Biradical Intermediates Research Articles

Experimental and Computational Evidence of the Biradical Structure and Reactivity of Titanium(IV) Enolates.

Quantum chemical calculations have unveiled the unexpected biradical character of titanium(IV) enolates from N-acyl oxazolidinones and thiazolidinethiones. The electronic structure of these species therefore involves a valence tautomerism consisting of an equilibrium between a closed shell (formally Ti(IV) enolates) and an open shell, biradical, singlet (formally Ti(III) enolates) electronic states, whose origin is to be basically found in changes of the Ti-O distance. Spectroscopic studies of the intermediate species lend support to such a model, which also turns out to be crucial for a better understanding of the overall reactivity of titanium(IV) enolates. In this context, a thorough computational analysis of the radical addition of titanium(IV) enolates from N-acyl oxazolidinones to TEMPO has permitted us to suggest an entire mechanism, which accounts for the experimental details and the diastereoselectivity of the process. All together, this evidence highlights the relevance of biradical intermediates from titanium(IV) enolates and may be a useful contribution to the foundations of a more insightful comprehension of the structure and reactivity of titanium(IV) enolates.

Thermal decomposition reaction in ethanol solution of deuterated acetone cyclic diperoxide and acetone diperoxide. Secondary inverse isotopic effect

The characterization by mass spectrometry and the kinetic study of the thermal decomposition reaction of deuterated acetone diperoxide (dACDP) was studied in ethanol in the 140-165 oC temperature range. The comparison with the non deuterated species (ACDP) was also made. The kinetic behavior observed for both compounds follows a pseudo first order kinetic law up to at least 86 % peroxide conversions. It could be observed that under the established experimental conditions, the dACDP decomposes ca. 1.2 times faster than the ACDP. The activation parameters were calculated for both peroxides and allowed to postulate a single process initial step, the unimolecular thermal decomposition through the O-O bond cleavage to form an intermediate biradical. The products of the acetone derived peroxides thermal decomposition support a radical-based decomposition mechanism. The changes in kinetic parameters between dACDP and ACDP were justified attending to differences in ring substituents sizes. A secondary inverse kinetic isotope effect is observed (kH/kD <1).

N2 elimination thermolysis reactions of 9-(4- and 5-substituted-1,2,3-triazol-1-yl)acridines to produce 1H-pyrido-[4,3,2-kl] derivatives – A theoretical study

9-azidoacridine reacts under 1,3-dipolar reaction with alkyne derivatives to yield 9-(4- and 5-substituted-1,2,3-triazol-1-yl)acridine derivatives. The extrusion of N2 from these compounds leads to formation of carbene and biradical intermediates. Radical moieties interact with the acridine ring to form 1H-pyrido-[4,3,2-kl] derivatives. The focus of this study was on the theoretical and computational studies of the pathways of the products. The energy levels of the reactant species, TS forms (transition states), products, the free energies of reaction (ΔrG and ΔG#), HOMO & LUMO orbital levels, the ΔEHOMO-LUMO, dipolmoments, rate constants by using Eyring's equation (k and k′), structural data were calculated by DFT (B3LYP/6-31G∗) method. The relative energies (in kcalmol−1) of the transition states as well as the biradical (singlet (S) and triplet (T); and carbene (singlet (S) and triplet (T); intermediates of the pyrolysis reactions on the reactants were investigated as well. The stepwise of the N2 elimination reactions have also investigated. The values of the free activation energy (ΔG#) in the concerted N2 elimination pyrolysis reactions were correlated to the decomposition temperature (TDecom.) of reactants.

PH Dependent Photodeprotection of Formaldehyde: Homolytic C-C Scission in Acidic Aqueous Solution versus Heterolytic C-C Scission in Basic Aqueous Solution.

The photodeprotection of formaldehyde was investigated for 3-(1-hydroxypropan-2-yl)benzophenone (3-HPBP) with ultrafast time-resolved spectroscopy. The femtosecond transient absorption results indicated the singlet excited state of 3-HPBP transformed efficiently into its triplet state by a fast intersystem crossing. In acidic (pH = 0) and basic (pH = 12.5) aqueous solutions, the triplet intermediate was a key precursor for the deprotection of formaldehyde via two different pathways. However, little photodeprotection was observed in neutral (pH = 7) aqueous solution where the triplet intermediate appeared to undergo a proton coupled electron transfer process to form a ketyl radical transient. The important benzylic biradical intermediates seen in the acidic and basic aqueous solutions were identified by time-resolved resonance Raman spectra whose vibrational frequency patterns were consistent with DFT calculation results for the benzylic biradical intermediate. The results here indicate that the β-carbon alcohol group of the triplet state 3-HPBP is deprotonated in basic aqueous solutions and this leads to a heterolytic C-C bond cleavage to deprotect formaldehyde and produce the benzylic carbanion triplet state species, whereas protonation of the carbonyl moiety of the triplet state 3-HPBP leads to direct generation of a benzylic biradical intermediate and the deprotection of formaldehyde in acidic aqueous solutions via a homolytic C-C bond cleavage.

ChemInform Abstract: High Diastereoselectivity in the Yang Photocyclization via Remote Hydrogen Abstraction Reaction.

1-Benzoyl-1-(o-alkoxyphenyl)cyclopropanes undergo Yang photocyclization to form dihydrobenzo-pyranols in a stereospecific manner. The cyclopropyl group at alpha position to carbonyls gives not only a bias in the most stable geometries of the starting ketones but also conformational restriction on geometries of biradical intermediates. More importantly, intramolecular hydrogen bonds seem to give an additional effect on conformational control of the biradical reactivity.

High Diastereoselectivity in the Yang Photocyclization via Remote Hydrogen Abstraction Reaction

1‐Benzoyl‐1‐(o‐alkoxyphenyl)cyclopropanes undergo Yang photocyclization to form dihydrobenzo‐pyranols in a stereospecific manner. The cyclopropyl group at alpha position to carbonyls gives not only a bias in the most stable geometries of the starting ketones but also conformational restriction on geometries of biradical intermediates. More importantly, intramolecular hydrogen bonds seem to give an additional effect on conformational control of the biradical reactivity.

Photochemistry of 1,4-Dihydropyridine Derivatives: Diradical Formation, Delocalization and Trapping as a Route to Novel Tricyclic and Tetracyclic Nitrogen Heterocyclic Ring Systems.

Irradiation of an acetonitrile solution of 4-aryl-3,5-dibenzoyl-1,4-dihydropyridine derivatives 1a–c and maleimides 2a–c using medium pressure Hg-arc lamp (λ > 290) nm afforded three different cycloadducts 4, 5, 6 in addition to the oxidation products 3. These results indicate that compounds 1a–c undergoes intermolecular cycloaddition reaction through three biradical intermediates and behave photochemically different than those reported previously for the analogous 3,5-diacetyl and 3,5-dicarboxylic acid derivatives. The present work also offers simple access to novel tricyclic and tetracyclic nitrogen heterocyclic ring systems of potential biological and synthetic applications. The structure of the photoproducts was established spectroscopically and by single crystal X-ray crystallography.

Ultrafast time resolved spectroscopic studies on the generation of the ketyl-sugar biradical by intramolecular hydrogen abstraction among ketoprofen and purine nucleoside dyads.

Intramolecular hydrogen abstraction reactions among ketoprofen (KP) and purine nucleoside dyads have been proposed to form ketyl-sugar biradical intermediates in acetonitrile. Femtosecond transient absorption studies on KP and purine nucleoside dyads reveal that the triplet state of the KP moiety of the dyads with cisoid structure decay faster (due to an intramolecular hydrogen abstraction reaction to produce a ketyl-sugar biradical intermediate) than the triplet state of the KP moiety of the dyads with transoid structure detected in acetonitrile solvent. For the cisoid 5-KP-dG dyad, the triplet state of the KP moiety decays too fast to be observed by ns-TR(3); only the ketyl-sugar biradical intermediates are detected by ns-TR(3) in acetonitrile. For the cisoid 5-KP-dA dyad, the triplet states of the KP moiety could be observed at early nanosecond delay times, and then it quickly undergoes intramolecular hydrogen abstraction to produce a ketyl-sugar biradical intermediate. For the cisoid 5-KPGly-dA and transoid 3-KP-dA dyads, the triplet state of the KP moiety had a longer lifetime due to the long distance chain between the KP moiety and the purine nucleoside (5-KPGly-dA) and the transoid structure (3-KP-dA). The experimental and computational results suggest that the ketyl-sugar biradical intermediate is generated with a higher efficiency for the cisoid dyad. However, the transoid dyad exhibits similar photochemistry behavior as the KP molecule, and no ketyl-sugar biradical intermediate was observed in the ns-TR(3) experiments for the transoid 3-KP-dA dyad.

Mechanism of low-molecular alkenes interaction with sulfur-containing spatially hindered phenols under conditions of thermal modification of polymer materials

Transformations in the course of high-temperature modification of polyolefins under action of sulfur-containing modifiers have been studied using hexene-1 and hexane as model compounds. Composition of products of thermolysis of bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl] disulfide and bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propyl] sulfide at 200–270°C has been elucidated by means of thermogravimetry and gas chromatography-mass spectrometry. Mechanism of olefins modification with sulfides and disulfides involving the formation of biradical intermediates is discussed.

A DFT Study of the Photochemical Dimerization of Methyl 3-(2-Furyl)acrylate and Allyl Urocanate

A DFT study of the photochemical dimerization of methyl 3-(2-furyl)acrylate is reported. The photochemical reaction gave a mixture of two dimers with high regioselectivity and good stereoselectivity. Calculations showed that benzophenone was able to act as a photosensitizer of the reaction. This compound populated the first excited triplet state of the substrate. The frontier orbitals interaction between LSOMO of the triplet state and HOMO of the ground state accounted for the observed high regioselectivity. Furthermore, the energy of all the possible triplet biradicals has been calculated, showing that the precursor of the main product was the triplet biradical with the lowest energy. The coupling of the atomic coefficients on the radical centres in the biradical intermediates allowed to justify the observed products. The same behavior was observed in the case of the photochemical dimerization of an urocanate ester and in the dimerization of liquid methyl cinnamate.

Theory of substituent effects on the regioselectivity of di-π-methane rearrangements of dibenzobarrelenes.

The regioselectivities of the di-π-methane rearrangements of unsymmetrically substituted dibenzobarrelenes have been explored with DFT (UM06-2X). Regioselectivity depends on the intramolecular hydrogen bonding and originates from specific stabilization of the triplet biradical intermediates.

Shock Wave Study of the Thermal Dissociations of C3F6 and c-C3F6. II. Dissociation of Hexafluorocyclopropane and Dimerization of CF2

The thermal dissociation of c-C3F6 has been studied in shock waves over the range 620-1030 K monitoring the UV absorption of CF2. The reaction was studied close to its high-pressure limit, but some high-temperature falloff was accounted for. Quantum-chemical and kinetic modeling rationalized the experimental data. The reaction is suggested to involve the 1,3 biradical CF2CF2CF2 intermediate. CF2 formed by the dissociation of c-C3F6 dimerizes to C2F4. The measured rate of this reaction is also found to correspond to the falloff range. Rate constants for 2CF2 → C2F4 as a function of temperature and bath gas concentration [Ar] are given and shown to be consistent with literature values for the high-pressure rate constants from experiments at lower temperatures and dissociation rate constants obtained in the falloff range at higher temperatures. The onset of falloff at intermediate temperatures is analyzed.

Intermediate Partitioning Kinetic Isotope Effects for the NIH Shift of 4-Hydroxyphenylpyruvate Dioxygenase and the Hydroxylation Reaction of Hydroxymandelate Synthase Reveal Mechanistic Complexity

4-Hydroxyphenylpyruvate dioxygenase (HPPD) and hydroxymandelate synthase (HMS) are similar enzymes that catalyze complex dioxygenation reactions using the substrates 4-hydroxyphenylpyruvate (HPP) and dioxygen. Both enzymes decarboxylate HPP and then hydroxylate the resulting hydroxyphenylacetate (HPA). The hydroxylation reaction catalyzed by HPPD displaces the aceto substituent of HPA in a 1,2-shift to form 2,5-dihydroxyphenylacetate (homogentisate, HG), whereas the hydroxylation reaction of HMS places a hydroxyl on the benzylic carbon forming 3'-hydroxyphenylacetate (S-hydroxymandelate, HMA) without ensuing chemistry. The wild-type form of HPPD and variants of both enzymes uncouple to form both native and non-native products. We have used intermediate partitioning to probe bifurcating steps that form these products by substituting deuteriums for protiums at the benzylic position of the HPP substrate. These substitutions result in altered ratios of products that can be used to calculate kinetic isotope effects (KIE) for the formation of a specific product. For HPPD, secondary normal KIEs indicate that cleavage of the bond in the displacement reaction prior to the shift occurs by a homolytic mechanism. NMR analysis of HG derived from HPPD reacting with enantiomerically pure R-3'-deutero-HPP indicates that no rotation about the bond to the radical occurs, suggesting that collapse of the biradical intermediate is rapid. The production of HMA was observed in HMS and HPPD variant reactions. HMS hydroxylates to form exclusively S-hydroxymandelate. When HMS is reacted with R-3'-deutero-HPP, the observed kinetic isotope effect represents geometry changes in the initial transition state for the nonabstracted proton. These data show evidence of sp(3) hybridization in a HPPD variant and sp(2) hybridization in HMS variants, suggesting that HMS stabilizes a more advanced transition state in order to catalyze H-atom abstraction.

Phototriggered Release of a Leaving Group in Ketoprofen Derivatives via a Benzylic Carbanion Pathway, But not via a Biradical Pathway

2-Acetoxymethyl-2-(3-benzoylphenyl)propionic acid (KP-OAc) was used as a model to elucidate the solvent-mediated photochemistry mechanism of Ketoprofen (KP). In solutions with a low concentration of water, KP-OAc exhibits a benzophenone-like photochemistry, reacting with water molecules through some reaction to form a ketyl radical intermediate. In neutral solutions with a high concentration of water or acidic solutions, KP-OAc undergoes a photodecarboxylation reaction with the assistance of water molecules or with the catalysis of perchloric acid to directly generate a biradical intermediate that cannot induce the phototrigger reaction to release the AcO(-) group. Therefore, the lifetime of the biradical intermediate of KP-OAc is almost same as that of the biradical intermediate formed from KP in the same kinds of solutions. However, the photodecarboxylation of KP-OAc in phosphate buffer solution directly produces the benzylic carbanion intermediate, which can induce the phototrigger reaction to release the AcO(-) group. Therefore, the lifetime of the biradical intermediate of KP-OAc is significantly shorter than the lifetime of the biradical intermediate of KP in phosphate buffer solution. Interestingly, the investigation of the photochemistry of KP-OAc not only verifies the solvent-mediated photochemistry mechanism of KP but also provides some new insight into the potential of using this kind of platform for phototrigger applications. The biradical intermediate is not the key species leading to the phototrigger reaction but the benzylic carbanion species is the key reactive intermediate that can mediate the phototrigger reaction of KP-OAc. Therefore, a change in the pH of the solutions can be utilized to switch on and switch off the photorelease reactions of KP derivative phototrigger compounds.

Generation and Characterization of a Distonic Biradical Anion Formed from an Enediynone Prodrug in the Gas Phase

A negatively charged biradical intermediate was successfully generated in the gas phase via cyclization of the deprotonated bicyclo[8.3.0]trideca-12-ene-2,7-diyn-1-one precursor. The inherent negative charge of this biradical allows its characterization via collision-activated dissociation and reactions with a variety of neutral substrates in an FT-ICR mass spectrometer. Although the biradical is unreactive toward reagents that usually react rapidly with positively charged biradicals, such as dimethyl disulfide, it reacts with the halogen-containing substrates carbon tetrachloride, carbon tetrabromide, and bromotrichloromethane via bromine or chlorine atom abstraction, which supports its biradical structure. The results presented in this study indicate that cyclizations commonly used in solution to form biradical intermediates from enediyne compounds may also occur in the gas phase.

A comparative study on the gas-phase and liquid-phase thermal isomerization reaction of α-pinene

In this paper, a method of preparation of ocimene is investigated, which is obtained from isomerization reaction of α-pinene. Two kinds of experimental apparatus are established for the investigation of the thermal isomerization reaction of α-pinene. The behavior of thermal isomerization reaction of α-pinene is respectively discussed in the gas phase and in the liquid phase. Under gas phase conditions, the conversion of α-pinene is 80% and the selectivity of ocimene is 30%–33%. Under liquid phase conditions, the conversion of α-pinene is 60% and the selectivity of ocimene is 50%–54%. According to the kinetic-molecular theory of ideal gases, two kinds of reaction models are proposed to visualize the reaction process. In addition, the mechanism and kinetics of thermal isomerization reaction of α-pinene are respectively discussed. The conclusion is that the gas phase reaction temperature is calculated to be 390–450 °C and the liquid phase reaction temperature is calculated to be 450–550 °C. From a bond dissociation energy point of view, results support the hypothesis that the reaction involves biradical intermediates. Copyright © 2012 John Wiley & Sons, Ltd.

Regio- and sterochemistry of the [2+2]-cycloaddition reaction between enones and alkenes. A DFT study

Calculations at DFT/B3LYP/6-31G+(d,p) level of theory have been performed on the photochemical interaction between enones and alkenes. The photochemical reaction of cyclopentenone with ethyl vinyl ether can be explained assuming the reaction occurs through the triplet excited state of the enone. The interaction between the LSOMO of triplet cyclopentenone and the HOMO of ethyl vinyl ether accounts for the observed stereochemistry. The same behaviour has been observed in the reaction of 3-methylcyclohexenone with 1,1-dimethoxyethene, vinyl acetate, and allene. In the reaction of 3,5,5-trimethylcyclohexenone with methyl cyclobutene-1-carboxylate, the observed regiochemistry can be explained assuming a sensitized reaction able to populate the triplet state of methyl cyclobutene-1-carboxylate. The coupling of the HSOMO of this species with the LUMO of the cyclohexenone derivative account for the observed regiochemistry. Furthermore, the coupling of the radical carbon atoms on the biradical intermediate accounts for the observed stereochemistry. In the reaction of 3-methylcyclohexenone with methyl cyclohexene-1-carboxylate the coupling between the LSOMO of triplet state of 3-methylcyclohexenone and the HOMO of the alkene gave two possible biradical intermediates. The most stable one accounts for the observed regiochemistry. The coupling of the radical carbon atom on the HSOMO and LSOMO of the biradical intermediate accounts for the observed stereochemistry. The coupling between the LSOMO of the triplet state of 3-phenylcyclohexenone and the HOMO of cyclopentene accounts for the observed regiochemistry. The stereochemistry can be explained considering the coupling of the LSOMO and HSOMO in the biradical intermediate.

Substituent Effects in Thermal Reactions of a Silene with Silyl-Substituted Alkynes: A Theoretical Study

Thermal reactions of a silene derivative (Me3Si)2Si═C(OSiMe3)(t-Bu) (1) with silyl-substituted acetylenes, bis(trimethylsilyl)butadiyne, tert-butyldimethylsilylacetylene, and bis(trimethylsilyl)acetylene have been investigated with density functional theory calculations for the understanding of substituent effects in the reactivity of the silene. The first critical reaction step for determining the final product is the formation of a biradical intermediate from 1 and the acetylenes. A stepwise [2 + 2] cycloaddition via the biradical intermediate gives a silacyclobutene derivative, which is the precursor of the final product. The activation energy for this reaction step as well as thermodynamic stability of the biradical intermediate is governed by an interplay between geometric and electronic factors. The biradical intermediate is destabilized by steric hindrance between bulky substituents on 1 and acetylene, while it can be stabilized by delocalization of an unpaired electron in the acetylene moiety. Silacyclobutene derivatives undergo Si–C bond cleavage to give silabutadiene derivatives. The second critical reaction step is the attack of the OSiMe3 group on the silene Si atom in the silabutadienes. If the substituent on one of the acetylene C atoms does not easily migrate, the SiMe3 group of the OSiMe3 group rebounds to the silene C atom to form an oxasilacyclopentene derivative. If this substituent migrates easily, on the other hand, it migrates to the silene C atom with a simultaneous migration of the OSiMe3 group, resulting in the formation of an allene derivative.

ChemInform Abstract: The Cope Rearrangement — The First Born of a Great Family

AbstractReview: 124 refs.

The Rearrangement of 2,2‐Diphenyl‐1‐[(E)‐2‐phenylethenyl]cyclopropane to 3,4,4‐Triphenylcyclopent‐1‐ene: a DFT Analysis

AbstractA computational study on the rearrangement of 2,2‐diphenyl‐1‐[(E)‐2‐phenylethenyl]cyclopropane (1) is presented, using density functional theory (DFT), (U)B3LYP with the 6‐31G* basis set (DFT1) and (U)M05‐2X with the 6‐311+G** basis set (DFT2). In agreement with a biradical character of the transition structure (TS) or intermediate, the potential‐energy hypersurface is lowered by the influence of three conjugated Ph groups. Surprisingly, two conformations of the geminal diphenyl group (different twist angles) induce two different minimum‐energy pathways for the rearrangement. Independent of the functional used, the first hypersurface harbors true biradical intermediates, whereas the second energy surface is a flat, slightly ascending slope from the starting material to the TS. The functional (U)M05‐2X with the basis set 6‐311+G** provides realistic energies which seem to be close to experiment. The activation energy for racemization of enantiomers of 1 is lower than that of rearrangement by 2.5 kcal mol−1, in agreement with experiment.