Synthesis and Hierarchical Structures of Amphiphilic

南京邮电大学硕士研究生学位论文摘要摘要近年来，水溶性共轭高分子显示出的独特光电性质在化学生物传感器中获得了广泛的应用，由于水溶性共轭聚合物可溶于水等环境友好溶剂，通过聚合物与带相反电荷猝灭剂之间的电子或能量转移对周围环境中微量物质进行检测，而电子或能量极易在整个聚合物链上离域，荧光猝灭信号被放大，因此可以简便实现对多种有机、无机甚至生物大分子的高灵敏度检测。

从水溶性共轭高分子的结构设计来看，多支化构型的发光共轭高分子能够更好的改善线型高分子由于聚集引起的荧光自身猝灭，从而更好的提高水溶性共轭高分子传感材料的抗干扰能力和检测灵敏度。

另一方面，水溶性共轭聚合物作为高灵敏度传感材料在酶的检测方面具有信号倍增和实时检测的优势，可大大提高酶检测方法的灵敏度、方便性和广谱性。

本论文从制备多支化水溶性共轭高分子入手，设计合成新型阳离子型水溶性共轭聚芳撑乙炔，同时利用某些已制得的水溶性共轭高分子进行新的生物传感应用探索。

主要研究工作包括以下几个方面：1．将超支化反应的方法引入到水溶性共轭高分子的设计合成中，利用单体A2 + A2’ + B3的方法，先通过Sonogashira聚合得到中性超支化共轭聚合物，然后进行季胺化得到水溶性超支化共轭聚合物。

2．利用已制得的阳离子型水溶性共轭聚合物PFEP与酶底物探针的相互作用检测磷酸酯酶。

由于聚合物可以通过静电吸引与荧光素修饰的带负电荷的三磷酸腺苷结合并发生荧光共振能量转移。

当加入磷酸酯酶时，它可以催化底物三磷酸腺苷上的磷酸酯基团逐渐水解，得到不带电荷的腺苷，从而使阳离子型共轭聚合物得以释放，能量转移效率下降。

结果表明，能量转移效率下降的程度与酶的浓度相关，该方法灵敏度高，检测限可达到1 × 10-6 unit/µL。

关键词：水溶性共轭聚合物，超支化，合成，荧光检测，传感，酶ABSTRACTIn recent years, water-soluble conjugated polymers (WSCP) have been used as chemical and biological sensors due to their unique optical and electrical properties. Because of WSCP is soluble in water and other environment-friendly solvent, micro substances can be detected through between the polymer and the oppositely charged-quencher. Hence electronic or energy transfer tends to delocalize easily throughout the polymer chain and fluorescence quenching signal is amplified, thus high-sensitivity detection of a variety of organic or inorganic and even biological macromolecules can be easily achieved. From the structural design of point, the multi-branched WSCP can improve the self-quenching of fluorescence causing by configuration compared to the linear WSCP. Consequently, the anti-interference ability and detection sensitivity can also be increased when WSCP is applied as sensory materials. On the other hand, as sensing materials with high sensitivity, WSCP has the advantages of real-time and signal-amplified in the detection of the enzyme using. As a result, the enzyme assay high sensitivity, convenience and wide-spectrum can all be achieved by WSCP. In the thesis, we prepared multi-branched water-soluble conjugated polymers first, besides this, we have designed a novel sensing method using of cationic water-soluble conjugated aromatic acetylene which has been obtained. This dissertation is focused on modifying the aggregation of WSCPs by means of structure design and changing environmental conditions, and studying the structure-property relationship. The contents are as follows:1. Hyperbranched reaction method is introduced to the design of water-soluble conjugated polymer synthesis. The synthesis of water-soluble conjugated hyperbranched polymer was adopted A2 + A2' + B3 method. At first, AB n monomer with conjugated aromatic structures was synthesized and then polymer was obtained by one-step reaction. In the beginning, the neutral polymer was gained through Sonogashira polymerization, and then got water-soluble conjugated polymers from post-quaternization treatment.2. The cationic conjugated polymer (CCP) associated with the fluorescein-labeled anionic adenosine triphosphate (ATP) by electrostatic attractions and fluorescence resonance energy transfer (FRET) from the CCP to the fluorescein-labeled ATP occurred. When phosphatase was added, it catalyzed the hydrolysis of phosphate groups from its substrate, ATP, and the final productadenosine was neutral, which made the CCP detached from adenosine. Then the FRET efficiency decreased. The results showed that the degree of FRET efficiency decrease was related to the concentration of phosphatase, the detection limit can be 1×10-6 unit/µL.Keywords: Water-soluble conjugated polymers, Hyperbranched, Synthesize, Fluorescence detection, Sensory，Enzyme南京邮电大学学位论文原创性声明本人声明所呈交的学位论文是我个人在导师指导下进行的研究工作及取得的研究成果。

药学专业文献翻译Enzymatic Synthesis and Antioxidant Properties of Poly (rutin) 聚(芦丁)的酶促合成与抗氧化性质†‡†‡††Motoichi Kurisawa, Joo Eun Chung, Hiroshi Uyama,* and Shiro Kobayashi*Abstract 摘要Rutin, quercetin-3-rutinoside, is one of the most famous glycosides of flavonoid and widely present in many plants. In this study, we performed an oxidative polymerization of rutin using Myceliophthora laccase as catalyst in a mixture of methanol and buffer to produce a flavonoid polymer and evaluated antioxidant properties of the resultant polymer. Under selected conditions , the polymer with molecular weight of several thousands was obtained in good yields. The resulting polymer was readily soluble in water, DMF, and DMSO, although rutin monomer showed very low water solubility. UV measurement showed that the polymer had broad transition peaks around 255 and 350 nm in water, which were red-shifted in an alkaline solution. Electron spin resonance (ESR) measurement showed the presence of a radical in the polymer. The polymer showed greatly improved superoxide scavenging activity and inhibition effects on human low-density lipoprotein (LDL) oxidation initiated by 2,2‘-azobis(2-amidino-propane) dihydrochloride (AAPH), compared with the rutin monomer. The polymer also protected endothelial cells from oxidative injuryinduced by AAPH as a radical generator with a much greater effect than the rutin monomer.芦丁，槲皮素芸香糖苷，是最著名的黄酮类糖苷之一，广泛存在于很多植物中。

硅酸盐学报· 1730 ·2009年新型镍锡铝水滑石的合成及还原性能潘国祥1,2，倪哲明2，曹枫1，李小年2(1. 湖州师范学院化学系，浙江湖州 313000；2. 浙江工业大学化学工程与材料学院，杭州 310032)摘要：通过改变Ni/Sn和(Ni+Sn)/Al的摩尔比，采用共沉淀法成功合成了新型NiSnAl水滑石(layered double hydroxides，LDHs)。

当n(Ni)/n(Sn)≥16和n[(Ni+Sn)]/n(Al)=2～5时可制备纯水滑石相材料。

当n(Ni)/n(Sn)≤12时，合成样品中除存在水滑石相外，还伴随有SnO杂相。

合成的Ni20SnAl7– LDHs样品形貌呈六边形，其尺寸约为80nm，并且分散性良好。

热重–差热分析显示：在Ni3Al–LDHs基础上添加Sn，其热稳定性变差；随着n[(Ni+Sn)]/n(Al)增大，水滑石层板羟基及层间碳酸根的热分解温度降低。

H2程序升温还原分析表明：样品还原过程包含2个阶段，低温还原峰对应于Ni/Sn 从水滑石层板中直接还原，高温还原峰则为Ni/Sn从氧化物NiSnAl(O)中还原。

并且Sn含量越高，Al含量越低，NiSnAl–LDHs样品越容易被还原。

关键词：镍锡铝水滑石；合成与表征；热稳定性；还原特性中图分类号：O611.6 文献标志码：A 文章编号：0454–5648(2009)10–1730–05SYNTHESIS AND REDUCTIVE PROPERTIES OF NEW Ni–Sn–Al LAYERED DOUBLE HYDROXIDESP AN Guoxiang1,2，NI Zheming2，CAO Feng1，LI Xiaonian2(1. Department of Chemistry, Huzhou Teachers College, Huzhou 313000, Zhejiang; 2. College of Chemical Engineering andMaterials Science, Zhejiang University of Technology, Hangzhou 310032, China)Abstract: New Ni–Sn(Ⅱ)–Al layered double hydroxides (NiSnAl–LDHs) were successfully synthesized using coprecipitation by modifying the mole ratio of n(Ni)/n(Sn) and n(Ni+Sn)/n(Al). The synthesized materials with unitary hydrotalcite phase can be ob-tained if n(Ni)/n(Sn)≥16 or n(Ni+Sn)/n(Al)=2–5. When n(Ni)/n(Sn)≤12, the synthesized samples contain a SnO phase as well as a hydrotalcite phase. The structure of Ni20SnAl7–LDHs particles is hexagonal and the powders are well dispersed with a size of 80nm. Sn-substituted LDHs samples showed less thermal stability compared to Ni3Al–LDHs. With the ratio of n(Ni+Sn)/n(Al) increasing, the de-composition temperature of the hydroxyl layer and interlayer carbonate decreased. The H2–TPR (temperature programmed reduction) char-acterization of NiSnAl–LDHs showed that the reductive process of LDHs contains two steps. The low-temperature reductive peak seems to be resulted from the direct reduction of Ni/Sn ions within the layers, while the high-temperature reductive peak seems to be resulted from the reduction of NiSn(O). Additionally, the NiSnAl–LDHs tend to be reduced as the Sn content increases or the Al content decreases.Key words: nickel–tin–aluminum layered double hydroxides; synthesis and characterization; thermal stability; reductive property水滑石类材料(layered double hydroxides，LDHs)，也称层状阴离子黏土，是一种重要的无机功能材料。

本科生科研训练题目高能量密度柔性赝电容器中的二维磷酸氧钒超薄结构（翻译）院系物理科学与技术学院专业物理学基地班年级2012级学生姓名李赫学号**********二0一三年十二月二十日natureCOMMUNICATIONS2013年2月5号收到稿件2013年8月12日接受稿件2013年9月12日发表稿件DOI: 10.1038/ncomms3431高能量密度柔性赝电容器中的二维磷酸氧钒超薄结构二维材料一直以来在柔性薄膜型超级电容器，以及表现有关灵活性，超薄度甚至透明度的强劲优势上都是一个理想的构建平台。

要探索新的具有高电化学活性的二维赝电容材料，我们需要获得具有高能量密度的柔性薄膜超级电容器。

这里我们介绍一个无机石墨烯类似物，a1钒，一种少于6个电子层的磷酸盐超薄纳米片来作为一个有发展前景的材料去构建柔性全固态超薄赝电容器。

这种材料展示了一个在水溶液中氧化还原电位(~1.0V)接近纯水电化学窗口电压（1.23V）的赝电容柔性平面超级电容器。

通过层层组装构建出的柔性薄膜型超级电容器的氧化还原电位高达1.0V，比容量高达8360.5 μF∙cm-2，能量密度达1.7 mWh ∙cm-2，功率密度达5.2 mW∙cm-2。

现在，便携式消费电子产品的需求在快速增长，如柔性显示器，手机和笔记本电脑，极大推动了在全固态下的柔性能源设备的开发。

作为未来一代的储能装置，柔性薄膜型超级电容器在全固态下提供柔韧性，超薄型和透明度的协同效益。

在不同的类型的超级电容器中，与电双层电容器相比，赝电容器因为自身的高活性表面的电极材料可以快速发生的氧化还原反应而具有明显优势。

与锂离子电池相比，它表现出更高的能量密度，以及更高的功率密度。

因此，承载着为实现高性能的柔性薄膜型超级电容器的全固态伟大的承诺（FUSA）与电容行为。

具有赝电容特性的二维（2D）类石墨烯材料代表着一个有前途的方向可以去实现全固态下的高能量密度柔性超级电容器，和潜在的优良的机械柔性。

化工进展Chemical Industry and Engineering Progress2024 年第 43 卷第 4 期具有烷基磺酸侧链的凝胶型聚苯并咪唑质子交换膜的制备与表征朱泰忠1，张良1，黄泽权1，罗伶萍1，黄菲1，薛立新1，2（1 浙江工业大学化工学院膜分离与水科学技术中心，浙江 杭州 310014；2温州大学化学与材料工程学院，浙江 温州 325035）摘要：磷酸（PA ）掺杂聚苯并咪唑（PBI ）以其优异的热化学稳定性和高玻璃化转变温度成为高温质子交换膜燃料电池（HT-PEMFCs ）的首选材料。

然而，由于低温下磷酸较弱的解离度和传递速率，导致膜的质子传导性能不佳，电池冷启动困难。

因此，研发可在宽温湿度范围内高效运行的高温质子交换膜成为当前挑战。

特别是拓宽其低温运行窗口、实现冷启动对这类质子交换膜燃料电池在新能源汽车领域的实际应用具有重要意义。

本文通过多聚磷酸溶胶凝胶工艺与内酯开环反应设计并合成了一系列磷酸掺杂的具有柔性烷基磺酸侧链的凝胶型聚苯并咪唑质子交换膜。

重点探究了烷基磺酸的引入以及侧链长度对磷酸掺杂水平、不同温湿度下的质子传导率及稳定性的影响规律。

研究结果表明，所制备的质子交换膜具有凝胶型自组装片层堆叠的多孔结构，有利于吸收大量磷酸并提供质子快速传输通道。

其中，PA/PS-PBI 展现出了在宽温域范围内均优于目前所报道的其他工作的质子传导性能。

特别是常温下，其质子传导率从原膜的0.0286S/cm 提升至0.0694S/cm 。

80℃下，其质子传导率从原膜的0.1117S/cm 提升至0.1619S/cm 。

200℃下，其质子传导率从原膜的0.2609S/cm 提升至0.3578S/cm 。

此外，该膜在80℃和0%相对湿度（RH ）条件下仍可具有与Nafion 膜在100%RH 时相当的质子传导率，为打破质子交换膜经典定义、实现宽温域（25~240℃）运行提供新的方案。

齐齐哈尔大学毕业设计(论文)题目年产6万吨2-丙基庚醇车间合成工段工艺初步设计学院化学与化学工程专业班级学生姓名指导教师成绩2013 年 6 月日摘要本课题是年产6万吨2-丙基庚醇车间合成工段工艺的初步设计。

第一论述了二丙基庚醇合成的意义与作用、国内外研究现状及进展前景，并简要介绍了二丙基庚醇的性质及合成方式，第二介绍了课题的设计背景、厂址选择和原料产品规格；通过国内外几种相关工艺的比较肯定本设计的工艺流程，对整个生产进程进行了物料衡算、热量衡算和Aspen plus模拟；对反映釜等主要设备进行了设备计算与选型，而且对车间设备进行了布置，对自动控制、安全和环境保护和公用工程进行了概述。

最后按照毕业设计的要求利用AutoCAD绘制戊醛缩合反映釜装配图和合成工段设备平立面布置图，手绘了带控制点的工艺流程图，而且完成了20 000字的毕业设计说明书。

关键词：初步设计；合成工段；2-丙基庚醇；衡算AbstractThe preliminary design of workshop of the synthesis section of 60,000 tons annual production capacity of 2-propyl heptanol was completed. Firstly, the significance, the function of 2-propyl heptanol, the development of research on 2-propyl heptanol was stated. The nature of 2-propyl heptanol and synthetic methods were described briefly. Secondly, the design background, plant location and materials and product specification were introduced; comparion of the productive processed in the domestic and aboard, the design process was determined. Meanwhile the material balance, heat balance, and the simulation of process by Aspen plus were finished. The reactor equipment and other major equipments were calculated and selected. And the layout of the equipment for the workshop, safety, environmental protection and public works were outlined. Thirdly, the equipments arrangement diagram of the workshop and the pentanal condensation reactor equipment were drawn with Auto CAD, the process flow diagram with control points was drawn by hand. Finally, the design instruction of 20 thousand words was finished.Key words：Preliminary design; Synthesis section; 2 - propyl heptanol; Balance calculation目录摘要 (I)Abstract (II)第一章总论 (1)概述 (1)项目建设意义 (1)国内外现状及进展前景 (1)设计依据 (3)厂址选择 (4)厂址肯定 (4)厂址优势分析 (4)设计规模与生产制度 (5)设计规模 (5)生产制度 (5)原料和产品规格 (6)经济核算 (6)第2章工艺设计和计算 (7)工艺线路的选择 (7)2-丙基庚醇工艺介绍 (7)2-丙基庚醇工艺的肯定 (8)工艺流程简述 (8)物料衡算 (9)反映器R101的物料衡算 (9)分离罐V103的物料衡算 (10)换热器E101的物料衡算 (11)精馏塔T101的物料衡算 (12)换热器E104的物料衡算 (12)反映器R102的物料衡算 (13)换热器E105的物料衡算 (14)闪蒸罐V105的物料衡算 (15)热量衡算 (16)反映器R101的热量衡算 (16)换热器E101的热量衡算 (17)T101冷凝器E102的热量衡算 (18)T101再沸器E103的热量衡算 (19)精馏塔T101的热量衡算 (21)换热器E104的热量衡算 (22)反映器R102的热量衡算 (24)换热器E105的热量衡算 (25)全流程模拟 (26)总工艺的模拟 (26)反映器R101的模拟 (27)精馏塔T101的模拟 (28)反映器R102的模拟 (28)第3章设备计算及选型 (30)关键设备R101计算及选型 (30)R101筒体直径和高度的计算 (30)筒体壁厚的计算 (30)夹套的计算 (31)水压实验及强度校核 (32)换热计算 (33)釜体法兰的选择 (33)搅拌器的选择 (33)搅拌传动装置和密封装置的选择 (34)容器支座的选择 (35)人孔、视镜、温度计和工艺接管的选择 (35)其他设备计算与选型 (36)反映器R102的计算 (36)精馏塔T101的计算 (37)换热器的计算与选型 (40)泵计算与选型 (43)储罐和回流罐的计算与选型 (44)紧缩机C101的计算与选型 (46)第4章设备一览表 (47)第5章车间布置 (49)反映器和塔的布置 (49)换热器的布置 (50)泵和紧缩机的布置 (50)罐的布置 (51)第6章自动控制 (52)2-丙基庚醇合成工段自动控制 (52)泵P101的控制 (52)塔顶冷凝器E102的控制 (52)反映器R101的控制 (53)精馏塔T101的控制 (53)第7章公用工程 (55)供水 (55)供热 (55)供电 (56)第8章安全环境保护 (57)结束语 (58)参考文献 (59)致谢 (61)第一章总论概述项目建设意义分子总碳数为4～13的脂肪族伯醇，其全世界近50％产量用于生产增塑剂，所以国内外俗称其为增塑剂醇[1]。

Transactions of Tianjin University (2019) 25:237–244https:///10.1007/s12209-018-0169-zS trategy for Synthesizing Novel Acetamidines as C O 2 -Triggered Switchable Surfactants via AcetimidatesY an X u 1 · F an W ang 1 ·Q ingfeng H ou2 · Y ujun Z hao 1 ·G uosheng D ing3 · X ingguang X u 4R eceived: 15 March 2018 / Revised: 28 April 2018 / Accepted: 3 May 2018 / Published online: 15 June 2018©T he Author(s)2018A bstractI n this study, we developed a strategy for using the Scoggins procedure in the synthesis of acetamidines as novel C O 2 -triggered switchable surfactants via acetimidates by eff ectively tuning the chemical equilibrium. The as-synthesized N’-alkyl- N,N-diethylacetamidines exhibit excellent C O 2 /N 2 switchability and their bicarbonate salts have the ability to emulsify oil–water mixtures.K eywords C O 2 switchable surfactants · A cetimidate · A cetamidine · C onsecutive reactionI ntroductionS urfactants, whose amphiphilic structures enable the stabili-zation of emulsions with two immiscible phases, are widely applied in many processes such as cleaning [ 1], viscous oil transportation [ 2], and enhancing oil recovery [ 3]. Excellent stabilization is required in these processes, usually followed by a subsequent emulsion-destabilization step to eff ectively recover the two immiscible phases. However, this remains a challenging task for most commonly used surfactants. To tackle this problem, it is necessary for the surfactants that can be “switched on and off ” to reversibly stabilize/desta-bilize the emulsion under certain trigger conditions. The switchable surfactants reported in the literature can undergo reversible interconversions from surface-active to surface-inactive forms upon command, and their switchability can usually be triggered by altering the external conditions, such as pH [ 4], electrochemical redox [ 5], magnetic-fi eld intensity [ 6], or light source (UV or visible light) [ 7]. Com-pared with these triggers, C O 2 is environmentally benign, inexpensive, and renewable, and more important, it does not accumulate in a system after repeated cycles. Therefore, it has been identifi ed as an innovative and ideal “trigger” for stimuli-responsive surfactants and has recently been studied for use in reversible solvents [ 8–10 ], switchable Pickering emulsions [ 11 ,12 ], and repeatable polymer-based materials [ 13 ,14 ], particularly for application in enhanced oil recov-ery[15,16].T hus far, the majority of C O 2 /N 2 reversible surfactants include guanidines, imidazoles, tertiary amines, and ami-dines. In their inactive forms, these surfactants can be pro-tonated to form charged bicarbonates that become active upon the addition of C O 2 in aqueous media, increasing their solubility in water. The bicarbonate ions can then be deprotonated by bubbling with N2 or air [ 17 ]. However, these common C O 2 /N 2 reversible surfactants have some inherent drawbacks that hinder their wide application. The headgroup of imidazole surfactants limits their triggering effi ciency due to their hydrolysis in aqueous media [ 18 ]. Surfactants containing a hydrophilic headgroup of guani-dine are generally basic and require more rigorous condi-tions to achieve deprotonation (such as high temperature, long reaction time, or heavy fl ow rate of bubbling gas) [ 19 ].E lectronic supplementary material T he online version of thisarticle ( h ttps :///10.1007/s1220 9-018-0169-z )containssupplementary material, which is available to authorized users.*Q ingfeng H ouh ouqingfeng@*Y ujun Z haoy ujunzhao@1K ey Laboratory for Green Chemical Technology of Ministryof Education, Collaborative Innovation Center of ChemicalScience and Engineering, School of Chemical Engineeringand T echnology,T ianjin University,T ianjin 300072,C hina2 R esearch Institute of Petroleum Explorationand Development (RIPED) ,C NPC ,B eijing 100083 ,C hina3 A nalysis Center ,T ianjin University ,T ianjin 300072 ,C hina4 E nergy Business Unit ,C SIRO ,K ensington ,W A 6151 ,A ustralia1 3238 Y. Xu et al.1 3With respect to tertiary amines, their basicity is so weak that stable emulsions can hardly be formed [ 20 ]. As such, compounds containing an amidine head [ 21 , 22 ] are attract-ing more attention due to their mild basicity and superior stability. In addition, the exceptional demulsifying ability of amidines in their neutral form is an unexpected advan-tage. Scheme 1 illustrates the protonation and deprotonation processes of amidines stimulated by C O 2and N 2 (or air), respectively, in aqueous media, where R represents a long-chain alkyl or ethoxylated groups. Amidine surfactants can easily and reversibly transform into bicarbonate salts. A midines can be synthesized using various strategies, such as the nucleophilic addition of amines to nitriles [ 23 ], reaction of catalytic three-component coupling [ 24 ], dis-placement reaction of imidates with amines [ 25 , 26 ], and the Scoggins procedure [ 27 , 28 ]. Of these synthetic meth-ods, the Scoggins procedure involving primary amines and N , N -dimethylacetamide dimethyl acetal can synthesize long-chain aliphatic amidines and aromatic amidines with a high yield of 90% accompanied by the formation of a small amount of imidates as a by-product [ 27 , 28 ]. This is par-ticularly attractive since an encouraging acetamidines yield of 99% was achieved by Jessop et al. [ 21 ] when they added an excess amount of dimethylamine to the reaction sys-tem. However, the types of amidines used in this synthesis method have been fairly limited thus far, due to the limita-tion of commercially available reactants. The structure of amidines generated by this method diff ered from those in the hydrophobic tail group, which are mainly long-chain alkyl or ethoxylated groups, or both [ 16 , 21 ], and the hydrophilic head is bonded only with the dimethyl group. A s stated earlier, imidates were the only by-product of the Scoggins procedure. At the same time, the potent elec-trophilicity of imidates supports the synthesis of amidines through displacement reactions with amines. Therefore, imi-dates have potential for use in the synthesis of new C O 2 /N 2switchable amidines if various imidates can be generated as the main product by modifying the Scoggins procedure. We also believe it is important to gain insight into the reaction path of the Scoggins procedure to facilitate the development of this novel synthesis strategy. In this study, we mainly investigated the reaction path of the Scoggins procedure foruse in developing a new approach for the synthesis of novel C O 2 /N 2switchable surfactants. E xperimental Section M aterials and Methods To avoid light and moisture, we conducted all the reactions in the dark environment. We purchased N , N -dimethylaceta-mide dimethyl acetal (> 90%, stabilized by 5–10% methanol) and a series of primary amines (dodecylamine (AR) > 98%, tetradecylamine (AR) > 96%, hexadecylamine (AR) > 95%, octadecylamine (GC) > 98%) from Aladdin Reagent Com-pany (Shanghai, China) without further purifi cation. We pre-pared N ’-dodecyl- N , N -dimethylacetamidine ( 1b ) in experi-ments 1 and 2, as shown in Table 1 , according to methods reported in Refs. [ 21 , 28 ]. We recorded the proton nuclearmagnetic resonance ( 1H NMR) and carbon-13 nuclear mag-netic resonance ( 13C NMR) of the reaction products on a Varian Inova spectrometer (Varian, America, 500 MHz), forwhich all the chemical shift values refer to C DCl 3( δ ( 1H), 7.26 ppm; δ ( 13C), 77.16 ppm). We obtained high-resolution electrospray ionization mass spectrometry (ESI-HRMS) data on a Bruker micrOTOF-QII mass spectrometer (Bruker, America) and infrared (IR) spectra on a Nicolet Avatar 320 spectrometer (Thermo Fisher, America) with a smart miracle accessory.G eneral Procedure for the Synthesis of N -alkyl- O -MethylacetimidatesW e put N , N -dimethylacetamide dimethyl acetal (1.72 g, 0.012 mol) and dodecyl amine (1.89 g, 0.01 mol) into a three-neck round-bottom brown fl ask in a dark environment and an oil bath, to which we then added methanol (40 mL). We kept this mixture at 68 °C for 2 h with a methanol refl ux in the condenser. To determine when the conversion of the dodecylamine was complete, we used the thin-layer chromatography method (Merck TLC plates, silica gel 60 F254, with chloroform and methanol as developing sol-vents, V CHCl3 / V CH3OH = 3:1). Then, we removed the metha-nol and dimethylamine from the reaction mixture by rotary evaporation at 50 °C and − 0.1 MPa for 20 min, obtaining a light-yellow liquid product consisting of N -dodecyl- O -methylacetimidate ( 1a , 71.7% yield) and N ’-dodecyl- N , N -dimethylacetamidine ( 1b , 28.3% yield). We calculated theyield based on its 1H NMR spectrum. Then, we subjected the resulting mixture to fl ash column chromatography on aluminum oxide (active, neutral, 200–300 mesh) using ethyl acetate and dichloromethane ( V CH3COOCH2CH3 / V CH2Cl2 = 1:2) as mobile phases to obtain purifi ed N -dodecyl- O -methyl-acetimidate ( 1a )as a colorless liquid. We also synthesizedS cheme 1P rotonation and deprotonation processes of amidines andbicarbonate salts239Strategy for Synthesizing Novel Acetamidines as C O 2 -Triggered Switchable Surfactants… 1 3other N -alkyl- O -methylacetimidates, including N -tetradecyl- O -methylacetimidate ( 2a ), N -hexadecyl- O -methylacetimi-date ( 3a ), and N -octadecyl- O -methylacetimidate ( 4a ), by the same method, using diff erent primary amines as the reactants, i.e., tetradecylamine (0.22 g), hexadecylamine (0.25 g), and octadecylamine (0.28 g), respectively.N -dodecyl- O -methylacetimidate ( 1a ): Colorless oil, 1H NMR (500 MHz, C DCl 3) δ = 7.27 (s, 1H), 3.60 (s, 3H), 3.18 (t, 2H), 1.86 (s, 3H), 1.54–1.49 (m, 2H), 1.33–1.26(m, 18H), 0.88 (t, 3H); 13C NMR (125 MHz, C DCl 3 )δ = 161.10, 77.67–76.74, 52.07, 49.40, 32.13, 31.74, 29.90, 29.87, 29.86, 29.77, 29.57, 27.54, 22.89, 14.59, 14.28; HRMS m/z (ESI) calcd for C 15 H 31NO (M + H) + 242.2478, found 242.2512. IR absorption W –N=C– at 1685.48 cm −1,W –C–O–C– at 1253.50 cm −1. N -tetradecyl- O -methylacetimidate ( 2a ): Colorless oil, 1H NMR (500 MHz, C DCl 3) δ = 7.27 (s, 1H), 3.60 (s, 3H), 3.18 (t, 2H), 1.86 (s, 3H), 1.55–1.49 (m, 2H), 1.30–1.26 (m,22H), 0.88 (t, 3H); 13C NMR (125 MHz, C DCl 3) δ = 161.02, 77.67–76.74, 52.07, 49.50, 32.04, 31.57, 29.81, 29.78, 29.68, 29.49, 27.51, 22.79, 14.47, 14.17; HRMS m/z (ESI) calcd for C 17 H 35NO (M + H) + 270.2791, found 270.2811; IR absorption W –C=N– at 1685.48 cm −1, W –C–O–C–at 1253.50 cm −1. N -hexadecyl- O -methylacetimidate ( 3a ): Colorless oil, 1H NMR (500 MHz, C DCl 3) δ = 7.27 (s, 1H), 3.60 (s, 3H), 3.17 (t, 2H), 1.86 (s, 3H), 1.59–1.49 (m, 2H), 1.30–1.26(m, 26H), 0.88 (t, 3H); 13C NMR (125 MHz, C DCl 3 )δ = 161.17, 77.67–76.74, 52.21, 49.53, 32.16, 31.68, 29.94, 29.90, 29.89, 29.79, 29.61, 27.63, 22.91, 14.63, 14.30; HRMS m/z (ESI) calcd for C 19 H 39NO (M + H) + 298.3104, found 298.3128; IR absorption W –C=N–at 1685.48 cm −1, W –C–O–C– at 1253.50 cm −1.N -octadecyl- O -methylacetimidate ( 4a ): Colorless oil, 1H NMR (500 MHz, C DCl 3) δ = 7.27 (s, 1H), 3.58 (s, 3H), 3.17 (t, 2H), 1.85 (s, 3H), 1.54–1.49 (m, 2H), 1.30–1.25(m, 30H), 0.88 (t, 3H); 13C NMR (125 MHz, C DCl 3 ) δ = 161.01, 77.67–76.74, 52.14, 49.51, 32.16, 31.71, 29.94, 29.90, 29.79, 29.61, 27.63, 22.91, 14.56, 14.28; HRMS m/z (ESI) calcd for C 21 H 43NO (M + H) + 326.3417, found 326.3444; IR absorption W –C=N– at 1685.48 cm −1,W –C–O–C– at 1253.50 cm −1.G eneral Procedure for Reaction Pathway Studies Using 1 H NMRE xperimental Process for the Results Shown in Fig. 1 W e added N , N -dimethylacetamide dimethyl acetal (1.72 g) and dodecyl amine (1.89 g) to a three-neck round-bottom brown fl ask in a dark environment, to which we added 40 mL of methanol. Then we maintained the mixture at 68 °C for 2 h by controlling the temperature of the oil bath with a methanol refl ux in the condenser. We extracted 1 mL samples at intervals and immediately transferred them into an ice bath. Then, we removed the methanol and dimethylamine from the samples using a rotary evapora-tor at 10 °C and − 0.1 MPa. The remaining product was a mixture of N -dodecyl- O -methylacetimidate ( 1a ) and N ’-dodecyl- N , N -dimethylacetamidine ( 1b ). Based on their 1 H NMR spectra, we calculated the selectivities of 1a and 1b at different reaction times.T able 1P roduct distribution results using the Scoggins procedureaC onversion of dodecylaminebY ield of 1a was calculated based on the relative integration of the peak at δH = 3.60 (the group of –O(CH 3)) [ 29 ] with respect to the peak at δH = 2.87 (the group of –N(CH 3 ) 2 ) [ 21 ]cY ield of 1b was calculated based on the relative integration of δH = 2.87 with respect to δH = 3.60240 Y. Xu et al.1 3E xperimental Process for the Results Shown in Fig. 2F irst, we prepared a certain amount of purifi ed N ’-dode-cyl- N , N -dimethylacetamidine ( 1b ) using the methoddeveloped by Jessop et al. [ 21 ]. We added about 0.012 mol of N , N -dimethylacetamide dimethyl acetal (1.72 g) and 76.4 mmol of M e 2NH (38 mL, 2 mol/L solution in tet-rahydrofuran) into a three-neck round-bottom brown fl ask and stirred the mixture (100 r/min) at 25 °C. After that, we added about 0.01 mol dodecylamine (1.89 g) drop-wise to this mixture at room temperature, stirred it for 10 min, and then left it for 18 h in the dark. To remove most of the tetrahydrofuran and M e 2NH, we kept the mixture at 55 °C and − 0.1 MPa in a rotary evaporator for 8 h, which yielded a yellow liquid consisting of N ’-dodecyl- N , N -dimethylacetamidine ( 1b , yield = 97.6%) anda trace impurity of N -dodecyl- O -methylacetimidate ( 1a ,yield = 2.4%), which we identifi ed based on its 1H NMR spectrum. We then reacted the above product (2.54 g) with methanol (40 mL) in a three-neck round-bottom brown fl ask with a condenser and thermometer and kept this mixture at 68 °C for 2 h. We extracted 1 mL samples at intervals, which we immediately transferred into an ice bath. Then, we removed the methanol and dimethylamine from the samples using a rotary evaporator at 10 °C and−0.1 MPa. By 1H NMR, we identifi ed the remaining prod-uct as a mixture of N -dodecyl- O -methylacetimidate ( 1a ) and N ’-dodecyl- N , N -dimethylacetamidine ( 1b ). Based ontheir 1H NMR spectra, we calculated the normalized con-centrations of 1a and 1b at different reaction times.G eneral Synthesis of N ’-Alkyl- N , N -DiethylacetamidinesW e obtained purifi ed N -hexadecyl- O -methylacetimidate ( 3a ) and N -octadecyl- O -methylacetimidate ( 4a ) by the method described above in section “ G eneral Procedure for the Synthesis of N -alkyl- O -Methylacetimidates ”. We put the obtained N -hexadecyl- O -methylacetimidate (1.48 g, 0.005 mol) into a three-neck round-bottom brown fl ask and reacted it with diethylamine (7.31 g, 0.1 mol) in the solvents triethylamine (20 mL) and dioxane (30 mL) at 85 °C (reaction temperature) for 36 h. After the reaction, we removed the volatile components from the mixture, including diethylamine and the solvents triethylamine and dioxane, using a rotary evaporator at 60 °C and −0.1 MPa for 30 min, obtaining N ’-hexadecyl- N , N -diethylacetami-dine ( 3c , 60.5% yield) as a yellow liquid. We also syn-thesized N ’-octadecyl- N , N -diethylacetamidine ( 4c , 53.7% yield) by the same method, using 1.63 g N -octadecyl- O -methylacetimidate (0.005 mol) as the reactant. N ’-hexadecyl- N , N -diethylacetamidine ( 3c ): Yellow oil, 1 H NMR (500 MHz, C DCl 3) δ = 7.27 (s, 1H), 3.29 (q, 4H), 3.17 (t, 2H), 1.87 (s, 3H), 1.52–1.47 (m, 2H),1.30–1.26 (m, 26H), 1.08 (t, 6H), 0.88 (t, 3H); 13C NMR (125 MHz, C DCl 3) δ = 156.57, 49.73, 41.68, 32.31, 31.46, 29.68–27.38, 22.65, 14.34, 14.04, 13.67; HRMS m/z (ESI) calcd for C 22 H 46NO (M + H) + 339.3733, found 339.3752; IR absorption W –N=C–N– at 1620.76 cm −1. N ’-octadecyl- N , N -diethylacetamidine ( 4c ): Yellow oil, 1H NMR (500 MHz, C DCl 3) δ = 7.27 (s, 1H), 3.29 (q, 4H), 3.17 (t, 2H), 1.88 (s, 3H), 1.53–1.48 (m, 2H),1.30–1.26 (m, 30H), 1.08 (t, 6H), 0.88 (t, 3H); 13C NMR (125 MHz, C DCl 3) δ = 156.55, 49.77, 41.63, 32.32, 31.89, 29.67– 26.94, 22.64, 14.34, 14.03, 13.67; HRMS m/z (ESI) calcd for C 22 H 46NO (M + H) + 367.4046, found 367.4064; IR absorption W –N=C–N– at 1621.46 cm −1.F ig. 1 P roduct distributions of 1a and 1b as a function of reactiontime in the Scoggins procedure in the presence of methanolF ig. 2 N ormalized concentrations of 1a and 1b as a function of reac-tion time in the reaction between acetamidine and methanol241Strategy for Synthesizing Novel Acetamidines as C O 2 -Triggered Switchable Surfactants…1 3G eneral Procedure for the Switchable Characterization Tests on N ’-Octadecyl- N , N -DiethylacetamidineWe determined the conductivity of the solution bubbled by C O 2 or N 2 using a DDSJ-308F conductivity meter (Shanghai Leici, China) and controlled the gas-fl ow rate using a mass fl ow controller (Beijing Shengye, China). We bubbled the solution of DMSO and water ( V DMSO / V water = 45 mL/5 mL) with N ’-octadecyl- N , N -diethylacetamidine ( 4c , 0.22 g) by C O 2 , followed by N 2 at 65 °C, during which we recorded the conductivity. We obtained four reversible cycles by bubbling C O 2 (400 mL/min) for 40 min and then N 2(800 mL/min) for 40 min. We also determined the conductivity of the solution containing purifi ed N -octadecyl- O -methylacetimidate ( 4a , 0.08 g) using the same method as that in the blank experi-ment. We examined the capability of stabilizing an emulsion by mixing dodecane and water (5 mL, v / v = 1:1) contain-ing N ’-octadecyl- N , N -diethylacetamidine ( 4c , 0.022 g) and observed the state of the oil–water emulsion layers formed by the bubbling C O 2at diff erent stages. R esults and Discussion C onsecutive Reactions of Scoggins Procedure in the Presence of Excess MethanolT o eff ectively regulate product distribution in the Scoggins procedure, we conducted this reaction by varying the organic additives. Table 1 summarizes the reaction results based onthe 1H NMR characterization. Compared with the results (Fig. S2) obtained in experiment 1 using the Oszczapow-icz’ method [ 28 ] without any additives, we obtained a high N ’-dodecyl- N , N -dimethylacetamidine ( 1b ) yield of about 97.6% (Fig. S3) when using NH(CH 3 ) 2 as the additive, as developed by the Jessop et al. [ 21 ]. It seems that NH(CH 3 ) 2 can inhibit the formation of N -dodecyl- O -methylacetimidate. Interestingly, the addition of methanol (experiment 3) led to a dramatic decrease in the yield of 1b , which represents only 28.3% of the total conversion of dodecylamine, whereas we found 1a to be the only by-product with a yield of 71.7% (Fig. S4). This remarkable decline in the acetamidine yield and the formation of such a large amount of acetimidate demonstrates that the presence of methanol may control the product distribution to a great extent. T o further understand the reaction path of the Scoggins procedure in the presence of excess methanol, we designed an experiment (experiment 3), in which we performed interval sampling during the reaction process to obtain a detailed product distribution as a function of the reactiontime. We used 1H NMR to analyze the relative selectivity of acetamidine and acetimidate during the reaction. Figure 1shows plots of the evolution of the selectivities of 1a and1b versus reaction time. In Fig. 1 , we can see that the selec-tivity of 1b increases rapidly to its peak within 2 min and then decreases slowly until reaching a constant selectivity of 28.1%, whereas the selectivity of 1a increases gradually until reaching 71.9% at 120 min. These results indicate that the process is likely a consecutive reaction, in which 1b is easily formed as an intermediate in the fi rst step and then reacts with methanol to generate 1a in the second step. The fact that 1b is readily generated in this reaction may be due to a bimolecular nucleophilic substitution reaction (SN2) between N , N -dimethylacetamide dimethyl acetal with high electrophilicity and the nucleophilic reagent dodecylamine. This reaction may be constrained by a thermodynamic equi-librium, in which the excess methanol in the mixture pro-motes the generation of acetimidates. T o better confi rm the consecutive reaction pathway of this reaction system, we performed a reaction between 1b (synthesized during experiment 2 in advance) and methanol.Using 1H NMR analysis, we identifi ed only 1a and 1b in the resulting mixture by after removing the volatile phase from the samples in high vacuum conditions. Figure 2 shows the normalized concentrations of 1a and 1b in the samples as a function of reaction time. We can see that the normal-ized concentration of 1b signifi cantly decreases with reac-tion time, reaching a constant value of about 28.3% after about 90 min. The normalized concentration of 1a shows the opposite trend at fi rst and ultimately remains constant at 71.7%. The time required to reach the equilibrium con-centration is about 90 min, which is shorter than that of the Scoggins procedure (120 min) in the conditions described above. These results indicate that 1a is generated from the reaction between 1b and methanol, thereby providing fur-ther evidence that the Scoggins procedure involves a con-secutive reaction. In addition, the higher selectivity of 1b at the beginning stage of the Scoggins procedure and the lower equilibrium yield of 1b due to the limiting eff ect of the thermodynamic equilibrium prove that the reaction of 1b with methanol in the second step is the control step for the formation of 1a . B ased on the above fi ndings, we successfully synthe-sized a class of N -alkyl- O -methylacetimidates ( A , Fig. S1) by enhancing the Scoggins procedure with the excess methanol (using the same reaction conditions as experi-ment 3 in Table 1 ). As listed in Table 2 , all the yields ofA are around 70% (Figs. S4–S7), which means that all these reactions reach roughly the same level of equilib-rium regardless of the diff erent hydrophobic groups of the primary amines. Next, we purifi ed a series of product A to colorless liquids using fl ash column chromatography withA l 2 O 3as the stationary phase and ethyl acetate/hexane ( v / v , 2:3) as the eluent. We then confi rmed the resultingstructures by HRMS (Figs. S8–S11), 1H NMR (Figs. S14,242Y. Xu et al.1 3S17, S20, S23), 13C NMR (Figs. S15, S18, S21, S24), and IR spectroscopy (Figs. S32–S35). Taking into considera-tion the characteristic of the equilibrium reaction, these acetimidates might have potential for use as precursors in the preparation of novel acetamidines via reactions with different primary or secondary amines.S ynthesis of Novel Acetamidines via AcetimidatesTo verify the feasibility of generating new acetamidines from acetimidates, we performed a series of reactions between purifi ed A and NH(CH 2 CH 3 ) 2 . As expected, we successfully produced two N ’-alkyl- N , N -diethylacetamidines ( C ) with a diethyl group linked to the amidine group for the fi rst time via a displacement reaction (Table 3 ) with anT able 2Y ield of A in experiment 3 of Table 1Entry R-group ProductsYield A a (%)Yield B b (%)Purity A c (%)1 C 12H 2571.728.31002 C 14H 2972.227.81003 C 16H 3370.429.61004 C 18H 3769.130.9100T he conversion of primary amines is 100% aT he acetimidates yield was calculated based on the relative integration of the peak at δH = 3.60 with respect to δH = 2.87, which represents the groups of –O(CH 3 ) and –N(CH 3 ) 2, respectively bT he acetamidines yield was calculated based on the relative integration of the peaks at δH = 2.87 and δH = 3.60 cW e observed no characteristic peak at δH = 2.87 T able 3P roduction of acetamidines from acetimidatesEntry R-group ProductsConversion A a (%)Yield C b (%)1C 16H 3360.560.52C 18H 3753.753.7T he selectivity to C is 100%, from which C is obtained as the exclusive productaT he conversion of acetimidates bT he yields of 3c and 4c were calculated from the relative integration of the quartet near δH = 3.30 (4H, –N(CH 2 CH 3 ) 2) [ 30 ] with the triplet atδH = 3.60 (3H, –OCH 3 ) based on the 1H NMR spectrum243Strategy for Synthesizing Novel Acetamidines as C O 2 -Triggered Switchable Surfactants…1 3extremely high selectivity of nearly 100%. We confi rmed the structures of N ’-hexadecyl- N , N -diethylacetamidine ( 3c ) and N ’-octadecyl- N , N -diethylacetamidine ( 4c ) by HRMS (Figs.S12, S13), 1 H NMR (Figs. S26, S29), 13C NMR (Figs. S27, S30) and IR spectroscopy (Figs. S36, S37). The quartets atδH = 3.29 in the 1H NMR spectra and at δC = 41.68 in the 13C NMR spectra indicate methylene in the -N(CH 2 CH 3 ) 2 group. We also detected solution peaks of trace 1,4-diox-ane at δH = 3.70 and δC = 67.03 [ 30 ]. This strategy opens a new possible way to design and effi ciently synthesize novel acetamidines with various terminal alkyl groups by simply replacing NH(CH 2 CH 3 ) 2with other dialkylamines. C O 2 -Triggered Switchable Characterization of Novel AcetamidinesN ext, we examined the C O 2 /N 2 switchability of N ’-octade-cyl- N , N -diethylacetamidine by monitoring the conductivity in wet dimethyl sulfoxide. As shown in Fig. 3 , N ’-octadecyl- N , N -diethylacetamidine ( 4c ) exhibited excellent switchabil-ity when C O 2 and then N 2were bubbled through the solution over four cycles, which indicates the reversible transforma-tion between neutral amidine and bicarbonate ions. We also examined the capability of N ’-octadecyl- N , N -diethylaceta-midine bicarbonates salts to stabilize an emulsion by mixing dodecane and water containing 4c . As shown in Fig. 4 , the two immiscible phases became a homogeneous emulsion after the bubbling of C O 2. When kept at room temperature for 12 h, the emulsion volume still accounted for about 90% of the oil–water system, including a thin cloudy liquid at the bottom of the measurement cylinder (Fig. 4 c ). Then, bubbling N 2 rapidly breaks the emulsion into two separate phases (Fig. 4 d ). The conductivity and emulsifi cation testscontaining only 4a evidenced that the rest of 4a had little eff ect and can be ignored. These results demonstrate that the synthesized N ’-alkyl- N , N -diethylacetamidines have C O 2 /N 2 switchability in the emulsifi cation and demulsifi cation of the oil–water system.C onclusionsIn conclusion, in this study, we developed a new approach for synthesizing C O 2-triggered switchable surfactants by the reaction between amines and imidates, produced using an enhanced Scoggins procedure. This reaction process consists of two reactions in a series, and the yield of acetimidates can be signifi cantly improved by shifting the reaction equilib-rium using excess methanol as an additive. This method pro-vides an eff ective route for synthesizing varieties of C O 2 /N 2 switchable acetamidines with the desired functional groups bonded to the amidine group.A cknowledgements T his study was supported by the China National Petroleum Corporation (RIPED-2017-JS-87). O pen Access T his article is distributed under the terms of the Crea-tive Commons Attribution 4.0 International License ( h ttp://creat i veco mmons .org/licen s es/by/4.0/), which permits unrestricted use, distribu-tion, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.F ig. 3 C onductivity of wet DMSO solution containing 4c and puri-fi ed 4a as a function of time during four cycles of treatment with C O 2followed by N 2. Conditions: T = 65 °C, V DMSO / V water = 45 mL/5 mL,F CO2 = 400 mL/min, 40 min, F N2 = 800 mL/min, 40 min; 4c : 0.22 g/50 mL; 4a : 0.08 g/50 mL (as blank experiment)F ig. 4 P hotographs of dodecane/water system (5 mL, v / v = 1:1) con-taining 4c (0.022 g) at diff erent stages. a Sample a after shaking for5 min without C O 2 at 25 °C; b sample b bubbled with C O 2at 25 °C; c sample c standing for 12 h at 25 °C; d sample d bubbled with N 2 for 30 min at 45 °C; e dodecane/water containing 4a (0.011 g) after bub-bling C O 2for 5 min at 25 °C。

Simple and Stereoselective Preparation of an4-(Aminomethyl)-1,2,3-triazolylNucleoside Phosphoramiditeby Natalia A.Kolganova,Vladimir L.Florentiev,Alexander V.Chudinov,Alexander S.Zasedatelev,andEdward N.Timofeev*Engelhardt Institute of Molecular Biology,32Vavilov St.,Moscow119991,Russia (phone:þ7495-135-6591;fax:þ7495-135-1405;e-mail:edward@eimb.ru)A simple and stereoselective synthesis of a protected4-(aminomethyl)-1-(2-deoxy-b-d-ribofurano-syl)-1,2,3-triazole cyanoethyl phosphoramidite was developed for the modification of synthetic oligonucleotides.The configuration of the1,2,3-triazolyl moiety with respect to the deoxyribose was unambiguously determined in ROESY experiments.The aminomethyl group of the triazolyl nucleotide was fully functional in labelling reactions.Furthermore,the hybridization behavior of5’triazole-terminated oligonucleotide was similar to that of5’aminohexyl-terminated oligomer with the same sequence.Internal modifications of the oligonucleotide strands resulted in significant decrease of duplex stability.Introduction.–Recently,several successful examples of azideÀalkyne1,3-dipolar cycloadditions have been reported in nucleoside and oligonucleotide chemistry[1–4]. This relatively new method is promising for the regio-and stereoselective synthesis of substituted triazole deoxynucleosides because of the easy access to protected b-azido-deoxyribose2[5].Triazolyl nucleoside derivatives have received much attention because of their potential antiviral and antitumor properties[6–8].In addition to this therapeutic aspect,we were interested in a nucleoside analog containing an aminoalkyl side chain that would not participate in WatsonÀCrick base pairing.Several applications in molecular biology require the presence of different functional,reactive, linker,and reporter groups in a single oligonucleotide chain[9][10].Amino modifiers are the most commonly used building blocks to introduce a reactive amino group into oligonucleotides for their post-synthetic modification or labelling[11].There are two types of amino modifiers to date,aliphatic amino modifiers with a flexible linker arm [12–16],and nucleosidic-type amino modifiers[17][18].Non-hybridizable aminoalkyl nucleoside units have not been described so far.This type of amino modifier would feature useful properties such as defined configuration,possibility for both internal and terminal modification,standard DMTr protecting group at the5’-end,and unchanged sugar-phosphate backbone.In addition,for a short aminoalkyl arm,it would be possible to place the group of interest inside the helical structure.This possibility is important for applications based on the intercalation and stacking interactions[19][20].In a recent study,a number of substituted1,2,3-triazolyl nucleosides have been synthesized by the Huisgen reaction[2].The synthesis of aminoalkyl derivatives by this method,however,has not been reported.Here,we report a simple and stereoselective synthesis of a protected4-(aminomethyl)-1,2,3-triazolyl deoxynucleoside and its2011Verlag Helvetica Chimica Acta AG,Zürichphosphoramidite derivative,as well as the hybridization properties of triazole-modified oligonucleotides.Results and Discussion.– 1.Synthesis of Phosphoramidite 6(Scheme ).The cycloaddition of propargylamine to 1-azido-2-deoxyribofuranosyl 3is an attractive route for the stereoselective preparation of the b -anomer of 4-(aminomethyl)-1,2,3-triazolyl nucleoside [21].We have optimized the synthetic route to reduce the number of steps for the preparation of a protected nucleoside phosphoramidite.The azide Àalkyne cycloaddition was conducted with Fmoc-protected propargylamine and the unprotected azido sugar 3to provide the shortest route to the target phosphor-amidite derivative 6.The unprotected azido compound 3is readily soluble in organic solvents,and this facilitated the choice of conditions for the cycloaddition reaction.On the other hand,the presence of free OH groups at C(5’)and C(3’)of the triazolyl nucleoside allow direct introduction of DMTr protecting group and subsequent phosphitylation.We prepared the protected 1-azido-2-deoxyribofuranosyl 2from 2-deoxy-3,5-di-O -(p -toluoyl)-a -d -erythro -pentofuranosyl chloride (1)and LiN 3in DMF at 08[3][21].The highest stereoselectivity observed in the formation of the azido derivative from the protected a -chloride 1was 85%,as evidenced by 1H-NMR.This selectivity is comparable to the published procedure that is based on a p -chlorobenzoyl-deoxyribose analog and CsN 3or KN 3in DMSO at room temperature (9:1anomer ratio)[5].It was found that the chromatographic separation of the a -and b -anomers is best performed for DMTr derivatives of the triazolyl nucleoside due to the noticeable difference in R f values (0.49vs .0.55in CH 2Cl 2/MeOH/hexane 9:1:10).For this reason,we have usedSchemea )LiN 3,DMF.b )K 2CO 3,MeOH.c )Fmoc-protected propargyl amine,CuBr,CH 2Cl 2.d )DMTrCl (¼bis(4-methoxyphenyl)(phenyl)methyl chloride),Py.e )(i Pr 2N)2P(OCH 2CH 2CN),1H -tetrazole,Py.anomeric mixtures in the cycloaddition reaction and during the protection of the5’-OH group with DMTrCl.The cycloaddition reaction was performed in CH2Cl2in the presence of0.15equiv. of EtN i Pr2and1.6equiv.of Me3PO3.Both the Fmoc-amine and the unprotected azido sugar3are readily soluble in CH2Cl2.This allows for a smooth Huisgen coupling in the presence of0.4equiv.of CuBr to yield61%of the triazolyl nucleoside4after purification.The configuration of the triazolyl nucleoside at C(1’)was unambiguously determined by ROESY experiments for derivative5.2D-ROESY Spectrum displayed a strong HÀC(1’)/HÀC(4’)correlation,consistent with the b-configuration at the glycosidic bond[2].Additionally,analysis of the correlations between the H-atoms at C(3’),C(2’),and C(1’)confirms b-configuration of the nucleoside.There are two predominant sugar conformations of the pentafuranose ring,N and S[22],that do not differ considerably from each other in terms of the distance between the H-atoms H pro-SÀC(2’)and H pro-SÀC(3’).Therefore,it was possible to assign pro-S or pro-R configuration for either of the H-atoms at C(2’).We followed the NOEs between the H-atoms at C(3’)and C(2’)to identify the pro-S and pro-R H-atoms at C(2’)(Fig.1).In turn,following the NOEs between HÀC(1’)and either one of the H-atoms at C(2’)Fig.1.Correlations between HÀC(1’),HÀC(2’),HÀC(3’),and HÀC(4’)in the ROESY spectrum of the nucleoside5.H aÀC(2’)and H bÀC(2’)were identified as pro-S and pro-R,resp.should be indicative of the nucleoside configuration.The larger value of the correlation between HÀC(1’)and the pro-R H-atom strongly supports the b-configuration of the 1,2,3-triazolyl nucleoside.This conclusion is consistent with the assumed S N2 mechanism of N3substitution at C(1’).The phosphoramidite derivative6was prepared by treatment of the protected nucleoside5with2-cyanoethyl N,N,N’,N’-tetraisopropylphosphoramidite in dry MeCN in the presence of pyridinium tetrazolide[23].2.Synthesis and Hybridization Properties of Modified Oligonucleotides.Modified oligonucleotides ON1–ON3(Table)were synthesized,and the effect of the modifi-cation on the duplex stability was assessed.The standard reaction cycle of oligonucleotide synthesis and deprotection procedures were used without modifica-tions.The purification of modified oligomers was performed with5’-DMTr-protected oligonucleotides using reversed-phase(RP)HPLC.The final deprotection was achieved using2%aqueous CF3COOH.Both DMTr-protected and unprotected oligomers showed a single peak in the RP-HPLC analysis.MALDI Mass spectra of synthesized oligonucleotides confirmed incorporation of the modified residue.The MALDI mass spectrum of the oligodeoxynucleotide ON1is shown in Fig.2.Fig.2.MALDI-TOF Spectra of the oligonucleotide ON1(M calc¼5486.7).Values M exp/M calc for ON2and ON3are5153.2/5157.4and5065.1/5064.4,resp.Analysis was carried out in negative-ion mode withhydroxypicolinic acid as a matrix.In the thermal denaturation studies,the triazole-modified oligonucleotide ON1was compared with amino-terminated oligonucleotide ON4.The complementary strand contained one of four natural bases opposite to modified unit.Normalized UV denaturation profiles of all eight duplexes virtually coincided and gave melting temperatures in the range of 61.2–62.58in 0.1m NaCl and 0.02m NaPO 4at pH 7.0.These results clearly demonstrate that there is no difference between a terminal aminotriazole and an aminohexyl linker with respect to the stability of duplexes.According to these data,the nature of the nucleotide in the complementary strand opposite to the 5’modification has no effect regardless of the modifying amine unit.This observation is in good agreement with the poor hybridization properties of unsubstituted azole-based nucleosides,which have been reported to considerably destabilize the DNA duplex when placed in the middle of the sequence [24].The ability to support stacking in the double helix was observed only for nitrazole nucleobase analogs,such as a universal nucleoside 1-(2-deoxy-b -d -ribofuranosyl)-3-nitropyrrole [25].Protonation of the amino group in the case of modified nucleotide in an aqueous environment should account for even less favorable conditions for stacking or H-bonding as compared with unsubstituted triazoles.The influence of a single positive charge on the duplex stability is the same in ON1and ON4,and is rather low if noticeable at all [26].To estimate the effect of internal strand modifications on the duplex stability,we incorporated one or two triazole units into the sequence (see ON2and ON3).Thermal denaturation of four duplexes with a single modification showed considerable decrease in T m values as compared with the reference duplex containing unmodified strand ON5(Table ).The average D T m was À13.18(Fig.3).Furthermore,two modified units in the oligonucleotide ON3induced a drop of T m by 26.78.These results provide a convincing proof of poor base-pairing properties of (aminomethyl)-triazolyl nucleoside.The aminomethyl group of the triazolyl nucleotide was fully functional in labelling reactions with N -hydroxysuccinimide esters of fluorescent dyes.Fluorescent conjugates of modified oligonucleotide ON1and the corresponding 5’-aminohexyl control ON4with sulfonated derivatives of indocyanine dyes [27]were synthesized with similarTable.Thermal Stability of DNA DuplexesDNA Duplexes a )T m [8]X ¼A G C T 5’-M ATGCAGGTCCATGAGCT (ON1)3’-AAC X TACGTCCAGGTACTCGA61.961.262.262.55’-H ATGCAGGTCCATGAGCT (ON4)3’-AAC X TACGTCCAGGTACTCGA62.362.362.062.05’-ATGCAG M TCCATGAGCT (ON2)3’-TACGTC X AGGTACTCGA49.249.347.048.45’-ATGCAG C TCCATGAGCT (ON5)3’-TACGTC G AGGTACTCGA61.65’-ATGCA M CTCCAT M AGCT (ON3)3’-TACGT C GAGGTA C TCGA34.9a )M designates aminotriazole nucleotide,H designates 6-aminohexyl residue.efficiencies.The yields of labelled oligonucleotides were in the range of 60–80%regardless of the terminus modifier.The presence of a fluorescent label in triazole-terminated oligonucleotides SCy3-ON1and SCy5-ON1was confirmed by UV spectroscopy,fluorescence,and MALDI-MS analysis.Fluorescently labelled oligomers showed absorbance peaks at 551and 645nm,as well as emission peaks at 566and 662nm for SCy3and SCy5derivatives,respectively.Finally,we examined hybridization behavior of the labelled oligonucleotide SCy3-ON1with a hydrogel-pad array [28]of four immobilized probes (5’-AGCTCATG-GACCTGCAT X CAA,where X ¼A,G,C or T).Hybridization was carried out for 24h at 258in 0.1m NaCl and 0.02m Na phosphate at pH 7.0.Quantification of the fluorescent signals from the gel-pads generally confirmed data from the thermal denaturation studies and showed the close efficiency of hybridization of the modified labelled target with all four immobilized probes (Fig.4).Fig.4.Hybridization of SCy3-ON1with four immobilized probes (5’-AGCTCATGGACCTGCAT X-CAA,where X ¼A,G,C or T)in 0.1m NaCl and 0.02m Na phosphate at pH 7.0.a )Hybridization images.b )Normalized average fluorescent signals from gel-pads.Fig.3.Denaturation profiles of duplexes with ON5,ON2,and ON3strand in 0.1m NaCl and 0.02m Naphosphate at pH 7.0Conclusions.–We proposed a simple and stereoselective synthesis of an(amino-methyl)-triazolyl nucleoside phosphoramidite for the modification of synthetic oligonucleotides.The synthetic scheme was optimized for the preparation of the protected4-(aminomethyl)-1-(2-deoxy-b-d-ribofuranosyl)-1,2,3-triazole cyanoethyl phosphoramidite6.The modification of oligonucleotides does not require modifica-tions in the standard protocols of oligonucleotide synthesis and deprotection.Thermal denaturation and hybridization studies of the5’-modified oligonucleotide have demonstrated that the modification has no effect on the duplex stability when compared to oligonucleotide with a terminal5’-aminohexyl group.The(aminomethyl)-triazolyl nucleotide at the5’end of the oligonucleotide does not form base pairs and does not discriminate between natural bases in the complementary strand.Internal modifications of the oligonucleotide strand induce considerable decrease in thermal stability of duplexes.The amino group of the modified nucleotide was shown to be accessible for conjugation reactions such as fluorescent labelling.We thank Dr.A.A.Stomakhin for recording the MALDI-TOF mass spectra.This work was supported by the research grants No.027********and025********from the Russian Federal Agency of Science and Innovations and by the research programme Molecular and Cell Biology of the Russian Academy of Sciences.Experimental PartGeneral.Unless otherwise stated,all reagents were purchased from commercial sources and used without purification.TLC:Kieselgel260F(Merck)plates;solvent systems A and B refer to CH2Cl2/ MeOH/hexane9:1:30and CH2Cl2/MeOH/hexane9:1:10,resp.UV Measurements and thermal denaturation studies:Shimadzu UV-160A spectrophotometer.Fluorescent spectroscopy:Shimadzu RF-5301PC spectrofluorophotometer.1H-13C-,and31P-NMR:Bruker AMX400MHz instrument.MALDI-MS:Bruker Reflex IV mass spectrometer in negative-ion mode with hydroxypicolinic acid as a matrix. The microarray analysis was performed with a home-made portable biochip analyzer.2-Deoxy-3,5-di-O-(p-toluoyl)-b-d-ribofuranosyl Azide(¼(2R,3S,5R)-5-Azido-2-{[(4-methylben-zoyl)oxy]methyl}tetrahydrofuran-3-yl4-Methylbenzoate;2).Chloride1[29](1.5g,4.42mmol)was added to an intensively stirred suspension of LiN3(1.08g,22.06mmol)in DMF(8ml)at08.The mixture was stirred for1h at08and then1h at258.It was diluted with Et2O(150ml)and consequently washed with10%aq.NaHCO3(100ml)and H2O(100ml).The yer was dried(Na2SO4)and evaporated in vacuo to give2(1.2g,80%).R f(A)0.75,mixture of isomers.1H-NMR(400MHz,(D6)DMSO;b-anomer):7.91,7.87(2d,J¼8.4,4arom.o-H);7.34,7.33(2d,J¼8.4,4arom.m-H);5.88(dd,J¼4.0,5.6, HÀC(1));5.51–5.56(m,HÀC(3));4.40–4.57(m,HÀC(4),CH2(5));2.43–2.47(m,H aÀC(2));2.31–2.36 (m,H bÀC(2)).13C-NMR(100MHz,CDCl3):130.0;129.9;129.4;129.3;92.3;82.9;77.5;77.2;76.8;75.1;64.4;38.9;21.8.Anal.calc.for C21H21N3O5:C63.79,H5.35,N10.63;found:C63.83,H5.29,N10.58.2-Deoxy-b-d-ribofuranosyl Azide(¼(2R,3S,5R)-5-Azido-2-(hydroxymethyl)tetrahydrofuran-3-ol;3).Azide2(0.63g,1.59mmol)was added to a stirred suspension of K2CO3(0.56g)in MeOH(10ml). The mixture was stirred for16h at558.Excess K2CO3was neutralized with aq.HCl(36%),and the inorg. salt was removed by filtration.The resulting soln.was concentrated under reduced pressure.The product was purified by CC(SiO2;CH2Cl2/MeOH/hexane9:1:10):0.19g(73%)of3.R f(B)0.25,mixture of isomers.1H-NMR(400MHz,(D6)DMSO;b-anomer):5.54(dd,J¼4.4,6.0,HÀC(1));5.13(d,J¼4.8, HOÀC(3));4.76(t,J¼5.2,HOÀC(5));4.11–4.16(m,HÀC(3));3.74–3.77(m,HÀC(4));3.37–3.48(m, CH2(5));1.92–2.04(m,CH2(2)).13C-NMR(100MHz,CDCl3):104.0;91.3;87.6;84.9;70.3;70.0;62.0;61.3;40.9;40.3;39.9;39.7;39.5;39.3;39.1.Anal.calc.for C5H9N3O3:C37.74,H5.70,N26.40;found: C37.80,H5.65,N26.48.(9H-Fluoren-9-yl)methyl(Prop-2-yn-1-yl)carbamate.(9H-Fluoren-9-yl)methoxycarbonyl(Fmoc) chloride(1.2g,4.65mmol)in CH2Cl2(10ml)was added slowly to an intensively stirred aq.soln.(15ml) of Na2CO3(2.6g)and propargyl amine hydrochloride(0.57g,6.26mmol)at08.The mixture was stirredfor2h.The product was extracted with CH2Cl2(2Â50ml),and the solvent was removed in vacuo.The residue was crystallized from EtOH.Yield1.4g(73%).R f(B)0.67.1H-NMR(400MHz,(D6)DMSO): 7.89(d,J¼7.6,HÀC(4),HÀC(5)of Fmoc);7.69(d,J¼7.6,HÀC(1),HÀC(8)of Fmoc);7.42(t,J¼7.6, HÀC(3),HÀC(6)of Fmoc);7.33(t,J¼7.6,HÀC(2),HÀC(7)of Fmoc);4.31(d,J¼6.8,CH2of Fmoc);4.23(t,J¼6.8,CH of Fmoc);3.78(dd,J¼2.4,5.6,C H2NH);3.08(s,CH).13C-NMR(100MHz,CDCl3): 143.7;140.7;127.6;127.0;125.1;120.0;72.9;65.6;46.6;39.9;39.7;39.5;39.3;39.1;29.7.Anal.calc.for C18H15NO2:C77.96,H5.45,N5.05;found:C77.89,H5.55,N4.98.1-(2-Deoxy-b-d-ribofuranosyl)-4-({[(9H-fluoren-9-yl)methoxycarbonyl]amino}methyl)-1H-1,2,3-triazole(4).To a soln.of3(0.42g,2.68mmol)and Fmoc-protected propargyl amine(1g,3.61mmol)in 15ml CH2Cl2were added Me3PO3(0.51ml,4.32mmol),CuBr(0.15g,1.07mmol),and EtN i Pr2(0.07ml, 0.41mmol).The mixture was stirred for12h at r.t.and then concentrated under reduced pressure.The product was purified by CC(SiO2;CH2Cl2/MeOH/hexane9:1:10):0.71g(61%)of4,mixture of isomers. R f(B)0.15.An anal.sample of the b-anomer was purified by prep.TLC.1H-NMR(400MHz, (D6)DMSO):8.07(s,HÀC(5));7.88(d,J¼7.6,HÀC(4),HÀC(5)of Fmoc);7.69(d,J¼7.6,HÀC(1), HÀC(8)of Fmoc);7.41(t,J¼7.6,HÀC(3),HÀC(6)of Fmoc);7.32(t,J¼7.6,HÀC(2),HÀC(7)of Fmoc);6.33(t,J¼6.0,HÀC(1’));5.30(d,J¼4.4,HOÀC(3’));4.83(t,J¼5.6,HOÀC(5’));4.36–4.39(m, HÀC(3’));4.20–4.31(m,CH2and CH of Fmoc,C H2NH);3.85–3.89(m,HÀC(4’));3.52(dd,J¼4.8,11.6, H aÀC(5’)); 3.43(dd,J¼4.8,11.6,H bÀC(5’));2.55–2.61(m,H aÀC(2’));2.32–2.38(m,H bÀC(2’)). 13C-NMR(100MHz,(D6)DMSO):156.1;143.8;140.7;127.6;127.0;125.1;121.3;120.0;88.2;87.9;70.5;65.5;61.7;46.7.Anal.calc.for C23H24N4O5:C63.29,H5.54,N12.84;found:C63.34,H5.61,N12.78.1-{5-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-2-deoxy-b-d-ribofuranosyl}-4-({[(9H-fluoren-9-yl)-methoxycarbonyl]amino}methyl)-1H-1,2,3-triazole(5).A soln.of4(0.45g,1.03mmol)in pyridine(5ml) was treated with DMTrCl(0.37g,1.08mmol)at r.t.for2h.The mixture was then concentrated under reduced pressure,diluted with CH2Cl2(50ml),and subsequently washed with10%aq.NaHCO3(50ml) and H2O(50ml).The yer was dried(Na2SO4)and concentrated.The product was purified by CC (SiO2;linear gradient from CH2Cl2/hexane1:1to CH2Cl2/MeOH/hexane9:1:10):0.56g(74%)of5.R f (B)0.49.1H-NMR(400MHz,(D6)DMSO):8.58(d,J¼4.4,HÀC(5));7.87(d,J¼7.6,HÀC(4),HÀC(5) of Fmoc);7.67(d,J¼7.6,HÀC(1),HÀC(8)of Fmoc);7.76–7.81,7.16–7.42(2m,5arom.of Ph,4arom.o-H of DMTr,HÀC(2),HÀC(3),HÀC(6),HÀC(7)of Fmoc);6.85,6.84(2d,J¼8.8,4arom.m-H of DMTr);6.36(t,J¼5.6,HÀC(1’));5.36(d,J¼4.8,HOÀC(3’));4.36–4.42(m,HÀC(3’));4.18–4.30(m, CH2,CH in Fmoc,C H2NH);3.96–4.00(m,HÀC(4’));3.72(s,2MeO);3.05–3.13(m,CH2(5’));2.63–2.69(m,H aÀC(2’));2.34–2.40(m,H bÀC(2’)).13C-NMR(100MHz,(D6)DMSO):158.0;143.8;140.7; 129.7;129.6;127.7;127.6;127.0;126.5;125.1;120.0;113.1;87.3;86.0;70.5;86.0;70.5;65.5;55.0;46.7;40.2;40.0;39.8;39.6;39.3;39.1;38.9.Anal.calc.for C44H42N4O7:C71.53,H5.73,N7.58;found:C71.60,H5.63, N7.57.1-(5-O-[Bis(4-methylphenyl)(phenyl)methyl]-3-O-{(2-cyanoethoxy)[di(propan-2-yl)amino]phos-phinyl}-2-deoxy-b-d-ribofuranosyl)-4-({[(9H-fluoren-9-yl)methoxycarbonyl]amino}methyl)-1H-1,2,3-triazole(6).Compound6was synthesized from5(0.44g,mmol)according to the method described in [7].Yield0.44g(79%);mixture of diastereomers.R f(B)0.7.1H-NMR(400MHz,(D6)DMSO);selected signals):8.03(d,J¼2.8,HÀC(5));7.87(d,J¼7.6,HÀC(4),HÀC(5)of Fmoc);7.67(d,J¼7.6,HÀC(1), HÀC(8)of Fmoc);7.76–7.81,7.18–7.42(m,5arom.H of Ph,4arom.o-H of DMTr,HÀC(2),HÀC(3), HÀC(6),HÀC(7)of Fmoc);6.81–6.85(m,4arom.m-H of DMTr);6.39;6.41(d,J¼5.6,HÀC(1’));3.71, 3.72(s,2MeO).13C-NMR(100MHz,(D6)DMSO):158.0;144.5;143.8;140.6;135.4;129.6;127.7;127.6; 127.5;126.9;126.5;125.1;122.1;120.0;113.0;87.2;85.5;65.4;54.9;46.6;42.6;42.5;40.1;39.9;39.7;39.5;39.3;39.1;38.9;24.2;22.5;19.7.31P-NMR(162MHz,(D6)DMSO):150.7;150.2.Anal.calc.for C53H59N6O8P:C67.79,H6.33,N8.95;found:C67.88,H6.25,N8.87.Oligodeoxynucleotides were synthesized with an ABI3400DNA Synthesizer(Applied Biosystems, Forster City,CA,USA)according to standard manufacturer protocols.Purification of oligodeoxynu-cleotides was performed using a Hypersil ODS column(5m m; 4.6mmÂ250mm),0.05m TEAA (pH7.0),and a linear gradient of MeCN(10–50%,30min for DMTr-protected oligodeoxynucleotides, and0–25%,30min for fully deblocked oligodeoxynucleotides).The flow rate was1ml/min.Removal of the5’-O-DMTr group was achieved by treatment with2%aq.CF3COOH for1min,followed by Et3N neutralization and precipitation with2%LiClO4in acetone.Absorbance vs.temp.profiles were determined with a Shimadzu UV160A spectrophotometer equipped with a H2O-jacketed cell holder.Dry N2was flushed through the cuvette chamber to prevent moisture condensation at low temp.Melting experiments were carried out at260nm and with the oligonucleotide concentration at1m m.The solns.were heated at a rate of0.28/min.T m Values were calculated from D H and D S values.Thermodynamic parameters were obtained by fitting of experimental curves using two-state intramolecular model with sloping base lines.Labelling of aminooligonucleotides ON1and ON2with NHS esters of sulfonated fluorescent dyes (SCy3and SCy5)[11]was carried out in0.1m NaHCO3/Na2CO3buffer(pH9.5)at48for16h.HPLC Purification of labelled oligonucleotides was carried out as mentioned above with a linear gradient of MeCN(10–50%,30min).MALDI-MS Analysis:SCy3-ON1:m/z6027.5;calc.6020.3;SCy5-ON1:m/z 6049.3;calc.6046.3.REFERENCES[1]U.Pradere,V.Roy,T.R.McBrayer,R.F.Schinazi,L.A.Agrofoglio,Tetrahedron2008,38,9044.[2]R.Guezguez,K.Bougrin,K.El Akri,R.Benhida,Tetrahedron Lett.2006,47,4807.[3]P.Chittepu,V.R.Sirivolu,F.Seela,Bioorg.Med.Chem.2008,18,8427.[4]M.Nakahara,T.Kuboyama,A.Izawa,Y.Hari,T.Imanishi,S.Obika,Bioorg.Med.Chem.2009,19,3316.[5] A.Sˇtimac,J.Kobe,Carbohydr.Res.2000,329,317.[6]Y.Xia,Y.Liu,J.Wan,M.Wang,P.Rocchi,F.Qu,J.L.Iovanna,L.Peng,J.Med.Chem.2009,52,6083.[7] D.-H.Chung,S.C.Kumarapperuma,Y.Sun,Q.Li,Y.-K.Chu,J.B.Arterburn,W.B.Parker,J.Smith,K.Spik,H.N.Ramanathan,C.S.Schmaljohn,C.B.Jonsson,Antiviral Res.2008,79,19.[8]I.Pe´rez-Castro,O.Caaman˜o,F.Ferna´ndez,M.D.García,C.Lo´pez,E.De Clercq,Org.Biomol.Chem.2007,5,3805.[9] C.Situma,A.J.Moehring,M.A.F.Noor,S.A.Soper,Anal.Biochem.2007,363,35.[10]T.Krusin´ski,skowska,A.Oz˙yhar,P.Dobryszycki,J.Biomol.Screen.2008,13,899.[11]H.Lçnnberg,Bioconjugate Chem.2009,20,1065.[12]P.S.Nelson,R.Sherman-Gold,R.Leon,Nucleic Acids Res.1989,17,7179.[13] E.Jablonski,E.W.Moomaw,R.H.Tullis,J.L.Ruth,Nucleic Acids Res.1986,14,6115.[14] B.A.Connolly,Nucleic Acids Res.1987,15,3131.[15]P.S.Nelson,R.A.Frye,E.Liu,Nucleic Acids Res.1989,17,7187.[16] C.Goussu,J.-J.Vasseur,H.Bazin,F.Morvan,Nucleosides,Nucleotides Nucleic Acids2005,24,623.[17]J.Telser,K.A.Cruickshank,L.E.Morrison,zel,J.Am.Chem.Soc.1989,111,6966.[18]M.S.Urdea,B.D.Warner,J.A.Running,M.Stempien,J.Clyne,T.Horn,Nucleic Acids Res.1988,16,4937.[19] A.Yamane,Nucleic Acids Res.2002,30,e97.[20] A.Okamoto,T.Ichiba,I.Saito,J.Am.Chem.Soc.2004,126,8364.[21] F.Amblard,J.H.Cho,R.F.Schinazi,Chem.Rev.2009,109,4207.[22] C.Altona,M.Sundaralingam,J.Am.Chem.Soc.1972,94,8205.[23] E.N.Timofeev,S.N.Mikhailov,A.N.Zuev,E.V.Efimtseva,P.Herdewijn,R.L.Somers,M.M.Lemaitre,Helv.Chim.Acta2007,90,928.[24] D.E.Bergstrom,P.Zhang,W.T.Johnson,Nucleic Acids Res.1997,25,1935.[25]R.Nichols,P.C.Andrews,P.Zhang,D.E.Bergstrom,Nature1994,369,492.[26] C.R.Noe,J.Winkler,E.Urban,M.Gilbert,G.Haberhauer,H.Brunar,Nucleosides,NucleotidesNucleic Acids2005,24,1167.[27] E.N.Timofeev,V.E.Kuznetsova,A.S.Zasedatelev,A.S.Chudinov,.Chem.2009,6,71.[28] A.Y.Rubina,S.V.Pan kov,E.I.Dementieva,D.N.Pen kov,A.V.Butygin,V.A.Vasiliskov,A.V.Chudinov,A.L.Mikheikin,V.M.Mikhailovich,A.D.Mirzabekov,Anal.Biochem.2004,325,92.[29]M.Hoffer,Chem.Ber.1960,93,2777.Received February11,2010。

第53卷第3期2021年3月Vol.53No.3Mar.,2021无机盐工业INORGANIC CHEMICALS INDUSTRY催化材料Doi：10.11962/1006-4990.2020-0232开放科学(资源服务)标志识码(OSID)微反应器水热法耦合制备纳米片状氧化铝王梦迪“,罗瑾周靖辉",于海斌吴巍",李晓云"(1.中海油天津化工研究设计院有限公司，天津300131；2.天津市炼化催化技术工程中心)摘要:以偏铝酸钠和硫酸铝为原料，通过一种高通量撞击流微反应器，提岀了将微反应法与老化、水热法高效集成制备纳米片状氧化铝的新工艺。

利用X射线衍射(XRD)、扫描电镜(SEM)、透射电镜(TEM)、BET法比表面积测定(BET)、热重-差热分析(TG-DTG)等方式对不同工艺耦合制备的产物进行了测试分析，研究了不同耦合方式对产物晶型、形貌、介孔结构等物理性质的影响。

结果表明:通过微反应器-水热法耦合技术能够制备粒径为30~100nm、厚度为2~5nm、纯度为99.7%以上的纳米片层状勃姆石(酌-AlOOH),经550益焙烧4h可制得同样形貌的酌-氧化铝(酌-Al J O i)。

通过不同工艺耦合能够调控氧化铝的形貌、介孔结构，为工业化制备片层状纳米氧化铝提供了很好的科研支撑。

关键词:高通量;微反应;水热;纳米片状氧化铝中图分类号:TQ131.1文献标识码:A文章编号：1006-4990(2021)03-0087-06Microreactor-hydrothermal coupling preparation of nano-flaky aluminaWang Mengdi1,2,Luo Jin1袁Zhou Jinghui1,2,Yu Haibin1,Wu Wei1,2,Li Xiaoyun1,2(1.CenerTech Tianjin Chemical Research and Design Institute Co.,Ltd.,Tianjin300131,China；2.Tianjin Refining Catalytic Technology Engineering Center)Abstract: A novel preparation process of nano-flaky alumina is proposed by using a high-throughput impinging stream microreactor with sodium metaaluminate and aluminum sulfate as raw materials,which efficiently integrates the mi­cro-reaction method with aging and hydrothermal method.The effect of different coupling methods on the physical properties of the product such as crystal shape,morphology and pore structure was studied by XRD,SEM,TEM,BET,TG-DTG and oth­er test methods.The flaky酌-AlOOH with purity of more than99.7%,particle size of30~100nm and thickness of2~5nm can be produced by microreaction-hydrothermal coupling technology.The酌-Al2O3with the same morphology can be obtained after calcination at550益for4h.The morphology and mesoporous structure of alumina powder can be regulated by the coupling of different processes.It provides theoretical support for the industrial production of nano-flaky alumina.Key words:high-throughput；microreaction；hydrothermal；nano-flaky alumina纳米氧化铝因具有优异的机械和化学性能,被广泛用于催化剂、复合增强材料、陶瓷材料、生物医学材料、半导体材料等。