抗高血压药马西替坦的合成工艺优化

以4-溴苯乙酸甲酯为起始原料,经碳负离子亲核取代、关环、氯代、氮负离子亲核取代、氧负离子亲核取代等6步反应制得抗高血压药马西替坦,并对合成工艺进行了优化。优化后的工艺使中间体的纯度得到了提高,操作更加简便,更有利于工业化生产。中间体和产物的结构均经~1H-NMR和ESI-MS确证。     

瑞卢戈利中间体的合成

以4-硝基苯丙酮(2)和氰基乙酸乙酯(3)为原料,经与硫粉环合、缩合、亲核取代、溴代反应、二甲胺取代和水解后得到瑞卢戈利的关键中间体2-[(2,6-二氟苄基)乙氧基羰基氨基]-4-二甲基氨基甲基-5-(4-硝基苯基)噻吩-3-甲酸(1),并对合成路线中反应条件及提纯方法进行优化,总收率51.5%,纯度98.7%以上,中间体的结构经¹H NMR和ESI-MS确证。优化后的工艺操作更加简便,更有利于工业化生产。     

芳基离子及芳基自由基与 环己二烯离子及环己二烯自由基的区别

通过比较芳香亲电取代与芳基重氮盐的水解反应和芳香亲核取代与芳基金属有机试剂参与的反应中芳香部分结构的差别来说明芳基正离子与环己二烯正离子以及芳基负离子与环己二烯负离子的区别。讨论了芳香自由基偶联中的芳基自由基及其对芳香环的自由基加成中的环己二烯自由基的差别。还讨论了芳基离子和自由基结构与芳香性的关系。反应中涉及芳烃芳香环碳原子的sp2杂化轨道形成的σ键断裂时,苯环的6电子大π键不被破坏,根据电子转移的情况,可以形成芳基正离子、芳基负离子或芳基自由基。而亲电试剂、亲核试剂或自由基对芳烃的苯环π键发生的加成反应,都会破坏苯环的6电子大π键,使其失去芳香性,相应地形成环己二烯正离子、环己二烯负离子和环己二烯自由基中间体。     

α-羟基辛酸及其交酯的合成工艺改进

以正庚醛为原料,经过亲核取代、置换反应、酸水解及碱化脱氨等4步反应合成了制备3,6二已基-1,4-二氧杂-2,5-二酮(辛交酯)的中间体--α-羟基辛酸(1);1经对甲苯磺酸催化脱水得辛交酯.改进并优化了合成工艺,1收率由58.0%提高至77.6%,辛交酯收率由65.0%提高至71.0%.     

含邻手性碳原子双键亲电加成反应的立体选择性模型

本文主要介绍了预测邻位具有手性中心π体系亲电加成反应的立体选择性模型,尤其是α,β-不饱和羰基化合物亲核共轭加成形成的烯醇负离子及其类似物和硝基烯烃亲核加成形成的氮酸根类中间体的烷基化和动力学控制质子化反应的立体选择性模型。立体位阻效应控制的Zimmerman前过渡态模型主要适用于底物构象受限的环状或联烯型烯醇负离子的动力学质子化。对于构象转化相对灵活的直链底物,Houk基于量子化学计算研究提出了亲电试剂的进攻角度或接触角在经过环状过渡态时是锐角还是钝角决定了亲电加成反应的立体选择性控制(Houk模型)。而Fleming模型首次将烯丙基A-1,3张力引入各类烯醇负离子烷基化和质子化的过渡态。Mohrig模型在考虑A-1,3张力的基础上,将吸电子取代基与即将形成的σ键反式共平面,主要阐述了立体电子效应对酯的烯醇负离子动力学控制质子化立体选择性的影响,后来又提出了金属离子参与的立体电子效应控制的六元环状半椅式模型。本文希望对理解亲电加成反应的立体化学控制提供一些有用的信息。     

新型含吲唑环嘧啶衍生物的合成

以6-硝基-1H-吲唑为原料,经氮原子甲基化、催化氢化还原、亲核取代以及烷基化反应制得关键中间体N(2′-氯嘧啶-4′-基)-N,1-二甲基-1H-吲唑-6-胺(5);5与芳香胺进行亲核取代反应合成了一系列新型取代氨基嘧啶衍生物——N-(2′-取代氨基嘧啶-4′-基)-N,1-二甲基-1H-吲唑-6-胺,其结构经1H NMR和MS表征.     

脱镁叶绿酸-α甲酯的制备及其化学修饰

采用新的方法从蚕沙中提取脱镁叶绿酸-α甲酯（1）并制备了焦脱镁叶绿酸-α-甲酯（2）。对1和2的13b位上氢的活性进行了研究,结果表明1的13b位上氢在乙醇钠作用下生成负碳离子,负电荷转移到13a位上形成氧负离子,氧原子作为亲核原子和卤代烃进行亲核取代反应;2的13b位上生成负碳离子后直接和卤代烃进行亲核取代反应。通过对2的3-乙烯基的修饰,获得了3-N-取代类衍生物。新化合物的结构均经^1H NMR,IR,MS及元素分析确证。     

氢键活化的苯环上C-F键的亲核取代反应研究

以2,4,5-三氟苯乙酮在氢化钠作用下与碳酸二乙酯反应制得3,4-二氟-6-乙氧基苯甲酰乙酸乙酯(2);2经对甲基苯磺酸催化水解脱羧,合成3,4-二氟-6-乙氧基苯乙酮(3)路线为模型,研究了苯环上C-F键的亲核取代反应.实验结果证明,在形成分子内氢键的活化作用下,苯环上的C-F键能够被烷氧负离子亲核取代.2和3的结构经1H NMR, 19F NMR和MS表征.     

顺式-和反式-2,5-二取代四氢呋喃的立体选择性合成

内酯与有机锂试剂发生亲核加成反应,再在酸催化下用NaBH3CN还原,反应的立体选择性可能是由氢负离子在中间体氧鎓离子位阻最小的一侧进攻所引起.所得的三环化合物经热分解和加氢反应,制备顺式和反式-2,5-二取代四氢呋喃.     

硝基烯类化合物在有机合成中的应用

本文总结了硝基烯类化合物在有机合成中的应用。硝基烯是用途广泛的合成子,易受到亲核试剂如碳负离子、亚磷酸酯等的进攻形成加成产物。它和碳负离子的加成产物可以视为羰基的极性转换(umpolung)试剂,是合成取代羰基化合物的有效方法,它也是良好的亲双烯体,易于发生Diels-Alder反应。     

三丁胺胺化强碱性阴离子交换树脂催化合成羧酸苄酯

用组合化学方法筛选出的对无外加碱条件下的亲核取代催化活性最高的聚合物季铵盐-三丁胺胺化强碱性阴离子交换树脂为相转移催化剂,催化合成了乙酸苄酯、丙酸苄酯、丁酸苄酯、戊酸苄酯等羧酸苄酯。讨论了各种反应条件对合成丙酸苄酯的产率的影响,并对传统合成方法进行了改进。在优化反应条件下,反应产率接近100%。     

One-pot process in phosphonium-iodonium ylides: nucleophilic substitution and the Wittig reaction

The nucleophilic substitution in mixed phosphonium-iodonium ylides was investigated. The iodonium group is replaced by such S-containing nucleophiles as the thiocyanate anion or thiourea, as well as by halide ions. The structure of the reaction product with the thiocyanate ion was established by X-ray diffraction. A one-pot process involving the nucleophilic substitution and the Wittig reaction was developed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 391–395, February, 2008.     

Silyldefluorination of Fluoroarenes by Concerted Nucleophilic Aromatic Substitution

The reaction of readily generated silyl lithium reagents with various aryl fluorides to provide the corresponding aryl silanes is reported. DFT calculations reveal that the nucleophilic aromatic substitution of the fluoride anion by the silyl lithium reagent proceeds through concerted ipso substitution. In contrast to the classical nucleophilic aromatic substitution, this concerted ionic silyldefluorination also occurs on more electron‐rich aryl fluorides.     

Rearrangement, nucleophilic substitution, and halogen switch reactions of alkyl halides over NaY Zeolite: formation of the bicyclobutonium cation inside the zeolite cavity

Rearrangement and nucleophilic substitution of cyclopropylcarbinyl bromide over NaY and NaY impregnated with NaCl was observed at room temperature. The first-order kinetics are consistent with ionization to the bicyclobutonium cation, followed by internal return of the bromide anion or nucleophilic attack by impregnated NaCl to form cyclopropylcarbinyl, cyclobutyl, and allylcarbinyl chlorides. The product distribution analysis revealed that neither a purely kinetic distribution, similar to what is found in solution, nor the thermodynamic ratio, which favors the allylcarbinyl halide, was observed. Calculations showed that bicyclobutonium and cyclopropylcarbinyl carbocations are minimal over the zeolite structure, and stabilized by hydrogen bonding with the framework structure. A new process of nucleophilic substitution is reported, namely halogen switch, involving alkyl chlorides and bromides of different structures. The reaction occurs inside the zeolite pores, due to the confinement effects and is an additional proof of carbocation formation on zeolites. The results support the idea that zeolites act as solid solvents, permitting ionization and solvation of ionic species.     

Nucleophilic substitution reactions of 1,4-dichlorobenzene chromium tricarbonyl with mono- and diphenoxides

The nucleophilic substitution reactions of 1,4-dichlorobenzene chromium tricarbonyl ( 1 ) with the phenoxide anion were investigated. The substitution of the first chlorine was very fast and gave the mono-substituted product in high yield. The substitution of the second chlorine group was significantly retarded by the presence of the phenoxy group incorporated during the first reaction and also due to the competing decomplexation reaction. The application of 1,4-dichlorobenzene chromium tricarbonyl ( 1 ) to the synthesis of new monomers was demonstrated by the preparation of 2,2′-bis[4-(4-chlorophenoxy)phenyl]propane ( 9 ). 2,2′-Bis[4-(4-chlorophenoxyl)phenyl]propane ( 9 ) was synthesized by a nucleophilic substitution reaction of 4,4′-isopropylidenediphenolate with 1,4-dichlorobenzene chromium tricarbonyl ( 1 ) followed by decomplexation with I₂. 2,2′-Bis[4-(4-chlorophenoxy)-phenyl]propane ( 9 ) was also synthesized via a three-step reaction starting from the nucleophilic substitution reaction of 4,4′-isopropylidenediphenol ( 7a ) with 1-chloro-4-nitrobenzene ( 10 ). 2,2′-Bis[4-(4-chlorophenoxy)phenyl]propane ( 9 ) was polymerized by a Ni(0)-catalyzed reaction to yield amorphous aromatic polyethers with number-average molecular weights of up to 11,200 g/mol. © 1993 John Wiley & Sons, Inc.     

Nucleophilic aromatic substitution of methacrylamide anion and its application to the synthesis of the anticancer drug bicalutamide

The anticancer drug (R,S)-biscaltamide was prepared in three steps in >90% overall yield. A key step in the new synthesis involved a new nucleophilic aromatic substitution reaction of methacrylamide anion.     

THE RADICAL NUCLEOPHILIC SUBSTITUTION REACTION OF HETEROCYCLIC KETENE AMINALS WITH 2,4-DINITROHALOBENZENES

The anion of heterocyclic ketene aminals reacted with 2,4-dini-tro-halobenzenes to give an arylated product through the radical nucleo-philic substitution confirmed by ESR spectroscopy,ESR-spin trapping techni-que,and depression of the reaction rate by the addition of inhibitor.     

Nucleophilic substitution of hydrogen in naphthalene by chloride(Cl~-)in ionic liquids

Nucleophilic aromatic substitution of hydrogen in non-activated aromatic ring,a very rare phenomenon in organic chemistry,is found in ionic liquids containing Cl^- as anion under mild reaction conditions.The reaction may be carried out by the addition of the halogen-bonding adduct（Br₂Cl^-） as nucleophile to aromatic ring carbon atom,leading to the formation of the nucleophilic substitution product.     

The loss of carbon dioxide from activated perbenzoate anions in the gas phase: unimolecular rearrangement via epoxidation of the benzene ring

The unimolecular reactivities of a range of perbenzoate anions (X-C6H5CO3-), including the perbenzoate anion itself (X = H), nitroperbenzoates (X = para-, meta-, ortho-NO2), and methoxyperbenzoates (X = para-, meta-OCH3) were investigated in the gas phase by electrospray ionization tandem mass spectrometry. The collision-induced dissociation mass spectra of these compounds reveal product ions consistent with a major loss of carbon dioxide requiring unimolecular rearrangement of the perbenzoate anion prior to fragmentation. Isotopic labeling of the perbenzoate anion supports rearrangement via an initial nucleophilic aromatic substitution at the ortho carbon of the benzene ring, while data from substituted perbenzoates indicate that nucleophilic attack at the ipso carbon can be induced in the presence of electron-withdrawing moieties at the ortho and para positions. Electronic structure calculations carried out at the B3LYP/6-311++G(d,p) level of theory reveal two competing reaction pathways for decarboxylation of perbenzoate anions via initial nucleophilic substitution at the ortho and ipso positions, respectively. Somewhat surprisingly, however, the computational data indicate that the reaction proceeds in both instances via epoxidation of the benzene ring with decarboxylation resulting--at least initially--in the formation of oxepin or benzene oxide anions rather than the energetically favored phenoxide anion. As such, this novel rearrangement of perbenzoate anions provides an intriguing new pathway for epoxidation of the usually inert benzene ring.