Effect Of Ring Strain Research Articles

Stepwise Photochromism of Large Macrocycles Incorporating Two Negative Photochromic Units.

Macrocyclic photochromic molecules incorporating multiple photochromic units are known to exhibit cooperative and nonlinear photochromic reactions among distinct photochromic components. While extensive research has concentrated on positive photochromic molecules, this study presents a pioneering attempt in synthesizing macrocyclic photochromic molecules that integrate negative photochromic units. Binaphthyl-bridged phenoxyl imidazolyl radical complex, BN-PIC, exhibits unique negative photochromism in which the thermally stable colored isomer converts to the metastable colorless isomer via a short-lived biradical upon visible-light irradiation. Macrocyclic biphotochromic molecules incorporating two BN-PIC units were synthesized and the effects of ring strain on the photochromic properties including the photoconversion efficiencies and the rates of the thermal reverse reaction were investigated. The photokinetic study of these macrocyclic biphotochromic molecules demonstrated that the structural distortion of the ring caused by the isomerization of one photochromic unit significantly influenced the photoisomerization efficiency and the rate of the thermal reverse reaction of the other photochromic unit.

Breaking the Rules: On the Relative Stability of Some Methylencyclopropane and Methylcyclopropene Derivatives.

The structure of the spirocyclic product obtained by reacting catechol with 1,1-dichloro-2-(chloromethyl)cyclopropane is shown by NMR and X-ray analysis to be that of a 2-methylcyclopropene (MeCP), instead of the previously reported 2-methylenecyclopropane (MCP) one. The study of the equilibration between the two isomeric forms by experimental and computational means (including both Density Functional Theory - DFT - and Coupled Cluster with single, double, and perturbative triple excitations - CCSD(T) - calculations) revealed that, at variance with most of the alkylidenecyclopropane/alkylcyclopropene systems described to date, for the compounds of the present study the MeCP derivative is more stable by≈ 2.5-3.0 Kcal mol-1 than the MCP one. The extension of the DFT and CCSD(T) study to other spiro-MCP/MeCP pairs suggests that the origin of the unexpected shift of the equilibrium position can be tracked back to a combination of electronic and ring-strain effects. These findings lead to re-think a long-standing, and substantially undisputed belief in the area of unsaturated cyclopropane derivatives.

Influence of Oxygen Atoms and Ring Strain on the Low-Temperature Oxidation Pathways of 1,3-Dioxolane

Biohybrid fuels are a promising solution for making the transportation sector more environmentally friendly. One such interesting fuel candidate is 1,3-dioxolane, which can be produced from inedible biomass. However, very little kinetics data are available for the low-temperature oxidation of this fuel molecule. To remedy this, we present the reaction kinetics of O2 addition to 1,3-dioxolanyl radicals in this work. All energies have been calculated at the DLPNO-CCSD(T)/CBS//B2PLYPD3BJ/6-311+g(d,p) level of theory. Temperature- and pressure-dependent reaction rate constants have been calculated with the RRKM/master equation method. The effects of heterocyclic oxygen atoms and ring strain on the low-temperature oxidation of 1,3-dioxolane are also compared to that of similar fuel molecules containing five heavy atoms: cyclopentane, tetrahydrofuran, and diethyl ether (DEE). The ring-opening β-scission reactions of the dioxolane hydroperoxy species are found to be the most dominant pathways following the oxidation of 1,3-dioxolanyl radicals. The heterocyclic oxygen atoms in 1,3-dioxolane weaken its C-O bonds, which leads to low barrier heights of the ring-opening reactions. Ring strain in 1,3-dioxolane increases the barriers for isomerization reactions of peroxy radicals compared to the similar reactions of DEE, which has a chain structure.

Visible Light Photoredox-Catalyzed Decarboxylative Alkylation of 3-Aryl-Oxetanes and Azetidines via Benzylic Tertiary Radicals and Implications of Benzylic Radical Stability

Four-membered heterocycles offer exciting potential as small polar motifs in medicinal chemistry but require further methods for incorporation. Photoredox catalysis is a powerful method for the mild generation of alkyl radicals for C-C bond formation. The effect of ring strain on radical reactivity is not well understood, with no studies that address this question systematically. Examples of reactions that involve benzylic radicals are rare, and their reactivity is challenging to harness. This work develops a radical functionalization of benzylic oxetanes and azetidines using visible light photoredox catalysis to prepare 3-aryl-3-alkyl substituted derivatives and assesses the influence of ring strain and heterosubstitution on the reactivity of small-ring radicals. 3-Aryl-3-carboxylic acid oxetanes and azetidines are suitable precursors to tertiary benzylic oxetane/azetidine radicals which undergo conjugate addition into activated alkenes. We compare the reactivity of oxetane radicals to other benzylic systems. Computational studies indicate that Giese additions of unstrained benzylic radicals into acrylates are reversible and result in low yields and radical dimerization. Benzylic radicals as part of a strained ring, however, are less stable and more π-delocalized, decreasing dimer and increasing Giese product formation. Oxetanes show high product yields due to ring strain and Bent's rule rendering the Giese addition irreversible.

Swift C-C bond insertion by a 12-electron palladium(0) surrogate.

The selective activation of C-C bonds holds vast promise for catalysis. So far, research has been primarily directed at rhodium and nickel under harsh reaction conditions. Herein, we report C-C insertion reactions of a 12-electron palladium(0) surrogate stabilized by a cyclic(alkyl)(amino) carbene (CAAC) ligand. Benzonitrile (1), biphenylene (2), benzocyclobutenone (3), and naphtho[b]cyclopropene (4) were studied. These substrates allow elucidation of the effect of ring strain as well as hybridization encompassing sp3, sp2 and sp hybridized carbon atoms. All reactions proceed quantitatively at or below room temperature. This work therefore outlines perspectives for mild C-C bond functionalization catalysis.

Syntheses of Bufospirostenin A and Ophiopogonol A by a Conformation-Controlled Transannular Prins Cyclization

Controlling the conformation of medium-sized rings is challenging because of their flexibility and ring strain effects. Herein, we report non-Curtin-Hammett conditions for the precise control of the conformation of cyclodecenones to effect the first cis-selective transannular Prins cyclization, which enabled concise syntheses of the 5(10→1)abeo-steroids bufospirostenin A and ophiopogonol A in only seven steps from inexpensive starting materials. Computational results indicated that the key cyclization was kinetically controlled and proceeded via either a Prins pathway or a carbonyl-ene pathway, depending on the reaction conditions. Moreover, conformational isomerization played a critical role in determining the stereochemistry of the products.

Experimental and theoretical investigations into the mechanisms of haliranium ion π-ligand exchange reactions with cyclic alkenes in the gas phase.

Haliranium ions are intermediates often involved in complex cyclisations, where their structure allows for control over stereospecific outcomes. Extending previous studies into their structure and reactivity in the gas phase, this work focuses on the bimolecular reactivity of ethyl bromiranium and iodiranium ions with cyclic alkenes. The products observed via mass spectrometry were broadly attributed to either addition by cyclohexene at the iranium carbon or attack at the heteroatom to undergo associative π-ligand exchange. The model proposed was supported by both kinetic experiments and DFT calculations, where the rate of parent ion consumption proceeded at the collision rate (Br: k2 = 1.25 × 10-9 and I: k2 = 1.28 × 10-9 cm3 molecule-1 s-1) with the subsequent partitioning dependent on the relative stability of the initial intermediates and the relatively large barriers present in the addition pathway. Exploration of the effect of cycloalkene ring strain on the iodiranium ion reactivity was conducted with a series of crossover experiments with 50 : 50 mixtures of either cyclohexene or cis-cyclooctene and styrene, where the outcomes were dependent on the competing ring strain relief gained by reaction with each neutral. The nature of the exchange transition state was determined to be pseudocoarctate following both natural bond orbital (NBO) and anisotropy of the induced current density (ACID) analysis.

Effect of aromaticity and ring strain on proton affinity of aziridine and amidine skeletons: a DFT study

Based on density functional theory (DFT) calculations, aziridine derivatives bearing vinylcyclopropane, vinylcycloheptatriene, amidine and guanidine substituents offer suitable skeletons for engineering of organosuperbases. Protonation of the aziridine led to ring opening and complete relief of the internal strain. The positive charge placed in the cyclic π-electron networks resulted in the aromaticity and delocalization of the charge. The calculated proton affinities of the proposed organosuperbases were in the range of 958–1227 kJ mol−1. Isomerization process for some aziridine derivatives and their protonated forms was also investigated by DFT calculations.

Effects of ring-strain on the ultrafast photochemistry of cyclic ketones.

Ring-strain in cyclic organic molecules is well-known to influence their chemical reactivity. Here, we examine the consequence of ring-strain for competing photochemical pathways that occur on picosecond timescales. The significance of Norrish Type-I photochemistry is explored for three cyclic ketones in cyclohexane solutions at ultraviolet (UV) excitation wavelengths from 255–312 nm, corresponding to an π* ← n excitation to the lowest excited singlet state (S1). Ultrafast transient absorption spectroscopy with broadband UV/visible probe laser pulses reveals processes common to cyclobutanone, cyclopentanone and cyclohexanone, occurring on timescales of ≤1 ps, 7–9 ps and >500 ps. These kinetic components are respectively assigned to prompt cleavage of an α C–C bond in the internally excited S1-state molecules prepared by UV absorption, vibrational cooling of these hot-S1 molecules to energies below the barrier to C–C bond cleavage on the S1 state potential energy surface (with commensurate reductions in the energy-dependent α-cleavage rate), and slower loss of thermalized S1-state population. The thermalized S1-state molecules may competitively decay by activated reaction over the barrier to α C–C bond fission on the S1-state potential energy surface, internal conversion to the ground (S0) electronic state, or intersystem crossing to the lowest lying triplet state (T1) and subsequent C–C bond breaking. The α C–C bond fission barrier height in the S1 state is significantly reduced by the ring-strain in cyclobutanone, affecting the relative contributions of the three decay time components which depend systematically on the excitation energy above the S1-state energy barrier. Transient infra-red absorption spectra obtained after UV excitation identify ring-opened ketene photoproducts of cyclobutanone and their timescales for formation.

Development of Rhodamine 6G-Based Fluorescent Chemosensors for Al3+-Ion Detection: Effect of Ring Strain and Substituent in Enhancing Its Sensing Performance.

Four rhodamine 6G-based chemosensors (H3L1–H3L4) are designed for selective detection of Al3+ ion. They are characterized using various spectroscopic techniques and X-ray crystallography. All absorption and emission spectral studies have been performed in 10 mM N-(2-hydroxyethyl)piperazine-N′-ethanesulfonic acid (HEPES) buffer solution at pH 7.4 in H2O/MeOH (9:1, v/v) at 25 °C. In absorption spectra, chemosensors exhibit an intense band around 530 nm in the presence of Al3+ ion. Chemosensors (H3L1–H3L4) are nonfluorescent when excited around 490 nm. The presence of Al3+ ion enhances the emission intensity (555 nm) many times. The formation of complexes 1–4 is established with the aid of different spectroscopic techniques. The limit of detection value obtained in the nanomolar range confirms the high sensitivity of the probes toward Al3+ ion. It has been observed that the presence of aliphatic spacers in the diamine part and different halogen substituents in the salicylaldehyde part strongly influences the selectivity of the chemosensors toward Al3+ ion. The propensity of the chemosensors to identify intracellular Al3+ ions in triple-negative human breast cancer cell line MDA-MB-468 by fluorescence imaging is also examined in this study.

Theoretical kinetic and thermodynamic studies of the strain energies and ring size effects of the 1,3-dipolar cycloaddition reactions on ethinamate medicine analogs

In this study, strain effects of a side ring on the 1,3-dipolar cycloaddition reactions were investigated. It was important to find a reactant with a ring closed at the structure of the selected dipolarophile. To this aim, the ring-closed structure, ethinamate (E1), medicine for insomnia, and its analogous compounds (E2-E4) selected as dipolarophile for 1,3-DC reaction with azide derivatives (a, b and c) as 1,3-dipoles to achieve the 1,2,3-triazole products. For each set of reactions was employed DFT method to determine the critical structures (reactants, transition states and products) energy pathways and results analyzed and discussed from kinetic and thermodynamic point of view. The DFT-B3LYP/6-31G* method was accepted to calculate energy levels of the RTP (Reactants, Transition states (TS), Products) of the reactions, the free energies of reaction (ΔrG and ΔG#; in kcal mol−1), rate constants by using Eyring’s equation (k and k′), and structural data were obtained and discussed. The side ring size and strain effects have been investigated in the 1,3-DC reactions to produce the 1,2,3-triazole derivatives from ethinamate and its analogs.

The crucial role of strained ring in enhancing the hydrogen evolution catalytic activity for the 2D carbon allotropes: a high-throughput first-principles investigation

Based on the density functional theory (DFT) calculations, we have firstly investigated the hydrogen evolution reaction (HER) catalytic activities for three kinds of two-dimensional (2D) carbon allotropes consisted of four-, six- and eight-membered rings, including net C, net W and net Y. Different from the inert graphene only consisted of six-membered rings, all these three carbon allotropes can exhibit the HER catalytic activity, with the net C superior to net W and net Y. It is revealed that the strain in four- or eight-membered ring with the antiaromaticity can play a crucial role in dominating their HER activities. Furthermore, the HER catalytic activities for all of three carbon allotropes can be effectively enhanced by doping N, B, O, P and S atoms with the different electronegativity, and the achievement of their high HER activities can be mainly due to the cooperation of foreign-atom doping with the ring strain effect. The correlative carbon atoms, shared by four-, six- and eight-membered rings, can uniformly serve as the most active site for all these 2D pure or doped carbon systems. Undoubtedly, introducing the correlative rings with the strain or antiaromaticity can be considered as the new and effective strategy to realize the highly efficient and nonprecious HER electrocatalysts, and all these intriguing findings obtained in this work can be advantageous for designing new kind of promising HER electrocatalysts.

Conformational Control of Macrocycles by Remote Structural Modification.

The conformational analysis of macrocycles is a complex and challenging problem. There are many factors that contribute to this complexity. These include a large number of degrees of freedom, transannular interactions such as hydrogen bonds and hydrophobic interactions, and a range of steric interactions, along with ring strain effects. To a greater extent than within acyclic molecules, these interactions within macrocycles are coupled such that changing one dihedral angle can significantly affect other dihedral angles, further complicating the situation. However, this coupling of bond rotations and transannular interactions enables the transmission of three-dimensional information from one side of a macrocycle to the other. Making relatively small structural modifications to a macrocycle can result in local conformational changes that propagate along the ring to affect distal structural features. The factors that control how such changes can propagate are poorly understood, and it is difficult to predict which modifications will result in significant conformational reorganizations of remote regions of a macrocycle. This review discusses examples where small structural modifications to macrocyclic scaffolds change the conformational preferences of structurally remote regions of the ring. We will highlight evidence provided for conformational changes triggered by remote substituents and explanations of how these changes might occur in an effort to further understand the factors that control such phenomena.

Tuning the ring strain effect in acridine derivatives on binding affinity with G-quadruplex-DNA: A computational and experimental study

Search for inhibitors to stabilize the telomeric G-quadruplex in order to deter telomerase activity is an active area of research. Inhibitors play an important role to initiate the tumor cell mortalization process. This work reports for the first time of acridine derivative with four membered ammonium rings at the side chain to surpass the binding ability against BRACO-19 with G-quadruplex-DNA. It is known in the literature that acridine based molecule BRACO-19 can effectively bind with G-quadruplex-DNA. The computational study performed in this study revealed that the binding ability of acridine based molecule can be augmented with subtle variation in the molecular structure of the drug like candidates. Steered molecular dynamics (SMD) performed with the acridine derivatives and G-quadruplex DNA showed the importance of ring strain to the side chain of those ligand molecules. The rupture force analysis, hydrogen bonding interactions and the calculated free energies in MM-PBSA method suggest that ligand 3 is superior than that of BRACO-19. The synthesized ligand 3 and BRACO-19 showed the binding constants obtained from ITC measurements are 4 × 106 mol−1 and 2.6 × 106, which corroborates the computational findings.

Computational Kinetics of Hydroperoxybutylperoxy Isomerizations and Decompositions: A Study of the Effect of Hydrogen Bonding

Hydroperoxyalkylperoxy (OOQOOH) radicals are important intermediates in combustion chemistry. The conventional isomerization of OOQOOH radicals to form ketohydroperoxides has been long believed to be the most important chain branching reaction under the low-temperature combustion conditions. In this work, the kinetics of competing pathways (alternative isomerization, concerted elimination, and H-exchange pathways) to the conventional isomerization of different β-, γ- and Δ-OOQOOH butane isomers are investigated. Six- and seven-membered ring conventional isomerizations are found to be the dominant pathways, whereas alternative isomerizations are more important than conventional isomerization, when the latter proceeded via a more strained transition state ring. The oxygen atoms in OOQOOH radicals introduce intramolecular hydrogen bonding (HB) that significantly affects the energies of reacting species and transition states, ultimately influencing chemical kinetics. Conceptually, HB has a dual effect on the stability of chemical species, the first being the stabilizing effect of the actual intramolecular HB force, and the second being the destabilizing effect of ring strain imposed by the HB conformer. The overall effect can be quantified by determining the difference between the minimum energy conformers of a chemical species or transition state that have HB and that do not have HB (non-hydrogen bonding (NHB)). The stabilization effect of HB on the species and transition sates is assessed, and its effect on the calculated rate constants is also considered. Our results show that, for most species and transition states, HB stabilizes their energies by as much as 2.5 kcal/mol. However, NHB conformers are found to be more stable by up to 2.7 kcal/mol for a few of the considered species. To study the effect of HB on rate constants, reactions are categorized into two groups ( groups one and two) based on the structural similarity of the minimum energy conformers of the reactant and transition state, for a particular reaction. For cases where the reactant and transition state conformers are similar (i.e., both HB or NHB structures), group one, the effect of HB on reaction kinetics is major only if the magnitudes of the stabilization energy of the reactant and transition state are quite different. Meanwhile, for group two, where the reactant and transition state prefer different conformers (one HB and the other NHB), HB affects the kinetics when the stabilization energy of the reactant or transition state is significant or the entropy effect is important. This information is useful in determining corrections accounting for HB effects when assigning rate parameters for chemical reactions using estimation and/or analogy, where analogies usually result in inaccuracies when modeling atmospheric and combustion processes.

Insights into unusual stability of 5‐membered‐ring endocyclic benzyl carbocations in aqueous solution

AbstractThe acyclic o‐oxygen benzyl carbocation 1, the 6‐membered‐ring endocyclic o‐oxygen benzyl carbocation 2, and the 5‐membered‐ring endocyclic o‐oxygen benzyl carbocation 3 were used as model compounds to get insights into the general phenomenon for the unusual stability of the 5‐membered‐ring endocyclic benzyl carbocations in aqueous solution. The hydride‐ion affinities of 1, 2, and 3 in gas phase, acetonitrile, and DMSO were calculated and compared by the density functional theory method, and 3 isodesmic reactions were designed to confirm their thermodynamic stability. What we found is that the 5‐membered‐ring endocyclic o‐oxygen stabilizes the benzyl carbocation 3 less than the acyclic o‐oxygen stabilizes the benzyl carbocation 1 in gas phase because of ring strain and through‐bond induction. However, the high solvation energies of the 5‐membered‐ring endocyclic o‐oxygen benzyl carbocation 3 not only offset the destabilizing effects of ring strain and through‐bond induction but also make it even more stable than the acyclic o‐oxygen benzyl carbocation 1 in polar solvents like acetonitrile, DMSO, and water.

Cationic ring-opening polymerization of cyclic carbonates and lactones by group 4 metallocenes: A theoretical study on mechanism and ring-strain effects

Group 4 metallocene-mediated cationic ring-opening polymerizations of a series of lactones and cyclic carbonates, with different ring sizes ([Formula: see text]–8) have been theoretically studied. Using the “naked cation” approach in combination with density functional theory, the activated chain-end mechanism and the influence of transition metals, solvent and monomer ring size on the polymerizability were explored in detail. The results showed that the cationic metallocene–monomer complex, [catalyst][monomer][Formula: see text], is formed, generating cationic (carbocation ion) species responsible for polymer chain growth. We found that poor polymerizability of five-membered lactone and six-membered ring carbonate depends not only on the nature of the monomer ring size but also the relative stability of the complex, which was found to correlate well with the ring strain. Subsequently, several propagation steps take place through an SN2 reaction which involves ring opening of an active monomer, via alkyl–oxygen bond cleavage. Based on the computed activation energies of all metallocene systems, the first propagation was found to be the rate-determining step of the overall propagation and the hafnocene was found to be most active with the energy barrier of 17.6[Formula: see text]kcal/mol, followed by zirconocene (18.6[Formula: see text]kcal/mol) and titanocene (19.5[Formula: see text]kcal/mol), respectively. The mechanistic study may be applicable to the cationic ROP of lactides and other related monomers.

The first synthesis of meso-dicycloalkylporphycenes: ring strain effects on structural and optical properties of isomeric porphyrins

Two novel meso-dicycloalkylporphycenes, namely meso-dicyclopentyl- (Cy5Pc) and meso-dicyclohexylporphycenes (Cy6Pc) are synthesized for the first time in porphycene chemistry. We use intermolecular oxidative coupling of 5,6-dicycloalkydipyrroethenes mediated by hypervalent iodine(iii) reagents. The solution fluorescence maxima of Cy5Pc are more than 400 times as intense as that of Cy6Pc. The results suggested that photoluminescence switching is achieved through the ring strain perturbation of the meso-substituted cycloalkyl groups on the porphycene cavity.

Selective and Sequential Aminolysis of Benzotrifuranone: Synergism of Electronic Effects and Ring Strain Gradient.

Benzotrifuranone (BTF), bearing three symmetry-equivalent lactone rings, is unique in its ability to undergo highly selective and sequential aminolysis reactions in one-pot to afford multifunctionalized molecules (>80% overall yield). New insight into this behavior is presented through kinetics measurements (by stopped-flow IR spectroscopy), X-ray crystal structure analysis, quantum chemical calculations, and comparison of BTF to other benzoate esters, including its ring expanded congener benzotripyranone (BTP). While the structure-property investigation confirms stepwise electronic/inductive lactone deactivation for both BTF and BTP, the unusually fast and selective aminolysis of BTF is only fully explained through synergistic ring strain effects. Experimental signatures of the significant ring strain of BTF (∼28 kcal mol-1 based on DFT calculations vs 17 kcal mol-1 for BTP) include its high lactone carbonyl stretching energy (1821 cm-1 in acetonitrile vs 1777 cm-1 for BTP) and bond length alternation within its benzenoid ring. While ring strain is relieved upon the sequential aminolysis of both BTF and BTP, it is only for the former that a ring strain gradient is established that contributes to the stepwise aminolysis rate differences and enhanced selectivity. The work shows how a combination of electronic effects and ring strain can underpin the design of small molecules capable of stepwise functionalization, of which there are notably few examples.

A theoretical prediction of the relationships between the impact sensitivity and electrostatic potential in strained cyclic explosive and application to H-bonded complex of nitrocyclohydrocarbon.

Seven models that related the features of molecular surface electrostatic potentials (ESPs) above the bond midpoints and rings, statistical parameters of ESPs to the experimental impact sensitivities h 50 of eight strained cyclic explosives with the C-NO2 bonds were theoretically predicted at the DFT-B3LYP/6-311++G** level. One of the models was used to investigate the changes of h 50 for the nitrocyclohydrocarbon frameworks in the H-bonded complexes of HF with nitrocyclopropane, nitrocyclobutane, nitrocyclopentane, and nitrocyclohexane. The results show that the correlation coefficients of the obtained models are small. When adding the effect of ring strain, the value of correlation coefficient is increased. According to the calculated h 50, the sensitivities in the frameworks are increased after hydrogen bonding. As a global feature of molecules, surface electrostatic potential is more available to judge the sensitivity change than the trigger bond dissociation energy or ring strain energy in H-bonded complex.