The nature of the monomer insertion step in the allylnickel(II)-catalyzed 1,4-polymerization of 1,3-butadiene: sigma-allyl-insertion mechanism versus pi-allyl-insertion mechanism

We present a theoretical investigation on the nature of the monomer insertion step in the allylnickel(II)-catalyzed 1,4-polymerization of 1,3-butadiene that employed a gradient-corrected DFT method. We have explored critical elementary steps of the whole polymerization cycle for the trans-1,4 regulating cationic allylnickel(II) [RC3H4NiII(C4H6)L]+ catalyst. These steps are i) cis-butadiene insertion into either the eta 1-sigma-butenyl-NiII bond (sigma-allyl insertion mechanism) or the eta 3-pi-butenyl-NiII bond (pi-allyl insertion mechanism) along with competing pathways for generation of trans-1,4 and cis-1,4 polymer units, and ii) anti-syn isomerization. Based on the analysis of geometric and electronic structures of key species involved and the energetics, we present a detailed insight into the different nature of the monomer insertion step according to the two mechanistic alternatives. An understanding of why the pi-allyl insertion mechanism is favored over the sigma-allyl insertion mechanism is provided. eta 1-sigma-butenyl-NiII Species are predicted to be sparsely populated and also distinctly less reactive than eta 3-pi-butenyl-NiII species. Although they are commonly believed to be reactive intermediates, eta 1-sigma-butenyl-NiII species are, therefore, not likely to be involved along viable pathways for cis-butadiene insertion into the butenyl-NiII bond. The present investigation corroborates our previous conclusion that the pi-allyl insertion mechanism represents the preferred mechanism for the monomer insertion step in the allylnickel(II)-catalyzed 1,4-polymerization of 1,3-butadiene. On the other hand, the suggested alternative sigma-allyl insertion mechanism has to be considered to be not operative, for both thermodynamic and kinetic reasons. Furthermore, the sigma-allyl insertion mechanism would neither provide a rationalization of cis-trans selectivity nor of chemoselectivity in the allylnickel(II)-catalyzed 1,4-polymerization of 1,3-butadiene.     

Complex behavior in coupled bromate oscillators

In this study, coupled bromate-oscillators constructed by adding 1,4-cyclohexanedione (1,4-CHD) to the ferroin-catalyzed Belousov-Zhabotinsky reaction are investigated in a batch reactor under anaerobic conditions. Various complex behaviors such as sequential oscillations and bursting phenomena are observed. At low concentrations of ferroin or malonic acid (MA), the development of sequential oscillations is found to depend on the ratio of [1,4-CHD]/[ferroin] and [1,4-CHD]/[MA] rather than their absolute concentrations. As the concentration of MA or ferroin was increased gradually, however, the minimum 1,4-CHD concentration required to induce complex oscillations reaches a plateau. Perturbations by light illustrate that the first oscillatory window is governed by the ferroin-MA-BZ mechanism, whereas the 1,4-CHD-bromate oscillator plays a prominent role during the non-oscillatory evolution and the second oscillatory window. Our conclusion is further supported by numerical simulations in which sequential oscillations observed in experiments are qualitatively reproduced by a modified FKN mechanism.     

A radical-anion chain mechanism initiated by dissociative electron transfer to a bicyclic endoperoxide: insight into the fragmentation chemistry of neutral biradicals and distonic radical anions

The electron-transfer (ET) reduction of two diphenyl-substituted bicyclic endoperoxides was studied in N,N-dimethylformamide by heterogeneous electrochemical techniques. The study provides insight into the structural parameters that affect the reduction mechanism of the O-O bond and dictate the reactivity of distonic radical anions, in addition to evaluating previously unknown thermochemical parameters. Notably, the standard reduction potentials and the bond dissociation energies (BDEs) were evaluated to be -0.55+/-0.15 V and 20+/-3 kcal mol(-1), respectively, the last representing some of the lowest BDEs ever reported. The endoperoxides react by concerted dissociative electron transfer (DET) reduction of the O-O bond yielding a distonic radical-anion intermediate. The reduction of 1,4-diphenyl-2,3-dioxabicyclo[2.2.2]oct-5-ene (1) results in the quantitative formation of 1,4-diphenylcyclohex-2-ene-cis-1,4-diol by an overall two-electron mechanism. In contrast, ET to 1,4-diphenyl-2,3-dioxabicyclo[2.2.2]octane (2) yields 1,4-diphenylcyclohexane-cis-1,4-diol as the major product; however, in competition with the second ET from the electrode, the distonic radical anion undergoes a beta-scission fragmentation yielding 1,4-diphenyl-1,4-butanedione radical anion and ethylene in a mechanism involving less than one electron. These observations are rationalized by an unprecedented catalytic radical-anion chain mechanism, the first ever reported for a bicyclic endoperoxide. The product ratios and the efficiency of the catalytic mechanism are dependent on the electrode potential and the concentration of weak non-nucleophilic acid. A thermochemical cycle for calculating the driving force for beta-scission fragmentation is presented, and provides insight into why the fragmentation chemistry of distonic radical anions is different from analogous neutral biradicals.     

Mechanism of the condensation reaction between 1-aryl- and heteroaryl-1,4-dihydro-3(2H)-isoquinolinones and aldehydes

4-Benzylidene-1-phenyl-1,4-dihydro-3(2H)-isoquinolinone, the intermediary product of the carbonyl condensation reaction between 1-phenyl-1,4-dihydro-3(2H)-isoquinolinone and benzaldehyde, rearranges in the presence of an equivalent quantity of sodium hydride into 4-benzyl-1-phenyl-3(2H)-isoquinolinone. As the possibility of the migration of the hydrogen at C-1 in the form of a proton or a hydrogen atom (radical reaction) was excluded, the mechanism of the rearrangement could be depicted as an intermolecular hydride anion migration. In case of the 1-(4-pyridyl)- and 1-(3-pyridyl)-1,4-dihydro-3(2H)-isoquinolinones, however, the rearrangement can be carried out also in polyphosphoric acid and in this case a proton loss-proton gain mechanism was proved.     

Chemistry of a 1-silacyclopropene. Thermal production of 1,4-disilacyclohexa-2,5-dienes

Thermolysis of 1,1-dimethyl-2-phenyl-3-trimethylsilyl-1-silacyclopropene in the presence or absence of an alkyne such as diphenylacetylene or ethyl-dimethylsilylphenylacetylene gave a mixture of 1,1,4,4-tetramethyl-2,5-diphenyl-3,6-bis(trimethylsilyl- and 1,1,4,4-tetramethyl-2,6-diphenyl-3,5-bis(trimethylsilyl)-1,4-disilacyclohexa-2,5-diene in high yield. The formation of the 1,4-disilacyclohexa-2,5-diene system can be best rationalized in terms of a mechanism involving direct dimerization of the 1-silacyclopropene.     

Phthalimido-nitren I. Bleitetraacetat-Oxydation von N-Aminophthalimid in inerten Lösungsmitteln. Bildung und Eigenschaften von trans-1,4-Bisphthaloyl-2-tetrazen

Lead tetraacetate oxidation of N-aminophthalimide ( 11 ) in inert solvents gives as major products phthalimide ( 15 ) or trans-1,4-bisphthaloyl-2-tetrazene ( 12 ), the former ( 15 ) on slow, the latter ( 12 ) on fast addition of the oxidizing agent. As by-products are found: (a) in the presence of acetic acid: N-acetylamino-phthalimide ( 14 ), and (b) in its absence (especially at higher temperatures): benzocyclobutenedione ( 13 ) along with N-phthalimido-phthalimide ( 16 ) as well as traces of phthalic anhydride ( 17 ). The tetrazene 12 and phthalimide ( 15 ) are considered to be formed by oxidation and fragmentation, respectively, of the intermediate 1,4-bisphthaloyl-tetrazane ( 18 ). Phthalimido-nitrene ( 22 ), or its conjugated acid 23 , is postulated to be the species which initiates the major reactions, namely: (a) addition to the educt 11 to give the tetrazane 18 and (b) fragmentation with loss of N₂ to give the dione 13 . The minor by-products 16 and 17 may be the result of cross-amidation of 11 with 15 and rearrangement-oxidation via phthalazine-1,4-dione ( 30 ), respectively. The structure of the tetraacyltetrazene 12 follows from its properties, among others a comparison of its UV. spectrum with that of the known 1,4-dimethoxycarbonyl-1,4-dimethyl-2-tetrazene ( 32 ). Methanolysis of 12 affords 1,4-di-(o-methoxycarbonyl-benzoyl)-2-tetrazene ( 33 ). The diacyltetrazene 33 is converted to methyl N-methoxycarbonyl-anthranilate ( 36 ), N₂ and phthalimide ( 15 ) on thermolysis, or to methyl N-acetylphthalamate ( 35 ), methyl N, N′-carbonyldianthranilate ( 37 ) and methyl N-acetyl-anthranilate ( 38 ) on acetylation in pyridine. The intermediate in these reactions, leading to 36 , 37 and 38 , probably is o-methoxycarbonyl-phenylisocyanate ( 34 ), itself the result of a Curtius-type rearrangement. Acetolysis of the tetrazene 12 gives phthalimide ( 15 ), N₂ and N-carboxyanthranilic anhydride ( 42 ) by a mechanism analogous to that of the methanolysis of 12 . In the preparation of 1,4-dimethoxycarbonyl-1,4-dimethyl-2-tetrazene ( 32 ), required for the above mentioned comparison, by zinc reduction of methyl N-methyl-N-nitro-carbamate ( 43 ), followed by bromine oxidation of methyl N-amino-N-methylcarbamate ( 44 ), a deamination of 43 to methyl N-methyl-carbamate ( 45 ) was observed both in the reductive and in the oxidative step. Both formations of 45 can be formulated via a nitrene and a tetrazane, namely via 47 and 48 .     

The Dehydrogenation of 1,4-Cyclohexadienes with 2,3-Dichloro-5,6-dicyanobenzoquinone and Triphenylmethylfluoroborate

The dehydrogenation of 1,4-cyclohexadiene ( 1 ) cis-3,6-dimethyl-1,4-cyclohexadiene ( 2 ) and trans-3,6-dimethyl-1,4-cyclohexadiene ( 3 ) with triphenylmethylfluoroborate in acetonitrile or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) proceeds in the same reactivity sequences 2 > 1 > 3 . The mechanism of the dehydrogenation of 1,4-cyclohexadienes with triphenylmethylfluoroborate and DDQ is discussed in the light of these results and in view of the kinetic isotope effects.     

醌类化合物在苯酚羟化反应中的电子传递作用

Fenton试剂是某些烃类化合物的有效氧化剂^[1],该体系对芳香化合物具有羟化作用。我们^[2]曾报道了含Cu类钙钛石型复合氧化物在苯酚烃化反应中的催化活性,并提出了相应的反应机理。高价态的过渡金属离子如C^3 [2]和Fe^3 [3]通常被认为是中间自由基的氧化剂。实际上,醌类化合物及其还原形式半醌、氢醌与生物体内许多电子转移过程密切相关^[4],如泛醌或辅酶Q在生物体呼吸链电子传递过程中起重要作用^[5]。在实验中我们观察到苯酚羟化反应中不仅有苯醌生成,而且生成的苯醌还能促进羟化反应。本文报道了醌类化合物在苯酚羟化循环中的传递电子作用。     

Synthesis of 1,4-benzodiazepine-3,5-diones

Even though benzodiazepines have a strong position in medicinal chemistry, very few synthetic routes to 1H-1,4-benzodiazepine-3,5(2H,4H)-diones have ever been published and the claimed products have often been poorly characterized. Through the present work several 1H-1,4-benzodiazepine-3,5(2H,4H)-diones have become available from N-carbamoylmethylanthranilic acids. The required ring closures were achieved only when the amino groups of the starting materials were substituted with electron withdrawing groups such as acetyl, alkyloxycarbonyl, or nitroso. During the synthetic work a novel ring contraction rearrangement from a 1-nitroso-1H-1,4-benzodiazepine-3,5(2H,4H)-dione to a 3H-quinazoline-4-one was observed. The proposed mechanism involves elimination of HNO followed by a proton-mediated loss of CO. The 1-nitrosated 1,4-benzodiazepinediones could be separately denitrosated to the corresponding amino compounds.     

Photorearrangements of hydrocarbon polymers with pendant double bonds

A study was made of the microstructural changes that occur in ultraviolet irradiation under vacuum of thin films of 1,2-poly(cis-1,4-hexadiene) (CHD), 1,2-poly(trans-1,4-hexadiene) (THD), 1,2-poly(trans-1,3-pentadiene) (TPD), equibinary (1,2,-1,4) polybutadiene (EB), and equibinary (3,4-1,4) polyisoprene (EI). These polymers—all containing pendant double bonds—undergo important photoinduced loss of unsaturation, presumably through cyclization of the double bonds, by analogy to the previously reported photocyclization of 1,2-polybutadiene (VB) and 3,4-polyisoprene (VI)films. For the equibinary polymers, which contain internal as well as external (or pendant) double bonds, the loss of unsaturation is considered to involve photocyclization of 1,2-1,4 and 1,2-1,2 dyads in EB and of 3,4-1,4 and 3,4-3,4 dyads in EI. Accompanying thecyclization process in CHD, THD, and TPD is a direct photochemical cis-trans isomerization of ? CH?CH? double bonds analogous to that originally noted for 1,4-polybutadiene. The photorearrangements in the above polymers with pendant double bonds were compared to the corresponding thermally induced rearrangements reported previoulsy;for VB and VI, in particular, the thermal, photo-and radiation-induced cycli-zations were found to be very similar, possibly having a common nonradical, nonionic mechanism involving excited double bonds.     

Photoreactions of 1,4-Naphthoquinones: effects of substituents and water on the intermediates and reactivity

The photochemistry of lapachol and other 1,4-naphthoquinone (NQ) derivatives, e.g. 2-methoxy-1,4-naphthoquinone (MeONQ), 2-hydroxy-1,4-naphthoquinone (2-HONQ) or 5-hydroxy-1,4-naphthoquinone (5-HONQ) and 2-methyl-5-hydroxy-1,4-naphthoquinone (P-NQ) in solution at room temperature was studied by ultraviolet-visible spectroscopy after nanosecond laser pulses at 248 nm. The triplet state and semiquinone radicals were observed for MeONQ, HONQ and P-NQ, whereas for lapachol, intramolecular H-atom and charge transfer processes take place, as in the case of vitamin K1. The photoinduced reaction of NQ into HONQ is initiated by nucleophilic water addition to the triplet state, and for the secondary reactions, a modified mechanism is proposed.     

Experimental and semiemprical studies of chemical reactivity of dialkylcadmium reagents addition to α,β-enones

Experimental and semiempirical calculations were carried out to study the reactivity of dialkylcadmium reagents addition to α,β-enones. It was demonstrated that α,β-enone such as benzoquinone with low lying LUMO energy reacts via single electron transfer (SET) mechanism with the formation of the 1,2 or 1,4-type alkyl addition product depending on the reaction temperature and substrate structure. Site and chemoselectivity in unsymmetrical benzoquinone derivatives are determined by the stability of the cadmium coordinated semienone complex intermediates and the carbon spin densities of these reactive species respectively. On the other hand, by increasing the LUMO energy of α,β-enone system, the reaction mechanism changes from SET to polar addition affording the 1,4-type alkyl addition product. The establishment of a correlation scale between substrate LUMO energies and reaction mechanism presented in this article will be discussed.     

Regioselective synthesis of fluoroalkylated [1,2,3]-triazoles by Huisgen cycloaddition

A series of fluoroalkylated 1,4-disubstituted [1,2,3]-triazoles were synthesized by the 1,3-dipolar cycloaddition of fluoroalkylated azides with terminal alkynes in the presence of Cu(I) salt as catalyst at room temperature. All the reactions were performed in highly regioselective with 1,4-disubstituted, no 1,5-disubstituted product was formed. For aryl or alkyl-alkyne, triethylamine should be used as ligand. But for propiolic ester(amide), triethylamine couldn’t be used, otherwise no products was formed. A mechanism of Cu(I) inserting the internal alkyne was suggested.     

Contribution a l'etude de la transformation thermique des aldazines α-ethyleniques. nouvelle voie d'acces aux pyrazoles halogenes ou substitues par des groupements phenoxy,thiophenoxy et thioethoxy en 3(5)

Azines of β-halogen-, aryloxy-, alkylthio- and arylthio-substituted acroleines when heated gave pyrazole derivatives which may be hydrolysed very easily to give N-unsubstituted pyrazoles bearing in the 3(5) position halogen, ArO, RS or ArS groups. The observed heterocyclisation was compared with thermal decomposition of cinnamald azine for which an ionic mechanism had been previously proposed, whereas we show that the involved mechanism is an internal 1,4-addition and, according to the nature of the migrating group, a thermal [1,3] or [1,5] sigmatropic rearrangement.     

A polarographic study of the hydrolysis of 1,4-benzodiazepines and its analytical applications

The mechanism of hydrolysis of flurazepam (Dalmane) and six of its metabolites was investigated in mildly acidic solution (pH 0–2) by differential pulse polarography. Simultaneous determinations of the “parent” compound(s) and hydrolytic degradation product(s) are possible because of the different reduction potentials. The kinetic results can be explained if the hydrolytic reaction is considered reversible; this is important for evaluation of the hydrolysis and absorption of 5-(o-fluorophenyl)-1,4-benzodiazepines in the stomach. The rate constants and the pK_a values corresponding to protonation of the azomethine groups are shown to be correlated. Appropriate kinetic data for other 1,4-benzodiazepines make it possible to evaluate the effects of certain substituents on the rate of hydrolysis and on the peak potentials of the “parent” compounds and their hydrolytic degradation products. The results of the kinetic investigations can be used for the identification of an isolated 5-(o-fluorophenyl)-1,4-benzodiazepine or identification of any 1,4-benzodiazepine studied here which exhibits some degree of acid hydrolysis within 24 h.     

Manganese(III) acetate-mediated free radical reactions of [60]fullerene with beta-dicarbonyl compounds

[60]Fullerene reacted with various beta-dicarbonyl compounds in the presence of Mn(OAc)3*2H2O to generate dihydrofuran-fused [60]fullerene derivatives or 1,4-bisadducts. Dihydrofuran-fused [60]fullerene derivatives 2 could be formed by treatment of alpha-unsubstituted beta-diketones 1a-e or beta-ketoesters 1f and 1g with [60]fullerene in refluxing chlorobenzene in the presence of Mn(III). Solvent-participated unsymmetrical 1,4-bisadducts 3 were obtained through the reaction of [60]fullerene with dimethyl malonate 1h or alpha-substituted beta-dicarbonyl compounds 1i-1n in toluene. A possible reaction mechanism for the formation of different fullerene derivatives is proposed.     

1,4-Dehydrogenation with a Two-Coordinate Cyclic (Alkyl)(amino)silylene

Cyclic (alkyl)(amino)silylene (CAASi) 1 has been found to successfully dehydrogenate 1,4-dihydroaromatic compounds containing various substituents to afford the corresponding aromatic compounds. The observed high substrate generality proves 1 to be a potential 1,4-dehydrogenation reagent for organic compounds. For the reaction with 9,10-dimethyl-9,10-dihydroanthracene, silylene 1 activated not only benzylic C−H bonds but also aromatic C−H bonds to yield a silaacenaphthene derivative, which is an unprecedented reaction of silylenes. The results of the experimental and computational study of the reaction of CAASi 1 with 9,10-dihydroanthracene and 1,4-cyclohexadiene are consistent with the notion that 1,4-dehydrogenation with CAASi 1 proceeds mainly through a stepwise hydrogen-abstraction mechanism.     

Coupled processes in carbon monoxide oxidation: Kinetics and mechanism of CO oxidation by oxygen in PdX<Subscript>2</Subscript>-organic solvent-water systems

PdX₂-organic solvent-water solutions, where X = halide (preferably bromide or iodide) and the organic solvent is 1,4-dioxane or tetrahydrofuran, are suggested as catalytic systems for CO oxidation. A number of coupled processes take place in these systems. The kinetics and mechanism of CO oxidation by oxygen in the PdI₂-LiI-1,4-dioxane-water system are reported. Cyclohexene hydrocarboxylation into cyclohexanecarboxylic acid can be carried out as part of the coupled process occurring in the PdBr₂-tetrahydrofuran-water system.     

Rapid-scan time-resolved FT-IR spectroelectrochemistry studies on the electrochemical redox process

The electron transfer to or from molecules containing multiple redox centers has been extensively investigated. Rapid scan time-resolved FT-IR-RAS spectroelectrochemistry was used to investigate the electron-transfer mechanism in this report. The electron transfer of two typical compounds, 1,4-benzoquinone and 1,4-bis(2-ferrocenylvinyl)benzene, was examined with this method. Although the two compounds show two-electron transfer in the redox process, 1,4-benzoquinone exhibits two single electron waves while 1,4-bis(2-ferrocenylvinyl)benzene exhibits a single wave in cyclic voltammetric experiments. The IR absorption of the intermediate, BQ*- and p-(Fc-CH=CH)+2-benzene, at 1506 and 1589 cm(-1), respectively, appeared and disappeared on the experimental time scale in the oxidation and reduction process was observed. In the oxidation process of the p-(Fc-CH=CH)2-benzene molecule, one Fc was oxidated to Fc+ first and the electron-withdrawing ability of Fc+ was stronger than that of Fc, which resulted in the D-pi-A structure and the band at 1589 cm(-1) becoming visible. Then as the oxidation continues, the other Fc was oxidated to Fc+ too, which resulted in the reforming of the symmetry of the benzene ring A-pi-A, so the band at 1589 cm(-1) disappeared. Similar phenomenon can be elucidated in the reduction process but the configuration type changed from A-pi-A to D-pi-A and finally to D-pi-D. Hence, not only 1,4-benzoquinone but also 1,4-bis(2-ferrocenylvinyl)benzene show two consecutive one-electron processes. In addition, it is observed that the existing time of the electrochemical reaction intermediate (BQ*- and p-(Fc-CH=CH)+2-benzene) is prolonged at low temperatures due to slow reaction kinetics.     

1,4-bis(3-aminopropyl)piperazine libraries: from the discovery of classical chloroquine-like antimalarials to the identification of new targets

The purpose of this review is to provide an update on our work based on the 1,4-bis(3-aminopropyl)piperazine skeleton and how it allowed our group to validate a new target. After a brief introduction where we will relate the way this substructure was introduced in our 4-aminoquinolinyl derivatives, we will present first the different libraries synthesized around this moiety: (1) libraries of sulfonamides, amides and amines derived from 4-aminoquinolines and, (2) libraries where the 4-aminoquinoline nucleus is replaced. High throughput evaluation of biological activity and physicochemical parameters will be presented. The evaluation of the anti-malarial activity of the compounds will be discussed in the light of a chloroquine-like mechanism (accumulation in the acidic food vacuole and inhibition of beta-hematin formation). In a second part we will present active 1,4-bis(3-aminopropyl)piperazine as tools for identification and/or validation of new antimalarial targets. Fluorescence assays on some derivatives show that they are surprisingly localized outside the food vacuole, suggesting the existence of other target(s). Secondly, we will present a library of 1,4-bis(3-aminopropyl)piperazine as inhibitors of the cytosolic aminopeptidase Pfa-M1, a new potential target for antimalarials.