Reactivity of p-nitrostyrene oxide as an alkylating agent. A kinetic approach to biomimetic conditions

The alkylating potential of p-nitrostyrene oxide (pNSO)--a compound used as a substrate to study the activity of epoxide hydrolases as well as in polymer production and in the pharmaceutical industry--was investigated kinetically. The molecule 4-(p-nitrobenzyl)pyridine (NBP), as a model nucleophile for DNA bases, was used as an alkylation substrate. In order to gain insight into the effect of the hydrolysis of pNSO, as well as the hydrolysis of the NBP-pNSO adduct on the pNSO alkylating efficiency, these two competing reactions were studied in parallel with the main NBP-alkylation reaction. The following conclusions were drawn: (i) pNSO reacts through an S(N)2 mechanism, with NBP to form an adduct, pNSO-NBP (AD). The rate equation for the adduct formation is: r = d[AD]/dt = k(alk)[NBP][pNSO]-k(hyd)(AD) [AD] (k(alk), and k(hyd)(AD) being the alkylation rate constant and the NBP-pNSO adduct hydrolysis rate constant, respectively); (ii) the alkylating capacity of pNSO, defined as the fraction of initial alkylating agent that forms the adduct, is similar to that of mutagenic agents as effective as β-propiolactone. The instability of the pNSO-NBP adduct formed could be invoked to explain the lower mutagenicity shown by pNSO; (iii) the different stabilities of the α and β-adducts formed between NBP and styrene oxides show that the alkylating capacity f = k(alk)[NBP]/(k(alk)[NBP] + k(hyd)) (k(hyd) being the pNSO hydrolysis rate constant) as well as the alkylating effectiveness, AL = f/k(hyd)(AD), are useful tools for correlating the chemical reactivity and mutagenicity of styrene oxides; (iv) a pNSO-guanosine adduct was detected.     

4-Acetylpyridine 2-Benzothiazolylhydrazone as a Chromogenic Reagent for Common Epoxides

Abstract

A simple and sensitive color reaction of common epoxides as well as other some alkylating agents with 4-acetylpyrldine 2-benzothiazolylhydrazone (ABH) is described. These compounds gave a purpllsh red color after reaction with ABH for 2 hrs at 110°C in methyl cellosolve or for 20 min at 120°C followed by treatment with plperazlne on silica gel thin-layer plates. Four aliphatic terminal epoxides could be determined spectrophotometrically in the range from 20 to 125 nmol/ml. The limits of detection of these epoxides on silica gel thin-layer plates were 10 pmol/spot order by the visual inspection. The reaction mechanism is also discussed based on the chemical structure of the isolated chromophore.     

Sorbic Acid as an Alkylating Agent

A kinetic study of the alkylating potential of the sorbic acid + NaOH and sorbic acid + KOH systems was performed in 7:3 (volume/volume) water + dioxane solvent mixtures. The following conclusions were drawn. First, the sorbic acid + sorbate system shows alkylating activity on the nucleophile 4-(p-nitrobenzyl)pyridine (NBP), which is used as a trap for alkylating agents having nucleophilic characteristics similar to DNA bases. Second, the maximum alkylating capacity is observed in the pH = 5.0 to 6.5 range. Third, the alkylation reactions comply with the rate equation r=k _alk[H⁺][S][NBP]/(K _a +[H⁺]), with K _a being the dissociation constant of sorbic acid. Fourth, an enthalpy–entropy (ΔH ^#/ΔS ^#) compensation effect for activation quantities is observed by comparing NBP alkylation reactions due to sorbic acid + NaOH, sorbic acid + KOH, as well as potassium sorbate + HCl mixtures. Fifth, the results may help to establish suitable expiration times for products preserved with sorbic acid.     

Determination of small amounts of some sulfonamide drugs by resonance raman spectrometry

Resonance Raman spectrometric determinations of eight sulfonamide drugs are discussed. All the samples were colorless and exhibited no resonance Raman effect with argon ion laser excitation. After conversion to colored derivatives by diazotization and coupling reactions of the aromatic primary amine moiety, the sulfonamides could be determined from their resonance Raman spectra; the detection limits were about 2 × 10^-3 M. However, the method cannot be used for identification of the individual drugs because the spectra obtained exhibited exactly the same spectral features. In order to obtain characteristic spectra, color development for the R—NH₂ molecule produced by hydrolysis of the sulfonamide with hydrochloric acid was examined. Three of the samples tested (sulfathiazole, sulfisoxazole and sulfisomezole) gave colored derivatives by a common chemical reaction system; the resonance Raman spectra then obtained exhibited characteristic spectral patterns.     

A PM3 study of the critical distance factor in the activation/cyclization of selected Neocarzinostatin analogs

Semiempirical MOPAC RHF/PM 3 and BIRADICAL/PM 3 calculations are performed on several selected analogs of the Neocarzinostatin chromophore. The critical distance parameter, heat of formation, and pertinent bond orders are reported for each model compound. Heats of reaction are also reported for the cyclization of several model compounds to their corresponding diradical products. It is suggested that 3.49 ÅR represents an upper bound to the critical distance in the cyclization of compound related to Neocarzinostatin chromophore. © 1994 John Wiley & Sons, Inc.     

White light electroluminescence from graphene‐enhanced single polymer comprising two color emitters of equal molar ratios

White polymeric light‐emitting diode (WPLED) based on a single polymer, poly(3‐hexylthiophene‐alt‐9,9‐dioctylfluorene) (PTAF), has been successfully demonstrated. This conjugated alternating copolymer, PTAF, comprises 50 mol % of 3‐hexylthiophene which is an orange‐red color chromophore and 50 mol % 9,9‐dioctylfluorene which is a bluish‐green color chromophore. It was synthesized by Suzuki cross‐coupling reaction and has a molecular weight of 15,021 and polydispersity of 1.36. Nanocomposite consisting PTAF and graphene nanosheets enhances the optoelectronic properties and the device fabricated with a configuration of ITO/PEDOT:PSS/(PTAF + 1% graphene)/Ca/Al shows two‐color white electroluminescence with CIE 1931 coordinates of (0.28, 0.34). The white luminescence from a single polymer affords the WPLED device a simple structure and low fabrication cost. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Enantioselective DNA alkylation by a pyrrole-imidazole S-CBI conjugate

Conjugates 12S and 12R of N-methylpyrrole (Py)-N-methylimidazole (Im) seven-ringed hairpin polyamide with both enantiomers of 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) were synthesized, and their DNA alkylating activity was examined. High-resolution denaturing gel electrophoresis revealed that 12S selectively and efficiently alkylated at one match sequence, 5'-TGACCA-3', in 450-bp DNA fragments. The selectivity and efficiency of the DNA alkylation by 12S were higher than those of the corresponding cyclopropapyrroloindole (CPI) conjugate, 11. In sharp contrast, another enantiomer, 12R, showed very weak DNA alkylating activity. Product analysis of the synthetic decanucleotide confirmed that the alkylating activity of 12S was comparable with 11 and that 12S had a significantly higher reactivity than 12R. The enantioselective reactivity of 12S and 12R is assumed to be due to the location of the alkylating cyclopropane ring of the CBI unit in the minor groove of the DNA duplex. Since the CBI unit can be synthesized from commercially available 1,3-naphthalenediol, the present results open up the possibility of large-scale synthesis of alkylating Py-Im polyamides for facilitating their use in future animal studies.     

(6-4)-photolyase activity requires a charge shift reaction

A model compound containing a thymine oxetane moiety linked to a flavin chromophore was investigated regarding (6-4)-photolyase activity. The need for a charge shift reaction was demonstrated by a detailed pH-dependent kinetic analysis.     

Synthesis and characterization of photoswitchable lipids containing hemithioindigo chromophores

The synthesis of four lipids containing the hemithioindigo chromophore as part of the fatty acid is described. Heck reaction of bromophenyl thioacetate esters with acrylonitrile, followed by reduction, ester hydrolysis, and Friedel--Craft acylation--cyclization gave a substituted thioindoxyl that condensed with an alkoxy benzaldehyde to produce the hemithioindigo. "Solventless" nitrile hydrolysis followed by mixed anhydride coupling of the acid with glycerophosphocholine produced lipids bearing two hemithioindigo chromophores. The photochemistry of various hemithioindigo derivatives was studied to confirm the expected photoisomerization in both homogeneous organic solution, and in vesicle bilayer membranes. Characteristic changes in the UV--visible spectra are consistent with fully reversible Z--E photoisomerization. Chromatographic separation of the Z and E isomers of a compound containing a single hemithioindigo chromophore confirmed the spectroscopic analysis and provided a quantitative analysis of the compositions of Z--E isomer mixtures.     

Kinetic study of the fast step of the alkaline hydrolysis of p-chloranil using stopped flow technique

The alkaline hydrolysis of p-chloranil or 2,3,5,6-tetrachloro-1,4-benzoquinone (C₆Cl₄O₂, Q) was studied, using stopped flow spectrophotometry and Electron Spin Resonance techniques (E.S.R.). In the present study it was shown for the first time, that a free radical is produced chemically and that it can account for the propagation of the reaction. It was found that in alkaline conditions chloranil in a “Michael” fashion undergoes 1,2 addition being hydrolyzed and in turn produces a chloranil free radical (Q^•) The hydrolysis then proceeds via a number of intermediates yielded by this radical and a number of different products is formed. The formation of these products, both quantitatively and qualitatively has a strong dependence on the concentration of the OH⁻ species and chloranil. The various possible routes of the hydrolysis are studied either spectrophotometrically or by E.S.R. Two different intermediates are observed absorbing at 426 nm and at 540 nm, respectively. Each species was formed and destroyed within 10 s to 30 min depending on the exact conditions. The reaction rate constants for the formation and the decay of the intermediates was estimated using the Guggenheim method. At both wavelengths the rate constants seem to have a complex relation to the concentration of the anion. © 1997 John Wiley & Sons, Inc. Int J Chem Kinet 29: 385–391, 1997     

(R)-N-(β-三氯锗丙酰基)四氢噻唑-2-硫酮-4-羧酸甲酯的合成及其晶体结构

三氯锗丙酰氯与(R)-四氢噻唑-2-硫酮-4-羧酸甲酯反应, 得到标题化合物1, [α]~D^2^0-89.40°。经水解得到取代丙酰四氢噻唑-2-硫酮-4-羧酸甲酯基锗倍半氧化物2, X射线衍射法测出标题化合物的晶体结构, 属于正交晶系, 晶胞参数: a=0.6192(1)nm,b=1.1147(4)nm,c=2.1796(8)nm, V=1.5045nm^3, Z=4, 空间群P2~12~12~1。分子中酰胺羰基C=O与C=S基团处于C(4)NC(3)键两侧呈反式。用MNDO分子轨道方法研究了该化合物的电子结构, 电荷和键序分布,前沿轨道性质,讨论了电子光谱性质。     

Kinetic study of the reaction of dimethyl carbonate with trialkylamines

Quaternary ammonium compounds are produced worldwide in hundreds of millions of pound volume annually for a plethora of end‐uses from fabric‐care formulations to asphalt emulsifiers, typically from nongreen alkylating reagents. The kinetics of a reaction employing dimethyl carbonate (DMC) as a green alkylating agent was investigated using three trialkylamines (tributylamine, trihexylamine, and trioctylamine) at several temperatures. Arrhenius and Eyring analysis of the data showed that values of E_a (79 kJ/mol), ΔH^? (75 kJ/mol), and ΔS^? (220 J/(mol K)) were the same for all three amine reactants, consistent with a report that E_a is independent of alkyl chain length when the chain length is greater than three carbons. Although rates are significantly slower with DMC than with other alkylating reagents, the resulting methyl carbonate anion has advantages for clean anion metathesis, which is important for some applications, especially those involving ionic liquids. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 221–225, 2010     

Theoretical study of mechanism of forming a silapolycyclic compound between methylenesilylene and acetone

The mechanism of the cycloaddition reaction of forming a silapolycyclic compound between singlet methylenesilylene and acetone has been investigated with MP2/6‐31G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. The energies of the different conformations are calculated by CCSD(T)//MP2/6‐31G* method. From the potential energy profile, we predict that the cycloaddition reaction of forming a silapolycyclic compound between singlet methylenesilylene and acetone has two competitive dominant reaction pathways. First dominant reaction pathway consists of four steps: (I) the two reactants (R1, R2) first form an intermediate (INT1) through a barrier‐free exothermic reaction of 46.2 kJ/mol; (II) intermediate (INT1) then isomerizes to a planar four‐membered ring product (P3) via transition state (TS3) with an energy barrier of 47.1 kJ/mol; (III) planar four‐membered ring product (P3) further reacts with acetone (R2) to form an intermediate (INT4), which is also a barrier‐free exothermic reaction of 40.0 kJ/mol; (IV) intermediate (INT4) isomerizes to a silapolycyclic compound (P4) via transition state (TS4) with an energy barrier of 57.0 kJ/mol. Second dominant reaction pathway consists of three steps: (I) the two reactants (R1, R2) first form a four‐membered ring intermediate (INT2) through a barrier‐free exothermic reaction of 0.5 kJ/mol; (II) INT2 further reacts with acetone (R2) to form an intermediate (INT5), which is also a barrier‐free exothermic reaction of 45.4 kJ/mol; (III) intermediate (INT5) isomerizes to a silapolycyclic compound (P5) via transition state (TS5) with an energy barrier of 49.3 kJ/mol. P4 and P5 are isomeric compounds. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Synthesis of side chain liquid crystalline copolymers and characterization of their polar structure

A series of side chain liquid crystalline copolymers having different spacer lengths, copolymer compositions, and chromophore types were synthesized and characterized both in the bulk and at the gas‐water interface. Liquid crystalline properties were identified by differential scanning calorimetry (DSC), optical microscopy, and X‐ray diffraction (XRD). Copolymer with spacer lengths 4, 5, 10, and 11 showed smectic A (S_A) phases with a bâtonnet texture. The liquid crystalline (LC) phase stabilized as the spacer increased. Copolymers with different compositions were investigated both as monolayers and transferred films. The isotherms suggest nanodomain formation at the gas‐water interface in copolymers with high nitrobiphenyl (NBP) content. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1057–1070, 1999     

奶粉中唾液酸的测定方法

利用酸水解把奶粉中的唾液酸释放出来,通过聚丙烯酰胺凝胶除去奶粉中大量乳糖的干扰。利用Cu^2＋和Cr^3＋协同催化唾液酸与间苯二酚的显色,用乙酸丁酯-正丁醇萃取有色物质,在610nm处测定牛奶中唾液酸含量。方法的线性范围0～55．90mg／L,回收率为94％～96％。     

The unusual ability of α‐angelicalactone to form adducts: A kinetic approach

Since α‐angelicalactone (AAL) substantially inhibits the formation of tumors, here its chemical reactivity was compared with that of carcinogenic lactones. Investigation of the electrophilic potential of AAL was carried out by studying the capacity of this lactone to form adducts with NBP, 4‐(p‐nitrobenzyl)pyridine, a substrate with nucleophilic characteristics similar to DNA bases. The formation of the AAL–NBP adduct occurs about 900,000‐fold faster than with β‐propiolactone, the most effective carcinogenic lactone (ΔG^#₃₅ = 52 and 87 kJ mol^?1, respectively). A stopped‐flow technique was required for this reaction to be monitored. It was concluded that the formation of AAL–NBP adducts takes place through an entropy‐strain‐catalyzed mechanism caused by early lactone ring cleavage. The kinetic results are consistent with the AAL potential as a chemoprotective agent. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 591–594, 2007     

Mechanistic aspects of oxidation of dextrose by N-bromophthalimide in acidic medium: a micellar kinetic study

Kinetic investigations of oxidation of dextrose by N-bromophthalimide (NBP) in acidic medium in the presence of mercuric(II) acetate as a scavenger have been studied. In both the absence and presence of surfactants, the oxidation kinetics of dextrose by NBP shows a first-order dependence on NBP, fractional order on dextrose, and negative fractional order dependence on sulfuric acid. The determined stoichiometric ratio was 1:1 (dextrose:NBP). The variation of Hg(OAC)₂ and phthalimide (reaction product) have an insignificant effect on reaction rate. Effects of surfactants, added acrylonitrile, added salts, and solvent composition variation have been studied. Activation parameters for the reaction have been evaluated from Arrhenius plot by studying the reaction at different temperature. The rate law has been derived on the basis of obtained data. A plausible mechanism has been proposed from the results of kinetic studies, reaction stoichiometry and product analysis. The role of anionic and non-ionic micelle was best explained by the Berezin’s model.     

Coupling of two diazotized 3‐aminothieno[3,4‐c]coumarins with aromatic amines

The coupling reactions of two diazotized 3‐aminothieno[3,4‐c]coumarins were investigated. Compounds 1a , 1b both react with sodium nitrite in concentrated sulphuric acid at 0–5°C to give the diazotized intermediates 2 and 3 , the latter resulting from the acid ‐catalyzed hydrolysis of the lactonic ring of 2 . The in situ formed diazonium salts react with aromatic amines ( 4 ) to afford a series of arylazothiophenes dyes in the form of their ammonium sulfate salts. With diazotized aniline, besides the normally expected phenylazothiophene 10 from the reaction with compound 1a , the corresponding product of acid hydrolysis 11 was also isolated. In at least one of the cases, the thienyl diazonium salt 2 undergoes a Gomberg–Bachmann arylation reaction with p‐nitroaniline to give the 2‐arylthiophene 9 . The direct hydrolysis of compounds 1a , 1b by concentrated sulphuric acid and subsequent oxidative dimerization of the primary product of acid hydrolysis led to compound 12 . J. Heterocyclic Chem., (2011).     

Kinetic study of the ruthenium(III)-catalyzed oxidation of glycine by <Emphasis Type="Italic">N</Emphasis>-bromophthalimide in acidic medium

The kinetics of ruthenium(III) chloride-catalyzed oxidation of glycine by N–bromophthalimide (NBP) was studied in aqueous perchloric acid at 35 °C. The results showed first- and zero-order behavior with respect to NBP and Gly, respectively. Ru(III) showed a catalytic effect on the reaction which followed first-order kinetics with respect to [Ru(III)] at a low concentration range and tended to zero order at high concentration range. The rates decreased with increase in the proton concentration, while chloride positively influenced the rate of the reaction. Two moles of NBP were required to oxidize one mole of Gly, and the products were identified as phthalimide (NHP), HCN, CO₂, and Br⁻. Neither added NHP nor Br⁻ influenced the reaction rate. Ionic strength and dielectric constant of the medium had no significant effect on the rate. Activation parameters were determined by studying the reaction at different temperatures. A reaction scheme of the catalytic oxidation is proposed.     

Studies on the Wittig Reaction (IV) A Stereoselective Synthesis of the Insect Sex Pheromone of Laspeyresia pomonella,E,E,-8,10-Dodecadien-1-ol

Abstract

The Wittig reaction was widely used in the synthesis of natural products particularly in the area of insect pheromore synthesis. But unfortunately when a moderated triphenylphosphonium ylid is used, the resultant compound is a impractical E, Z, mixture. For instance, the title compound was once synthesized by the Wittig between butenylidene triphenylphosphorane and 8-oxo-octanoate, followed by hydrolysis and reduction. The product was a mixture containing 75% 8E,10E, isomer and 25% 8Z,10E isomer. Recently we have reported that a simple change in phosphorus substituents from Ph₃P=CHR to Ph₂(RCH₂)P=CHR(R′=alkenyl or H) dramatically increases the proportion of Eolefin formed from moderated ylides(R=alkenyl) and aliphatic aldehydes. According to this fact, here we report a stereoselective synthesis of E,E,-8,10-dodecadien-1-ol from butenylidene methyl diphenylphosphorane and 8-oxo-octanoate in the absence of lithium salt(Schemel). After hydrolysis and reduction, the title compound containing 94.7% 8E, 10E isomer was obtained. This approach affords a convenient synthesis for insect pheromones bearing a E,E,conjugated diene moiety. This experimental fact once again illustrates the stereochemistry of allylic diphenylphosphonium ylid is quite different from the corresponding triphenylphosphonium one.