氰基化合物非均相加氢制备有机胺的研究进展

介绍了不同结构的氰基化合物加氢还原制备有机胺的研究工作,重点对用非均相催化剂的氰基化合物加氢研究现状进行了综述,指出高性能催化剂的开发仍是今后研究的主要方向。     

2-氰基-3-N-烷氨基-3-(N-2-氟苯乙氨基)丙烯酸乙酯类化合物的合成及生物活性研究

把由氰基乙酸乙酯、二硫化碳、硫酸二甲酯在乙醇钠作用下反应得到的2-氰基.3,3-二甲硫基丙烯酸乙酯中间体用邻氟苯乙胺胺化,再和甲胺等烷胺进行胺化反应,合成了含氟2-氰基丙烯酸乙酯类化合物.结构经元素分析、IR、1H NMR、13C NMR等证实,抗烟草花叶病毒(TMV)生物活性的初步测定表明,所合成的化合物有一定抗TMV活性.     

Cu-Ni-Zn三元脂肪醇胺化催化剂的研究

 长链烷基二甲基叔胺是一类重要的有机中间体,目前其主要的制备工艺是由脂肪醇和二甲胺在脱氢－加氢类催化剂的作用下进行胺化反应．改进脂肪醇胺化催化剂的主要目标是提高其选择性．对以Cu和Ni为活性组分,以碳酸钙为载体的催化剂体系中加入Zn助催化剂组分对催化剂选择性的影响进行了研究．结果发现,在相同Cu／Ni比的条件下,Zn在Cu－Ni催化剂体系中的一个主要作用是能够阻碍氧化态镍的还原,而催化剂的选择性与催化剂中镍的还原程度密切相关．     

负载型Ni催化剂高效催化2-羟基四氢吡喃还原胺化制备5-氨基-1-戊醇（英文）

伯胺等含氮化合物是最重要的化工中间体之一,被广泛应用于聚合物、医药、农药、染料和表面活性剂等产品的生产.当前,商业化伯胺主要通过卤代烃或环氧化合物直接胺化以及腈类或酰胺类化合物加氢制备,这些过程受具有特定官能团的有机原料短缺以及产生较多废物等问题的限制,导致其生产成本较高.因此,高效可持续生产伯胺化合物路径的开发得到了广泛关注.醛和酮类化合物直接与氨还原胺化反应所需温度一般较低(≤120℃),为伯胺的高选择性合成提供了一个重要途径.基于此,本文利用2-羟基四氢吡喃能够原位转化为其互变异构体5-羟基戊醛,而5-羟基戊醛中醛基具有较高还原胺化活性的特征,发展了一种以生物糠醛衍生二氢吡喃为原料,通过先水合得到2-羟基四氢吡喃再在温和条件下还原胺化合成5-氨基-1-戊醇的新方法.5-氨基-1-戊醇是一种分子中同时含有羟基和氨基的重要双官能团化合物,广泛用于医药和农药合成,也常被用作有机合成砌块,目前其主要用途是合成具有很高药用价值的生物碱Manzamine A.5-氨基-1-戊醇的一条传统合成路线是以石化基1,5-戊二醇经浓盐酸进行单氯取代制备5-氯戊醇中间体,该中间体经分离后再与氨气反应制得5-氨基-1-戊醇的方法.该方法原料成本高,产生大量废弃物,且只取得中等目标产物收率(66.6%).本文重点研究了不同氧化物载体包括SiO2,TiO2,γ-Al2O3,ZrO2和MgO负载Ni催化剂的2-羟基四氢吡喃还原胺化性能,并对比考察了CuCr2O4,雷尼Ni,Ru/C,Pd/C,Pt/C和Rh/C等商业加氢催化剂的性能.研究发现,ZrO2负载Ni催化剂的活性高于其他氧化物载体负载Ni催化剂的活性,也明显优于所对比的系列商业加氢催化剂.系列物理化学表征结果显示,Ni/ZrO2催化剂同时表现出较高的还原性和表面酸密度,这可能是该催化剂表现出最高5-氨基-1-戊醇收率的原因.以Ni/ZrO2为催化剂,于80℃,2 MPa H2条件下在间歇式反应器中催化2-羟基四氢吡喃水溶液还原胺化可取得90.8%的5-氨基-1-戊醇收率.通过固定床反应器研究了Ni/ZrO2催化剂稳定性,发现5-氨基-1-戊醇初始收率可达83%,反应90 h活性缓慢下降至初活性的81%.Ni流失和表面氧化可能是催化剂的失活的主要原因.通过对反应温度、H2压力、2-羟基四氢吡喃/NH3摩尔比等因素对反应活性调变规律的探究,推测2-羟基四氢吡喃催化还原胺化制备5-氨基-1-戊醇反应机理如下:首先,受化学平衡作用,2-羟基四氢吡喃逐渐转化为其互变异构体5-羟基戊醛;然后,5-羟基戊醛中醛基迅速与NH3反应生成亚胺中间体;最后,亚胺中间体在金属催化剂上加氢得到5-氨基-1-戊醇.     

3-氰基-5-甲氧基苯磺酰氯的合成

3-氰基-5-甲氧基苯磺酰氯是合成多种具有药物活性分子的重要中间体。本文以3,5-二硝基苯甲酸为起始原料,经过取代,酰胺化,脱水,硝基还原,重氮化以及磺化首次合成了目标化合物,其结构经MS和1H NMR确证。该方法原料廉价易得,操作简便易控且收率较高,反应总收率为65.9%。     

羰基α-位胺化反应研究进展

α-氨基羰基衍生物是一类重要分子骨架,存在于许多药物分子和天然产物分子中;同时,也是一类重要的有机合成中间体,用于合成许多重要的有机化合物分子.发展简单、高效的方法合成结构多样性的α-氨基羰基衍生物具有重要的研究意义.总结了近几十年来羰基α-位碳氢键的直接胺化反应,根据反应所经历的不同活化模式,对这类反应进行了分类总结,主要分为亲电胺化、氧化胺化、卤化物介导的胺化和电化学胺化四类反应.     

C—H氰烷基化:导向基控制的萘酰亚胺C—H氰烷基化

氰基广泛存在药物活性分子中,且氰基可以很容易转化成酰胺、酯基、醛基以及伯胺等官能团,因此有机分子的氰烷基/甲基化反应得到有机和药学研究者的广泛关注。尽管已有合成策略可以选择性引入氰基,近年来最有效的方法是通过C—H键激活直接与乙腈或取代乙腈发生氰甲基/氰烷基化反应,因其具有高效的原子经济性以及可规避预官能团化等优点。因此,本文详细评述了自由基促进的氰甲基化、光化学催化直接氰甲基化、芳环或杂环脱氢偶联氰甲基化、导向基促进的氰甲基化、本课题组发展的荧光团(Fluorophore C—H)直接氰甲基化反应的研究进展。     

基于热、光以及电化学过程的无过渡金属碳-氢键硫氰化和硒氰化反应（英文）

硫氰基和硒氰基均在有机合成中具有广泛应用的重要官能团.这类结构也经常出现在具有生物药物活性、光学活性以及催化功能的分子中.因此,发展可用于合成具有结构多样性的有机硫氰化和硒氰化物及相关串联转化合成多样性杂环分子的方法持续吸引着研究者的兴趣,总结了无过渡金属条件下的碳-氢键的硫氰化和硒氰化反应合成有机硫氰化物和硒氰化物以及相关串联环化反应的研究进展.     

不对称Petasis反应在手性胺类化合物合成中的应用

手性胺类化合物广泛存在于天然产物、药物分子和多功能材料中, 而且作为重要中间体、催化剂和手性辅剂在有机合成中也有广泛的应用, 因此, 发展高效的方法合成各种手性胺化合物及相应的骨架结构具有重要的科学意义和应用价值. 有机硼试剂、胺和羰基化合物参与的不对称Petasis三组分反应是构建手性胺及其衍生物最简洁、高效的方法之一. 近年来, 利用该策略来构建手性胺类化合物引起了广泛的关注. 文章综述了不对称Petasis反应合成手性胺类化合物的近期研究进展, 主要包括手性胺源、手性羰基化合物和手性硼试剂参与的底物诱导的不对称Petasis反应, 以及手性催化剂促进的不对称Petasis反应, 并对该领域的挑战和未来发展方向进行简要讨论.     

富马酸福莫特罗的合成工艺研究

富马酸福莫特罗作为特效哮喘治疗药物被临床广泛应用,本文对其合成工艺进行了研究并对重要中间体的合成工艺进行了优化。以4-羟基-3-硝基-苯乙酮为原料,经苄基化、溴代、还原、环氧化四步反应得到重要中间体4-苄氧基-3-硝基苯基环氧乙烷(3)。在制备中间体3时,采用一锅法,简化了反应步骤,同时在反应中加入了缚酸剂碳酸钾,加快了反应速率并提高了收率。此外,以对甲氧基苯基丙酮为原料,经过还原胺化反应一步生成另一个重要中间体1-(4-甲氧基苯基-2-甲基乙基)苄胺(4)。中间体3和4经偶合生成化合物5,在制备5时,采用微波合成,大大缩短了反应时间。中间体5再经硝基还原、甲酰化、去保护、成盐得到富马酸福莫特罗。该工艺操作简单,适合工业化生产,总收率达7. 46%。     

In situ hydrothermal synthesis of tetrazole coordination polymers with interesting physical properties

Tetrazole compounds have been studied for more than one hundred years and applied in various areas. Several years ago Sharpless and his co-workers reported an environmentally friendly process for the preparation of 5-substituted 1H-tetrazoles in water with zinc salt as catalysts. To reveal the exact role of the zinc salt in this reaction, a series of hydrothermal reactions aimed at trapping and characterizing the solid intermediates were investigated. This study allowed us to obtain a myriad interesting metal-organic coordination polymers that not only partially showed the role of the metal species in the synthesis of tetrazole compounds but also provided a class of complexes displaying interesting chemical and physical properties such as second harmonic generation (SHG), fluorescence, ferroelectric and dielectric behaviors. In this tutorial review, we will mainly focus on tetrazole coordination compounds synthesized by in situ hydrothermal methods. First, we will discuss the synthesis and crystal structures of these compounds. Their various properties will be mentioned and we will show the applications of tetrazole coordination compounds in organic synthesis. Finally, we will outline some expectations in this area of chemistry. The direct coordination chemistry of tetrazoles to metal ions and in situ synthesis of tetrazole through cycloaddition between organotin azide and organic cyano group will be not discussed in this review.     

Direct organocatalytic hydroalkoxylation of α,β-unsaturated ketones

The direct addition of a variety of alcohols to in situ activated olefins was observed in the presence of mild bifunctional amine/acid catalysts. Unlike existing methods, the reactions proceed at room temperature and in the absence of transition metals. The use of simple commercially available catalysts, amines and acids makes this an attractive method for the preparation of β-alkoxy ketones, which are prevalent targets and intermediates in organic synthesis.     

有机化学反应中间体的质谱分析

有机化学反应中活性中间体的性质各异,对反应中间体的表征和研究对于阐明和确证反应机理、优化反应条件、筛选催化剂和发现新类型反应至关重要.近年来,质谱技术和在线微量采样技术的发展,极大程度地拓展了质谱学在该领域的应用.本文总结了近年来本领域发展的新策略、技术和方法,以及有机质谱技术在反应中间体研究中的应用.     

Reversing the role of the metal[bond]oxygen pi-bond. Chemoselective catalytic reductions with a rhenium(V)-dioxo complex

The metal-oxygen bond plays a critical role in some of the most important biological and synthetic reactions. However, the majority of these processes result in the oxidation of the target organic substrate; applications of this class of metal complexes to other organic transformations are extremely rare. In this paper, we report a new type of catalytic process in which complexes with metal-oxygen multiple bonds are used as reductants rather than oxidants. The overall reaction provides a highly chemoselective reduction/protection of carbonyl groups. In addition to providing a new way of catalyzing organic reactions, these catalysts can be used in the presence of a wide range of other functional groups such as amino, cyano, nitro, aryl halo, ester, and alkene; unlike many of their late metal relatives, they are inexpensive as well as air and moisture tolerant.     

Expanding the catalytic activity of nucleophilic N-heterocyclic carbenes for transesterification reactions

[reaction: see text] Currently, there is a renewed interest in reactions that are catalyzed by organic compounds. Typical organic catalysts for acylation or transesterification reactions are based on either nucleophilic tertiary amines or phosphines. This communication discusses the use of nucleophilic N-heterocyclic carbenes as efficient transesterification catalysts. These relatively unexplored and highly versatile organic catalysts were found to be mild, selective, and more active than traditional organic nucleophiles.     

Agostic bonds in cyclometalation

Cyclometalation reactions proceed very easily with one step reaction between metal compounds and substrates having a heteroatom such as O, S, N, P and As. However, under mild reaction conditions, many agostic compounds which are intermediates in these cyclometalation reactions, can be isolated. The metal compounds used for the formation of these agostic intermediates are both transition metal and main group metal compounds. The substrates are nitrogen-containing compounds, phosphorus-containing compounds, oxygen-containing compounds and sulfur-containing compounds. These agostic intermediates are mainly δ-C-H agostic compounds, some are γ-C-H agostic compounds and very few are ?-C-H-agostic compounds. The agostic intermediates are prepared, usually, under mild reaction conditions in the cyclometalation reaction. These agostic compounds are also prepared from cyclometalation reaction products, e.g., by the protonation, irradiation, and elimination of ligand molecules by vacuum, inert gas current, dehydration with a molecular sieves 4A, etc. Some agostic compounds are utilized for preparation of stable catalysts, e.g., hydrogenation catalysts.     

Catalytic Oxidation of Alcohols and Amines to Value‐Added Chemicals using Water as the Solvent

Designing reactions in aqueous media has been one of the major challenges in modern organic synthesis, especially to avoid the use of large amounts of organic solvents whose disposal is a matter of grave concern from an environmental perspective. The oxidation of alcohols and amines is an essential and important step in the synthesis of many valuable products including polymers and pharmaceuticals. In recent times, there has been a surge in the use of water as a solvent in many organic reactions. This review focuses specifically on the oxidation reactions of alcohols and amines carried out in water media using transition metal catalysts, metal‐free catalysts and photocatalysts.     

Visible‐Light Photocatalysis: Does It Make a Difference in Organic Synthesis?

Visible‐light photocatalysis has evolved over the last decade into a widely used method in organic synthesis. Photocatalytic variants have been reported for many important transformations, such as cross‐coupling reactions, α‐amino functionalizations, cycloadditions, ATRA reactions, or fluorinations. To help chemists select photocatalytic methods for their synthesis, we compare in this Review classical and photocatalytic procedures for selected classes of reactions and highlight their advantages and limitations. In many cases, the photocatalytic reactions proceed under milder reaction conditions, typically at room temperature, and stoichiometric reagents are replaced by simple oxidants or reductants, such as air, oxygen, or amines. Does visible‐light photocatalysis make a difference in organic synthesis? The prospect of shuttling electrons back and forth to substrates and intermediates or to selectively transfer energy through a visible‐light‐absorbing photocatalyst holds the promise to improve current procedures in radical chemistry and to open up new avenues by accessing reactive species hitherto unknown, especially by merging photocatalysis with organo‐ or metal catalysis.     

新轴手性N,N-Dioxide Biscarbolin衍生物催化酮亚胺的不对称硅氢化反应

以L-色氨酸为原料合成了5个伯酰胺结构的轴手性双咔啉N—O催化剂N2,N2'-二氧-9,9'-二甲基-3,3'-取代甲酰胺-β-双咔啉(4A~4E),并用于不对称催化酮亚胺的还原反应.结果表明,催化剂的催化转化率较高(80%~98%),立体选择性(e.e.值)较好,其中催化剂N2,N2'-二氧-9,9'-二甲基-3,3'-环己基甲酰胺-β-双咔啉(4B)的催化转化率达到了98%,e.e.值达68%.     

Metal-based Heterogeneous Catalysts for One-Pot Synthesis of Secondary Anilines from Nitroarenes and Aldehydes

Recently, N-substituted anilines have been the object of increasing research interest in the field of organic chemistry due to their role as key intermediates for the synthesis of important compounds such as polymers, dyes, drugs, agrochemicals and pharmaceutical products. Among the various methods reported in literature for the formation of C–N bonds to access secondary anilines, the one-pot reductive amination of aldehydes with nitroarenes is the most interesting procedure, because it allows to obtain diverse N-substituted aryl amines by simple reduction of nitro compounds followed by condensation with aldehydes and subsequent reduction of the imine intermediates. These kinds of tandem reactions are generally catalyzed by transition metal-based catalysts, mainly potentially reusable metal nanoparticles. The rapid growth in the last years in the field of metal-based heterogeneous catalysts for the one-pot reductive amination of aldehydes with nitroarenes demands for a review on the state of the art with a special emphasis on the different kinds of metals used as catalysts and their recyclability features.