Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin

Alkyl, aryl, heteroaryl and acyl radicals have been cyclised onto the 2-position of 3H-quinazolin-4-one. The side chains containing the radical precursors were attached to the nitrogen atom in the 3-position. The cyclisations take place by aromatic homolytic substitution hence retain the aromaticity of the 3H-quinazolin-4-one ring. The highest yields were obtained using hexamethylditin to facilitate cyclisation rather than reduction without cyclisation. The alkaloids deoxyvasicinone , mackinazolinone , tryptanthrin , luotonin A and rutaecarpine were synthesised by radical cyclisation onto 3H-quinazolin-4-one.     

A theoretical study on the destruction of typical biomass tar components (toluene,phenol and naphthalene) by OH radical

The detailed reaction mechanism of OH radical destroying toluene, phenol and naphthalene was studied through quantum chemical calculations in the research. Theoretical results indicate that for phenol and toluene, OH radical preferentially attack the ortho C atom due to the functional group on the benzene ring. But for naphthalene, OH radical preferentially attack the para-position C atoms because of its inherent benzo structure. To further study of the kinetics, the rate constant was calculated by the transition state theory. The comparison shows that the theoretical reaction rate constants for the degradation of tar by the OH radical were consistent with those obtained from literature experiments. And the rate constant of destructing naphthalene by OH radical was larger than that of destructing toluene, but lower than that of destructing phenol. The degradation sequence of OH radical to tar is: phenol ​> ​naphthalene ​> ​toluene. Because of the activation of hydroxyl group in benzene ring, phenol is the most easily attacked and destroyed by OH radical. The theoretical results can provide theoretical basis and data reference for further research on the removal of biomass tar and aromatics by OH radical.     

Mechanistic insights on how hydroquinone disarms OH and OOH radicals

Phenol derivatives are distinguished as successful free radical scavengers. We present a detailed analysis of hydroxyl hydrogen abstraction from hydroquinone by hydroxyl and hydroperoxyl radical with emphasis on changes that take place in the vicinity of the transition state. Quantum theory of atoms in molecules is employed to elucidate the sequence of positive and negative charge transfer by studying selected properties of the three key atoms (the transferring hydrogen, the donor atom, and the acceptor atom) along intrinsic reaction path. The presented results imply that in both reactions, which are examples of proton coupled electron transfer, proton, and electron get simultaneously transferred to the radical oxygen atom. The fact that the hydrogen's charge and volume do not monotonously change in the vicinity of the transition state in the product valley results from the adjacency of the proton and the electron to the donor and the acceptor oxygen atoms. Obtaining a detailed understanding of mechanisms by which free radicals are disarmed is of paramount importance given the effects of those highly reactive species on biological systems. A comprehensive analysis of hydroxyl hydrogen abstraction from hydroquinone by hydroxyl and hydroperoxyl radicals, based on changes of selected electronic properties of the three most relevant atoms (hydrogen donor, hydrogen acceptor, and the hydrogen itself), along the reaction coordinate, can be obtained by first‐principles calculations.     

Mechanism of hydroxyl radical-induced breakdown of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-d)

Oxidative transformations by the hydroxyl radical are significant in advanced oxidation processes for the breakdown of organic pollutants, yet mechanistic details of the reactions are lacking. A combination of experimental and computational methods has been employed in this study to elucidate the reactivity of the hydroxyl radical with the widely used herbicide 2,4-D (2,4-dichlorophenoxyacetic acid). The experimental data on the reactivity of the hydroxyl radical in the degradation of the herbicide 2,4-D were obtained from gamma-radiolysis experiments with both (18)O-labeled and unlabeled water. These were complemented by computational studies of the (.)OH attack on 2,4-D and 2,4-DCP (2,4-dichlorophenol) in the gas phase and in solution. These studies firmly established the kinetically controlled attack ipso to the ether functionality as the main reaction pathway of (.)OH and 2,4-D, followed by homolytic elimination of the ether side chain. In addition, the majority of the early intermediates in the reaction between the hydroxyl radical and 2,4-DCP, the major intermediate, were identified experimentally. While the hydroxyl radical attacks 2,4-D by (.)OH-addition/elimination on the aromatic ring, the oxidative breakdown of 2,4-DCP occurs through (.)OH addition followed by either elimination of chlorine or formation of the ensuing dichlorophenoxyl radical.     

Carbon-13 NMR spectra of DDT,its analogues and related compounds

Carbon-13 NMR spectra of mono- and disubstituted aromatic compounds including DDT, its analogues, homologues, derivatives and certain model compounds have been studied. The Savitsky scheme of carbon chemical shifts in disubstituted benzenes is applicable to these compounds. The data obtained show that in mono- and disubstituted aromatic compounds containing two different substituents in the α- and β-positions of the side chain, the substituted ring carbon atom shifts follow the additivity rule and can be calculated from substituent increments. Mutual effects of substituents in the ring and in the side chains are analysed. The chlorine atoms in α-position to the phenyl ring give rise to an additive α-effect of about 25 ppm, as in perchloroalkanes. The influence of a β-chlorine atom in the side chain on the substituted carbon atom in the ring is, however, only 3 ppm as against the usual value of about 10 ppm for the β-effect in alkyl chains. Moreover, the first β-chlorine substituent has no noticeable influence on the substituted ring carbon chemical shift: the effect of 3 ppm is transferred to the para-carbon atom almost without attenuation. The ring substituted carbon atom signal shifts caused by the γ-effect of chlorine in the side chain are similar to those observed in aliphatic chains. The ortho-chlorine substituents shift the side chain α-carbon atom signal by 3.6-5.2 ppm to high field compared to para-chlorophenyl compounds. This is similar to the chlorine γ-effect in aliphatic chains.     

Thermodynamic and kinetic study of ibuprofen with hydroxyl radical: A density functional theory approach

Ibuprofen, a frequently detected pharmaceutical in natural and engineered waters, was studied in both neutral and anionic forms using density functional theory at the B3LYP/6‐311++G**//B3LYP/6‐31G* level of theory in its reaction with hydroxyl radical ( ? OH). The reaction pathways included ? OH addition to aromatic ring, abstraction of a H‐atom, and nucleophilic attack on the carbonyl group. The results showed that H‐atom abstraction pathways are the most favorable. The free energy change for H‐atom abstraction reaction ranges from ?37.8 to ?15.9 kcal/mol; for ? OH addition ranges from ?3.85 to ?1.23 kcal/mol; and for nucleophilic attack on the carbonyl group is 13.9 kcal/mol. The calculated rate constant between neutral ibuprofen and ? OH, 6.72 × 10⁹ M^?1s^?1, is consistent with the experimental value, 6.5 ± 0.2 × 10⁹ M^?1s^?1. Our results provide direct evidence for byproduct formation and identification on the molecular level. © 2013 Wiley Periodicals, Inc.     

2,2,6,6-四甲基哌啶-1-氧自由基促进的钒基催化剂催化苯直接氧化制苯酚

以钒基化合物为催化剂,在TEMPO(2,2,6,6-四甲基哌啶-1-氧自由基)存在下,能形成快速催化分子氧氧化苯制苯酚的催化体系.在反应过程中,由类似芬顿试剂反应过程生成的羟基自由基亲核进攻苯环,形成羟基环己二烯自由基;该羟基氢可在TEMPO存在的催化体系中消除,同时苯环氢可立即转移至氧原子而生成苯酚.在以[(CH3)...     

Identification of position isomers by energy‐resolved mass spectrometry

This study reports an energy‐resolved mass spectrometric (ERMS) strategy for the characterization of position isomers derived from the reaction of hydroxyl radicals (^●OH) with diphenhydramine (DPH) that are usually hard to differentiate by other methods. The isomer analogues formed by ^●OH attack on the side chain of DPH are identified with the help of a specific fragment ion peak (m/z 88) in the collision‐induced dissociation (CID) spectrum of the protonated molecule. In the negative ion mode, the breakdown curves of the deprotonated molecules show an order of stability (supported by density functional theory (DFT) calculations) ortho > meta > para of the positional isomers formed by the hydroxylation of the aromatic ring. The gas phase stability of the deprotonated molecules [M ? H]^? towards the benzylic cleavage depends mainly on the formation of intramolecular hydrogen bonds and of the mesomeric effect of the phenol hydroxyl. The [M ? H]^? molecules of ortho and meta isomers result a peak at m/z 183 with notably different intensities because of the presence/absence of an intramolecular hydrogen bonding between the OH group and C9 protons. The ERMS approach discussed in this report might be an effective replacement for the conventional methods that requires very costly and time‐consuming separation/purification methods along with the use of multi‐spectroscopic methods. Copyright © 2015 John Wiley & Sons, Ltd.     

Ionizing radiation induced reactions of 2,6-dichloroaniline in dilute aqueous solution

In pulse radiolysis investigations the hydroxyl radical formed in water radiolysis reacts with 2,6-dichloroaniline in radical addition to the ring forming hydroxy-cyclohexadienyl radical and also in hydrogen atom abstraction from the amino group resulting in anilino radical. The hydroxy-cyclohexadienyl radical in the absence of dissolved O₂ partly transforms to anilino radical, when dissolved oxygen is present the radical transforms to peroxy radical. According to chemical oxygen demand measurements the reaction of one OH radical induces the incorporation of 0.6 O₂ into the products. It is a typical value for chlorine atom substituted aromatic molecules, and smaller than found for molecules without chlorine atom (1.0–2.0).     

Electron predators are hydrogen atom traps. Effects of aryl groups on N—Cα bond dissociations of peptide radicals

Effects of substituted aryl groups on dissociations of peptide aminoketyl radicals were studied computationally for model tetrapeptide intermediates GXD^?G where X was a cysteine residue that was derivatized by S‐(3‐nitrobenzyl), S‐(3‐cyanobenzyl), S‐(3,5‐dicyanobenzyl), S‐(2,3,4,5,6‐pentafluorobenzyl), and S‐benzyl groups. The aminoketyl radical was placed within the Asp amide group. Aminoketyl radicals having the S‐(3‐nitrobenzyl) group were found to undergo spontaneous and highly exothermic migration of the hydroxyl hydrogen atom onto the nitro group in conformers allowing interaction between these groups. Competing reaction channels were investigated for aminoketyl radicals having the S‐(3‐cyanobenzyl) and S‐(3,5‐dicyanobenzyl) groups, e.g. H‐atom migration to the C and N atoms of the C≡N group, migration to the C‐4 position of the phenyl ring, and dissociation of the radical‐activated N? C_α bond between the Asp and Gly residues. RRKM kinetic analysis on the combined B3LYP and ROMP2/6‐311++G(2d,p) potential energy surface indicated > 99% H‐atom transfer to the C≡N group forming a stable iminyl intermediate. The N? C_α bond dissociation was negligible. In contrast, peptides with the S‐(2,3,4,5,6‐pentafluorobenzyl) and S‐benzyl groups showed preferential N? C_α bond dissociation that outcompeted H‐atom migration to the C‐4 position and fluorine substituents in the phenyl ring. These computational results are used to suggest an alternative mechanism for the quenching effect on electron‐based peptide backbone dissociations of benzyl groups with electron‐withdrawing substitutents, as reported recently. Copyright © 2010 John Wiley & Sons, Ltd.     

OH-initiated oxidation mechanism and kinetics of organic sunscreen benzophenone-3: A theoretical study

Benzophenone-3 (BP-3), as an important organic UV filter, is widely used in the sunscreen, cosmetic, and personal care products. The chemical reaction mechanism and kinetics of BP-3 degradation initiated by hydroxyl (OH) radical was investigated in the atmosphere based on the density functional theory (DFT). The results showed that the OH radical is more easily added to the C3 position of the aromatic ring (pathway 3), while the H atom abstraction from the OH group on the aromatic ring (pathway 23) is an energetically favorable reaction pathway. At ambient temperature, 298 K, the overall rate constant for the primary reaction is about 1.50 × 10^?10 cm³ mol^?1 s^?1 with the lifetime of 1.92 h. OH addition reactions play the key role in the OH-initiated reaction of BP-3. The study is helpful for better understanding of the removal, transformation, and fate of BP-3 in the atmosphere.     

Microwave-assisted syntheses of N-heterocycles using alkenone-, alkynone- and aryl-carbonyl O-phenyl oximes: formal synthesis of neocryptolepine

This research aimed to provide a new and "clean" synthetic method that would enable both known and novel N-heterocycles to be prepared efficiently. O-Phenyl oximes were found to be excellent precursors for iminyl radicals with a variety of acceptor side chains. Dihyropyrroles were made in good yields from O-phenyl oximes containing pent-4-ene acceptors. The analogous process with a hex-5-enyl acceptor did not yield a dihydropyridine, probably because the 6-exo-trig ring closure of the iminyl radical was too slow to compete with H-atom abstraction. The iminyl radical from a precursor with a pent-4-yne type side chain underwent ring closure followed by rearrangement to afford a pyrrole derivative. Suitably substituted iminyl radicals ring closed readily onto aromatic acceptors, thus enabling several polycyclic systems to be accessed. Quinolines were made from 3-phenylpropanones via their O-phenyl oximes. Syntheses of phenanthridines starting from 2-formylbiphenyls were particularly efficient, and this approach enabled the natural product trisphaeridine to be made. Starting from 2-phenylnicotinaldehyde derivatives, ring closures of the derived iminyl radicals onto the phenyl rings yielded benzo[h][1,6]naphthyridines. Similarly, ring closure onto a phenyl ring from a benzothiophene-based iminyl yielded a benzo[b]thieno[2,3-c]quinoline. By way of contrast, iminyl radical ring closure onto pyridine rings was not observed. However, iminyl radicals did cyclize onto indoles, enabling indolopyridines to be prepared. The latter route was exploited in a short formal synthesis of neocryptolepine starting from 2-((1H-indol-3-yl)methyl)cyclohexanone.     

Charge-remote fragmentation and the two-step elimination of alkanols from fast atom bombardment-desorbed (M + H)+, (M + Cat)+, and (M - H)− ions of aromatic β-hydroxyoximes

Aromatic β-hydroxyoximes undergo unusual fragmentation reactions as protonated or cationized species, as radical cations, or as (M - H)^? ions, As protonated species, they expel OH ’ from the oxime functionality in violation of the even electron rule. Parallel eliminations of alkyl radicals follow OH’ loss when the aromatic ring is substituted with an alkyl chain. Alkyl radical losses appear to be characteristic of radical cations that can isomerize to ions in which the alkyl chain bears a radical site and the charged site is the conjugate acid of a basic functionality (e.g., oxime or imine). Evidence for the mechanisms was found in the ion chemistry of oxime and imine radical cations. The imine reference compounds were conveniently generated by fast atom bombardment-induced reduction of oximes, removing the requirement for using conventional chemical synthesis. Protonated imines and the (M - H)^? ions of oximes fragment extensively via charge-remote processes to eliminate the elements of alkanes. This chemistry is not shared by the protonated oximes.     

Trapping of the OH radical by alpha-tocopherol: a theoretical study

The antioxidant activity of alpha-tocopherol against the damaging hydroxyl radical was analyzed theoretically by hybrid density functional theory, following the direct dynamics method, where the thermal rate constants were calculated using variational transition-state theory with multidimensional tunneling. We found that the OH radical is only slightly or not at all selective, attacking by different mechanisms at several positions of the alpha-tocopherol molecule, giving competitive reactions. The most favorable pathways are the hydrogen abstraction reaction from the phenolic hydrogen and the electrophilic addition onto the aromatic ring. We propose a final rate constant, the sum of the competitive hydrogen abstraction and addition reactions, > or =2.7 x 10(8) M(-1) s(-1) at 298 K, where the hydrogen abstraction reaction represents only 20% of the total OH radical reaction. This result indicates that, molecule by molecule, in an apolar environment, alpha-tocopherol is less effective than coenzyme Q (which presents a rate constant of 6.2 x 10(10) M(-1) s(-1) at 298 K) as a scavenger of OH radicals. It was also found that both mechanisms are not direct but pass through intermediates in the entry channel, with little or no influence on the dynamics of the reactions. The hydrogen abstraction reaction also presents another intermediate in the exit channel, which may have a significant role in preventing the pro-oxidant effects of alpha-tocopherol, although less important than with free radicals other than OH.     

Hydrogen atom abstraction reactions of the sugar moiety of 2′‐deoxyguanosine with an OH radical: A quantum chemical study

Mechanisms of hydrogen atom abstraction reactions of the sugar moiety of 2′‐deoxyguanosine with an OH radical were investigated using the B3LYP and BHandHLYP functionals of density functional theory and the second order Møller–Plesset Perturbation (MP2) theory in gas phase and aqueous media. The 6‐31+G* and AUG‐cc‐pVDZ basis sets were used. Gibbs free barrier energies and rate constants of the reactions in aqueous media suggest that an OH radical would abstract the hydrogen atoms of the sugar moiety of 2′‐deoxyguanosine in the following order of preference: H5′ ≈ H5″ > H3′ > H4′ > H1′ ≈ H2′ > H2″, the rate constant for H5′ abstraction being 10³–10⁵ times greater than that for H2″ at the different levels of theory. Relative stabilities of the different deoxyribose radicals are also discussed. The most and least favored hydrogen abstraction reactions found here are in agreement with experimental observation. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Ab-initio study of initial atmospheric oxidation reactions of C3 and C4 alkanes

Second-order, Møller–Plesset (MP2)-unrestricted Hartree–Fock calculations with full geometry optimization in the 6-31G(d, p) basis set were carried out to study the initial atmospheric oxidation reactions of alkanes. All structures in the initial hydrogen abstraction reaction by an OH radical and the subsequent addition of molecular oxygen to the alkyl radical were characterized for alkanes with three and four carbon atoms. The reaction paths for the formation of the peroxyl radicals were obtained and discussed in the light of similarities along series involving primary, secondary, and tertiary hydrogens. A 0.999 correlation was found between the height of our barriers for the OH abstraction of a primary hydrogen atom from alkanes containing one to four carbon atoms and the optimally estimated activation energies for this reaction recently presented. From the slope and the intersection at zero activation energy an equation was obtained that yields scaled values of the activation energies to account for the tunnel effect and for the error due to the basis set and the method employed. We present new results for the abstraction of the less favored primary hydrogens in propane, butane, and isobutane, which should be important at high temperatures. Negative net activation energies were obtained for the addition of molecular oxygen to all the alkyl radicals formed in the first reaction. The structure of the peroxyl radicals is discussed; and very good correlations are observed for similar compounds, regardless of the length of the carbon chain. A revision of some experimental values is suggested. Single point density functional calculations at the MP2 geometries were also performed with the B3LYP functional for comparison. The observed trends are exactly the same for the two methods. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 845–856, 1999     

Studies on some radical transfer reactions. Part I. Hydrogen atom abstraction from some organic substrates by ȮH radicals

Polymerization of methyl methacrylate was carried out in aqueous and nonaqueous media in the presence of some sulfonated and carboxylic organic compounds, hydroxyl radicals generated from hydrogen peroxide being used as initiators of polymerization. The occurrence of radical transfer reactions by way of hydrogen atom abstraction from the organic substrates by the ?H radicals was demonstrated by the detection of sulfonate and carboxyl endgroups in the respective polymers. It was found that the radical transfer reactions were more favored in aqueous media than in nonaqueous systems.     

Reaction of sulphate radical anion (SO<Superscript>.</Superscript><Subscript>4</Subscript><Superscript>-</Superscript>) with hydroxy-and methyl-substituted pyrimidines: a pulse radiolysis study

Reactions of sulphate radical anion (SO·₄ ^-) with 4,6-dihydroxy-2-methyl pyrimidine (DHMP), 2,4-dimethyl-6-hydroxy pyrimidine (DMHP), 6-methyl uracil (MU) and 5,6-dimethyl uracil (DMU) have been studied by pulse radiolysis at pH 3 and at pH 10. The transient intermediate spectra were compared with those from the reaction of hydroxyl radical (·OH). It is proposed that SO·₄ ^- produces radical cations of these pyrimidines in the initial stage. These radical cations are short-lived except in the case of DMHP where a relatively longer lived radical cation is proposed to be formed. When there is a hydrogen atom attached to the N(1) or N(3) position, a deprotonation from these sites is highly favored. When there is no hydrogen attached to these sites, deprotonation from a substituted methyl group is favored. At acidic pH, deprotonation from nitrogen is observed for DHMP, MU and DMU. At basic pH, the radical cation reacts with OH^- leading to the formation of OH adducts.     

Backbone and side-chain cleavages in electron detachment dissociation (EDD)

Ab-initio electronic structure methods are used to explore potential energy profiles pertinent to the fragmentations of gas-phase radicals thought to be formed in the new negative-ion mode EDD mass spectroscopic studies of peptides. Barriers to fragmentation as well as the associated overall energy differences are computed for the observed Calpha-C backbone bond cleavage as well as for side-chain loss for a variety of side chains (valine, arginine, glutamic acid, and tyrosine). It is found that Calpha-C bond cleavage is favored over side-chain loss, although loss of a tyrosine side chain may compete with Calpha-C cleavage because the tyrosine radical formed can delocalize its unpaired electron over its aromatic ring. In addition, it is found that fragmentation of the nitrogen-centered radicals formed in EDD results in cleavage to produce so-called a*/x fragments rather than a/x* fragments both because producing the former involves a significantly smaller barrier and is nearly thermoneutral, while cleavage to yield a/x* is significantly endothermic.