Ring-opening Transition State Research Articles

Consequences of Pore Polarity and Solvent Structure on Epoxide Ring-Opening in Lewis and Brønsted Acid Zeolites.

The structure of solvent molecules within zeolite pores influences the rates and selectivities of catalytic reactions by altering the free energies of reactive species. Here, we examine the consequences of these effects on the kinetics and thermodynamics of 1,2-epoxybutane (C4H8O) ring-opening with methanol (CH3OH) in acetonitrile (CH3CN) cosolvent over Lewis acidic (Zr-BEA) and Brønsted acidic (Al-BEA) zeolites of varying (SiOH) x density. Despite ostensibly identical reaction mechanisms across materials, turnover rates depend differently on (SiOH) x density between acid types. (SiOH) x -rich Zr-BEA (Zr-BEA-OH) provides ∼10 times greater rates than a (SiOH) x -poor material (Zr-BEA-F), while Al-BEA-OH and Al-BEA-F give turnover rates within a factor of 2. Zr-BEA-OH shows more positive activation enthalpies and entropies than Zr-BEA-F across the range of [CH3OH], which reflect the displacement of solvent molecules and lead to greater rates in Zr-BEA-OH due to the dominant role of entropic gains. Measurements of the density and composition of solvent within the pores show that the (SiOH) x nests within Zr-BEA-OH promote hydrogen-bonded solvent structures distinct from Zr-BEA-F, while the Brønsted acid sites confer interactions similar to (SiOH) x nests and give solvent structures within Al-BEA-F that resemble those within Al-BEA-OH. Correlations between apparent activation enthalpies and C4H8O adsorption enthalpies show that interactions with solvent molecules give proportional changes to both C4H8O adsorption and ring-opening transition state formation. The differences in intrapore environment carry consequences for both rates and regioselectivities of epoxide ring-opening, as demonstrated by product regioselectivities that increase by a factor of 3 in response to changes in solvent composition and the type of acid site in the *BEA structure (i.e., Lewis or Brønsted). These results demonstrate the ability to control rates, regioselectivities, and adsorption thermodynamics relevant for industrially relevant liquid-phase reactions through the design of noncovalent interactions among solvating molecules, reactive species, and (SiOH) x functions.

Ligand-Metal Cooperation Enables Net Ring-Opening C-C Activation / Difunctionalization of Cyclopropyl Ketones.

Reactions that cleave C-C bonds and enable functionalization at both carbon sites are powerful strategic tools in synthetic chemistry. Stereodefined cyclopropyl ketones have become readily available and would be an ideal source of 3-carbon fragments, but general approaches to net C-C activation / difunctionalization are unknown. Herein we demonstrate the cross-coupling of cyclopropyl ketones with organozinc reagents and chlorotrimethylsilane to form 1,3-difunctionalized, ring-opened products. A combination of experimental and theoretical studies rule out more established mechanisms and shed light on how cooperation between the redox-active terpyridine (tpy) ligand and the nickel atom enables the C-C bond activation step. The reduced (tpy•-)NiI species activates the C-C bond via a concerted asynchronous ring-opening transition state. The resulting alkylnickel(II) intermediate can then be engaged by aryl-, alkenyl-, and alkylzinc reagents to furnish cross-coupled products. This allows quick access to products that are difficult to make by conjugate addition methods, such as β-allylated and β -benzylated enol ethers. The utility of this approach is demonstrated in the synthesis of a key (±)-taiwaniaquinol B intermediate and the total synthesis of prostaglandin D1.

Theoretical Study on the Origin of Abnormal Regioselectivity in Ring-Opening Reaction of Hexafluoropropylene Oxide

That nucleophiles preferentially attack at the less sterically hindered carbon of epoxides under neutral and basic conditions has been generally accepted as a fundamental rule for predicting the regioselectivity of this type of reaction. However, this rule does not hold for perfluorinated epoxides, such as hexafluoropropylene oxide (HFPO), in which nucleophiles were found to attack at the more hindered CF3 substituted β-C rather than the fluorine substituted α-C. In this contribution, we aim to shed light on the nature of this intriguing regioselectivity by density functional theory methods. Our calculations well reproduced the observed abnormal regioselectivities and revealed that the unusual regiochemical preference for the sterically hindered β-C of HFPO mainly arises from the lower destabilizing distortion energy needed to reach the corresponding ring-opening transition state. The higher distortion energy required for the attack of the less sterically hindered α-C results from a significant strengthening of the C(α)-O bond by the negative hyperconjugation between the lone pair of epoxide O atom and the antibonding C-F orbital.

Ultrafast Excited State Aromatization in Dihydroazulene

Excited-state aromatization dynamics in the photochemical ring opening of dihydroazulene (DHA) is investigated by nonadiabatic molecular dynamics simulations in connection with the mixed-reference spin-flip (MRSF)-TDDFT method. It is found that, in the main reaction channel, the ring opening occurs in the excited state in a sequence of steps with increasing aromaticity. The first stage lasting ca. 200 fs produces an 8π semiaromatic S1 minimum (S1,min) through an ultrafast damped bond length alternation (BLA) movement synchronized with a partial planarization of the cycloheptatriene ring. An additional ca. 200 fs are required to gain the vibrational energy needed to overcome a ring-opening transition state characterized by an enhanced Baird aromaticity. Unlike other BLA motions of ππ* state, it was shown that their damping is a characteristic feature of aromatic bond-equalization process. In addition, some minor channels of the reaction have also been discovered, where noticeably higher barriers of the S1 non/antiaromatic transition structures must be surmounted. These anti-Baird channels led to reformation of DHA or other closed-ring products. The observed competition between the Baird and anti-Baird channels suggests that the quantum yield of photochemical products can be controllable by tipping their balance. Hence, here we suggest including the concept of anti-Baird, which would expand the applicability of Baird rule to much broader situations.

VUV photoprocessing of oxygen-containing polycyclic aromatic hydrocarbons: iPEPICO study of the unimolecular dissociation of ionized benzofuran

Oxygen-containing polycyclic aromatic hydrocarbons (OPAHs) are potential contributors to the 11.3 µm band in interstellar observations. To further explore their role in the interstellar medium, we investigated their fate after photoprocessing by VUV radiation; in particular, we studied the dissociative photoionization of the simplest OPAH, benzofuran, with imaging photoelectron photoion coincidence (iPEPICO) spectroscopy. Ionized benzofuran dissociates by loss of CO, followed by a sequential H-atom loss. The parallel HCO-loss channel, leading to the same bicyclic C7H5+ fragment ion, is not competitive at low excess energies above the ionization threshold. However, the collision-induced dissociation tandem mass spectrometry results suggest that CO and HCO may be formed in parallel at higher energies. A Rice–Ramsperger–Kassel–Marcus fragmentation model reproduced the iPEPICO data well, assuming the initial 1,2-H shift transition state to be rate determining to CO loss. The breakdown diagram and the measured dissociation rates agreed well at the CBS-QB3-calculated activation energy of 2.99 eV, which could be relaxed to 3.25 eV, and only a slight adjustment of the ab initio activation entropy. The model barrier to sequential H loss is larger than the computed H-loss threshold and the breakdown diagram rises less steeply than predicted, which indicates suprastatistical kinetic energy release after the tight H-transfer transition state of the first step. HCO cleavage is possible after a ring-opening transition state, which is looser than and isoenergetic with the CO-loss transition state. However, a subsequent ring formation transition state at 3.85 eV is moderately tight, which suppresses HCO loss at low excess energies.

Mechanism and Origins of Product Selectivity of Au‐Catalyzed Coupling Benzisoxazoles with Ynamides: A Computational Study

AbstractAu(I)‐catalyzed coupling of benzisoxazoles and ynamides was recently reported to synthesize challenging indoloquinoline core structures. In this report, we employed DFT methods to elucidate the mechanistic details of this reaction. The results reveal that the catalytic cycle involves initial coupling of ynamide with benzisoxazole, simultaneous ring opening of the isoxazole unit and attack of the dimethoxybenzene (DMOB) unit to gold carbenoid, proton transfer from the DMOB group to hydroxyl group, thioether migration, ring closure, and proton transfer. The experimentally observed ligand‐controlled product selectivity is reproduced well by the calculations. The product selectivity‐determining step is the ring opening of the isoxazole unit. The flexible P(t‐Bu)2(o‐biphenyl) ligand facilitates the approach of the DMOB group to gold carbenoid, which brings about significant C−H/π interactions in the transition state for ring opening, and thus leads to the indoloquinoline product. The rigid 1,3‐bis(diisopropylphenyl)imidazol‐2‐ylidene ligand prefers keeping the DMOB group away from the gold carbenoid, which can cause strong orbital interaction in the transition state for ring opening, and thus results in indole product.

Formation mechanism of HCN and NH3 during indole pyrolysis: A theoretical DFT study

Coal is a major contributor to the global emission of nitrogen oxides. The NOx formation during coal utilisation typically derives from thermal decomposition of N-containing compounds pyrrole, which usually combines with an aromatic ring in the form of indole. NH3 and HCN are common precursors of NOx from the decomposition of N-containing compounds. In this study, possible pathways of indole pyrolysis to form HCN and NH3 are investigated using the density functional theory (DFT) method. Calculation results indicate that indole pyrolysis has two type of possible initial reactions, which are internal hydrogen transfer and hydrogen homolysis reaction, respectively. The initial reaction mode of indole has a great impact on the subsequent pyrolysis pathway. Additionally, it is shown that indole can produce two nitrogen-containing products, i.e. HCN and NH3. Five pathways will result in the formation of HCN (path-1, path-3, path-a, path-b, path-c), and another two pathways will lead to the NH3 (path-2, path-4). Furthermore, among all the reaction mechanisms of indole pyrolysis, the path-1 is the optimal reaction pathway. During which, indole is converted to a diradical intermediate, then the intermediate undergoes a synergy ring-opening transition state to form a new intermediate. Afterwards, the new intermediate decomposes into CN by homolysis of the C–C bond.

Ring-opening attachment as an explanation for the long lifetime of the octafluorooxolane anion.

Octafluorooxalane, C4F8O, has recently attracted attention as a possible replacement of SF6 in high voltage insulation, and its reactivity with respect to free-electron attachment was investigated by mass spectrometry. The most intense signal peaks at 0.9 eV and corresponds to the parent anion, C4F8O-; fragments stemming from complex breakup reactions are detected starting above ∼1.6 eV. Since parent anions in free-electron attachment are normally associated with threshold attachment or an embedding environment allowing excess energy deposition, this observation is highly unusual. Based on density functional calculations, it was nevertheless interpreted as attachment followed by intermolecular-vibrational-relaxation. Here, electron-attachment to octafluorooxalane is studied computationally. First, the electron affinity (EA) is characterized using density functionals and ab initio methods. Moreover, the negative vertical EA is estimated by extrapolating electron binding energies computed in the vicinity of C4F8O- to the geometry of neutral octafluorooxalane. Then, alternative explanations for the 0.9 eV peak are considered. Specifically, a ring-opening reaction that yields a distonic isomer of C4F8O- is identified. Our analysis reveals that the chain isomer possesses many conformers, all of which are considerably more stable than the ring isomer, and that the time scale for the unimolecular ring opening reaction is significantly faster than 1 μs. Thus, at the experimental energy, the ring isomer of C4F8O- is predicted to convert practically completely into the chain isomer, and we argue that the long lifetime and the peak position are effectively determined by the properties of the ring-opening transition state.

TfOH Catalyzed [3+2] Cycloaddition of Cyclopropane 1,1‐Diesters with Nitriles: A Density Functional Study

AbstractThe mechanistic pathways for TfOH catalyzed [3+2] cycloaddition reaction between cyclopropane 1, 1 diesters and MeCN has been investigated using density functional theory. The study sheds light on selective synthesis of 1‐pyrroline or γ‐lactone derivatives in two different reaction conditions. Analysis of global reactivity descriptors in the solvent free medium predicts the protonated cyclopropane 1,1 diesters and MeCN as strong electrophile and nucleophile respectively, favoring intermolecular reaction to give 1‐pyrroline derivative as the product. On the other hand, the presence of solvent environment with DCM solvent significantly supresses this nature of the two molecules to undergo intermolecular reaction. Protonated cyclopropane 1,1 diester, therefore, prefers intramolecular rearrangement to yield γ‐lactone. While the synthesis of 1‐pyrroline derivative follows pathway involving a transition state showing weak interaction between two reactants, γ‐lactone synthesis undergo mechanism preferring initial cyclopropane ring opening transition state. Molecular electron density topography yield support to the proposed mechanism.

Electron attachment to the phthalide molecule.

Phthalide, the simplest chain of conductive polymer thin film, was investigated by means of Electron Transmission Spectroscopy, Negative Ion Mass Spectrometry, and density functional theory quantum chemistry. It has been found that formation of gas-phase long-lived molecular anions of phthalide around 0.7 eV takes place through cleavage of a C-O bond of the pentacyclic ring of the parent molecular anion to give a vibrationally excited (electronically more stable) open-ring molecular anion. The energy of the transition state for ring opening of the parent negative ion is calculated to be 0.65 eV above the neutral ground state of the molecule. The energy (2.64 eV) evaluated for the corresponding transition state in the neutral molecule is much higher, so that the process of electron detachment from the anion must lead to a neutral molecule with its initial pentacyclic structure. The average lifetime of the molecular negative ions formed at an electron energy of 0.75 eV and 80 °C is measured to be about 100 μs. The known switching effect of thin phthalide films could stem from the presence of a similar open/closed transition state also in the polymer.

Structures of 4-Iminopyrido[1,2-a]pyrimidines, Pyrido[1,2-a]pyrimidin-4-ones, Pyridopyrimidinium Olates, and Thiazolo[3,2-a]pyrimidine Analogues

The Structure-Correlation Principle of Bürgi and Dunitz is invoked in an analysis of the structures of 2-chloro-8-methyl-4-(2-(4-picolinyl)imino-4H-pyrido[1,2-a]pyrimidine 8, 7-chloro-5-(2-thiazolyl)imino-5H-thiazolo[3,2-a]pyrimidine 9, 2-methylamino-4H-pyrido[1,2-a]pyrimidin-4-one 10, 7-methylthio-5H-thiazolo[3,2-a]pyrimidin-5-one 11, 2,3-dihydro-7-methylthio-5H-thiazolo[3,2-a]pyrimidin-5-one 12, and 1-methyl-2-[(o-tert-butylphenyl)imino]-1,2-dihydropyrido[1,2-a]pyrimidin-1-ium-4-olate 13, which have been determined by X-ray crystallography. The most notable structural peculiarities are the long ‘amidine’ and ‘amide’ C–N bonds (1.40–1.50 Å) and the tilting of the ‘amidine’ C=N and ‘amide’ C=O groups towards a ring nitrogen atom (NCX = 114–118°). Also the ‘amidine’ C=N (1.28 Å) and ‘amide’ C=O bonds (1.22–1.24 Å) are long, i.e. in the normal range for resonance-stabilized amidines and amides in spite of the lack of such resonance in these compounds. These features mimic the transition states for ring opening to ketenes. The long amidine and amide C–N bonds and acute NCX angles are in accord with the observed thermal ring opening to ketenimines and ketenes, respectively.

Computational studies on the mechanism of the gold(i)-catalysed rearrangement of cyclopropenes

Density functional theory calculations have been employed to investigate the mechanism of gold(I)-catalysed rearrangements of cyclopropenes. Product formation is controlled by the initial ring-opening step which results in the formation of a gold-stabilised carbocation/gold carbene intermediate. With 3-phenylcyclopropene-3-methylcarboxylate, the preferred intermediate allows cyclisation via nucleophilic attack of the carbonyl group and hence butenolide formation. Further calculations on simple model systems show that substituent effects can be rationalised by the charge distribution in the ring-opening transition state and, in particular, a loss of negative charge at what becomes the β-position of the intermediate. With 1-C(3)H(3)R cyclopropenes (R = Me, vinyl, Ph), ring-opening therefore places the substituent at the β-position.

A mechanistic study of sialic acid mutarotation: Implications for mutarotase enzymes

The mutarotation of N-acetylneuraminic acid (Neu5Ac) proceeds by four kinetically distinct pathways: (i) the acid-catalyzed reaction of neutral Neu5Ac; (ii) the spontaneous reaction of the carboxylic acid (the kinetically equivalent acid-catalyzed reaction on the anion being ruled out by the solvent deuterium kinetic isotope effect of 3.74 ± 0.68); (iii) a spontaneous, water-catalyzed, reaction of the anion; and (iv) a specific-base catalyzed reaction of the anion. The magnitude of the solvent kinetic isotope effect, k(H2O)/k(D2O) = 4.48 ± 0.74 is consistent with a ring-opening transition state in which a water molecule is deprotonating the anomeric hydroxyl group in concert with strengthening solvation of the ring oxygen atom. The mechanistic implications for Neu5Ac mutarotases are discussed.

ChemInform Abstract: The Ring Opening of Cyclopropylidene to Allene. Key Features of the Accurate Reaction Surface.

The global potential energy surface, determined in the first paper [1] for the groundstate ring opening of cyclopropylidene to allene, is complemented by accurate calculations of its key regions. The basis set is extended and polarization functions are included. The full configuration space of four electrons in four reactive orbitals is enlarged to the full configuration space of eight electrons in eight active orbitals by including correlations in the unbroken, but stretched CC sigma bonds. The effect of further single and double excitations is examined. The geometries and relative energies of the critical regions are found to change only little except for the ring-opening energy barrier which is lowered to about 7 kcal/mol, in good agreement with the experimental estimate of about 6 kcal/mol. Furthermore, the bifurcation is shown to occurafter the transition state, in the neighborhood of a conical intersection on the steepest descent path from the ring-opening transition state to the allene isomerization transition state. The steepest descent paths and the conical intersection are documented in detail. The cogwheel-like free internal rotation of the two methyl groups is confirmed by the accurate calculations. A similar richness of features is believed to exist on many potential energy surfaces governing chemical reactions.

Detailed Kinetic Study of the Ring Opening of Cycloalkanes by CBS-QB3 Calculations

This work reports a theoretical study of the gas-phase unimolecular decomposition of cyclobutane, cyclopentane and cyclohexane by means of quantum chemical calculations. A biradical mechanism has been envisaged for each cycloalkane, and the main routes for the decomposition of the biradicals formed have been investigated at the CBS-QB3 level of theory. Thermochemical data(DeltaHf(o), S(o), Cp(o)) for all the involved species have been obtained by means of isodesmic reactions. The contribution of hindered rotors has also been included. Activation barriers of each reaction have been analyzed to assess the energetically most favorable pathways for the decomposition of biradicals. Rate constants have been derived for all elementary reactions using transition-state theory at 1 atm and temperatures ranging from 600 to 2000 K. Global rate constant for the decomposition of the cyclic alkanes in molecular products have been calculated. Comparison between calculated and experimental results allowed us to validate the theoretical approach. An important result is that the rotational barriers between the conformers, which are usually neglected, are of importance in decomposition rate of the largest biradicals. Ring strain energies (RSE) in transition states for ring opening have been estimated and show that the main part of RSE contained in the cyclic reactants is removed upon the activation process.

Disrotatory and Conrotatory Transition Structures for the Fe(CO)3-Templated Rearrangement of Methylenecyclopropane to Trimethylenemethane

Hybrid HF-DFT calculations were used to compute the structures and relative energetics of competing disrotatory and conrotatory transition states for ring-opening of Fe(CO)3-complexed methylenecyclopropanes.

Kinetics of Cyclopropylcarbinyl Radical Ring Openings Measured Directly by Laser Flash Photolysis

The kinetics of ring openings of cyclopropylcarbinyl radicals containing reporter groups were measured directly by laser flash photolysis (LFP) methods. The reporter groups are aryl-substituted cyclopropanes at the position of the radical center in the incipient product, and the initial ring-opening reaction gives an aryl-substituted cyclopropylcarbinyl radical that opens “instantly” on the nanosecond time scale to give benzylic and diphenylalkyl radical products that are detected by UV spectroscopy. Three reporter group designs have been studied. The most useful design is that in substituted (trans-2-(2,2-diphenylcyclopropyl)cyclopropyl)methyl radicals (7). The important synthetic intermediate for production of this series is N-methoxy-N-methyl-trans-2-(2,2-diphenyl-1R*-cyclopropyl)-1S*,2R*-cyclopropanecarboxamide (15a) which has been prepared diastereomerically pure. The syntheses of 15a and a series of PTOC ester radical precursors derived from 15a are described. Laser photolysis (355 nm) of PTOC esters gave acyloxyl radicals that decarboxylated to give cyclopropylcarbinyl radicals that were studied. The substitutions at the cyclopropylcarbinyl position of radicals 7 were H, H (7a); H, Me (7b); Me, Me (7c); H, CO2Et (7d); Me, CO2Et (7e); and H, Ph (7f). The kinetics of ring openings of radicals 7 were measured in THF and in four cases in CH3CN in the temperature range −41 to +50 °C. Alkyl radicals 7a and 7b displayed no kinetic solvent effect, whereas ester-substituted radicals 7d and 7e did. The ester-substituted radicals react about as fast as the alkyl-substituted radicals due to favorable polarization in the transition states for ring opening. The phenyl-substituted radical 7e ring-opens about 3 orders of magnitude less rapidly than the parent radical 7a. The structures and energies of the ground states, rotational transition states, and ring-opening transition states for a series of substituted cyclopropylcarbinyl radicals corresponding to 7a−e were computed by the hybrid density functional theory B3LYP/6-31G*, and the ring-opening kinetics were compared to those predicted from the computational barriers. The precision in the Arrhenius functions for ring openings of radicals 7 permits meaningful comparisons of the log A terms to those predicted from thermochemical considerations.

Conical Intersection Mechanism for Photochemical Ring Opening in Benzospiropyran Compounds

The photoinduced ring-opening process in spiropyran compounds has been modeled through CASSCF calculations on the lowest excited state (S1) of benzopyran. The documented S1 reaction coordinate is characterized by a ring-opening transition state connecting a cyclic intermediate to a much more stable acyclic structure. Remarkably this structure does not correspond to a real S1 intermediate but to a crossing point (i.e., a conical intersection) between the excited- and ground-state energy surfaces. At this crossing the excited-state system can undergo fully efficient decay to S0. Using the parent pyran molecule as a model, we have characterized two ground-state valleys which develop from the crossing point. The first valley leads to reactant (pyran) regeneration. The second valley leads to cZc-penta-2,4-dienal indicating that the primary ring-opened photoproduct is formed in an unstable conformation. The benzopyran/pyran reaction coordinates suggest that the first step in the benzospiropyran photochromic reaction must correspond to the excited-state ring opening of the benzopyran moiety. It is shown that while this process can be controlled by a small energy barrier, it ultimately leads to ultrafast radiationless decay at a structure where the C−O bond distance is ca. 2.3 Å. Upon ground-state relaxation this structure can generate either a cZc precursor of merocyanine (via full ring opening) or the starting benzospiropyran (via ring closure). This mechanistic picture seems to be consistent with the present experimental knowledge.

The lowest energy structures of C +7, C 7 and C −7. An ab initio study

Ab initio calculations have been carried out, indicating the ground state of C + 7 is cyclic (≈ 0.9 eV more stable than linear C + 7) but C 7 and C − 7 have linear ground states. Calculations also indicate that the ring opening transition state in C + 7 lies ≈ 2.3 eV above the ground state and is of near C 2v symmetry.

Electron demand in the transition state of the cyclopropylidene to allene ring opening

The electronic structure of the transition state for the cyclopropylidene to allene conversion has been probed. The methodology involved the relative rates of ring opening vs trapping by MeOH for a series of variously substituted 2,3-diarylcyclopropylidenes. With the assumption that the rate of trapping was unaffected by substituents, a Hammett correlation was constructed. The negative values (-0.72) for ρ indicated that the carbenic ceter attracts electron density in the ring-opening transition state, much like the cyclopropyl cation to allyl cation transition state