Ortho Position Research Articles

V‐Catalyzed Direct ortho‐Aminomethylation of Phenols

A strategy for cross‐dehydrogenative C(sp2)–C(sp3) coupling was developed by direct and highly selective V‐catalyzed ortho‐aminomethylation of phenol with aniline derivatives. A series of aminomethylphenol compounds were obtained in moderate to good yields under mild reaction conditions and with a broad substrate scope. A possible radical mechanism was proposed, and it was found that the coordination of phenolic hydroxyl groups with V5+ was crucial for the effective activation of the ortho position.

Engineering the Substrate Specificity of (S)-β-Phenylalanine Adenylation Enzyme HitB.

Adenylation enzymes catalyze the selective incorporation of aminoacyl building blocks in the biosynthesis of nonribosomal peptides and related natural products. Although β-amino acid units are one of the important aminoacyl building blocks in natural product biosynthesis, very little is known about the engineering of β-amino acid adenylation enzymes. In this study, we engineered the substrate specificity of the (S)-β-phenylalanine adenylation enzyme, HitB, involved in the biosynthesis of macrolactam polyketide hitachimycin. Based on the previously determined structure of HitB wild-type, we mutated Phe328 and Ser293, which are located near the meta and ortho position of the (S)-β-phenylalanine moiety, respectively. As a result, the HitB F328V and F328L mutants efficiently activated meta-substituted (S)-β-phenylalanine analogs, and the HitB T293G and T293S mutants efficiently activated ortho-substituted (S)-β-phenylalanine analogs. Structural analysis of the HitB F328L and T293G mutants with the corresponding nonhydrolyzable intermediate analogs revealed an enlarged substrate binding pocket for (S)-β-phenylalanine analogs, providing detailed insights into the structural basis for creating enzyme substrate promiscuity. Our findings may be useful for production of various β-amino acid-containing natural product analogs.

Synthesis and Enzymatic Evaluation of a Small Library of Substituted Phenylsulfonamido-Alkyl Sulfamates towards Carbonic Anhydrase II.

A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, 1b-79b, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates 1a-79a, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds 1a-79a showed no inhibition of the enzyme, in contrast to sulfamates 1b-79b. Thus, the inhibitory potential of compounds 1b-79b towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the para position proved to be better for inhibiting CAII than compounds with the same substituent in the meta or ortho position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as Ki = 0.67 μM (for 49b) and a tert-butyl substituent in para position and acted as a competitive inhibitor of the enzyme.

Molecular Docking Studies of Ortho-Substituted Phenols to Tyrosinase Helps Discern If a Molecule Can Be an Enzyme Substrate.

Phenolic compounds with a position ortho to the free phenolic hydroxyl group occupied can be tyrosinase substrates. However, ortho-substituted compounds are usually described as inhibitors. The mechanism of action of tyrosinase on monophenols is complex, and if they are ortho-substituted, it is more complicated. It can be shown that many of these molecules can become substrates of the enzyme in the presence of catalytic o-diphenol, MBTH, or in the presence of hydrogen peroxide. Docking studies can help discern whether a molecule can behave as a substrate or inhibitor of the enzyme. Specifically, phenols such as thymol, carvacrol, guaiacol, eugenol, isoeugenol, and ferulic acid are substrates of tyrosinase, and docking simulations to the active center of the enzyme predict this since the distance of the peroxide oxygen from the oxy-tyrosinase form to the ortho position of the phenolic hydroxyl is adequate for the electrophilic attack reaction that gives rise to hydroxylation occurring.

Thermosetting benzoxazoles with endo-alkynyl groups: Excellent thermal stability and low dielectric loss

In this study, six thermosetting benzoxazole monomers with endo-alkynyl groups are prepared, and the effect of the endo-alkynyl groups and substituent group on the curing behavior and solubility of monomers, and on the thermal properties and dielectric properties of polybenzoxazoles are investigated. Our findings reveal that incorporating endo-alkynyl groups enhances the cross-linked network in the benzoxazole monomers, thereby improving their thermal stability, hydrophobicity, and dielectric constant. However, this modification also results in decreased solubility and curing properties of the monomers. In addition, the position of the fluorine atoms can affect the curing behavior of monomer and the dielectric properties of polybenzoxazoles. When a fluorine atom is positioned ortho to the cyano group, it impedes the curing of the cyanide group, which increases the curing reaction temperature. Moreover, while it is generally believed that the addition of fluorine typically lowers the dielectric constant of a material, the placement of fluorine atoms ortho to the cyano group can lead to overlapping electronic effects. This overlap may increase the polarity of the curing network, which increases the dielectric constant and dielectric loss of the polybenzoxazoles. Among the six thermosetting benzoxazole monomers studied, poly (2 F-JQ) containing m-diethynyl groups exhibit a 5 % thermal decomposition temperature (Td5) of 610 °C, and a low dielectric loss of 0.0045 at 1 MHz. Compared with other polybenzoxazoles, poly (2 F-JQ) possesses a moderate dielectric constant, excellent thermal stability, and extremely low dielectric loss. In summary, this study provides a new approach for preparing resins that feature high-temperature resistance and low dielectric loss.

Theoretical study on the isomerization mechanism of visible light-driven azobenzene-based materials

This article investigates the geometric structure and isomerization mechanism of 4,4-acetamidazobenzene molecules with halogen atoms (F, Cl, Br) substituted at four ortho positions through density functional theory (DFT) calculations. The calculation method was b3lyp/g, and the base set was def2-tzvp. According to DFT calculations, the ortho substitution of the halogen atoms differently distorted the molecular plane of the trans isomers, resulting in obvious absorption peaks in the visible range, giving them visible-light driven properties. In addition, the transition state (TS) of the cis–trans isomerization reaction in the ground state was also found. To study the molecular isomerization mechanism, the potential energy surfaces (PESs) of the ground state (S0), first excited state (S1), and second excited state (S2) of halogen substituted azobenzene derivatives were scanned separately. Through the potential energy surface curve of the ground state, the mechanism of isomerization reaction in the ground state of the four molecules is realized through a rotation-assisted inversion pathway, which is consistent with the calculation of TS. When the molecules are in the excited states, the isomerization pathways are realized through rotation pathways.

Site‐Selective Ortho/Ipso C−H Difunctionalizations of Arenes using Thianthrene as a Leaving Group

AbstractSite‐selective ortho/ipso C−H difunctionalizations of aromatic compounds were designed to afford polyfunctionalized arenes including challenging 1,2,3,4‐tetrasubstituted ones (62 examples, up to 97 % yields). To ensure the excellent regioselectivity of the process while keeping high efficiency, an original strategy based on a “C−H thianthenation/Catellani‐type reaction” sequence was developed starting from simple arenes. Non‐prefunctionalized arenes were first regioselectively converted into the corresponding thianthrenium salts. Then, a palladium‐catalyzed, norbornene (NBE)‐mediated process allowed the synthesis of ipso‐olefinated/ortho‐alkylated polyfunctionalized arenes using a thianthrene as a leaving group (revisited Catellani reaction). Pleasingly, using a commercially available norbornene (NBE) and a unique catalytic system, synthetic challenges known for the Catellani reaction with aryl iodides were smoothly and successfully tackled with the “thianthrenium” approach. The protocol was robust (gram‐scale reaction) and was widely applied to the two‐fold functionalization of various arenes including bio‐active compounds. Moreover, a panel of olefins and alkyl halides as coupling partners was suitable. Pleasingly, the “thianthrenium” strategy was successfully further applied to the incorporation of other groups at the ipso (CN/alkyl/H, aryl) and ortho (alkyl, aryl, amine, thiol) positions, showcasing the generality of the process.

Site-Selective Ortho/Ipso C-H Difunctionalizations of Arenes using Thianthrene as a Leaving Group.

Site-selective ortho/ipso C-H difunctionalizations of aromatic compounds were designed to afford polyfunctionalized arenes including challenging 1,2,3,4-tetrasubstituted ones (62 examples, up to 97 % yields). To ensure the excellent regioselectivity of the process while keeping high efficiency, an original strategy based on a "C-H thianthenation/Catellani-type reaction" sequence was developed starting from simple arenes. Non-prefunctionalized arenes were first regioselectively converted into the corresponding thianthrenium salts. Then, a palladium-catalyzed, norbornene (NBE)-mediated process allowed the synthesis of ipso-olefinated/ortho-alkylated polyfunctionalized arenes using a thianthrene as a leaving group (revisited Catellani reaction). Pleasingly, using a commercially available norbornene (NBE) and a unique catalytic system, synthetic challenges known for the Catellani reaction with aryl iodides were smoothly and successfully tackled with the "thianthrenium" approach. The protocol was robust (gram-scale reaction) and was widely applied to the two-fold functionalization of various arenes including bio-active compounds. Moreover, a panel of olefins and alkyl halides as coupling partners was suitable. Pleasingly, the "thianthrenium" strategy was successfully further applied to the incorporation of other groups at the ipso (CN/alkyl/H, aryl) and ortho (alkyl, aryl, amine, thiol) positions, showcasing the generality of the process.

Synthesis of a New Class of β-Carbonyl Selenides Functionalized with Ester Groups with Antioxidant and Anticancer Properties-Part II.

A series of phenyl β-carbonyl selenides with o-ester functionality substituted on the oxygen atom with chiral and achiral alkyl groups was synthesized. All compounds are the first examples of this type of organoselenium derivatives with an ester substituent in the ortho position. The obtained derivatives were tested as antioxidants and anticancer agents to see the influence of an ester functionality on the bioactivity of β-carbonyl selenides by replacing the o-amide group with an o-ester group. The best results as an antioxidant agent were observed for O-((1R,2S,5R)-(-)-2-isopropyl-5-methylcyclohexyl)-2-((2-oxopropyl)selanyl)benzoate. The most cytotoxic derivative against breast cancer MCF-7 cell lines was O-(methyl)-2-((2-oxopropyl)selanyl)benzoate and against human promyelocytic leukemia HL-60 was O-(2-pentyl)-2-((2-oxopropyl)selanyl)benzoate.

Ring Fusion Elevates the Electronic Mobility of Azabenzannulated Perylene Diimide.

The backwardness of n-type organic semiconductors still exists compared with the p-type counterparts. Thus, the development of high-performance n-type organic semiconductors is of great importance for organic electronic devices and their integrated circuits. In recent years, azabenzannulated perylene diimide (PDI), as one of immense bay-region-annulated PDI derivatives, has drawn considerable attentions. However, the electronic mobilities of azabenzannulated PDI derivatives are barely satisfactory. In this contribution, the peripheral benzene ring in azabenzannulated PDI 2 was fused to the ortho position by intramolecular C-H arylation cyclization. This endows the resultant azabenzannulated PDI 4 a planar configuration as well as electron deficient pentagonal ring. As a result, the electronic mobility of 4 is almost two orders of magnitude higher than that of the nonfused azabenzannulated PDI 2. This work shall pave a new avenue in elevating the performance of azabenzannulated PDI in organic electronics.

Pendant Group Functionalization of Cyclic Olefin for High Temperature and High-Density Energy Storage.

High-temperature flexible polymer dielectrics are critical for high-power-density energy storage and conversion under harsh operating conditions. These types of dielectrics will need to simultaneously possess a high bandgap, dielectric constant and glass transition temperature - a substantial challenge when designing novel dielectric polymers. In this work, by varying halogen substituents of an aromatic pendant hanging off a bicyclic mainchain polymer, a class of high-temperature olefins with adjustable thermal stability are obtained, all with uncompromised large bandgaps. Halogens substitution of the pendant groups at para or ortho position of polyoxanorborneneimides (PONB) imparts it with tunable high glass transition temperature from ∼220 to 245°C, while with also moderate dielectric constant of ∼ 2.8-3.0 and high breakdown strength of ∼625-800MV/m. A high energy density of 7.1 J/cc at 200°C is achieved with p-POClNB, representing the highest reported energy density among all-organic homo-polymer dielectrics. Molecular dynamic simulations and ultrafast infrared spectroscopy were used to probe the free volume element distribution and chain relaxations of the polymers to provide insights to the dielectric thermal properties. An increase in free volume element is observed with the change in the pendant group from fluorine to bromine at the para position; however, a decrease in free volume element is observed as we change the pendant group from fluorine to chlorine at the ortho position because of the steric hindrance. Overall, the dielectric constant and band gap remain stable while the glass transition temperature changes more obviously. Consequently, by proper designing the pendant groups, the thermal stability of PONB can be improved for harsh condition electrification. This article is protected by copyright. All rights reserved.

Innovative Approach to Chiral Polyurethanes: Asymmetric Copolymerization with Isocyanates.

The introduction of nitrogen-containing functional groups to chiral polymer backbones enables the tailoring of physical properties and offers opportunities for further post-polymerization modification. However, the substrate scope of such polymers is extremely limited because monomers having nitrogen-containing groups can change coordination state with respect to the metal centers, thus decreasing the activity and enantioselectivity and even poisoning the catalyst completely. In this paper, we report our attempts to carry out the asymmetric copolymerization of meso-epoxide with highly reactive isocyanates. In particular, we found that biphenol-linked bimetallic Co(III) complexes with multiple chiral centers are very efficient in catalyzing this asymmetric copolymerization reaction, affording optically active polyurethanes with a completely alternating nature and a high enantioselectivity of up to 94% ee. Crucially, we identified that the steric hindrance at the phenolate ortho position of the ligand strongly influences the catalytic activity and product enantioselectivity. In addition, density functional theory calculations revealed that the highly sterically bulky substituents change the mechanism from bimetallic to monometallic, and result in the unexpected inversion of the chiral induction direction. Moreover, the high stereoregularity of the produced polyurethanes enhances their thermal stability. This study offers a versatile methodology for the synthesis of chiral polymers containing nitrogen functionalities.

Innovative Approach to Chiral Polyurethanes: Asymmetric Copolymerization with Isocyanates

AbstractThe introduction of nitrogen‐containing functional groups to chiral polymer backbones enables the tailoring of physical properties and offers opportunities for further post‐polymerization modification. However, the substrate scope of such polymers is extremely limited because monomers having nitrogen‐containing groups can change coordination state with respect to the metal centers, thus decreasing the activity and enantioselectivity and even poisoning the catalyst completely. In this paper, we report our attempts to carry out the asymmetric copolymerization of meso‐epoxide with highly reactive isocyanates. In particular, we found that biphenol‐linked bimetallic Co(III) complexes with multiple chiral centers are very efficient in catalyzing this asymmetric copolymerization reaction, affording optically active polyurethanes with a completely alternating nature and a high enantioselectivity of up to 94 % ee. Crucially, we identified that the steric hindrance at the phenolate ortho position of the ligand strongly influences the catalytic activity and product enantioselectivity. In addition, density functional theory calculations revealed that the highly sterically bulky substituents change the mechanism from bimetallic to monometallic, and result in the unexpected inversion of the chiral induction direction. Moreover, the high stereoregularity of the produced polyurethanes enhances their thermal stability, and they can be selectively decomposed into oxazolidinones. This study offers a versatile methodology for the synthesis of chiral polymers containing nitrogen functionalities.

N-Bu4NI/K2S2O8-MEDIATED C-N COUPLING BETWEEN ALDEHYDES AND AMIDES.

n-Bu4NI/K2S2O8 mediated C-N coupling between aldehydes and amides is reported. A strong electronic effect is observed on the aromatic aldehyde substrates. The transformylation from aldehyde to amide takes place exclusively when an aromatic aldehyde bears electron-donating groups at either the ortho or para position of the formyl group, while the cross-dehydrogenative coupling dominates in the absence of these groups. Both the density functional theory (DFT) thermochemistry calculations and experimental data support the proposed single electron transfer mechanism with the formation of an acyl radical intermediate in the cross-dehydrogenative coupling. The n-Bu4NI/K2S2O8 mediated oxidative cyclization between 2-aminobenzamide and aldehydes is also reported, with four quinazolin-4(3H)-ones prepared in 65-99% yields.

The influence of debromination and TR on the microstructure and properties of CMSMs

One unique challenging in achieving advanced carbon molecular sieve membranes (CMSMs) is tailoring their gas separation properties from the precursor. To clarify this, we designed two homo-polyimides with a bromine (PI-Br) and a hydroxyl (PI-OH) groups in the ortho position of imide group, and carbonized them into CMSMs at 550 °C (PI-Br-550 and PI-OH-550). There are debromination (510 °C) and carbonization occurred for PI-Br-550 whereas the PI-OH underwent thermally rearrangement (TR, 450 °C) and then pyrolysis to CMSM. After carbonization, both CMSMs showed excellent gas separation properties, with their CO2/CH4 separation performance surpassed the latest 2019 pure-gas and 2018 mixed-gas trade-off curves, additionally, the PI-Br-550 demonstrated a relatively smaller CO2 permeability (12462 vs 14,253 Barrer), lower PCO2 increment ratio (199 vs 1480), and less CO2/CH4 dropping ratio (69.7 to 45.5 vs 87.5 to 36.1) than the PI-OH-550 from their precursors. Their XPS, Raman, and WXRD characterization results indicated that debromination boosts the gas separation performance of CMSM by creating more ultra-micropore “plate” (pyrrolic-N of 36.0 % vs 19.0 %) and smaller d-spacing (3.89 vs 4.15 Å) than the TR precursor, which boosts the permeability of CMSM is due to the high stability of PBO intermediates that retarded the decomposition of the polymer main chian and caused some big pores. The above results provided a good route to get highly efficient CMSM by molecular designing of their precursors.

Precise Modulation of CO2 Sorption in Ti8Ce2-Oxo Clusters: Elucidating Lewis Acidity of the Ce Metal Sites and Structural Flexibility.

Investigating the structure-property correlation in porous materials is a fundamental and consistent focus in various scientific domains, especially within sorption research. Metal oxide clusters with capping ligands, characterized by intrinsic cavities formed through specific solid-state packing, demonstrate significant potential as versatile platforms for sorption investigations due to their precisely tunable atomic structures and inherent long-range order. This study presents a series of Ti8Ce2-oxo clusters with subtle variations in coordinated linkers and explores their sorption behavior. Notably, Ti8Ce2-BA (BA denotes benzoic acid) manifests a distinctive two-step profile during the CO2 adsorption, accompanied by a hysteresis loop. This observation marks a new instance within the metal oxide cluster field. Of intrigue, the presence of unsaturated Ce(IV) sites was found to be correlated with the stepped sorption property. Moreover, the introduction of an electrophilic fluorine atom, positioned ortho or para to the benzoic acid, facilitated precise control over gate pressure and stepped sorption quantities. Advanced in situ techniques systematically unraveled the underlying mechanism behind this unique sorption behavior. The findings elucidate that robust Lewis base-acid interactions are established between the CO2 molecules and Ce ions, consequently altering the conformation of coordinated linkers. Conversely, the F atoms primarily contribute to gate pressure variation by influencing the Lewis acidity of the Ce sites. This research advances the understanding in fabricating metal-oxo clusters with structural flexibility and provides profound insights into their host-guest interaction motifs. These insights hold substantial promise across diverse fields and offer valuable guidance for future adsorbent designs grounded in fundamental theories of structure-property relationships.

A comparative DFT study of monosubstituted silabenzene and benzene structures: Effects of Si atom incorporation in benzene ring

In the present study, monosubstituted structures with 16 substitutions in the ortho, meta, and para positions of silabenzene have been comprehensively compared with similar structures in benzene. This study aimed to investigate the effect of Si atom incorporation in the benzene ring. This comparison investigated the chemical properties, including structural geometries of molecules, molecular orbitals and reactivity, ring aromaticity, and excitation energy of each monosubstituted silabenzene and benzene structure. The density functional theory (DFT) at the B3LYP/6–311G++(d,p) level of theory was used to perform all relevant calculations. In addition to changes in ring geometry values and electron donating, the results showed that the Si atom incorporation in benzene ring and its monosubstituted derivatives in different positions caused a significant decrease in LUMO, chemical hardness, ring aromaticity, excitation energy, and a significant increase in HOMO, electrophilicity, nucleophilicity, and NMR chemical shift values. Among the positions of the substituents concerning the Si atom in the ring, the ortho and para positions exhibited the most optimal values. In contrast, the meta position displayed different values compared to the ortho and para positions. This difference is attributed to the electron-withdrawing effects of the substituents. Also, among substitutions, electron-donating substitutions especially -NH2 compared to electron-withdrawing substitutions especially -NO2 decreased HOMO, electrophilicity, excitation energy, and increased LUMO, chemical hardness, nucleophilicity, and ring aromaticity.

Intramolecular singlet fission: Quantum dynamical simulations including the effect of the laser field.

In the previous work [Reddy et al., J. Chem. Phys. 151, 044307 (2019)], we have analyzed the dynamics of the intramolecular singlet fission process in a series of prototypical pentacene-based dimers, where the pentacene monomers are covalently bonded to a phenylene linker in ortho, meta, and para positions. The results obtained were qualitatively consistent with the experimental data available, showing an ultrafast population of the multiexcitonic state that mainly takes place via a mediated (superexchange-like) mechanism involving charge transfer and doubly excited states. Our results also highlighted the instrumental role of molecular vibrations in the process as a sizable population of the multiexcitonic state could only be obtained through vibronic coupling. Here, we extend these studies and investigate the effect of the laser field on the dynamics of intramolecular singlet fission by explicitly including the coupling to the laser field in our model. In this manner, and by selectively tuning the laser field to the different low-lying absorption bands of the systems investigated, we analyze the wavelength dependence of the intramolecular singlet fission process. In addition, we have also analyzed how the nature of the initially photoexcited electronic state (either localized or delocalized) affects its dynamics. Altogether, our results provide new insights into the design of intramolecular singlet fission-active molecules.

Synthesis and evaluation of pyridine-3-carboxamide analogs as effective agents against bacterial wilt in tomatoes

This study focused on developing novel pyridine-3-carboxamide analogs to treat bacterial wilt in tomatoes caused by Ralstonia solanacearum. The analogs were synthesized through a multistep process and their structures confirmed using spectroscopy. Molecular docking studies identified the most potent analog from the series. A specific analog, compound 4a, was found to significantly enhance disease resistance in tomato plants infected with R. solanacearum. The structure–activity relationship analysis showed the positions and types of substituents on the aromatic rings of compounds 4a–i strongly influenced their biological activity. Compound 4a, with a chloro group at the para position on ring C and hydroxyl group at the ortho position on ring A, was exceptionally effective against R. solanacearum. When used to treat seeds, the analogs displayed remarkable efficacy, especially compound 4a which had specific activity against bacterial wilt pathogens. Compound 4a also promoted vegetative and reproductive growth of tomato plants, increasing seed germination and seedling vigor. In plants mechanically infected with bacteria, compound 4a substantially reduced the percentage of infection, pathogen quantity in young tissue, and disease progression. The analogs were highly potent due to their amide linkage. Molecular docking identified the best compounds with strong binding affinities. Overall, the strategic design and synthesis of these pyridine-3-carboxamide analogs offers an effective approach to targeting and controlling R. solanacearum and bacterial wilt in tomatoes.

Study of mesomorphism behavior and protonation-induced emission of symmetrical benzalazines

Rod-shaped and polycatenar symmetric benzalazines with protonation-induced emission were synthesized, characterized, and studied for their thermal and optical behavior. Benzalazines lacking hydroxy groups at the ortho position did not show luminescence in the solid state or solution. In the presence of HCl (either in solution or vapor form) these compounds became good emitters. The protonation of azine nitrogen that may hinder the NN bond rotation by intermolecular interactions toward aggregates provided an explanation for the emission characteristics observed. The protonation-induced emission was thermally reversible. A benzalazine derived from 4-alkoxysalicylaldehyde with AIE property was prepared. For this compound with ortho-OH groups, the optical properties were not affected by the presence of acidic media. It exhibited a stable SmC phase characterized by POM, DSC, and XRD. The luminescence capability of the molecular arrangement within the smectic phase was investigated. The intense yellow-green emission in the crystals decreased significantly at the phase transition due to the non-radiative decay that occurs with increasing temperature, and loss of intermolecular H-bonding which prevents molecular rotations in the crystal.