CN114618459A - 一种含多卤素官能团的混合模式色谱固定相及其制备和应用 - Google Patents
一种含多卤素官能团的混合模式色谱固定相及其制备和应用 Download PDFInfo
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01D15/32—Bonded phase chromatography
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01D15/08—Selective adsorption, e.g. chromatography
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B—PERFORMING OPERATIONS; TRANSPORTING
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Abstract
Description
技术领域
本发明涉及液相色谱固定相,具体地说是一种含多卤素的混合模式色谱固定相。
技术背景
混合模式色谱(mixed-mode chromatography,MMC)是在一根色谱柱上同时存在两种或多种分离机理的色谱分离技术,是多种化合物分离和分析的有力工具。在MMC中固定相与分析物质间存在多种作用力,如疏水作用、静电作用、氢键作用、偶极-偶极等作用力为同时分离多种化合物提供更好地选择性,扩大样品的检测范围,可实现根据样品特性在不同模式下进行分离,这对复杂样品的分析是十分有利的。如固定相带有烷基链和极性基团,则可以提供疏水和亲水作用,而能够实现反相/亲水(RPLC/HILIC) 的分离,能同时用于极性和非极性物质的分析。
反相/离子交换混合模式色谱是在反相色谱固定相表面上引入带有静电作用的极性基团,将静电作用与疏水作用结合,使分离效果不同于常规普通反相色谱的分离效果[McCalley D.V,J.Chromatogra.A.2007,1138,65-72]。亲水/离子交换混合模式色谱可广泛应用于多肽与蛋白的分离,通过使用带有电荷的极性色谱固定相和含有高比例有机相的流动相,利用分析目标物通过与固定相发生亲水作用与电荷作用以达到分离效果[Hodges,R.S.et al,J. Sep.Sci,2008,31,2754-2773]。反相/亲水混合模式色谱固定相可在水相较高的流动相条件下具有更好的兼容性与稳定性,且能够很好地改善碱性化合物的峰形,可以实现酸性化合物、碱性化合物与中性化合物的分离[Shi,Z.G. et al,Anal.Chim.Acta,2015,182-190]。当前,尚未出现制备含多卤素的混合模式色谱固定相的报道。
发明内容
本发明的目的是提供一种含多卤素官能团的混合模式色谱固定相。该键合相包含氨基、羧基、酰胺基团及多卤素,其制备方法简单,适用性广泛。
本发明的技术方案是:液相色谱固定相,其特征在于结构为:
其中Silica Gel为硅胶,R1是C1-C10的烷基链,R2是C1-C10的烷基链,R3是含卤素的C1-C20的烷基链或环烷烃(F、Cl、Br中的一种或二种以上), R4是含卤素的C1-C20的烷基链或环烷烃(F、Cl、Br中的一种或二种以上)。
本发明还提供了上述固定相的制备方法,其特征在于包括如下步骤:
a.硅烷化:在氮气和/或氩气保护下,在有机溶剂中加入硅烷偶联剂和经120-160℃干燥8~24小时的微球形硅胶,在80~100℃下反应8~24小时,过滤,依次用甲醇、体积比1-5:1的乙醇水、甲醇、四氢呋喃洗涤,所得固体于干燥箱中40~80℃条件下干燥8~24小时,制备得到多氨基硅胶;
以每克硅胶计,硅烷偶联剂的用量为1-10mmol,有机溶剂的用量为 5-10mL;
b.亲核反应:在上述制备的多氨基硅胶中加入有机溶剂和含多卤素酸酐,再加入碱性催化剂,在25~80℃下反应8~48小时,过滤,依次用乙醇、乙酸钠溶液、水、甲醇洗涤,所得固体于干燥箱中40~80℃条件下干燥8~24小时,制备得到色谱固定相。
以每克多氨基硅胶计,含多卤素酸酐的用量为0.3-2.4mmol,有机溶剂的用量为5-10mL,碱性催化剂的用量为0.1-15mmol。
本发明具有如下优点:
1.结构新颖。本发明首次提出含有多卤素的混合模式色谱固定相。该固定相结构中多卤素和酰胺官能基团,同时带有可电离的氨基和羧基基团,使得固定相具有多种作用力如静电作用力、氢键作用力、偶极-偶极等,对绝大部分天然产物及药物具有很好的分离选择性,可广泛用于各类样品的分离分析及纯化制备。
2.本发明提供的液相色谱固定相制备过程简单可靠,有利于实现产业化。
附图说明
图1为实施例5的色谱图;
图2为实施例6的色谱图。
具体实施方式
下面结合实例,对本发明做进一步说明。实例仅限于说明本发明,而非对本发明的限定。
实施例1
在氮气保护下,向100mL烧瓶中加入10g经160℃干燥16小时的微球形硅胶(粒径为3.5μm,孔径为10nm)、6mL N-(2-氨乙基)-氨丙基三甲氧基硅烷和60mL二甲苯,在110℃下反应16小时,过滤,依次用甲醇、体积比5:1的乙醇水、甲醇、四氢呋喃洗涤,所得固体在干燥箱中80℃条件下干燥16个小时,制备得到N-(2-氨乙基)-氨丙基硅胶。
向250mL烧瓶中加入10g氨基硅胶、3g 4-二甲氨基吡啶、8.9g氯菌酸酐(摩尔数为24mmol)和100mL N,N-二甲基甲酰胺在60℃下反应24 小时,过滤,依次用乙醇、50mM乙酸钠溶液、水、甲醇洗涤,所得固体在干燥箱中80℃条件下干燥16个小时,得到色谱固定相1,结构如下:
实施例2
在氮气保护下,向100mL烧瓶中加入10g经160℃干燥16小时的微球形硅胶(粒径为2.5μm,孔径为10nm)、6mL N-(2-氨丙基)-氨丙基三甲氧基硅烷和60mL二甲苯,在80℃下反应24小时,过滤,依次用甲醇、体积比5:1的乙醇水、甲醇、四氢呋喃洗涤,所得固体在干燥箱中80℃条件下干燥16个小时,制备得到N-(2-氨丙基)-氨丙基硅胶。
向250mL烧瓶中加入10g氨基硅胶、5mL吡啶、5.5g 3,4-(3-氯丙基) 丁二酸酐(摩尔数为20mmol)和100mL N,N-二甲基甲酰胺在40℃下反应 24小时,过滤,依次用乙醇、50mM乙酸钠溶液、水、甲醇洗涤,所得固体在干燥箱中80℃条件下干燥24个小时,得到色谱固定相2,结构如下:
实施例3
操作过程和条件同实施例2,与实施例2不同之处在于,使用4,5,6,7- 四氯六氢苯酐(摩尔数为15mmol)代替3,4-(3-氯丙基)丁二酸酐(摩尔数为16mmol),得到色谱固定相3,结构如下:
实施例4
在氮气保护下,向100mL烧瓶中加入10g经160℃干燥16小时的微球形硅胶(粒径为5μm,孔径为10nm)、8mL N-(2-氨己基)-氨丙基三甲氧基硅烷和60mL二甲苯,在110℃下反应16小时,过滤,依次用甲醇、体积比3:1的乙醇水、甲醇、四氢呋喃洗涤,所得固体在干燥箱中80℃条件下干燥16个小时,制备得到N-(2-氨己基)-氨丙基硅胶。
向250mL烧瓶中加入10g氨基硅胶、3mL 1,5-二氮杂双环[4.3.0]壬-5- 烯、8.9g氯菌酸酐(摩尔数为24mmol)和100mL二甲亚砜在40℃下反应 48小时,过滤,依次用乙醇、50mM乙酸钠溶液、水、甲醇洗涤,所得固体在干燥箱中80℃条件下干燥16个小时,得到色谱固定相4,结构如下:
实施例5
使用实施例1所得色谱固定相1装填4.6×50mm色谱柱,用于中性化合物的分离分析,该固定相对中性化合物具有良好的选择性。如图1所示,色谱条件为:
色谱柱:4.6×50mm;
样品:中性化合物混标(尿嘧啶1mg/mL,硝基苯1mg/mL,萘2mg/mL,芴2.2mg/mL);
溶剂:A:乙腈,B:水;
洗脱:A:B=50:50(V/V);
流速:1.5mL/min;
检测波长:PDA(190nm-400nm)&UV(254nm);
实施例6
使用实施例1所得色谱固定相1装填4.6×50mm色谱柱,用于中性化合物与碱性化合物的分离分析,对不同类型化合物具有良好的选择性。如图2所示,色谱条件为:
色谱柱:4.6×50mm;
样品:中性和碱性化合物混标(尿嘧啶1mg/mL,对羟基苯甲酸丁酯 1.2mg/mL,阿米替林2.5mg/mL);
溶剂:A:乙腈,B:200mM甲酸铵(pH=3.2);
洗脱:A:B=70:30(V/V);
流速:1.5mL/min;
检测波长:PDA(190nm-400nm)&UV(254nm);
实施例7
使用不同类型的色谱固定相装填4.6×50mm色谱柱,用于酚酸类和苯丙酸类化合物的分离分析。测试结果见下表,色谱条件为:
色谱柱:4.6×50mm;
样品:混标(咖啡酸0.10mg/mL,阿魏酸0.05mg/mL);
溶剂:A:乙腈,B:0.1%甲酸水;
洗脱:梯度0~10~15min,5%~30%~90%A;
流速:1.0mL/min;
检测波长:PDA(190nm-400nm)&UV(254nm);
实施例1中制备的固定相A由于存在多卤素原子,极性作用增强,因此对咖啡酸的保留比另外两种固定相的保留更短;且固定相A具有特殊的立体结构,并且根据咖啡酸与阿魏酸的立体结构间的差异,对两种化合物的分离选择性更好。
实施例8
使用不同类型的色谱固定相装填4.6×50mm色谱柱,用于木脂素类和蒽醌类化合物的分离分析。测试结果见下表,色谱条件为:
色谱柱:4.6×50mm;
样品:混标(羟基茜草素0.20mg/mL,五味子甲素0.50mg/mL);
溶剂:A:乙腈,B:0.1%甲酸水;
洗脱:梯度0~10min,50%~90%A;
流速:1.0mL/min;
检测波长:PDA(190nm-400nm)&UV(203nm);
实施例1中制备的固定相A由于存在多卤素原子且具有特殊的立体结构,因此对两种化合物的分离选择性更好。
Claims (10)
2.按照权利要求1所述的色谱固定相,其特征在于:每克硅胶上含有0.3-2.4mmolR3。
3.一种权利要求1或2所述的固定相的制备方法,其特征在于,包括如下步骤:
a.硅烷化:在氮气和/或氩气保护下,在有机溶剂中加入硅烷偶联剂和经120-160℃干燥8~24小时的微球形硅胶,在80~100℃下反应8~24小时,过滤,依次用甲醇、体积比1-5:1的乙醇水、甲醇、四氢呋喃洗涤,所得固体于干燥箱中40~80℃条件下干燥8~24小时,制备得到多氨基硅胶;
b.亲核反应:在上述制备的多氨基硅胶中加入有机溶剂和含多卤素酸酐,再加入碱性催化剂,在25~80℃下反应8~48小时,过滤,依次用乙醇、乙酸钠溶液、水、甲醇洗涤,所得固体于干燥箱中40~80℃条件下干燥8~24小时,制备得到色谱固定相。
5.按照权利要求3所述的制备方法,其特征在于:步骤a所用的有机溶剂为氯苯、甲苯、二甲苯、正庚烷、异辛烷中的一种或二种以上;
步骤b所用的有机溶剂为N,N-二甲基甲酰胺、甲苯、二甲苯、二甲亚砜中的一种或二种以上。
7.按照权利要求3所述的制备方法,其特征在于:步骤b所用的碱性催化剂为二异丙基乙胺、1,8-二氮杂环[5,4,0]十一烯-7、1,5-二氮杂双环[4.3.0]壬-5-烯、N,N-二甲基吡啶、吡啶、咪唑中的一种。
8.按照权利要求3所述的制备方法,其特征在于:
步骤a所用的有机溶剂的用量为每克硅胶5-10mL;
步骤a所用的硅烷偶联剂的用量为每克硅胶1-10mmol;
步骤b所用的有机溶剂的用量为每克多氨基硅胶5-10mL;
步骤b所用的含多卤素酸酐的用量为每克多氨基硅胶0.3-2.4mmol;
步骤b所用的碱性催化剂的用量为每克多氨基硅胶0.1-15mmol。
9.一种权利要求1或2所述的固定相在色谱分离过程中的应用。
10.按照权利要求9所述的应用,其特征在于:色谱分离模式为反相色谱分离和离子交换分离,对含有极性基团的化合物具有良好的保留及分离选择性。
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