Kinetics and mechanism of the reaction of ozone with 3,6-di-tert-butylpyrocatechol

The reaction of ozone with 3,6-di-tert-butylpyrocatechol at 20°C was investigated, and it was found that the main reaction product was 3,6-di-tert-butylquinone, while the reaction rate was proportional to the concentrations of the reagents. A reaction scheme explaining the mechanism of formation of the main and side products is proposed.N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 6, pp. 1443–1447, June, 1992.     

Synthesis of 1,8-, 1,6- and 3,6-dichloro-9H-thioxanthen-9-ones

Cyclization of 2-chloro-6-[(3-chlorophenyl)thio]benzoic acid ( 2 ) gave a mixture of 1,8-, 3 , and 1,6-dichloro-9H-thioxanthen-9-ones 4 . The mixture was converted to 1,8-diamino- 7 , and 1-amino-6-chloro-9H-thioxanthen-9-ones 8 , from which 3 and 4 were prepared separately, respectively. From a mixture of 4 and 3,6-dichloro-9H-thioxanthen-9-one ( 11 ) obtained by cyclizing 4-chloro-2-[(3-chlorophenyl)thio]benzoic acid ( 10 ) was separated 11 by conversion of 4 to 8 .     

Synthesis, chemical properties and mutagenicity of 1,6- and 3,6-dinitrobenzo[a]pyrenes

Nitration of benzo[a]pyrene (BaP) with HNO3 (d = 1.38) produced a mixture of dinitroBaPs (1,6- and 3,6-isomers) and mononitroBaPs (1-, 3- and 6-isomers). Pure 1,6-dinitroBaP and 3,6-dinitroBaP were obtained by the reduction of the dinitroBaPs mixture with NaSH to yield the separable products 1-amino-6-nitroBaP and 3-amino-6-nitroBaP, followed by conversion to dinitroBaPs via the the diazonium salts. The half-wave potentials (E1/2) corresponding to the one-electron reduction of dinitroBaPs were measured and the relationship of these values to the mutagenicity is discussed.     

Synthesis of 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydro- 1,6-naphthyridines by a directed lithiation reaction

N-(tert-butoxycarbonyl)anilines (7), are easily converted in a one pot reaction sequence into the N- (tert-butoxycarbonyl)-1,2,3,4-tetrahydroquinolines (8), by directed ortho lithiation followed by reaction with 1- chloro-3-iodopropane, hence providing a new versatile quinoline ring nucleus synthesis. In an analogous reaction 2-N-(tert-butoxycarbonyl)- and an 2-N-(pivaloylamino) pyridine are converted to 1,2,3,4-tetrahydro-1,6- naphthyridines.     

Quantum mechanical/molecular mechanical study on the mechanism of the enzymatic Baeyer-Villiger reaction

We report a combined quantum mechanical/molecular mechanical (QM/MM) study on the mechanism of the enzymatic Baeyer-Villiger reaction catalyzed by cyclohexanone monooxygenase (CHMO). In QM/MM geometry optimizations and reaction path calculations, density functional theory (B3LYP/TZVP) is used to describe the QM region consisting of the substrate (cyclohexanone), the isoalloxazine ring of C4a-peroxyflavin, the side chain of Arg-329, and the nicotinamide ring and the adjacent ribose of NADP(+), while the remainder of the enzyme is represented by the CHARMM force field. QM/MM molecular dynamics simulations and free energy calculations at the semiempirical OM3/CHARMM level employ the same QM/MM partitioning. According to the QM/MM calculations, the enzyme-reactant complex contains an anionic deprotonated C4a-peroxyflavin that is stabilized by strong hydrogen bonds with the Arg-329 residue and the NADP(+) cofactor. The CHMO-catalyzed reaction proceeds via a Criegee intermediate having pronounced anionic character. The initial addition reaction has to overcome an energy barrier of about 9 kcal/mol. The formed Criegee intermediate occupies a shallow minimum on the QM/MM potential energy surface and can undergo fragmentation to the lactone product by surmounting a second energy barrier of about 7 kcal/mol. The transition state for the latter migration step is the highest point on the QM/MM energy profile. Gas-phase reoptimizations of the QM region lead to higher barriers and confirm the crucial role of the Arg-329 residue and the NADP(+) cofactor for the catalytic efficiency of CHMO. QM/MM calculations for the CHMO-catalyzed oxidation of 4-methylcyclohexanone reproduce and rationalize the experimentally observed (S)-enantioselectivity for this substrate, which is governed by the conformational preferences of the corresponding Criegee intermediate and the subsequent transition state for the migration step.     

CH3+HNCO反应机理的理论研究

异氰酸(HNCO)分解引发的一系列自由基反应是氮氧化物快速消除机理[1,2](RAPRENOX)所研究的领域,该反应涉及到燃烧化学中氮氧化物NOX的消除,所以获得这些反应准确的位垒就成为实验化学和理论化学所要解决的问题。本文中我们重点研究CH3+HNCO反应机理,探讨CH3自由基是否也能象氮氢自由基一样,在异氰酸(HNCO)分解反应中起作用。1　计算方法用量子化学MP2方法,在6 311++G 水平上计算了CH3自由基与HNCO反应的反应物、产物、中间体和过渡态的几何构型,用QCISD(T)方法在6 311++G 水平上计算了它们的能量。通过振动分析确定…     

Kinetics and mechanism of the thermal decomposition reaction of dihydro-3,6-diphenyl-5-benzyl-1,2,4,5-trioxazine

The thermal decomposition reactions of dihydro-3,6-diphenyl-5-benzyl-1,2,4,5-trioxazine (DHT) in the initial concentrations and temperature ranges of 0.004–0.013 M and 353–393 K, respectively, have been investigated in benzene, toluene, and methanol solutions. In these solvents the reaction follows a first-order kinetic law up to ca. 50% DHT conversions. However, at the higher temperatures and higher initial concentrations, an induced decomposition reaction of the DHT molecule is observed, which is suppresed by the addition of a free radical scavenger. The pseudo-first-order rate constant values for the reactions of the trioxazine in acetic acid solution (0.004 M) in the temperature range of 313–323 K, lead to activation parameters significantly different from those of the unimolecular thermolysis in other media. This supports a marked effect of the solvent on that reaction. The kinetics and the nature of the products observed in the DHT thermolysis favors a general stepwise mechanism of decomposition which resembles the type of reaction already postulated for other cyclic peroxides in solution. © 1996 John Wiley & Sons, Inc.     

Synthesis and conformational study of 1,2,3,4,5,6,7,8-octahydro-1,6-naphthiridines

A new class of endocyclic enamines, 1,6-disubstituted 1,2,3,4,5,6,7,8-octahydro-1,6-naphthiridines, was synthesized from 4-piperidone imines by successive subjecting the latter to lithiation with lithium diethylamide, to alkylation with 1-bromo-3-chloropropane, and to intramolecular cyclization. All stages were carried out as a unique process without isolation of the intermediate compounds. A thorough optimization of the process conditions, workup, and product storage was carried out. The conformational study of 1,6-disubstituted 1,2,3,4,5,6,7,8-octahydro-1,6-naphthiridines was performed.     

Oxidation reaction by xanthine oxidase: theoretical study of reaction mechanism

The oxidation process by molybdenum-containing enzyme, xanthine oxidase, is theoretically studied with a model complex representing the reaction center and a typical benchmark substrate, formamide. Comparisons were systematically made among reaction mechanisms proposed previously. In the concerted and stepwise mechanisms that were theoretically discussed previously, the oxidation reaction takes place with a moderate activation barrier. However, the product is less stable than the reactant complex, which indicates that these mechanisms are unlikely. Moreover, the product of the concerted mechanism is not consistent with the isotope experimental result. In addition to those mechanisms, another mechanism initiated by the deprotonation of the active site was newly investigated here. In the transition state of this reaction, the carbon atom of formamide interacts with the oxo ligand of the Mo center and the hydrogen atom is moving from the carbon atom to the thioxo ligand. This reaction takes place with a moderate activation barrier and considerably large exothermicity. Furthermore, the product by this mechanism is consistent with the isotope experimental result. Also, our computations clearly show that the deprotonation of the active site occurs with considerable exothermicity in the presence of glutamic acid and substrate. The intermediate of the stepwise mechanism could not be optimized in the case of the deprotonated active site. From all these results, it should be concluded that the one-step mechanism with the deprotonated active site is the most plausible.     

Synthesis of sulfur-bridged piperazinediones by reaction of 3,6-dibromo-1,4-dimethyl-2,5-piperazinedione with geminal dithiols

The reaction of several geminal dithiols with 3,6-dibromo-1,4-dimethyl-2,5-piperazinedione gave in good yields piperazinedione derivatives substituted at the 3,6-position with a geminal dithiol-bridging group. These sulfur-bridged piperazinediones formally represent derivatives of the 2,4-dithia-6,8-diaza-7,9-dioxobicyclo[3.2.2]nonane ring system. Attempts to transform these sulfur-bridged piperazinediones to 3,6-epidithiopiperazinediones by removal of the bridging group common to the sulfur functionality were unsuccessful. Studies also are reported of addition of thioacetic acid to 3,6-dimethylene-2,5-piperazinedione to give 3,6-diacetylthio-3,6-dimethyl-2,5-piperazinedione. Conversion of the 3,6-diacetylthio derivative to the epithiopiperazinedione ring system yielded a mixture of epimono- and epidithiopiperazinediones.     

Synthesis of 2,3-di- and 2,3,4-trisubstituted furans from 1,2-dioxines generated by an enyne-RCM/Diels-Alder reaction sequence

An efficient method for the synthesis of 2,3- and 2,3,4-substituted furans starting from acyclic enynes was developed using an enyne-RCM/Diels-Alder reaction sequence. The reaction conditions for the transformation of 1,2-dioxines having an adjacent 1,2-oxazine ring into furans and the cleavage of N-O bonds are discussed.     

Studies on the interaction mechanism between CXS and papain by spectroscopic and molecular modeling methods

We have studied the interaction between cefuroxime sodium (CXS) and papain at different temperatures by a fluorescence method, and confirmed that the mechanism of fluorescence quenching of CXS to papain is mainly static quenching. We also determined the binding constant K. Based on the thermodynamic functions at different temperatures, the results show that the major forces between CXS and papain are van der Waals’ forces and H bond. According to the Forster non-radiation energy transfer mechanism, we determined the binding distance between CXS and papain, and studied the confirmation effect of CXS to papain by synchronous fluorescence and UV–Vis spectroscopy. Molecular simulations show that the binding types of CXS and papain are van der Waals’ forces, hydrophobic interaction, and H-bond.     

The reaction of 3,6-di-tert-butyl-1,2-benzoquinone and 3,6-di-tert-butylcatechol withtert-butyl hydroperoxide

Reaction of 3,6-di-tert-butyl-1,2-benzoquinone and 3,6-di-tert-butylcatechol withtert-butyl hydroperoxide in aprotic solvents leads to the generation of semiquinone (SQ^.H), alkylperoxy (ROO^.), and alkyloxy radicals. The reaction of SQ^.H and ROO^. produces 2,5-di-tert-butyl-6-hydroxy-1,4-benzoquinone, 3,6-di-tert-butyl-1-oxacyclohepta-3,5-diene-2,7-dione, and 2,5-di-tert-butyl-3,6-dihydroxy-1,4-benzoquinone. The radical generated from solvent attacks SQ^.H at position 4 with C−C bond formation. 4-Benzyl-2,5-di-tert-butyl-6-hydroxycyclohexa-2,5-diene-1-dione produced in this way is transformed into 4-benzyl-3,6-di-tert-butyl-1,2-benzoquinone under the reaction conditions. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 943–946, May, 1999.     

Modification of gelatin by reaction with 1,6-diisocyanatohexane

1,6-Diisocyanatohexane and dimethyl sulfoxide were exploited as crosslinking agent and reaction solvent, respectively, for gelatin modification. Crosslinked samples were fractionated and analyzed by thermogravimetric analysis, infrared spectroscopy, acid and base titrations, and swelling measurements. The yield of crosslinking was found to increase with increasing diisocyanate and gelatin concentrations and the amount of bound crosslinker was evaluated. The chemical analysis of the reaction products allowed the process parameters to be related to the properties of the textile/gelatin composites. For this purpose poly(propylene)-, poly(ethylene terephthalate)-, and cotton-based textiles were treated to prepare soft and dimensionally stable supported materials with a gel phase composed of gelatin.     

Molecular mechanism of interaction between norfloxacin and trypsin studied by molecular spectroscopy and modeling

The molecular mechanism of the binding of norfloxacin (NRF) to trypsin was investigated by fluorescence, synchronous fluorescence and UV–vis absorbance spectroscopy and molecular modeling at physiological conditions. The quenching mechanism and the binding mode were investigated in terms of the association constants and basic thermodynamic parameters. The results of spectroscopic measurements suggested that NRF have a strong ability to quench the intrinsic fluorescence of trypsin through static quenching procedure. Moreover, fluorescence experiments were also performed at different values of pH to elucidate the effect of pH on the binding. The NRF–trypsin complex was stabilized by hydrophobic forces and hydrogen bonding, via tryptophan residue as indicated from the thermodynamic parameters, which was consistent with the results of molecular docking and accessible surface area calculations.     

Reactivity Tournament of Isothiocyanato-Functionalized Saccharides with 1,6-Diamino-3,6-oxaoctane

Summary.  Thiourea-bridged glycoclusters and glycodendrimers are described in the literature as mimetics of (oligoantennary) oligosaccharides to serve as high-affinity lectin ligands. In extension of this concept, the assembly of different, structurally varied isothiocyanato-functionalized sugar derivatives on an oligoamine scaffold would lead to novel mixed glycoclusters. To control this approach, the relative reactivities of the isothiocyanates used in the thiourea-bridging reaction have to be known. Therefore, competition experiments with six different sugar isothiocyanates were carried out using 1,8-diamino-3,6-dioxaoctane as a symmetrical difunctionalized core molecule. Reactivities were ranked on the basis of integration ratios in the ¹H NMR spectra. A first mixed thiourea-bridged glycocluster was successfully prepared. Received June 13, 2001. Accepted October 31, 2001