与4-羟基喹啉酮

2005年第25卷有机化学Vol.25,2005第9期,1110～1112ChineseJournalofOrganicChemistryNo.9,1110～1112*E-mail:[e-mail]14,2004;revisedFebruary2,2005;acceptedMarch24,2005.江苏省青蓝工程基金(No.QL98001)和江苏省高校自然科学基金(No.04KJB150139)资助项目.·研究简报·KF/Al2O3催化下芳醛和4-羟基喹啉-2-酮的反应研究王香善*,a,b,c曾兆森a史达清a,c屠树江a,c魏贤勇b宗志敏b(a徐州师范大学化学系徐州221116)(b中国矿业大学化学工程学院徐州221008)(c江苏省药用植物生物技术重点实验室徐州221116)摘要以芳醛和4-羟基喹啉-2-酮为原料,在KF/Al2O3催化下以乙醇为溶剂,在80℃合成了一系列新的双(4-羟基-2-氧代喹啉-3-基)-芳基甲烷衍生物,反应条件温和,产率较高,并通过IR,1HNMR和元素分析确证产物的结构.关键词4-羟基喹啉-2-酮;KF/Al2O3;合成StudyontheReactionofArylAldehydeand1,2-Dihydro-4-hydroxyquinolin-2-oneWANG,Xiang-Shan*,a,b,cZENG,Zhao-SenaSHI,Da-Qinga,cTU,Shu-Jianga,cWEI,Xian-YongbZONG,Zhi-Minb(aDepartmentofChemistry,XuzhouNormalUniversity,Xuzhou221116)(bSchoolofChemicalEngineering,ChinaUniversityofMiningandTechnology,Xuzhou221008)(cKeyLaboratoryofBiotechnologyonMedicalPlant,Xuzhou221116)AbstractAseriesofnewbis(1,2-dihydro-4-hydroxyl-2-oxoquinolin-3-yl)arylmethanederivativesweresynthesizedfromarylaldehydeand1,2-dihydro-4-hydroxyquinolin-2-oneinethylalcoholat80℃,catalyzedbyKF/Al2O3undermildreactionconditioningoodyields.ThestructuresoftheproductswereconfirmedbyIR,1HNMRspectraandelementalanalysis.Keywords4-hydroxyquinoline-2-one;KF/Al2O3;synthesis喹啉酮据文献报道具有潜在的抗肿瘤活性[1],常被用作微管蛋白聚合的抑制剂[2]、异构酶场所抑制剂[3]和抗血小板试剂[4].近年来无机载体氟化物作为一种碱性催化剂在有机合成中已获得广泛的应用[5,6],特别是KF/Al2O3,与其它催化剂相比,该催化剂具有反应条件温和、催化活性高、选择性强和可以循环再利用等优点.目前已经成功地用于Wittig反应[7]、Henry加成反应[8]、Darzens反应[9]等的催化剂,我们已经报道了KF/Al2O3催化下的羰基与活性亚甲基化合物的缩合反应[10],查尔酮与丙二腈的加成反应[11]和其它一些反应[12].为了进一步扩大KF/Al2O3在有机合成中的应用,本文报道KF/Al2O3催化下芳醛和4-羟基喹啉-2-酮的反应.将芳醛(1)、4-羟基喹啉-2-酮(2)在KF/Al2O3催化下,在乙醇中于80℃反应3～5h,可生成双(4-羟基-2-氧代喹啉-3-基)-芳基甲烷衍生物(3)(Eq.1).1实验部分1.1仪器及试剂熔点测定使用XT-5型数字熔点仪;红外光谱采用No.9王香善等：KF/Al2O3催化下芳醛和4-羟基喹啉-2-酮的反应研究1111TENSOR27型红外光谱仪测定(KBr压片);核磁共振氢谱采用Bruker-400MHz型核磁共振仪上测定,DMSO-d6为溶剂,TMS为内标;元素分析在Perkin-Elmer240型元素分析仪上测定.KF/Al2O3参考文献[6]的方法制备,芳醛、4-羟基喹啉-2-酮均为市售的分析纯试剂.1.2双(4-羟基-2-氧代喹啉-3-基)-芳基甲烷衍生物3的合成方法50mL的圆底烧瓶中加入的2mmol芳醛(1),4mmol4-羟基喹啉-2-酮(2),250mg的KF/Al2O3和10mL的无水乙醇,在80℃下反应3～5h,冷却过滤,热DMF和水混合溶剂溶解,趁热除去不溶性的杂质,冷却结晶,过滤后所得到的晶体在80℃下真空干燥4h得化合物3.3a:88%,m.p.＞300℃;1HNMR(DMSO-d6)δ:6.32(s,1H,CH),7.32～7.35(m,2H,ArH),7.47(d,J＝8.0Hz,2H,ArH),7.56～7.67(m,4H,ArH),7.89(s,1H,ArH),7.99(d,J＝7.6Hz,2H,ArH),8.10(d,J＝7.6Hz,1H,ArH),12.32(s,2H,2NH),12.95(b,2H,2OH);IR(KBr)ν:3053(b),1633,1590,1523,1457,1371,1328,1254,1087,802,794cm－1.Anal.calcdforC25H17N3O6:C65.93,H3.76,N9.23;foundC65.88,H3.80,N9.11.3b:82%,m.p.＞300℃;1HNMR(DMSO-d6)δ:6.17(s,1H,CH),7.13(d,J＝8.4Hz,2H,ArH),7.30～7.32(m,4H,ArH),7.45(d,J＝8.4Hz,ArH,2H),7.60～7.64(m,2H,ArH),7.96(s,2H,ArH),12.24(s,2H,2NH),12.70(b,1H,OH),13.11(b,1H,OH);IR(KBr)ν:3068(b),1641,1606,1488,1387,1321,1207,1145,1087,896,829,763cm－1.Anal.calcdforC25H17ClN2O4:C67.50,H3.85,N6.30;foundC67.29,H4.10,N6.35.3c:86%,m.p.＞300℃;1HNMR(DMSO-d6)δ:6.20(s,1H,CH),7.11(d,J＝8.4Hz,1H,ArH),7.28～7.34(m,3H,ArH),7.45(d,J＝8.4Hz,2H,ArH),7.51(d,J＝8.4Hz,1H,ArH),7.61～7.64(m,2H,ArH),7.97(d,J＝8.8Hz,2H,ArH),12.28(s,2H,2NH),12.94(b,2H,2OH);IR(KBr)ν:3068(b),1641,1607,1547,1488,1473,1399,1321,1270,1153,1028,888,837,756cm－1.Anal.calcdforC25H16Cl2N2O4:C62.65,H3.36,N5.84;foundC62.47,H3.50,N5.93.3d:89%,m.p.＞300℃;1HNMR(DMSO-d6)δ:5.98(s,2H,CH2),6.12(s,1H,CH),6.58(d,J＝8.0Hz,1H,ArH),6.62(s,1H,ArH),6.80(d,J＝8.0Hz,1H,ArH),7.29～7.32(m,2H,ArH),7.44(d,J＝8.0Hz,2H,ArH),7.59～7.63(m,2H,ArH),7.96(s,2H,ArH),12.20(s,2H,2NH),12.65(b,1H,OH),13.18(b,1H,OH);IR(KBr)ν:3067(b),1651,1607,1496,1387,1321,1247,1145,1095,1036,939,891,763cm－1.Anal.calcdforC26H18N2O6:C68.72,H3.99,N6.16;foundC68.68,H3.89,N6.24.3e:79%,m.p.＞300℃;1HNMR(DMSO-d6)δ:3.72(s,3H,CH3O),6.13(s,1H,CH),6.83(d,J＝8.4Hz,2H,ArH),7.01(d,J＝8.4Hz,2H,ArH),7.28～7.32(m,2H,ArH),7.45(d,J＝8.0Hz,2H,ArH),7.59～7.63(m,2H,ArH),7.96(s,2H,ArH),12.20(s,2H,2NH),12.68(b,1H,OH),13.14(b,1H,OH);IR(KBr)ν:3069(b),1649,1607,1516,1481,1415,1340,1222,1188,1130,1048,873,771cm－1.Anal.calcdforC26H20N2O5:C70.90,H4.58,N6.36;foundC71.16,H4.40,N6.50.3f:81%,m.p.＞300℃;1HNMR(DMSO-d6)δ:6.52(s,1H,CH),6.96～7.00(m,2H,ArH),7.14(d,J＝8.0Hz,2H,ArH),7.18～7.21(m,1H,ArH),7.26(s,1H,ArH),7.29～7.33(m,2H,ArH),7.38(d,J＝8.4Hz,1H,ArH),7.79(d,J＝8.0Hz,2H,ArH),8.21(d,2H,2OH),10.63(s,2H,2NH);IR(KBr)ν:3069(b),1633,1599,1504,1465,1399,1263,1165,1115,1056,954,872,814,763cm－1.Anal.calcdforC25H16Cl2N2O4:C62.65,H3.36,N5.84;foundC62.70,H3.30,N5.79.3g:86%,m.p.＞300℃;1HNMR(DMSO-d6)δ:2.85(s,6H,2CH3),6.10(s,1H,CH),6.64(d,J＝8.8Hz,2H,ArH),6.90(d,J＝8.8Hz,2H,ArH),7.28～7.32(m,2H,ArH),7.44(d,J＝8.0Hz,2H,ArH),7.58～7.62(m,2H,ArH),7.96(s,2H,ArH),12.11(s,1H,NH),12.22(s,1H,NH),12.65(b,1H,OH),13.12(b,1H,OH);IR(KBr)ν:3069(b),1649,1607,1523,1481,1339,1328,1289,1223,1153,1122,970,861,771cm－1.Anal.calcdforC27H23-N3O4:C71.51,H5.11,N9.27;foundC71.70,H5.20,N9.333h:76%,m.p.＞300℃;1HNMR(DMSO-d6)δ:3.55(s,3H,CH3O),3.73(s,3H,CH3O),6.16(s,1H,CH),6.65～6.67(m,2H,ArH),6.85(d,J＝8.4Hz,1H,ArH),7.28～7.32(m,2H,ArH),7.45(d,J＝8.4Hz,2H,ArH),7.59～7.61(m,2H,ArH),7.96(s,2H,ArH),12.20(s,2H,2NH),12.68(b,1H,OH),13.12(b,1H,OH);IR(KBr)ν:3069(b),1656,1613,1562,1523,1473,1406,1340,1254,1112有机化学Vol.25,20051153,1114,1048,903,837,779cm－1.Anal.calcdforC