-transfer catalyzed carbanion generation in two-phase systems

Abstract Competitive of addition of CCl − 3 anions to N-alkyl-pyridinium salts and to vinyl acetate, t-butyl acrylate and benzaldehyde was studied in a two-phase system, chloroform / conc. aqueous NaOH, and in a homogeneous medium. The results support an interfacial mechanism for generation of carbanions and indicate that chloroform is deprotonated by NaOH at the interface.

Cocatalysis in phase-transfer catalyzed base induced β-elimination. Part 2: Model studies of dehydrobromination of trans-β-bromostyrene

Abstract Phase-transfer catalyzed β-elimination of HBr from trans -β-bromostyrene proceeds as a cocatalytic process when cocatalysts of low acidity such as n -butanol and highly concentrated aqueous NaOH at elevated temperatures are used. Without added cocatalyst the reaction is autocatalyzed because the produced phenylacetylene forms lipophilic acetylenide anion acting as a base in the organic phase. Competition between the β-elimination of HBr from trans -β-bromostyrene and the Hofmann degradation of tetrabutylammonium cation as a function of base was studied.

Oxidative nucleophilic substitution of hydrogen in nitroarenes by silyl enol ethers

Abstract Enolates generated by treatment of silyl ketene acetals and enol ethers with fluoride ion sources add to nitroarenes to produce σH adducts that oxidize either with KMnO4 to give substituted nitroarenes or with dimethyldioxirane to give substituted phenols. In the latter case the oxidation results in replacement of the nitro group with a hydroxy group. It was shown that high effectiveness of these reactions is not due to stabilization of the σH adducts via O-silylation but due to the nature of the accompanying cation.