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Inhibitors of monoamine oxidases (MAOs) are of interest for the treatment of neurodegenerative disorders and other human pathologies. In this frame, the present work describes different synthetic strategies to obtain MAO inhibitors via the coupling of the aminocoumarin core with arylsulfonyl chlorides followed by copper azide-alkyne cycloaddition, leading to coumarin–sulfonamide–nitroindazolyl–triazole hybrids. The nitration position on the coumarin moiety was confirmed through nuclear magnetic resonance spectroscopy and molecular electron density theory in order to elucidate the molecular mechanism and selectivity of the electrophilic aromatic substitution reaction. The coumarin derivatives were evaluated for their inhibitory potency against monoamine oxidases and cholinesterases. Molecular docking calculations provided a rational binding mode of the best compounds in the series with MAO A and B. The work identified hybrids 14a–c as novel MAO inhibitors, with a selective action against isoform B, of potential interest to combat neurological diseases. [ABSTRACT FROM AUTHOR]

A straightforward approach is employed to synthesize methylene‐bridged poly(hetero aromatic)s based on furan, pyrrole, thiophene, and thiophene derivatives. The process involves an electrophilic aromatic substitution reaction facilitated by a visible light‐initiated system consisting of manganese decacarbonyl and an iodonium salt. The approach mainly relies on the formation of halomethylium cation, the attack of this cation to heteroaromatic, regeneration of methylium cation on the heteroaromatic, and reactivity differences between halomethylium and heteroaromatic methylium cations for successful polymerizations. This innovative synthetic strategy lead to the formation of polymers with relatively high molecular weights as the stoichiometric imbalance between the comonomers increased. Accordingly, these newly obtained polymers exhibit remarkable fluorescence properties, even at excitation wavelengths as low as 330 nm. Moreover, by harnessing the halogens at chain ends of homopolymers, block copolymers are successfully synthesized, offering opportunities for tailored applications in diverse fields. [ABSTRACT FROM AUTHOR]

Im Beitrag werden zwei Modellexperimente zum Themengebiet „Elektroorganische Synthesen" vorgeschlagen. Hierbei handelt es sich um die Bromierung von Thymolblau und Phenolrot. Beide Verbindungen sind pH‐Indikatoren, deren Bromierung zu ebenfalls pH‐sensitiven Produkten führt. Diese können mit schulischen Mitteln leicht identifiziert werden. Darüber hinaus werden Hinweise zur Implementierung der Experimente in den Chemieunterricht gegeben. [ABSTRACT FROM AUTHOR]

Inhibitors of monoamine oxidases (MAOs) are of interest for the treatment of neurodegenerative disorders and other human pathologies. In this frame, the present work describes different synthetic strategies to obtain MAO inhibitors via the coupling of the aminocoumarin core with arylsulfonyl chlorides followed by copper azide-alkyne cycloaddition, leading to coumarin–sulfonamide–nitroindazolyl–triazole hybrids. The nitration position on the coumarin moiety was confirmed through nuclear magnetic resonance spectroscopy and molecular electron density theory in order to elucidate the molecular mechanism and selectivity of the electrophilic aromatic substitution reaction. The coumarin derivatives were evaluated for their inhibitory potency against monoamine oxidases and cholinesterases. Molecular docking calculations provided a rational binding mode of the best compounds in the series with MAO A and B. The work identified hybrids 14a–c as novel MAO inhibitors, with a selective action against isoform B, of potential interest to combat neurological diseases.

Agelastatin A is a marine alkaloid with potent biological activity. To date, at least 17 different strategies have achieved its total synthesis, along with many analogues. The present study focuses on the acidity stability of some N-methyl derivatives of agelastatin A. The study made use of chemical reactions and spectroscopic acquisitions. The chemical structure of some derivatives can undergo a profound rearrangement. The results could shed light on the mechanism of action of agelastatin A and suggest the preparation of analogues with improved pharmacological efficacy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An expedient and efficient synthesis of acetyl phloroglucinol from phloroglucinol under continuous flow is reported. This compound is an important building block to access numerous flavonoids. The reported acetylation reaction of phloroglucinol is more efficient than under batch conditions (residence time of 1 min in flow vs 10–15 h in batch; ≥ 98% yield in flow vs 65–86% yield in batch), and proceeds without any formation of the diacetylated product. The desired product was produced with a throughput of ≥ 98 g/h using a simple set-up. The conditions that highlight the use of ethyl acetate, a biomass-derived solvent and acetic anhydride or acetyl chloride were tested in the Friedel–Crafts acetylation of other electron-rich phenols and heterocycles. Highlights: • Development of an efficient continuous flow synthesis of Friedel–Crafts acetylation reactions. • Use of ethyl acetate as a biomass-derived solvent. • Versatility of the acetylating agent (acetic anhydride or acetyl chloride). • Readily available and cheap Lewis acid (BF3•OEt2). • Acetylation of other electron-rich arenes and heteroarenes under homogenous and flow compatible conditions. • Readily scalable (up to 99 g/h) using laboratory scale equipment. [ABSTRACT FROM AUTHOR]

This paper presents the use of O,S-acetals in a new modification of the oxo-Friedel–Crafts–Bradsher cyclization. In this reaction, under mild reaction conditions (25 °C), three- and four-ring fused RO-acenes (major) and/or HO(CH2)2S-acenes (minor) are formed, the latter products having never been observed before in this type of cyclization. In this way, two electronically different fluorophores could be obtained in a single cyclization reaction, one of them having strong electron donor properties (+M effect of alkoxy groups) and the other having donor-acceptor properties (+M and −I effects of the HO(CH2)2S-group, Hammett's constants). Further increasing the reaction temperature, HCl concentration or prolonging reaction time, surprisingly, yielded a 2:1 mixture of cis and trans dimeric isomers, as the only products of this cyclization. The DFT calculations confirmed a greater stability of the cis isomer compared to the trans isomer. The formation of unexpected dimeric products and HO(CH2)2S-acenes sheds light on the mechanism of oxo-Friedel–Crafts–Bradsher cyclization, involving competitive O/S atom protonation in strained O,S-acetals and in strain-free side groups of intermediate species. [ABSTRACT FROM AUTHOR]

Regioselectivity in electrophilic aromatic substitution (EAS) is partly governed by how well a preexisting substituent stabilizes or destabilizes the cationic intermediate formed by addition of an electrophile. Such intermediates were modeled computationally (G4) by adding a proton ortho, meta, or para to an existing substituent on a benzene ring. The effect of a meta substituent depends on the electronic character, as measured by the Hammett substituent constant σm or, better yet, σ+m. Similarly, the effect of a para or ortho substituent correlates with σ+p (= σ+). However, the influence of a substituent at the para position is 10% stronger than at the ortho position. Frontier molecular orbital arguments rationalize this observation. Consequently, the ortho:para product ratio in EAS is expected to depend, at least in part, on σ+p, with greater electron‐donating character associated with a greater preference for para over ortho. The ortho‐substituted cationic intermediate can even be favored over both meta and para if the electron‐withdrawing character is sufficient to favor ortho over para but insufficient to favor meta over either. This phenomenon is observed to occur in at least some cases when the quantity σ+p–σm falls between –0.5 and 0. [ABSTRACT FROM AUTHOR]

The browning of plant-based food is commonly understood to result from the enzymatic polymerization of phenolic compounds to pigments, called melanin. However, during the thermal treatment of food, enzymes are deactivated, and non-enzymatic reactions predominate. The extent of the contribution of phenolic compounds to these non-enzymatic reactions has been speculated ("melanin-like vs. melanoidin-like"), but the literature is limited. Therefore, the aim of the present study was to investigate the heat-induced reactions of caffeic acid (CA), para-coumaric acid (CS), ferulic acid (FA), hydrocaffeic acid (HC), and 5-O-caffeoylquinic acid (CGA) under dry conditions. The model systems were characterized by color formation, reactant conversion, and antioxidant properties. Reaction products were analyzed by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Decarboxylation could be classified as the driving force for the observed color formation and was significantly impacted by the substitution of the aromatic system. Reaction products were found to contribute to an increase in the antioxidant properties of the model systems. The oligomers described in this study could be incorporated into food melanoidins, contributing to the color and antioxidant properties observed in roasted food rich in phenolic compounds, such as coffee or cocoa. [ABSTRACT FROM AUTHOR]

Agelastatin A is a marine alkaloid with potent biological activity. To date, at least 17 different strategies have achieved its total synthesis, along with many analogues. The present study focuses on the acidity stability of some N-methyl derivatives of agelastatin A. The study made use of chemical reactions and spectroscopic acquisitions. The chemical structure of some derivatives can undergo a profound rearrangement. The results could shed light on the mechanism of action of agelastatin A and suggest the preparation of analogues with improved pharmacological efficacy.

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.

Instructional guidance, provided using worked examples, helps the inexperienced learner cope with complex information, that may be difficult to process in limited capacity working memory. For students of chemistry, such complex information can pertain to the visualisation of structural changes in molecules throughout chemical reactions. This can be alleviated through the affordances of augmented reality (AR) technology. 3D structures are important as they have a crucial impact on the chemical and physical properties of molecules. Within a framework of Cognitive Load Theory, this study illustrates how AR-supported worked examples may enhance learning of electrophilic aromatic substitution. The participant cohort were FHEQ level 5 undergraduate students studying a module of organic chemistry. In addition, the achievement motivation of learner's was also explored, and how this may be impacted by the provision of AR technology and worked examples. The control group was provided with a copy of our worked examples that contained 2D reaction mechanism drawings. Data was collected using a combination of quantitative instruments and qualitative surveys/interviews. For this cohort of students, significant intragroup improvements, and greater normalised change values, in conceptual understanding were observed in the AR group. This was not observed in the control group. No significant intergroup differences in reported cognitive load or achievement motivation of students were found. This was unaffected when introducing prior relevant chemistry experience as a covariate. Student feedback and subsequent thematic analysis show not only the positive impacts on student engagement, but also how students convey their understanding of electrophilic aromatic substitution principles.

5,10,15,20-Tetraphenylporphyrin-copper(II) complex when nitrated with 25% aqueous nitric acid in CHCl3 led to three β,β-substituted dinitro-isomers. One of the structures of products reported in the original paper was assigned incorrectly (as 2,8-dinitro-5,10,15,20-tetraphenylporphyrin derivative). Investigations using high-resolution NMR allowed to assign this compound (examined as demetallated free base) a different structure: 2,13-dinitro-5,10,15,20-tetraphenylporphyrin. These types of products, being practically unavailable by alternative methods, are attractive starting material for synthesis of more complex porphyrinoid moieties. [ABSTRACT FROM AUTHOR]

The generation of ε-carbonyl cations and their reactions with nucleophiles is accomplished readily without transition metal cation stabilization, using the ε-bromide dienoate or dienone starting materials and GaCl3 or InCl3 catalysis. Arene nucleophiles are somewhat more straightforward than allyltrimethylsilane, but allyltrimethylsilane and propiophenone trimethysilyl enol ether each react successfully with InCl3 catalysis. The viability of these cations is supported by DFT calculations. [ABSTRACT FROM AUTHOR]

This paper presents the use of O,S-acetals in a new modification of the oxo-Friedel–Crafts–Bradsher cyclization. In this reaction, under mild reaction conditions (25 °C), three- and four-ring fused RO-acenes (major) and/or HO(CH2)2S-acenes (minor) are formed, the latter products having never been observed before in this type of cyclization. In this way, two electronically different fluorophores could be obtained in a single cyclization reaction, one of them having strong electron donor properties (+M effect of alkoxy groups) and the other having donor-acceptor properties (+M and −I effects of the HO(CH2)2S-group, Hammett’s constants). Further increasing the reaction temperature, HCl concentration or prolonging reaction time, surprisingly, yielded a 2:1 mixture of cis and trans dimeric isomers, as the only products of this cyclization. The DFT calculations confirmed a greater stability of the cis isomer compared to the trans isomer. The formation of unexpected dimeric products and HO(CH2)2S-acenes sheds light on the mechanism of oxo-Friedel–Crafts–Bradsher cyclization, involving competitive O/S atom protonation in strained O,S-acetals and in strain-free side groups of intermediate species.

A novel visible light induced step‐growth polymerization by electrophilic aromatic substitution between photochemically generated carbocations and dimethoxybenzene nucleophile is described. Conventional step‐growth polymerization and chain‐growth condensation polymerization (CCP) mechanisms are presented. It is found that by changing the molar ratios of the monomers slightly, the CCP mechanism becomes operative and relatively higher molecular weight polymers are obtained because of the higher reactivity of the end groups of the intermediates and oligomers than that of the monomers. The possibility of grafting onto polymers containing epoxide at their side chains by photoinduced chain end activation of poly(dimethoxyphenylene methylene) is demonstrated. This study is expected to promote potential applications of the combination of photoinduced electron transfer reactions and CCP in macromolecular synthesis and material science. [ABSTRACT FROM AUTHOR]

The primary objective of this study is to identify the aromatic intermediate products in p-cresol degradation by ozonation, peroxone, and ozone-persulfate, and elucidate the pathways and mechanisms involved in the processes. The experiments were conducted in semi-batch operating mode, where ozone was bubbled into p-cresol in a 1.0 L cylindrical jacketed glass reactor. In general, the aromatic intermediate products of p-cresol is less toxic compared to p-cresol. All intermediate products degrade to shorter chain of carboxylic acids with further oxidation. The major degradation pathway of p-cresol is benzene ring oxidation through electrophilic aromatic substitution reaction by molecular ozone and hydroxyl radical, and single electron transfer by persulfate radical, evidenced by the presence of methyl group in majority of the detected compounds. Hydroxyl radical also oxidizes p-cresol through hydrogen atom abstraction at methyl group side-chain; evidenced by the detected 4-methylbenzyl alcohol, 4-hydroxy-benzaldehyde, 3,4-dihydroxy-benzaldehyde, and 3,4-dihydroxy-benzoic acid; the simultaneous oxidation pathway in peroxone leads to faster p-cresol degradation as compared to ozonation and ozone-persulfate. [ABSTRACT FROM AUTHOR]

The browning of plant-based food is commonly understood to result from the enzymatic polymerization of phenolic compounds to pigments, called melanin. However, during the thermal treatment of food, enzymes are deactivated, and non-enzymatic reactions predominate. The extent of the contribution of phenolic compounds to these non-enzymatic reactions has been speculated (“melanin-like vs. melanoidin-like”), but the literature is limited. Therefore, the aim of the present study was to investigate the heat-induced reactions of caffeic acid (CA), para-coumaric acid (CS), ferulic acid (FA), hydrocaffeic acid (HC), and 5-O-caffeoylquinic acid (CGA) under dry conditions. The model systems were characterized by color formation, reactant conversion, and antioxidant properties. Reaction products were analyzed by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Decarboxylation could be classified as the driving force for the observed color formation and was significantly impacted by the substitution of the aromatic system. Reaction products were found to contribute to an increase in the antioxidant properties of the model systems. The oligomers described in this study could be incorporated into food melanoidins, contributing to the color and antioxidant properties observed in roasted food rich in phenolic compounds, such as coffee or cocoa.

Electrophilic aromatic substitution (EAS) reactions are widely regarded as characteristic reactions of aromatic species, but no comparable reaction has been reported for molecules with Craig-Möbius aromaticity. Here, we demonstrate successful EAS reactions of Craig-Möbius aromatics, osmapentalenes, and fused osmapentalenes. The highly reactive nature of osmapentalene makes it susceptible to electrophilic attack by halogens, thus osmapentalene, osmafuran-fused osmapentalene, and osmabenzene-fused osmapentalene can undergo typical EAS reactions. In addition, the selective formation of a series of halogen substituted metalla-aromatics via EAS reactions has revealed an unprecedented approach to otherwise elusive compounds such as the unsaturated cyclic chlorirenium ions. Density functional theory calculations were conducted to study the electronic effect on the regioselectivity of the EAS reactions. [ABSTRACT FROM AUTHOR]

A synthetic novel strategy involving a pseudo-three-component reaction to obtain 1,6-dihydroazaazulenes derivates via cyclization of pyrrolyl-enones was developed. This reaction is carried out under mild conditions from simple starting materials and catalyzed with ionic liquid. Notably, three new C–C bonds are formed in the one-pot process. The target molecules are of interest in medicinal chemistry as they contain a privileged scaffold and are considered indole homologues. [ABSTRACT FROM AUTHOR]

The 13C chemical shift concentration dependence of phenol, anisole, thiophenol, and thioanisole in CDCl3 was acquired and analyzed over various concentration ranges and reported with the intention of observing the effect of hydrogen bonding on the electron density around aromatic nuclei. Of the para carbon chemical shift concentration dependences observed, phenol exhibited the most significant concentration dependence. Attempts were made to determine the functions describing concentration dependence of the 13C chemical shifts observed. Notably, CDCl3 was found to exhibit relatively nonlinear concentration dependence in the same range as the compounds observed, suggesting that trace impurity and solvent peaks are not reliable references for the identification shifts at an accuracy greater than ± 0.15 ppm for the concentration range 1.0 - 7.0 molal. [ABSTRACT FROM AUTHOR]

A series of semi-fluorinated polymers were obtained by Friedel-Crafts polymerization of hexafluoroacetone trihydrate (HFAH) with a variety of activated and non-activated aromatic monomers. Interfacial (water/dichloroethane) electrophilic aromatic substitution (EAS) polymerizations were carried out with trifluoromethanesulfonic anhydride (Tf 2 O) and Aliquat® 336 as phase transfer catalyst. This versatile and straightforward method achieved the synthesis of moderate to high molecular weight (12.0–29.6 kDa) polyaryl ethers and polyphenylenes with 1,1,1,3,3,3-hexafluoroisopropylene (6F) main chain linkages. Predominantly amorphous film-forming materials were obtained with low branching, high solubilities in common organic solvents, thermo-oxidative stabilities up to 500 °C, and glass transitions (T g) ranging from 157 to 250 °C. The optical and dielectric properties of these materials were also studied from which high visible region transmittance and low dielectric constant values comparable with commercial materials were found. [Display omitted] • Semi-fluorinated polyaryl ethers and polyarylenes from inexpensive aromatic monomers. • Mild conditions for direct EAS polymerization of hexafluoroacetone with aromatic monomers. • Soluble polymers with high thermal oxidative stability and high glass transition temperature. • Methodology to prepare random or segmented EAS copolymers with unique properties. • Amorphous thermoplastics with good optical transparency and low dielectric constant. [ABSTRACT FROM AUTHOR]

A two-step synthetic sequence was developed for the undergraduate organic chemistry laboratory using vanillin as the starting material. The multi-step synthesis was designed to replace two traditional experiments teaching electrophilic aromatic substitution and carbon–carbon bond forming chemistries with greener transformations. Vanillin is iodinated using Oxone® and potassium iodide in refluxing water, and students are tasked with determining the position of aromatic substitution using 1H NMR spectroscopy. The tan, shiny, pleasant-smelling iodovanillin is subsequently used in an aqueous Suzuki-Miyaura reaction with para-methylphenylboronic acid; strategically chosen to afford a second instructive 1H NMR spectrum. Both conventional heating and microwave conditions can be employed for the palladium-catalyzed reaction. This synthetic sequence, successfully performed over multiple semesters by hundreds of students, models green chemistry principles through the use of a potentially renewable feedstock and safer reagents, the choice of water as a safer reaction solvent, and the employment of a catalytic reaction. Additionally, the sequence minimizes waste in teaching labs through use of an intermediate product.

The generation of ε-carbonyl cations and their reactions with nucleophiles is accomplished readily without transition metal cation stabilization, using the ε-bromide dienoate or dienone starting materials and GaCl3 or InCl3 catalysis. Arene nucleophiles are somewhat more straightforward than allyltrimethylsilane, but allyltrimethylsilane and propiophenone trimethysilyl enol ether each react successfully with InCl3 catalysis. The viability of these cations is supported by DFT calculations.

Electrophilic aromatic substitution reactions are of profound importance for the synthesis of biologically active compounds and other advanced materials. They represent an important means to activate specific aromatic C–H bonds without requiring transition-metal catalysts. Surprisingly, few stereoselective variants are known for electrophilic aromatic substitutions, which limits the utility of these classical reactions for stereoselective synthesis. While many electrophilic aromatic substitutions lead to achiral products (due to the planar nature of aromatic rings), there are important examples where chiral products are produced, including desymmetrization reactions of aromatic cyclophanes and of prochiral substrates with multiple aromatic rings. This Synpacts article now illustrates how chiral arms, when placed precisely above and underneath delocalized carbocations, can act as chiral auxiliaries to convert classical electrophilic aromatic substitution reactions into powerful diastereo- and enantioselective transformations. [ABSTRACT FROM AUTHOR]

The reactivity of benzyl hypervalent iodine intermediates was explored in congruence with the reductive iodonio-Claisen rearrangement (RICR) to show that there may be an underlying mechanism which expands the reasoning behind the previously known C–C bond-forming reaction. By rationalizing the hypervalent iodine’s metal-like properties it was concluded that a transmetallation mechanism could be occurring with metalloid groups such as silicon and boron. Hypervalent iodine reagents such as Zefirov’s reagent, cyclic iodonium reagents, iodosobenzene/BF3, and PhI(OAc)2/BF3 or triflate-based activators were tested. A desirable facet of the reported reaction is that iodine(I) is incorporated into the product thus providing greater atom economy and a valuable functional group handle for further transformations. The altering of the RICR’s ortho-selectivity to form para-selective products with benzyl hypervalent iodine intermediates suggests a mechanism that involves hypervalent iodine-guided electrophilic substitution (HIGES).

The reactions of quinoline-2(6,8)-carbaldehydes with arenes by the action of strong Brønsted (H2SO4, CF3SO3H) or Lewis (AlCl3, AlBr3) acids led to the formation of substituted diarylmethylquinolines in high yields. [ABSTRACT FROM AUTHOR]

Cyclodehydration of α-phenoxy ketones promoted by Eaton's reagent (phosphorus pentoxide–methanesulfonic acid) is used to prepare 3-substituted or 2,3-disubstituted benzofurans with moderate to excellent yields under mild conditions. The method provides a facile access to benzofurans from readily available starting materials such as phenols and α-bromo ketones. The reaction is highly efficient, which is attributed to the good reactivity and fluidity of Eaton's reagent. The reaction can be applied to prepare naphthofurans, furanocoumarins, benzothiophenes, and benzopyrans. [ABSTRACT FROM AUTHOR]

The nitration reaction of nitrobenzene with nitronium ion yielding ortho‐, meta‐ and para‐dinitrobenzenes has been studied within the Molecular Electron Density Theory, using DFT computational methods at the B3LYP/6‐311G(d,p) level. This electrophilic aromatic substitution (EAS) reaction takes place through a two‐step mechanism involving the formation of a tetrahedric cation intermediate. The electrophilic attack of nitronium ion on nitrobenzene is the rate‐determining step of this EAS reaction, and consequently, responsible for the composition of the reaction mixture. The subsequent proton abstraction from the cation intermediate is barrierless. From the computed activation Gibbs free energies, a relationship 11.0 (ortho) : 87.3 (meta) : 1.7 (para) of the dinitrobenzenes is estimated, in clear agreement with the experimental outcome. The similar nucleophilic activation of the ortho and meta carbons of nitrobenzene makes it possible to question the hypothesis for the orientation in EAS reactions involving nucleophilically deactivated benzenes based on the relative stability of the tetrahedric cation intermediates. [ABSTRACT FROM AUTHOR]

In this article, a new experiment is presented, which links the topics "electrophilic aromatic substitution" and "electrochemical writing". In electrochemical writing, an electrode is used to write on filter paper that has previously been soaked in an electrolyte solution [1]. In the experiment presented, bromide ions are oxidized to bromine at the anode and this is immediately reacted with fluorescein [2]. [ABSTRACT FROM AUTHOR]

A new general approach to double nitration of 6,12-di(hetero)aryl-substituted and 6,12-unsubstituted 5,11-dialkyl-5,11-dihydroindolo[3,2-b]carbazoles by acetyl nitrate has been developed to obtain their 2,8-dinitro and 6,12-dinitro derivatives, respectively. A formation of mono-nitro derivatives (at C-2 or C-6) from the same indolo[3,2-b]carbazoles has also been observed in several cases. Reduction of 2-nitro and 2,8-dinitro derivatives with zinc powder and hydrochloric acid has afforded 2-amino- and 2,8-diamino-substituted indolo[3,2-b]carbazoles, while reduction of 6,12-dinitro derivatives under similar reaction conditions has been accompanied by denitrohydrogenation of the latter compounds into 6,12-unsubstituted indolo[3,2-b]carbazoles. Formylation of 6,12-dinitro derivatives has proved to occur only at C-2, while bromination of these compounds has taken place at both C-2 and C-8 of indolo[3,2-b]carbazole scaffold. Moreover, 6,12-dinitro-substituted indolo[3,2-b]carbazoles have been modified by the reactions with S- and N-nucleophiles. Notably, the treatment of 6,12-dinitro compounds with potassium thiolates has resulted in the displacement of both nitro groups, unlike potassium salts of indole or carbazole, which have caused substitution of only one nitro group.

Abstract Triarylmethyl cations serve as tunable organocatalysts for the synthesis of bisindolylmethanes. The catalyst structure can be modified to increase or decrease reactivity as needed to match the requirements of the substrate. High yields are achieved for a variety of substrates by using these green catalysts. Catalyst tuning allows for the use of less reactive electrophiles by increasing the reactivity of the catalyst. Acid-sensitive products can be isolated under these mild reaction conditions.

The Maillard reaction is a vital part of food processing, involving a vast number of complex reaction pathways, resulting in high-molecular-weight colorants. So far, studies have been focused on the conversion of carbohydrates and amino compounds, but the literature elaborating the contribution of phenolic compounds to the formation of the colored end-products is still rare. The aim of this study was to characterize early reactions, underlying the formation of phenol-containing melanoidins. For this purpose, binary model systems of the prominent phenolic compounds caffeic acid and ferulic acid combined with α-dicarbonyl compounds typically formed in the Maillard reaction such as glyoxal, methylglyoxal, and diacetyl were analyzed after heat treatment. High-resolution mass spectrometry revealed that decarboxylation, aromatic electrophilic substitution, and nucleophilic addition are important reaction steps that lead to colored heterogeneous oligomers. Polymerization was favored for phenolic compounds with a high electron density in the aromatic system and for α-dicarbonyl compounds carrying aldehyde functions.

A new method for the synthesis of 5,9‐diaza[5]helicenes is presented using 2,3‐bis(acylamino)‐substituted ortho‐terphenyls as precursors. Activation of the amide groups and electrophilic substitution at the ortho positions of the adjacent phenyl groups leads to the 5,9‐diaza[5]helicenes. A stepwise reaction including protection of the first amino group, amide formation at the second amino group with subsequent cyclization, followed by deprotection, amide formation and cyclization at the first amino group ensures that both electrophilic substitutions take place at sufficiently activated arenes and allows for the different substituents at the diaza[5]helicenes brought in with the amide groups. The terphenyl precursors are synthesized by two Suzuki couplings of suitably substituted building blocks. Three different 5,9‐diaza[5]helicenes with aliphatic, alkenyl and methoxycarbonylalkyl substituents were prepared; the latter would allow to attach further functionalities by ester or amide linkage. [ABSTRACT FROM AUTHOR]

Indoles are privileged heterocycles found in many biologically active pharmaceuticals and natural products. However, the selective functionalization of the benzenoid moiety in indoles in preference to the more reactive pyrrolic unit is a significant challenge. Herein we report that N‐acyl directing groups enable the C7‐selective C−H borylation of indoles using just BBr3. This transformation shows some functional‐group tolerance and notably proceeds with C6 substituted indoles. The directing group can be readily removed in situ and the products isolated as the pinacol boronate esters. Acyl‐directed electrophilic borylation can be extended to carbazoles and anilines with excellent ortho selectivity. 4‐amino‐indoles are amenable to this process, with acyl group installation and directed electrophilic C−H borylation enabling selective formation of C5‐BPin‐indoles. [ABSTRACT FROM AUTHOR]

Indoles are privileged heterocycles found in many biologically active pharmaceuticals and natural products. However, the selective functionalization of the benzenoid moiety in indoles in preference to the more reactive pyrrolic unit is a significant challenge. Herein we report that N‐acyl directing groups enable the C7‐selective C−H borylation of indoles using just BBr3. This transformation shows some functional‐group tolerance and notably proceeds with C6 substituted indoles. The directing group can be readily removed in situ and the products isolated as the pinacol boronate esters. Acyl‐directed electrophilic borylation can be extended to carbazoles and anilines with excellent ortho selectivity. 4‐amino‐indoles are amenable to this process, with acyl group installation and directed electrophilic C−H borylation enabling selective formation of C5‐BPin‐indoles. [ABSTRACT FROM AUTHOR]

A two-step synthetic sequence was developed for the undergraduate organic chemistry laboratory using vanillin as the starting material. The multi-step synthesis was designed to replace two traditional experiments teaching electrophilic aromatic substitution and carbon–carbon bond forming chemistries with greener transformations. Vanillin is iodinated using Oxone® and potassium iodide in refluxing water, and students are tasked with determining the position of aromatic substitution using 1H NMR spectroscopy. The tan, shiny, pleasant-smelling iodovanillin is subsequently used in an aqueous Suzuki-Miyaura reaction with para-methylphenylboronic acid; strategically chosen to afford a second instructive 1H NMR spectrum. Both conventional heating and microwave conditions can be employed for the palladium-catalyzed reaction. This synthetic sequence, successfully performed over multiple semesters by hundreds of students, models green chemistry principles through the use of a potentially renewable feedstock and safer reagents, the choice of water as a safer reaction solvent, and the employment of a catalytic reaction. Additionally, the sequence minimizes waste in teaching labs through use of an intermediate product. [ABSTRACT FROM AUTHOR]

Here we described the behavior of phosphinyl nitrosoalkenes with indole, pyrrole and 2,5-dimethylpyrrole. 3-Substituted indoles have been prepared through the reaction of nitrosoalkenes with indole. The reaction of phosphinyl nitrosoalkenes with pyrrole leads to the formation of 2-substituted pyrroles, while the behavior of 2,5-dimethylpyrrole with these nitrosoalkenes affords bicyclic 1,2-oxazines. [ABSTRACT FROM AUTHOR]

A safe, convenient, and regioselective synthesis of 3-halo coumarins using a metal halide (CuX2 alone or with ZnX2) promoted halogenation with N -halosuccinimide (NXS) as halide source is reported. The synthesis involved the steady in situ generation of highly reactive positive halogen (X+) by the coordination of copper or zinc with the N -halosuccinimide and subsequent electrophilic aromatic substitution of the electron-deficient coumarins. This procedure works well also for the halogenation of less electron-rich naphthoquinones, flavones, and methoxypsoralen in moderate to quantitative yields. This protocol features simple experimental conditions using readily available inexpensive reagents and provides a convenient approach to the chlorination or bromination of some useful heteroaromatic compounds. [ABSTRACT FROM AUTHOR]

Abstract Abstraction of chloride from [Fe(CO) 4 (PPh 2 Cl)] (1) in the presence of PPh 3 leads to [Fe(CO) 4 (PPh 2 (PPh 3))][AlCl 4 ] (2), an iron complex of a phosphine-coordinated phosphenium ion. The PPh 3 is readily displaced by ferrocene, leading to an electrophilic aromatic substitution reaction, and formation of [Fe(CO) 4 {PPh 2 Fc}] (3) (Fc = ferrocenyl). Alternately, chloride abstraction from 1 in the presence of ferrocene leads directly to 3 , via a transient phosphenium ion complex. The transient phosphenium ion complex also reacts with N,N-diethylaniline, indole, and pyrrole to form the respective p -anilinyl, 3-indolyl, and 2-pyrryl phosphine complexes via electrophilic aromatic substitution. Chloride abstraction from [Fe(CO) 4 (PPhCl 2)] in the presence of ferrocene leads to a double substitution reaction, forming [Fe(CO) 4 {PPhFc 2 }] (13). Graphical abstract Image 1 Highlights • Transient Fe(CO) 4 -bound phosphenium ions have been formed and trapped. • Phosphenium ion complexes undergo rapid electrophilic aromatic substitution reactions. • Room temperature P-C bond formation without lithiation or precious metals. [ABSTRACT FROM AUTHOR]

Thia‐bridged triarylamine hetero[4]helicenes (TBTH[4]H) are a peculiar class of geometrically stable [4]helicenes that have shown promising applications as organic electronic materials. Their structure comprises a bis‐phenothiazine moiety, with a nitrogen atom and an aromatic ring in common, forced into a helix‐shaped arrangement by four carbon–sulfur bonds. We describe a detailed study on the scope and application of the electrophilic sulfur insertion path to TBTH[4]H, with particular emphasis on the regioselective preparation of asymmetric (not dissymmetric) derivatives. The regio‐controlled synthesis of several thia‐bridged triarylamine hetero[4]helicenes (TBTH[4]H), a peculiar class of geometrically stable [4]helicenes, is achieved using triarylamines or N‐aryl phenothiazines as suitable starting materials. The control of the regiochemistry allows modifications of these peculiar compounds that have promising applications as organic electronic materials. [ABSTRACT FROM AUTHOR]

Graphical abstract The present study describes the optimization of a new method of synthesis of highly functionalized 5-bromo-2-amino-1,3-thiazoles by a rapid and efficient one-pot method, using simple starting materials and mild conditions. Interestingly some of the synthesized compounds demonstrate promising monoacylglycerol lipase inhibition properties. Highlights • Convenient one-pot synthesis of highly functionalized 5-bromo-2-amino-1,3-thiazoles. • Potential MAGL inhibitors. • Safe and efficient bromination reaction. Abstract Highly functionalized 5-bromo-2-amino-1,3-thiazoles bearing various substituents could be easily prepared by a rapid and efficient one-pot method, using simple starting materials and mild conditions while avoiding the use of metal catalysts or inconvenient reagents such as elemental halogens. These useful products can serve as starting materials for other reactions or as pharmacologically interesting compounds. In our work we have shown that the resulting 5-bromothiazole compounds could lead to monoacylglycerol lipase (MAGL) inhibition in the μM range. [ABSTRACT FROM AUTHOR]