CN115304465A - 一种将1,3-二噻烷衍生物转化为羰基化合物的绿色方法 - Google Patents
一种将1,3-二噻烷衍生物转化为羰基化合物的绿色方法 Download PDFInfo
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Abstract
本发明提供了一种将1,3‑二噻烷衍生物转化为羰基化合物的绿色方法,属于绿色有机化学领域。该方法以MBrx(M为Fe3+、Ce3+、Ce4+等,x为3‑4)为催化剂,H2O2为唯一氧化剂,在中性、敞口、室温条件下原位生成活性溴(RBS)作为直接氧化剂快速完成硫代缩醛(酮)的脱保护反应。本发明所用催化剂(如CeBr3、FeBr3等)、氧化剂H2O2和溶剂(如乙醇、正丁醇等)价廉易得,反应时间短且条件温和,具有广泛的官能团相容性,产品收率高(75%‑99%),后处理简单,容易操作,是当前非常绿色、环保、安全的缩硫醛(酮)脱保护成羰基化合物的方法,具有广阔的应用前景。
Description
技术领域
本发明属于绿色化学和有机合成技术领域,具体涉及一种将1,3-二噻烷衍生物转化为羰基化合物的绿色方法。
背景技术
在众多有机合成反应中,羰基保护往往是必不可少的步骤,特别是在天然产物和多功能有机化合物的全合成中。硫代缩醛(酮)因其在酸性和碱性条件下易于制备和稳定性高而成为广泛应用的羰基保护基团。
目前,关于1,3-二噻烷衍生物去保护的方法有很多,例如可用化学计量或过量的有毒反应物,包括汞(II)和其他重金属盐;此外,还有利用多相条件、使用各种Fe(III)和Cu(II)盐的方法,以及其他无溶剂的方法等,但这些方法通常需要苛刻的反应条件。硫代缩醛(酮)类化合物在复杂分子合成中的应用往往因为缺乏温和、通用的去除方法而受到阻碍。传统上,硫代缩醛(酮)的裂解主要是通过氧化手段或汞(II)盐的作用来实现的,然而,这些方法经常在烯烃、芳香环、易被氧化的基团和酸敏感性官能团的存在下导致竞争性副反应且会对环境造成一定的污染。
因此,开发一种绿色、高效、易于操作且普遍适用的缩硫醛(酮)脱保护成羰基化合物的方法具有重要意义。
发明内容
本发明的目的是,开发一种将1,3-二噻烷衍生物转化为羰基化合物的通用、绿色的方法。
本发明采用的技术方案为:
一种将1,3-二噻烷衍生物转化为羰基化合物的绿色方法:
在中性、敞口、室温条件下,以MBrx(M为Fe3+、Ce3+、Ce4+等,x为3-4)作催化剂,H2O2作唯一氧化剂,短时间内完成1,3-二噻烷衍生物转化为羰基化合物的反应。
反应于溶剂中进行,所用溶剂可为甲醇、乙醇、正丁醇、乙腈、四氢呋喃、***、二氯甲烷、二甲基四氢呋喃等。
反应底物为具有不同官能团的1,3-二噻烷衍生物,所述官能团可为氢基、烷基、烯基、炔基、芳基、酯基、脂环烃等不同官能团或呋喃、吡啶、噻吩、吡咯以及其他杂环等不同取代基,也可为常用的保护基团如Ac、TBS、THP、Bn、Boc和TIPS等。
反应在催化剂条件下进行,所用催化剂为CeBr3、FeBr3、CeBr4以及Ce(NO3)3-KBr、CeCl3-KBr、Ce2(C2O4)3-KBr、FeCl3-KBr、Fe(NO3)3-KBr、Ce(SO4)2-KBr等金属(Ce3+、Fe3+、Ce4+)和溴化物的组合中的任意一种。
具体操作时,提供一种方案:将1,3-二噻烷衍生物和催化剂如FeBr3、CeBr3等(0.01-0.2eq)加入适量乙醇中搅拌均匀,然后向搅拌悬浮液中加入H2O2水溶液(30wt%,2-10eq)。反应混合物在室温下继续搅拌反应5-40min。反应完成后用稀释的Na2S2O3溶液(0.1M)淬灭和乙酸乙酯萃取。收集有机相,水相用乙酸乙酯萃取2-3次。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得产物。
本发明的有益效果:
本发明与现有技术相比具有以下优点和效果:
本发明首次实现了在中性条件下由MBrx-H2O2原位生成RBS催化1,3-二噻烷衍生物转化为羰基化合物的反应,是一种可放大的脱除羰基保护基的绿色方法。与现有的缩硫醛(酮)脱保护成羰基化合物的方法相比,该方法具有原料易得、成本低、反应快、底物适用范围广、路线简单、容易操作、对环境友好等特点,比之前所有的方法更具优势,具有良好的应用前景。
附图说明
图1和图2是实施例1的1H-NMR及13C-NMR谱图
图3和图4是实施例2的1H-NMR及13C-NMR谱图
图5和图6是实施例3的1H-NMR及13C-NMR谱图
图7和图8是实施例4的1H-NMR及13C-NMR谱图
图9和图10是实施例5的1H-NMR及13C-NMR谱图
图11和图12是实施例6的1H-NMR及13C-NMR谱图
图13和图14是实施例7的1H-NMR及13C-NMR谱图
图15和图16是实施例8的1H-NMR及13C-NMR谱图
图17和图18是实施例9的1H-NMR及13C-NMR谱图
图19和图20是实施例10的1H-NMR及13C-NMR谱图
图21和图22是实施例11的1H-NMR及13C-NMR谱图
图23和图24是实施例12的1H-NMR及13C-NMR谱图
具体实施方式
下面用具体实施方案详述本发明,但本发明的保护范围不仅限于此。
以下实施例中的1H-NMR及13C-NMR谱均在室温条件下测定,记录在400MHz光谱仪上,1H为400MHz,13C为100MHz,光谱仪来自布鲁克公司。
实施例1
将乙醇40ml、1a(4mmol,1g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物1b(产率:95%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ2.37(t,J=7.5Hz,4H),1.66-1.47(m,4H),1.40-1.16(m,8H),0.87(t,J=7.1Hz,6H).13C-NMR(100MHz,CDCl3)δ211.82(s),42.90(s),31.58(s),23.70(s),22.59(s),14.04(s).
实施例2
将乙醇40ml、2a(4mmol,1g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物2b(产率:87%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ8.46(s,1H),8.03(dd,J=8.6,1.7Hz,1H),7.96(d,J=8.0Hz,1H),7.88(dd,J=8.1,5.7Hz,2H),7.66-7.51(m,2H),2.72(s,3H).13C-NMR(100MHz,CDCl3)δ198.20(s),135.70(s),134.61(s),132.63(s),130.30(s),129.66(s),128.55(d,J=5.2Hz),127.89(s),126.88(s),124.01(s),26.79(s).
实施例3
将乙醇50ml、3a(5mmol,1.1g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.4mmol,0.152g),H2O2水溶液(30wt%,15mmol,1.53ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,75mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物3b(产率:92%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ7.70(dd,J=3.8,1.1Hz,1H),7.63(dd,J=5.0,1.1Hz,1H),7.13(dd,J=4.9,3.8Hz,1H),2.57(s,3H).13C-NMR(100MHz,CDCl3)δ190.86(s),144.74(s),133.90(s),132.58(s),128.24(s),27.08(s).
实施例4
将乙醇40ml、4a(4mmol,1.1g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物4b(产率:97%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ7.80(dd,J=5.2,3.3Hz,1H),7.63-7.55(m,1H),7.48(dd,J=10.5,4.7Hz,1H).13C-NMR(100MHz,CDCl3)δ196.84(s),137.71(s),132.52(s),130.16(s),128.38(s).
实施例5
将乙醇40ml、5a(4mmol,0.95g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物5b(产率:81%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ8.14-7.98(m,1H),7.46(td,J=7.5,1.4Hz,1H),7.39-7.10(m,2H),2.96(t,J=6.1Hz,2H),2.84-2.55(m,2H),2.14(dt,J=12.6,6.4Hz,2H).13C-NMR(100MHz,CDCl3)δ198.48(s),144.59(s),133.49(s),132.72(s),128.87(s),127.26(s),126.72(s),39.27(s),29.81(s),23.39(s).
实施例6
将乙醇40ml、6a(4mmol,0.96g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物6b(产率:78%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ8.13-7.83(m,2H),7.11-6.68(m,2H),3.87(s,3H),2.55(s,3H).13C-NMR(100MHz,CDCl3)δ196.91(s),163.62(s),130.72(s),130.49(s),113.81(s),55.60(s),26.47(s).
实施例7
将乙醇40ml、7a(4mmol,1.1g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物7b(产率:75%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ7.99(d,J=8.7Hz,1H),7.19(d,J=8.7Hz,1H),2.59(s,2H),2.32(s,2H).13C-NMR(100MHz,CDCl3)δ196.90(s),168.93(s),154.43(s),134.81(s),130.02(s),121.85(s),26.66(s),21.21(s).
实施例8
将乙醇30ml、8a(3mmol,0.95g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.24mmol,0.091g),H2O2水溶液(30wt%,9mmol,0.92ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,45mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物8b(产率:82%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ8.05-7.83(m,2H),7.54-7.28(m,5H),7.11-6.89(m,2H),5.13(s,2H),2.55(s,3H).13C-NMR(100MHz,CDCl3)δ196.83(s),162.71(s),136.28(s),130.66(d,J=6.8Hz),128.79(s),128.34(s),127.56(s),114.64(s),70.22(s),26.44(s).
实施例9
将乙醇40ml、9a(4mmol,1.1g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物9b(产率:96%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ7.65(d,J=7.3Hz,2H),7.48(ddd,J=8.9,8.4,4.0Hz,4H),7.35-7.20(m,2H).13C-NMR(100MHz,CDCl3)δ194.04(s),144.56(s),134.80(s),134.28(s),129.20(s),124.44(s),120.43(s).
实施例10
将乙醇40ml、10a(4mmol,1g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物10b(产率:89%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ10.11(s,1H),8.27(s,1H),7.90(ddd,J=25.8,13.7,8.6Hz,4H),7.68-7.43(m,2H).13C-NMR(100MHz,CDCl3)δ192.24(s),136.45(s),134.56(s),134.12(s),132.65(s),129.55(s),129.12(d,J=4.0Hz),128.10(s),127.12(s),122.75(s).
实施例11
将乙醇40ml、11a(4mmol,1g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物11b(产率:83%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ9.81(s,1H),7.49-7.33(m,2H),6.94(d,J=8.2Hz,1H),3.92(d,J=10.7Hz,6H).13C-NMR(100MHz,CDCl3)δ190.96(s),154.49(s),149.61(s),130.13(s),126.94(s),110.40(s),108.88(s),56.12(d,J=19.1Hz).
实施例12
将乙醇40ml、12a(4mmol,0.95g)依次加入100ml圆底烧瓶中,搅拌均匀,然后向二者混合物中依次加入CeBr3(0.32mmol,0.122g),H2O2水溶液(30wt%,12mmol,1.23ml),在室温下搅拌反应10min。反应完成后用Na2S2O3溶液(0.1M,60mL)淬灭反应,用乙酸乙酯(100mL)萃取。收集有机相,水相用乙酸乙酯(2x50mL)萃取。合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得目标产物12b(产率:75%)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ9.80(s,1H),7.88-7.50(m,2H),6.85(d,J=8.2Hz,1H),4.66(t,J=8.8Hz,2H),3.24(t,J=8.8Hz,2H).13C-NMR(100MHz,CDCl3)δ190.71(s),165.70(s),133.05(s),130.46(s),128.51(s),125.96(s),109.66(s),72.48(s),28.80(s).
Claims (9)
2.根据权利要求1所述的方法,其特征在于:反应在催化剂条件下进行,所用催化剂为CeBr3、FeBr3、CeBr4以及Ce(NO3)3-KBr、CeCl3-KBr、Ce2(C2O4)3-KBr、FeCl3-KBr、Fe(NO3)3-KBr、Ce(SO4)2-KBr等金属(Ce3+、Fe3+、Ce4+)和溴化物的组合中的任意一种,催化剂与1,3-二噻烷衍生物的摩尔比为0.01-0.2∶1。
3.根据权利要求1所述的方法,其特征在于:H2O2为唯一氧化剂,其浓度为3-30%,H2O2与1,3-二噻烷衍生物的摩尔比为2-10∶1。
4.根据权利要求1所述的方法,其特征在于:反应于溶剂中进行,所用溶剂可为甲醇、乙醇、正丁醇、乙腈、四氢呋喃、***、二氯甲烷、二甲基四氢呋喃等,1,3-二噻烷衍生物与溶剂用量的比例为1mmol/10-20ml。
5.根据权利要求1所述的方法,其特征在于:反应温度为室温。
6.根据权利要求1所述的方法,其特征在于:反应在不排除空气和水分的情况下即可进行,即敞口条件下进行;反应在pH为中性条件下进行。
7.根据权利要求1所述的方法,其特征在于:较佳反应时间为5-40min。
8.根据权利要求1所述的方法,其特征在于:具体操作时,将1,3-二噻烷衍生物和催化剂加入适量溶剂中搅拌均匀,然后向搅拌悬浮液中加入H2O2水溶液,反应混合物在室温下继续搅拌反应5-40min,完成1,3-二噻烷衍生物转化为羰基化合物的反应。
9.根据权利要求1所述的方法,其特征在于:所述缩硫醛(酮)脱保护成羰基化合物的反应的处理方法为,反应完成后用稀释的Na2S2O3溶液淬灭和与水分层的有机溶剂如乙酸乙酯萃取,收集有机相,水相再用有机溶剂萃取2-3次,合并有机相后依次用水洗,无水硫酸钠干燥,过滤,减压浓缩,即可得羰基化合物。
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