Nonbenzenoid Aromatics Research Articles

Four-Membered Ring-Embedded Cycloarene Enabling Anti-Aromaticity and Ultra-Narrowband Emission.

The synthesis of fully fused π-conjugated cycloarenes embedded with nonbenzenoid aromatics is challenging. In this work, the first example of four-membered ring-embedded cycloarene (MF2) was designed and synthesized in single-crystal form by macrocyclization and ring fusion strategies. For comparison, single bond-linked chiral macrocycle MS2 without two fused four-membered rings and its linear-shaped polycyclic benzenoid monomer L1 were also synthesized. The pronounced anti-aromaticity of four-membered rings significantly adjusts the electronic structures and photophysical properties of cycloarene, resulting in an enhancement of the photoluminescence quantum yield (PLQY) from 10.66 % and 10.74 % for L1 and MS2, respectively, to 54.05 % for MF2, which is the highest PLQY among the reported cycloarenes. Notably, owing to the embedded anti-aromatic four-membered rings that reduce structural displacements, MF2 exhibits an ultra-narrowband emission with a single-digit full-width at half-maximum (FWHM) of only 7 nm (0.038 eV), which sets a new record among all reported organic narrowband luminescent molecules, and represents the first example of ultra-narrowband emission in conventional polycyclic aromatic hydrocarbons (PAHs) devoid of heteroatoms.

Four‐Membered Ring‐Embedded Cycloarene Enabling Anti‐Aromaticity and Ultra‐Narrowband Emission

AbstractThe synthesis of fully fused π‐conjugated cycloarenes embedded with nonbenzenoid aromatics is challenging. In this work, the first example of four‐membered ring‐embedded cycloarene (MF2) was designed and synthesized in single‐crystal form by macrocyclization and ring fusion strategies. For comparison, single bond‐linked chiral macrocycle MS2 without two fused four‐membered rings and its linear‐shaped polycyclic benzenoid monomer L1 were also synthesized. The pronounced anti‐aromaticity of four‐membered rings significantly adjusts the electronic structures and photophysical properties of cycloarene, resulting in an enhancement of the photoluminescence quantum yield (PLQY) from 10.66 % and 10.74 % for L1 and MS2, respectively, to 54.05 % for MF2, which is the highest PLQY among the reported cycloarenes. Notably, owing to the embedded anti‐aromatic four‐membered rings that reduce structural displacements, MF2 exhibits an ultra‐narrowband emission with a single‐digit full‐width at half‐maximum (FWHM) of only 7 nm (0.038 eV), which sets a new record among all reported organic narrowband luminescent molecules, and represents the first example of ultra‐narrowband emission in conventional polycyclic aromatic hydrocarbons (PAHs) devoid of heteroatoms.

Discovery of potential components characteristic by conjugated enone from the branches and leaves of Croton lauioides with anti-neuroinflammatory activity via regulating the NF-κB pathway

In this study, the chemical composition and pharmacological activity of Croton lauioides were investigated for the first time. The bioactive and HPLC-UV guided isolation led to the discovery of twenty-three conjugated enone-type components (1–23), including nine previously unknown sesquiterpenoid derivatives (1–4, 9–10, 12–14). Notably, compounds 1 and 12 are epoxides containing an endoperoxide bridge (1) or a unique dioxaspiro core (12), respectively. Compounds 2–7 are non-benzenoid aromatics featuring a tropone function, while 9–11 possess a rare rearranged scaffold with tropone shift into benzene. Extensive characterization was performed using NMR spectra, HRESIMS data, and electronic circular dichroism (ECD) calculations. Furthermore, we evaluated the bioactivities of all isolated compounds against neuroinflammation in LPS-stimulated BV-2 microglial cells. Remarkably, most sesquiterpenoid derivatives exhibited significant NO inhibit activities, and compound 5 showed the most potent effect with an IC50 value of 0.14 ± 0.04 μM. Structure-activity relationship (SAR) analysis revealed that sesquiterpenoids modified with endocyclic enone conjugation may serve as a key pharmacophore for NO inhibition, particularly involving aromatic tropone moiety. The qPCR and Western blot results demonstrated that 5 exerted an inhibitory effect on the mRNA levels of iNOS, TNF-α and COX-2 in a time-dependent manner, as well as suppressed the protein expression of iNOS, TNF-α, COX-2. In mechanism, 5 could prevented activation of NF-κB pathway by suppressing phosphorylation of p65 and IκB-α. These findings revealed C. lauioides might be a promising resource for drug candidate development targeting neuroinflammation.

Carbocycloaddition strategies for troponoid synthesis

Tropone is the prototypical aromatic 7-membered ring, and can be found in virtually any undergraduate textbook as a key example of non-benzenoid aromaticity. Aside from this important historical role, tropone is also of high interest as a uniquely reactive synthon in complex chemical synthesis as well as a valuable chemotype in drug design. More recently, there has been growing interest in the utility of tropones for catalysis and material science. Thus, synthetic strategies capable of synthesizing functional tropones are key to fully exploiting the potential of this aromatic ring system. Cycloaddition reactions are particularly powerful methods for constructing carbocycles, and these strategies in turn have proven to be powerful for generating troponoids. The following review article provides an overview of strategies for troponoids wherein the 7-membered carbocycle is generated through a cycloaddition reaction. Representative examples of each strategy are also provided.

Nonbenzenoid aromaticity of 1-phosphafulvenes: synthesis of phosphacymantrenes.

The coordination chemistry of 1-phosphafulvenes was investigated by employing their [6 + 4] adducts or α-C2-bridged biphospholes as a precursor. Unbridged phosphacymantrenes arise from 1-phosphafulvenes via proton abstraction. α-C2-bridged biphosphacymantrenes are probably yielded by the reductive coupling of 1-phosphafulvene with Mn2(CO)10. The coordination behavior of 1-phosphafulvenes is comparable to that of pentafulvenes, which again demonstrates the phosphorus-carbon analogy in low-coordinate organophosphorus chemistry.

Antiaromaticity Gain Activates Tropone and Nonbenzenoid Aromatics as Normal-Electron-Demand Diels-Alder Dienes.

We propose a carbonyl umpolung strategy for activating tropone as a normal-electron-demand Diels-Alder diene. Tropone has low reactivity for Diels-Alder reactions because of its [4n+2] π-aromaticity. Conversion of the carbonyl group into a hydrazone ion (═N-NR-) reverses the polarity of the exocyclic double bond, increases the [4n] ring π-antiaromaticity, and raises the HOMO energy. Computed gas-phase activation free energies for a Diels-Alder reaction with maleimide suggest a billion-fold rate increase when the tropone C═O is replaced by ═N-NR- (R = H or SO2CH3). Other nonbenzenoid aromatics can be activated as normal-electron-demand Diels-Alder dienes in the same way.

Synthesis of Colchicinoids and Allocolchicinoids through Rh(I)-Catalyzed [2+2+2+1] and [2+2+2] Cycloadditions of o-Phenylenetriynes with and without CO.

The nonbenzenoid aromatics, tropones and tropolones, are found in various natural products such as colchicine and hinokitol, which possess significant biological activities. The traditional methods to construct the tropone skeletons include oxidation of cycloheptatriene and [4+3] cycloadditions. In addition, the total synthesis of colchicine and its analogues requires laborious organic transformations in the formations of 6-7-7 fused-ring systems. Transition metal-catalyzed carbocyclization and cycloaddition reactions have proven to be among the most efficient methods for constructing complex polycyclic systems. On the basis of our recent discovery of the Rh-catalyzed carbonylative [2+2+2+1] cycloaddition of triynes to the formation of a fused tropone system, we report here the application of this methodology to the one-step formation of the 6-7-7-5 fused tetracyclic scaffold of colchicinoids based on the [2+2+2+1] cycloaddition of o-phenylenetriynes with CO. In addition, the one-step formation of allocolchicinoids bearing the 6-7-6-5 fused tetracyclic system through the Rh-catalyzed [2+2+2] cycloaddition of o-phenylenetriynes is also described.

Recent Advances in the Chemistry of Pentafulvenes.

Pentafulvenes are a unique class of compounds that originally attracted attention due to their propensity to display nonbenzenoid aromaticity. Subsequently, they were recognized as valuable synthons for the construction of a wide range of compounds by virtue of their ability to display multiple cycloaddition profiles. Naturally, this area of organic chemistry has experienced rapid growth over the last five decades, fueled by elegant work showcasing the unique reactivity of pentafulvenes in a plethora of cycloaddition reactions. In this Review, we have attempted to provide a systematic account of the methods for the generation of pentafulvenes, their rich and varied cycloaddition chemistry, organometallic reactions, and theoretical studies that support their versatility. Further, we have highlighted their applications in the synthesis of a variety of complex structural frameworks. It is our conviction that this Review will be useful to a wide range of chemists, and will spur further research in this promising area.

ChemInform Abstract: Carbo‐Benzene′s Aromaticity, Before and Beyond: A Tribute to Nozoe

AbstractReview: [52 refs.

Carbo‐Benzene's Aromaticity, Before and Beyond: A Tribute to Nozoe

Beyond rigorous inspection of the literature, selected comments and drawings from the Nozoe Autograph Books show how concepts and targets of the chemistry of today already existed 40 years ago. This is illustrated for the chemistry of carbo-mers, which was actually unknowingly inspired by chemists of the golden age. After a personal travel through time and pages by the last author of this essay, who meets autographs by people who have been important in his career, in particular on the occasions of Nozoe's visits to France or past ISNA events, unpublished results in non-benzenoid chemistry are dedicated to Nozoe's memory. Experimental advances are first disclosed on the comparative chemistry of the three ortho, meta and para isomers of tetraphenyl-carbo-benzene C18 H2 Ph4 , the known ortho isomer serving as a reference. The two CH vertices of these chromophores make their [6]pericyclyne precursors quite sensitive and their yields and purifications challenging to optimize. The meta isomer was, however, isolated in 18% yield, and described by NMR and UV-vis absorption spectroscopy and crystallography. The para isomer was characterized both in pure form and in a 1:1 mixture with a single isomer of its HCl adduct, including by X-ray diffraction analysis of a co-crystal showing that the interior of the C18 ring of the HCl adduct is filled by the Cl atom. Theoretical advances are then offered regarding the "aromatic character" of a triple bond, by showing that the topological acyclic reference of acetylene is the Möbius-twisted cyclobutadiene. Acetylenoids are finally proposed as a novel class of non-benzenoid aromatics.

Non-Traditional Aromatic Topologies and Biomimetic Assembly Motifs as Components of Functional Pi-Conjugated Oligomers

This article will highlight our recent work using conjugated oligomers as precursors to electroactive polymer films and self-assembling nanomaterials. One area of investigation has focused on nonbenzenoid aromaticity in the context of charge delocalization in conjugated polymers. In these studies, polymerizable pi-conjugated units were coupled onto unusual aromatic cores such as methano[10]annulene. This article will also show how biologically-inspired assembly of molecularly well-defined oligopeptides that flank pi-conjugated oligomers has resulted in the aqueous construction of 1-dimensional nanomaterials that encourage electronic delocalization among the pi-electron systems.

William von Eggers Doering’s Many Research Achievements during the First 65 Years of his Career in Chemistry

This Account highlights William von Eggers Doering's important discoveries in many fields of chemistry. His synthetic and mechanistic studies have contributed to areas including non-benzenoid aromatics, carbenes, pericyclic reactions, and diradical intermediates. Doering's synthesis with L. H. Knox of the highly stable tropylium ion and their investigation of its reactivity were the starting point for the development of the field of non-benzenoid aromatics. Working with A. K. Hoffmann, Doering demonstrated the synthesis of dichloro- and dibromocarbene by base-induced alpha elimination of HCl or HBr from CHCl3 or CHBr3 under anhydrous conditions. These results allowed for the synthesis of a variety of cyclopropanes and derivatives including allenes. Using 14C labeling experiments, Doering and Prinzbach showed that the mechanism of insertion of singlet methylene into a C-H bond was a concerted process.In their work on the Cope rearrangement, Doering and Roth's outstanding stereochemical analysis showed that the rearrangement of acyclic 1,5-hexadienes proceeds concertedly, passing over a chairlike transition state. This work has had an enormous impact on the understanding of stereochemical control in synthetic organic chemistry, and many fruitful applications in synthesis have stemmed directly from this finding. Transition-state resonance structures analogous to those for ground-state aromatics can qualitatively explain the relatively large substituent effects on the rate of the Cope rearrangement. However, quantum chemical calculations have quantitatively described these effects. The rapid degenerate Cope rearrangements in the cis-divinylcyclopropane units of 3,4-homotropilidene, barbaralone, and bullvalene establish these molecules as having fluxional structures. The unique molecule bullvalene has more than 1.2 million possible structures interconnected by degenerate Cope rearrangements, which average all H and all C atoms. Doering has also examined stepwise thermal reorganizations that pass through intermediary 1,3- or 1,4-diradicals and do not show conformational equilibration as would be expected for classical intermediates. Doering calls these processes "not-obviously concerted". He discusses "continuous diradicals" as transition states and rationalizes the course of these reactions through the concept of a "caldera" (a flat surface with small energy wells as found on the top of volcanoes).The understanding of fundamental chemical reactions remains the focus of Doering's research. In his terms, "understanding" means not only gaining deep insight but also the intellectual control that allows researchers to predict a reaction's course. Because the interplay between theory and experiment has led to great progress in this predictive ability, Doering's experimental work has provided an important input for computational chemistry and to the essential understanding of chemical reactions.

Trifluoromethanesulfonic Acid Catalyzed Friedel—Crafts Acylation of Aromatics with β‐Lactams.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Trifluoromethanesulfonic acid catalyzed Friedel–Crafts acylation of aromatics with β-lactams

N-Protected and unprotected 2-azetidinones, protolytically activated by superacidic trifluoromethanesulfonic acid, react with aromatic compounds to give β-amino aromatic ketones in good to excellent yields (65–98%). Non-benzenoid aromatics (pyrrole and ferrocene) produced good yield (64–89%) of the corresponding ketones.

Redox troponization of (η5-cyclopentadienyl)(η4-4-menthyl-4-exo-trichloromethylcyclohexa-2,5-dien-1-one)rhodium as a novel approach to the synthesis of metal-coordinated nonbenzenoid aromatics of the tropone seriesas a novel approach to the synthesis of metal-coordinated nonbenzenoid aromatics of the tropone series

The possibility of redox troponization of a gem-polyhalomethylated semiquinoid system, π-coordinated to a metal atom, was shown in relation to the reaction of (η5-cyclopentadienyl)(η4-4-menthyl-4-exo-trichloromethylcyclohexa-2,5-dien-1-one)rhodium with Pd(PPh3)4. The reaction occurs with retention of the metal coordination affording a sevenmembered organometallic derivative of the nonbenzoid aromatic series, namely, (η5-cyclopentadienyl)(η4-4-chloro-5-menthylcyclohepta-2,4,6-trien-1-one)rhodium, whose structure was established by means of elemental analysis, NMR, and mass-spectral data.

Synthetic Analytical Studies on Organic Reagents for Biomaterials

Synthetic analytical chemistry: Analytical with the aid of synthetic organic chemistry is proposed by the present author as a new field of analytical chemistry. Such is developing on the basis of investigations of π-electron systems such as non-benzenoid aromatics (e.g. annulenes) or conjugated polyene and polyyne systems. Various kinds of organic reagents for analyses (ultraviolet/visible and near-infrared absorption, fluorescence, chemiluminescence and new silica gel column packings for high-performance liquid chromatography) were developed and applied to the analyses of many biomaterials. In this paper, synthetic analytical is illustrated mainly by the author′s own studies.

Modified neglect of diatomic overlap calculations on boron‐nitrogen derivatives of nonbenzenoid aromatics. II. The analysis of the 130 possible nonfully boron‐nitrogen‐alternating isomers of pentaazapentaboraazulene

AbstractModified neglect of diatomic overlap (MNDO) calculations have been used to investigate the ground state properties of the 130 nonfully boron‐nitrogenalternating isomers of pentaazapentaboraazulene (PAPBAZ), N5B5H8. The two most stable of these nonfully boron‐nitrogen‐alternating isomers, 1,2,3a, 5,7‐pentaaza‐3,4,6,8,8a‐pentaboraazulene, (1,2,3a, 5,7‐PAPBAZ) (3), and 1,3,3a,5,7‐PAPBAZ (4) have strongly exothermic heats of formation (−142.5 and −142.4 kcal/mol, respectively), while the two least stable isomers, 1,6,7,8,8a‐PAPBAZ (131) and 1,2,3,3a,8a‐PAPBAZ (132), are calculated to have endothermic heats of formation (+95.43 and +96.31 kcal/mol, respectively). Each isomer optimized as a slightly to extremely nonplanar molecule, but each remained a bicyclic system containing a seven‐membered ring fused to a five‐membered ring. Thus, no ring‐opened structures were observed. An empirical relationship between the heat of formation and the number, position, and type of homonuclear (NN or BB) bonds present in the molecules could be established, but as the heat of formation for the molecules became more positive, the relationship became less strong. A general trend of diminishing energy difference between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) was observed as the heat of formation became more positive. In addition to a discussion of the structures of (3), (4), (131), and (132), the structures of 2,3a,4,6,8‐PAPBAZ (9), 2,3a,5,6,8‐PAPBAZ (11), 1,2,4,6,8‐PAPBAZ (15), 2,3a,4,7,8a‐PAPBAZ (19), 1,3a,4,5,8‐PAPBAZ (32), 1,2,3,5,7‐PAPBAZ (47), 1,3a,5,8,8a‐PAPBAZ (67), 1,3a,6,7,8a‐PAPBAZ (87), 3a,4,6,8,8a‐PAPBAZ (106), 1,2,3,5,6‐PAPBAZ (109), 1,2,3a,8,8a‐PAPBAZ (116), and 4,5,6,7,8‐PAPBAZ (130) are discussed in detail. Some of these molecules were chosen because they represent the minima and maxima, respectively, in heats of formation [(3), (4), (130), (131), and (132)], ionization potentials [(9) and (32)], differences in LUMO and HOMO energies [(106) and (32)], and dipole moments [(11) and (87)]. The remaining molecules were chosen because each represent the most stable system containing the following homonuclear chains: B‐B‐B (15), N‐N‐N (19), B‐B‐B‐B (47), N‐N‐N‐N (67), B‐B‐B‐B‐B (109), and N‐N‐N‐N‐N (116).

MNDO calculations on boron–nitrogen derivatives of nonbenzenoid aromatics: I. The two fully boron–nitrogen‐alternating isomers of “inorganic azulene”

AbstractModified neglect of diatomic overlap (MNDO) calculations have been used to investigate the ground state properties of the two fully boron‐nitrogen‐alternating isomers of “inorganic azulene”: 1,3,4,6,8‐pentaaza‐2,3a, 5,7, 8a‐pentaboraazulene (1, 1,3,4,6,8‐PAPBAZ) and 2,3a,5,7,8a‐pentaaza‐1,3,4,6,8‐pentaboraazulene (2, 2,3a,5,7,8a‐PAPBAZ). Both molecules optimize to planar structures, have exothermic heats of formation (−194.4 kcal/mol and −161.4 kcal/mol, respectively), and exhibit some bond delocalization. The relationship of these two PAPBAZ isomers to their organic parent molecule, azulene, is discussed.

キノノイド構造を有する拡張環状交差共役系の化学

One of the recent advances in the field of non-benzenoid aromatics would be the chemistry of the extended cyclic cross-conjugated compounds derived by insertion of more complex conjugated π-electron system instead of the exo-double bond in fulvene-, fulvalene-, annulenone-, and oxocarbon-systems. Many physical and chemical properties of remarkable interest have been developed in these newly designed cross-conjugated variations. The present review deals with the chemistry of quinarenes, quinarenones, quinocarbons, and their hetero analogs which are the extended cyclic cross-conjugated π-electron systems comprising one or more quinonoid structures. The fundamental insights mentioned here would provide helpful suggestions for the molecular design of organic dyes, highly polarized compounds, electron acceptors or electron donors having a bright prospect of developing the new field of application to the optoelectronics, organic super conductors, and so on.

Synthetic Application of 1,3-Dithiolium and 1,3-Oxathiolium Cations

Abstract 1,3-Dithiolium and 1,3-oxathiolium salts are positively charged 6φ electronically conjugated cations containing two hetero atoms in a five-membered ring. They exhibit a high reactivity toward nucleophiles. This study has shown that 1,3-dithiolium cations form an interesting class of compounds because of their non-benzenoid aromaticity and that 1,3-oxathiolium cations are highly versatile synthetic intermediates which can provide a number of novel heterocyclic compounds and their precursors depending on the nature of the nucleophiles and the reaction conditions.