5-卤代1,2,3,-三唑互变异构的密度泛函理论研究

用密度泛函B3LYP/6-311 G**方法,对气相和水相中的1,2,3三,-唑及5-卤(-F、C l和-B r)代1,2,3,-三唑互变异构体进行了几何构型全自由度优化,获得了它们在气相和水相中的几何结构和电子结构。计算结果显示,在气相和水相中1,2,3三-唑和5-卤代1,2,3三-唑的N2-H型要比对应的N1-H型和N3-H型稳定。讨论了不同的取代基团和溶剂化效应对互变异构体的几何结构、能量和电荷分布以及互变异构反应活化能的影响带。并进一步研究了N1-H、N2-H和N3-H型三唑之间的互变异构机理:(a)分子内质子转移;(b)水助质子转移。计算结果表明,途径(b)所需要的活化能较小,为120.06KJ/mol,途径(a)为204.12KJ/mol。     

5-氟胞嘧啶互变异构的密度泛函理论计算

采用BH-HLYP/6-311＋G**方法对10种气相和水相中可能存在的5-氟胞嘧啶互变异构体进行了几何全优化, 并计算出它们的总能量和吉布斯自由能. Onsager反应场溶剂模型用于水相的计算. 计算结果表明, 5-氟胞嘧啶在气相中主要以烯醇式-氨基式形式存在, 在水相中主要以酮式-氨基式形式存在. 溶剂化自由能与异构体的气相偶极矩存在相关性．进一步求得互变异构化以及构象异构化和顺反异构化的过渡态, 探讨异构化过程中的几何结构和能量的变化.     

5-氟尿嘧啶和5-氯尿嘧啶及其互变异构体的理论计算研究

采用HF/3-21G方法, 对6种气相和水相中可能存在的5-氟尿嘧啶(和5-氯尿嘧啶)互变异构体进行了构象分析.采用B3LYP/6-311＋G**方法对处于优势构象时的各互变异构体进行了几何全优化, 并计算出它们的总能量、焓、熵、吉布斯自由能. Onsager反应场溶剂模型用于水相的计算. 计算结果表明, 5-氟尿嘧啶和5-氯尿嘧啶在气相中和水相中主要以双酮形式存在. 5-氟尿嘧啶和5-氯尿嘧啶的熵效应小, 对互变异构平衡没有显著的影响, 而焓变对互变异构产生了主要的影响. 讨论了水溶剂化作用对异构体的能量、电荷分布和偶极矩的影响. 溶剂化自由能与异构体的气相偶极矩存在相关性. 另外, 详细地将5-氟尿嘧啶和5-氯尿嘧啶与尿嘧啶进行了对比, 获得三者最稳定异构体间电子结构异同的有用信息.     

吲唑、3-卤代吲唑互变异构反应机理的理论研究

The molecular structures of indazole and 3-halogeno-indazole tautomers were calculated by the B3LYP method at the 6-311G** level, both in the gaseous and aqueous phases, with full geometry optimization.The geometry and electronic structure of the tautomers of indazole, 3-halogeno-indazole and their transition states were obtained. The Onsager solvate theory model was employed for the aqueous solution calculations.The results of the calculation indicated that the N1-H form of the studied molecule is more stable than that of the N2-H form. The influences of the different 3-halogeno and solvent effects on the geometry, energy,charge and activation energy were discussed. The reaction mechanism of the tautomerization of indazole and 3-halogeno-indazole was also studied and a three-membered cyclic transition state of the tautomer reaction has been obtained.     

1-对甲苯基-5-取代苯基亚胺基-1,2,3-三唑甲酸/甲酰胺的合成及生物活性研究

以对甲基苯胺为原料,经过重氮化反应生成对甲基叠氮苯(1).在强碱性条件下,1分别与氰基乙酸乙酯、氰基乙酰胺反应,制得中间体1-对甲苯基-5-氨基-1,2,3-三唑甲酸乙酯(2)和1-对甲苯基-5-氨基-1,2,3-三唑甲酰胺(5);中间体2经水解生成1-对甲苯基-5-氨基-1,2,3-三唑甲酸(3),进而在弱酸性条件下与取代苯甲醛反应得到6个未见文献报道的目标化合物1-对甲苯基-5-取代苯基亚胺基-1,2,3-三唑甲酸(4a～4f),5与取代苯甲醛反应得到6个未见文献报道的目标化合物1-对甲苯基-5-取代苯基亚胺基-1,2,3-三唑甲酰胺(6a～6f),化合物的结构均经IR,1H NMR,13C NMR确证.初步生物测试表明,12个化合物均表现出良好的抑菌活性,其中化合物4d～4f和6d～6f对金黄色葡萄球菌、白色念球菌的最小抑菌浓度(MIC)值为2～8μg/mL,抗菌效果优于氟康唑和三氯生.     

3-氨基-2-吡啶酮互变异构的密度泛函理论计算

采用密度泛函理论,在B3LYP/6-3 l1G**基组水平上,计算并考察了3-氨基-2-吡啶酮分子酮式和烯醇式结构进行结构互变的质子迁移过程中的2种可能途径:(a)分子内质子迁移,(b)水助质子迁移.计算结果表明,途经b所需要的活化能较小,氢键在降低反应活化能方面起着重要作用.     

8-羟基喹啉单体及二聚体质子转移反应的理论研究

Density functional theory （DFT） of quantum chemistry method was employed to investigate proton transfer reactions of 8-hydroxyquinoline （8-HQ） monomers and dimers. By studying the potential energy curves of the isomerization, the most possible reaction pathway was found. The total energy of 8-hydroxyquinoline was lower than that of quinolin-8（1H）-one, whereas the order was reversed in dimers. The findings explained the contrary experimental phenomena. The minimum reaction barrier of intramolecular proton transfer was 47.3 kJ/mol while that in dimer was only 25.7 kJ/mol. Hence it is obvious that proton transfer reactions of 8-HQ monomer have a considerable rate but it is easier to proceed for 8-HQ dimer than monomers. It implied that the hydrogen bond played an important role in depressing the activation energy of reaction. The mechanism of the tautomerization was discussed on the basis of theoretical results.     

1,2,3-三唑化合物的合成研究进展

1,2,3-三唑化合物是重要的N-杂环化合物, 近年来被广泛应用于工业生产、药物研发、材料科学等多个领域. 因此1,2,3-三唑的合成受到越来越多的关注. 从合成不同取代类型的1,2,3-三唑化合物入手对近年来研究发现的合成方法的进展进行了综述.     

硝酰氯和顺/反亚硝酸氯及其互变异构反应的理论研究

用密度泛函理论（DFT）的B3LYP方法和6－311＋G（3df）基组，计算了气态下硝酰氯和顺／反应硝酸氯的几何构型、电子结构、红外光谱以及热力学性质，并讨论了它们的互变异构反应，分析了过渡态的结构。结果表明，B3LYP／6－311＋G（3df）计算得到的结果与实验值及CCSD（T）方法计算结果吻合，且更适应于研究反应机理，ClNO2转变为cis-ClONO的过渡态（TS1）偏离平面构型；cis-ClONO和trans-ClONO互变反应的过渡态（TS2）属于内旋转位垒；高水平计算表明不存在由ClNO2直接转变为trans-ClONO的过渡态，而是得到了一个十分接近异裂产物的二级马鞍点（2SP）。根据得到的热力学函数计算了气态时各温度下互变异构反应的平衡常数。     

喹唑啉酮互变异构的理论计算

采用密度泛函理论B3LYP/6-311+G(d,p)方法,计算并考察了喹唑啉酮进行结构互变的质子迁移过程的两种可能途径:(a)分子内质子迁移,(b)水助质子迁移.结果表明,途经b所需要的能垒小,氢键在降低反应能垒方面起重要作用.     

Azomethine Derivatives on the Basis of 5-Formyl-2,2'-bithienyl and 5-Formyl-2,2'-dithienyl Sulfide

Six azomethine derivatives of 2,2'-dithienyl sulfide and five of 2,2'-bithienyl have been synthesized for the first time.     

Three-component assembly of 5-halo-1,2,3-triazoles via aerobic oxidative halogenation

An effective synthetic protocol for 5-halo-1,2,3-triazoles was developed by novel TBDMSCl (tert-butyldimethylsilyl chloride)-activated aerobic oxidative halogenations in this Letter. TBDMSCl, for the first time, was found to activate aerobic oxidation of CuX to produce X₂ with Cu⁺ which then could effectively promote one-pot syntheses of 5-halo-1,2,3-triazole from alkyne, azide, and CuX (X = I, Br) under O₂ atmosphere at room temperature. The advantages in this method include inexpensive and green O₂ as oxidant, use of mild and non-oxidative additive, and wide scope of substrates.     

Theoretical Studies on Intermolecular Interactions of 4-Amino-5-nitro-1,2,3-triazole Dimers

1 INTRODUCTION Triazole, a five-membered heterocyclic compound with three nitrogen atoms, is an important interme- diate product of medicine and chemical industry as well as insecticide [1]. Due to its small volume and high nitrogenous density, triazole holds more and more attraction for the material researchers, espe- cially the researchers of high-energy insensitive explosive. It is reported that its nitro and amino deri- vatives are a sort of important high-energy mate- rials[2]. Previ…     

3-醛基-2-羟基-5-甲基苯甲酸二胺类Schiff碱配体的合成

合成了3-醛基-2-羟基-5-甲基苯甲酸,将其与乙二胺,1,2-丙二胺,1,3-丙二胺反应合成了3种Sch iff碱配体.用元素分析,IR,MS,1H NMR和13C NMR对它们进行了结构表征.     

5-氯尿嘧啶质子转移异构化的密度泛函理论研究

采用密度泛函B3LYP/6-311+G**方法,对5-氯尿嘧啶分子内质子转移及水助催化质子转移引起的互变异构反应机理进行了计算研究,获得了互变异构过程的反应焓、活化能、活化吉布斯自由能和质子转移反应的速率常数等参数。计算结果表明,5-氯尿嘧啶无论是孤立分子还是一水合物,其双酮式CU1是最稳定异构体,由双酮式向烯醇式异构化找到3条通道(P1,P2,P3),各通道速控步骤的活化能分别为177.85、177.05和197.58kJ/mol。当水分子参与反应以双质子转移机理异构化时,活化能显著降低,各通道速控步骤的活化能依次降为66.24、69.36和77.85kJ/mol,有利于双酮式向烯醇式或酮醇式转变。计算结果还表明,氢键作用在增大5-氯尿嘧啶一水复合物稳定性、降低质子转移异构化反应活化能等方面起着重要作用。     

New 1,2,3-Triazoles from (R)-Carvone: Synthesis,DFT Mechanistic Study and In Vitro Cytotoxic Evaluation

Aseries of novel 1,4-disubstituted 1,2,3-triazoles were synthesized from an (R)-carvone terminal alkyne derivative via a Cu (I)-catalyzed azide–alkyne cycloaddition reaction using CuSO₄,5H₂O as the copper (II) source and sodium ascorbate as a reducing agent which reduces Cu (II) into Cu (I). All the newly synthesized 1,2,3-triazoles 9a–h were fully identified on the basis of their HRMS and NMR spectral data and then evaluated for their cell growth inhibition potential by MTS assay against HT-1080 fibrosarcoma, A-549 lung carcinoma, and two breast adenocarcinoma (MCF-7 and MDA-MB-231) cell lines. Compound 9d showed notable cytotoxic effects against the HT-1080 and MCF-7 cells with IC₅₀ values of 25.77 and 27.89 µM, respectively, while compound 9c displayed significant activity against MCF-7 cells with an IC₅₀ value of 25.03 µM. Density functional calculations at the B3LYP/6-31G* level of theory were used to confirm the high reactivity of the terminal alkyne as a dipolarophile. Quantum calculations were also used to investigate the mechanism of both the uncatalyzed and copper (I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC). The catalyzed reaction gives complete regioselectivity via a stepwise mechanism streamlining experimental observations. The calculated free-energy barriers 4.33 kcal/mol and 29.35 kcal/mol for the 1,4- and 1,5-regioisomers, respectively, explain the marked regioselectivity of the CuAAC reaction.     

Excited state intramolecular proton transfer in 5-hydroxy flavone: A DFT study

Potential energy surfaces (PES) for the ground and excited state intramolecular proton transfer (ESIPT) processes in 5-hydroxy-flavone (5HF) were studied using DFT-B3LYP/6-31G(d) and TD-DFT/6-31G(d) level of theory, respectively. Our calculations suggest the non-viability of ground state intramolecular proton transfer (GSIPT) in 5HF. Excited states PES calculations support the existence of ESIPT process in 5HF. ESIPT in 5HF has been explained in terms of HOMO, LUMO electron density of the enol and keto tautomer of 5HF. PES scan by phenyl group rotation suggests that the twisted form, i.e., phenyl group rotated by 18.7° out of benzo-γ-pyrone ring plane is the most stable conformer of 5HF.     

DFT studies on key intermediates in thiamin catalysis

The diphosphate ester (ThDP) of thiamin (vitamin B₁) is an important cofactor of enzymes within the carbohydrate metabolism. From experiments of site‐specific variants and nuclear magnetic resonance (NMR) studies, it is known that the protonation of the N1′ atom is a significant step in the coenzyme activation by the enzymatic environment. Therefore, we have performed density functional theory (DFT) calculations on the B3LYP/6‐31G* level of N1′H and N1′CH₃ thiamin as model systems to study the protonation and methylation effect on the structure and the electronic properties of the 4′‐amino group. The relaxed rotational barriers related to the C4′‐4′N bond are correlated with findings of ¹H NMR studies and proton/deuterium exchange experiments. Moreover, the effect of N1′ protonation was studied in more detail on the hydroxyethyl‐thiamin carbanion (HETh^?), a key intermediate during catalysis of some ThDP‐dependent enzymes. The relaxed rotational barriers related to the C2? C2α bond and the reaction coordinates of the proton transfer 4′N? H→C2α of HETh^? and N1′H‐HETh^? show that they are significantly determined by the protonation at N1′ of HETh^?. The influence of the apoenzyme environment on the active coenzyme conformation is modeled in a very simple way. The characteristic torsion angles Φ_T and Φ_P are considered to be restricted in terms of their values in the corresponding enzyme as well as free optimization parameters. Frequency calculations were performed to characterize the minima and transition state structures, respectively. The applicability of the DFT method was checked by comparing calculations on the MP2‐HF‐SCF/6‐31G* level. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004     

3—芳基—5—巯基—1,2,4—均三唑的双—Mannich反应研究

研究了在氯化氢－乙醇溶液中，３－芳基－５－巯基－１，２，４－均三唑与甲醛和伯胺（芳胺或脂肪胺）的双Ｍａｎｎｉｃｈ反应，合成了１３的的稠杂环化合物３，５－二取代０四氢均三唑并「３，４－ｂ」「１，３，５」噻二嗪，经元素分析、Ｉ手ＭＳ确定了结构，初步测定了该类化合物的生物活性。