CN105884681A - 一种聚乙二醇中吡啶衍生物的合成方法 - Google Patents

一种聚乙二醇中吡啶衍生物的合成方法 Download PDF

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CN105884681A
CN105884681A CN201410592110.1A CN201410592110A CN105884681A CN 105884681 A CN105884681 A CN 105884681A CN 201410592110 A CN201410592110 A CN 201410592110A CN 105884681 A CN105884681 A CN 105884681A
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pyridine
glycol
aldehyde
methylene
double
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宋飞跃
单文华
杜百祥
李玉玲
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Jiangsu Normal University
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Jiangsu Normal University
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Abstract

本发明涉及一种吡啶衍生物的合成，具体是涉及3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)衍生物的合成，是以聚乙二醇为溶剂，以醛、2，4-二羟基吡啶为原料，在醋酸铵的催化下，一锅法一步反应生成。合成路线简捷，条件温和，总收率达到75％以上。

Description

一种聚乙二醇中吡啶衍生物的合成方法
技术领域
本发明属于有机合成技术领域，涉及3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)的有机合成方法。
背景技术
3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)化合物中具有吡啶结构。近年来，二氢吡啶酮衍生物由于其显着的治疗和生物活性而受到越来越多的关注，如抗菌，抗真菌，抗肿瘤，而且还是抗HIV-1特异性逆转录酶的抑制剂。2-吡啶酮已经被发现可作为特定的人类免疫缺陷病毒1(HIV-1)的非核苷类逆转录酶抑制剂的和具有很强的抗原生动物和抗菌活性，还可以作为强心药，用于治疗心脏衰竭。在最近研究具有喜树碱结构的抗肿瘤剂的合成方法中，2-吡啶酮也可以作为一些生物及其药理学上有力的多环化合物的重要中间体。2009年Demuner以芳醛，6-甲基-4-羟基吡啶-2-酮为原料在吡啶催化下合成吡啶衍生物(A.J.Demuner，V.M.M.Valente，L.C.A.Barbosa，A.Rathi，T.J.Donohoe，A.L.Thompson，Molecules，14(12)，4973-4986；2009)；1976年，Findlay等人以芳醛，6-甲基-4-羟基吡啶-2-酮为原料在醇中以吡啶、哌啶为催化剂合成该类化合物(J.A.Findlay，J.Krepinsky，F.Y.Shum，W.H.J.T am.Canadian Journal of Chemistry，54(2)，270-4；1976.)。上述合成方法使用了有机溶剂或有毒的催化剂，有较大的污染，而在聚乙二醇中通过芳醛、2，4-二羟基吡啶为原料一步合成含2-吡啶酮衍生物还未见报道。
发明内容
本发明的目的在于提供一种合成3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)的方法：醛、2，4-二羟基吡啶为原料，醋酸铵为催化剂，按摩尔比1∶2在聚乙二醇(PEG)中经一锅法一步生成(如图1所示)。本发明在合成过程中引入聚乙二醇，提供一种温和高效环境友好、应用范围广，产率高且反应介质可重复使用的合成方法。
本发明通过下述方法实现的：在5毫升聚乙二醇中加入1毫摩尔的醛，2毫摩尔的2，4-二羟基吡啶和0.2毫摩尔的醋酸铵，在80℃下反应0.75-5.5小时，即得到相应的3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)衍生物。
所述的聚乙二醇为PEG-400。
所述的醛为芳香醛或杂芳醛。
与文献中已有方法相比，本发明具有以下优点：
本发明在合成3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)衍生物的过程中引入聚乙二醇，是一种绿色合成方法。低分子量聚乙二醇PEG-400是一种常见的液体低聚物，具有低毒、可生物降解、不挥发、不可燃、价格低廉等优点；它对大多数有机及金属有机化合物溶解性能良好，在酸、碱、O2和H2O2氧化体系以及NaBH4还原体系中都很稳定，目前用PEG-400作为绿色反应介质已开始引起人们的广泛关注。
附图说明
图1是化合物3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)的合成路线图；
具体实施方式
下面结合附图1及实施例对本发明作进一步描述。
实施例1：
3，3’-[(3-氯苯基)亚甲基]双(吡啶-2，4-二醇)的制备：在5毫升PEG-400中加入1毫摩尔的3-氯苯甲醛(0.141g)，和2毫摩尔的2，4-二羟基吡啶(0.222g)，0.2毫摩尔的醋酸铵(0.154g)，在80℃下反应1小时，TLC跟踪监测，反应结束后，直接过滤，产物用少量水洗涤，干燥后用乙醇重结晶即得到相应的3，3’-[(3-氯苯基)亚甲基]双(吡啶-2，4-二醇)(0.279g，产率81％)。本品为白色粉末，mp：159-161℃。
实施例2：
3，3’-[(4-氯苯基)亚甲基]双(吡啶-2，4-二醇)的制备：在5毫升PEG-400中加入1毫摩尔的4-氯苯甲醛(0.141g)，和2毫摩尔的2，4-二羟基吡啶(0.222g)，0.2毫摩尔的醋酸铵(0.154g)，在80℃下反应2小时，TLC跟踪监测，反应结束后，直接过滤，产物用少量水洗涤，干燥后用乙醇重结晶即得到相应的3，3’-[(4-氯苯基)亚甲基]双(吡啶-2，4-二醇)(0.289g，产率84％)。本品为白色粉末，mp：233-234℃。
实施例13：
3，3’-[(4-甲基苯基)亚甲基]双(吡啶-2，4-二醇)的制备：在5毫升PEG-400中加入1毫摩尔的3-甲基苯甲醛(0.120g)，和2毫摩尔的2，4-二羟基吡啶(0.222g)，0.2毫摩尔的醋酸铵(0.154g)，在80℃下反应4小时，TLC跟踪监测，反应结束后，直接过滤，产物用少量水洗涤，干燥后用乙醇重结晶即得到相应的3，3’-[(4-甲基苯基)亚甲基]双(吡啶-2，4-二醇)(0.259g，产率80％)。本品为白色粉末，mp：280-282℃。
实施例1-18的反应原料，反应条件及产率见表1。
表1实施例1-18的反应原料，反应条件及产率
Entry Ar product Time(h) Yield(％)
1 3-ClC6H4 4a 1 81
2 4-ClC6H4 4b 2 84
3 2，3-Cl2C6H3 4c 3 75
4 2，4-Cl2C6H3 4d 2 85
5 2-NO2C6H4 4e 5.5 70
6 3-NO2C6H4 4f 1 85
7 2-CH3OC6H4 4g 1.5 90
8 3-CH3OC6H44 4h 4.5 86
9 3，4-(OCH3)2C6H3 4i 4 70
10 3-HOC6H4 4j 2 83
11 4-HOC6H4 4k 1.75 82
12 3，4-(CH3)2C6H3 4l 3 82
13 4-H3CC6H4 4m 4 80
14 4-BrC6H4 4n 2 83
15 3-FC6H4 4o 1.75 88
16 3，5-(OCH3)2-4-HOC6H2 4p 1.75 78
17 3-OH-4-CH3OC6H3 4q 1 80
18 3，4-(OCH2O)C6H3 4r 0.75 87
由表1可知，本发明的方法原料易得，操作简单安全，反应条件温和、收率高，后处理简单，原子经济性高，而且使用PEG-400环境污染小，因而具有极大的实施价值和潜在社会经济效益。

Claims (4)

1.本发明涉及3，3-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)的合成，是以醛、2，4-二羟基吡啶为原料，经三组分一锅法一步反应生成。
2.按照权利要求(1)所述的3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)衍生物的合成方法，其特征是合成的反应条件是以醋酸铵为催化剂，醛、2，4-二羟基吡啶在聚乙二醇中反应，适宜的条件是常压、80℃和反应0.75-5.5小时，物料的摩尔比为醛：2，4-二羟基吡啶：醋酸铵＝1∶2∶0.2。
3.按照权利要求(1)所述的3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)衍生物的合成方法，其特征在于所述的聚乙二醇为PEG-400。
4.按照权利要求(1)所述的3，3’-[(4-芳基)亚甲基]双(吡啶-2，4-二醇)衍生物的合成方法，其特征在于所述的醛为芳香醛或杂芳醛。
CN201410592110.1A 2014-10-24 2014-10-24 一种聚乙二醇中吡啶衍生物的合成方法 Pending CN105884681A (zh)

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Cited By (1)

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CN111944139A (zh) * 2020-06-30 2020-11-17 名畔科技(镇江)有限公司 一种表面活性剂、表面活性剂的合成方法及应用

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CN111944139B (zh) * 2020-06-30 2023-06-06 名畔科技(镇江)有限公司 一种表面活性剂、表面活性剂的合成方法及应用

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Application publication date: 20160824