Computational description and kinetic properties based on density functional theory methods of the key step of the addition reaction between a model nucleophile and nitroaromatic ring in positions occupied by hydrogen are presented.

The aim of this essay is to disclose the similarity of a great variety of reactions that proceed between nucleophiles and π-electrophiles-both aromatic and aliphatic. These reactions proceed via initial reversible addition, followed by a variety of transformations that are common for the adducts of both aliphatic and aromatic electrophiles. We hope that understanding of this analogy should help to expand the scope of the known reactions and inspire the search for new reactions that were overlooked.

Due to the electronic configuration of the atom and charge of the nucleus, the chlorine in organic molecules can exert a variety of effects. It can depart as a chloride anion in the process of substitution and elimination, facilitates the abstraction of protons and stabilizes generated carbanions, exerts moderate stabilizing effect of carbenes, carbocations and radicals. There are frequent cases where chlorine substituent promotes more than one transformation. These rich effects of chlorine substituent will be illustrated by examples of our work.

The electrophilic nature of quinoxaline has been explored in the vicarious nucleophilic substitution (VNS) of hydrogen with various carbanions as nucleophiles in an attempt to develop a general method for functionalizing the heterocyclic ring. Only poorly stabilized nitrile carbanions were found to give the VNS products. 2-Chloroquinoxaline gave products of SNAr of chlorine preferentially. A variety of quinoxaline derivatives containing cyanoalkyl, sulfonylalkyl, benzyl or ester substituents, including fluorinated ones, have been prepared in the VNS reactions with quinoxaline N-oxide.

Upon the action of strong bases at low temperature, benzyl chloride and its ring-substituted derivatives undergo deprotonation at the benzylic position and the produced carbanions react with aldehydes, ketones and Michael acceptors to form aryl oxiranes and cyclopropanes.

The discovery and studies of chemistry of dichlorocarbene and other electron deficient carbenes are discussed.

Confrontation of the recently formulated general mechanism of nucleophilic substitution in electron-deficient arenes with the well-known mechanism of electrophilic substitution revealed that these fundamental processes are mechanistically identical but proceed according to opposite polarity-an Umpolung relation. In this viewpoint this apparently controversial concept is supported by discussion of a variety of experimental results.

In this study, we present a complete description of the addition of a model nucleophile to the nitroaromatic ring in positions occupied either by hydrogen (the first step of the SNAr-H reaction) or a leaving group (SNAr-X reaction) using theoretical parameters including aromaticity (HOMA), electrophilicity and nucleophilicity indices. It was shown both experimentally and by our calculations, including kinetic isotope effect modeling, that the addition of a nucleophile to the electron-deficient aromatic ring is the rate limiting step of both SNAr-X and SNAr-H reactions when the fast transformation of σH-adduct into the products is possible due to the specific reaction conditions, so this is the most important step of the entire reaction. The results described in this paper are helpful for better understanding of the subtle factors controlling the reaction direction and rate.

After short historical introduction, interfacial mechanism of phase transfer catalyzed (PTC) reactions of organic anions, induced by aqueous NaOH or KOH in two-phase systems is formulated. Subsequently experimental evidence that supports the interfacial deprotonation as the key initial step of these reactions is presented.

Benzyl chloride and its derivatives are efficiently deprotonated with strong bases to form alpha-chlorocarbanions. These anions are long-lived enough to enter VNS reactions with nitroarenes or nitroheteroarenes to give a variety of unsymmetrical o- and p-nitrodiarylmethanes. Selectivity of the reaction can be controlled to some extent by changing metal counterions of the base.

Nucleophilic substitution in electron-deficient arenes is one of the fundamental processes in organic chemistry; however, its mechanism as presented in textbooks does not adequately describe the process. According to this generally accepted mechanism, it is limited to substitution of halogens via nucleophilic addition at positions occupied by halogens. The possibility of addition at positions occupied by hydrogen is totally ignored. Research papers have shown that nucleophilic addition at positions occupied by hydrogen is a fast and reversible process, and σ H adducts are initially formed as intermediates. These σ H adducts can be converted into products of nucleophilic substitution of hydrogen in a few different ways or dissociate so that substitution of halogen can proceed. This general picture is confirmed by many examples presented.

Nitrobenzyl benzothiazol-2-yl sulfones and nitrobenzyl 1-phenyl-1H-tetrazol-5-yl sulfones react with chlorides of aromatic acids to form β-acyl derivatives. These products undergo the Smiles rearrangement resulting in the formation of the corresponding nitrophenyl arylacetylenes in 50–60% overall yields (approx. 75% per step). Sulfones bearing CF3 or CN groups instead of a NO2 substituent form mixtures of the acetylenes in moderate yields and benzyl aryl ketones in yields above 40%.

Acetals of the cyanohydrins of aromatic aldehydes were deprotonated to generate carbanions, which were used in the vicarious nucleophilic substitution of the hydrogen atom of aromatic and heteroaromatic nitro compounds to form p‐nitro‐substituted diarylacetonitriles. The reaction selectively occurred para to the nitro group. The anion of the hemiacetal of acetaldehyde was shown to be an efficient leaving group in the base‐induced β‐elimination step.

We present the first unambiguous evidence of the interfacial mechanism of phase-transfer catalysis (PTC) by direct observation of the formation of carbanions in the interfacial region between the aqueous and the organic phase by using a surface-sensitive spectroscopic method known as second harmonic generation (SHG). Ion exchange of carbanions adsorbed at the surface after addition of lipophilic tetraalkylammonium salts (TAA) to organic phase and transport of the lipophilic ion-pairs to the organic phase is observed. Results allow for the formulation of a more detailed mechanism of PTC.

The aim of this paper is to present a correct and complete mechanistic picture of nucleophilic substitution in nitroarenes based on the results obtained by theoretical calculations and experimental observations coming from numerous publications, reviews, and monographs. This work gives the theoretical background to the very well documented experimentally yet still ignored observations that the addition of nucleophiles to halo nitroarenes resulting in the formation of σ(H) adducts, which under proper reaction conditions can be transformed into the product of the SNArH reaction, is faster than the competing process of addition to the carbon atom bearing a nucleofugal group (usually a halogen atom) resulting in the "classic" SNAr reaction. Only when the σ(H) adduct cannot be transformed into the SNArH reaction product, SNAr reaction is observed.

Oxiranes are formed in a highly diastereoselective one-pot process, in which aldehydes react with -chloronitrobenzylic carbanions produced in the vicarious nucleophilic substitution (VNS) reaction of nitroarenes with tert-butyl dichloroacetate.

Acetylenic carbanions add to nitroarenes (dinitrobenzenes, nitropyridines, etc.) to form σH-adducts that are subsequently oxidized by DDQ according to the oxidative nucleophilic substitution of hydrogen (ONSH) pathway to give nitroaryl acetylenes.