CN110606843A - 双吡啶酮腙-2-乙酰基吡嗪的结构、制备和用途 - Google Patents

双吡啶酮腙-2-乙酰基吡嗪的结构、制备和用途 Download PDF

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CN110606843A
CN110606843A CN201910939457.1A CN201910939457A CN110606843A CN 110606843 A CN110606843 A CN 110606843A CN 201910939457 A CN201910939457 A CN 201910939457A CN 110606843 A CN110606843 A CN 110606843A
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谭学杰
刘帅
邢殿香
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Abstract

本发明涉及一种化合物的结构、制备方法及部分性质。这种化合物外观呈块状黄色晶体，熔点126‑127℃，分子式C17H14N6，化学名为：E‑2‑(1‑((二(吡啶‑2‑基)亚甲基)亚肼基)乙基)吡嗪。这种化合物的结构详见说明书，它具有一定的荧光性质及抗癌活性。

Description

双吡啶酮腙-2-乙酰基吡嗪的结构、制备和用途
【技术领域】
本发明涉及有机合成、光学材料和药物化学领域，可以使用简单方法合成较复杂的产物，其优点在于化合物结构的新颖性和简单易行的合成方法。
背景技术
席夫碱类化合物具有一定的药理学和生理学活性，近年来一直是引人注目的研究对象。席夫碱类化合物及其配合物具有抗结核、抗癌、抗菌等药理作用；且其生物活性和金属的配位有关，广泛应用于疾病治疗、药物合成、生化反应、催化、生物调节剂、热敏或者压敏材料中的染料、聚合物改性、分析试剂、螯合剂等方面。
席夫碱主要是指含有亚胺或甲亚胺特征基团(-RC＝N-)的一类有机化合物，通常席夫碱是由胺和活性羰基缩合而成。席夫碱类化合物及其金属配合物主要在医药学、催化、分析化学、腐蚀以及光致变色领域有重要应用。在医学领域，席夫碱具有抑菌、杀菌、抗肿瘤、抗病毒的生物活性；在催化领域，席夫碱的钴、镍和钯的配合物已经作为催化剂使用；在分析化学领域，席夫碱作为良好配体，可以用来鉴别、鉴定金属离子和定量分析金属离子的含量；在腐蚀领域，某些芳香族的席夫碱经常作为铜的缓蚀剂；在光致变色领域，某些含有特征基团的席夫碱也具有独特的应用。
发明内容
本发明的内容是合成一种可用作荧光材料及药物分子的化合物，其化合物外观呈淡黄色块状晶体，熔点126-127℃，分子式C17H14N6，分子量 302.14；元素分析结果(％)：实验值：C,67.55，H,4.77，N,27.81；理论值： C,67.54，H,4.7，N,27.80；化学名为：E-2-(1-((二(吡啶-2-基)亚甲基) 亚肼基)乙基)吡嗪，结构如下：
1、结构鉴定:
元素分析表明这种化合物具有的分子式为C17H14N6；单晶结构分析表明，该化合物晶体属于单斜晶系，空间群为Cc， β＝127.041(6)°，Z＝4，1HNMR谱见附图1；附图2、附图3分别是该化合物的热椭球晶体结构图和晶体结构堆积图。
2、合成方法。
合成方法一，特征在于：以双(2-吡啶)酮腙和2-乙酰基吡嗪为原料，在合适的有机溶剂中一步完成。步骤如下：
1)将双(2-吡啶)酮腙全部溶于合适的有机溶剂后，按照一定的物质的量之比加入2-乙酰基吡嗪，在一定温度下搅拌或研磨反应几小时即可完成。
2)过滤，待滤液自然挥发，析出的淡黄色块状晶体即为目标产物；若采用固相反应，则反应完毕用合适的有机溶剂重结晶即可得目标产物晶体。
合成方法二，特征在于：以双(2-吡啶)酮腙和2-乙酰基吡嗪为原料，在合适的有机溶剂中一步完成。步骤如下：
1)将2-乙酰基吡嗪全部溶于合适的有机溶剂后，按照一定的物质的量之比加入双(2-吡啶)酮腙，在一定温度下搅拌或研磨反应几小时即可完成。
2)过滤，待滤液自然挥发，析出的淡黄色块状晶体即为目标产物；若采用固相反应，则反应完毕用合适的有机溶剂重结晶即可得目标产物晶体。
以上两种方法的区别在于反应物的加料顺序不同，但反应物的摩尔比均介于4:1至1:4之间。
以上两种方法中的有机溶剂(包括反应用溶剂或重结晶用溶剂)选自：甲醇、乙醇、乙腈、二氯甲烷、氯仿、四氢呋喃、丙酮等，反应时也可以不用有机溶剂，原料之间直接反应(即固相反应)。
优选的,所述反应温度为常温或加热回流，反应方法为搅拌或研磨。
优选的，所述反应时间选自：1－6h。
本发明的有益效果是：能够以比较简单的步骤和反应物合成比较复杂的功能分子材料。
3、紫外和荧光性质
此化合物的紫外谱图中，292nm附近有一个强吸收峰；从荧光光谱上可见，在380-410nm范围内有很强的荧光发射峰。紫外光谱、荧光光谱分别见附图 4、附图5，实验结果表明该物质具有较好的荧光性质。
4、体外抗肿瘤活性：
将处于对数期生长的A549肺癌细胞，A375人类恶性黑色素瘤细胞和HeLa宫颈癌细胞，分别用0.25％胰酶消化细胞，使其成为单细胞，用含10％胎牛血清的F12K培养液制成浓度为1.25×107个/L的单细胞悬液，将细胞接种于 96孔培养板中，每孔200μL(每孔2.5×103个细胞)。将96孔细胞培养板置于CO2培养箱中，在37℃，5％CO2条件下，培养48h。
当孔内细胞长满(90％满即可)时，按实验分组加入不同剂量的本席夫碱溶液(200μL/孔)，使待测化合物的终浓度分别为6.25μM、12.5μM、25μM、 50μM、100μM、200μM，每组设3个复孔，培养96h。
各个孔中分别加入20μL浓度为0.5g/L的MTT，继续培养4h，使MTT 还原为甲瓒(Formazan)。吸出全部上清液后，每孔加入200μL的DMSO，震摇15min，使甲瓒充分溶解后，运用酶联免疫检测仪测定490nm处的吸光度(OD 值)。然后按照下式进行计算：
细胞抑制率％＝(对照组OD值-实验组OD值)/对照组OD值×100％
测试结果表明，该席夫碱对A549肺癌细胞，A375人类恶性黑色素瘤细胞和HeLa宫颈癌细胞的IC50(药物的半数抑制浓度)分别为350、460、453μ mol/L，表明该化合物对这三种癌细胞有微弱的抑制效果。
具体实施方式
为了更好的理解本发明内容，下面通过一个具体实施例进一步说明本发明的技术方案：
实施例1
称取1.982g(约0.01mol)双(2-吡啶)酮腙溶于20ml无水乙醇中，将溶液放入烧瓶内，放在恒温加热磁力搅拌器上搅拌，称取1.221g(约0.01mol) 2-乙酰基吡嗪加入溶液中，50℃恒温回流反应3小时。溶液由无色透明变为橙黄色，反应结束后，过滤，滤液静置，自然挥发。得到两种物质，一种为橘红色棒状晶体，一种为块状黄色晶体，块状黄色晶体即为目标产物，产率约为86％。
附图说明
附图1是E-2-(1-((二(吡啶-2-基)亚甲基)亚肼基)乙基)吡嗪的1HNMR谱图(DMSO-D6)。
附图2是E-2-(1-((二(吡啶-2-基)亚甲基)亚肼基)乙基)吡嗪的晶体结构图。
附图3是E-2-(1-((二(吡啶-2-基)亚甲基)亚肼基)乙基)吡嗪的晶体结构堆积图。
附图4是E-2-(1-((二(吡啶-2-基)亚甲基)亚肼基)乙基)吡嗪的紫外光谱图(10-5mol/L,CH2CL2)。
附图5是E-2-(1-((二(吡啶-2-基)亚甲基)亚肼基)乙基)吡嗪的荧光光谱图(10-5mol/L,CH2CL2)。

Claims (4)

1.一种化合物晶体，外观呈块状黄色晶体，熔点126-127℃，分子式C17H14N6，化学名为：E-2-(1-((二(吡啶-2-基)亚甲基)亚肼基)乙基)吡嗪，结构如下：
该物质晶体属于单斜晶系，空间群为Cc， β＝127.041°，Z＝4。
2.如权利要求1中所述化合物晶体的合成方法，其特征在于：以2-乙酰基吡嗪和双(2-吡啶)酮腙为原料，反应温度为常温或加热至回流，在甲醇、乙醇、乙腈、二氯甲烷、氯仿、四氢呋喃、丙酮等有机溶剂中反应，步骤如下：
1)将2-乙酰基吡嗪全部溶于有机溶剂后，按4:1-1:4的物质的量之比加入双(2-吡啶)酮腙，在一定温度下搅拌反应3h即可完成；固相反应可以不用溶剂，原料之间直接反应；
2)过滤，待滤液自然挥发，析出的块状黄色晶体即为目标产物；若采用固相反应，则可用甲醇、乙醇、乙腈、二氯甲烷、氯仿、四氢呋喃、丙酮等有机溶剂重结晶，可得目标产物晶体。
3.如权利要求1所述化合物晶体在染料、有机颜料、光学增白剂、光氧化剂、涂料、化学及生化标记分析、太阳能捕集器、防伪标记、药物示踪、荧光探针、荧光分析、光学电子器件、光化学传感器、激光染料、有机电致发光器件等领域的用途，该用途基于其荧光性质。
4.如权利要求1中所述化合物晶体或其他药物学上可接受的盐在制备治疗肿瘤药物中的应用，其特征在于：所述肿瘤为肺癌、恶性黑色素瘤和宫颈癌。
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CN113730405A (zh) * 2021-09-18 2021-12-03 齐鲁工业大学 双吡啶酮腙-4-吲哚甲醛西弗碱的用途
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