Electrophilic Aromatic Substitution Research Articles

A Molecular Electron Density Theory Study of the Domino Reaction of N-Phenyl Iminoboranes with Benzaldehyde Yielding Fused Bicyclic Compounds.

The reaction of N-phenyl iminoborane with benzaldehyde yielding a fused aromatic compound, recently reported by Liu et al., has been studied within the Molecular Electron Density Theory (MEDT). Formation of the fused aromatic compound is a domino process that comprises three consecutive reactions: (i) formation of a weak molecular complex between the reagents; (ii) an intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent of iminoborane; and (iii) a formal 1,3-hydrogen shift yielding the final fused aromatic compound. The two last steps correspond to a Friedel-Crafts acylation reaction, the product of the second reaction being the tetrahedral intermediate of an electrophilic aromatic substitution reaction. However, the presence of the imino group adjacent to the aromatic ring strongly stabilizes the corresponding intermediate, being the reaction product when the ortho positions are occupied by t-butyl substituents. This domino reaction shows a great similitude with the Brønsted acid catalyzed Povarov reaction. Although N-phenyl iminoborane can experience a formal [2+2] cycloaddition reaction with benzaldehyde, its higher activation Gibbs free energy compared to the intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent, 6.6 kcal·mol-1, prevents the formation of the formal [2+2] cycloadduct. The present MEDT study provides a different vision of the molecular mechanism of these reactions based on the electron density.

Regioselective Direct C-H Bond Heteroarylation of Thiazoles Enabled by an Iminopyridine-Based α-Diimine Nickel(II) Complex Evaluated by DFT Studies.

Direct C-H bond arylation is a highly effective method for synthesizing arylated heteroaromatics. This method reduces the number of synthetic steps and minimizes the formation of impurities. We report an air- and moisture-stable iminopyridine-based α-diimine nickel(II) complex for direct C5-H bond arylation of thiazole derivatives. Under a low catalyst loading and performing the reactions at lower temperatures (80 °C) under aerobic conditions, we produced mono- and diarylated thiazole units. Competition experiments and density functional theory calculations revealed that the mechanism of C-H activation in 4-methylthiazole involves an electrophilic aromatic substitution.

Chemische Synthese mit Gasförmigen Molekularen Ionen: Gewinnung von [B12Br11N2]− aus einem Massenspektrometer

AbstractIn der Massenspektrometrie werden häufig kurzlebige Ionen in der Gasphase beobachtet, die zuvor nicht in Lösung oder in der Bulkphase synthetisiert worden sind. Diese schwer zugänglichen Ionen werden daher oft primär als analytisch wertvoll für grundlegende Gasphasenstudien angesehen. Hier wird der Nachweis erbracht, dass die Produkte von Ionen‐Molekül‐Reaktionen in Massenspektrometern auf Oberflächen gesammelt werden können, um kondensierte Materie zu erzeugen und somit als Bausteine für die Synthese neuer Verbindungen zu dienen. Das hochreaktive Fragmentanion [B12Br11]− wurde in einem Massenspektrometer erzeugt und in Anwesenheit von molekularem Stickstoff in [B12Br11N2]− umgewandelt, gefolgt von seiner Massenselektion und sanften Deposition auf Oberflächen. Die Molekularstruktur des bisher nie zuvor synthetisierten [B12Br11N2]− wurde mit konventionellen Methoden der Molekularanalyse, einschließlich magnetischer Kernresonanz‐ und Infrarotspektroskopie, bestätigt. Das [B12Br11N2]−‐Ion ist auf Oberflächen und in Lösung bei Raumtemperatur stabil, aber Erhitzen führt zur Abspaltung von N2 und ermöglicht den Zugang zu dem hochreaktiven Zwischenprodukt [B12Br11]− in der kondensierten Phase, das beispielsweise als Reagenz für elektrophile aromatische Substitutionen weiterverwendet werden kann. Die Isolierung von [B12Br11N2]− erweitert somit das Repertoire der verfügbaren Diazo‐Ionen, die als vielseitige Zwischenprodukte bei verschiedenen chemischen Umwandlungen eingesetzt werden können.

Chemical Synthesis with Gaseous Molecular Ions: Harvesting [B12 Br11 N2 ]- from a Mass Spectrometer.

Mass spectrometry frequently reveals the existence of transient gas phase ions that have not been synthesized in solution or in bulk. These elusive ions are, therefore, often considered to be primarily of analytical value in fundamental gas phase studies. Here, we provide proof-of-concept that the products of ion-molecule reactions in mass spectrometers may be collected on surfaces to generate condensed matter and thus serve as building blocks to synthesize new compounds. The highly reactive fragment anion [B12 Br11 ]- was generated in a mass spectrometer and converted to [B12 Br11 N2 ]- in the presence of molecular nitrogen followed by its mass-selection and soft-landing on surfaces. The molecular structure of [B12 Br11 N2 ]- , which has not been synthetically obtained before, was confirmed by conventional methods of molecular analysis, including nuclear magnetic resonance and infrared spectroscopy. The [B12 Br11 N2 ]- ion is stable on surfaces and in solution at room temperature, but thermal annealing induces elimination of N2 and provides access to the highly reactive intermediate [B12 Br11 ]- in the condensed phase, which can be further used as a reagent, for example, for electrophilic aromatic substitutions. Thus, isolation of [B12 Br11 N2 ]- expands the repertoire of the available diazo ions that can be employed as versatile intermediates in various chemical transformations.

Through-Space, Lone-Pair Promoted Aromatic Substitution: A Relay Mechanism Can Beat Out Direct Activation.

We report a detailed experimental and theoretical analysis of through-space arene activation with halogens, tetrazoles and achiral esters and amides. Contrary to previously assumed direct activation through σ-complex stabilization, our results suggest that these reactions proceed by a relay mechanism wherein the lone pair-containing activators form exothermic π-complexes with electrophilic nitronium ion before transferring it to the probe ring through low barrier transition states. Noncovalent interactions (NCI) plots and Quantum Theory of Atoms in Molecules (QTAIM) analyses depict favorable interactions between the Lewis base (LB) and the nitronium ion in the precomplexes and the transition states, suggesting directing group participation throughout the mechanism. The regioselectivity of substitution also comports with a relay mechanism. In all, these data pave the way for an alternate platform of electrophilic aromatic substitution (EAS) reactions.

Computational and photophysical probing interactions of newly synthesized benzothiazole azo-bonded molecules acting as potent antitubercular agents

In the present work, we have presented a very detailed study of unprecedented mono-azo benzothiazole derivatives. The targeted molecules were synthesized by a single-step involving diazotizing the primary aromatic amines followed by resultant diazonium salts coupling with N, N-Diethyl-m-toluidine (DEMT) through electrophilic substitution reaction influenced by positive mesomeric effect (+M effect) under suitable experimental conditions. The FT-IR, UV–vis, Photoluminescence (PL), 1H NMR, 13C NMR, and HRMS techniques were used to investigate the synthesized mono-azo benzothiazole dye derivatives. Additionally, for the first time, calculations based on density functional theory have been used to examine the ground state geometry, electronic structure, and molecular characteristics potential region maps of four benzothiazole mono-azo architectures (CR1-CR4). The effectiveness of the synthesized dye colourants against M. tuberculosis, H37Rv was assessed by utilizing the agar well diffusion assay method (ATCC 27,294), amongst the studied mono-azo derivatives, CR3 and CR4 exhibited a good zone of inhibition compared to CR1 and CR2. The compound CR1 demonstrated sensitivity at 20 µM, compared to 48.2 µM for the reference gentamicin. The antibacterial activity of the CR1 and CR4 compounds was revealed to have a 19 mm zone of inhibition. The derivative CR1 displayed 42.86 and CR3 displayed 38.75 of the concentration IC50 in 100 μl/ml, respectively, based on their cytotoxic potentiality.

Perborate accelerated copper-immobilized carbon nanofibers activating peroxymonosulfate process for sulfadiazine degradation: Performance and mechanisms understanding

In this work, perborate (BO3−) was applied to promote the degradation of sulfadiazine (SDZ) in copper-immobilized carbon nanofibers (Cu-CNF-x) activated peroxymonosulfate (PMS) system. Results showed that in BO3−/Cu-CNF-3/PMS ternary system, 100% of SDZ (40 μM) could be efficiently eliminated in 5 min with 0.1 g/L Cu-CNF-3, 1 mM BO3− and 1 mM PMS; while Cu-CNF-3/PMS and BO3−/PMS systems only achieved 58.4% and 47.3% degradation in 30 min. In initial pH range of 5.0–9.0, the ternary system removed over 92.6% of SDZ, and the treated solution pH maintained neutral, effectively relieving the water acidification introduced by PMS. Electron paramagnetic resonance analysis and radical scavenger tests evidenced the production of SO4−•, •OH, 1O2 and H2O2BO•O•−. Mechanisms analysis proposed the activation process as follows: initially, BO3− promptly activated PMS to generate H2O2BO•O•− via electrophilic substitution reaction, and H2O2 was produced due to the decomposition of BO3−; thereafter, PMS was activated by Cu-CNF-x to yield SO4−•, •OH and 1O2; the obtained H2O2 was then utilized by Cu-CNF-x to produce •OH and 1O2 as well. Density functional theory (DFT) calculations showed that the adsorption energy (Ead) between PMS and Cu-CNF-x was 0.43 eV. BO3− greatly increased the Ead of PMS on Cu-CNF-x by ten times to 4.75 eV, which extremely promoted the PMS activation. This work provided a novel strategy of BO3−/Cu-CNF-3/PMS for the efficient degradation of refractory organic pollutants, and managed to understand the synergistic role of BO3− to PMS based heterogeneous catalytic processes.

Pd(II) and Rh(I) Catalytic Precursors for Arene Alkenylation: Comparative Evaluation of Reactivity and Mechanism Based on Experimental and Computational Studies.

We combine experimental and computational investigations to compare and understand catalytic arene alkenylation using the Pd(II) and Rh(I) precursors Pd(OAc)2 and [(η2-C2H4)2Rh(μ-OAc)]2 with arene, olefin, and Cu(II) carboxylate at elevated temperatures (>120 °C). Under specific conditions, previous computational and experimental efforts have identified heterotrimetallic cyclic PdCu2(η2-C2H4)3(μ-OPiv)6 and [(η2-C2H4)2Rh(μ-OPiv)2]2(μ-Cu) (OPiv = pivalate) species as likely active catalysts for these processes. Further studies of catalyst speciation suggest a complicated equilibrium between Cu(II)-containing complexes containing one Rh or Pd atom with complexes containing two Rh or Pd atoms. At 120 °C, Rh catalysis produces styrene >20-fold more rapidly than Pd. Also, at 120 °C, Rh is ∼98% selective for styrene formation, while Pd is ∼82% selective. Our studies indicate that Pd catalysis has a higher predilection toward olefin functionalization to form undesired vinyl ester, while Rh catalysis is more selective for arene/olefin coupling. However, at elevated temperatures, Pd converts vinyl ester and arene to vinyl arene, which is proposed to occur through low-valent Pd(0) clusters that are formed in situ. Regardless of arene functionality, the regioselectivity for alkenylation of mono-substituted arenes with the Rh catalyst gives an approximate 2:1 meta/para ratio with minimal ortho C-H activation. In contrast, Pd selectivity is significantly influenced by arene electronics, with electron-rich arenes giving an approximate 1:2:2 ortho/meta/para ratio, while the electron-deficient (α,α,α)-trifluorotoluene gives a 3:1 meta/para ratio with minimal ortho functionalization. Kinetic intermolecular arene ethenylation competition experiments find that Rh reacts most rapidly with benzene, and the rate of mono-substituted arene alkenylation does not correlate with arene electronics. In contrast, with Pd catalysis, electron-rich arenes react more rapidly than benzene, while electron-deficient arenes react less rapidly than benzene. These experimental findings, in combination with computational results, are consistent with the arene C-H activation step for Pd catalysis involving significant η1-arenium character due to Pd-mediated electrophilic aromatic substitution character. In contrast, the mechanism for Rh catalysis is not sensitive to arene-substituent electronics, which we propose indicates less electrophilic aromatic substitution character for the Rh-mediated arene C-H activation.

Reaction Mechanism and Kinetics Study of Wheat Polysaccharide via Modified Reductor Technique in Bead Making Process

The reaction mechanism and kinetics investigation of the substitution of titanium in wheat flour polysaccharide (referred to here as titaniumation) in aqua medium during bead making process was carried out. The use of the Modified Reductor Technique was implored to study the reaction kinetics. The study was carried out at varying temperatures between 25 – 70oC. The study showed that the titaniumation of the wheat polysaccharide molecules increased with time and temperature. Hence, at 25oC, the degree of titaniumation (DT) of the ring increased from 0.41 % to 0.49 % and at elevated temperature of 70oC, DT increased from 0.58 to 0.94 % as time progressed from 30 to 210 mins, respectively, while keeping both amount of wheat polysaccharide and TiO2 constant, and thus achieving >1.9-fold. This also implies that the titaniumation of wheat polysaccharide using TiO2 is favourable at elevated temperature. The study was able to reveal that the reaction mechanism of the titaniumation of the polysaccharide molecules is an electrophilic substitution reaction, favouring the ortho position, while the kinetics study showed that the titaniumation reaction is of first order reaction.

Lewis acid/acetic acid-catalysed electrophilic amidation of simple arenes with O-acetyl acetohydroxamic acid

Electrophilic arene CH amination constitutes an intrinsically more atom- and step-economical pathway towards arylamines than CX → CN methods. However, most literature examples are restricted to arenes with extensive directing groups (DG) and/or nitrogen coupling partners with large leaving groups (LG). Moreover, only few cases of EAs using cheap metals (e.g., Fe) have been reported. Herein, we demonstrate the catalytic activity of various Lewis acids in the electrophilic amidation of simple arenes with O-acetyl acetohydroxamic acid in acetic acid. With 5 mol% FeIII(citrate)·H2O, up to 27 % yield was achieved, whereas 5 mol% BiCl3 gave up to 31 % yield. Instability of the amidation agent and product inhibition were identified as the yield-limiting factors. The observed regioselectivity, as well as kinetic and spectroscopic data suggest an electrophilic aromatic substitution mechanism, in which acetic acid and the Lewis acid generate a highly electrophilic species from AcNHOAc.

ProHSO4: An efficient catalyst for solvent-free synthesis of bis(indolyl)methanes and their in silico screening for potential biological activity

A simple, mild, and efficient protocol has been developed for the synthesis of 3,3′-bis(indolyl)methanes (BIMs) using prolinium hydrogen sulfate (ProHSO4) as a catalyst under solvent-free and support-free conditions. This mechanochemical method undergoes electrophilic substitution reaction of indole with diverse aldehydes to afford the desired BIMs in high yields at room temperature. Due to diverse pharmacological utility, the synthesized BIMs were subjected to in silico studies. The structure activity analysis of BIMs revealed their ability to bind Eg5 kinesin, Human p38 α MAP Kinase, and Human 3 alpha HSD type 3 as a potential protein target for anticancer activity. The compounds exhibited higher binding affinities with Eg5 kinesin having hydrophobic interactions with α2, α3 helices and loop5 amino acid residues. Moreover, molecular docking with Human p38 α MAP Kinase protein depicted compounds as ATP-competitive molecules interacting with hydrophobic region I, II and allosteric DFG motif. A total of 13 derivatives were synthesized and subjected for in silico screening for predicting potential biological activity. Among them,3b, 3d, 3f, 3 g, 3i, 3j, and 3 k compoundswere identified as potential inhibitors of Eg5 kinesin, Human p38 α MAP Kinase, and Human 3 alpha HSD type 3, and their evaluation in the biological experimental system is warranted.

PHARMACOLOGICAL APPLICATION OF THIOPHENE DERIVATIVES

Thiophene nucleus has been established as the potential entity in the largely growing chemical world of heterocyclic compounds processing promising pharmacological characteristics.The knowledge of various synthetic pathway and the diverse physicochemical parameters of such compounds draw the especial attention of medical chemist to produce combanitorial library and carry out exhaustive efforts in the search of lead molecules. Thiophene is a five membered , sulfur containing hetero aromatic ring generally used as building block in drugs. It is structural metabolism leads to the formation of reactive metabolites. This compounds are widely spread in nature & have diversified application in design of new drug molecule. Thiophene has been established as the potential entity in largely growing chemical world of heterocyclic compounds possessing a pharmacological characteristics. A series of thiophene compound can be synthesize through various routes with pharmacological activity. The simple five – membered heterocycle are thiophene, with sulphur atom. It also undergo electrophilic aromatic substitution very readily.Sulphur is the least electron donor as compare to nitrogen and oxygen.Thiophene is similar to benzene in reactivity. Thiophene is the least reactive of the three because the p orbital of the lone pair of electrons on sulphur that conjugates with the ring is a 3p orbital rather than the 2p orbital of N or O, so overlap with 2p orbitals on carbon is less good. Thiophene undergo more or less normal Friedel- Craft reactions, although the less reactive unhydrides( aceticunhydride, Ac2O ) are used instead of acid chlorides, and weaker Lewis acid than AlCl3 are preferred. The regioselectivity is the – the 2- position is more reactive than 3- position. The present review includes the properties, synthesis, and a wide spectrum of biological activities of thiophene based scaffolds, and summary of thiophene containing active pharmaceutical ingredients (APIs) available in the market. KEY WORDS :Thiophene, Medicinal Importance, Biological Importance, Reaction of thiophene

Copper‐Catalyzed Intramolecular SEAr Reaction–Oxidation under Aerobic Conditions: Synthesis of Styryl‐/Alkenyl‐Substituted Xanthone Derivatives

AbstractHerein, we report a copper‐catalyzed intramolecular electrophilic aromatic substitution (SEAr)−oxidation process to access a wide range of diversified xanthone derivatives using air as a sole oxidant. Specifically, this protocol affords hitherto unknown styryl‐/alkenyl‐substituted xanthone derivatives in moderate to high yields. The practicality of the method has been demonstrated by gram‐scale syntheses.

Room temperature colossal superparamagnetic order in aminoferrocene–graphene molecular magnets

Intensive studies are published for graphene-based molecular magnets due to their remarkable electric, thermal, and mechanical properties. However, to date, most of all produced molecular magnets are ligand based and subject to challenges regarding the stability of the ligand(s). The lack of long-range coupling limits high operating temperature and leads to a short-range magnetic order. Herein, we introduce an aminoferrocene-based graphene system with room temperature superparamagnetic behavior in the long-range magnetic order that exhibits colossal magnetocrystalline anisotropy of 8 × 105 and 3 × 107 J/m3 in aminoferrocene and graphene-based aminoferrocene, respectively. These values are comparable to and even two orders of magnitude larger than pure iron metal. Aminoferrocene [C10H11FeN]+ is synthesized by an electrophilic substitution reaction. It was then reacted with graphene oxide that was prepared by the modified Hammers method. The phase structure and functionalization of surface groups were characterized and confirmed by XRD, FT-IR, and Raman spectroscopy. To model the behavior of the aminoferrocene between two sheets of hydroxylated graphene, we have used density functional theory by placing the aminoferrocene molecule between two highly ordered hydroxylated sheets and allowing the structure to relax. The strong bowing of the isolated graphene sheets suggests that the charge transfer and resulting magnetization could be strongly influenced by pressure effects. In contrast to strategies based on ligands surface attachment, our present work that uses interlayer intercalated aminoferrocene opens routes for future molecular magnets as well as the design of qubit arrays and quantum systems.

Ru(II)-Catalyzed Weakly Coordinating Carbonyl-Assisted Dialkynylation of (Hetero)Aryl Ketones.

Functionalized aryl(heteroaryl) ketones are present in many natural products as key structural components and serve as basic synthetic building blocks for various organic transformation reactions. Therefore, the development of an effective and sustainable route for making these classes of compounds remains challenging yet highly desirable. Herein, we report a simple and efficient catalytic system for dialkynylation of aromatic/heteroaromatic ketones via a double C-H bond activation in the presence of less expensive ruthenium(II)-salt as a catalyst using the weakly and native carbonyl group as the desired directing group. The developed protocol is highly compatible, tolerant, and sustainable toward various functional groups. The synthetic utility of the developed protocol has been demonstrated through the scale-up synthesis and functional group transformation. Control experiments support the involvement of the base-assisted internal electrophilic substitution (BIES) reaction pathway.

How Do Face-to-Face Stacked Aromatic Rings Activate Each Other to Electrophilic Aromatic Substitution?

We have found that face-to-face π-stacked aromatic rings show the propensity to activate one another toward electrophilic aromatic substitution through direct influence of the probe aromatic ring by the adjacent stacked ring, rather than through the formation of relay or "sandwich complexes." This activation remains in force even when one of the rings is deactivated through nitration. The resulting dinitrated products are shown to crystallize in an extended parallel offset stacked form, in stark contrast to the substrate.

Electrophilic substitution reactions of thiophene and thieno[2,3-b]thiophene heterocycles: a DFT study

Abstract We determined the most preferred site for the electrophilic aromatic substitution (SEAr) reactions of thiophene 1 and thieno[2,3-b]thiophene 2 using the N-chlorosuccinimide electrophile in the gas phase and in acetic acid. The B3LYP/6-311G(d), B3LYP-D3/6-311G(d) and M06-2X/6-311G(d) methods were employed to investigate the SEAr reaction mechanisms. We found that, compared to the β-carbon atom, the α-carbon atom in both 1 and 2 is preferred for electrophilic attack both kinetically and thermodynamically.

The reaction pathway and mechanism of 2,4-dichlorophenol removal by modified fly ash-loaded nZVI/Ni particles.

Nanoscale zero-valent iron (nZVI) is more valuable in environmental restoration than other materials. Chemical treatment of fly ash (CFA) was employed as a support material to disperse iron nickel bimetal nanoparticles (CFA-nZVI/Ni) to remove 2,4-dichlorophenol (2,4-DCP). Batch experiments showed that 2,4-DCP was completely removed by CFA-nZVI/Ni, and an optimal loading ratio was 8:1. The degradation of 2,4-DCP by CFA-nZVI/Ni was a chemical control reaction with an activation energy of 95.6 kJ mol-1 and followed pseudo-first-order kinetics. The addition of Cl- increased the removal rate of 2,4-DCP by 4%, while the addition of CO32- and SO42- decreased the removal rate of 2,4-DCP by 32% and 72.3%, respectively. The removal process of 2,4-DCP by CFA-nZVI/Ni included adsorption and reduction. The 2-CP (7.1 mg/L) and 4-CP (11.6 mg/L) could be converted to phenol using the CFA-nZVI/Ni system. Cl on the para-position of 2,4-DCP was simpler to remove than on the ortho-position. The following steps were taken in the electrophilic substitution reaction between substituted phenols and hydrogen radicals: 2,4-DCP > 2-CP > 4-CP > phenol. This research provides a novel concept to effectively remove 2,4-DCP and mechanism analysis.

Chlorination of amides: Kinetics and mechanisms of formation of N-chloramides and their reactions with phenolic compounds

Amides are common constituents in natural organic matter and synthetic chemicals. In this study, we investigated kinetics and mechanisms of the reactions of chlorine with seven amides, including acetamide, N-methylformamide, N-methylacetamide, benzamide, N-methylbenzamide, N-propylbenzamide, and N-(benzoylglycyl)glycine amide. Apparent second-order rate constants for the reactions of the amides with chlorine at pH 8 are in the range of 5.8 × 10−3 – 1.8 M−1s−1 and activation energies in the range of 62-88 kJ/mol. The second-order rate constants for the reactions of chlorine with different amides decrease with increasing electron donor character of the substituents on the amide-N and N-carbonyl-C in the amide structures. Hypochlorite (‒OCl) dominates the reactions of chlorine with amides yielding N-chloramides with species-specific second-order rate constants in the range of 7.3 × 10−3 – 2.3 M−1s−1. Kinetic model simulations suggest that N-chlorinated primary amides further react with HOCl with second-order rate constants in the order of 10 M−1s−1. The chlorination products of amides, N-chloramides are reactive towards phenolic compounds, forming chlorinated phenols via electrophilic aromatic substitution (phenol and resorcinol) and quinone via electron transfer (hydroquinone). Meanwhile, N-chloramides were recycled to the parent amides. At neutral pH, apparent second-order rate constants for the reactions between phenols and N-chloramides are in the order of 10−4-0.1 M−1s−1, comparable to those with chloramine. The findings of this study improve the understanding of the fate of amides and chlorine during chlorination processes.

Skeletal Transformation of Unactivated Arenes Enabled by a Low-Temperature Dearomative (3 + 2) Cycloaddition.

Simple aromatic compounds like benzene are abundant feedstocks, for which the preparation of derivatives chiefly begins with electrophilic substitution reactions or, less frequently, reductions. Their high stability makes them particularly reluctant to participate in cycloadditions under ordinary reaction conditions. Here, we demonstrate the exceptional ability of 1,3-diaza-2-azoniaallene cations to undergo formal (3 + 2) cycloadditions with unactivated benzene derivatives below room temperature, providing thermally stable dearomatized adducts on a multi-gram scale. The cycloaddition, which tolerates polar functional groups, activates the ring toward further elaboration. On treatment with dienophiles, the cycloadducts undergo a (4 + 2) cycloaddition-cycloreversion cascade to yield substituted or fused arenes, including naphthalene derivatives. The overall sequence results in the transmutation of arenes through an exchange of the ring carbons: a two-carbon fragment from the original aromatic ring is replaced with another from the incoming dienophile, introducing an unconventional disconnection for the synthesis of ubiquitous aromatic building blocks. Applications of this two-step sequence to the preparation of substituted acenes, isotopically labeled molecules, and medicinally relevant compounds are demonstrated.