Studies on the mechanism of action of prekinamycin, a member of the diazoparaquinone family of natural products: evidence for both sp2 radical and orthoquinonemethide intermediates

The putative reductive activation chemistry of the diazoparaquinone antibiotics was modeled with Bu(3)Sn-H and prekinamycin dimethyl ether along with prekinamycin itself. Reaction in various combinations of aromatic solvents, with and without the nucleophile benzylmercaptan present, led to isolation of both radical-trapping arene adducts and nucleophilic capture benzyl thioether products. On the basis of these product distribution studies, the intermediacies of, first, a cyclopentenyl radical and, next, an orthoquinonemethide electrophile are postulated.     

Selective generation and reactivity of 5'-adenosinyl and 2'-adenosinyl radicals

The reaction of hydrated electrons (e(-)(aq) with 8-bromoadenosine 7 has been investigated by radiolytic methods coupled with product studies. Pulse radiolysis revealed that one-electron reductive cleavage of the C-Br bond gives the C8 radical 8 followed by a fast radical translocation to the sugar moiety. The reaction is partitioned between C5' and C2' positions in a 60:40 ratio leading to 5'-adenosinyl radical 9 and 2'-adenosinyl radical 11. This radical translocation from C8 to different sites of the sugar moiety has also been addressed computationally by means of DFT B3LYP calculations. In addition, ketone 21 was prepared and photolyzed providing an independent generation of C2' radical 11. Both C5' and C2' radicals undergo unimolecular reactions. Radical 9 attacks adenine with a rate constant of 1.0 x 10(4) s(-1) and gives the aromatic aminyl radical 10, whereas C2' radical 11 liberates adenine with a rate constant of 1.1 x 10(5) s(-1).     

Formation of benzo-fused carbocycles by formal radical cyclization onto an aromatic ring

An indirect method for effecting radical carbocyclization onto aromatic rings is described. Cross-conjugated dienones such as 13, readily prepared by Birch reduction of aromatic tert-butyl esters, in situ alkylation, and oxidation (10 --> 11 --> 12 --> 13), undergo radical cyclization; the products (14) are aromatized by silylation, Saegusa oxidation, and treatment with BiCl3.H2O. A noteworthy feature of this route is that it provides opportunities to attach an additional substituent to the original aromatic ring.     

Kinetics of the reaction of the 2,4,6-tri-tert-butylphenoxyl radical with aromatic amines under quasiequilibrium conditions,and the dissociation energy of the N-H bond in aromatic amines

We have studied the kinetics of the reaction of the 2,4,6-tri-tert-butylphenoxyl radical with 11 aromatic amines under quasiequilibrium conditions. The equilibrium constant for each amine was determined from the kinetic results. These values, together with their temperature dependence, were used to calculate the dissociation energy of the N-H bond in the 11 aromatic amines. By using earlier results for the reaction of the aroxyl radical with cumyl hydroperoxide, catalyzed by aromatic amines, we have calculated the rate constants for the reaction of 10 aminyl radicals with cumyl hydroperoxide and of cumylperoxy radicals with 10 aromatic amines.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 743–749, April, 1990.     

Highly conjugated p-quinonoid pi-extended tetrathiafulvalene derivatives: a class of highly distorted electron donors

A new class of pi-extended TTF-type electron donors (11 a-c) has been synthesized by Wittig-Horner olefination of bianthrone (9) with 1,3-dithiole phosphonate esters (10 a-c). In cyclic voltammetry experiments, donors 11 a-c reveal a single, electrochemically irreversible oxidation-yielding the corresponding dicationic products-at relatively low oxidation potentials (approximately 0.7-0.8 V). Theoretical calculations, performed at the DFT level (B3 P86/6-31 G*), predict a highly-folded C(2h) structure for 11 a. In the ground state, the molecule adopts a double saddle-like conformation to compensate the steric hindrance. The calculations suggest that the intramolecular charge transfer associated with the HOMO-->LUMO transition is responsible for an absorption band observed above 400 nm. While the radical cation 11 a*+ retains the folded C(2h) structure predicted for the neutral molecule as the most stable conformation, the dication 11 a(2+) has a fully aromatic D(2) structure, formed by an orthogonal 9,9'-bianthryl central unit to which two singly-charged dithiole rings are attached. The drastic conformational changes that compounds 11 undergo upon oxidation account for their electrochemical properties. By means of pulse radiolysis measurements, radical-induced one-electron oxidation of 11 a-c was shown to lead to the radical cation species (11 a-c*+), which were found to disproportionate with generation of the respective dication species (11 a-c(2+)) and the neutral molecules (11 a-c).     

Gas-phase reactions of aryl radicals with 2-butyne: experimental and theoretical investigation employing the N-methyl-pyridinium-4-yl radical cation

Aromatic radicals form in a variety of reacting gas-phase systems, where their molecular weight growth reactions with unsaturated hydrocarbons are of considerable importance. We have investigated the ion-molecule reaction of the aromatic distonic N-methyl-pyridinium-4-yl (NMP) radical cation with 2-butyne (CH(3)C≡CCH(3)) using ion trap mass spectrometry. Comparison is made to high-level ab initio energy surfaces for the reaction of NMP and for the neutral phenyl radical system. The NMP radical cation reacts rapidly with 2-butyne at ambient temperature, due to the apparent absence of any barrier. The activated vinyl radical adduct predominantly dissociates via loss of a H atom, with lesser amounts of CH(3) loss. High-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry allows us to identify small quantities of the collisionally deactivated reaction adduct. Statistical reaction rate theory calculations (master equation/RRKM theory) on the NMP+2-butyne system support our experimental findings, and indicate a mechanism that predominantly involves an allylic resonance-stabilized radical formed via H atom shuttling between the aromatic ring and the C(4) side-chain, followed by cyclization and/or low-energy H atom β-scission reactions. A similar mechanism is demonstrated for the neutral phenyl radical (Ph˙)+2-butyne reaction, forming products that include 3-methylindene. The collisionally deactivated reaction adduct is predicted to be quenched in the form of a resonance-stabilized methylphenylallyl radical. Experiments using a 2,5-dichloro substituted methyl-pyridiniumyl radical cation revealed that in this case CH(3) loss from the 2-butyne adduct is favoured over H atom loss, verifying the key role of ortho H atoms, and the shuttling mechanism, in the reactions of aromatic radicals with alkynes. As well as being useful phenyl radical analogues, pyridiniumyl radical cations may form in the ionosphere of Titan, where they could undergo rapid molecular weight growth reactions to yield polycyclic aromatic nitrogen hydrocarbons (PANHs).     

Radikalinduzierte intramolekulare 1, 4-Verschiebung einer Formylgruppe

Radical-induced Intramolecular 1,4-Transfer of a Formyl Group A further example of a radical-induced intramolecular shift of a functional group in steroids is described. In analogy to the sequence leading to the 1, 4-transfer of cyano groups [3], 11 β-nitrite photolysis was used to generate the appropriate C (18) radical in the 20-hydroxy-11 β-nitrosyloxy-pregnene-21-al 6 . Intramolecular addition of the radical center to the double-bond of the specially adjacent aldehyde function, followed by fragmentation of the intermediate cyclic alkoxy radical and subsequent oxidation lead directly to the rearranged 18-formyl compound 10 .     

Radical C−N Borylation of Aromatic Amines Enabled by a Pyrylium Reagent

Herein, we report a radical borylation of aromatic amines through a homolytic C(sp²)−N bond cleavage. This method capitalizes on a simple and mild activation via a pyrylium reagent (^ScPyry-OTf) thus priming the amino group for reactivity. The combination of terpyridine and a diboron reagent triggers a radical reaction which cleaves the C(sp²)−N bond and forges a new C(sp²)−B bond. The unique non-planar structure of the pyridinium intermediate, provides the necessary driving force for the aryl radical formation. The method permits borylation of a wide variety of aromatic amines indistinctively of the electronic environment.     

Photocatalytic Difunctionalization of Vinyl Ureas by Radical Addition Polar Truce–Smiles Rearrangement Cascades

We report tandem alkyl‐arylations and phosphonyl‐arylations of vinyl ureas by way of a photocatalytic radical‐polar crossover mechanism. Addition of photoredox‐generated radicals to the alkene forms a new C?C or C?P bond and generates a product radical adjacent to the urea function. Reductive termination of the photocatalytic cycle generates an anion that undergoes a polar Truce–Smiles rearrangement, forming a C?C bond. The reaction is successful with a range of α‐fluorinated alkyl sodium sulfinate salts and diarylphosphine oxides as radical precursors, and the conformationally accelerated Truce–Smiles rearrangement is not restricted by the electronic nature of the migrating aromatic ring. Formally the reaction constitutes an α,β‐difuctionalisation of a carbon–carbon double bond, and proceeds under mild conditions with visible light and a readily available organic photocatalyst. The products are α,α‐diaryl alkylureas typically functionalized with F or P substituents that may be readily converted into α,α‐diaryl alkylamines.     

Ascorbic Acid as an Initiator for the Direct CH Arylation of (Hetero)arenes with Anilines Nitrosated In Situ

Ascorbic acid (vitamin C) has been used as a radical initiator in a metal‐free direct C? H arylation of (hetero)arenes. Starting from an aniline, the corresponding arenediazonium ion is generated in situ and immediately reduced by vitamin C to an aryl radical that undergoes a homolytic aromatic substitution with a (hetero)arene. Notably, neither heating nor irradiation is required. This procedure is mild, operationally simple, and constitutes a greener approach to arylation.     

Ascorbic Acid as an Initiator for the Direct C?H Arylation of (Hetero)arenes with Anilines Nitrosated In Situ

Ascorbic acid (vitamin C) has been used as a radical initiator in a metal‐free direct C H arylation of (hetero)arenes. Starting from an aniline, the corresponding arenediazonium ion is generated in situ and immediately reduced by vitamin C to an aryl radical that undergoes a homolytic aromatic substitution with a (hetero)arene. Notably, neither heating nor irradiation is required. This procedure is mild, operationally simple, and constitutes a greener approach to arylation.     

A crossed molecular beams and ab initio study on the formation of C6H3 radicals. an interface between resonantly stabilized and aromatic radicals

The crossed molecular beams reaction of dicarbon molecules, C(2)(X(1)Σ(g)(+)/a(3)Π(u)) with vinylacetylene was studied under single collision conditions at a collision energy of 31.0 kJ mol(-1) and combined with electronic structure calculations on the singlet and triplet C(6)H(4) potential energy surfaces. The investigations indicate that both reactions on the triplet and singlet surfaces are dictated by a barrierless addition of the dicarbon unit to the vinylacetylene molecule and hence indirect scattering dynamics via long-lived C(6)H(4) complexes. On the singlet surface, ethynylbutatriene and vinyldiacetylene were found to decompose via atomic hydrogen loss involving loose exit transition states to form exclusively the resonantly stabilized 1-hexene-3,4-diynyl-2 radical (C(6)H(3); H(2)CCCCCCH; C(2v)). On the triplet surface, ethynylbutatriene emitted a hydrogen atom through a tight exit transition state located about 20 kJ mol(-1) above the separated stabilized 1-hexene-3,4-diynyl-2 radical plus atomic hydrogen product; to a minor amount (<5%) theory predicts that the aromatic 1,2,3-tridehydrobenzene molecule is formed. Compared to previous crossed beams and theoretical investigations on the formation of aromatic C(6)H(x) (x = 6, 5, 4) molecules benzene, phenyl, and o-benzyne, the decreasing energy difference from benzene via phenyl and o-benzyne between the aromatic and acyclic reaction products, i.e., 253, 218, and 58 kJ mol(-1), is narrowed down to only ～7 kJ mol(-1) for the C(6)H(3) system (aromatic 1,2,3-tridehydrobenzene versus the resonantly stabilized free radical 1-hexene-3,4-diynyl-2). Therefore, the C(6)H(3) system can be seen as a "transition" stage among the C(6)H(x) (x = 6-1) systems, in which the energy gap between the aromatic isomer (x = 6, 5, 4) is reduced compared to the acyclic isomer as the carbon-to-hydrogen ratio increases and the acyclic isomer becomes more stable (x = 1, 2).     

Computational Study on the Attack of .OH Radicals on Aromatic Amino Acids

The attack of hydroxyl radicals on aromatic amino acid side chains, namely phenylalanine, tyrosine, and tryptophan, have been studied by using density functional theory. Two reaction mechanisms were considered: 1) Addition reactions onto the aromatic ring atoms and 2) hydrogen abstraction from all of the possible atoms on the side chains. The thermodynamics and kinetics of the attack of a maximum of two hydroxyl radicals were studied, considering the effect of different protein environments at two different dielectric values (4 and 80). The obtained theoretical results explain how the radical attacks take place and provide new insight into the reasons for the experimentally observed preferential mechanism. These results indicate that, even though the attack of the first ^.OH radical on an aliphatic C atom is energetically favored, the larger delocalization and concomitant stabilization that are obtained by attack on the aromatic side chain prevail. Thus, the obtained theoretical results are in agreement with the experimental evidence that the aromatic side chain is the main target for radical attack and show that the first ^.OH radical is added onto the aromatic ring, whereas a second radical abstracts a hydrogen atom from the same position to obtain the oxidized product. Moreover, the results indicate that the reaction can be favored in the buried region of the protein.     

Biphotonic photodissociation of phenylalanine in aqueous solution at 20°C

The photophysical processes leading to the photochemical changes in the aromatic amino acid phenylalanine were examined as a function of pH in aqueous solutions at 20°C, using the technique of flash photolysis. The photodissociation reaction to form the benzyl (φCH₂) radical was found to occur via a biphotonic process at pH 5.9 and pH 0.45, and via a monophotonic process at pH 11.0. Using characteristics quenches, the precursor of the photodissociation of phenylalanine at all pH values was shown to be a long-lived (triplet) excited state.     

Mechanism of dehydrodimerization of aromatic substrates by aluminium chloride-cupric chloride

The following results were obtained from oxidation of the appropriate aromatic hydrocarbons with AlCl₃-CuCl₂: 1-(2,4,6-trimethylphenyl)naphthalene from naphthalene-meistylene, 2,2'-bifluorene from nuorene, 2,2'-bifluorene from fluorene-mesitylene, and bimesityl and 3,3'-dichlorobimesityl from mesitylene. Mechanistically, radical cations are presumed to function as intermediates. Generally, coupling seems to proceed by cation attack on an aromatic molecule. Other pathways may pertain in certain cases, e.g. radical dimerization of radical cations.     

Photocatalytic Difunctionalization of Vinyl Ureas by Radical Addition Polar Truce–Smiles Rearrangement Cascades

We report tandem alkyl-arylations and phosphonyl-arylations of vinyl ureas by way of a photocatalytic radical-polar crossover mechanism. Addition of photoredox-generated radicals to the alkene forms a new C−C or C−P bond and generates a product radical adjacent to the urea function. Reductive termination of the photocatalytic cycle generates an anion that undergoes a polar Truce–Smiles rearrangement, forming a C−C bond. The reaction is successful with a range of α-fluorinated alkyl sodium sulfinate salts and diarylphosphine oxides as radical precursors, and the conformationally accelerated Truce–Smiles rearrangement is not restricted by the electronic nature of the migrating aromatic ring. Formally the reaction constitutes an α,β-difuctionalisation of a carbon–carbon double bond, and proceeds under mild conditions with visible light and a readily available organic photocatalyst. The products are α,α-diaryl alkylureas typically functionalized with F or P substituents that may be readily converted into α,α-diaryl alkylamines.     

Mechanistic dichotomy in the gas‐phase addition of NO3 to polycyclic aromatic hydrocarbons: Theoretical study

The gas‐phase addition mechanism of the NO₃ radical (an important tropospheric nocturnal oxidizing species) to some selected polycyclic aromatic hydrocarbons (PAHs), important pollutants of the troposphere, has been computationally analysed. Purpose of this work is to verify whether the reaction can take place through a mechanism different from the simple radical addition to the π aromatic system. This mechanism could consist in an Electron Transfer (ET) from the aromatics to NO₃, thus generating an aromatic radical‐cation and a nitrate anion at long C O distances. The coulomb attraction should finally bind the two species and generate the radical adduct without any electronic energy barrier. The CASPT2 results show that, while benzene and naphthalene react with NO₃ through a plain radical mechanism, anthracene reacts by a mechanism with a partial ET character, and pentacene reacts with a sort of inner‐sphere ET pathway. These results concur to explain the high reactivity of NO₃ with larger PAHs whose ionization energy is below 7 eV and could be important in studies of environmental PAH oxidative degradation.     

Catalytic C–H arylation of unactivated heteroaromatics with aryl halides by cobalt porphyrin

Direct C–H arylation of unactivated heteroaromatics with aryl halides catalyzed by cobalt porphyrin is reported. The reaction is proposed to go through a homolytic aromatic substitution reaction. The aryl radical is electrophilic and a SOMO–HOMO interaction is predominant in the aryl radical addition process.     

Reaction of the i-C4H5 (CH2CCHCH2) radical with O2

The resonantly stabilized radical i-C(4)H(5) (CH(2)CCHCH(2)) is an important intermediate in the combustion of unsaturated hydrocarbons and is thought to be involved in the formation of polycyclic aromatic hydrocarbons through its reaction with acetylene (C(2)H(2)) to form benzene + H. This study uses quantum chemistry and statistical reaction rate theory to investigate the mechanism and kinetics of the i-C(4)H(5) + O(2) reaction as a function of temperature and pressure, and unlike most resonantly stabilized radicals we show that i-C(4)H(5) is consumed relatively rapidly by its reaction with molecular oxygen. O(2) addition occurs at the vinylic and allenic radical sites in i-C(4)H(5), with respective barriers of 0.9 and 4.9 kcal mol(-1). Addition to the allenic radical form produces an allenemethylperoxy radical adduct with only around 20 kcal mol(-1) excess vibrational energy. This adduct can isomerize to the ca. 14 kcal mol(-1) more stable 1,3-divinyl-2-peroxy radical via concerted and stepwise processes, both steps with barriers around 10 kcal mol(-1) below the entrance channel energy. Addition of O(2) to the vinylic radical site in i-C(4)H(5) directly forms the 1,3-divinyl-2-peroxy radical with a small barrier and around 36.8 kcal mol(-1) of excess energy. The 1,3-divinyl-2-peroxy radical isomerizes via ipso addition of the O(2) moiety followed by O atom insertion into the adjacent C-C bond. This process forms an unstable intermediate that ultimately dissociates to give the vinyl radical, formaldehyde, and CO. At higher temperatures formation of vinylacetylene + HO(2), the vinoxyl radical + ketene, and the 1,3-divinyl-2-oxyl radical + O paths have some importance. Because of the adiabatic transition states for O(2) addition, and significant reverse dissociation channels in the peroxy radical adducts, the i-C(4)H(5) + O(2) reaction proceeds to new products with rate constant of around 10(11) cm(3) mol(-1) s(-1) at typical combustion temperatures (1000-2000 K). For fuel-rich flames we show that the reaction of i-C(4)H(5) with O(2) is likely to be faster than that with C(2)H(2), bringing into question the importance of the i-C(4)H(5) + C(2)H(2) reaction in initiating ring formation in sooting flames.