CN112939749A - 一种绿色的溴化方法 - Google Patents
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Abstract
本发明公开了一种绿色的溴化方法，属于绿色有机化学领域。在室温、敞口、中性的条件下，反应原料为具有不同官能团的芳烃、烯烃、炔烃、色胺、色醇及其衍生物，溴源为MBrx(M为Fe2+、Fe3+、Ce3+等，x为2‑3)，唯一氧化剂为H2O2。可以生成溴代烷烃、烯烃、芳烃、吡咯并吲哚啉和呋喃并吲哚啉及其衍生物。本发明通过使用市面上易获得且廉价的试剂(如FeBr2、CeB3和H2O2)和溶剂进行溴代反应，其特点在于反应条件温和，底物适用范围广泛，步骤简洁，易于操作，无需分离，是一种绿色、环保、安全的溴代反应方法，具有良好的应用前景。
Description
技术领域
本发明涉及绿色化学和有机合成技术领域，具体涉及一种新的制备溴代烷烃、烯烃、芳烃、吡咯并吲哚啉和呋喃并吲哚啉及其衍生物的绿色方法。
背景技术
有机溴化物是一种常见的有机合成中间体，在天然产物全合成中起到了重要作用，能广泛应用于材料、医药、农药、电子产品等行业中，具有广泛的应用范围和市场前景。溴代反应是有机化合物分子中的氢被溴取代，生成含溴化合物的反应，因此制备溴代烷烃、烯烃、芳烃、吡咯并吲哚啉和呋喃并吲哚啉及其衍生物十分重要。
目前，报道制备溴代产物的文献很多，典型的制备方法包括使用Br2，N-溴代丁二酰亚胺(NBS)和卤化盐等。其中用NBS做溴源操作相对简单、对多种官能团耐受性强，且大多数情况下产率较高，是应用最广泛的氧化剂。但是其原子利用率不高,副产物是分子量相对较大的丁二酰亚胺，这通常需要进一步分离纯化，步骤繁琐且不够绿色。由此可见，开发一种绿色、成本低、易制得且步骤简洁的制备溴代烷烃、烯烃、芳烃、吡咯并吲哚啉和呋喃并吲哚啉及其衍生物的新方法十分有意义。
发明内容
本发明的目的在于开发一种绿色、高效的溴代方法，用于制备溴代烷烃、烯烃、芳烃、吡咯并吲哚啉和呋喃并吲哚啉及其衍生物。
本发明采用的技术方案为：
一种绿色的溴化方法：
在室温、敞口、中性条件下，反应原料为具有不同官能团的芳烃、烯烃、炔烃、色胺、色醇及其衍生物，溴源为MBrx(M为Fe2+、Fe3+、Ce3+等，x为2-3)，唯一氧化剂为H2O2，可以生成溴代烷烃、烯烃、芳烃、吡咯并吲哚啉和呋喃并吲哚啉及其衍生物。
反应以官能团化的芳烃、烯烃、炔烃、色胺、色醇及其衍生物为原料，如图1，R1、R2、R3、R4、R5、R6可为烷烃、烯烃、炔烃、脂环烃、芳烃、酯、呋喃、噻吩、吡啶、吡咯等不同官能团以及常用的保护基团包括TIPS、TBS、Bn、Ac、Bz、Piv和Boc等。
所述溴源为FeBr2、CeBr3、FeBr3以及FeCl2-KBr、、Fe(NO3)3-KBr、Ce(NO3)3-KBr、CeCl3-KBr、Ce2(C2O4)3-KBr、Ce(SO4)2-KBr、Ce(OTf)3-KBr等，金属(Fe2+、Fe3+、Ce3+、Ce4+)和溴化物的组合中的任意一种。
反应所用的溶剂为四氢呋喃、二氯甲烷、乙腈、叔丁醇、1,4-二氧六环、乙二醇二甲醚以及其它有机溶剂。
具体操作时，提供一种方案：将官能团化的芳烃、烯烃、炔烃、色胺、色醇及其衍生物溶于反应溶剂如MeCN等，然后加入溴源如FeBr2(0.5-4.5eq)、CeBr3等(0.33-3eq)，搅拌均匀后分多次加入H2O2水溶液(30wt％，1-5eq)。混合物在室温下持续搅拌反应0.5-3h。用稀释的Na2S2O3溶液(0.1M)淬灭已经结束的反应，并用乙酸乙酯等有机溶剂分多次萃取，过滤，减压浓缩，即可得目标产物。
本发明的有益效果：
本发明与现有方法相比具有以下优点和效果：
本发明首次实现了以H2O2为氧化剂，FeBr2、CeBr3等MBrx类化合物为溴源的绿色溴代反应，能够广泛、大量合成官能团化溴代烷烃、烯烃、芳烃、吡咯并吲哚啉和呋喃并吲哚啉及其衍生物。在中性条件下由MBrx-H2O2原位生成RBS催化，FeBr2、CeBr3等MBrx类化合物作为简单的HPO功能模拟物，催化的溴代反应绿色且非酸性，解决了许多其他HPO功能模拟物用H2O2溴代物所需的强酸性环境问题。本发明通过使用市面上易获得且成本较低的试剂(如FeBr2、CeBr3和H2O2等)和常见的有机溶剂进行溴代反应，步骤简洁，反应条件温和，室温敞口，且无需进一步提取分离产物，比以前所有的方法更具优势，有望在有机合成、医药、农药及电子产品等行业中得到广泛应用。
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4的1H-NMR及13C-NMR谱图
图5和图6是实施例5的1H-NMR及13C-NMR谱图
图7和图8是实施例6的1H-NMR及13C-NMR谱图
图9和图10是实施例9的1H-NMR及13C-NMR谱图
图11和图12是实施例10的1H-NMR及13C-NMR谱图
图13和图14是实施例12的1H-NMR及13C-NMR谱图
图15和图16是实施例13的1H-NMR及13C-NMR谱图
图17和图18是实施例14的1H-NMR及13C-NMR谱图
图19和图20是实施例15的1H-NMR及13C-NMR谱图
图21和图22是实施例17的1H-NMR及13C-NMR谱图
图23和图24是实施例18的1H-NMR及13C-NMR谱图
图25和图26是实施例19的1H-NMR及13C-NMR谱图
图27和图28是实施例21的1H-NMR及13C-NMR谱图
具体实施方式
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-NMR为400MHz，13C-NMR为100MHz，光谱仪来自布鲁克公司。
下面用具体实施方案详述本发明，但本发明实施不局限于这些实施例：
实施例1
将1a(9.25mmol,1g)溶于MeCN(46ml)中，向二者混合物中依次加入FeBr2(13.88mmol,2.99g)或CeBr3(6.48mmol，2.46g),H2O2水溶液(30wt％,使用FeBr2时,30.53mmol,3.12ml；使用CeBr3时,20.35mmol,2.08ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,308ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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2a(产率:FeBr2:81％；CeBr3:92％)。该化合物的表征数据如下:1H-NMR(400MHz,CDCl3)δ:7.41-7.34(m,2H),6.83-6.74(m,2H),3.78(s,3H).13C-NMR(100MHz,CDCl3)δ:158.8,132.4,115.8,112.9,55.6.IR 2946.2,2835.5,1585.1,1484.6,1452.1,1287.4,1239.9,1173.5,1070.6,1028.7,815.3,595.9cm-1；HRMS(CI+)(m/z)calcd.forC7H7BrO[M]+185.9675；found 185.9680.
实施例2
将1b(4.80mmol,1g)溶于MeCN(24ml)中，向二者混合物中依次加入FeBr2(7.20mmol,1.55g)或CeBr3(3.36mmol，1.28g),H2O2水溶液(30wt％,使用FeBr2时,15.84mmol,1.62ml；使用CeBr3时,10.56mmol,1.08ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,160ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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(FeBr2:76％；CeBr3:94％).1H-NMR(400MHz,CDCl3)δ:7.35(d,J＝7.5Hz,2H),6.75(d,J＝7.6Hz,2H),1.01(s,9H),0.22(s,6H).13C-NMR(100MHz,CDCl3)δ:155.0,132.4,122.0,113.8,25.8,18.3,-4.4.IR2935.8,2858.2,1584.6,1480.5,12254.8,906.5,830.0,725.2cm-1；HRMS(CI+)(m/z)calcd.for C12H19BrOSi[M]+286.0383；found 286.0388.
实施例3
将1c(5.18mmol,1g)溶于MeCN(26ml)中，向二者混合物中依次加入FeBr2(7.77mmol,1.68g)或CeBr3(3.63mmol，1.38g),H2O2水溶液(30wt％,使用FeBr2时,17.10mmol,1.75ml；使用CeBr3时,11.40mmol,1.16ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,173mll)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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2c(FeBr2:71％；CeBr3:85％).1H-NMR(400MHz,CDCl3)δ:7.39(d,J＝8.4Hz,2H),7.27(d,J＝8.4Hz,2H),6.65(s,1H),1.53(s,9H).13C-NMR(100MHz,CDCl3)δ:152.7,137.6,131.9,120.2,115.5,81.0,28.4.IR3365.3,2980.1,1693.6,1589.4,1515.4,1392.7,1238.4,1159.0,1061.8,816.5,765.7,615.2,528.7cm-1；HRMS(CI+)(m/z)calcd.for C11H14BrNO2[M]+271.0202；found 271.0205.
实施例4
将1d(4.27mmol,1g)溶于MeCN(21ml中，向二者混合物中依次加入FeBr2(6.41mmol,1.38g)或CeBr3(2.99mmol，1.14g),H2O2水溶液(30wt％,使用FeBr2时,14.10mmol,1.44ml；使用CeBr3时,9.39mmol,0.96ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,142ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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2d(FeBr2:90％；CeBr3:95％).1H-NMR(400MHz,CDCl3)δ:7.86(brs,1H),7.39(d,J＝8.7Hz,1H),6.66(d,J＝8.7Hz,1H),3.84(brs,3H).13C-NMR(100MHz,CDCl3)δ:2932.7,2834.7,1566.6,1463.8,1247.9,1036.6,869.8,798.1,659.7,613.1,537.6cm-1；HRMS(CI+)(m/z)calcd.for C7H8BrIO[M]+331.8641；found 331.8655.
实施例5
将1e(6.33mmol,1g)溶于MeCN(32ml)中，向二者混合物中依次加入FeBr2(9.5mmol,2.05g)或CeBr3(4.43mmol，1.68g),H2O2水溶液(30wt％,使用FeBr2时,20.88mmol,2.13ml；使用CeBr3时,13.92mmol,1.42ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,211ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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2e(FeBr2:52％；CeBr3:74％).1H-NMR(400MHz,CDCl3)δ:8.30(d,J＝8.4Hz,1H),8.19(d,J＝8.4Hz,1H),7.65–7.50(m,3H),6.66(d,J＝8.4Hz,1H),3.98(s,3H).13C-NMR(100MHz,CDCl3)δ:155.3,132.5,129.6,127.9,127.0,126.9,126.0,122.5,113.3,104.6,55.8.IR 3064.8,2936.4,2836.1,1583.6,1503.2,1451.2,1369.2,1320.7,1232.7,1156.2,1080.6,1025.0,987.9,903.2,804.4,756.6.619.5cm-1；HRMS(CI+)(m/z)calcd.forC11H9BrO[M]+235.9831；found 235.9838.
实施例6
将1f(8.33mmol,1g)溶于MeCN(42ml)中，向二者混合物中依次加入FeBr2(12.49mmol,2.69g)或CeBr3(5.83mmol，2.21g),H2O2水溶液(30wt％,使用FeBr2时,27.49mmol,2.81ml；使用CeBr3时,18.33mmol,1.87ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,278ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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2f(FeBr2:75％；CeBr3:88％).1H-NMR(400MHz,CDCl3)δ:7.30–7.17(m,2H),6.66(d,J＝8.4Hz,1H),4.57(t,J＝8.7Hz,2H),3.20(t,J＝8.7Hz,2H).13C-NMR(100MHz,CDCl3)δ:159.3,130.7,129.5,127.9,112.1,110.9,71.6,29.7.IR 2900.8,1466.7,1228.4,1152.9,1102.1,977.5,935.2,808.2,647.1,537.4cm-1；HRMS(CI+)(m/z)calcd.forC8H7BrO[M]+197.9675；found 197.9682.
实施例7
将1g(8.19mmol,1g)溶于MeCN(41ml)中，向二者混合物中依次加入FeBr2(12.29mmol,2.65g)或CeBr3(5.74mmol，2.18g),H2O2水溶液(30wt％,使用FeBr2时,27.04mmol,2.76ml；使用CeBr3时,18.03mmol,1.84ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,273ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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2g(FeBr2:51.9mg,86％；CeBr3:97％).1H-NMR(400MHz,CDCl3)δ:6.99–6.90(m,2H),6.71–6.67(m,1H),5.97(s,2H).13C-NMR(100MHz,CDCl3)δ:148.7,147.1,124.5,113.2,112.4,109.7,101.7.IR 2893.9,1470.7,1422.3,1227.8,1152.6,1106.3,1034.0,931.9,867.6,845.9,797.3,668.4,569.6cm-1；HRMS(CI+)(m/z)calcd.for C7H5BrO2[M]+199.9467；found 199.9475.
实施例8
将1h(5.65mmol,1g)溶于MeCN(28ml)中，向二者混合物中依次加入FeBr2(8.47mmol,1.83g)或CeBr3(3.95mmol，1.50g),H2O2水溶液(30wt％,使用FeBr2时,18.64mmol,1.90ml；使用CeBr3时,12.42mmol,1.27ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,188ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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2h(FeBr2:83％；CeBr3:96％).1H-NMR(400MHz,CDCl3)δ:7.83–7.16(m,3H),3.97(brs,2H),3.81(brs,3H),3.07(t,J＝8.7Hz,2H).13C-NMR(100MHz,CDCl3)δ:153.5,141.9,133.2,130.3,127.7,116.0,114.8,52.7,47.5,27.3.IR 2949.7,1700.1,1479.0,1442.8,1389.0,1333.0,1219.1,1136.7,1057.4,829.9,758.4cm-1；HRMS(CI+)(m/z)calcd.for C10H10BrNO2[M]+254.9889；found 254.9886.
实施例9
将1i(3.95mmol,1g)溶于MeCN(20ml)中，向二者混合物中依次加入FeBr2(5.93mmol,1.28g)或CeBr3(2.77mmol，1.05g),H2O2水溶液(30wt％,使用FeBr2时,13.04mmol,1.33ml；使用CeBr3时,8.69mmol,0.89ml)，在室温下搅拌反应0.5-3h。反应完成后用Na2S2O3溶液(0.1M,132ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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2i(FeBr2:90％；CeBr3:97％).1H-NMR(400MHz,CDCl3)δ:7.40–6.90(m,3H),3.76(t,J＝6.5Hz,2H),2.72(t,J＝6.7Hz,2H),2.23(s,3H),2.02–1.85(m,2H).13C-NMR(100MHz,CDCl3)δ:169.7,137.9,134.9,131.1,128.8,126.0,117.8,42.8,26.7,23.6,23.1.IR2942.8,1651.5,1481.1,1375.7,1328.1,1179.9,1084.7,1029.0,961.5,818.8cm-1；HRMS(CI+)(m/z)calcd.for C11H12BrNO[M+H]+254.0175；found 254.0170.
实施例10
将3a(9.61mmol,1g)溶于DCM(45ml)中，向二者混合物中分多次加入FeBr2(19.22mmol,4.14g)或一次加入CeBr3(12.49mmol，4.75g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,28.83mmol,2.94ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,320ml)淬灭反应，用二氯甲烷(100ml)萃取。收集有机相，水相用二氯甲烷(2×50ml)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4a(FeBr2:68％；CeBr3:92％).1H-NMR(400MHz,CDCl3)δ:7.46–7.32(m,5H),5.16(dd,J＝10.6,5.5Hz,1H),4.13–3.99(m,2H).13C-NMR(100MHz,CDCl3)δ:138.7,129.3,129.0,127.8,51.0,35.1.IR 23063.0,2925.5,1489.9,1446.7,1263.9,1232.4,1196.3,1142.5,906.6,737.6,691.8,588.1cm-1；HRMS(CI+)(m/z)calcd.for C8H8Br2[M]+261.8987；found261.8996.
实施例11
将3b(7.13mmol,1g)溶于DCM(36ml)中，向二者混合物中分多次加入FeBr2(14.27mmol,3.08g)或一次加入CeBr3(9.28mmol，3.52g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,21.4mmol,2.19ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,238ml)淬灭反应，用二氯甲烷(100ml)萃取。收集有机相，水相用二氯甲烷(2×50ml)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(FeBr2:84％；CeBr3:96％).1H-NMR(400MHz,CDCl3)δ:4.21–4.11(m,1H),3.84(dd,J＝10.2,4.4Hz,1H),3.62(t,J＝10.0Hz,1H),2.18–2.07(m,1H),1.83–1.72(m,1H),1.61–1.50(m,1H),1.47–1.21(m,11H),0.88(t,J＝6.8Hz,3H).13C-NMR(100MHz,CDCl3)δ:53.3,36.5,36.2,32.0,29.5,29.3,29.0,26.9,22.8,14.2.IR 2923.3,2855.4,1459.5,1145.4,647.0,570.9cm-1；HRMS(CI+)(m/z)calcd.for C10H10Br2[M-H]+296.9848；found 296.9839.
实施例12
将3c(8.47mmol,1g)溶于DCM(42ml)中，向二者混合物中分多次加入FeBr2(16.94mmol,3.65g)或一次加入CeBr3(11mmol，4.18g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,25.41mmol,2.6ml)，在室温下搅拌反应0.5-2h。反应完成后用Na2S2O3溶液(0.1M,282ml)淬灭反应，用二氯甲烷(100ml)萃取。收集有机相，水相用二氯甲烷(2×50ml)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4c(FeBr2:60.0mg,72％；CeBr3:84％).1H-NMR(400MHz,CDCl3)δ:7.44–7.31(m,5H),5.07(d,J＝10.2Hz,1H),4.63(dq,J＝10.1,6.5Hz,1H),2.06(d,J＝6.5Hz,3H).13C-NMR(100MHz,CDCl3)δ:140.7,128.9,128.7,127.8,59.3,51.3,25.9.IR 2978.6,2927.2,1493.5,1448.3,1376.8,1148.9,1001.9,916.5,762.5,691.4,658.7,568.1cm-1；HRMS(CI+)(m/z)calcd.for C9H10Br2[M]+275.9144；found275.9162.
实施例13
将3d(12.18mmol,1g)溶于DCM(61ml)中，向二者混合物中分多次加入FeBr2(24.37mmol,5.25g)或一次加入CeBr3(15.84mmol，6.05g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,36.55mmol,3.73ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,406ml)淬灭反应，用二氯甲烷(100ml)萃取。收集有机相，水相用二氯甲烷(2×50ml)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4d(FeBr2:66％；CeBr3:80％).1H-NMR(400MHz,CDCl3)δ:4.44(brs,2H),2.51–2.37(m,2H),1.98–1.68(m,4H),1.59–1.40(m,2H).13C-NMR(100MHz,CDCl3)δ:55.3,32.1,22.5.IR 2937.2,2858.6,1438.7,1332.7,1263.2,1172.3,997.8,901.6,857.2,810.3,690.1,658.3,536.5cm-1；HRMS(CI+)(m/z)calcd.for C6H10Br2[M]+239.9144；found239.9139.
实施例14
将3e(8.62mmol,1g)溶于DCM(43ml)中，向二者混合物中分多次加入FeBr2(17.23mmol,3.72g)或一次加入CeBr3(11.2mmol，4.25g),之后向圆底烧瓶中分四次加入H2O2水溶液分(30wt％,25.85mmol,2.64ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,287ml)淬灭反应，用二氯甲烷(100ml)萃取。收集有机相，水相用二氯甲烷(2×50ml)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4e(FeBr2:55％；CeBr3:64％).1H-NMR(400MHz,CDCl3)δ:7.54–7.29(m,4H),5.66(s,1H),4.94–4.85(m,1H),3.83(dd,J＝17.6,5.2Hz,1H),3.29(d,J＝17.6Hz,1H).13C-NMR(100MHz,CDCl3)δ:140.7,129.8,128.1,125.8,125.5,57.9,54.6,41.5.IR 3024.3,1467.8,1420.4,1309.7,1273.7,1209.1,1145.0,1017.7,950.9,908.6,849.2,766.1,723.6,657.1,565.1,530.4cm-1；HRMS(CI+)(m/z)calcd.for C9H8Br2[M]+273.8987；found273.8998.
实施例15
将3f(9.80mmol,1g)溶于DCM(49ml)中，向二者混合物中分多次加入FeBr2(19.60mmol,4.23g)或一次加入CeBr3(12.74mmol，4.84g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,29.40mmol,3ml)，在室温下搅拌反应0.5-2h。反应完成后用Na2S2O3溶液(0.1M,327ml)淬灭反应，用二氯甲烷(100ml)萃取。收集有机相，水相用二氯甲烷(2×50ml)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4f(FeBr2:54％；CeBr3:57％).1H-NMR(400MHz,CDCl3)δ:7.54–7.49(m,2H),7.43–7.36(m,3H),6.81(s,1H).13C-NMR(100MHz,CDCl3)δ:137.2,129.5,129.3,128.4,121.5,103.2.IR3077.5,2341.6,1485.2,1443.0,1267.0,1161.6,1072.0,995.7,866.5,787.0,761.6,685.0cm-1；HRMS(CI+)(m/z)calcd.for C8H6Br2[M]+259.8831；found 259.8831.
实施例16
将3g(10.41mmol,1g)溶于DCM(52ml)中，向二者混合物中分多次加入FeBr2(20.81mmol,4.49g)或一次加入CeBr3(13.53mmol，5.14g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,31.22mmol,3.19ml)，在室温下搅拌反应0.5-2h。反应完成后用Na2S2O3溶液(0.1M,347ml)淬灭反应，用二氯甲烷(100ml)萃取。收集有机相，水相用二氯甲烷(2×50ml)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4g(FeBr2:60％；CeBr3:79％).1H-NMR(400MHz,CDCl3)δ:6.40(s,1H),2.65–2.52(t,J＝7.6Hz,2H),1.60–1.55(m,2H),1.36–1.30(m,4H),0.91(t,J＝6.9Hz,3H).13C-NMR(100MHz,CDCl3)δ:127.2,102.2,37.0,30.7,26.9,22.6,14.1.IR 2926.1,2861.8,1458.5,1114.4,995.6,776.9,700.7,629.6,551.6cm-1；HRMS(CI+)(m/z)calcd.for C7H12Br2[M]+253.9300；found 253.9302.
实施例17
将5a(2.78mmol,1g)溶于THF(14ml)中，向二者混合物中加入FeBr2(1.94mmol,0.42g)或一次加入CeBr3(1.11mmol，0.42g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,6.11mmol,0.62ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,93ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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6a(FeBr2:78％；CeBr3:77％).1H-NMR(400MHz,CDCl3)δ:7.58(brs,1H),7.35(dd,J＝7.7,1.2Hz,1H),7.30–7.26(m,1H),7.08(td,J＝7.5,1.0Hz,1H),6.43(s,1H),3.78–3.66(m,1H),2.85–2.65(m,3H),1.57(s,9H),1.48(s,9H).13C-NMR(100MHz,CDCl3)δ:153.5,152.2,142.1,132.7,130.4,124.1,123.9,117.5,83.9,82.2,80.8,62.3,46.2,41.6,28.5,28.4.IR 2977.4,1705.6,1474.0,1389.0,1319.4,1245.1,1148.9,1103.8,1042.6,851.2,734.3cm-1；HRMS(CI+)(m/z)calcd.for C20H27BrN2O4[M]+438.1149；found 438.1159.
实施例18
将5b(3.62mmol,1g)溶于THF(18ml)中，向二者混合物中加入FeBr2(2.54mmol,0.55g)或一次加入CeBr3(1.45mmol，0.42g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,6.11mmol,0.55ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,121ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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(FeBr2:75％；CeBr3:74％).1H-NMR(400MHz,CDCl3)δ:7.54(d,J＝8.2Hz,1H),7.16(brs,1H),7.10(d,J＝8.3Hz,1H),6.37(brs,1H),3.87(s,3H),3.80–3.65(m,4H),2.92–2.66(m,3H),2.30(s,3H).13C-NMR(100MHz,CDCl3)δ:154.5,153.6,139.1,134.2,132.0,131.3,124.0,116.7,84.1,62.2,53.0,52.8,46.2,40.9,20.9.IR2953.6,1707.6,1489.6,1446.1,1387.1,1329.5,1269.1,1232.3,1198.4,1153.1,1116.4,1080.2,1041.5,976.6,897.0,864.4,820.8,767.9,723.4,687.6cm-1；HRMS(CI+)(m/z)calcd.for C15H17BrN2O4[M]+368.0366；found 368.0365.
实施例19
将5c(3.01mmol,1g)溶于THF(15ml)中，向二者混合物中加入FeBr2(2.11mmol,0.45g)或一次加入CeBr3(1.20mmol，0.46g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,6.62mmol,0.68ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,100ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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6c(FeBr2:70％；CeBr3:83％).1H-NMR(400MHz,CDCl3)δ:7.89(brs,1H),6.91–6.79(m,2H),6.13(brs,1H),3.77(s,3H),3.74–3.62(m,1H),2.89–2.63(m,3H),2.57(brs,3H),1.42(brs,9H).13C-NMR(100MHz,CDCl3)δ:170.6,157.3,153.6,135.7,133.7,120.1,116.0,108.4,85.4,81.2,62.5,55.8,46.7,40.7,28.4,23.5.IR 2970.7,2927.5,1697.1,1669.6,1483.4,1452.0,1393.3,1368.8,1315.9,1268.8,1232.1,1156.9,1118.3,1030.5,977.1,932.3,873.6,829.6,772.8,731.6,693.9,643.9cm-1；HRMS(CI+)(m/z)calcd.for C18H23BrN2O4[M]+410.0836；found 410.0837.
实施例20
将5d(2.39mmol,1g)溶于THF(12ml)中，向二者混合物中加入FeBr2(1.67mmol,0.36g)或一次加入CeBr3(0.96mmol，0.36g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,5.26mmol,0.54ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,80ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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6d(FeBr2:75％；CeBr3:82％).1H-NMR(400MHz,CDCl3)δ:7.55(brs,1H),7.38–7.27(m,2H),7.10(t,J＝7.5Hz,1H),6.38(s,1H),3.87(dd,J＝10.0,6.4Hz,1H),3.72(s,3H),3.20(dd,J＝12.6,6.3Hz,1H),2.80(t,J＝11.4Hz,1H),1.57(brs,9H),1.38(brs,9H).13C-NMR(100MHz,CDCl3)δ:171.6,152.3,141.6,132.9,130.7,124.5,123.3,118.6,83.9,82.4,81.5,59.8,59.5,52.5,42.1,28.33,28.27.IR 2978.6,1711.0,1472.5,1393.8,1327.5,1259.4,1154.4,1017.7,850.3,737.3cm-1；HRMS(CI+)(m/z)calcd.for C22H29BrN2O6[M]+496.1204；found496.1204.
实施例21
将5e(3.17mmol,1g)溶于THF(16ml)中，向二者混合物中加入FeBr2(2.22mmol,0.48g)或一次加入CeBr3(1.27mmol，0.48g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,6.98mmol,0.71ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,106ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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6e(FeBr2:88％；CeBr3:89％).1H-NMR(400MHz,CDCl3)δ:7.81(d,J＝7.5Hz,2H),7.47(d,J＝8.2Hz,1H),7.36(d,J＝7.6Hz,1H),7.31–7.22(m,3H),7.11(t,J＝7.5Hz,1H),6.26(s,1H),4.01(t,J＝8.2Hz,1H),3.43(td,J＝10.0,4.7Hz,1H),2.84(td,J＝11.7,7.6Hz,1H),2.74(dd,J＝12.5,4.6Hz,1H),2.37(s,3H).13C-NMR(100MHz,CDCl3)δ:144.5,140.5,135.6,132.4,130.7,129.7,127.4,125.3,124.9,114.1,103.2,68.0,61.5,44.7,21.6.IR 3041.6,2880.2,1598.4,1466.2,1354.4,1163.3,1088.0,1024.6,959.1,859.6,810.7,755.5,659.9,624.7,574.5,544.1cm-1；HRMS(CI+)(m/z)calcd.for C17H16BrNO3S[M]+393.0029；found 393.0024.
实施例23
将5f(3.46mmol,1g)溶于THF(17ml)中，向二者混合物中加入FeBr2(2.42mmol,0.52g)或一次加入CeBr3(1.38mmol，0.53g),之后向圆底烧瓶中分多次加入H2O2水溶液分(30wt％,7.61mmol,0.78ml)，在室温下搅拌反应0.5-1h。反应完成后用Na2S2O3溶液(0.1M,115ml)淬灭反应，用乙酸乙酯(100ml)萃取。收集有机相，水相用乙酸乙酯(2×50ml)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6f(FeBr2:89％；CeBr3:93％).1H-NMR(400MHz,CDCl3)δ:7.32–7.08(m,3H),6.20(s,1H),3.94(t,J＝7.9Hz,1H),3.39(ddd,J＝10.3,8.1,5.2Hz,1H),2.90–2.69(m,4H),1.58(s,9H),1.20(t,J＝7.5Hz,3H).13C-NMR(100MHz,CDCl3)δ:152.5,139.7,134.6,134.2,130.7,125.9,121.5,102.7,82.0,67.8,61.5,43.4,28.1,25.8,13.4.IR 2971.4,2929.7,2879.5,1718.0,1446.3,1364.7,1328.0,1300.7,1253.6,1156.6,1112.9,1047.6,1010.2,961.9,911.8,856.6,762.1,683.4cm-1；HRMS(CI+)(m/z)calcd.for C17H22BrNO3[M+H]+370.0835；found370.0845.
本发明的研究工作得到南方海洋科学与工程广东省实验室(广州)香港分部(SMSEGL20Sc01-B)基金的支持，在此加以致谢。
Claims (7)
1.一种绿色的溴化方法。其特征在于，所述方法包括：在室温、敞口、中性条件下，原料为具不同官能团的芳烃、烯烃、炔烃、色胺、色醇及其衍生物，其中R1、R2、R3、R4、R5、R6可为烷烃、烯烃、炔烃、脂环烃、富电子芳烃、酯基等常见官能团或呋喃、噻吩、吡啶、吡咯以及其他杂环等不同取代基，也可为常用的保护基团包括TIPS、TBS、Bn、Ac、Bz、Piv和Boc等，以MBrx(M为Fe2+、Fe3+、Ce3+、Ce4+，x为2-3)为溴源，H2O2为唯一氧化剂，通过溴化反应生成溴代芳烃、二溴代烷烃、二溴代烯烃、溴代吡咯并吲哚啉和溴代呋喃并吲哚啉及其衍生物。
2.根据权利要求1所述的方法，其特征在于：所用溴源为FeBr2、CeBr3、FeBr3、CeBr4以及FeSO4-KBr、FeCl2-KBr、FeCl3-KBr、Fe(NO3)3-KBr、Ce(NO3)3-KBr、CeCl3-KBr、Ce2(C2O4)3-KBr、Ce(SO4)2-KBr等。金属(Fe2+、Fe3+)和溴化物的组合中的任意一种，溴化源与芳烃、烯烃和炔烃、色胺、色醇及其衍生物的摩尔比为0.5-3:1；金属(Ce3+、Ce4+)和溴化物的组合中的任意一种，溴化源与芳烃、烯烃和炔烃、色胺、色醇及其衍生物的摩尔比为0.33-4.5:1。
3.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，所用溶剂为四氢呋喃、二氯甲烷、乙腈、叔丁醇、1,4-二氧六环、乙二醇二甲醚以及其它有机溶剂。
4.根据权利要求1所述的方法，其特征在于：H2O2为唯一氧化剂，双氧水与芳烃、烯烃、炔烃、色胺、色醇及其衍生物的摩尔比为1-5:1；较佳双氧水与底物的摩尔比为2-4：1。
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；反应在敞口条件下进行；反应在pH为中性条件下进行；较佳反应时间为0.5-3h。
6.根据权利要求1所述的方法，其特征在于：具体操作时，将芳烃、烯烃、炔烃、色胺、色醇及其衍生物溶于反应溶剂中，向二者加入溴源，再向反应混合物中加入H2O2水溶液(30wt％)，在室温下搅拌反应0.5-3h，生成溴代芳烃、烯烃、炔烃、色胺、色醇及其衍生物。
7.根据权利要求1所述的方法，其特征在于：所述溴代反应反应完成后用稀释的Na2S2O3溶液(0.1M)淬灭，用乙酸乙酯或其他有机溶剂分多次萃取，过滤，减压浓缩，即可得目标产物。
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