苯并三呋咱氧化物中主要杂质对其热安定性的影响

根据苯并三呋咱氧化物（BTF）中主要杂质的种类，分别选择了三叠氮三硝基苯（TNTAB）、三氯三硝基苯（TCTNB）和叠氮化钠（NaN3)作为杂质研究对象，采用机械混合的方法制备了一系列不同配比的BTF混合物，再通过差热（DTA）、差示扫描量热（DSC）、真空安定性试验（VST）、布氏压力法、热失重、5s爆发点等热分析方法进行测试，结果表明TCTNB和NaN3对BTF热安定性影响较小，而TNTAB是影响BTF热安定性的主要因素。     

4,6—二硝基苯并氧化呋咱的合成

采用新的合成方法，以苦基氯为原料，经过叠氮化和脱氮环化反应，合成了苯并氧化呋咱化合物。对其结构作了理论分析和实验鉴定，认为该化合物具有杂芳结构。     

苯并氧化呋咱类化合物研究概述

对苯并氧化呋咱类化合物的结构，制备和研究进展作了综述，在芳环上用苯并氧化呋咱化替硝基可以使含能材料密度增加，苯并氧化呋咱类化合物的生物活性和医药方面的运用前景已经引起人们的重视，参考文献２５篇。     

4，6－二硝基苯并氧化呋咱的合成

采用新的合成方法，以苦基氯为原料，经过叠氮化和脱氮环化反应，合成了苯并氧化呋咱化合物。对其结构作了理论分析和实验鉴定，认为该化合物具有杂芳结构。     

苯并氧化呋咱稳定性和异构化的DFT和ab initio研究

运用B3LYP/6-31G(d)密度泛函理论（DFT）方法对苯并氧化呋咱、邻二亚硝基苯及其间的异构化反应进行了计算研究。结果表明,苯并氧化呋咱的分子总能量比邻二亚硝基苯的低;由苯并氧化呋咱异构为邻二亚硝基苯的正向反应活化能（Ea+=51.0kJ/mol）,与文献实测值（58.6kJ/mol）较接近,而其逆向反应活化能（Ea-=4.6kJ/mol）很小,从而揭示了苯并氧化呋咱比邻二亚硝基苯更稳定·此外,进行了HF/3-21G、HF/6-31G(d)和MP2/6-31G(d)//6-31G(d)水平下相应的计算,发现B3LYP-DFT的结果较abinitio为优。谐振动频率的B3LYP/6-31G(d)计算还支持了邻二亚硝基苯为苯并氧化呋咱“自-自”互变重排反应的中间体。     

5(4H)-吡啶酮并氧化呋咱及其核苷衍生物的合成及结构表征

设计了一个新化合物——5(4H)-吡啶酮并氧化呋咱(4H,5H-[1,2,5]噁二唑[3,4-b]吡啶-5-酮-1-氧化物),对它的合成方法及四乙酰核糖核苷衍生物的合成进行了研究.合成产物及中间体经1HNMR、质谱和元素分析进行了结构鉴定.     

叠氮化物及其苯并衍生物的研究概况

本文对叠氮化物及其衍生物的研究进展作了阐述，对叠氮基团的结构进行了探讨，指出脂肪族叠氮化物的性能和芳香族叠氮化物脱氮环化生成苯并氧化呋咱这种叠氮衍生物的特征。     

多硝基化合物分子内电荷转移(CT)现象的XPS研究——Ⅱ.苯并氧化呋咱类(benzofuroxans)硝基衍生物电子结构的探讨

本文对10种苯并氧化呋咱及其衍生物的XPS谱做了系统的分析。发现E_b~*值与分子内CT作用间存在良好的相关关系,并获得了CNDO/2理论计算的有力支持。此外,XPS结合能的分析可为了解氧化呋咱电子结构提供重要信息。     

5-氯-2-硝基苯胺合成5-氯-苯并氧化呋咱反应的密度泛函研究

利用密度泛函理论(DFT)的B3LYP/6-31G(d,p)计算方法研究了次氯酸钠氧化环化5-氯-2-硝基苯胺合成5-氯-苯并氧化呋咱的反应, 采用连续介质模型(PCM)评估了溶剂效应. 提出两种可能的分步反应通道: (1)氧化、移氢、脱水和环化, (2)移氢、亚氨基氢扭转、氧化、脱水和环化|前者为优势通道. 非极性的CCl₄溶剂有较低的活化能垒, 比极性的乙醇溶剂更有利于5-氯-2-硝基苯胺的合成. 标题反应的机理类似于次氯酸钠氧化邻硝基苯胺合成苯并氧化呋咱, 但其速控步的活化能垒更低, 反应更易进行.     

3,4-二氨基呋咱基氧化呋咱的制备及晶体结构研究

首次通过3-氨基-4-氯肟基呋咱在热作用下脱HCl、[4 2]关环反应制备了新型呋咱(氧化呋咱)类含能化合物3,4-二氨基呋咱基氧化呋咱(DAFF),并培养出了DAFF单晶.用X射线单晶衍射、元素分析和红外光谱对其分子结构进行了表征.测试结果表明:DAFF晶体属三斜晶系,空间群P1,a=0.6400(4)nm,b=1.0609(8)nm,c=1.4634(7)nm,α=83.53(5)°,β=87.27(4)°,γ=77.74(5)°,V=0.9645(11)nm3,Z=4,Dc=1.737g?cm-3,F(000)=512,μ(MoKα)=0.149mm-1;R1=0.0568,wR2=0.1137.DAFF分子不共面,三环面扭曲,面间夹角为27.18(1.99)°和30.48(2.07)°,晶体中存在分子内和分子间氢键.     

Periodic DFT approach to benzotrifuroxan crystal

Density Functional Theory (DFT) calculations at the B3LYP/6‐21G* level were performed on crystalline benzotrifuroxan (BTF). The frontier bands are generally quite flat. The energy gap between the highest occupied crystal orbital (HOCO) and the lowest unoccupied crystal orbital (LUCO) is 3.89 eV, indicating that the crystal is an electrical insulator. All the atoms of BTF make up both the lower and the higher energy bands. The projection of density of state (DOS) indicates that there exists no region with much higher reactivity as other explosives, since the coplanar rings of BTF are conjugated. An anisotropic impact on the bulk makes the electron transfer from carbon atoms to nitrogen and oxygen atoms, which lowers the strength of the C–C bond. The crystal lattice energy is predicted to be –47.39 kJ/mol. The elastic constants C₁₁, C₂₂, and C₃₃ are predicted to be 191.48 GPa, 94.39 GPa, and 347.42 GPa, respectively. The large differences of C₁₁, C₂₂, and C₃₃ indicate the anisotropic properties of BTF upon impacting. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Thermal decomposition mechanisms of the energetic benzotrifuroxan:1,3,3-trinitroazetidine cocrystal using ab initio molecular dynamics simulations

Ab initio molecular dynamics simulations were performed to investigate the thermal decomposition mechanisms of the energetic benzotrifuroxan (BTF):1,3,3-trinitroazetidine (TNAZ) cocrystal at high temperature. It is found that there are four initial reaction mechanisms involved in the decomposition of the cocrystal. Subsequent decomposition channels can be divided into three types: BTF-chain isomerization, C─NO₂ bond homolysis, and ring opening. After that, one main path is that long chains decomposed into small radicals gradually after the ring opening. The other is that a new ring was formed after the ring opening and then it will break by degrees. Releasing of the H radicals and oxygen-containing groups plays an important role in the whole decomposition process. We also studied the release mechanisms of nitrogen gas and carbon dioxide in the later decomposition stage. Our study may provide new insights into the initiation mechanisms and subsequent decomposition of cocrystal explosives at high temperature.     

化学药品杂质控制的现状与展望

对药品中杂质的控制是保证药品用药安全的重要环节.伴随着对药品杂质特性的深入了解,依据杂质的生理活性逐一制定每一个杂质限度的杂质谱控制理念已经被国内外普遍接受.与杂质谱控制相关的关键技术问题可概括为:复杂体系样本的分离分析、微量组分的结构分析和微量组分的毒性评价三方面.本文从杂质控制理念和杂质分析技术两方面,综述了化学药品杂质控制的现状,并就今后的发展提出自己的观点.     

药物泰瑞沙的质谱分析及其未知杂质的结构解析

利用气相色谱-质谱法在电子电离源下对用于治疗肺癌的药物泰瑞沙(Tagrisso)进行分析,对主成分奥斯替尼(Osimertinib)在质谱中产生的主要的碎片离子进行归属,推测其可能的质谱裂解途径。参考主成分奥斯替尼的质谱裂解方式,由质谱裂解机理的角度出发对该药物中的4个未知的关键杂质的结构进行有效解析。此外,发现奥斯替尼及其个别杂质在质谱裂解过程中出现了显著的违背偶电子规则的碎片离子。通过对药物泰瑞沙的质谱分析期望能够提供一些分析、解析药物中未知杂质的思路和方法。     

Effect of dimensionality of a crystal lattice on the properties of a localized impurity

The changes of electron density due to the presence of a localized impurity in a crystal lattice are examined in dependence on the lattice dimensionality. The Koster–Slater impurity model developed for the case of a three‐dimensional simple cubic lattice has been taken as the basis of examinations. Ordinary bound states, virtual bound states, and delocalized electron states are considered in each lattice case. For the delocalized states extended in a one‐dimensional lattice the amplitude of the oscillatory changes of the electron density due to the impurity perturbation does not decrease with the distance from the impurity position, whereas for a two‐dimensional lattice this amplitude decreases roughly proportionally to the reciprocal value of the square root of the distance from the impurity. Let us note that a well‐known amplitude characterizing the decrease of the oscillatory change of the electron density in a three‐dimensional system is proportional to the reciprocal value of the third power of the distance from the impurity position. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 80: 61–78, 2000     

Effect of dimensionality of a crystal lattice on the properties of a localized impurity

The changes of electron density due to the presence of a localized impurity in a crystal lattice are examined in dependence on the lattice dimensionality. The Koster–Slater impurity model developed for the case of a three-dimensional simple cubic lattice has been taken as the basis of examinations. Ordinary bound states, virtual bound states, and delocalized electron states are considered in each lattice case. For the delocalized states extended in a one-dimensional lattice the amplitude of the oscillatory changes of the electron density due to the impurity perturbation does not decrease with the distance from the impurity position, whereas for a two-dimensional lattice this amplitude decreases roughly proportionally to the reciprocal value of the square root of the distance from the impurity. Let us note that a well-known amplitude characterizing the decrease of the oscillatory change of the electron density in a three-dimensional system is proportional to the reciprocal value of the third power of the distance from the impurity position. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 79: 57–74, 2000     

基于自制气体循环系统测定全氟异丁腈中杂质成分

建立了基于自制全密闭进样系统的气相色谱-质谱测定全氟异丁腈(C₄F₇N)商品气中杂质的方法。待测气体在自制的密封系统内稀释并混合均匀,使用在线自动六通阀进样,采用Agilent GS-GASPRO色谱柱(30 m×0.32 mm×5μm)分离,测定了国内某公司(DC公司)和国外某公司(AC公司)的全氟异丁腈绝缘气体的杂质成分。结果表明,全氟异丁腈商品气中含有微量的N₂、O₂、C₃HF₇和痕量的C₃F₆,其中AC公司的C₄F₇N商品气体中的杂质总含量为0.13%, C₄F₇N纯度为99.87%; DC公司的C₄F₇N商品气体中的杂质总含量为0.83%, C₄F₇N纯度为99.17%,两家公司的C₄F₇     

The importance of impurity analysis in pharmaceutical products: an integrated approach

To purify a material and remove the excess impurities one should first recognize that whether they are actually present and what their nature is. In the past, this was not always done. But presently drug analysis and pharmaceutical impurities are the subjects of constant review in the public interest. The International Conference on Harmonisation (ICH) guidelines achieved a great deal in harmonizing the definitions of the impurities in new drug substances. It is necessary to perform all the investigations on appropriate reference standards of drug and impurities to get meaningful specifications. In order to meet the challenges to ensure high degree of purity of drug substances and drug products, a scheme is proposed for profiling drug impurity. Finally, analytical methods based on analytical instrumentation must be employed to quantitate drug substance and its impurities. Important aspects and suggestions related to drug analysis and pharmaceutical impurities are discussed.