【作者】 时蕾；

【导师】 张贵生；

【作者基本信息】 河南师范大学 ， 环境科学， 2012， 博士

【摘要】 绿色溶剂或介质的开发和应用已成为现代绿色化学研究的热点领域之一，特别是水作为资源最丰富、最廉价、环境友好的绿色溶剂之一，水相中的合成反应尤其水相中具有高选择性的反应越来越受到人们的关注。荧光化学传感器由于具有高灵敏度、可实时或者远程检测等优点，在识别分子或离子领域中的应用得到了蓬勃发展。最近几年，能够在水溶液中识别检测离子的荧光探针由于可应用到生物细胞内的离子检测，因而引起人们极大的兴趣和重视。设计合成高灵敏、高选择性可在水溶液中检测离子的荧光探针备受人们关注。从绿色化学原则出发，本文考察了水相中胺硼烷还原剂对各种羰基化合物的选择性还原反应，在水中合成了1,4-二羟基-9,10-蒽醌-2-醛缩氨基硫脲及酰腙、8-羟基喹啉-7-醛缩氨基硫脲及酰腙等4个系列的化合物，研究了几种荧光探针对重金属离子的荧光识别作用，发现了在水溶液中能够灵敏地选择性识别铜离子、镉离子和锌离子的荧光探针分子，并实现了在细胞体内荧光探针对铜离子、镉离子及锌离子的识别。论文的研究内容主要包括以下几个方面：1.以纯水为溶剂研究了胺基硼烷对不同羰基化合物的选择性还原反应，发现胺硼烷在水中室温下能够快速高效还原羰基化合物为醇，对各种二羰基化合能够选择性还原酮羰基而不还原酯羰基。反应底物醛酮中的其它各取代基团如对酸敏感的TBDMS-和-OTr；对碱敏感的乙酰基、-OBn、酯基、磺酰基等以及其它不饱和基团都不受影响。扩大规模到1kg的苯甲酰甲酸甲酯的还原反应也能高收率地在水溶液中完成。甲胺硼烷还能够实现醛酮分子间分子内区域选择性还原醛基而不影响酮羰基。2.在水中通过1,4-二羟基-9-10-蒽醌醛与取代氨基硫脲、取代酰肼的简单缩合反应合成了17种新型取代蒽醌醛缩氨基硫脲类衍生物和15种蒽醌酰腙类衍生物。我们改变了传统的合成方法，用纯水为溶剂，少量PEG-400为相转移催化剂，微波600W辐射下反应，反应在30分钟内完成，粗产物经抽滤、水洗，真空干燥即得到目标化合物。反应不需要加酸催化，避免了有机溶剂的使用，时间短，后处理操作简单，符合绿色化学合成的原则。3.在水中通过8-羟基喹-7-醛与取代氨基硫脲、取代酰肼的缩合反应合成了15种8-羟基喹啉醛缩氨基硫脲和15种8-羟基喹啉酰腙Schiff衍生物。我们用纯水代替常用的有机溶剂或者醇-水体系，少量PEG-400为相转移催化剂，微波600W辐射下搅拌反应，反应在15-30分钟内完成，粗产物经抽滤、水洗，干燥即得到目标化合物。反应不需要加酸催化，避免了有机溶剂的使用，反应快速，操作简便，符合绿色化学合成的原则。4.研究了1,4-二羟基-9,10-蒽醌2-醛缩氨基硫脲化合物(ESN1)和1,4-二羟基-9,10-蒽醌-2-醛缩水杨酰肼(EXZ2)与15种金属阳离子的荧光识别作用。系统考察了水溶液中，磷酸盐缓冲体系，中性pH值下荧光受体与金属离子的荧光光谱性质，发现蒽醌缩氨基硫脲和酰腙化合物都对铜离子有选择性识别作用。Cu2+使其荧光强度猝灭，其它离子则不影响受体分子的荧光吸收。荧光受体分子和铜离子配合比例应为1：1。我们还通过激光共聚焦技术成功地实现了这两种荧光探针对动物肾上皮细胞MDCK中的铜离子的检测。5.研究了8-羟基喹啉-7-醛缩氨基硫脲（KSN1）和8-羟基喹啉水杨酰腙化合物（KXZ2）对15种金属阳离子的荧光识别作用。考察了水溶液，在HEPES缓冲体系中，pH值为7.2条件下，荧光传感分子与不同金属阳离子的荧光识别作用，发现KSN1和KXZ2都对镉离子、锌离子有选择性识别作用，镉离子和锌离子使荧光受体分子荧光增强，其它离子则不影响或者淬灭受体分子的荧光。我们也考察了两类喹啉荧光探针对不同细胞内的镉离子和锌离子的检测，并成功地在低浓度下实现了对MDCK细胞和肺癌细胞H1299内镉离子和锌离子的荧光识别。本论文考察了氨基硼烷在水相中对羰基化合物的选择性还原反应，用价廉易得、无毒无害的环境友好试剂水为反应介质，合成了多个系列具有荧光探针作用的蒽醌类和喹啉类氨基硫脲和酰腙化合物，并开发了几种以水为测试介质的重金属离子荧光探针分子，能够在水溶液中和细胞内有效检测铜离子、镉离子和锌离子，检测快速、灵敏，有潜在的应用价值。更多还原

【Abstract】 The exploration and application of green solvent or reaction media in various chemical processes,especially in synthetic procedures has been a focus topic in both academia and industrial research. In thisregard, reactions in neat water especially high selective reactions in aqueous phase have attracted more andmore attentions in synthetic chemistry, because water is one of the most abundant,cheapest andenvironmental benign solvent. Design and synthesis of fluorescent chemsensor have drawn much interestsin supramolecular chemistry in recent years due to its intrinsic distinct advantages in terms of highsensitivity, able to monitor substrate concentration in real-time and real-space and remote sensing In thelast few years, it is of great interest to develop some fluorescent probes which could recognize detect ionsin the aqueous solution and could be applied in biological cells.Under the guidance of the principles of green chemistry, The chemselective reductions of carbonylcompounds to alcohols in neat water using amine boranes as reductants have been studied in the thesis.Four series of new fluorescent probes based on1,4-dihydroxy-9,10-anthraquinonealdehydethiosemicarbazone，1,4-dihydroxy-9,10-anthraquinone acylhydrazones，8-hydroxyquinoline-7-aldehydethiosemicarbazide and8-hydroxyquinoline acylhydrazones derivatives were designed and synthesized inwater. The recognitions for heavy metal cations of new fluorescent sensors have been searched and somehighly sensitive and selective fluorescent chemosensor for the detection of Cu2+，Cd2+，Zn2+with a fast timeresponse in aqueous solution is demonstrated and an imaging study of Cu2+，Cd2+，Zn2+in living cells isalso successfully shown in this dissertation.This thesis mainly containing the following aspects:1、Chemoselective reduction of various carbonyl compounds to alcohols with ammonia borane (AB、MAB), nontoxic, environmentally benign, and easily handled reagents, in neat water was achieved inquantitative conversions and excellent isolated yields. Interestingly, α-and β-keto esters can be selectivelyreduced by amine borane reagent(AB,MAB) to corresponding hydroxyl esters in water with excellentyields, while diols are efficiently obtained using sodium borohydride as a reducing agent. The procedure is perfectly compatible with the presence of a variety of base-labile protecting groups, such as tosyl, acetyl,benzoyl, ester groups, and acid-labile protecting groups such as trityl and TBDMS groups, and theunsaturated double bond, nitro and cyano groups are intact in the process. A1-kg scale ction of methylbenzoylformate with AB was conducted in water and gave methyl mandelate in94%yield.The competitiveand intra-chemoselective experiments show that MAB effectively discriminates between aldehydes andketones.2、Seventeen1,4-dihydroxy-9,10-anthraquinonealdehyde thiosemicarbazones and fifteen1,4-dihydroxy-9,10-anthraquinone acylhydrazones were synthesized by the condensation of1,4-dihydroxy-9,10-anthraquinone-2-aldehyde and aryl or alkyl thiosemicarbazides or substitudedhydrazides for the first time. The reactions were completed in30min under the microwave radiation in neatwater with little amount of PEG-400as phase transfer catalyst and the products were obtained in excellentyields.The target products could be gotted by only simple filtration, washing and drying. The mainadvantages of this method are that reaction is quick, with excellent isolated yields, operation is simple,avoiding the use of poisonous organic solvents and acid, in line with the principles of green chemicalprinciple.3、 Fifteen8-hydroxyquinolin-7-aldehyde thiosemicarbazones and fifteen acylhydrazones weresynthesized via the condensation of8-hydroxyquinolin-7-aldehyde and aryl or alkyl thiosemicarbazidesand substituded aryl hydrazides. The reactions were completed in15-30min under the microwave radiationin neat water with little amount of PEG-400as phase transfer catalyst and the products were obtained inexcellent yields.The products could be gotted by only simple filtration, washing and drying. Theadvantages of this method are that reaction is quick, excellent isolated yields, operation is simple, avoidingthe use of poisonous organic solvents and acid, in line with the principles of green chemical principle.4、The influence of various metal ions on the absorption and fluorescence spectra of some new sensorsbased on anthraquinone thiosemicarbazone compounds and anthraquinone hydrazide compounds(ESN1and EXZ2) were investigated in detail.Two fluorescent sensors ESN1and EXZ2were found to besensitive to the copper (II) ion in aquerous. In the investiganted15metal ions such asFe3+,Co2+,Ni2+,Cd2+,Zn2+,Hg2+,Ag+and Pb2+have little variations of the fluorescence, However, only Cu2+can lead to the fluorescence quenching in aqueous and PBS as the buffer solution in7.2pH. Therefore, ESN1and EXZ2were the favorable in cognition of Cu2+with high selectivity and sensitivity in aqueoussolution.1:.1binding stoichiometry was confirmed by the experimental results. In addition, biologicalimaging studies have demonstrated that ESN1and EXZ2can detect Cu2+in living kidney epithelialMDCK cells.5、The influence of various metal ions on the absorption and fluorescence spectra of some sensorsbased on8-hydroxyquothiosemicarbazone compounds and anthraquinone hydrazide compounds (KSN1andKXZ2) were investigated in detail.Two fluorescent sensors KSN1and KXZ2were found to be sensitive tothe Cd2+and Zn2+in aquerous. In the investiganted15metal ions such as Fe3+, Co2+, Ni2+, Hg2+, Ag+, Pb2+and so on, only Cd2+and Zn2+can lead to the fluorescence enhancement to7-10times in aqueous andHEPES as the buffer solution in7.0pH. Therefore, KSN1and KXZ2were the favorable in cognition ofCd2+with high selectivity and sensitivity in aqueous solution.1:.1binding stoichiometry was confirmed bythe experimental results. In addition, biological imaging studies have demonstrated that can detect Cu2+inliving kidney epithelial MDCK cells.and lung cancer H1299cells.In this thesis, the chemselected reduction of series carbonyl compounds in neat water, the one of themost abundant, cheapest, and environmentally benign sovent, with amine boranes were achieved inquantitative conversions and excellent yields. Some series of1,4-dihydroxy-9,10-anthraquinonealdehydeand1,4-dihydroxy-9,10-anthraquinonealdehyde derivatives were synthesized in water and their cognitionof heavy ions were investigated in detail. A few of highly sensitve and selective fluorescent probes forCu2+，Cd2+，Zn2+in aqueous solution is demonstrated.An imaging study of heavy ions in living cells isalso successing shown.更多还原