CN110669023B - 一种手性噁唑啉铜配合物的用途 - Google Patents

一种手性噁唑啉铜配合物的用途 Download PDF

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CN110669023B
CN110669023B CN201910988370.3A CN201910988370A CN110669023B CN 110669023 B CN110669023 B CN 110669023B CN 201910988370 A CN201910988370 A CN 201910988370A CN 110669023 B CN110669023 B CN 110669023B
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罗梅
李国雄
谢蓝
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Abstract

一种由以下化学式所示的双{2‑[4(R)‑苯基‑4,5‑二氢化]‑2‑噁唑啉基}苯酚铜配合物的用途是作为催化剂在二苯亚胺与三甲基硅腈的反应中及二苯甲酮腙的缩合反应显示了较好的催化性能，其转化率分别达68％及99％；该手性配合物(I)在多种癌细胞如：肺癌(A549)、白血病细胞(HB‑60)及肝癌细胞(SMMC‑7721)试验中均显示出较强的抑制活性。该配合物的化学式如下：
Figure DDA0002237432420000011

Description

一种手性噁唑啉铜配合物的用途
一、技术领域
本发明涉及一种金属有机配位化合物(配合物)及其制备方法，特别涉及含氮的噁唑啉金属有机配合物及其制备方法，确切地说是一种手性噁唑啉的铜配合物及其合成方法。
二、背景技术
随着有机化学的发展,金属有机化合物在有机合成中的应用愈来愈广,是现在有机化学中极为活跃的领域之一,已经广泛应用于有机合成反应中。20世纪60年代后期出现的使用手性配体与过渡金属络合物催化的不对称合成反应大大加速了手性药物的研究。化学催化不对称合成法的重要内容便是手性配体及含金属催化剂的设计,从而使反应具有高效和高对映选择性。近年来手性双噁唑啉配体一铜金属配合物在不对称催化领域取得了较好的催化效果。
参考文献：
1.Evans,David A.；Rovis,Tomislav；Johnson,Jeffrey S.Pure and AppliedChemistry(1999),71(8),1407-1415.
2.Li,Xin；Cun,Lin-Feng；Gong,Liu-Zhu；Mi,Ai-Qiao；Jiang,Yao-Zhong,Tetrahedron:Asymmetry(2003),14(24),3819-3821.
3.Evans,David A.；Shaughnessy,Eileen A.；Barnes,David M.TetrahedronLetters(1997),38(18),3193-3194.
三、发明内容
本发明旨在提供一种Cu-N金属有机配合物以应用于催化领域，所要解决的技术问题遴选邻羟基噁唑啉作为配体并合成手性双噁唑啉的铜配合物。
本发明所称的手性双噁唑啉的铜配合物一种是由邻羟基苯甲腈、D-苯甘氨醇与一水合醋酸铜制备的由以下化学式所示的配合物：
Figure BDA0002237432400000011
化学名称：双{2-[4(R)-苯基-4,5-二氢化]-2-噁唑啉基}苯酚铜配合物，简称配合物(I)。
该配合物在二苯甲酮亚胺与三甲基硅腈及二苯甲酮腙的缩合反应中显示了较好的催化性能，其转化率分别达68％及99％。
本合成方法包括合成和分离，所述的合成用55.8mol％乙酸铜或氯化铜做催化剂,邻羟基苯甲腈15.1mmol，D-苯甘氨醇3.8g，用50mL氯苯做溶剂，回流反应72小时，纯化，即反应结束后脱去氯苯，加水溶解后用氯仿萃取，萃取相脱溶后用柱层析纯化；用石油醚及二氯甲烷淋洗，柱层析分离，将第二组分点自然挥发得手性双噁唑啉铜配合物单晶。
合成反应如下：
Figure BDA0002237432400000021
本合成方法一步得到目标产物，工艺简单，操作方便。
四、附图说明
图1双{2-[4(R)-苯基-4,5-二氢化]-2-噁唑啉基}苯酚铜配合物的X-衍射分析图。
五、具体实施方式
在100mL两口瓶中,加入一水合醋酸铜或二水合氯化铜25.7mmol,50mL氯苯，邻羟基苯甲腈1.7966g,D-苯甘氨醇3.8g,将混合物在高温下回流72h,停止反应,用石油醚及二氯甲烷淋洗，柱层析分离，将最后的组分点自然挥发得配合物单晶,产率分别为65％及85％,m.p.:>200℃,[a]5 D＝+235.7°(c＝0.0488,CH3OH),元素分析：测试值：C:66.22％,H:4.39％,N:5.26％；计算值：66.72％,4.44％,N,5.18％；IR(KBr):3439,3025，2967,2902，1617,1583,1541,1475,1447,1394,1349，1266,1155,1077,1030,949,935,855,755,695,666,574,533,414；
配合物晶体数据如下：
Figure BDA0002237432400000022
Figure BDA0002237432400000031
晶体典型的键长数据：
Figure BDA0002237432400000032
Figure BDA0002237432400000041
晶体典型的键角数据：
Figure BDA0002237432400000042
Figure BDA0002237432400000051
二苯甲酮亚胺与三甲基硅腈的缩合反应应用
Figure BDA0002237432400000052
称取0.025mL二苯甲酮亚胺和三甲基硅腈0.2mL放置于25mL小烧瓶中，加入2mLTHF及配合物I 0.027g，常温下搅拌26h，取少量样品做核磁检测，转化率:68％；1H NMR(600MHz,CDCl3,27℃)δ7.23–7.59(m,10H),4.10(s,2H)。
二苯甲酮腙的缩合反应应用
Figure BDA0002237432400000061
称取0.084g二苯甲酮腙放置于25mL小烧瓶中，加入2mLTHF及化合物I0.0232g，常温下搅拌26h，取少量样品做核磁检测，转化率>99％；1H NMR(600MHz,CDCl3,27℃),δ7.50–7.44(m,4H),7.43–7.36(m,6H),7.36–7.25(m,10H)；13C NMR(100MHz,CDCl3)δ158.93,138.20,135.56,129.60,129.34,128.68,128.66,128.04,127.88.；IR:3422,3057,1664,1622,1491,1444,1321,1278,1176,1076,1028,956,914,767,694,655。
抗癌活性应用
本发明依据活性天然产物的结构设计合成的铂配合物在多种癌细胞如：肺癌、肝癌及白血病试验中均显示出较强的抑制活性，因此，预期本发明的化合物可用于治疗多种癌症，本发明化合物的部分抗癌活性测试结果见表1：
表1.铜配合物(I)的抗癌活性数据
Figure BDA0002237432400000062

Claims (2)

1.一种由以下化学式所示及晶胞参数的双{2-[4(R)-苯基-4,5-二氢化]-2-噁唑啉基}苯酚铜配合物的用途，其特征在于：作为催化剂在二苯亚胺与三甲基硅腈的反应中及二苯甲酮腙的缩合反应显示了较好的催化性能，其转化率分别达68％及99％，该配合物的化学式如下：
Figure FDA0003882421410000011
其晶胞参数如下：在273k温度下，在牛津X-射线单晶衍射仪上，用经石墨单色器单色化的MoKα射线，
Figure FDA0003882421410000012
以ω-θ扫描方式收集衍射数据，其特征在于晶体属斜方晶系,空间群P2(1)2(1)2(1)，晶胞参数：
Figure FDA0003882421410000013
beta＝99.848(2)°；
Figure FDA0003882421410000014
γ＝90°。
2.由权利要求1所述的手性配合物(I)在制备抗癌药物中的用途，其特征在于：所述的癌症为肺癌、肝癌及白血病。
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