CN115490638A - 5-官能团化吡唑啉及其制备方法 - Google Patents
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Abstract
5‑官能团化吡唑啉及其制备方法,涉及药学及农业学等相关产物制备范畴,尤其涉及在吡唑啉环的5‑位引入官能团,制备5‑官能团化吡唑啉类化合物。5‑官能团化吡唑啉的制备方法为:以1,3‑二芳基‑5‑(3,5‑二甲基)吡唑酰基吡唑啉为原料,加入相应的反应试剂及催化剂,即可得到目标产物。本发明涉及的吡唑啉类化合物,制备方法简易,产率优良,为5‑官能团化吡唑啉的构建提供新思路。
Description
技术领域
涉及药学及农业学等相关产物制备范畴,尤其涉及在吡唑啉环的5-位引入官能团,制备5-官能团化吡唑啉类化合物。
背景技术
杂环化学是有机化学的重要构造成分,也是有机合成领域近些年来探究最为积极的领域之一。尽管五元杂环化合物在功能上具有庞大的发展潜力,但在很大程度上仍未被开发利用,所以在对含氮杂环化合物的构建和功能改造上一直是科学工作者研讨的热点。吡唑啉骨架是一类十分重要的五元氮杂环骨架,是材料科学、药物、生物活性分子和有机合成等领域用来合成目标产物的核心结构单元。在材料科学领域,铁及其合金是石油精炼设施中常用的材料,但金属材料的腐蚀是当今钢铁行业面临最严重的问题之一,吡唑啉类化合物在室温下延缓腐蚀,在较高温度下表现出高抑制效率,其在缓蚀过程中体现了价值所在;在药物领域,吡唑啉类化合物可以治疗包括癌症、糖尿病和疟疾等多种疾病;在生物活性分子领域,吡唑啉类化合物显示出抗血小板、抗结核、抗菌和抗炎等活性;在有机合成领域,是一类重要的合成中间体,可以发生开环、重排反应,在新药的策画和合成进程中有着显著的发展远景;此外,其独到的配位、诱导功能,使其在手性催化中也表现出不可取代的作用。对于在吡唑啉环的5-位引入官能团的衍生化反应,研究发现只有制备出了5-乙酰基吡唑啉化合物,而对于在吡唑啉环上引入新官能团的方法还缺少系统性的研究。
发明内容
本发明利用吡唑酰基良好的离去活性,以1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉为原料,制备1,3-二芳基-5-取代吡唑啉的方法。
本发明制备的1,3-二芳基-5-取代吡唑啉分子结构为:
其中,R1选自-CH2OH,-C(CH3)2OH,-CONHNH2;R2选自-H,-Cl,-Br,-OCH3;R3选自-H,-Br。
进一步地,式Ⅰ所示化合物中选自如下式Ⅱ~IⅤ所示结构中的任一种,
进一步地,R2=H,4-Cl,4-Br,4-OCH3;R3=H,4-Br。
进一步地,化合物I是以化合物V即1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉为原料制备的
进一步地,1,3-二芳基-5-羟甲基吡唑啉II的制备方法是:0℃下,以THF做溶剂,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉与硼氢化钠反应4h后,加少量水淬灭反应,乙酸乙酯和饱和食盐水萃取,浓缩有机相,得到1,3-二芳基-5-羟甲基吡唑啉,产率为92~95%。
进一步地,1,3-二芳基-5-(1,1-二甲基)羟甲基吡唑啉III的制备方法是:氮气氛围下,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉用精致的THF溶解后,0℃反应条件下滴加MeMgBr,体系逐渐恢复至室温1.5h后,加入少量水淬灭反应,乙酸乙酯和饱和食盐水萃取,浓缩有机相,得到1,3-二芳基-5-(1,1-二甲基)羟甲基吡唑啉,产率为71~74%。
进一步地,1,3-二芳基-5-肼酰基吡唑啉IV的制备方法是:0℃下,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉溶解于DCM中,滴加1~2当量的80%的水合肼,逐渐恢复至室温,2.5h后反应结束,萃取,干燥,用正己烷:乙酸乙酯=12:1的体积比重结晶,得到白色固体,产率为91~95%。
本发明的原理:
本发明是利用1,3-偶极环加成反应制备出的1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉,再利用3,5-二甲基吡唑酰基的易离去性,使进攻试剂可以高产率地取代3,5-二甲基吡唑酰基,进而制备出新的1,3-二芳基-5-取代吡唑啉。
与现有技术相比,本发明具有如下有益效果:
1)本发明首次以1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉为原料制备出多种5-取代吡唑啉衍生物。
2)本发明制备方法简易,反应条件温和,后处理过程不复杂。
3)本发明适用性普及,产率高,具有优异的实用价值。
具体实施方式
本发明技术方案不局限于以下所列举具体实施方式,还包括各具体实施方式间的任意组合。
具体实施方式一:本实施方式制备的1,3-二芳基-5-取代吡唑啉分子结构为:
其中,R1选自-CH2OH,-C(CH3)2OH,-CONHNH2;R2选自-H,-Cl,-Br,-OCH3;R3选自-H,-Br。
具体实施方式二,本实施方式制备的化合物中选自如下式Ⅱ~IⅤ所示结构中的任一种,
具体实施方式三,本实施方式制备的化合物I是以化合物V即1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉为原料制备的
具体实施方式四,本实施方式制备的1,3-二芳基-5-羟甲基吡唑啉II的制备方法是:
0℃下,以THF做溶剂,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉与硼氢化钠反应4h后,加少量水淬灭反应,乙酸乙酯和饱和食盐水萃取,浓缩有机相,得到1,3-二芳基-5-
羟甲基吡唑啉,产率为92~95%。
具体实施方式五,本实施方式制备的1,3-二芳基-5-(1,1-二甲基)羟甲基吡唑啉III的制备方法是:氮气氛围下,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉用精致的THF溶解后,0℃反应条件下滴加MeMgBr,体系逐渐恢复至室温1.5h后,加入少量水淬灭反应,乙酸乙酯和饱和食盐水萃取,浓缩有机相,得到1,3-二芳基-5-(1,1-二甲基)羟甲基吡唑啉,产率为71~74%。
具体实施方式六,本实施方式制备的,1,3-二芳基-5-肼酰基吡唑IV的制备方法是:0℃下,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉溶解于DCM中,滴加1~2当量的80%的水合肼,逐渐恢复至室温,2.5h后反应结束,萃取,干燥,用正己烷:乙酸乙酯=10:1的体积比重结晶,得到白色固体,产率为91~95%。
下面对本发明的实施例做详细说明,以下实施例是在以本发明技术方案为前提下进行实施,给出了详细的实施方案和具体的操作过程,但本发明的保护范围不限于下述的实施例。
实施例1:本实施例是1,3-二苯基-5-羟甲基吡唑啉的制备方法,按以下步骤进行:
0℃下,1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉0.144mmol,硼氢化钠0.576mmol和4mL THF加入到10mL圆底烧瓶中,逐渐恢复到室温,反应4h后,薄层色谱监控,Rf=0.34(正己烷:乙酸乙酯=2:1),加少量水淬灭反应,乙酸乙酯与饱和食盐水萃取,浓缩有机相后,使用300~400目硅胶粉湿法过柱,流动相比例是正己烷:乙酸乙酯=3:1,得到无色油状液体,产率为93%。1,3-二苯基-5-羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.76(d,J=9Hz,2H),7.44-7.24(m,7H),6.89(s,1H),4.68-4.31(m,1H),3.90(dd,J=6,12Hz,1H),3.76(qd,J=6,9Hz,2H),3.54-3.33(m,1H),1.87(s,1H)ppm.13C NMR(75MHz,CDCl3):δ=148.92,145.14,132.62,129.23,128.75,128.51,125.87,119.49,67.97,62.48,61.43,36.00,25.60ppm.FTIR(KBr):ν=3384,3060,2926,2855,1596,1566,1510,1493,1450,1395,1338,1287,1126,1069,1037,1007,879,748,691cm-1.HRMS(ESI)m/zCalcd.for C16H17N2O+([M+H]+)253.1263,Found 253.1350。
实施例2:本实施例是1-苯基-3-(4-氯芳基)-5-羟甲基吡唑啉的制备方法,所有实验条件和处理方法与实施例1相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-氯芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,最终产品收率为92%。1-苯基-3-(4-氯苯基)-5-羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.66(d,J=6Hz,2H),7.37(d,J=9Hz,2H),7.30(d,J=6Hz,2H),7.21(d,J=9Hz,2H),6.91(t,J=7.5Hz,1H),4.49-4.31(m,1H),3.93(dd,J=3,9Hz,1H),3.74(dd,J=3,12Hz,1H),3.46-3.23(m,2H),1.88(s,1H)ppm.13C NMR(75MHz,CDCl3):δ=147.72,144.85,134.45,131.10,129.29,128.73,127.02,119.74,99.99,62.41,61.45,35.79,29.73ppm.FTIR(KBr):ν=3381,3057,2929,2858,1598,1557,1510,1492,1412,1394,1334,1290,1180,1132,1093,1069,1037,1013,959,882,831,751,701,674cm-1.HRMS(ESI)m/z Calcd.for C16H16ClN2O+([M+H]+)287.0873,Found 287.0945。
实施例3:本实施例是1-苯基-3-(4-溴芳基)-5-羟甲基吡唑啉的制备方法,所有实验条件和处理方法与实施例1相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-溴芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,最终产品收率为94%。1-苯基-3-(4-溴芳基)-5-羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.60(d,J=9Hz,2H),7.52(d,J=9Hz,2H),7.33(d,J=9Hz,2H),7.21(d,J=9Hz,2H),6.90(t,J=7.5Hz,1H),4.50-4.28(m,1H),3.94(dd,J=3,12Hz,1H),3.74(dd,J=3,9Hz,1H),3.41-3.26(m,2H),1.82(s,1H)ppm.13C NMR(75MHz,CDCl3):δ=147.65,144.73,131.66,131.54,129.29,127.27,122.71,119.78,113.46,62.40,61.47,35.73,29.68ppm.FTIR(KBr):ν=3384,3066,2925,2858,1724,1598,1572,1554,1501,1457,1405,1387,1333,1275,1251,1180,1129,1070,1040,1007,956,882,824,748,693,674cm-1.HRMS(ESI)m/z Calcd.forC16H16BrN2O+([M+H]+)331.0368,Found 331.0439。
实施例4:本实施例是1-苯基-3-(4-甲氧基芳基)-5-羟甲基吡唑啉的制备方法,所有实验条件和处理方法与实施例1相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-甲氧基芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,最终产品收率为93%。1-苯基-3-(4-甲氧基芳基)-5-羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.70(d,J=9Hz,2H),7.32(d,J=9Hz,2H),7.21(d,J=6Hz,2H),6.94(d,J=9Hz,2H),6.88(t,J=7.5Hz,1H),4.47-4.39(m,1H),3.91(dd,J=3,12Hz,1H),3.85(s,3H),3.74(dd,J=3,12Hz,1H),3.42(dd,J=12,18Hz,1H),3.27(dd,J=6,15Hz,1H),2.00(s,1H)ppm.13CNMR(75MHz,CDCl3):δ=160.24,149.07,145.55,129.21,127.40,125.37,119.28,113.98,113.36,62.65,61.45,55.35,36.21ppm.FTIR(KBr):ν=3420,3060,2925,2852,1727,1597,1517,1498,1459,1423,1391,1337,1310,1252,1177,1125,1069,1033,1004,959,876,832,748,695,674cm-1.HRMS(ESI)m/z Calcd.for C17H19N2O2 +([M+H]+)283.1368,Found283.1440。
实施例5:本实施例是(1,3-二(4-溴芳基))-5-羟甲基吡唑啉的制备方法,所有实验条件和处理方法与实施例1相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为(1,3-二(4-溴芳基))-5-(3,5-二甲基)吡唑酰基吡唑啉,最终产品收率为95%。(1,3-二(4-溴芳基))-5-羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.58(d,J=9Hz,2H),7.51(d,J=9Hz,2H),7.36(d,J=9Hz,2H),7.06(d,J=9Hz,2H),4.48-4.41(m,1H),3.84(dd,J=3,12Hz,1H),3.45(qd,J=6,15Hz,2H),3.26(dd,J=3,15Hz,1H),2.05(s,1H)ppm.13C NMR(75MHz,CDCl3):δ=148.16,143.66,131.95,131.69,131.33,127.28,122.91,114.86,111.53,67.95,65.84,62.11,61.33,35.90,29.69,25.59ppm.FTIR(KBr):ν=3399,2959,2924,2855,1727,1592,1487,1412,1387,1340,1275,1180,1135,1071,1010,962,820,709,632cm-1.HRMS(ESI)m/z Calcd.for C16H15Br2N2O+([M+H]+)408.9473,Found408.9555。
实施例6:本实施例是1,3-二苯基-5-(1,1-二甲基)羟甲基吡唑啉的制备方法,按以下步骤进行:
氮气氛围下,1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉0.144mmol和4mL精致的THF加入到10mL圆底烧瓶中,0℃条件下滴加MeMgBr(1.152mmol),体系逐渐恢复至室温1.5h后薄层色谱监控,Rf=0.3(正己烷:乙酸乙酯=5:1),加入少量水淬灭反应,乙酸乙酯和饱和食盐水萃取,浓缩有机相,使用300~400目硅胶粉湿法过柱,流动相比例是正己烷:乙酸乙酯=4:1,得到无色油状液体,产率为72%。1,3-二苯基-5-(1,1-二甲基)羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.79(d,J=9Hz,2H),7.46-7.38(m,5H),7.32(d,J=9Hz,2H),6.90(t,J=7.5Hz,1H),4.32(dd,J=3,12Hz,1H),3.39(dd,J=9,18Hz,1H),3.11(dd,J=3,18Hz,1H),1.87(s,1H),1.33(s,3H),1.22(s,3H)ppm.13C NMR(75MHz,CDCl3):δ=171.16,151.06,147.82,132.28,129.11,128.89,126.17,119.80,114.67,74.32,68.71,60.40,35.78,26.22,24.45,21.04,14.20ppm.FTIR(KBr):ν=3444,3063,2980,2929,2855,1595,1493,1450,1388,1328,1275,1180,1105,1069,1040,1001,882,763,760,691,674cm-1.HRMS(ESI)m/z Calcd.for C18H21N2O+([M+H]+)281.1576,Found281.1653。
实施例7:本实施例是1-苯基-3-(4-氯芳基)-5-(1,1-二甲基)羟甲基吡唑啉的制备方法,所有实验条件和处理方法与实施例6相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-氯芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,产品收率是71%。产物1-苯基-3-(4-氯芳基)-5-(1,1-二甲基)羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.70(d,J=9Hz,2H),7.41-7.30(m,6H),6.91(t,J=7.5Hz,1H),4.34(dd,J=3,12Hz,1H),3.35(dd,J=12,18Hz,1H),3.08(dd,J=6,18Hz,1H),1.87(s,1H),1.31(s,3H),1.21(s,3H)ppm.13C NMR(75MHz,CDCl3):δ=149.75,147.48,134.85,130.80,128.93,128.76,127.33,120.01,114.74,74.31,68.61,60.37,35.63,26.32,24.54ppm.FTIR(KBr):ν=3444,3063,2980,2926,2855,1598,1493,1409,1376,1328,1269,1182,1092,1072,1004,950,888,828,750,698,680cm-1.HRMS(ESI)m/z Calcd.forC18H20ClN2O+([M+H]+)315.1186,Found 315.1261。
实施例8:本实施例是1-苯基-3-(4-溴芳基)-5-(1,1-二甲基)羟甲基吡唑啉的制备方法,所有实验条件和处理方法与实施例6相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-溴芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,产品收率是73%。产物1-苯基-3-(4-溴芳基)-5-(1,1-二甲基)羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.63(d,J=9Hz,2H),7.53(d,J=9Hz,2H),7.39(d,J=9Hz,2H),7.31(d,J=9Hz,2H),6.90(t,J=7.5Hz,1H),4.34(dd,J=3,12Hz,1H),3.35(dd,J=12,18Hz,1H),3.08(dd,J=3,18Hz,1H),1.86(s,1H),1.30(s,3H),1.20(s,3H)ppm.13C NMR(75MHz,CDCl3):δ=149.70,147.41,131.69,131.25,128.90,127.54,123.09,119.99,114.73,74.26,68.60,67.95,35.55,31.59,26.28,25.60,22.65,14.12ppm.FTIR(KBr):ν=3438,3060,2977,2923,2852,1721,1597,1495,1400,1379,1328,1275,1185,1123,1072,1037,1013,944,888,831,751,698,680cm-1.HRMS(ESI)m/z Calcd.for C18H19BrN2ONa+([M+Na]+)381.0681,Found381.0578。
实施例9:本实施例是1-苯基-3-(4-甲氧基芳基)-5-(1,1-二甲基)羟甲基吡唑啉的制备方法,所有实验条件和处理方法与实施例6相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-甲氧基芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,产品收率为72%。产物1-苯基-3-(4-甲氧基芳基)-5-(1,1-二甲基)羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.73(d,J=6Hz,2H),7.39-7.28(m,4H),6.97-6.89(m,3H),4.36-4.31(m,1H),3.86(s,3H),3.34(s,1H),3.10-3.04(m,1H),1.95(s,1H),1.33(s,3H),1.21(s,3H)ppm.13C NMR(75MHz,CDCl3):δ=160.53,151.33,148.24,128.87,127.75,124.99,119.60,114.56,113.99,74.23,68.88,55.35,35.90,29.76,26.22,24.40,22.65,14.14ppm.FTIR(KBr):ν=3375,3069,2959,2925,2855,1727,1598,1513,1497,1462,1378,1304,1252,1177,1126,1037,962,837,754,698cm-1.HRMS(ESI)m/z Calcd.for C19H23N2O2 +([M+H]+)311.1681,Found 311.1764。
实施例10:本实施例是(1,3-二(4-溴芳基))-5-(1,1-二甲基)羟甲基吡唑啉的制备方法,所有实验条件和处理方法与实施例6相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为(1,3-二(4-溴芳基))-5-(3,5-二甲基)吡唑酰基吡唑啉,产品收率是74%。产物(1,3-二(4-溴芳基))-5-(1,1-二甲基)羟甲基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.62(d,J=9Hz,2H),7.53(d,J=6Hz,2H),7.36(d,J=9Hz,2H),7.26(d,J=9Hz,2H),4.32-4.22(m,1H),3.35(dd,J=9,18Hz,1H),3.07(dd,J=3,18Hz,1H),1.86(s,1H),1.29(s,3H),1.27(s,3H)ppm.13C NMR(75MHz,CDCl3):δ=150.26,146.48,131.75,131.56,127.56,116.22,115.49,112.13,74.33,67.95,46.13,31.58,29.69,25.60,22.65,14.11ppm.FTIR(KBr):ν=3435,2962,2924,2854,1727,1589,1487,1465,1409,1377,1322,1267,1185,1126,1071,1013,956,882,820,754,709,632cm-1.HRMS(ESI)m/z Calcd.for C18H19Br2N2O+([M+H]+)436.9786,Found 436.9868。
实施例11:本实施例是1,3-二苯基-5-肼酰基吡唑啉的制备方法,具体步骤如下:0℃下,1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉0.144mmol和4mL DCM加入到10mL圆底烧瓶中,滴加1mL 80%的水合肼,逐渐恢复至室温,2.5h后薄层色谱监控,Rf=0.1(正己烷:乙酸乙酯=1:1),萃取,干燥,用正己烷:乙酸乙酯=10:1重结晶,得到白色固体,产率为92%。产物1,3-二苯基-5-肼酰基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.70(d,J=6Hz,2H),7.40(d,J=6Hz,3H),7.22(d,J=6Hz,2H),7.04(d,J=9Hz,2H),6.77(t,J=7.5Hz,1H),4.78(dd,J=6,12Hz,1H),4.35(s,2H),3.66(dd,J=9,18Hz,1H)3.22(dd,J=6,15Hz,1H),2.49(s,1H)ppm.13C NMR(75MHz,CDCl3):δ=170.25,147.75,144.97,132.43,129.41,129.09,126.08,119.23,113.02,61.14,40.49,40.20,39.93,39.65,39.37,17.90,15.73ppm.FTIR(KBr):ν=3328,3301,3054,2926,1662,1623,1599,1560,1507,1493,1450,1399,1331,1266,1150,1126,1078,998,941,882,760,701cm-1.HRMS(ESI)m/z Calcd.forC16H17N4O+([M+H]+)281.1324,Found 281.1406。
实施例12:本实施例是1-苯基-3-(4-氯芳基)-5-肼酰基吡唑啉的制备方法,所有实验条件和处理方法与实施例18相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-氯芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,产率95%。产物1-苯基-3-(4-氯芳基)-5-肼酰基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.72(d,J=6Hz,2H),7.48(d,J=6Hz,2H),7.24(d,J=6Hz,2H),7.04(d,J=9Hz,2H),6.80(t,J=7.5Hz,1H),4.72(dd,J=6,12Hz,1H),4.37(s,2H),3.67(dd,J=9,18Hz,1H),3.21(dd,J=6,12Hz,1H),2.49(s,1H)ppm.13C NMR(75MHz,CDCl3):δ=170.22,146.82,144.76,133.73,131.55,129.44,129.15,127.74,119.45,113.06,61.36,40.80,40.53,40.25,39.97,39.69,39.41,39.14,16.65ppm.FTIR(KBr):ν=3301,3042,2923,2855,1655,1596,1578,1507,1492,1409,1391,1328,1266,1147,1093,1043,1013,944,885,834,754,698,677,534cm-1.HRMS(ESI)m/z Calcd.for C16H16ClN4O+([M+H]+)315.0934,Found 315.1014。
实施例13:本实施例是1-苯基-3-(4-溴芳基)-5-肼酰基吡唑啉的制备方法,所有实验条件和处理方法与实施例18相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-溴芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,产率91%。产物1-苯基-3-(4-溴芳基)-5-肼酰基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.60-7.31(m,4H),7.21-6.77(m,5H),4.80(dd,J=6,18Hz,1H),4.35(s,2H),3.19-3.10(m,2H),2.48(s,1H)ppm.13C NMR(75MHz,CDCl3):δ=170.14,146.73,144.66,132.05,131.64,129.46,127.97,122.19,119.50,113.06,61.20,40.63,40.35,40.07,39.79,39.52,39.24,35.08,15.73ppm.FTIR(KBr):ν=3554,3476,3411,3334,3290,3057,2926,1664,1623,1599,1575,1506,1489,1456,1409,1388,1328,1267,1153,1078,1013,941,885,834,760,703,683cm- 1.HRMS(ESI)m/z Calcd.for C16H16BrN4O+([M+H]+)359.0429,Found 359.0513。
实施例14:本实施例是1-苯基-3-(4-甲氧基芳基)-5-肼酰基吡唑啉的制备方法,所有实验条件和处理方法与实施例18相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为1-苯基-3-(4-甲氧基芳基)-5-(3,5-二甲基)吡唑酰基吡唑啉,产率92%。产物1-苯基-3-(4-甲氧基芳基)-5-肼酰基吡唑啉的结构数据是:1H NMR(300MHz,CDCl3):δ=7.66(d,J=6Hz,2H),7.32(d,J=9Hz,2H),7.09(d,J=9Hz,2H),6.95-6.91(m,3H),4.64(dd,J=6,15Hz,2H),3.85(s,3H),3.78(dd,J=3,12Hz,2H),3.33(dd,J=6,18Hz,2H)ppm.13C NMR(75MHz,CDCl3):δ=171.67,160.78,149.60,145.46,129.36,127.68,124.16,120.53,114.14,113.34,63.57,55.37,39.50,35.07,26.94,19.79ppm.FTIR(KBr):ν=3322,3009,2935,2840,1655,1598,1522,1503,1462,1406,1340,1263,1182,1150,1046,1019,944,885,837,751,701,677cm-1.HRMS(ESI)m/z Calcd.for C17H19N4O2 +([M+H]+)311.1430,Found311.1513。
实施例15:本实施例(1,3-二(4-溴芳基))-5-肼酰基吡唑啉的制备方法,所有实验条件和处理方法与实施例18相同,只是将1,3-二苯基-5-(3,5-二甲基)吡唑酰基吡唑啉改为(1,3-二(4-溴芳基))-5-(3,5-二甲基)吡唑酰基吡唑啉,产率93%。产物(1,3-二(4-溴芳基))-5-肼酰基吡唑啉的结构数据:1H NMR(300MHz,CDCl3):δ=7.64-7.60(m,4H),7.39(d,J=9Hz,2H),6.97(d,J=9Hz,2H),4.74(d,J=6,12Hz,1H),4.36(s,2H),3.67(dd,J=9,12Hz,1H),3.26(dd,J=12,18Hz,1H),2.50(s,1H)ppm.13C NMR(75MHz,CDCl3):δ=169.94,147.74,143.85,132.08,131.43,128.12,122.50,114.97,110.59,61.27,40.82,40.53,40.26,39.98,39.70,39.42,39.14,12.30ppm.FTIR(KBr):ν=3337,3298,3039,2929,1653,1591,1528,1501,1487,1415,1394,1322,1275,1147,1102,1072,1013,953,885,831,757,712,665cm-1.HRMS(ESI)m/z Calcd.for C16H15Br2N4O+([M+H]+)436.9534,Found 436.9619。
Claims (8)
3.根据权利要求1和2所述的化合物,其特征在于R2=H,4-Cl,4-Br,4-OCH3;R3=H,4-Br。
6.根据权利要求1-5所述的5-官能团吡唑啉,其特征在于1,3-二芳基-5-羟甲基吡唑啉II的制备方法是:0℃下,以THF做溶剂,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉与硼氢化钠反应4h后,加少量水淬灭反应,乙酸乙酯和饱和食盐水萃取,浓缩有机相,得到1,3-二芳基-5-羟甲基吡唑啉,产率为92~95%。
7.根据权利要求1-5所述的5-官能团吡唑啉,其特征在于1,3-二芳基-5-(1,1-二甲基)羟甲基吡唑啉III的制备方法是:氮气氛围下,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉用精致的THF溶解后,0℃反应条件下滴加MeMgBr,体系逐渐恢复至室温1.5h后,加入少量水淬灭反应,乙酸乙酯和饱和食盐水萃取,浓缩有机相,得到1,3-二芳基-5-(1,1-二甲基)羟甲基吡唑啉,产率为71~74%。
8.根据权利要求1-5所述的5-官能团吡唑啉,其特征在于1,3-二芳基-5-肼酰基吡唑啉IV的制备方法是:0℃下,1,3-二芳基-5-(3,5-二甲基)吡唑酰基吡唑啉溶解于DCM中,滴加1~2当量的80%的水合肼,逐渐恢复至室温,2.5h后反应结束,萃取,干燥,用正己烷:乙酸乙酯=12:1的体积比重结晶,得到白色固体,产率为91~95%。
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