A facile access to bridged 1,2,4-trioxanes

Bicyclo[3.2.1] type 1,2,4-trioxanes are readily synthesized from precursors that may form intramolecular hemiketals using UHP (H₂O₂-urea complex) as the source of the peroxy bond and p-TsOH or CSA as the catalyst. The ring closure through an intramolecular Michael addition occurred in a highly stereoselective way, giving only one diasteromer as shown by the NMR spectra.     

ab initio molecular orbital and density functional analysis of acetylene + O2 reactions with CHEMKIN evaluation

A number of researchers have indicated that a direct reaction of acetylene with oxygen needs to be included in detailed reaction mechanisms in order to model observed flame speeds and induction times. Four pathways for the initiation of acetylene oxidation to chain propagation are considered and the rate constants are compared with values used in the mechanisms:

• 1 ³O₂ + HCCH to triplet adduct and reaction on the triplet surface
• 2 ³O₂ + HCCH to triplet adduct, conversion of triplet adduct to singlet adduct via collision in the reaction environment, with further reaction of the singlet adduct
• 3 ¹O₂ + HCCH to singlet adduct
• 4 Isomerization of HCCH to vinylidene and then vinylidene insertion reaction with ³O₂

Elementary reaction pathways for oxidation of acetylene by addition reaction of O₂(³Σ) on the triplet surface are analyzed. ab initio molecular orbital and density functional calculations are employed to estimate the thermodynamic properties of the reactants, transition states, and products in this system. Acetylene oxidation reaction over the triplet surface is initiated by addition of molecular oxygen, O₂(³Σ), to a carbon atom, forming a triplet peroxy‐ethylene biradical. The reaction path to major products, either two formyl radicals or glyoxal radical plus hydrogen atom, involves reaction through three transition states: O₂(³Σ) addition to acetylene (TS1), peroxy radical addition at the ipso‐carbon to form a dioxirane (TS2), and cleavage of O O bond in a three‐member ring (TS3). Single‐point QCISD(T) and B3LYP calculations with large basis sets were performed to try to verify barrier heights on important transition states. A second pathway to product formation is through spin conversion of the triplet peroxy‐ethylene biradical to the singlet by collision with bath gas. Rapid ring closure of the singlet peroxy‐ethylene biradical to form a four‐member ring is followed by breaking of the peroxy bond to form glyoxal, which further dissociates to either two formyl radicals or a glyoxal radical plus hydrogen atom. The overall forward rate constant through this pathway is estimated to be k_f = 2.21 × 10⁷ T^1.46e^{−33.1(kcal/mol)/RT}. Two additional pathways from the literature, HCCH + O₂(¹Δ) and pressure‐dependent isomerization of acetylene to vinylidene and then vinylidene reaction with O₂(³Σ), are also evaluated for completeness. CHEMKIN modeling on each of the four proposed pathways is performed and concentration profiles from these reactions are evaluated at 0.013 atm and 1 atm over 35 milliseconds. Through reaction on the triplet surface is evaluated to be not important. Formation of the triplet adduct with conversion (via collision) to a singlet and the vinylidene paths show similar and lower rates than those used in mechanisms, respectively. Our implementation of the HCCH + O₂(¹Δ) pathway of Benson suggests the need to include: (i) reverse reaction, (ii) barriers to further reaction of the initial adduct plus (iii) further evaluation of the O₂(¹Δ) addition barrier. The pathways from triplet adduct with conversion to singlet and from vinylidene are both recommended for initiation of acetylene oxidation. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 32: 623–641, 2000     

Synthesis and in vitro antimalarial activity of spiro-analogues of peroxyplakoric acids

Four 1,2,7-trioxa-spiro[5.5]undecanes and two 1,6,7-trioxa-spiro[4.5]decanes were synthesized using the hydrogen peroxide in UHP (urea-H₂O₂ complex) as the source of the peroxy bond. Incorporation of H₂O₂ into the organic molecular framework was facilitated by the potential to form a five- or six memberd cyclic hemiketal. Saturation of the double bond in a substituted γ-keto-butenal, a step required in all the syntheses, was achieved in one case with NaI/concd HCl at low temperature without cleaving the TBS protecting group or causing excessive side reactions as observed at ambient temperature. All these peroxides showed in vitro antimalarial activity comparable to that of natural peroxyplakoric acids and the known analogues.     

Hydrogen peroxide-or sodium hypochlorite-induced bromination of 1-arylbut-2-enes

Bromination of 1-arylbut-2-enes in the system [HBr or NaBr (KBr)-HX]-H₂O₂ (or NaOCl) under relatively mild conditions leads to electrophilic addition of bromine or hypobromous acid at the side-chain double bond. Under more severe conditions, the process is accompanied by bromination of the aromatic ring. Treatment of the title compounds with peroxy acids (RCOOH-H₂O₂) gives the corresponding epoxy derivatives which react with HBr and oxygen-containing nucleophiles to produce α-bromo alcohols, diols, and diol acetates.     

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).     

Simplified analogues of qinghaosu (artemisinin)

Three new simplified analogues of qinghaosu have been designed and synthesized through simple routes without recourse to the commonly employed photosensitized oxidation. The peroxy bonds in the target molecules were taken from UHP with the first peroxy-carbon bond formed through a hemiketal exchange reaction and the second by either an intramolecular Michael addition or a Hg(II)-mediated ring-closure reaction. All three peroxides possess a seven-membered peroxy ring fused to an all-carbon six-membered ring, a structural motif required for generating the carbon-centered substituted ethyl radicals.     

The interaction of radiation-generated radicals with myoglobin in aqueous solution—V. The indirect action of 2-methyl-2-hydroxypropyl radicals on oxymyoglobin

The interaction of radiation-generated 2-methyl-2-hydroxypropyl radicals (derived from t-butyl alcohol) with oxymyoglobin has been examined at pH 7.3. In N₂O-saturated solutions, oxymyoglobin is converted to the ferri and ferryl derivatives of myoglobin; the production of ferrylmyoglobin is essentially eliminated when catalase is present in solution during irradiation. In deaerated solutions containing catalase, oxymyoglobin is converted to both ferro- and ferrimyoglobin during irradiation. When added O₂ is initially present, all compositional changes occur after irradiation; the presence of catalase diminishes, but does not eliminate, the extent of these postirradiation conversions of oxymyoglobin to the ferri and ferryl derivatives. These observations are interpreted in terms of the scavenging of the 2-methyl-2-hydroxypropyl radicals by O₂ to generate their peroxy analogs, which causes a displacement of the equilibrium between oxy- and ferromyoglobin. The peroxy radicals decay to produce H₂O₂, an organic peroxide, and other products. These peroxides subsequently react with ferromyoglobin to produce the ferryl form; the rate of the reaction increases with decreasing [O₂] as [ferromyoglobin] increases. This reaction is sufficiently fast in deaerated solution that substantial conversion of ferromyoglobin to ferrylmyoglobin occurs during the time of irradiation. The formation of the ferryl derivative in the presence of unconverted ferromyoglobin drives a concurrent synproportion reaction which produces ferrimyoglobin. Overall, no direct interaction of 2-methyl-2-hydroxypropyl radicals, nor their peroxy analogs, with myoglobin is indicated; all reactivity is accountable by the peroxide products of these radicals.     

Sequential Pd2(dba)3 participated C–C bond cleavage of O-bromophenyl cyclobutanones/Michael addition en route to benzospirones

A tandem Pd₂(dba)₃ participated C–C bond cleavage of O-bromophenyl cyclobutanone derivatives/Michael addition reaction sequence was realized. We disclosed the first intramolecular C–Br bond triggered ring opening reaction of arylcyclobutanones, distinct from related reports in which the reactions were initiated by arylboron, silane or unsaturated chemical motifs, among others. The in situ generated palladium species underwent ring expansion process leading to methyleneindanones, which further reacted with dba to provide benzospirones in one step.     

An efficient synthesis of aryldithiocarbamic acid esters from Michael addition of electron-deficient alkenes with arylamines and CS2 in solid media alkaline Al2O3

An efficient synthesis of dithiocarbamic acid esters from Michael addition of electron-deficient alkenes with arylamines and CS₂ in solid media alkaline Al₂O₃ was presented. This method was suitable for a wide range of amines and a variety of Michael receptors. Specially, a series of aryldithiocarbamic acid esters was obtained from arylamines through this method. The protocol offers clean reactions and high yields with simple experimental procedures. Besides, the alkaline Al₂O₃ could be reused.     

Thermochemistry and kinetics of the 2-butanone-4-yl CH3C(=O)CH2CH2• + O2 reaction system

Thermochemistry and kinetic pathways on the 2-butanone-4-yl (CH₃C(=O)CH₂CH₂•) + O₂ reaction system are determined. Standard enthalpies, entropies, and heat capacities are evaluated using the G3MP2B3, G3, G3MP3, CBS-QB3 ab initio methods, and the B3LYP/6-311g(d,p) density functional calculation method. The CH₃C(=O)CH₂CH₂• radical + O₂ association reaction forms a chemically activated peroxy radical with 35 kcal mol⁻¹ excess of energy. The chemically activated adduct can undergo RO−O bond dissociation, rearrangement via intramolecular hydrogen transfer reactions to form hydroperoxide-alkyl radicals, or eliminate HO₂ and OH. The hydroperoxide-alkyl radical intermediates can undergo further reactions forming ketones, cyclic ethers, OH radicals, ketene, formaldehyde, or oxiranes. A relatively new path showing a low barrier and resulting in reactive product sets involves peroxy radical attack on a carbonyl carbon atom in a cyclic transition state structure. It is shown to be important in ketones when the cyclic transition state has five or more central atoms.     

Singlet Oxygen's Potential Role as a Nonoxidative Facilitator of Disulfide S–S Bond Rotation†

The role of singlet oxygen potentially mediating increased conformational flexibility of a disulfide was investigated. Density functional theory (DFT) calculations indicate that the singlet oxygenation of 1,2-dimethyldisulfane produces a peroxy intermediate. This intermediate adopts a structure with a longer S–S bond distance and a more planar torsional angle θ (C–S–S–C) compared with the nonoxygenated 1,2-dimethyldisulfane. The lengthened S–S bond enables a facile rotation about the torsional angle in the semicircle region 0° < θ < 210°, that is ~5 kcal mol⁻¹ lower in energy than the disulfane. The peroxy intermediate bears n_O → σ_S–S and n_O → σ*_S–S interactions that stabilize the S–O bond but destabilize the S–S bond, which contrasts with stabilizing n_S → σ*_S–S hyperconjugative effects in the disulfane S–S bond. Subsequent departure of O₂ from the disulfane peroxy intermediate is reminiscent of peroxy intermediates which also expel O₂, yet facilitate cis-trans isomerizations of stilbenes, hexadienes, cyanines, and carotenes. “Non-oxidative” ¹O₂ interactions with a variety of bond types are currently underappreciated. We hope to raise awareness of how these interactions can help elucidate the origins of molecular twisting.     

The mass spectra of benzofuroxans—an example of an ortho effect

The fragmentation behavior of a series of nine benzofuroxans has been studied under electron impact conditions. It was found that benzofuroxans without a nitro group in the 4-position fragment principally through loss of N₂O₂ (the furoxan ring), whereas those with a nitro group ortho to the furoxan ring exhibit predominant loss of NO from position 1 of the furoxan ring.     

Fluorocarbon oxy and peroxy radicals

This review deals with the most fundamental fluorocarbon oxy (x=1) and peroxy (x=2) radicals CF₃O_x, FC(O)O_x, CF₃C(O)O_x and CF₃OC(O)O_x. Their role in atmospheric and synthetic chemistry is described as well as their formation and characterisation in the gas phase and isolated in low temperature matrices. Reservoirs and hence thermal sources for oxy and peroxy radicals are peroxides (ROOR) and peroxynitrates (ROONO₂), while catenated trioxides (ROOOR) are precursors for both oxy and peroxy radicals simultaneously. The synthesis and some properties of these precursors are also described.     

Isomeric hexyl‐ketohydroperoxides formed by reactions of hexoxy and hexylperoxy radicals in oxygen

Isomerization reactions of peroxy radicals during oxidation of long‐chain hydrocarbons yield hydroperoxides, and therefore play an important role in combustion and atmospheric chemistry, because of their action as branching agents in these chain reaction processes. Different formation mechanisms and structures are involved. Three isomeric hexyl‐ketohydroperoxides are formed via isomerization reactions in oxygen of either hexoxy RO or hexylperoxy RO₂ radicals. In the temperature range 373–473 K, 2‐hexoxy (C₆H₁₃O) radical in O₂/N₂ mixtures gives 2‐hexanone‐5‐hydroperoxide via two consecutive isomerizations. The second one is a H transfer from a HC(OH) group occurring via a seven‐membered ring intermediate: Its rate constant has been determined at 453 and 483 K, and the general expression can be written as Hexylperoxy C₆H₁₃O₂ radical, present in n‐hexane oxidation by oxygen/nitrogen mixtures in the temperature range 543–573 K, gives 2‐hexanone‐4‐hydroperoxide, 3‐hexanone‐5‐hydroperoxide, and 2‐hexanone‐5‐hydroperoxide. The first two are formed through an isomerization reaction via a six‐membered ring intermediate, and the last through an isomerization reaction via a seven‐membered ring intermediate. The ratio of the rate constant of the isomerization reactions of RO₂ radicals via a seven‐membered ring intermediate to that via a six‐membered ring is found to be 0.795, and the rate constant expression via a seven‐membered ring intermediate is proposed: The role of these reactions in the formation of radicals in the troposphere is discussed. Other products arising in the reactional path, such as ketones, furans, and diketones, are identified. Identification of these ketohydroperoxides was made using gas chromatography/mass spectrometry with electron impact, and with NH₃ (or ND₃) chemical ionization. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 354–366, 2003     

N‐{4‐Bromo‐2‐[(3‐bromo‐1‐phenylsulfonyl‐1H‐indol‐2‐yl)methyl]‐5‐methoxyphenyl}acetamide

In the title compound, C₂₄H₂₀Br₂N₂O₄S, the indole ring system is planar and the S atom has a distorted tetrahedral configuration. The sulfonyl‐bound phenyl ring is orthogonal to the indole ring system and the conformation of the phenyl­sulfonyl substituent with respect to the indole moiety is influenced by intramolecular C—H⃛O hydrogen bonds involving the two sulfonyl O atoms. The mean plane through the acetyl­amido group makes a dihedral angle of 57.0 (1)° with the phenyl ring of the benzyl moiety. In the crystal, glide‐related mol­ecules are linked together by N—H⃛O hydrogen bonds and C—H⃛π interactions to form molecular chains, which extend through the crystal. Inversion‐related chains are interlinked by C—H⃛π interactions to form molecular layers parallel to the bc plane. These layers are interconnected through π–π interactions involving the five‐ and six‐membered rings of the indole moiety.     

A Divergent Enantioselective Total Synthesis of Post-Iboga Indole Alkaloids

Divergent enantioselective total syntheses of five naturally occurring post-iboga indole alkaloids, dippinine B and C, 10,11-demethoxychippiine, 3-O-methyl-10,11-demethoxychippiine, and 3-hydroxy-3,4-secocoronaridine, as well as the two analogues 11-demethoxydippinine A and D, are presented for the first time. The enantioenriched aza[3.3.1]-bridged cycle, a common core intermediate to the target molecules, was constructed through an asymmetric phase-transfer-catalyzed Michael/aldol cascade reaction. The challenging azepane ring fused around the indole ring and the [3.3.1]-bridged cycle were installed through an intramolecular S_N2′-type reaction. These cyclization strategies enabled rapid construction of the [6.5.6.6.7]-pentacyclic core at an early stage. Highlights of the late-stage synthetic steps include a Pd-catalyzed Stille coupling and a highly stereoselective catalyst-controlled hydrogenation to incorporate the side chain at C₂₀ with both R and S configurations in the natural products.     

A three component one-pot synthesis of N-amino-2-pyridone derivatives catalyzed by KF-Al2O3

Synthesis of 1,6-diamino-4-phenyl-3,5-dicyano-2-pyridone derivatives via a one-pot, three-component reaction of aryl aldehydes, malononitrile, and cyanoacetic hydrazide at room temperature using KF-Al₂O₃ as a recyclable catalyst have been developed. The reaction proceeds through the initial Knoevenagel condensation between aldehyde and malononitrile in the presence of KF-Al₂O₃ to form the benzylidene derivative which then undergoes Michael addition with cyanoacetic hydrazide followed by intramolecular cyclization of the resulting intermediate to produce the N-amino-2-pyridones in good to excellent yields. The structure of the synthesized compounds were characterized and established on the basis of their spectral data analysis and single-crystal XRD analysis.     

Methyl 3‐(4‐methoxyphenyl)prop‐2‐enoate

The title mol­ecule, C₁₁H₁₂O₃, is almost planar, with an average deviation of the C and O atoms from the least‐squares plane of 0.146 (4) Å. The geometry about the C=C bond is trans. The phenyl ring and –COOCH₃ group are twisted with respect to the double bond by 9.3 (3) and 5.6 (5)°, respectively. The endocyclic angle at the junction of the propenoate group and the phenyl ring is decreased from 120° by 2.6 (2)°, whereas two neighbouring angles around the ring are increased by 2.3 (2) and 0.9 (2)°. This is probably associated with the charge‐transfer interaction of the phenyl ring and –COOCH₃ group through the C=C double bond. The mol­ecules are joined together through C—H?O hydrogen bonds between the methoxy and ester groups to form characteristic zigzag chains extended along the c axis.     

两个单环有机过氧化物的合成

报道了两个新的环状有机过氧化物. 在1,2-二氧六环化合物的合成中, 首次探讨了利用对三取代碳—碳双键的分子内Michael加成来完成过氧环环合的可能性. 在1,2-二氧七环的合成中由于无法利用Michael加成来完成七元过氧环环合, 采用了汞离子媒介的反应来实现七元过氧环的构建.     

Mechanism of photolysis of peroxy complexes of titanium(IV)

Conditions were found under which radical pairs become stabilized during the photolysis of peroxy complexes of titanium(IV) in alcoholic solutions. It was shown that precursors are dimeric complexes of titanium(IV) comprising peripheral peroxy ligands as well as a peroxy bridge. Irradiation by light corresponding to the peroxy ligand — the central ion charge transfer bands, leads to the initiation of an intraspheric reaction, as a result of which two peripheral peroxy ligands undergo a one-electron oxidation, while the bridge undergoes a two-electron reduction. The radical particles (HO₂ ^. and O₂ ) formed from the peripheral peroxy ligands become stabilized at strictly delineated distances relative to one another, which are determined by the structure of the initial dimeric peroxy complex of titanium(IV).Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 24, No. 6, pp. 678–685, November–December, 1988.