Ring Substituents Research Articles

O- and N-Difluoromethylation of 2-Pyridones with Chlorodifluoromethane

Difluoromethylation of various 2-pyridones with the available industrial reagent chlorodifluoromethane (Freon-22) has been studied. Some relationships between the ratio of difluoromethylation products and the reaction conditions, as well as the presence of substituents in the pyridine ring, have been found. The possibility of obtaining difluoromethylation products at the nitrogen atom, in some cases with a preparative yield, has been investigated.

Synthesis, characterization and photophysical properties of phthalimide-pyrazole compounds: Effect of the substituent in the pyrazole ring on the crystal structures

Four phthalimide-pyrazole derivative compounds (L1 = H, L2 = NO2, L3 = Br, and L4 = I) were synthesized and fully characterized. Single crystals of each compound were obtained, and their conformational and supramolecular structures were analyzed. The four crystal structures (L1 to L4) are stabilized by different intermolecular interactions and therefore have different characteristics from each other. L1 is dominated by long-range Van der Waals forces and not by short hydrogen bonds. On the other hand, L2 packs into a molecular sheet along the b and c axes. L3 and L4 have a common monoclinic structure (P21/c) and thus allow stabilization of the respective compounds by halogen-halogen interactions (Br–Br, I–I) and σ-hole effects. In all compounds, these interactions, whether Van der Waals forces, π‧‧‧‧π stacking or halogen bonds, are responsible for their packing and molecular stability. Therefore, it was concluded that the substituent on the pyrazole ring is the determining factor in their crystallization. In addition, photophysical and theoretical studies showed that the compounds exhibit emission in the presence of DCM, acetonitrile (MeCN), and DMSO, primarily due to the HOMO-LUMO orbitals in the phthalimide ring.

Dihydro‐1H‐Pyrazoles as Donor Blocks in Donor–Acceptor Chromophores for Electro‐Optics: A DFT Study of Hyperpolaizability and Electronic Excitations

ABSTRACTA diverse set of promising donors for donor–acceptor chromophores based on dihydro‐1H‐pyrazole (pyrazoline) for use in electro‐optics was investigated using DFT at M06‐2X/aug‐cc‐pVDZ level of theory. These calculations showed that it is possible to achieve a molecular hyperpolarizability of up to 1700*10−30 esu (up to three times higher compared to conventional diethylaniline donors) for a simple tricyanofuran‐based acceptor by carefully tuning the donor structure. It was shown that the molecular hyperpolarizability is mainly affected by the substituents in the aryl rings in positions 3 and 1 of the pyrazoline cycle, while the substituents of the aryl ring in position 5 and the pyrazoline ring itself can be varied without significant effects on the hyperpolarizability. For one of the compounds, a detailed study of the lowest energy electronic excitation was performed using the TD‐DFT, confirming the role of the pyrazoline ring as a secondary donor.

Investigation of Apoptotic and Anticancer Effects of 2-substituted Benzothiazoles in Breast Cancer Cell Lines: EGFR Modulation and Mechanistic Insights.

Benzothiazole derivatives, a class of heterocyclic compounds, exhibited diverse biological activities influenced by substituents in the thiazole ring. This study aimed to synthesize these compounds with two functional groups to investigate their potential as anticancer agents, particularly against breast cancer. While previous research demonstrated the efficacy of 2-substituted benzothiazoles against glioma and cervical and pancreatic cancer cells, there is a gap in studies targeting breast cancer. The synthesized compounds were tested in vitro using MCF-7, MDA-MB-231, and MCF-10A cell lines, with Doxorubicin as the positive control. Various assays were conducted, including Annexin V/PI, cell cycle analysis, wound healing, and measurement of mitochondrial membrane potential. Protein expression of EGFR and transcription levels of apoptosis-related genes (Bax and Bcl-xL) and cancer progression-related genes (JAK, STAT3, ERK, AKT, mTOR) were analyzed. Additionally, the balance between antioxidants and oxidants was evaluated by measuring TAS and TOS levels. Our findings revealed that benzothiazole compounds significantly inhibited breast cancer cell growth by reducing cell motility, disrupting mitochondrial membrane potential, and inducing cell cycle arrest in the sub-G1 phase. These compounds increased reactive oxygen species accumulation, leading to cell death. Furthermore, they decreased EGFR protein levels, increased Bax gene transcription, and downregulated the expression of genes such as JAK, STAT3, ERK, AKT, and mTOR. In conclusion, benzothiazole derivatives exhibited potent inhibitory effects on breast cancer in vitro by promoting apoptosis, downregulating EGFR activity, and modulating key signaling pathways, including JAK/STAT, ERK/MAPK, and PI3K/Akt/mTOR. These results highlighted the potential of benzothiazole derivatives as novel therapeutic agents for breast cancer treatment.

Synthesis, structure, and solution chemistry of mixed-ligand oxidovanadium(IV) complexes incorporating ONO donor hydrazone ligands

Four mixed-ligand oxidovanadium(IV) complexes, [VIVO(L1-4)(phen)], 1-4, incorporating tridentate dibasic ONO donor hydrazone ligands (H2L1-4, general abbreviation H2L) derived from the condensation of 2-picolinyl hydrazide with 2-hydroxy acetophenone and its 5-substituted derivatives as primary ligands and 1,10-phenanthroline (phen) as auxiliary ligand have been synthesized in excellent yields. The complexes were characterized by elemental analyses, magnetic susceptibility measurements, and various spectral (e.g. IR, UV–Vis and EPR) studies. The molecular structure of one of the four complexes has been determined by single-crystal X-ray diffractometry. In 1, the hydrazone ligand is meridionally disposed of, coordinating through one enolic-O, one phenolic-O, and one imine-N. The other basal position is occupied by one pyridine-N of the phen moiety. The axial positions are occupied by one oxido-O atom and the other pyridine-N atom of the phen moiety. The complexes are paramagnetic with one unpaired electron (μeff ≈ 1.73 BM), suggesting no interaction with the neighboring molecules and are EPR active. The complexes display two d-d transitions, one near 725 and the other near 840 nm due to d xy → d xz , d yz and d xy → d x 2 − y 2 transitions, respectively. The other d-d transition associated with d xy → d z 2 transition was not observed as it falls in the UV region, which is masked by highly intense intra-ligand transitions. The complexes display one-electron oxidation peaks in the +0.75 to +0.89 V vs. Ag/AgCl region in the CH3CN solution that show a linear relationship with the Hammett parameter (σ) of the substituents in the aryloxy ring.

Synthesis and Properties of Highly Tilted Antiferroelectric Liquid Crystalline (R) Enantiomers.

This work reports the synthesis method and various properties of four rod-like antiferroelectric (R) laterally substituted enantiomers, with or without fluorine atoms used as substituents in the benzene ring. The influence of fluorine substitution on the mesophase temperature range was determined. The synthesized compounds are three-ring rod-like smectics with a chiral center based on (R)-(-)-2-octanol. Their chemical and optical purity was checked using high-performance liquid chromatography (HPLC). Two newly synthesized enantiomers and three previously reported (R) enantiomers were used to formulate two antiferroelectric mixtures. The mesomorphic behavior was characterized by polarizing optical microscopy, differential scanning calorimetry, and X-ray diffraction (XRD). The helical pitch and tilt angle measurements were done using the selective light reflection phenomenon and the electro-optical method, respectively. All the enantiomers exhibit a wide temperature range of the antiferroelectric phase, with a high tilt angle. Furthermore, the enantiomer with lateral fluorine substitution in the ortho position has a very long helical pitch (more than 2.0 µm), relatively low enthalpy of melting point, and a tilt angle close to 45 degrees. The designed (R) enantiomers can be useful for formulating eutectic mixtures for further use in various devices, including photonics and optoelectronics.

Synthesis of kanamycin-azole hybrids and investigation of their antifungal activities

The World Health Organization (WHO) recognizes Candida albicans and Cryptococcus neoformans as the critical priority fungal pathogens for which therapeutic solutions are needed. Azole-based antifungal agents, including triazoles, diazoles, and thiazoles, are widely used in the treatments for fungal infections. In light of past successes in the transformation of antibacterial kanamycin into antifungal derivatives via chemical modifications, a new library of kanamycin-azole hybrids was synthesized and tested against a panel of azole-resistant and susceptible Candida and Cryptococcus strains. Structure activity relationship (SAR) studies revealed pivotal roles for antifungal activity of the azole ring (imidazole vs triazole) and halogen substituents on the benzene ring (F vs Cl). Most notably, hybrids 13, 14 and 15 were active against resistant C. albicans, C. tropicalis and C. neoformans strains and non-toxic towards mammalian cells. Mode of action investigations using fluorogenic dyes, (SYTOXTM) showed the fungal active compounds could permeabilize fungal membranes even at ¼ MICs. These findings reveal novel azole-based antifungals that could offer new therapeutic options for candidiasis and cryptococcosis.

RP-HPLC Study of the Complexation of Acetamiprid, Imidacloprid and Carboxin Guest Molecules With Thiophosphorylated Calix [6] Arene in Dimethylformamide-Acetonitrile-Water Mobile Phase.

Reversed-phase high-performance liquid chromatography was used to study the host-guest complexation of thiophosphacalixarenes (TPC 1-3) with acetamiprid, imidacloprid and carboxin as guests. The Onyx Monolithic C 18 column (150 × 0.1mm) and Phenomenex® were used with UV detection at 254nm. The mobile phase consisted of dimethylformamide-acetonitrile-water. The association constant of the 1:1 guest-host complexes was determined from the relationship between the retention factor of the guest and concentration of the thiophosphacalix [6] arene host in the mobile phase. The stability constants are influenced by size, nature, position and quantity of substituents in the benzene ring of the calixarene skeleton. The detection limits for TPC 1, TPC 2 and TPC 3 are 0.95, 1.20 and 1.40μg/mL, while the quantification limits are 2.85, 3.60 and 4.20μg/mL for TPC 1, TPC 2 and TPC 3, respectively.

Efficient Production of 4’-Hydroxydihydrochalcones Using Non-Conventional Yeast Strains

The quest for novel therapeutic agents has rekindled interest in natural products, particularly those derived from biotransformation processes. Dihydrochalcones, a class of plant secondary metabolites, exhibit a range of pharmacological properties. Chalcone and dihydrochalcone compounds with the characteristic 4’-hydroxy substitution are present in ‘dragon’s blood’ resin, known for its traditional medicinal uses and complex composition, making the isolation of these compounds challenging. This study investigates the efficient production of 4′-hydroxydihydrochalcones using non-conventional yeast strains. We evaluated the biotransformation efficiency of various 4′-hydroxychalcone substrates utilizing yeast strains such as Yarrowia lipolytica KCh 71, Saccharomyces cerevisiae KCh 464, Rhodotorula rubra KCh 4 and KCh 82, and Rhodotorula glutinis KCh 242. Our findings revealed that Yarrowia lipolytica KCh 71, Rhodotorula rubra KCh 4 and KCh 82, and Rhodotorula glutinis KCh 242 exhibited the highest conversion efficiencies, exceeding 98% within one hour for most substrates. The position of methoxy substituents in the chalcone ring significantly influenced hydrogenation efficiency. Moreover, we observed isomerization of trans-4′-hydroxy-2-methoxychalcone to its cis isomer, catalyzed by light exposure. This study underscores the potential of using yeast strains for the sustainable and efficient production of dihydrochalcones, providing a foundation for developing new therapeutic agents and nutraceuticals.

Effects of Ring Functionalization in Anthracene-Based Cyclophanes on the Binding Properties Toward Nucleotides and DNA.

Supramolecular recognition of nucleobases and short sequences is an emerging research field focusing on possible applications to treat many diseases. Controlling the affinity and selectivity of synthetic receptors to target desired nucleotides or short sequences is a highly challenging task. Herein, we elucidate the effect of substituents in the phenyl ring of the anthracene-benzene azacyclophane on the recognition of nucleoside triphosphates (NTPs) and double-stranded DNA. We show that introducing phenyl rings increases the affinity for NTPs 10-fold and implements groove and intercalation binding modes with double-stranded DNA. NMR studies and molecular modeling calculations support the ability of cyclophanes to encapsulate nucleobases as part of nucleotides.

Insight into efficient degradation of pentacyclic and hexacyclic sulfonamide antibiotics by synthetic trivalent copper: Performance and mechanism

High valent metal species, including Mn(III), Fe(IV) and Cu(III), have been identified as key intermediates in the degradation of pollutants in many advanced oxidation processes. However, unlike Mn(III) and Fe(IV), the current exploration of the reaction activity and selective oxidation mechanism of Cu(III) towards pollutants with different structures is still quite limited. Herein, the copper(III) periodate was synthesized to investigate the reactivity towards six sulfonamide antibiotics (SAs) including typical two pentacyclic structures (sulfamethoxazole (SMX) and sulfathiazole (STZ)) and four hexacyclic structures (sulfadiazine (SDZ), sulfamerazine (SMR), sulfamonomethoxine (SMM) and sulfapyridine (SPD)). The results indicated that all SAs almost completely removed by Cu(III) system after 10 min with the molar ratio of approximately 3:1 (Cu(III):SAs) and Cu(III) direct oxidation played the most important role. SAs with 6-ring substituents were more readily degraded by Cu(III) than SAs with 5-ring substituents, and the presence of electron-rich group such as -CH3 and -S in ring substituent increased the reactivity towards Cu(III). The introduction of coexisting anions (Cl−, SO42− and HCO3−) hardly affected the degradation of SAs by Cu(III) oxidation, while the addition of HA to some extent inhibited SAs degradation. The solution pH greatly affected the degradation of SAs by Cu(III) and the removal efficiencies of SAs roughly followed the rule of neutral > acidic > alkaline. The degradation mechanism of SAs with 5-ring and 6-ring substituents in Cu(III) system mainly included amino nitration, self-coupling, hydroxylation, S-N cleavage in SAs with 5-ring substituents and SO2 extrusion in SAs with 6-ring substituents. Although the real water matrix inhibited the degradation of SAs to varying degrees, Cu(III) still played a satisfactory performance on SAs degradation especially for electron-rich structure.

The Role of the Nitro Group on the Formation of Intramolecular Hydrogen Bond in the Methyl Esters of 1-Vinyl-Nitro-Pyrazolecarboxylic Acids

All reactions involving the nitrogen atom in 3(5)-substituted pyrazoles inevitably lead to a mixture of N-substituted 3- and 5- isomers due to tautomerism. The position of substituent can affect the behavior of N-vinyl isomers, in particular, the ability of some functional groups to form =C-H...O or =C-H...N weak hydrogen bonding type interaction with α-hydrogen of vinyl group due to steric reasons. Moreover, the additional substituents in the pyrazole ring can further influence the possibility and nature of specific intramolecular interactions. Here we have shown the effect of the nitro group on the formation of hydrogen bonds in methyl esters of 1-vinyl-4-nitro-3(5)- and 1-vinyl-5-nitro-3(5)-pyrazole carboxylic acids. A comprehensive study, including synthesis, quantum chemical calculations, NMR and XRD analysis, allowed to conclude that, contrary to expected, in the methyl ester of 1-vinyl-4-nitro-5-pyrazolecarboxylic acid, the formation of a planar conformation is unfavorable, preventing formation of a classical hydrogen bond. On the other hand, there is a hydrogen bond between the nitro group and vinyl group in 1-vinyl-5-nitro-pyrazolecarboxylic acids.

Privileged Scaffold Hybridization in the Design of Carbonic Anhydrase Inhibitors.

Human Carbonic Anhydrases (hCA) are enzymes that contribute to cancer's development and progression. Isoforms IX and XII have been identified as potential anticancer targets, and, more specifically, hCA IX is overexpressed in hypoxic tumor cells, where it plays an important role in reprogramming the metabolism. With the aim to find new inhibitors towards IX and XII isoforms, the hybridization of the privileged scaffolds isatin, dihydrothiazole, and benzenesulfonamide was investigated in order to explore how it may affect the activity and selectivity of the hCA isoforms. In this respect, a series of isatin thiazolidinone hybrids have been designed and synthesized and their biological activity and selectivity on hCA I, hCA II, hCA IX, and hCA XII explored. The new compounds exhibited promising inhibitory activity results on isoforms IX and XII in the nanomolar range, which has highlighted the importance of substituents in the isatin ring and in position 3 and 5 of thiazolidinone. In particular, compound 5g was the most active toward hCA IX, while 5f was the most potent inhibitor of hCA XII within the series. When both potency and selectivity were considered, compound 5f appeared as one of the most promising. Additionally, our investigations were supported by molecular docking experiments, which have highlighted the putative binding poses of the most promising compound.

Kinetics of uptake, translocation, and metabolism of organophosphate esters in japonica rice (Oryza sativa L.): Hydroponic experiment combined with model

Hydroponics combined with fugacity model was employed to investigate the kinetics of uptake, accumulation, and metabolism of organophosphate esters (OPEs) by japonica rice. The time-dependent process for uptake and accumulation of 5 OPEs and their diester-metabolites in both rice root and shoot fitted well with the pseudo-first-order kinetic model. The peak OPE accumulations in rice root and shoot were significantly positively or negatively correlated with their octanol-water partition coefficient (logKow) respectively, but not for their apparent accumulation rates. Root concentration factors (RCFs) and root-to-shoot translocation factors (TFs) of OPEs were found to be positively and negatively correlated with their logKow, respectively. Triphenyl phosphate with benzene ring substituents showed the highest RCF, but the lowest TF, because of its high potential for root adsorption due to the π electron-rich structures. Sterilized root exudates can hinder the root adsorption and absorption of OPEs from solution probably through competitive adsorption of OPEs with root surface. The first-hand transport and metabolism rates were also obtained by generating these rates to fit the dynamic fugacity model with the measurement values. The simulation indicated that the kinetics of OPE accumulation in rice plants may be controlled by multiple processes and physicochemical properties besides Kow.

Iridium Complexes with Bidentate Pyridinylidene/N-Amidate Ligands for Transfer Hydrogenation Catalysis.

A series of iridium pentamethylcyclopentadienyl (Cp*) complexes, [Cp*Ir(κ2-RLp/m)Cl], that contain the strongly coordinating bidentate ligands RLp/m were synthesized. The donor groups of the bidentate ligands were an N-amidate and either a para-pyridinylidene remote N-heterocyclic carbene (RLp) or a meta-pyridinylidene remote N-heterocyclic carbene (RLm). For each type of bidentate ligand, a set of iridium complexes was synthesized, which differed only according to the substituents (R) on the phenyl ring associated with the amidate group. The iridium complexes were all fully characterized and molecular structures were obtained by single-crystal X-ray diffraction studies for representative examples. The complexes were found to be good precatalysts in iso-propanol for the transfer hydrogenation of benzaldehyde to give benzyl alcohol. The catalytic activity correlated with the Hammett σm/p parameters of the phenyl ring substituents, with more electron-donating substituents leading to increased catalytic activity. In all cases, the meta-pyridinylidene complexes, [Cp*Ir(κ2-RLm)Cl], performed better than the corresponding para analogues, [Cp*Ir(κ2-RLp)Cl].

Synthesis, Structure, Electrochemical Properties, and Antioxidant Activity of Organogermanium(IV) Catecholate Complexes.

A series of novel organogermanium(IV) catecholates 1-9 of the general formula R'2Ge(Cat), where R' = Ph, Et, have been synthesized. Compounds were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of 1-3, 6, and 8 in crystal state were established using single-crystal X-ray analysis. The complexes are tetracoordinate germanium(IV) compounds containing a dioxolene ligand in a dianion (catecholato) form. Electrochemical transformations of target germanium(IV) complexes have been studied by cyclic voltammetry. The electro-oxidation mechanism of complexes 1-5, 7, and 10 (the related complex Ph2Ge(3,5-Cat) where 3,5-Cat is 3,5-di-tert-butylcatecholate) involves the consecutive formation of mono- and dicationic derivatives containing the oxidized forms of redox-active ligands. The stability of the generated monocations depends both on the hydrocarbon groups at the germanium atom and on the substituents in the catecholate ring. Compounds 6, 8, and 9 are oxidized irreversibly under the electrochemical conditions with the formation of unstable complexes. The radical scavenging activity and antioxidant properties of new complexes were estimated in the reaction with DPPH radical, ABTS radical cation, and CUPRACTEAC assay. It has been found that compounds 8 and 9 with benzothiazole or phenol fragments are more active in DPPH test. The presence of electron-rich moieties in the catecholate ligand makes complexes 5 and 7-9 more reactive to ABTS radical cation. The value of CUPRACTEAC for organogermanium(IV) catecholates varies from 0.23 to 1.45. The effect of compounds 1-9 in the process of lipid peroxidation of rat liver (Wistar) homogenate was determined in vitro. It was found that most compounds are characterized by pronounced antioxidant activity. A feature of complexes 1, 3, and 5-9 is the intensification of the antioxidant action with the incubation time. In the presence of additives of complexes 3, 5, 6, and 8, an induction period was observed during the process of lipid peroxidation.

Discovery, Characterization and Engineering of the Free l-Histidine C4-Prenyltransferase.

Prenylation of amino acids is a critical step for synthesizing building blocks of prenylated alkaloid family natural products, where the corresponding prenyltransferase that catalyzes prenylation on free l-histidine (l-His) has not yet been identified. Here, we first discovered and characterized a prenyltransferase FunA from the antifungal agent fungerin pathway that efficiently performs C4-dimethylallylation on l-His. Crystal structure-guided engineering of the prenyl-binding pocket of FunA, a single M181A mutation, successfully converted it into a C4-geranyltransferase. Furthermore, FunA and its variant FunA-M181A show broad substrate promiscuity toward substrates that vary in substituents of the imidazole ring. Our work furthers our knowledge of free amino acid prenyltransferase and expands the arsenal of alkylation biocatalysts for imidazole-containing small molecules.

Unraveling the Potential of Vitamin B3-Derived Salts with a Salicylate Anion as Dermal Active Agents for Acne Treatment.

This study is focused on the utilization of naturally occurring salicylic acid and nicotinamide (vitamin B3) in the development of novel sustainable Active Pharmaceutical Ingredients (APIs) with significant potential for treating acne vulgaris. The study highlights how the chemical structure of the cation significantly influences surface activity, lipophilicity, and solubility in aqueous media. Furthermore, the new ionic forms of APIs, the synthesis of which was assessed with Green Chemistry metrics, exhibited very good antibacterial properties against common pathogens that contribute to the development of acne, resulting in remarkable enhancement of biological activity ranging from 200 to as much as 2000 times when compared to salicylic acid alone. The molecular docking studies also revealed the excellent anti-inflammatory activity of N-alkylnicotinamide salicylates comparable to commonly used drugs (indomethacin, ibuprofen, and acetylsalicylic acid) and were even characterized by better IC50 values than common anti-inflammatory drugs in some cases. The derivative, featuring a decyl substituent in the pyridinium ring of nicotinamide, exhibited efficacy against Cutibacterium acnes while displaying favorable water solubility and improved wettability on hydrophobic surfaces, marking it as particularly promising. To investigate the impact of the APIs on the biosphere, the EC50 parameter was determined against a model representative of crustaceans─Artemia franciscana. The majority of compounds (with the exception of the salt containing the dodecyl substituent) could be classified as "Relatively Harmless" or "Practically Nontoxic", indicating their potential low environmental impact, which is essential in the context of modern drug development.

Investigation of substituent effects on the electronic structure and antiviral activity of favipiravir derivatives for Covid-19 treatment using DFT and molecular docking

In this study, Density-functional theory/Time-dependent density-functional theory (DFT/TDDFT) and Molecular docking method was used to investigate the effect of methyl acetate, tetrahydrofuran and cyanobenzylidene substituents on the electronic structure and antiviral activity of favipiravir for treating COVID-19. The DFT and TDDFT computations were employed using the Gaussian 09 software package. The values were calculated using the 6-311++G(d, p) basis set and the hybrid B3LYP functional method. Autodock vina software was used for simulations to better predictions and to validate the modified compounds' binding affinities and poses. Results of the study indicate that compounds 1 to 6 all displayed a planar structure, where the pyrazine ring, carboxamide, hydroxyl groups, and other substituents are all situated within the same plane. In addition, the energy gaps (Egap) of these six compounds (Cpd 1, 2, 3, 4, 5, and 6) were compared. The significant dipole moment and binding affinity achieved implies a particular orientation for binding within the target protein, signaling the anticipated strength of the binding interaction. In all six compounds, the electrophilic domain is situated in the vicinity of the amine functional group within the carboxamide compound, whereas the nucleophilic domain encompasses both the carbonyl and hydroxyl groups. The most negatively charged sites are susceptible to electrophilic interactions. In conclusion, compounds 5 and 6 exhibit a high binding affinity of the target protein, while compound 6 has a high energy gap, which could enhance its antiviral activity against the COVID-19 virus.

Photochemical Generation and Characterization of C-Aminophenyl-Nitrilimines: Insights on Their Bond-Shift Isomers by Matrix-Isolation IR Spectroscopy and Density Functional Theory Calculations.

The intriguing ability of C-phenyl-nitrilimine to co-exist as allenic and propargylic bond-shift isomers motivated us to investigate how substituents in the phenyl ring influence this behavior. Building on our previous work on the meta- and para-OH substitution, here we extended this investigation to explore the effect of the NH2 substitution. For this purpose, C-(4-aminophenyl)- and C-(3-aminophenyl)-nitrilimines were photogenerated in an argon matrix at 15 K by narrowband UV-light irradiation (λ = 230 nm) of 5-(4-aminophenyl)- and 5-(3-aminophenyl)-tetrazole, respectively. The produced nitrilimines were further photoisomerized to carbodiimides via 1H-diazirines by irradiations at longer wavelengths (λ = 380 or 330 nm). Combining IR spectroscopic measurements and DFT calculations, it was found that the para-NH2-substituted nitrilimine exists as a single isomeric structure with a predominant allenic character. In contrast, the meta-NH2-substituted nitrilimine co-exists as two bond-shift isomers characterized by propargylic and allenic structures. To gain further understanding of the effects of phenyl substitution on the bond-shift isomerism of the nitrilimine fragment, we compared geometric and charge distribution data derived from theoretical calculations performed for C-phenyl-nitrilimine with those performed for the derivatives resulting from NH2 (electron-donating group) and NO2 (electron-withdrawing group) phenyl substitutions.