CN110698618A - 水溶性共聚物固载l-脯氨酸催化剂及其制备方法和应用 - Google Patents
水溶性共聚物固载l-脯氨酸催化剂及其制备方法和应用 Download PDFInfo
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Abstract
Description
技术领域
本发明属于催化剂技术领域,具体涉及一种水溶性共聚物固载L-脯氨酸催化剂及其制备方法和应用。
背景技术
随着活性可控聚合和特定序列聚合物架构设计的发展,众多具有复杂拓扑结构的聚合物得以实现。而由于天然蛋白与聚合物之间的相似性,聚合物的可控折叠引起国内外研究者的强烈关注。所谓可折叠聚合物通常是指分子内的聚合物塌陷形成的聚合物纳米颗粒,其通常由单一的高分子量聚合物前体来制备。聚合物前体能够折叠形成具有疏水隔室和亲水外壳的三维结构,可通过引入有机或有机金属催化剂来构建人造活性中心用以作为模拟酶的研究。脲基嘧啶酮(UPy)基团为自识别氢键基团,其在室温下由于自互补氢键作用发生二聚,其二聚体为活性中心创造疏水隔室,是一种典型的折叠聚合物。
L-脯氨酸是一种手性有机催化剂,它能有效地催化不对称羟醛缩合反应,产生良好的收率和高对映体过量。它在有机溶剂如二甲基甲酰胺、二甲基亚砜和氯仿中的催化效率已得到充分证明,然而以水作为溶剂来催化有机反应的研究仍然具有重要意义,这促使人们对具有独特的溶液性质的双亲性聚合物胶束越来越感兴趣。Annhelen等人报道的聚合物胶束作为纳米反应器在水中催化不对称羟醛反应,结果表明,与在水和有机溶剂中的无载体L-脯氨酸相比,聚合物纳米反应器显示出优异的催化性能,在水中有着更高的活性(Chem.Commun.,2012,48,9699-9701)。研究证明利用双亲性聚合物胶束作为载体固载L-脯氨酸在水中催化不对称羟醛反应的研究已成为了一种有效策略,但催化活性和选择性在循环使用后都有所降低,其循环使用性能有待提高。
基于此,将L-脯氨酸引入折叠聚合物中以寻求一种新的载体和固载方法,对合成能够在水中催化不对称反应的高活性、高选择性和良好的循环使用性能的催化体系有着重要的意义。
发明内容
本发明所要解决的技术问题是提供一种具有良好的催化活性和优异的循环使用性能的水溶性共聚物固载L-脯氨酸催化剂,以及该催化剂的制备方法,并为该催化剂提供一种新的应用。
解决上述技术问题所采用的水溶性共聚物固载L-脯氨酸催化剂的结构式如下所示:
式中x的取值为20~50的整数,y1取值为60~100的整数,y2取值为2~10的整数,z的取值为1~10的整数。
上述水溶性共聚物固载L-脯氨酸催化剂的具体合成路线和合成步骤如下:
1、以S-1-十二烷基-S′-(α,α′-二甲基-α″-乙酸)三硫代碳酸酯(CTA)、聚乙二醇单甲醚(mPEG)为原料,二氯甲烷(DCM)为溶剂,在4-二甲氨基吡啶(DMAP)和1-(3-二甲氨基丙基)-3-乙基碳二亚胺(EDC)的体系中进行酯化反应,得到式I所示大分子链转移剂(mPEG-CTA)。
2、以偶氮二异丁腈(AIBN)为催化剂、二甲基亚砜(DMSO)为溶剂,在在惰性气体保护下,将甲基丙烯酸二甲氨基乙酯(DMAEMA)和2-(6-(2-脲基-4[1H]-嘧啶酮)已基氨基甲酰氧基)甲基丙烯酸乙酯(UPy-HEMA)在mPEG-CTA的引发下进行可逆加成-断裂转移活性自由基聚合(RAFT)反应,得到式II所示双亲性嵌段共聚物(mPEG-b-P(DMAEMA-co-UPy))。
3、以mPEG-b-P(DMAEMA-co-UPy)为大分子链转移剂、N-叔丁氧基羰基甲基丙烯酰基-4-羟基-L-脯氨酸(Boc-ProlA)为单体、AIBN为催化剂、DMSO为溶剂,在惰性气体保护下进行RAFT反应,得到式III所示共聚物(mPEG-b-P(DMAEMA-co-UPy)-b-P(Boc-ProlA))。
4、将mPEG-b-P(DMAEMA-co-UPy)-b-P(Boc-ProlA)溶于DCM中,加入三氟乙酸(TFA),通过选择性水解脱去共聚物中L-脯氨酸单元的Boc保护基,得到式IV所示的水溶性共聚物固载L-脯氨酸催化剂(mPEG-b-P(DMAEMA-co-UPy)-b-PProlA)。
上述步骤1中,优选CTA与mPEG、DMAP、EDC的摩尔比为(8~12):(1~5):1:(4~6)。
上述步骤1中,进一步优选酯化反应的温度为20~35℃、时间为48~72小时。
上述步骤2中,优选mPEG-CTA与DMAEMA、UPy-HEMA、AIBN的摩尔比为(1~2):(80~95):(3~10):1。
上述步骤2中,进一步优选RAFT反应的温度为70~100℃、时间为24~30小时。
上述步骤3中,优选mPEG-b-P(DMAEMA-co-UPy)与Boc-ProlA、AIBN的摩尔比为(8~15):(70~100):3。
上述步骤3中,进一步优选RAFT反应的温度为50~70℃、时间为18~36小时。
上述步骤4中,优选mPEG-b-P(DMAEMA-co-UPy)-b-P(Boc-ProlA)与TFA的摩尔比为1:(3~8)。
上述步骤4中,进一步优选脱去共聚物中L-脯氨酸单元的Boc保护基的反应温度为25~40℃、时间为24~48小时。
上述CTA根据文献“ACS Appl.Mater.Interfaces,2011,3,3215-3223”合成;UPy-HEMA根据文献“Polymer Chemistry,2017,8,3066-3073”合成;Boc-ProlA根据文献“Organic Letters,2009,11,2968-2971”合成。
本发明水溶性共聚物固载L-脯氨酸催化剂可用于水相中催化不对称羟醛缩合反应,具体方法为:将醛和酮加入水中,然后加入催化剂,催化剂的加入量为醛摩尔量的5%~10%,在40~50℃下反应24小时,得到不对称羟醛缩合产物。
与现有技术相比,本发明具有以下优点:
1、本发明催化剂以具有多重氢键的脲基嘧啶酮(UPy)基团为疏水基团,其在水中可以折叠形成疏水空腔,提供一个类似于纳米反应器的反应环境;以甲基丙烯酸二甲氨基乙酯(DMAEMA)为亲水链段,赋予催化剂热响应性能,通过改变温度实现共聚物链的折叠-展开行为,构建了一种具有类似酶特性的催化体系。
2、本发明催化剂用于水相中催化不对称羟醛缩合反应具有良好的催化性能。以对硝基苯甲醛和环己酮为反应模型,随着温度的升高,氢键之间不断的进行解离和重组,催化位点不断和反应位点相接触,催化性能逐步提高,在45℃、催化剂的添加量为5mol%时,其催化性能达到最佳:反应转化率为94%,Anti/Syn值为81/19,ee值为90%。且其具有优异的循环使用性能,在循环使用九次之后,其反应转化率、Anti/Syn值和ee值均保持在较高水平。
3、本发明催化剂通过简单的“一锅法”制备,方法简单,无需复杂的后处理步骤,对环境和反应条件也无特殊要求。
附图说明
图1是实施例1制备的双亲性嵌段共聚物的核磁氢谱图(溶剂为氘代氯仿)。
图2是实施例1制备的水溶性共聚物固载L-脯氨酸催化剂的核磁氢谱图(溶剂为氘代氯仿)。
图3是芘在不同浓度实施例1制备的双亲性嵌段共聚物中的荧光谱图(激发波长为340nm)。
图4是实施例1制备的双亲性嵌段共聚物的临界胶束浓度测定曲线图。
图5是实施例1制备的双亲性嵌段共聚物和水溶性共聚物固载L-脯氨酸催化剂在不同温度下的透光率曲线图。
图6是实施例1制备的双亲性嵌段共聚物和水溶性共聚物固载L-脯氨酸催化剂在不同温度下的平均粒径曲线图。
图7是实施例1制备的水溶性共聚物固载L-脯氨酸催化剂在25℃下的粒径分布直方图。
图8是实施例1制备的水溶性共聚物固载L-脯氨酸催化剂在50℃下的粒径分布直方图。
图9是实施例1制备的水溶性共聚物固载L-脯氨酸催化剂在25℃(a)和50℃(b)下的透射电镜图。
图10是实施例1中UPy-HEMA单体以及制备的双亲性嵌段共聚物和水溶性共聚物固载L-脯氨酸催化剂25℃时在水溶液中的CD光谱。
图11是实施例1制备的水溶性共聚物固载L-脯氨酸催化剂在水溶液中随温度变化的CD光谱。
图12是实施例4制备不对称产物(R)-2-[(S)-羟基(4-硝基苯基)甲基]环己酮的核磁氢谱图(溶剂为氘代氯仿)。
图13是实施例4中水溶性共聚物固载L-脯氨酸催化剂的重复使用性分析图。
具体实施方式
下面结合具体附图和实施例对本发明进一步详细说明,但本发明的保护范围不仅限于这些实施例。
实施例1
1、将CTA(6.552g,18mmol)、干燥的mPEG(4.0000g,2mmol)和DMAP(0.2440g,2mmol)溶于60mL CH2Cl2中,完全溶解后,加入EDC(1.5336g,8mmol),25℃反应三天后除去不溶物,溶液浓缩后在乙醚中沉淀两次,所得固体溶解在80mL CH2Cl2中,用饱和Na2CO3水溶液洗涤三次,所得有机相用无水硫酸钠干燥12小时。过滤,旋蒸除去大部分溶剂后,在过量冰乙醚中沉淀,得到淡黄色粉末固体,即式I-1所示大分子链转移剂(mPEG33-CTA)。
2、将mPEG33-CTA(0.4668g,0.2mmol)、DMAEMA(1.4444g,9.2mmol)、UPy-HEMA(0.3176g,0.8mmol)和AIBN(0.0164g,0.1mmol)加入到50mL的史莱克管中,加入5mL DMSO使其溶解,连续冻融脱气3次,然后在氮气氛围下70℃反应24小时。反应结束后,把史莱克管放入液氮中冷冻终止反应,解冻后放置于透析袋(8kD)中透析3天,冷冻干燥得到淡黄色固体,即式II-1所示双亲性嵌段共聚物(mPEG33-b-P(DMAEMA74-co-UPy5))。
3、将mPEG33-b-P(DMAEMA74-co-UPy5)(1.62g,0.2mmol)、Boc-ProlA(0.60g,2mmol)、AIBN(0.0099g,0.06mmol)和5mL DMSO加入到50mL的史莱克管中,磁力搅拌至反应物固体完全溶解,反应体系经过3次连续冻融脱气后,将史莱克管放入预先加热好的60℃的油浴锅中,在氮气保护下反应36小时。反应结束后把史莱克管放入液氮中冷冻终止反应,解冻后放置于透析袋(8kD)中透析3天,冷冻干燥即得到式III-1所示共聚物(mPEG33-b-P(DMAEMA74-co-UPy5)-b-P(Boc-ProlA)3)。
4、将mPEG33-b-P(DMAEMA74-co-UPy5)-b-P(Boc-ProlA)3(3.2g)溶解在30mL CH2Cl2中,在氮气保护下搅拌,缓慢滴加1mL TFA,0℃搅拌1小时后,室温反应48小时。反应结束后,减压蒸馏除去溶剂,随后用20mL THF将反应产物溶解,装入透析袋(8kD)中透析3天,冷冻干燥后得到最终产物,即式IV-1所示水溶性共聚物固载L-脯氨酸催化剂
(mPEG33-b-P(DMAEMA74-co-UPy5)-b-PProlA3)。
发明人采用核磁共振谱仪、激光光散射凝胶色谱、激光粒度仪、紫外-可见分光光度计、圆二色谱和透射电子显微镜对上述步骤2和步骤4所得样品进行表征,结果见图1~11。图1中,化学位移分别在13.13ppm(h)、11.82ppm(i)和10.16ppm(j)处的质子峰是UPy基团上-NH-的氢质子峰,同时在2.53ppm(e)和2.18ppm(f)处分别出现了DMAEMA链段上的-N-CH2-和-N-CH3的氢质子峰,在3.64ppm(a)处也出现了mPEG链段上的特征氢的氢质子峰,说明式II-1所示双亲性嵌段共聚物被成功合成。图2中,在5.14ppm(l)处的质子峰是L-脯氨酸基团上的特征氢质子峰,同时在其他处分别出现了UPy基团和DMAEMA链段上的特征氢质子峰,说明水溶性共聚物固载L-脯氨酸催化剂被成功合成。通过凝胶渗透色谱分析得到,式II-1所示双亲性嵌段共聚物的Mn为15.6k,PDI为1.242;式IV-1所示催化剂的Mn为16.1k,PDI为1.178。由图3和图4可见,式II-1所示双亲性嵌段共聚物的CMC值为33mg/L。图5和图6是双亲性嵌段共聚物和催化剂的粒径和透光率根据温度变化而变化的曲线图,根据文献将最低临界共溶温度(LCST)值定义为透光率减小50%时所对应的温度,可以发现双亲性嵌段共聚物胶束和催化剂胶束的LCST在40℃左右。图7和图8是催化剂在25℃和50℃下的粒径分布直方图,由图可得,其催化剂胶束的粒径分别为137.2nm和76.4nm,且具有单峰分布,表明该催化剂在水溶液中形成的胶束尺寸大小均一,分布较窄;图9是催化剂胶束在25℃(a)和50℃(b)下的透射电镜图,由图可以观察到胶束纳米粒子呈规则的球形结构,当温度升高时,胶束的粒径发生明显变化,变小到62.1nm左右,且胶束仍保持球形结构。图10是UPy-HEMA单体以及双亲性嵌段共聚物和水溶性共聚物固载L-脯氨酸催化剂在25℃下的CD光谱,由图可以观察到,UPy-HEMA单体与双亲性嵌段共聚物在水中显示着相似的形状,而催化剂与双亲性嵌段共聚物的CD光谱显然不同。催化剂表现出具有正和负棉花效应的CD信号,而双亲性嵌段共聚物具有负的棉花效应的CD信号,表明它们之间存在显著的二级结构差异。通过圆二色谱进一步研究了催化剂的温度依赖性即在水中的折叠-展开行为,如图11所示,随着温度升高,在214nm处的正棉花效应(正的吸收信号)降低,催化剂从折叠状态逐渐变为展开状态。通过分析CD光谱,证明了催化剂能够在水中自组装形成疏水空腔。
实施例2
1、将CTA(7.2800g,20mmol)、干燥的mPEG(10.0000g,5mmol)和DMAP(0.2440g,2mmol)溶于60mLCH2Cl2中,完全溶解后,加入EDC(1.9170g,10mmol),25℃反应三天后除去不溶物,溶液浓缩后在乙醚中沉淀两次,所得固体溶解在80mL CH2Cl2中,用饱和Na2CO3水溶液洗涤三次,所得有机相用无水硫酸钠干燥12小时。过滤,旋蒸除大部分溶剂后,在过量冰乙醚中沉淀,得到淡黄色粉末固体,即式I-2所示大分子链转移剂(mPEG39-CTA)。
2、将mPEG39-CTA(0.7002g,0.3mmol)、DMAEMA(1.5700g,10mmol)、UPy-HEMA(0.4367g,1.1mmol)和AIBN(0.0164g,0.1mmol)加入到50mL史莱克管中,加入5mL DMSO使其溶解,连续冻融脱气3次,然后在氮气氛围下70℃反应24小时。反应结束后,把史莱克管放入液氮中冷冻终止反应,解冻后放置于透析袋(8kD)中透析3天,冷冻干燥得到淡黄色固体,即式II-2所示双亲性嵌段聚合物(mPEG39-b-P(DMAEMA86-co-UPy9)),其数均分子量为18.5k、PDI为1.061。
3、将mPEG39-b-P(DMAEMA86-co-UPy9)(1.62g,0.2mmol)、Boc-ProlA(0.60g,2mmol)、AIBN(0.0099g,0.06mmol)和5mL DMSO加入到50mL的史莱克管中,磁力搅拌至反应物固体完全溶解,反应体系经过3次连续冻融脱气后,将史莱克管放入预先加热好的60℃的油浴锅中,在氮气保护下反应36小时。反应结束后把史莱克管放入液氮中冷冻终止反应,解冻后放置于透析袋(8kD)中透析3天,冷冻干燥即得到式III-2所示共聚物(mPEG39-b-P(DMAEMA86-co-UPy9)-b-P(Boc-ProlA)3)。
4、将mPEG39-b-P(DMAEMA86-co-UPy9)-b-P(Boc-ProlA)3(3.2g)溶解在30mL CH2Cl2中,在氮气保护下搅拌,缓慢滴加1mL TFA,0℃搅拌1小时后,室温反应48小时。反应结束后,减压蒸馏除去溶剂,随后用20mL THF将反应产物溶解,装入透析袋(8kD)中透析3天,冷冻干燥后得到最终产物,即式IV-2所示水溶性共聚物固载L-脯氨酸催化剂(mPEG39-b-P(DMAEMA86-co-UPy9)-b-PProlA3)。
实施例3
1、将CTA(8.008g,22mmol)、干燥的mPEG(6.0000g,3mmol)和DMAP(0.2440g,2mmol)溶于60mL CH2Cl2中,完全溶解后,加入EDC(2.3004g,12mmol),25℃反应三天后除去不溶物,溶液浓缩后在乙醚中沉淀两次,所得固体溶解在80mL CH2Cl2中,用饱和Na2CO3水溶液洗涤三次,所得有机相用无水硫酸钠干燥12小时。过滤,旋蒸除去大部分溶剂后,在过量冰乙醚中沉淀,得到淡黄色粉末固体,即式I-3所示大分子链转移剂(mPEG35-CTA)。
2、将mPEG35-CTA(0.2334g,0.1mmol)、DMAEMA(1.4915g,9.5mmol)、UPy-HEMA(0.1985g,0.5mmol)和AIBN(0.0164g,0.1mmol)加入到50mL史莱克管中,加入5mL DMSO使其溶解,连续冻融脱气3次,然后在氮气氛围下70℃反应24小时。反应结束后,把史莱克管放入液氮中冷冻终止反应,解冻后放置于透析袋(8kD)中透析3天,冷冻干燥得到淡黄色固体,即式II-3所示双亲性嵌段聚合物(mPEG35-b-P(DMAEMA88-co-UPy2)),其数均分子量为16.1k、PDI为1.178。
3、将mPEG35-b-P(DMAEMA88-co-UPy2)(1.62g,0.2mmol)、Boc-ProlA(0.60g,2mmol)、AIBN(0.0099g,0.06mmol)和5mL DMSO加入到50mL的史莱克管中,磁力搅拌至反应物固体完全溶解,反应体系经过3次连续冻融脱气后,将史莱克管放入预先加热好的60℃的油浴锅中,在氮气保护下反应36小时。反应结束后把史莱克管放入液氮中冷冻终止反应,解冻后放置于透析袋(8kD)中透析3天,冷冻干燥即得到式III-3所示共聚物(mPEG35-b-P(DMAEMA88-co-UPy2)-b-P(Boc-ProlA)3)。
4、将mPEG35-b-P(DMAEMA88-co-UPy2)-b-P(Boc-ProlA)3(3.2g)溶解在30mL CH2Cl2中,在氮气保护下搅拌,缓慢滴加1mL TFA,0℃搅拌1小时后,室温反应48小时。反应结束后,减压蒸馏除去溶剂,随后用20mL THF将反应产物溶解,装入透析袋(8kD)中透析3天,冷冻干燥后得到最终产物,即式IV-3所示水溶性共聚物固载L-脯氨酸催化剂(mPEG35-b-P(DMAEMA88-co-UPy2)-b-PProlA3)。
实施例4
实施例1的水溶性共聚物固载L-脯氨酸催化剂在水相中催化不对称羟醛缩合反应的应用
以对硝基苯甲醛和环己酮的不对称羟醛缩合反应为反应模型,具体试验如下:
在10mL烧瓶中加入mPEG33-b-P(DMAEMA74-co-UPy5)-b-PProlA3(0.75g,0.05mmol)、2mL去离子水,充分溶解后,向烧瓶中加入环己酮(0.686g,0.007mol),搅拌后加入对硝基苯甲醛(1.51g,0.001mol),该反应45℃下反应24小时。反应结束后,混合液用乙酸乙酯萃取三次,回收水相,合并有机相,无水硫酸钠干燥,过滤,旋蒸除去有机溶剂,柱层析分离。反应方程式如下所示:
发明人采用核磁共振谱仪对上述所得的不对称产物进行了准确表征,图12中核磁氢谱(400MHz,CDCl3)的化学位移:δ8.18(d,2H),7.48(d,2H),5.45(dd,1H),4.87(d,1H),2.60-2.33(m,3H),2.08(m,1H),1.79-1.22(m,5H),证明不对称产物(R)-2-[(S)-羟基(4-硝基苯基)甲基]环己酮成功合成。
发明人进一步研究了反应温度和催化剂用量对催化剂催化性能的影响,以及催化剂的重复使用性能,具体操作步骤如下:
1、温度对催化性能的影响
分别在50℃、45℃、40℃、35℃和30℃下催化对硝基苯甲醛和环己酮的不对称羟醛缩合反应,催化剂用量为对硝基苯甲醛的5mol%,反应时间为24小时。催化结果见表1。
表1反应温度对催化性能的影响
温度(℃) | 反应转化率(%) | Anti/Syn | ee(%) | |
1 | 50 | 95 | 74/26 | 86 |
2 | 45 | 94 | 81/19 | 90 |
3 | 40 | 89 | 90/10 | 88 |
4 | 35 | 77 | 88/12 | 85 |
5 | 30 | 56 | 72/28 | 63 |
通过表1分析可得,反应温度影响催化反应的反应转化率和催化产物的选择性,由实施例1的分析结果可知催化剂的LCST温度在40℃左右,在30℃时,由于共聚物链段是亲水性的,不利于疏水性反应物靠近催化位点,此时的催化性能相对较低;温度升高到45℃时,共聚物链段中部分转变疏水性,疏水性链段与亲水性链段mPEG形成胶束,为疏水性反应物靠近催化位点提供了一个类似于纳米反应器的反应环境,其催化性能达到最佳(转化率为94%,Anti/Syn值为81/19,ee值为90%)。温度升高至50℃,共聚物链段的疏水性增强,反应转化率达到最高,但催化产物的选择性(Anti/Syn值为74/26,ee值为86%)有所降低。
2、催化剂用量对催化性能的影响
分别在催化剂添加量为对硝基苯甲醛的3mol%、5mol%和10mol%下进行反应,反应温度为45℃,反应时间为24小时。催化结果见表2。
表2催化剂用量对催化性能的影响
催化剂用量(mol%) | 反应转化率(%) | Anti/Syn | ee(%) | |
1 | 3 | 72 | 91/9 | 81 |
2 | 5 | 89 | 86/14 | 88 |
3 | 10 | 90 | 83/17 | 90 |
由表2可见,当催化剂用量为3mol%时,其Anti/Syn值(91/9)达到最高,随着催化剂用量的增加,其转化率逐渐增大,ee值增大,但催化剂用量为5mol%和10mol%时,催化性能相差不大。
3、催化剂的重复使用性能
按照上述方法进行催化剂的循环使用性能,反应温度为45℃,催化剂用量为5mol%,反应时间为24小时。催化结果如表3和图13。
表3催化剂的重复使用性能
循环次数 | 反应转化率(%) | Anti/Syn | ee(%) |
1 | 92 | 84/16 | 91 |
2 | 85 | 85/15 | 92 |
3 | 84 | 82/18 | 89 |
4 | 83 | 84/16 | 90 |
5 | 83 | 84/16 | 87 |
6 | 84 | 83/17 | 87 |
7 | 83 | 81/19 | 86 |
8 | 78 | 81/19 | 82 |
9 | 72 | 74/26 | 87 |
通过观察图13和分析表3可得,催化剂的循环使用性能较好,在两次循环后,转化率出现了下降,但在之后的循环中,反应转化率一直保持在较高水平,直到第九次循环后,有了下降的趋势,但催化活性一直保持稳定,九次循环后ee值仍能达到87%。这可能是由于共聚物链段中UPy基团所含的四重氢键作用,温度升高时,氢键处于不停的解离和重组的动态变化,使得胶束在催化过程具有动态自适应性,不断的与催化活性中心接触;其次,UPy基团的四重氢键起到一个物理交联剂的作用,提高了胶束的稳定性,从而提高了催化剂的循环使用性能。
Claims (7)
2.一种权利要求1所述的水溶性共聚物固载L-脯氨酸催化剂的制备方法,其特征在于它由下述步骤组成:
(1)以S-1-十二烷基-S′-(α,α′-二甲基-α″-乙酸)三硫代碳酸酯、聚乙二醇单甲醚为原料,二氯甲烷为溶剂,在4-二甲氨基吡啶和1-(3-二甲氨基丙基)-3-乙基碳二亚胺的体系中进行酯化反应,得到式I所示大分子链转移剂;
(2)以偶氮二异丁腈为催化剂、二甲基亚砜为溶剂,在惰性气体保护下,将甲基丙烯酸二甲氨基乙酯和2-(6-(2-脲基-4[1H]-嘧啶酮)已基氨基甲酰氧基)甲基丙烯酸乙酯在式I所示大分子链转移剂的引发下进行可逆加成-断裂转移活性自由基聚合反应,得到式II所示双亲性嵌段共聚物;
(3)以式II所示双亲性嵌段共聚物为大分子链转移剂、N-叔丁氧基羰基甲基丙烯酰基-4-羟基-L-脯氨酸为单体、偶氮二异丁腈为催化剂、二甲基亚砜为溶剂,在惰性气体保护下进行可逆加成-断裂转移活性自由基聚合反应,得到式III所示共聚物;
(4)将式III所示共聚物溶于二氯甲烷中,加入三氟乙酸,脱去共聚物中L-脯氨酸单元的Boc保护基,得到水溶性共聚物固载L-脯氨酸催化剂。
3.根据权利要求2所述的水溶性共聚物固载L-脯氨酸催化剂的制备方法,其特征在于:步骤(1)中,所述S-1-十二烷基-S′-(α,α′-二甲基-α″-乙酸)三硫代碳酸酯与聚乙二醇单甲醚、4-二甲氨基吡啶、1-(3-二甲氨基丙基)-3-乙基碳二亚胺的摩尔比为(8~12):(1~5):1:(4~6),所述酯化反应的温度为20~35℃,时间为48~72小时。
4.根据权利要求2所述的水溶性共聚物固载L-脯氨酸催化剂的制备方法,其特征在于:步骤(2)中,所述甲基丙烯酸二甲氨基乙酯与2-(6-(2-脲基-4[1H]-嘧啶酮)已基氨基甲酰氧基)甲基丙烯酸乙酯、式I所示大分子链转移剂、偶氮二异丁腈的摩尔比为(80~95):(3~10):(1~2):1,所述可逆加成-断裂转移活性自由基聚合反应的温度为70~100℃,时间为24~30小时。
5.根据权利要求2所述的水溶性共聚物固载L-脯氨酸催化剂的制备方法,其特征在于:步骤(3)中,所述双亲性嵌段共聚物与N-叔丁氧基羰基甲基丙烯酰基-4-羟基-L-脯氨酸、偶氮二异丁腈的摩尔比为(8~15):(70~100):3,所述可逆加成-断裂转移活性自由基聚合反应的温度为50~70℃、时间为18~36小时。
6.根据权利要求2所述的水溶性共聚物固载L-脯氨酸催化剂的制备方法,其特征在于:步骤(4)中,式III所示共聚物与三氟乙酸的摩尔比为1:(3~8),所述脱去共聚物中L-脯氨酸单元的Boc保护基的反应温度为25~40℃、时间为24~48小时。
7.权利要求1所述的水溶性共聚物固载L-脯氨酸催化剂在水相中催化不对称羟醛缩合反应的应用。
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