CN103664783A - 一类含萘环和吡唑啉结构的硫脲类衍生物及其制法 - Google Patents
一类含萘环和吡唑啉结构的硫脲类衍生物及其制法 Download PDFInfo
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- 150000003585 thioureas Chemical class 0.000 title claims abstract description 20
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- C—CHEMISTRY; METALLURGY
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- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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Abstract
Description
技术领域
本发明涉及一类含萘环和吡唑啉结构的硫脲类衍生物及其制备方法。
背景技术
硫脲类衍生物是一类用途广泛的化合物,其结构中的非对称单元是许多酶抑制剂和生物模拟肽的常见结构特征,多数具有生物活性。除在农药上广泛应用外,在生物医药领域也有着非常重要的地位,除普遍认可的广谱抗菌性以外,对白血病和肿瘤也有较好的药效,其应用前景十分广阔。
萘环结构具有一定的杀生能力并被广泛应于合成医药中间体,近期研究表明其结构与藏红花酸、番茄红素、维生素A等具有一定相似性。
本系列衍生物中作为辅助官能团的吡唑啉结构拥有广泛的药理特性:解热镇痛,抗风湿。在被报道具有较好抗炎活性的同时,也被认为具有抗癌活性。
基于以上研究我们合成了一系列含萘环和吡唑啉结构的硫脲类衍生物,此类化合物对于寻找具有更高或更广谱的生物活性、更高的选择性、更低的毒性、更长或更短的残效性的药物前体具有十分重要的意义,作为潜在的骨架结构,对于开展合理的分子设计和从天然生物活性物质中筛选新型活性分子,也有着理论指导价值。
发明内容
本发明的目的在于提供一类新型的含萘环和吡唑啉结构的硫脲类衍生物及其制备方法。
本发明的技术方案如下:
一类含萘环和吡唑啉结构的硫脲类衍生物,其特征是它有如下通式:
结构式中R1为如下基团之一:
R2为如下基团之一:
一种制备上述含萘环和吡唑啉结构的硫脲类衍生物的方法,它包括如下步骤:
步骤1.将取代基苯乙酮,萘甲醛溶于有机溶剂中,磁搅拌使混合均匀,缓慢滴入NaOH溶液,磁搅拌,常温反应2h(TLC检测反应进行程度),产物以固体析出。反应结束后抽滤,并以大量的蒸馏水和冷乙醇洗涤固体,干燥,重结晶;
步骤2.将步骤1中所得产物与硫代氨基脲,以有机溶剂加热溶解,加热搅拌反应10h(TLC检测)。反应结束后,冷却,产物以固体形态析出,抽滤并以冷乙醇洗涤,重结晶得到目标化合物。
步骤1中所述的取代苯乙酮与萘甲醛的投料摩尔比为1∶(1-1.1),最优投料摩尔比为1∶1.05,所属的有机溶剂为乙醇,所述的磁搅拌时间为10min,所述的萘甲醛可以分别为1-萘甲醛或2-萘甲醛,所述pH值为8-10,最优pH值为9.1,所述的反应温度为常温,所述的重结晶条件为采用体积比为10∶1的乙醇与丙酮混合液重结晶;
步骤2中所述的第一步产物与硫代氨基脲的投料摩尔比为1∶(1-1.1),最优投料摩尔比为1∶1.05,所述的有机溶剂为异丙醇或乙醇,所述的反应温度为75-85℃,最优反应温度为80℃,所述的冷却温度为5℃以下,所述的重结晶条件为采用体积比为10∶1的乙醇与丙酮混合液重结晶。
本发明的优点是:本发明所述的衍生物特殊的硫脲类骨架结构是许多酶抑制剂与生物模拟肽的常见结构特征,能与靶标形成较强的相互作用,从而被识别和结合;而在此基础上引入的辅助基团萘环与吡唑啉均是医药中间体中常见的具有抗菌和抗肿瘤活性的结构,增大了活性基团的比例,分别提供了亲脂端和亲水端,为分子在体内的传输和透膜提供了更大可能,其中萘环结构的引入是基于计算机辅助药物设计进行的合理骨架修饰。
具体实施方式
通过以下实施例进一步详细说明本发明,但应注意本发明的范围并不受这些实施例的任何限制。
实施例一:5-(萘-1-基)-3-苯基-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物1a)的制备
取5.0mmol苯乙酮和5.25mmol 1-萘甲醛加入到50ml的圆底烧中,加入20ml无水乙醇,磁搅拌10min使混合均匀,缓慢滴入40%NaOH溶液10ml(pH值为9.1),磁搅拌,常温反应2h(TLC检测反应进行程度),产物以固体析出,抽滤,并以大量的蒸馏水洗涤固体物,用冷乙醇洗涤3次(每次3ml),干燥,产物用乙醇与丙酮混合液(体积比乙醇∶丙酮=10∶1)重结晶;在50ml烧瓶中加入2.0mmol上述产物,2.1mmol硫代氨基脲,以20ml无水乙醇加热至80℃溶解,80℃回流反应10h(TLC检测)。反应结束后,冷却至5℃以下,产物以固体形态析出,抽滤并以冷乙醇洗涤3次(每次3ml),用乙醇与丙酮混合液(体积比乙醇∶丙酮=10∶1)重结晶,得到纯净的化合物1a(白色晶体)。White crystal,Yield 81%;mp:227-230℃.1H NMR(CDCl3,300MHz)δ:3.02-3.10(dd,J1=18.0Hz,J2=3.6Hz,1H),4.09-4.19(dd,J1=18.0Hz,J2=11.4Hz,1H),6.65-6.70(dd,J1=11.4Hz,J2=3.3Hz,1H),7.01-7.03(d,J=6.9Hz,1H),7.39-7.44(m,4H),7.54-7.64(m,2H),7.79-7.87(m,3H),7.95-7.98(d,J=8.1Hz,1H),8.16-8.19(d,J=8.1Hz,1H).MS(ESI):332.11(C20H18N3S,[M+H]+).Anal.Calcd for C20H17N3S:C,72.48;H,5.17;N,12.68;S,9.67.Found:C,72.31;H,7.18;N,12.70.
实施例二:3-(4-氟苯基)-5-(萘-1-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物2a)的制备
制备方法同实施例一。以对氟苯乙酮代替实例一中的苯乙酮,得到白色晶体状目标化合物。White crystal,Yield 78%,mp:218-220℃.1H NMR(CDCl3,300MHz)δ:3.12-3.19(dd,J1=17.4Hz,J2=3.7Hz,1H),3.95-4.05(dd,J1=17.4Hz,J2=11.4Hz,1H),6.36(s,1H),6.79-6.84(dd,J1=11.1Hz,J2=3.3Hz,1H),7.05-7.11(t,J=8.7Hz,1H),7.21-7.28(m,1H),7.39-7.45(t,J=7.5Hz,1H),7.51-7.62(m,2H),7.67-7.71(dd,J1=9.0Hz,J2=5.4Hz,2H),7.78-7.80(d,J=8.4Hz,1H),7.90-7.92(d,J=8.4Hz,1H),8.00-8.03(d,J=8.1Hz,1H).MS(ESI):350.10(C20H17FN3S,[M+H]+).Anal.Calcd for C20H16FN3S:C,68.75;H,4.62;F,5.44;N,12.03;S,9.18.Found:C,68.59;H,4.63;N,12.04.
实施例三:3-(4-氯苯基)-5-(萘-1-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物3a)的制备
制备方法同实施例一。以对氯苯乙酮代替实例一中的苯乙酮,得到淡黄色晶体状目标化合物。Yellow crystal,Yield 79%;mp:230-233℃.1H NMR(CDCl3,300MHz)δ:3.02-3.10(dd,J1=18.0Hz,J2=3.6Hz,1H),4.07-4.16(dd,J1=18.0Hz,J2=11.4Hz,1H),6.65-6.70(dd,J1=11.4Hz,J2=3.3Hz,1H),7.00-7.02(d,J=7.2Hz,1H),7.39-7.48(m,3H),7.53-7.64(m,2H),7.79-7.82(d,J=8.1Hz,1H),7.86-7.89(d,J=8.4Hz,2H),7.95-7.98(d,J=8.1Hz,1H),8.15-8.18(d,J=8.1Hz,1H).MS(ESI):366.08(C20H17ClN3S,[M+H]+).Anal.Calcd for C20H16ClN3S:C,65.65;H,4.41;Cl,9.69;N,11.48;S,8.76.Found:C,65.42;H,4.41;N,11.50.
实施例四:3-(4-溴苯基)-5-(萘-1-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物4a)的制备
制备方法同实施例一。以对溴苯乙酮代替实例一中的苯乙酮,得到淡黄色晶体状目标化合物。Yellow crystal,Yield 77%,mp:138-140℃.1H NMR(CDCl3,300MHz)δ:3.16-3.20(dd,J1=10.5Hz,J2=2.1Hz,1H),4.00-4.06(dd,J1=10.5Hz,J2=6.9Hz,1H),6.19(s,1H),6.81-6.83(d,J=6.6Hz,1H),7.08-7.11(t,J=5.1Hz,2H),7.41-7.44(t,J=4.6Hz,1H),7.53-7.56(t,J=4.2Hz,1H),7.59-7.62(t,J=4.5Hz,1H),7.70-7.73(m,2H),7.79-7.80(d,J=4.8Hz,1H),7.91-7.92(d,J=4.8Hz,1H),8.01-8.02(d,J=5.1Hz,1H).MS(ESI):410.02(C20H17BrN3S,[M+H]+).Anal.Calcd for C20H16BrN3S:C,58.54;H,3.93;Br,19.47;N,10.24;S,7.81.Found:C,58.43;H,3.94;N,10.25.
实施例五:3-(4-甲氧基苯基)-5-(萘-1-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物5a)的制备
制备方法同实施例一。以对甲氧基苯乙酮代替实例一中的苯乙酮,得到白色晶体状目标化合物。White crystal,Yield 79%,mp:211-214℃.1H NMR(CDCl3,300MHz)δ:3.15-3.19(dd,J1=10.4Hz,J2=2.1Hz,1H),3.83(s,3H),3.98-4.03(dd,J1=10.5Hz,J2=6.9Hz,1H),6.78-6.80(d,J=4.9Hz,1H),6.89-6.91(d,J=5.4Hz,2H),7.21-7.23(d,J=4.3Hz,1H),7.40-7.43(t,J=4.5Hz,1H),7.52-7.54(t,J=4.2Hz,1H),7.58-7.61(t,J=4.2Hz,1H),7.64-7.66(d,J=5.4Hz,2H),7.77-7.79(d,J=4.9Hz,1H),7.90-7.91(d,J=4.8Hz,1H),8.02-8.03(d,J=5.1Hz,1H).MS(ESI):362.12(C21H20N3OS,[M+H]+).Anal.Calcd for C21H19N3OS:C,69.78;H,5.30;N,11.63;O,4.43;S,8.87.Found:C,69.57;H,5.30;N,11.65.
实施例六:5-(萘-1-基)-3-(对甲苯基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物6a)的制备
制备方法同实施例一。以对甲基苯乙酮代替实例一中的苯乙酮,得到白色晶体状目标化合物。White crystal,Yield 76%,mp:223-227℃.1H NMR(CDCl3,300MHz)δ:2.33(s,3H),3.01-3.08(dd,J1=18.0Hz,J2=3.6Hz,1H),4.08-4.18(dd,J1=17.7Hz,J2=11.4Hz,lH),6.65-6.70(dd,J1=11.4Hz,J2=3.3Hz,1H),7.02-7.05(d,J=7.2Hz,1H),7.22-7.25(d,J=8.1Hz,1H),7.40-7.46(t,J=8.1Hz,1H),7.56-7.66(m,2H),7.75-7.78(d,J=8.1Hz,2H),7.81-7.84(d,J=8.1Hz,1H),7.98-8.00(d,J=7.8Hz,2H),8.17-8.20(d,J=8.4Hz,1H).MS(ESI):346.13(C21H20N3S,[M+H]+).Anal.Calcd for C21H19N3S:C,73.01;H,5.54;N,12.16;S,9.28.Found:C,72.82;H,5.55;N,12.17.
实施例七:3-(3,4-二氯苯基)-5-(萘-1-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物7a)的制备
制备方法同实施例一。以3,4-二氯苯乙酮代替实例一中的苯乙酮,得到淡黄色晶体状目标化合物。Yellow crystal,Yield 74%,mp:210-214℃.1H NMR(CDCl3,300MHz)δ:3.16-3.25(dd,J1=17.7Hz,J2=3.6Hz,1H),4.05-4.14(dd,J1=17.7Hz,J2=11.4Hz,1H),6.67-6.73(dd,J1=11.4Hz,J2=3.3Hz,1H),7.02-7.04(d,J=7.2Hz,1H),7.55-7.60(m,3H),7.64-7.68(m,2H),8.00-8.01(d,J=4.8Hz,1H),8.21-8.22(d,J=4.2Hz,1H),8.26(s,1H),8.35-8.37(d,J=5.1Hz,1H).MS(ESI):400.04(C20H16Cl2N3S,[M+H]+).Anal.Calcd for C20H15Cl2N3S:C,60.00;H,3.78;Cl,17.71;N,10.50;S,8.01.Found:C,59.91;H,3.78;N,10.50.
实施例八:5-(萘-2-基)-3-苯基-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物1b)的制备
制备方法同实施例一。以2-萘甲醛代替实例一中的1-萘甲醛,得到白色粉末状目标化合物。White powder,Yield 82%,mp:202-204℃.1H NMR(CDCl3,300MHz)δ:3.22-3.26(dd,J1=10.8Hz,J2=2.4Hz,1H),3.97-4.02(dd,J1=10.8Hz,J2=6.9Hz,1H),6.07-6.10(dd,J1=6.9Hz,J2=2.4Hz,1H),7.29-7.31(dd,J1=5.1Hz,J2=0.9Hz,1H),7.44-7.50(m,5H),7.64(s,1H),7.86-7.91(m,5H),7.95-8.06(d,J=33.6Hz,2H).MS(ESI):332.11(C20H18N3S,[M+H]+).Anal.Calcd for C20H17N3S:C,72.48;H,5.17;N,12.68;S,9.67.Found:C,72.28;H,5.18;N,12.68.
实施例九:3-(4-氟苯基)-5-(萘-1-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物2b)的制备
制备方法同实施例一。以对氟苯乙酮代替实例一中的苯乙酮并以2-萘甲醛代替实施例一中的1-萘甲醛,得到白色粉末状目标化合物。White powder,Yield 79%,mp:230-234℃.1H NMR(CDCl3,300MHz)δ:3.15-3.19(dd,J1=10.8Hz,J2=2.1Hz,1H),3.89-3.95(dd,J1=10.8Hz,J2=6.9Hz,1H),6.03(m,1H),7.45-7.47(d,J=5.1Hz,2H),7.54-7.55(m,2H),7.90-7.96(m,4H),8.06(m,1H),8.11(s,1H),8.16-8.18(d,J=5.1Hz,1H),8.22(s,2H).MS(ESI):350.10(C20H17FN3S,[M+H]+).Anal.Calcd for C20H16FN3S:C,68.75;H,4.62;F,5.44;N,12.03;S,9.18.Found:C,68.57;H,4.63;N,12.03.
实施例十:3-(4-氯苯基)-5-(萘-2-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物3b)的制备
制备方法同实施例一。以对氯苯乙酮代替实例一中的苯乙酮并以2-萘甲醛代替实施例一中的1-萘甲醛,得到淡黄色粉末状目标化合物。Yellow powder,Yield 78%;mp:170-173℃.1H NMR(CDCl3,300MHz)δ:3.21-3.26(dd,J1=11.1Hz,J2=2.4Hz,1H),3.95-4.01(dd,J1=11.1Hz,J2=6.9Hz,1H),6.07-6.10(dd,J1=6.9Hz,J2=2.1Hz,1H),7.28-7.30(d,J=4.5Hz,1H),7.46-7.50(m,3H),7.52-7.54(d,J=5.7Hz,1H),7.63(s,1H),7.85-7.93(m,5H),8.02-8.09(d,J=22.2Hz,2H).MS(ESI):366.08(C20H17ClN3S,[M+H]+).Anal.Calcd for C20H16ClN3S:C,65.65;H,4.41;Cl,9.69;N,11.48;S,8.76.Found:C,65.47;H,4.42;N,11.49.
实施例十一:3-(4-溴苯基)-5-(萘-2-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物4b)的制备
制备方法同实施例一。以对溴苯乙酮代替实例一中的苯乙酮并以2-萘甲醛代替实施例一中的1-萘甲醛,得到淡黄色粉末状目标化合物。Yellow powder,Yield 74%,mp:293-295℃.1H NMR(CDCl3,300MHz)δ:3.00-3.05(dd,J1=11.9Hz,J2=3.3Hz,1H),4.15-4.20(dd,J1=10.8Hz,J2=6.6Hz,1H),5.41(m,1H),7.17-7.18(d,J=5.1Hz,1H),7.25-7.36(m,4H),7.38-7.42(m,1H),7.48(m,1H),7.53-7.55(d,J=5.1Hz,1H),7.57-7.59(d,J=5.1Hz,1H),7.62-7.64(d,J=5.1Hz,1H),7.71-7.72(d,J=5.1Hz,1H),7.74-7.76(m,1H),7.89(s,1H).MS(ESI):410.02(C20H17BrN3S,[M+H]+).Anal.Calcd for C20H16BrN3S:C,58.54;H,3.93;Br,19.47;N,10.24;S,7.81.Found:C,58.39;H,3.94;N,10.24.
实施例十二:3-(4-甲氧基苯基)-5-(萘-2-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物5b)的制备
制备方法同实施例一。以对甲氧基苯乙酮代替实例一中的苯乙酮并以2-萘甲醛代替实例一中的1-萘甲醛,得到白色粉末状目标化合物。White powder,Yield 79%,mp:170-172℃.1H NMR(CDCl3,300MHz)δ:3.19-3.23(dd,J1=10.8Hz,J2=2.1Hz,1H),3.80(s,3H),3.92-3.98(dd,J1=10.8Hz,J2=6.9Hz,1H),6.04-6.07(dd,J1=6.9Hz,J2=2.1Hz,1H),7.00-7.01(d,J=5.1Hz,2H),7.28-7.30(d,J=5.1Hz,1H),7.45-7.50(m,2H),7.62(s,1H),7.83-7.88(m,6H),7.97(s,1H).MS(ESI):362.12(C21H20N3OS,[M+H]+).Anal.Calcd for C21H19N3OS:C,69.78;H,5.30;N,11.63;O,4.43;S,8.87.Found:C,69.56;H,5.31;N,11.63.
实施例十三:5-(萘-2-基)-3-(对甲苯基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物6b)的制备
制备方法同实施例一。以对甲基苯乙酮代替实例一中的苯乙酮并以2-萘甲醛代替实施例一中的1-萘甲醛,得到白色粉末状目标化合物。White powder,Yield 75%,mp:179-182℃.1H NMR(CDCl3,300MHz)δ:2.34(s,3H),3.20-3.23(dd,J1=10.8Hz,J2=2.4Hz,1H),3.94-4.00(dd,J1=11.1Hz,J2=6.9Hz,1H),6.05-6.08(dd,J1=6.9Hz,J2=2.4Hz,1H),7.26-7.28(d,J=4.8Hz,2H),7.29-7.30(d,J=0.9Hz,1H),7.46-7.50(m,2H),7.62(s,1H),7.78-7.80(d,J=5.1Hz,2H),7.85-7.88(m,4H),8.01(s,1H).MS(ESI):346.13(C21H20N3S,[M+H]+).Anal.Calcd for C21H19N3S:C,73.01;H,5.54;N,12.16;S,9.28.Found:C,72.85;H,5.54;N,12.18.
实施例十四:3-(3,4-二氯苯基)-5-(萘-2-基)-4,5-二氢-1H-吡唑-1-硫代酰胺(化合物7b)的制备
制备方法同实施例一。以3,4-二氯苯乙酮代替实例一中的苯乙酮并以2-萘甲醛代替实施例一中的1-萘甲醛,得到淡黄色粉末状目标化合物。Yellow powder,Yield75%,mp:201-204℃.1H NMR(CDCl3,300MHz)δ:3.25-3.30(dd,J1=10.8Hz,J2=2.4Hz,1H),3.93-3.99(dd,J1=11.1Hz,J2=7.2Hz,1H),6.07-6.10(dd,J1=6.9Hz,J2=2.1Hz,1H),7.28-7.29(d,J=4.2Hz,1H),7.47-7.50(m,2H),7.63(s,1H),7.71-7.73(d,J=5.1Hz,1H),7.80-7.82(dd,J1=5.1Hz,J2=1.2Hz,1H),7.86-7.88(m,3H),8.14-8.16(d,J=6.6Hz,2H),8.26(s,1H).MS(ESI):400.04(C20H16Cl2N3S,[M+H]+).Anal.Calcd for C20H15Cl2N3S:C,60.00;H,3.78;Cl,17.71;N,10.50;S,8.01.Found:C,59.87;H,3.79;N,10.51.
本发明的优点是:本发明所述的衍生物特殊的硫脲类骨架结构是许多酶抑制剂与生物模拟肽的常见结构特征,能与靶标形成较强的相互作用,从而被识别和结合;而在此基础上引入的辅助基团萘环与吡唑啉均是医药中间体中常见的具有抗菌和抗肿瘤活性的结构,增大了活性基团的比例,分别提供了亲脂端和亲水端,为分子在体内的传输和透膜提供了更大可能,其中萘环结构的引入是基于计算机辅助药物设计进行的合理骨架修饰。
Claims (6)
2.根据权利要求1所述的含萘环和吡唑啉结构的硫脲类衍生物,其特征是所述衍生物由以下步骤制备:
步骤1、将取代基苯乙酮,萘甲醛溶于有机溶剂中,磁搅拌使混合均匀,缓慢滴入NaOH溶液,磁搅拌,常温反应2h,产物以固体析出。反应结束后抽滤,并以大量的蒸馏水和冷乙醇洗涤固体,干燥,重结晶;
步骤2、将步骤1中所得产物与硫代氨基脲,以有机溶剂加热溶解,加热搅拌反应10h,反应结束后,冷却,产物以固体形态析出,抽滤并以冷乙醇洗涤,重结晶得到目标化合物。
3.根据权利要求1或2所述的含萘环和吡唑啉结构的硫脲类衍生物,其特征是步骤1中所述的取代苯乙酮与萘甲醛的投料摩尔比为1∶(1-1.1),最优投料摩尔比为1∶1.05,所述的有机溶剂为乙醇,所述的磁搅拌时间为10min,所述的萘甲醛可以分别为1-萘甲醛或2-萘甲醛,所述pH值为8-10,最优pH值为9.1,所述的反应温度为常温,所述的重结晶条件为采用体积比为10∶1的乙醇与丙酮混合液重结晶。
4.根据权利要求1或2所述的含萘环和吡唑啉结构的硫脲类衍生物,其特征是步骤2中所述的第一步产物与硫代氨基脲的投料摩尔比为1∶(1-1.1),最优投料摩尔比为1∶1.05,所述的有机溶剂为异丙醇或乙醇,所述的反应温度为75-85℃,最优反应温度为80℃,所述的冷却温度为5℃以下,所述的重结晶条件为采用体积比为10∶1的乙醇与丙酮混合液重结晶。
5.一类含萘环和吡唑啉结构的硫脲类衍生物的制备方法,其特征是所述方法包括以下步骤:
步骤1、将取代基苯乙酮,萘甲醛溶于有机溶剂中,磁搅拌使混合均匀,缓慢滴入NaOH溶液,磁搅拌,常温反应2h,产物以固体析出。反应结束后抽滤,并以大量的蒸馏水和冷乙醇洗涤固体,干燥,重结晶;
步骤2、将步骤1中所得产物与硫代氨基脲,以有机溶剂加热溶解,加热搅拌反应10h,反应结束后,冷却,产物以固体形态析出,抽滤并以冷乙醇洗涤,重结晶得到目标化合物。
6.根据权利要求5所述的含萘环和吡唑啉结构的硫脲类衍生物的制备方法,其特征是:
步骤1中所述的取代苯乙酮与萘甲醛的投料摩尔比为1∶(1-1.1),最优投料摩尔比为1∶1.05,所述的有机溶剂为乙醇,所述的磁搅拌时间为10min,所述的萘甲醛可以分别为1-萘甲醛或2-萘甲醛,所述pH值为8-10,最优pH值为9.1,所述的反应温度为常温,所述的重结晶条件为采用体积比为10∶1的乙醇与丙酮混合液重结晶;
步骤2中所述的第一步产物与硫代氨基脲的投料摩尔比为1∶(1-1.1),最优投料摩尔比为1∶1.05,所述的有机溶剂为异丙醇或乙醇,所述的反应温度为75-85℃,最优反应温度为80℃,所述的冷却温度为5℃以下,所述的重结晶条件为采用体积比为10∶1的乙醇与丙酮混合液重结晶。
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