8-取代喹哪啶的合成与晶体结构
时间：2021-02-05 04:00:23 来源：雅意学习网 本文已影响 人 
摘要: 2-取代苯胺与巴豆醛反应合成了5种8-取代喹哪啶。讨论了反应因素对反应的影响,得到了较好的结果。8-取代喹哪啶的结构经1HNMR和MS分析确证,并用单晶X-射线衍射测定了化合物Ⅰa和Ⅰb的晶体结构。化合物Ⅰa晶体属正交晶系,空间群为Pca21,晶胞参数为:a = 1.27961(9) nm, b = 0.50660(4) nm, c = 1.31181(9) nm, Z = 4,V = 850.38(11) nm3, Dx = 1.387g/cm3, F(000)= 368, R1 = 0.0288, ωR2 = 0.0731,S = 1.01;化合物Ⅰb晶体属单斜晶系,空间群为P21/c晶胞参数为:a = 0.50440(17) nm, b = 1.3467(4) nm, c = 1.3391(4) nm, β = 97.678(4)°;Z = 4,V = 901.4(5) nm3, Dx = 1.636g/cm3,F(000)= 440, R1 = 0.0711, ωR2 = 0.1951,S = 1.09。 选择合适溶剂和添加剂,反应收率较文献值有较大提高。
关键词 :8-取代喹哪啶;合成;晶体结构
中图分类号:TQ 253. 23文献标识码:A
Synthesis and Crystal structure of 8-Substitued Quinaldine
Wu Tian-Quan, Wang Jian-Hua, Shen Fang and Hu Ai-Xi *
(1 College of Chemistry and Chemical Engineering, Hunan Univ,410082 Changsha, China;2 Department of biology technology&environment science, ChangSha College, changsha, 410003)
Abstract: Five quinaldine derivatives were synthesized through the reaction of 2-substituted aniline and crotonaldehyde. We were investigated the effect of conditions on reaction. Their structure confirmed by 1HNMR and MS. Crystal structure of Ⅰa and Ⅰb have been determined by X-ray diffraction, The compound Ⅰa crystal belongs to orthorhombic system with space group Pca21 and cell parameters: a = 1.27961(9) nm, b = 0.50660(4)nm, c = 1.31181(9) nm, Z = 4,V = 850.38(11) nm3, Dx = 1.387 g/cm3, F(000)= 368, R1 = 0.0288, ωR2 = 0.0731,S = 1.01;The compound Ⅰb crystal belongs to monoclinic system with space group P21/c and cell parameters: a = 0.50440(17) nm,b = 13.467(4)nm, c = 13.391(4)nm, β = 97.678(4)°;Z = 4,V = 901.4(5) nm3, Dx = 1.636g/cm3,F(000) = 440, R1 = 0.0711, ωR2 = 0.1951,S = 1.09.The yields of 8-substituted quinaldine are higher than that of literature by using appropriate slovent and additives.
Key words: 8-substitued quinaldine, synthesis, crystal structure
8-取代喹哪啶是一类重要的精细化工中间体[1~2],Dehnert等[3]以8-氨基喹哪啶为原料合成了颜料C.I P.Y138;Bray等[4]以8-卤代喹哪啶为原料合成了治疗疟疾的伯喹及氯喹类衍生物;Andreas等[5]合成了缓激肽拮抗剂,Philippo等[6]以这类中间体为原料合成了肌肉收缩剂;Dyke等[7]合成了TNF 和 PDE-Ⅳ抑制剂;Deraeve等[8]合成了多喹啉金属配合物治疗神经退行性紊乱;吉民等[9]以8-甲氧基喹哪啶合成了多巴胺D3受体部分激动剂。Heuer等[10]以8-羟基喹哪啶和8-甲氧基喹哪啶为原料开发与制造有机电致光材料。其中以8-羟基喹哪啶为母体所开发的具抗病毒HIV 逆转录酶抑制Lavendamycin [11-12]尤为令人关注。
Gurnos [13]介绍了喹啉及其衍生物的合成方法有:Doebner-Miller合成法[14],Skraup合成法[15]和Friedlaender喹啉合成法[16]。这些方法的产率偏低,缺乏应用价值;1977年,Leir[17]提出改进方法,在稀盐酸中将85.0 %巴豆醛与15. 0%水的混合物滴加入2-取代苯胺溶液中,反应合成得到8-羟基喹哪啶、8-氯喹哪啶、8-溴喹哪啶和8-甲氧基喹哪啶,收率分别为55.0 %、43.0 %、50.0 %和48.0 %;Dockner等 [18]介绍了在氯苯中以对甲苯磺酸催化进行Doebner-Miller反应合成8-氯喹哪啶的方法,收率57.0 %;吉民等[9]以8-羟基喹哪啶在丙酮中与碘甲烷反应制得8-甲氧基喹哪啶,收率为86.0 %;Li等[19]在浓盐酸中,在相转移催化剂三乙基苄基氯化铵作用下,邻氨基苯甲酸与巴豆醛作用得到8-羧基喹哪啶,其收率达57.0 %。本文采用2-取代苯胺与巴豆醛反应合成了相应的8-取代喹哪啶,见图 1。
1 实验部分
1.1 主要试剂和仪器
氯苯、二氯甲烷、异丙醇、盐酸、无水氯化锌和碘化钾为分析纯;对甲苯磺酸、巴豆醛为化学纯。邻氯苯胺、邻溴苯胺、邻氨基酚、邻硝基酚、邻氨基苯甲醚、邻氨基苯甲酸、邻硝基苯胺、对氯苯胺和邻硝基溴苯为工业品。核磁共振仪,VARIANINOVA-400(美国Varan公司);质谱仪,LCQ-Advantage液-质联用仪(美国Thermo-Finngan公司); RY-1型熔点测定仪(天津市天分仪器厂)温度计未经校正。
1.2氯苯中合成喹哪啶
13.0 g邻氯苯胺、0.5 g对甲苯磺酸、200 mL氯苯搅拌回流,滴加14.0 g巴豆醛,回流2 h,减压蒸馏回收溶剂,收集145～150 ℃/246Pa馏分,得白色固体,二甲苯重结晶,得白色晶体 10.0 g。 mp 64 ℃,收率57.0 %。MS(m/z):M+ 177;1H NMR(CDCl3,400 MHz)δ:2.83(s,3H,CH3),7.38(m,2H,喹啉环3,6-H),7.80(d,J = 7.2 Hz,1H,喹啉环7-H),8.03(d, J = 8.0Hz,1H, 喹啉环5-H),8.00(d,J = 8.4 Hz,1H,喹啉环4-H)。
