Reactivity of the 4,5‐Didehydroisoquinolinium Cation

The chemical properties of a 1,8‐didehydronaphthalene derivative, the 4,5‐didehydroisoquinolinium cation, were examined in the gas phase in a dual‐cell Fourier‐transform ion cyclotron resonance (FT‐ICR) mass spectrometer. This is an interesting biradical because it has two radical sites in close proximity, yet their coupling is very weak. In fact, the biradical is calculated to have approximately degenerate singlet and triplet states. This biradical was found to exclusively undergo radical reactions, as opposed to other related biradicals with nearby radical sites. The first bond formation occurs at the radical site in the 4‐position, followed by that in the 5‐position. The proximity of the radical sites leads to reactions that have not been observed for related mono‐ or biradicals. Interestingly, some ortho‐benzynes have been found to yield similar products. Since ortho‐benzynes do not react via radical mechanisms, these products must be especially favorable thermodynamically.     

Reactivity of aromatic σ,σ-biradicals toward riboses

The gas-phase reactions of sugars with aromatic, carbon-centered sigma,sigma-biradicals with varying polarities [as reflected by their calculated electron affinities (EA)] and extent of spin-spin coupling [as reflected by their calculated singlet-triplet (S-T) gaps] have been studied. The biradicals are positively charged, which allows them to be manipulated and their reactions to be studied in a Fourier-transform ion cyclotron resonance mass spectrometer. Hydrogen atom abstraction from sugars was found to be the dominant reaction for the biradicals with large EA values, while the biradicals with large S-T gaps tend to form addition/elimination products instead. Hence, not all sigma, sigma-biradicals may be able to damage DNA by hydrogen atom abstraction. The overall reaction efficiencies of the biradicals towards a given substrate were found to be directly related to the magnitude of their EA values, and inversely related to their S-T gaps. The EA of a biradical appears to be a very important rate-controlling factor, and it may even counterbalance the reduced radical reactivity characteristic of singlet biradicals that have large S-T gaps.     

Does intersystem crossing in triplet biradicals generate singlets with conformational memory?

The effect of temperature, concentration, external magnetic fields and paramagnetic quenchers on the lifetime of biradicals produced in the Norrish Type II reaction has been examined. Analysis of this data and that available from earlier reports leads to the conclusion that in addition to controlling the biradical lifetimes, intersystem crossing in triplet-derived biradicals plays a critical role in determining the behaviour and products which result from singlet biradical reactions. The effect is attributed to conformational memory in the singlet biradical which reflects its short lifetime.     

Gas-phase reactivity of charged pi-type biradicals

Four pi,pi-biradicals, 2,6-dimethylenepyridinium and the novel isomers N-(3-methylenephenyl)-3-methylenepyridinium, N-phenyl-3,5-dimethylenepyridinium, and N-(3,5-dimethylenephenyl)pyridinium ions, were generated and structurally characterized in a Fourier transform ion cyclotron resonance mass spectrometer. Their gas-phase reactivity toward various reagents was compared to that of the corresponding monoradicals, 2-methylenepyridinium, N-phenyl-3-methylenepyridinium, and N-(3-methylenephenyl)pyridinium ions. The biradicals reactivity was found to reflect their predicted multiplicity. The 2,6-dimethylenepyridinium ion, the only biradical in this study predicted to have a closed-shell singlet ground state, reacts significantly faster than the other biradicals, which are predicted to have triplet ground states. In fact, this biradical reacts at a higher rate than the analogous monoradical, which suggests that to avoid the costly uncoupling of its unpaired electrons, the biradical favors ionic mechanisms over barriered radical pathways. In contrast, the second-order reaction rate constants of the isomeric biradicals with triplet ground states are well approximated by those of the analogous monoradicals, although the final reaction products are sometimes different. This difference arises from rapid radical-radical recombination of the initial monoradical reaction products. The overall reactivity toward the hydrogen-atom donors benzeneselenol and tributylgermanium hydride is significantly greater for the radicals with the charged site in the same ring system as the radical site. This finding indicates that polar effects play an important role in controlling the reactivity of pi,pi-biradicals, just as has been demonstrated for sigma,sigma-biradicals.     

Reactions of an aromatic σ,σ-biradical with amino acids and dipeptides in the gas phase

Gas-phase reactivity of a positively charged aromatic σ,σ-biradical (N-methyl-6,8-didehydroquinolinium) was examined toward six aliphatic amino acids and 15 dipeptides by using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR) and laser-induced acoustic desorption (LIAD). While previous studies have revealed that H-atom and NH₂ abstractions dominate the reactions of related monoradicals with aliphatic amino acids and small peptides, several additional, unprecedented reaction pathways were observed for the reactions of the biradical. For amino acids, these are 2H-atom abstraction, H₂O abstraction, addition — CO₂, addition — HCOOH, and formation of a stable adduct. The biradical reacts with aliphatic dipeptides similarly as with aliphatic amino acids, but undergoes also one additional reaction pathway, addition/C-terminal amino acid elimination (addition — CO — NHCHR_C). These reactions are initiated by H-atom abstraction by the biradical from the amino acid or peptide, or nucleophilic addition of an NH₂ or a HO group of the amino acid or peptide at the radical site at C-6 in the biradical. Reactions of the unquenched C-8 radical site then yield the products not observed for related monoradicals. The biradical reacts with aromatic dipeptides with an aromatic ring in N-terminus (i.e., Tyr-Leu, Phe-Val, and Phe-Pro) similarly as with aliphatic dipeptides. However, for those aromatic dipeptides that contain an aromatic ring in the C-terminus (i.e., Leu-Tyr and Ala-Phe), one additional pathway, addition/N-terminal amino acid elimination (addition — CO — NHCHR_N), was observed. This reaction is likely initiated by radical addition of the biradical at the aromatic ring in the C-terminus. Related monoradicals add to aromatic amino acids and small peptides, which is followed by Cα-Cβ bond cleavage, resulting in side-chain abstraction by the radical. For biradicals, with one unquenched radical site after the initial addition, the reaction ultimately results in the loss of the N-terminal amino acid. Similar to monoradicals, the C-S bond in amino acids and dipeptides was found to be especially susceptible to biradical attack.     

A strategy for the preparation of cyclic polyarenes based on single electron transfer-promoted photocyclization reactions

Single electron transfer (SET)-promoted photocyclization reactions of substrates comprised of benzylsilane tethered to phthalimides were subjected to an exploratory study in order to probe a new approach for the preparation of cyclic polyarenes. The results show that UV irradiation of the substrates leads to efficient photochemical reactions that are initiated by SET from benzylsilane moieties to the excited phthalimide acceptor. Ensuing desilylation reactions of the benzylsilane cation radical moieties in the intermediate zwitterionic biradicals and proton transfer gives biradical precursors of the cyclic polyarene products. The observations made in this effort suggests that SET photochemical methods, which have been employed earlier to generate cyclic poly-ethers, -thioethers and -amides, serve as a useful method to access potentially interesting macrocyclic targets.     

Lamp versus Laser Photolysis of a Bichromophoric Dichloroalkane: Chemical Evidence for the Two-Photon Generation of the 1,5-Diphenylpentanediyl Biradical

Low intensity (lamp) photolysis of 1,5-dichloro-1,5-diphenylpentane (1) leads to the formation of the 1-chloro-1,5-diphenylpentyl radical (7) through C-Cl bond cleavage. Radical 7 leads to the final products through typical free radical reactions. No cyclopentanes are formed under low intensity conditions. In contrast, high intensity laser irradiation leads to C-Cl photocleavage of radical 7 to yield the 1,5-diphenylpentanediyl biradical (11), which results in the formation of isomeric cis- and trans-1,2-diphenylcyclopentanes; the behavior of these biradicals agrees well with that observed when their precursor is 2,6-diphenylcyclohexanone. Two-color two-laser experiments suggest that both singlet and triplet biradicals are formed, even if only the latter are detectable with nanosecond techniques.     

Laser flash photolysis of [3,n]paracyclophan-2-ones. Direct observation and chemical behavior of 4,4'-(1,n-alkanediyl)bisbenzyl biradicals

The 4,4'-(1,n-alkanediyl)bisbenzyl biradicals (2b-d) have been generated from the Norrish type-I reaction of [3,n]paracyclophan-2-ones (1b-d) giving the paracyclophanes 3b-d as the only reaction products. The behavior of biradicals 2b-d has been studied in detail and compared with the previously reported biradical 2a. The lifetimes increase as the chain length decreases and are affected by the solvent viscosity, thus showing the effect of the length of the chain on the conformations of the biradicals. Quenching with persistent radicals such as TEMPO resulted in length-dependent rate constants. Finally, the study of the magnetic field effects on the biradical lifetimes suggest that ISC control determines biradical lifetimes for long-chain systems.     

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.     

Intermolecular Photocyclizations of N‐(ω‐Hydroxyalkyl)tetrachlorophthalimide with Alkenes Leading to Medium‐ and Large‐Ring Heterocycles—Reaction Modes and Regio‐ and Stereoselectivity of the 1,n‐Biradicals

A new photocyclization strategy by using intermolecular tandem reactions between N‐(ω‐hydroxyalkyl)‐4,5,6,7‐tetrachlorophthalimides ( 1 , 2 , and 3 ) and a series of acyclic and cyclic alkenes is reported. Electron transfer of the triplet‐excited phthalimide with the alkene and regioselective trapping of the alkene cation radical by the hydroxyl group at the phthalimide side chain gives a triplet 1,n‐biradical, which after intersystem crossing (ISC) leads to regio‐ and diastereoselective synthesis of polycyclic heterocycles with an N,O‐containing medium to large ring. Regio‐ and diastereoselectivity in the cyclizations are clarified by unambiguous steric structure assignments of the products by X‐ray diffraction or extensive 2D NMR measurements. The diastereoselectivity is decided by the stereochemical course of the ISC process of the triplet 1,n‐biradicals. These intermolecular photoreactions also furnish a new strategy to generate triplet 1,n‐biradicals. Therefore, in photoreactions of 1 and 2 with phenylcyclohexene, the unprecedented stereoselective formation of products by intramolecular hydrogen‐atom transfer in the 1,n‐biradical intermediate was found ( 9 and 23 ). These facts provide direct verification to the reaction pathways of the 1,n‐biradicals and give a new insight into the factors deciding reaction‐pathway partitioning and stereoselectivity.     

Reactivity Controlling Factors for an Aromatic Carbon‐Centered σ,σ,σ‐Triradical: The 4,5,8‐Tridehydroisoquinolinium Ion

The chemical properties of the 4,5,8‐tridehydroisoquinolinium ion (doublet ground state) and related mono‐ and biradicals were examined in the gas phase in a dual‐cell Fourier‐transform ion cyclotron resonance (FT‐ICR) mass spectrometer. The triradical abstracted three hydrogen atoms in a consecutive manner from tetrahydrofuran (THF) and cyclohexane molecules; this demonstrates the presence of three reactive radical sites in this molecule. The high (calculated) electron affinity (EA=6.06 eV) at the radical sites makes the triradical more reactive than two related monoradicals, the 5‐ and 8‐dehydroisoquinolinium ions (EA=4.87 and 5.06 eV, respectively), the reactivity of which is controlled predominantly by polar effects. Calculated triradical stabilization energies predict that the most reactive radical site in the triradical is not position C4, as expected based on the high EA of this radical site, but instead position C5. The latter radical site actually destabilizes the 4,8‐biradical moiety, which is singlet coupled. Indeed, experimental reactivity studies show that the radical site at C5 reacts first. This explains why the triradical is not more reactive than the 4‐dehydroisoquinolinium ion because the C5 site is the intrinsically least reactive of the three radical sites due to its low EA. Although both EA and spin–spin coupling play major roles in controlling the overall reactivity of the triradical, spin–spin coupling determines the relative reactivity of the three radical sites.     

Reactivity of the N-methylene-5,8-didehydroisoquinolinium triradical ion

The reactivity of a sigma,sigma,pi-triradical, N-methylene-5,8-didehydroisoquinolinium ion, has been compared to that of four related mono- and biradicals in a Fourier transform ion cyclotron resonance mass spectrometer. The triradical contains two weakly interacting orthogonal radical systems-the sigma,sigma-biradical moiety and the pi-monoradical moiety. The sigma,sigma-biradical moiety is found to be substantially more reactive than the pi-radical moiety. The pi-radical site reacts only after reactions have quenched the sigma-radical sites.     

Stereodifferentiation in the decay of triplets and biradicals involved in intramolecular hydrogen transfer from phenols or indoles to pi,pi aromatic ketones

Laser flash photolysis studies on (R,S) and (S,S) diastereoisomers of the bichromophoric compounds 1-6 have been used to investigate the possible chiral discrimination in the quenching of triplet excited ketones, resulting in formal hydrogen abstraction. Deuterium isotopic effects show that triplet deactivation in these bichromophores is dominated by hydrogen atom transfer. A remarkable stereodifferentiation is found in the intramolecular quenching of the ketone triplets of 1-3 and 5 by the phenolic or indolic moieties, either in methanol or acetonitrile as solvents. This indicates the existence of specific structural requirements for hydrogen transfer. On the other hand, the lifetimes of the generated biradicals show large solvent dependence; solvation appears to slow their reversion to the starting ketone. The considerable stereodifferentiation observed for the biradical lifetimes suggests that the kinetics of biradical decay is faster when the approach of the two radical termini becomes easier.     

Rigid orthogonal bis-TEMPO biradicals with improved solubility for dynamic nuclear polarization

The synthesis and characterization of oxidized bis-thioketal-trispiro dinitroxide biradicals that orient the nitroxides in a rigid, approximately orthogonal geometry are reported. The biradicals show better performance as polarizing agents in dynamic nuclear polarization (DNP) NMR experiments as compared to biradicals lacking the constrained geometry. In addition, the biradicals display improved solubility in aqueous media due to the presence of polar sulfoxides. The results suggest that the orientation of the radicals is not dramatically affected by the oxidation state of the sulfur atoms in the biradical, and we conclude that a biradical polarizing agent containing a mixture of oxidation states can be used for improved solubility without a loss in performance.     

Mechanism of thermal reactions of dimerization and trimerization of hexafluoro-1,3-butadiene: A quantum-chemical study

The mechanism of thermal oligomerization of hexafluoro-l,3-butadiene was examined using RHF, ROHF, and GVB/DH, and by B3LYP/6-31G* and /6-311G* quantum-chemical methods. The energies of highly reactive excited states of the monomer and of intermediate biradical species were estimated. Isomeric biradicals (excited monomers and dimers) with the free valences localized on two carbon atoms were shown to coexist in the reaction mixture. Recombination of such biradicals and their reactions with neutral stable molecules give rise to diverse products, depending on the reaction temperature.     

A computational study of the factors controlling triplet-state reactivity in 1,4-pentadiene

The triplet-state reactions of 1,4-pentadiene have been investigated using density functional theory (UB3LYP) and ab initio (CASSCF) calculations with a 6-31G basis set. Intramolecular [2 + 2] photocycloadditions and three different reaction pathways leading to vinylcyclopropane have been examined. The computed results are in good agreement with the experimental observations, predicting the dominant product to be vinylcyclopropane produced by a di-pi-methane rearrangement, and the favored [2 + 2] cycloaddition product to be bicyclo[2.1.0]pentane. Reaction pathways involving initial C-C or C-H bond cleavage were found to be too high in energy to be significant. Both the [2 + 2] cycloadditions and the di-pi-methane rearrangement proceed through cyclic biradical intermediates formed on the triplet surface. The relative rates of formation of these triplet biradicals are found to depend on three factors: biradical stability, the geometry of the transition structure, and orbital interactions through bonds.     

An EPR Study on Intramolecular Spin Exchange and Rotational Mobility of Nitroxides Linked by a Longchain

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The photochemistry of polydonor-substituted phthalimides: Curtin-Hammett-type control of competing reactions of potentially interconverting zwitterionic biradical intermediates

The results of studies designed to obtain information about the factors that control the chemical efficiencies/regioselectivities and quantum yields of single electron transfer (SET)-promoted reactions of acceptor-polydonor systems are reported. Photochemical and photophysical investigations were carried out with bis-donor tethered phthalimides and naphthalimides of general structure N-phthalimido- and N-naphthalimido-CH2CH2-D-CH2CH2-NMsCH2-E (E = SiMe3 or CO2NBu4 and D = NMs, O, S, and NMe). These substrates contain common terminal donor groups (NMsCH2SiMe3 or NMsCH2CO2NBu4) that have known oxidation potentials and cation radical fragmentation rates. Oxidation potentials and fragmentation rates at the other donor site in each of these substrates are varied by incorporating different heteroatoms and/or substituents. Photoproduct distribution, reaction quantum yield, and fluorescence quantum yield measurements were made. The results show that photocyclization reactions of alpha-trimethylsilylmethansulfonamide (E = SiMe3)- and alpha-carboxymethansulfonamide (E = CO2NBu4)-terminated phthalimides and naphthalimides that contain internal sulfonamide, ether, and thioether donor sites (D = NMs, O, or S) are chemically efficient (80-100%) and that they take place exclusively by a pathway involving sequential photoinduced SET (zwitterionic biradical desilylation or decarboxylation) biradical cyclization. In contrast, photoreactions of alpha-trimethylsilylmethansulfonamide- and alpha-carboxymethansulfonamide-terminated phthalimides and naphthalimides that that contain an internal tertiary amine donor site (D = NMe) are chemically inefficient and follow a pathway involving alpha-deprotonation at the tertiary amine radical cation center in intermediate, iminium radical-containing, zwitterionic biradicals. In addition, the quantum efficiencies for photoreactions of alpha-trimethylsilylmethansulfonamide- and alpha-carboxymethansulfonamide-terminated phthalimides are dependent on the nature of the internal donor (eg., phi = 0.12 for D = NMs, E = SiMe3; phi = 0.02 for D = S, E = SiMe3; phi = 0.04 for D = NMe, E = SiMe3). The results of this effort are discussed in terms of how the relative energies of interconverting zwitterionic biradical intermediates and the energy barriers for their alpha-heterolytic fragmentation reactions influence the chemical yields and quantum efficiencies of SET promoted photocyclization reactions of acceptor-polydonor substrates.     

What definitively controls the photochemical activity of methylbenzonitriles and methylanisoles? Insights from theory

CASPT2//CASSCF and B3LYP methodologies have been used to study the excited-state properties and photochemical isomerizations of p-, m-, and o-methylbenzonitriles and methylanisoles. Calculations show that the biradical mechanism is the most favored channel for the photoinduced interconversion of p-, m- and o-methylbenzonitriles, both dynamically and thermodynamically. The formation of biradical as a key intermediate is highly selective, and only the biradicals with a turned-up cyano-substituted carbon are involved in photoisomerization. Methylanisole isomers are inactive relative to methylbenzonitriles at 254 nm. Such remarkable activity difference between methylbenzonitrile and methylanisole in photochemistry arises from the accessibility of the S1/S0 conical intersection as well as the stability of prefulvene biradicals. For methylanisoles, the S1/S0 precursor and the reactive biradicals are inaccessible at 254 nm, which should be the origin of inactivity. The results suggest that the conical intersection accessibility plays a crucial role in the photochemistry of substituted benzenes at 254 nm.     

An EPR Study on Intramolecular Spin Exchange,Rotational Mobility of Nitroxides Linked by a Long-chain

The effects of pressure, solvent on the intramolecular spin exchange of biradicals having two nitroxide fragments linked by a long flexible chain were studied by means of highpressure EPR technique. It was found that the intramolecular exchange interaction between nitroxides of biradical took place through the direct contact between them. By analyzing the observed EPR spectra, we have estimated the ratio(Τ_in/Τ_out) value of the average lifetime of the radical fragments inside a cage(Τ_in) to that outside the cage(Τ_out). The Τ_in/Τ_out values decreased with decreasing temperature, increasing pressure. The results suggest that the nearly cyclic conformation in a cage is favorable in solution. Fur ther, the rotational correlation time of individual nitroxide was estimated from the anisotropic EPR signal,, the information on the segmental motion of the nitroxide group in biradical was obtained.