CN113797969B - 适于酸碱串联催化的单分子纳米胶束的制备方法 - Google Patents
适于酸碱串联催化的单分子纳米胶束的制备方法 Download PDFInfo
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Abstract
本发明公开了一种适用于串联催化的单分子纳米胶束的制备方法,包括以下步骤:利用NHS获得NB‑NHS;亲水单体NB‑PEGm的制备;开环易位聚合制备两亲性嵌段分子刷;利用两亲性嵌段分子刷进行核内含酸催化剂的单分子纳米反应器的构筑,利用两亲性嵌段分子刷进行核内含碱催化剂的单分子纳米反应器的构筑;将相同浓度的核内含酸催化剂的单分子纳米反应器溶液、核内含碱催化剂的单分子纳米反应器溶液,以等体积比融合;得到可酸碱串联催化的单分子纳米反应器。该单分子催化纳米胶束有利于一锅法串联催化反应的进行。
Description
技术领域
本发明公开了一种适用于不相容催化剂的区域化构筑可串联催化的单分子纳米胶束的制备方法,属于高分子合成及应用的技术领域,是一种基于降冰片烯开环易位聚合制备核内含有催化剂的单分子纳米胶束的方法。
背景技术
化工产品的生产通常涉及到从原料开始的多步催化过程,在每一步的合成中会涉及繁琐的中间体分离与提纯,这会造成不必要的浪费,中间过程产生的废弃物也会对生态环境造成破坏。一锅串联催化可一步法制备目标产物,简化了对中间体的处理。但是酸和碱作为不兼容的催化剂在“一锅法”的条件下容易相互影响,从而降低催化效率甚至使催化效率失活。为了实现酸碱串联催化反应,同时避免“狼与羊”的反应,科学家们主要采用二氧化硅等无机载体、聚合物载体负载并隔离不兼容的酸碱催化剂的策略。文献(J.Am.Chem.Soc.2006,128,27,8718–8719)制备了一种具有酸性骨架和碱性孔洞的双功能介孔材料,将二硫键还原为巯基,然后将其氧化为磺酸基并对氨基进行脱保护。该方法涉及到了对酸性位点氧化和碱性位点的脱保护,存在反应不完全以致于催化效果不理想的缺点。文献(Chem.Eur J.,2018,24,18648-18652)通过恶唑烷的阳离子聚合设计了一种两亲三嵌段聚合物,将不相容的有机催化剂负载到聚合物上,并在水相中自组装制备纳米胶束,实现位点分离,使它们在物理上不同的微环境中彼此充分隔开,从而在一锅中实现三步非正交串联反应。该方法存在单体结构单一,微结构不易调控的不足。
发明内容
本发明要解决的技术问题是提供一种适用于酸碱串联催化的单分子纳米反应器的制备方法。
为了解决上述技术问题,本发明提供了一种适用于串联催化的单分子纳米胶束的制备方法,包括以下步骤:
1)、利用NHS获得NB-NHS:
所述NHS为N-羟基琥珀亚酰胺;
NB-NHS为2,5-二氧吡咯烷-1-基(2S)-双环[2.2.1]庚-5-烯-2-羧酸酯;
2)、亲水单体NB-PEGm的制备:
将NB溶于溶剂A,加入PEGm、DCC、DMAP,在室温下搅拌反应12~16小时,反应结束后经后处理,得亲水单体NB-PEGm;
NB为5-羧酸-2-降冰片烯,PEGm为分子量是m的聚乙二醇单甲醚,DCC为二环己基碳二亚胺,DMAP为4-二甲氨基吡啶;
PEGm:NB:DCC:DMAP=0.8~1.5:1:0.9~1.7:0.1~0.8(优选0.8~1.1:1:1.2~1.5:0.3~0.5)的摩尔比;
说明:DCC、DMAP的加入方式均为如下所述:先溶于溶剂A,然后采用常规的溶液滴加的方式加入;
反应式为:
3)、开环易位聚合制备两亲性嵌段分子刷:
将步骤1)所得的NB-NHS溶解于溶剂B中;加入Grubbs催化剂,室温反应1~5min;再加入步骤2)所得的亲水单体NB-PEGm,继续在室温下反应5~10min,反应结束后经后处理,得两亲性嵌段分子刷;
所述NB-NHS:Grubbs催化剂:亲水单体NB-PEGm=5~50:1:50~95的摩尔比;
说明:催化剂和亲水单体NB-PEGm溶于溶液B中,采用常规的滴加的方式加入,反应方程式如下:
4)、核内含酸催化剂的单分子纳米反应器的构筑:
将步骤3)所得的两亲性嵌段分子刷溶于溶剂C中,加入氨基羧酸衍生物,在室温下反应1~15h,两亲性嵌段分子刷:氨基羧酸衍生物=1:10~60的摩尔比;经后处理,得到末端带有酸催化剂的两亲型嵌段分子刷;
反应式为:
将所得的末端带有酸催化剂的两亲型嵌段分子刷配制成浓度为0.5~1.5mg/ml(优选1mg/ml)的溶液,作为核内含酸催化剂的单分子纳米反应器溶液;
说明:氨基羧酸为末端带有-COOH的有机酸;如3-氨基丙酸、4-氨基丁酸、5-氨基戊酸、6-氨基己酸、7-氨基庚酸、8-氨基辛酸、9-氨基壬酸。
5)、核内含碱催化剂的单分子纳米反应器的构筑;
将步骤3)所得的两亲性嵌段分子刷溶于溶剂E中,添加末端带-NH2的衍生物,在室温下反应10~20h;两亲性嵌段分子刷:末端带-NH2的衍生物=1:10~60的摩尔比;
反应结束后进行沉淀处理(例如利用冷乙醚进行沉淀),将所得沉淀物(即,不溶物)溶于试剂F与TFA的混合溶液(试剂F:TFA=2~6:1)中,室温下反应2±0.5h;经后处理,得到末端带有碱催化剂的两亲性嵌段分子刷;
反应式为:
将末端带有碱催化剂的两亲性嵌段分子刷配制成浓度为0.5~1.5mg/ml(优选1mg/ml)的溶液,作为核内含碱催化剂的单分子纳米反应器溶液;
6)、可酸碱串联催化的单分子纳米反应器制备:
将相同浓度的核内含酸催化剂的单分子纳米反应器溶液、核内含碱催化剂的单分子纳米反应器溶液,以等体积比融合(超声处理0.5h);得到可酸碱串联催化的单分子纳米反应器。
作为本发明的适用于串联催化的单分子纳米胶束的制备方法的改进:
所述步骤4)中的氨基羧酸衍生物为3-氨基丙酸、4-氨基丁酸、5-氨基戊酸、6-氨基己酸、7-氨基庚酸、8-氨基辛酸、9-氨基壬酸;
所述步骤5)中的末端带-NH2的衍生物为TAEA-Boc、PDMA-Boc、EDA-Boc。
作为本发明的适用于串联催化的单分子纳米胶束的制备方法的进一步改进:步骤2)中的PEGm为PEG350、PEG2000、PEG5000。
作为本发明的适用于串联催化的单分子纳米胶束的制备方法的进一步改进:步骤3)中的Grubbs催化剂为Grubbs I,Grubbs II,Grubbs III。
作为本发明的适用于串联催化的单分子纳米胶束的制备方法的进一步改进:
步骤2)的后处理为:反应所得物减压旋蒸去除溶剂A,所得粗产品用正己烷:乙醚=1:1体积比的混合溶液进行洗涤;得到亲水单体NB-PEGm;
所述步骤3)中的反应结束后经后处理为:反应时间到达后,淬灭反应(例如用乙基乙烯基醚),将所得的反应液滴加至0~-10℃的正己烷:乙醚=1:1体积比的溶液中,收集不溶的固体,得到两亲性嵌段分子刷(两亲性嵌段刷型聚合物);
所述步骤4)中的后处理为:将两亲性嵌段分子刷与氨基羧酸衍生物进行反应所得的反应混合物进行透析处理(分子量为2000的透析袋),透析处理时间为12~15小时,取透析处理所得的截留液,冷冻干燥去除溶剂C,得到末端带有酸催化剂的两亲型嵌段分子刷;
所述步骤5)的后处理为:反应所得物减压旋蒸去除溶剂,所得固体溶解于DMSO中,加入过量的K2CO3,室温下继续搅拌6±2h,对反应混合物进行透析处理(使用分子量为2000的透析袋),透析处理时间为12~15小时;取透析处理所得的截留液,冷冻干燥去除溶剂(DMSO),得到末端带有碱催化剂的两亲性嵌段分子刷。
作为本发明的适用于串联催化的单分子纳米胶束的制备方法的进一步改进:
所述步骤4)中:先将末端带有酸催化剂的两亲性嵌段分子刷溶解于溶剂D中,再加入超纯水搅拌,干燥至溶剂D蒸发,得到核内含酸催化剂的单分子纳米反应器;
所述步骤5)中,先将末端带有碱催化剂的两亲型嵌段分子刷充分溶解于溶剂G中,再加入超纯水搅拌,干燥至溶剂G蒸发,得到核内含碱催化剂的单分子纳米反应器的溶液。
作为本发明的适用于串联催化的单分子纳米胶束的制备方法的进一步改进:
所述步骤2)中的溶剂A为二氯甲烷;
所述步骤3)中的溶剂B为二氯甲烷;
所述步骤4)中的溶剂C为二甲基亚砜、溶剂D为四氢呋喃;
所述步骤5)中:溶剂E为二甲基亚砜、溶剂F为二氯甲烷、溶剂G为四氢呋喃。
本发明的主要反应式如下:
本发明基于开环易位聚合法制备酸或碱可一锅法串联催化的两亲性嵌段刷型聚合物并在水相自组装成单分子纳米反应器。相对于非单分子纳米胶束,本发明设计的单分子纳米胶束不仅能在催化后进行回收利用,其结构更稳定不易受外界的影响,使酸或碱催化剂固定在疏水核内,亲水段避免了酸和碱催化剂在“一锅法”中的相互干扰,实现从缩醛到腈基衍生物的直接合成。
本发明通过合成末端带有降冰片烯的活化酯功能化单体,末端带有降冰片烯聚乙二醇的亲水单体;在Grubbs催化剂作用下利用末端带有降冰片烯的活化酯功能化单体和亲水单体进行顺序开环易位聚合(ROMP)制备了两亲性嵌段刷型聚合物;再将酸或碱催化剂负载到分子刷的疏水部分,通过水相自组装构建了核内包含酸或碱催化剂的两亲性单分子纳米胶束。该胶束的特点在于将酸或碱催化剂固定在单分子纳米胶束中,并利用物理结构将他们分隔开。此类单分子催化纳米胶束有利于一锅法串联催化反应的依次进行,提高了反应效率,减少了有机溶剂的使用,且催化剂可回收再利用,符合绿色化工的要求。
本发明具有以下技术优势:
本发明首次公开了一种将酸或碱催化剂封装在高分子聚合物中,通过在水相中自组装成单分子纳米胶束的方法,酸或碱催化剂分别封装于疏水核内,两个重要单元反应(脱缩醛-Knoevenagel反应)结合成一步反应,没有中间体的生成且得到较高的转化率,避免了能源的损耗以及中间体的富集对环境产生的危害;且催化反应结束后还可以对单分子纳米胶束的回收再利用,又避免了再催化过程中对环境造成的二次污染问题,具有重要的环境和经济效益。
综上所述,本发明公开了基于降冰片烯开环易位聚合制备一种适于酸碱串联催化的单分子纳米胶束的方法。通过合成末端带有降冰片烯的活化酯功能化单体,末端带有降冰片烯聚乙二醇的亲水单体;在Grubbs催化剂作用下利用末端带有降冰片烯的活化酯功能化单体和亲水单体进行顺序开环易位聚合(ROMP)制备了两亲性嵌段刷型聚合物;再将酸或碱催化剂负载到分子刷的疏水部分,通过水相自组装构建了核内包含酸或碱催化剂的两亲性单分子纳米胶束。该胶束的特点在于将酸或碱催化剂固定在单分子纳米胶束中,并利用物理结构将他们分隔开。单分子纳米胶束自身的小尺寸效应、表面效应以及底物浓缩等效应使得底物先在含酸催化剂的疏水核内转化成对应的醛,再进入另一端疏水核被碱催化剂催化成对应的腈基衍生物,实现了高效的串联催化。
附图说明
下面结合附图对本发明的具体实施方式作进一步详细说明。
图1为实施例1所得的两亲性嵌段分子刷的1H NMR;
图2为实施例1所得的含酸的单分子纳米反应器(酸催化剂NB-ACA);
a)1H NMR;b)DLS分布图;c)TEM图;
图3为实施例1所得的含碱的单分子纳米反应器(碱催化剂NB-TAEA);
a)1H NMR;b)DLS分布图;c)TEM图;
图4为实施例1所得的可酸碱串联的单分子纳米反应器;
a)DLS分布图、b)、TEM图;
图5为实施例2所得的两亲性嵌段分子刷的1H NMR。
图6为串联催化的通用示意图。
具体实施方式
下面结合具体实施例对本发明进行进一步描述,但本发明的保护范围并不仅限于此:
NHS为N-羟基琥珀亚胺;
NB为Exo-5-降冰片烯-2-羧酸;
G3为Grubbs第三代催化剂;
DCM为二氯甲烷;
TAEA-Boc为二叔丁基(((2-氨基乙基)氮杂二酰基)双(乙烷-2,1-二酰基))二氨基甲酸酯;
TFA为三氟乙酸;
DCC为二环己基碳二亚胺;
DMAP为4-二甲氨基吡啶;
NHS为N-丙烯酸琥珀酰亚胺酯;
ACA为6-氨基己酸;
PEG2000为分子量是2000的聚乙二醇单甲醚;
TAEA为三(2-氨基乙基)胺;
在本发明中,没有明确告知的均是在室温(10~25℃);
滴加时间为5~10min。
冷冻干燥的温度为-100℃~-40℃
实施例1、
1)NB-NHS的制备:
在氮气氛围和冰浴条件下,将5g N-羟基琥珀亚酰胺(NHS)溶于30ml二氯甲烷,充分搅拌使其均匀的溶解,加入6g NB溶于10ml的二氯甲烷所形成的溶液;再加入13.4g二环己基碳二亚胺(DCC)和0.53g 4-二甲氨基吡啶(DMAP)溶于50ml二氯甲烷所形成的溶液;在室温下搅拌15h;过滤(弃滤渣),滤液用60ml*3的饱和食盐水洗涤三次,再用60ml*3的二氯甲烷萃取3次,所得的萃取层(位于下层)减压旋蒸去除二氯甲烷,得到粗产品;
粗产品经过快速硅胶色谱纯化(固定相为200-300目的硅胶,流动相为二氯甲烷),收集rf=0.5~0.8之间的洗脱液,经过减压旋蒸去除溶液(二氯甲烷)后,得到NB-NHS(外型的NB-NHS)。
1H NMR(400MHz,CDCl3)δ6.21-6.13(ddd,J=23.9,5.6,3.0Hz,2H),3.27(s,1H),3.00(s,1H),2.52-2.49(dd,J=9.0,4.5Hz,1H),2.05-2.02(dd,J=8.0,4.0Hz,1H),1.55-1.50(m,2H),1.46-1.44(d,J=9.0Hz,1H).
所述NB-NHS为2,5-二氧吡咯烷-1-基(2S)-双环[2.2.1]庚-5-烯-2-羧酸酯。
2)亲水单体NB-PEG2000的制备:
在氮气氛围和冰浴条件下,将10.85mmol(约1.5g)NB加到30ml二氯甲烷中;添加8.7mmol(17.4g)平均分子量为2000聚乙二醇(PEG2000)溶于50ml二氯甲烷所形成的溶液;再加入13.06mmol(约2.69g)DCC和4.34mmol(约0.53g)4-二甲氨基吡啶(DMAP)溶于10ml二氯甲烷所形成的溶液;在室温下搅拌15h;减压旋蒸去除溶剂(二氯甲烷)后,所得的粗产品用正己烷:乙醚=1:1体积比的混合溶液洗涤3次(每次的用量约为300ml);得到亲水单体NB-PEG2000。
1H NMR(400MHz,CDCl3)δ6.14-6.08(ddd,J=14.9,5.5,3.0Hz,2H),4.25-4.23(m,2H),3.82-3.53(m,144H),3.47-3.37(m,3H),3.04(s,1H),2.91(s,1H),2.27-2.24(dd,J=9.4,3.6Hz,1H),1.53-1.51(d,J=8.5Hz,1H),1.39-1.33(dd,J=13.0,7.9Hz,2H),1.25(s,1H)。
3)顺序开环易位聚合制备两亲性嵌段分子刷:
制备15mg/ml G3的DCM储备溶液,并将其在氮气氛围下保存。将0.03mmol(约7mg)步骤1)所得的NB-NHS溶解于0.2ml二氯甲烷中;再加入0.001mmol(约1.3mg)Grubbs第三代催化剂溶于0.1ml二氯甲烷所形成的溶液;在室温反应1min;再将反应液加到0.07mmol(约151mg)步骤2)所得的亲水单体NB-PEG2000溶于8ml二氯甲烷所形成的溶液中,继续在室温下反应9min;用乙基乙烯基醚(约0.1ml)淬灭反应;将反应液滴加到0~-10℃的正己烷:乙醚=1:1体积比的溶液(约50ml)中,收集不溶的固体,得到两亲性嵌段分子刷(两亲性嵌段刷型聚合物),两亲性嵌段分子刷的1H NMR如图1所示。
4)酸催化剂NB-ACA的制备:
将0.09mmol(约12.2mg)6-氨基己酸加入到30ml二甲基亚砜(DMSO)中,充分搅拌使其均匀的溶解,再滴加0.0024mmol(约100mg)步骤3)所得的两亲性嵌段分子刷溶于8mlDMSO所形成的溶液,在室温下搅拌15h;使用分子量为2000的透析袋对反应混合物进行透析处理(使用超纯水),时间为12~15小时(每隔4~6小时换一次,每次超纯水用量为1000ml);取透析处理所得的截留液,将其冷冻干燥去除溶剂(DMSO),得到末端带有酸催化剂的两亲性嵌段分子刷。
将5mg上述所得的末端带有酸催化剂的两亲性嵌段分子刷充分溶解到1ml四氢呋喃中,缓慢滴加5ml超纯水,搅拌1h。用氮气吹扫混合溶液直到四氢呋喃全部蒸发;得到1mg/ml的单分子纳米反应器(即,含酸的单分子纳米反应器)作为酸催化剂NB-ACA;其1H NMR、DLS分布、TEM,如图2所示。
5)碱催化剂NB-TREA的制备:
将0.14mmol(约50mg)TAEA-Boc溶解到3ml DMSO中,充分搅拌使其均匀的溶解,再滴加0.0024mmol(约100mg)步骤3)所得的两亲性嵌段分子刷溶于8ml DMSO所形成的溶液,在室温下搅拌15h;反应结束后,加入50ml冷乙醚,从而使得粗产品在50ml冷乙醚中沉淀,收集不溶物,将其溶解到体积比为4:1的DCM:TFA混合溶液(约8ml)中,在室温下搅拌2h,减压旋蒸去除溶剂(所述溶剂即指DCM:TFA体积比为4:1混合溶液),将所获得的固体溶解到5ml的DMSO中,加入过量(约10mg)的K2CO3,室温下继续搅拌6h,使用分子量为2000的透析袋对反应混合物进行透析处理(使用超纯水),时间为12~15小时(每隔4~6小时换一次,每次超纯水用量为1000ml);取透析处理所得的截留液,冷冻干燥去除溶剂(DMSO),得到末端带有碱催化剂的两亲性嵌段分子刷。
将5mg末端带有碱催化剂的两亲性嵌段分子刷充分溶解到1ml四氢呋喃中,缓慢滴加5ml超纯水,搅拌1h。用氮气吹扫混合溶液直到四氢呋喃全部蒸发;得到1mg/ml的单分子纳米反应器(含碱的单分子纳米反应器)作为碱催化剂NB-TREA。其1H NMR、DLS分布、TEM如图3所示。
6)可酸碱串联催化的单分子纳米反应器制备
以同样的浓度(1mg/ml)制备纳米反应器,将步骤4)所得的酸单分子纳米反应器和步骤5)所得的碱单分子纳米反应器以相同浓度等体积比混合,并且超声处理0.5h,通过DLS表征数据可以明显的看出,酸单分子纳米反应器的粒径分布在28nm,碱单分子纳米反应器的粒径分布在30nm,融合后的混合体系(可酸碱串联催化的单分子纳米反应器)其粒径分布在35nm,这表明了该体系下纳米反应器对催化剂包覆形成了有效的物理隔离。同时,通过TEM对混合体系拍摄的图片上依旧可以很清楚看到胶束粒径分布在20-30nm左右。其DLS分布、TEM如图4所示。
实施例2:
1)等同于实施例1
2)等同于实施例1
3)顺序开环易位聚合制备两亲性嵌段分子刷:
制备15mg/ml G3的DCM储备溶液,并将其在氮气氛围下保存。将0.008mmol(约2mg)步骤1)所得的NB-NHS溶解于0.05ml二氯甲烷中;再加入0.001mmol(约0.7mg)Grubbs第三代催化剂溶于0.1ml二氯甲烷所形成的溶液;在室温反应1min;再将反应液加到0.086mmol(约186mg)步骤2)所得的亲水单体NB-PEG2000溶于6ml二氯甲烷所形成的溶液中,继续在室温下反应9min;用乙基乙烯基醚淬灭反应;将反应液滴加到0℃~-10℃的正己烷:乙醚=1:1体积比的溶液中,收集不溶的固体,得到两亲性嵌段刷型聚合物;两亲性嵌段分子刷的1H NMR如图5所示。
4)酸催化剂NB-ACA的制备:
将0.04mmol(约5.8mg)6-氨基己酸加入到30ml二甲基亚砜(DMSO)中,充分搅拌使其均匀的溶解,再滴加0.0024mmol步骤3)所得的两亲性嵌段分子刷溶于8ml DMSO所形成的溶液,在室温下搅拌15h;使用分子量为2000的透析袋对反应混合进行透析处理(使用超纯水),时间为12~15小时;取透析处理所得的截留液,将其冷冻干燥去除溶剂(DMSO),得到末端带有酸催化剂的两亲性嵌段分子刷。
将5mg上述的末端带有酸催化剂的两亲性嵌段分子刷充分溶解到1ml四氢呋喃中,缓慢滴加5ml超纯水,搅拌1h。用氮气吹扫混合溶液直到四氢呋喃全部蒸发;得到1mg/ml的含酸单分子纳米反应器。
5)碱催化剂NB-TREA的制备:
将0.07mmol的TAEA-Boc溶解到3mlDMSO中,充分搅拌使其均匀的溶解,再滴加0.0024mmol步骤3)所得的两亲性嵌段分子刷溶于8ml DMSO所形成的溶液,在室温下搅拌15h;反应结束后,加入50ml冷乙醚,从而使得粗产品在50ml冷乙醚中沉淀,收集不溶物,将其溶解到体积比为4:1的DCM:TFA混合溶液中,在室温下搅拌2h,减压旋蒸去除溶剂,将所获得的固体溶解到5ml的DMSO中,加入过量(约10mg)的K2CO3,室温下继续搅拌6h,使用分子量为2000的透析袋对反应混合进行透析处理(使用超纯水),时间为12~15小时;取透析处理所得的截留液,冷冻干燥去除溶剂,得到末端带有碱催化剂的两亲性嵌段分子刷。将5mg上述的分子刷充分溶解到1ml四氢呋喃中,缓慢将5ml超纯水滴加到反应液中,搅拌1h。用氮气吹扫混合溶液直到四氢呋喃全部蒸发;得到1mg/ml的含碱单分子纳米反应器。
6)等同于实施例1的步骤6)。
实施例3:
1)等同于实施例1的步骤1);
2)亲水单体NB-PEG350的制备
在氮气氛围下和冰浴条件下,将11.03mmol(约1.5g)NB加到30ml二氯甲烷中;添加12mmol(约4.2g)平均分子量为350聚乙二醇(PEG2000)溶于50ml二氯甲烷所形成的溶液;再加入14.339mmol(约2.95g)二环己基碳二亚胺(DCC)和4.34mmol(约0.53g)4-二甲氨基吡啶(DMAP)溶于10ml二氯甲烷所形成的溶液;在室温下搅拌15h;减压旋蒸去除溶剂后,粗产品用正己烷:乙醚=1:1体积比的混合溶液洗涤3次;得到亲水单体NB-PEG350。
1H NMR(400MHz,CDCl3)δ6.14-6.08(ddd,J=14.9,5.5,3.0Hz,2H),4.25-4.23(m,2H),3.82-3.53(m,78H),3.47-3.37(m,3H),3.04(s,1H),2.91(s,1H),2.27-2.24(dd,J=9.4,3.6Hz,1H),1.53-1.51(d,J=8.5Hz,1H),1.39-1.33(dd,J=13.0,7.9Hz,2H),1.25(s,1H)。
步骤3)~步骤6)等同于实施例1的步骤3)~步骤6)。
实验一、催化效果的测试:
在室温下,将0.01g反应底物1,0.006g反应底物2,0.5ml浓度10mg/ml的单分子纳米胶束充分混合,在室温下搅拌(反应时间如下表1所示)。反应完成后,加入2ml乙醚萃取小分子有机物。分成位于上层的有机相和位于下层的水相,针对有机相通过GC-MS分析底物的转化率。单分子纳米胶束留在水相中,通过高温离心(80℃、10000r/min的转速,离心5~10分钟),最后经冷乙醚(0~5℃的乙醚20ml)洗涤回收。串联催化的通用示意图如图6。
表1、单分子纳米胶束串联催化缩醛的脱保护与Knoevenagel反应
测定单分子纳米胶束的催化效果如表1所示。可以看出,缩醛(底物1)的脱保护产物与丙二腈(底物2)发生Knoevenagel反应可以直接通过“一锅法”串联催化制备目标产物腈基衍生物。大大的简化了生产过程,从而获得很好的催化效果。实施例2对比实施例1,含酸的单分子纳米反应器催化效率为80%,含碱的单分子纳米反应器催化效率为83%,而酸碱串联催化效率低至76%。这是由于疏水链段太短等原因,导致酸催化剂或碱催化剂在短时间内没有完全催化底物,从而催化反应较低。实施例3对比实施例1,含酸的单分子纳米反应器催化效率为95%,含碱的单分子纳米反应器催化效率为94%,而酸碱串联催化效率低至37%。这是由于亲水链段分子量太小等原因,无法将酸或碱催化剂完全的包覆在核内,从而使酸催化剂和碱催化之间难免发生碰撞而相互影响,从而降低了串联催化效率。
实验二、回收实验:
将实验一的实验组3洗涤回收所得的单分子纳米胶束加入0.5ml超纯水中,以此代替实验一中“0.5ml浓度10mg/ml单分子纳米胶束溶液”;其余按照实验组1进行实验,重复5次后,所得转化率均大于90%。
最后,还需要注意的是,以上列举的仅是本发明的若干个具体实施例。显然,本发明不限于以上实施例,还可以有许多变形。本领域的普通技术人员能从本发明公开的内容直接导出或联想到的所有变形,均应认为是本发明的保护范围。
Claims (7)
1.适用于串联催化的单分子纳米胶束的制备方法,其特征在于包括以下步骤:
1)、利用NHS获得NB-NHS:
所述NHS为N-羟基琥珀亚酰胺;
NB-NHS为2,5-二氧吡咯烷-1-基(2S)-双环[2.2.1]庚-5-烯-2-羧酸酯;
2)、亲水单体NB-PEGm的制备:
将NB溶于溶剂A,加入PEGm、DCC、DMAP,在室温下搅拌反应12~16小时,反应结束后经后处理,得亲水单体NB-PEGm;
NB为5-羧酸-2-降冰片烯,PEGm为分子量是m的聚乙二醇单甲醚,DCC为二环己基碳二亚胺,DMAP为4-二甲氨基吡啶;
PEGm:NB:DCC:DMAP=0.8~1.5:1:0.9~1.7:0.1~0.8的摩尔比;
3)、开环易位聚合制备两亲性嵌段分子刷:
将步骤1)所得的NB-NHS溶解于溶剂B中;加入Grubbs催化剂,室温反应1~5min;再加入步骤2)所得的亲水单体NB-PEGm,继续在室温下反应5~10min,反应结束后经后处理,得两亲性嵌段分子刷;
所述NB-NHS:Grubbs催化剂:亲水单体NB-PEGm=5~50:1:50~95的摩尔比;
4)、核内含酸催化剂的单分子纳米反应器的构筑:
将步骤3)所得的两亲性嵌段分子刷溶于溶剂C中,加入氨基羧酸衍生物,在室温下反应1~15h,两亲性嵌段分子刷:氨基羧酸衍生物=1:10~60的摩尔比;经后处理,得到末端带有酸催化剂的两亲型嵌段分子刷;
将所得的末端带有酸催化剂的两亲型嵌段分子刷配制成浓度为0.5~1.5mg/ml的溶液,作为核内含酸催化剂的单分子纳米反应器溶液;
5)、核内含碱催化剂的单分子纳米反应器的构筑:
将步骤3)所得的两亲性嵌段分子刷溶于溶剂E中,添加末端带-NH2的衍生物,在室温下反应10~20h;两亲性嵌段分子刷:末端带-NH2的衍生物=1:10~60的摩尔比;
反应结束后进行沉淀处理,将所得沉淀物溶于试剂F与TFA的混合溶液中,室温下反应2±0.5h;经后处理,得到末端带有碱催化剂的两亲性嵌段分子刷;
将末端带有碱催化剂的两亲性嵌段分子刷配制成浓度为0.5~1.5mg/ml的溶液,作为核内含碱催化剂的单分子纳米反应器溶液;
所述末端带-NH2的衍生物为TAEA-Boc、PDMA-Boc、EDA-Boc;
6)、可酸碱串联催化的单分子纳米反应器制备:
将相同浓度的核内含酸催化剂的单分子纳米反应器溶液、核内含碱催化剂的单分子纳米反应器溶液,以等体积比融合;得到可酸碱串联催化的单分子纳米反应器。
2.根据权利要求1所述的适用于串联催化的单分子纳米胶束的制备方法,其特征在于:
所述步骤4)中的氨基羧酸衍生物为3-氨基丙酸、4-氨基丁酸、5-氨基戊酸、6-氨基己酸、7-氨基庚酸、8-氨基辛酸、9-氨基壬酸。
3.根据权利要求2所述的适用于串联催化的单分子纳米胶束的制备方法,其特征在于所述步骤2)中:
PEGm为PEG350、PEG2000、PEG5000。
4.根据权利要求3所述的适用于串联催化的单分子纳米胶束的制备方法,其特征在于所述步骤3)中的Grubbs催化剂为Grubbs I,Grubbs II,Grubbs III。
5.根据权利要求4所述的适用于串联催化的单分子纳米胶束的制备方法,其特征在于:
步骤2)的后处理为:反应所得物减压旋蒸去除溶剂A,所得粗产品用正己烷:乙醚=1:1体积比的混合溶液进行洗涤;得到亲水单体NB-PEGm;
所述步骤3)中:反应时间到达后,淬灭反应,将所得的反应液滴加至0~-10℃的正己烷:乙醚=1:1体积比的溶液中,收集不溶的固体,得到两亲性嵌段分子刷;
所述步骤4)的后处理为,将两亲性嵌段分子刷与氨基羧酸衍生物进行反应所得的反应混合物进行透析处理,透析处理时间为12~15小时,取透析处理所得的截留液,冷冻干燥去除溶剂C,得到末端带有酸催化剂的两亲型嵌段分子刷;
所述步骤5)的后处理为:反应所得物减压旋蒸去除溶剂,所得固体溶解于DMSO中,加入过量的K2CO3,室温下继续搅拌6±2h,反应混合物进行透析处理,透析处理时间为12~15小时;取透析处理所得的截留液,冷冻干燥去除溶剂,得到末端带有碱催化剂的两亲性嵌段分子刷。
6.根据权利要求5所述的适用于串联催化的单分子纳米胶束的制备方法,其特征在于:
所述步骤4)中:先将末端带有酸催化剂的两亲性嵌段分子刷溶解于溶剂D中,再加入超纯水搅拌,干燥至溶剂D蒸发,得到核内含酸催化剂的单分子纳米反应器;
所述步骤5)中,先将末端带有碱催化剂的两亲型嵌段分子刷充分溶解于溶剂G中,再加入超纯水搅拌,干燥至溶剂G蒸发,得到核内含碱催化剂的单分子纳米反应器的溶液。
7.根据权利要求6所述的适用于串联催化的单分子纳米胶束的制备方法,其特征在于:
所述步骤2)中的溶剂A为二氯甲烷;
所述步骤3)中的溶剂B为二氯甲烷;
所述步骤4)中的溶剂C为二甲基亚砜、溶剂D为四氢呋喃;
所述步骤5)中:溶剂E为二甲基亚砜、溶剂F为二氯甲烷、溶剂G为四氢呋喃。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103992484A (zh) * | 2014-05-15 | 2014-08-20 | 长春理工大学 | 链端带有大分子的刷状嵌段共聚物及其制备方法 |
CN110437426A (zh) * | 2019-08-22 | 2019-11-12 | 苏州大学 | 一种刷形共聚物及其制备方法 |
CN111808247A (zh) * | 2020-05-23 | 2020-10-23 | 浙江理工大学 | 基于分子刷的tempo纳米反应器的制备及其用途 |
CN112876630A (zh) * | 2021-01-20 | 2021-06-01 | 浙江理工大学 | 基于溴代单体聚合改性的纳米胶束的制备方法及其用途 |
CN112876688A (zh) * | 2021-01-20 | 2021-06-01 | 浙江理工大学 | 适于串联催化的纳米胶束的制备方法 |
CN113354824A (zh) * | 2021-07-14 | 2021-09-07 | 天津大学 | 一种两亲性嵌段共聚物的应用及可降解光子晶体微球的制备方法 |
Family Cites Families (3)
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US20090298676A1 (en) * | 2005-10-26 | 2009-12-03 | Michael Meier | Unimolocular Micelles Containing Metal Nanoparticles and their Use as Catalyst for Synthesis of Carbon-Carbon-Bonds |
WO2015024093A1 (en) * | 2013-08-23 | 2015-02-26 | Her Majesty The Queen In Right Of Canada, As Represented By The Minister Of National Defence | Polymer-supported metal nanoparticles, process for production thereof and polymeric nanoreactors produced therefrom |
US20180067393A1 (en) * | 2016-09-02 | 2018-03-08 | California Institute Of Technology | Photoactive catalyst compositions |
-
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103992484A (zh) * | 2014-05-15 | 2014-08-20 | 长春理工大学 | 链端带有大分子的刷状嵌段共聚物及其制备方法 |
CN110437426A (zh) * | 2019-08-22 | 2019-11-12 | 苏州大学 | 一种刷形共聚物及其制备方法 |
CN111808247A (zh) * | 2020-05-23 | 2020-10-23 | 浙江理工大学 | 基于分子刷的tempo纳米反应器的制备及其用途 |
CN112876630A (zh) * | 2021-01-20 | 2021-06-01 | 浙江理工大学 | 基于溴代单体聚合改性的纳米胶束的制备方法及其用途 |
CN112876688A (zh) * | 2021-01-20 | 2021-06-01 | 浙江理工大学 | 适于串联催化的纳米胶束的制备方法 |
CN113354824A (zh) * | 2021-07-14 | 2021-09-07 | 天津大学 | 一种两亲性嵌段共聚物的应用及可降解光子晶体微球的制备方法 |
Non-Patent Citations (5)
Title |
---|
"Stereochemical Control Yields Mucin Mimetic Polymers";Austin G. Kruger et al.;《ACS Central Science》;第7卷;624-630 * |
"基于聚合物分子刷及其纳米管状材料的合成与催化应用";熊林峰;《中国博士学位论文全文数据库(工程科技I辑)》(第1期);1-125 * |
"负载三乙烯二胺纳米反应器的制备及其催化应用";王程展 等;《浙江理工大学学报》;第45卷(第4期);512-519 * |
Yanfeng Zhang et al.."PEG-Polypeptide Dual Brush Block Copolymers: Synthesis and Application in Nanoparticle Surface PEGylation".《ACS Macro Letters》.2013,第2卷809-813. * |
线型和星型聚乙二醇-聚己酸内酯两亲嵌段共聚物聚集行为;鲁成飞;郭圣荣;张亚琼;姚炎庆;;华东理工大学学报(自然科学版)(06);655-660 * |
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