董道青,胡東岳,尋之玉,李宗慧,史大鵬,楊家岐,王祖利

·研究論文·

Amberlyst-15催化C(sp3)—H對靛紅類化合物的加成反應

董道青,胡東岳,尋之玉,李宗慧,史大鵬,楊家岐,王祖利*

(青島農業(yè)大學 化學與藥學院，山東 青島 266109)

以Amberlyst-15為催化劑，甲基吡啶類化合物中的C(sp3)—H鍵對靛紅類化合物經加成反應合成了24個3-羥基-2-吲哚酮類化合物(3a～3x)，其中3u～3x為新化合物，其結構經1H NMR，13C NMR，IR和HR-MS(ESI)表征。催化劑Amberlyst-15循環(huán)使用8次，不影響反應收率。

C(sp3)—H鍵;Amberlyst-15;綠色化學;靛紅；合成；吲哚酮

Amberlyst-15 是一種磺化的聚苯乙烯樹脂，具有無毒，化學物理性質穩(wěn)定，容易從反應體系中分離等優(yōu)點，在有機合成中得到了廣泛應用。 其催化的各種有機反應已被報道[1]，如酯化反應[2-4]，Michael加成反應[5-6]，Prins反應[7]，傅克反應[8-9]，鹵化反應[10]，環(huán)氧化合物開環(huán)反應[11-13]，縮合反應[14-16]及多組分反應[17-18]等。

C(sp3)—H鍵能高，反應相對惰性。C(sp3)—H鍵的功能化反應是有機化學研究中的重要和熱點領域[19-23]。2014年，Yang等[24]研究了醋酸銀催化的C(sp3)—H鍵活化形成C—N鍵的反應；Qian等[25]實現(xiàn)了三氟甲磺酸鈧催化的C(sp3)—H鍵對亞胺的加成反應；Wang等[26]研究了醋酸促進的C(sp3)—H鍵對醛的加成反應合成醇類化合物的反應。

3-羥基-2-吲哚酮類化合物是許多天然產物及藥物活性分子的結構單元，對其合成的研究具有重要意義。本文研究了Amberlyst-15催化甲基吡啶類化合物(1)中的C(sp3)—H鍵對靛紅類化合物(2)的加成反應(Scheme 1)，高效合成了24個3-羥基-2-吲哚酮類化合物(3a～3x)，其中3u～3x為新化合物，其結構經1H NMR，13C NMR，IR和HR-MS(ESI)表征。催化劑Amberlyst-15循環(huán)使用8次，不影響反應收率。

Scheme 1

1 實驗部分

1.1 儀器與試劑

Bruker AV300型核磁共振儀(DMSO-d6為溶劑，TMS為內標)；MATRIX-1型紅外光譜儀；APEX II型質譜儀。

所用試劑均為分析純。

1.2 合成

(1) 3a～3x的合成通法

在25 mL的真空管中加入 1 0.75 mmol，2 0.25 mmol,Amberlyst-15催化劑30 mg和DMSO 0.6 mL，升溫至100 ℃反應24 h。反應液用乙醚(3×10 mL)萃取，合并有機相，用無水硫化鈉干燥，減壓旋蒸除溶,殘余物經硅膠柱層析[洗脫劑:A=V(石油醚)：V(乙酸乙酯)=1：3]純化得3a～3x。

3-羥基-1-甲基-3-[(6-甲基吡啶基-2-)甲基]-吲哚-2-酮(3a)：黃色固體，收率88%；1H NMRδ:7.42(t,J=7.65 Hz,1H),7.16(t,J=7.2 Hz,1H),6.97～6.79(m,5H),6.35(s,1H),3.29(d,J=10.8 Hz,1H),3.25(d,J=10.8 Hz,1H),3.03(s,3H)，2.22(s,3H);13C NMRδ:177.4,156.6,155.8,143.9,136.6,131.0,129.2,124.3,122.0,121.3,121.1,108.3,76.7,45.2,26.1,24.1。

3-羥基-3-[(6-甲基吡啶基-2-)甲基]-1-苯基吲哚-2-酮(3b)：白色固體，收率75%；1H NMRδ:8.01(s,1H),7.57～7.34(m,6H),7.25～7.11(m,2H),7.00～6.88(m,3H),6.82(d,J=7.8 Hz,1H),3.38(d,J=14.7 Hz,1H),3.20(d,J=14.7 Hz,1H),2.60(s,3H);13C NMRδ:176.1,157.2,156.7,142.8,137.4,134.2,131.0,129.5,129.1,127.9,126.4,124.2,123.1,122.0,121.6,109.5,76.2,42.8,24.2。

5-溴-3-羥基-3-[(6-甲基吡啶-2-)甲基]-吲哚-2-酮(3c)：白色固體，收率90%；1H NMRδ:10.28(s,1H),7.50(t,J=7.65 Hz,1H),7.27(dd,J=2.1 Hz,8.4 Hz,1H),7.01～6.96(m,3H),6.63(d,J=8.4 Hz,1H),6.39(s,1H),3.27(d,J=13.2 Hz,1H),3.10(d,J=13.2 Hz,1H),2.27(s,3H);13C NMRδ:178.7,156.8,155.5,141.5,136.7,134.0,131.7,128.2,121.7,121.3,113.0,111.5,76.1,49.9,24.1。

3-羥基-5-甲基-3-[( 6-甲基吡啶-2-)甲基]吲哚-2-酮(3d)：白色固體，收率73%；1H NMRδ:10.09(s,1H),7.55(t,J=7.65 Hz,1H),7.08～6.95(m,4H),6.73～6.61(m,3H),3.28(d,J=13.2 Hz,1H),3.13(d,J=13.2 Hz,1H),2.36(s,3H),2.21(s,3H);13C NMRδ:179.1,156.7,155.9,139.6,136.6,131.6,130.0,129.3,125.8,121.7,121.2,109.3,76.0,45.1,24.2,21.1。

3-羥基-3-[(6-甲基吡啶-2-)甲基]吲哚-2-酮(3e)：白色固體，收率80%；1H NMRδ:10.13(s,1H),7.48(t,J=7.5 Hz,1H),7.09(dt,J=1.2 Hz,6.9 Hz,1H),7.01～6.94(m,2H),6.89～6.79(m,2H),6.67(d,J=7.8 Hz,1H),6.39(s,1H),3.24(d,J=13.5 Hz,1H),3.11(d,J=13.5 Hz,1H),2.28(s,3H);13C NMRδ:179.0,156.8,155.9,142.2,136.6,131.6,129.1,125.0,121.6,121.4,121.3,109.6,76.0,45.1,24.2。

7-溴-3-羥基-3-[(6-甲基吡啶-2-)甲基)]吲哚-2-酮(3f)：淡黃色固體，收率92%；1H NMRδ:10.43(s,1H),7.48(t,J=7.65 Hz,1H),7.28(d,J=8.1 Hz,1H),6.99～6.93(m,3H),6.78(t,J=7.65 Hz,1H),6.44(s,1H),3.27(d,J=13.8 Hz,1H),3.18(d,J=13.8 Hz,1H),2.25(s,3H);13C NMRδ:178.9,156.8,155.5,141.8,136.7,133.8,131.9,123.9,123.1,121.4,121.3,102.1,76.7,44.9,24.0。

3-羥基-3-[(6-甲基吡啶-2-)甲基]-5-硝基吲哚-2-酮(3g)：淡黃色固體，收率95%；1H NMRδ:10.08(s,1H),8.10(dd,J=2.4 Hz,8.7 Hz,1H),7.82(d,J=2.1 Hz,1H),7.50(t,J=7.65 Hz,1H),7.01～6.97(m,2H),6.88(d,J=8.4 Hz,1H),6.53(s,1H),3.41(d,J=13.5 Hz,1H),3.22(d,J=13.5 Hz,1H),2.21(s,3H);13C NMRδ:179.5,156.9,155.1,149.1,142.0,136.8,132.7,126.5,121.7,121.3,120.8,109.7,75.5,44.6,23.9。

3-羥基-5-甲氧基-3-[(6-甲基吡啶-2-)甲基]吲哚-2-酮(3h)：白色固體，收率84%；1H NMRδ:9.97(s,1H),7.50(t,J=7.5 Hz,1H),7.03～6.97(d,J=8.1 Hz,2H),6.45(s,1H),6.36(s,1H),3.60(s,3H),3.24(d,J=13.5 Hz,1H),3.06(d,J=13.5 Hz,1H),2.31(s,3H);13C NMRδ:179.0,156.8,155.9,154.8,136.6,135.3,132.8,121.8,121.3,114.0,112.0,110.0,76.4,55.8,45.0,24.2。

3-羥基-5-硝基-3-(吡啶基-2-甲基)吲哚-2-酮(3i)：淡黃色固體，收率85%；1H NMRδ:10.86(s,1H),8.25(d,J=3.9 Hz,2H),8.08(dd,J=2.4 Hz,8.7 Hz,1H),7.83(d,J=2.1 Hz,H),7.60(dt,J=2.0 Hz,8.5 Hz,1H),7.20～7.11(m,2H),6.84(d,J=8.7 Hz,1H),6.56(s,1H),3.45(d,J=13.2 Hz,1H),3.28(d,J=13.2 Hz,1H);13C NMRδ:179.3,155.8,148.9,142.1,136.5,132.5,126.6,124.8,122.3,120.7,109.9,75.7,45.0。

5-溴-3-羥基-3-(吡啶基-2-甲基)吲哚-2-酮(3j)：白色固體，收率83%；1H NMRδ:10.30(s,1H),8.33(d,J=6.0 Hz,2H),7.33(d,J=2.1 Hz,1H),7.31(s,1H),6.94(d,J=6.0 Hz,2H),6.61(d,J=8.1 Hz,1H),6.40(s,1H),3.21(d,J=12.6 Hz,1H),3.00(d,J=12.6 Hz,1H);13C NMRδ:178.3,149.3,144.2,141.2,133.4,132.2,127.9,125.9,113.5,111.9,76.5,42.7。

3-羥基-5-甲氧基-3-(吡啶基-2-甲基)吲哚-2-酮(3k)：白色固體，收率81%；1H NMRδ:9.95(s,1H),8.31(d,J=4.2 Hz,1H),7.60(dt,J=1.5 Hz,7.65 Hz,1H),7.18～7.12(m,2H),6.65(dd,J=2.4 Hz,5.4 Hz,1H),6.56(d,J=8.4 Hz,1H),6.46(d,J=2.4 Hz,1H),6.28(s,1H),3.60(s,3H),3.30(d,J=12.9 Hz,1H),3.12(d,J=12.9 Hz,1H);13C NMRδ:178.9,156.6,154.8,148.7,136.2,135.2,132.6,124.9,122.1,113.9,112.0,110.0,76.4,55.7,45.5。

3-羥基-1-苯基-3-(吡啶基-2-甲基)吲哚-2-酮(3l)：白色固體，收率78%；1H NMRδ:8.58(d,J=4.2 Hz,1H),7.65(dt,J=7.8 Hz,1.8 Hz,1H),7.47(t,J=12.0 Hz,2H),7.41～7.35(m,3H),7.28(t,J=5.5 Hz,1H),7.22～7.16(m,1H),7.10(d,J=7.8 Hz,1H),6.98(d,J=4.2 Hz,2H),6.80(d,J=8.1 Hz,1H),3.42(d,J=14.7 Hz,1H),3.30(d,J=14.7 Hz,1H);13C NMRδ:176.1,157.3,148.1,142.9,137.2,134.2,130.6,129.5,129.3,127.9,126.4,124.8,124.3,123.2,122.3,109.5,76.3,43.2。

3-羥基-3-(吡啶基-2-甲基)吲哚-2-酮(3m)：白色固體，收率86%；1H NMRδ:10.12(s,1H),8.29(d,J=4.5 Hz,1H),7.57(dt,J=1.8 Hz,7.8 Hz,1H),7.14～7.05(m,3H),6.91(d,J=6.9 Hz,1H),6.82(t,J=7.5 Hz,1H),6.65(d,J=7.8 Hz,1H),6.28(s,1H),3.33(d,J=12.9 Hz,1H),3.17(d,J=12.9 Hz,1H);13C NMRδ:179.0,156.5,148.7,142.0,136.2,131.4,129.2,125.0,124.7,122.1，121.5,109.6,76.1,45.5。

3-羥基-5-甲基-3-(吡啶基-2-甲基)吲哚-2-酮(3n)：白色固體，收率77%；1H NMRδ:10.09(s,1H),8.30(t,J=2.7 Hz,1H),7.61～7.55(m,1H),7.15～7.12(m,2H),6.88(d,J=7.5 Hz,1H),6.71(s,1H),6.53(d,J=7.8 Hz,1H),6.23(s,1H),3.26(d,J=12.9 Hz,1H),3.14(d,J=12.9 Hz,1H),2.15(s,3H);13C NMRδ:179.0,156.6,148.7,139.6,136.2,131.5,130.1,129.4,125.7,124.7,122.0,109.3,76.1,45.6,21.1。

3-羥基-1-甲基-3-(吡啶基-4-甲基)吲哚-2-酮(3o)：白色固體，收率82%；1H NMRδ:8.24(d,J=6.0 Hz,2H),7.28～7.23(m,1H),7.17(d,J=6.9 Hz,1H),7.05(t,J=7.5 Hz,1H),6.88(d,J=6.0 Hz,2H),6.63(d,J=7.8 Hz,1H),3.29(d,J=12.6 Hz,1H),3.14(d,J=12.6 Hz,1H),2.97(s,3H);13C NMRδ:177.4,148.6,143.9,142.9,129.9,128.9,125.5,124.2,123.0,108.4,76.7,43.9,25.9。

3-羥基-3-(吡啶基-4-甲基)吲哚-2-酮(3p)：紅色固體，收率70%,m.p.209～210 ℃;1H NMRδ:10.14(s,1H),8.29(d,J=4.8 Hz,2H),6.94～6.89(m,3H),6.63(d,J=7.8 Hz,1H),6.24(s,1H),3.17(d,J=12.6 Hz,1H),2.98(d,J=12.6 Hz,1H);13C NMRδ:178.8,149.2,144.5,141.9,130.9,129.6,125.9,124.9,121.8,109.9,76.4,43.0;IRν:1 722,1 621,1 604,1 551,750 cm-1。

3-[(4,6-二甲基吡啶基-2-)甲基]-3羥基吲哚-2-酮(3q)：淡黃色固體，收率76%,m.p.217～218 ℃;1H NMRδ:10.13(s,1H),7.09(t,J=7.05 Hz,1H),6.84～6.69(m,5H),6.47(s,1H),3.18(d,J=13.5 Hz,1H),3.03(d,J=13.5 Hz,1H),2.24(s,3H),2.15(s,3H);13C NMRδ:179.0,156.5,155.9,147.0,142.1,131.8,129.1,124.9,122.5,122.2,121.4,109.6,76.0,44.7,24.0,20.8;IRν:1 712,1 620,1 560,1 485,768 cm-1。

3-羥基-1-甲基-3-(喹啉基-2-甲基)吲哚-2-酮(3r)：收率86%,白色固體,m.p.217～218 ℃;1H NMRδ:8.11(t,J=9.3 Hz,2H),7.85～7.31(m,3H),7.56(t,J=7.5 Hz,1H),7.28～7.16(m,2H),6.90～6.80(m,3H),3.56(d,J=15.0 Hz,1H),3.23(d,J=15.0 Hz,1H),3.20(s,3H);13C NMRδ:176.6,158.6,146.6,143.0,137.1,131.2,130.1,129.3,128.7,127.7,127.0,126.6,124.0,122.7,122.7,108.2,43.1,26.2;IRν:1 712,1 620,1 560,1 485,768 cm-1。

3-羥基-3-[(6-甲基喹啉基-2-)甲基]吲哚-2-酮(3s)：黃色固體,收率82%,m.p.197～199 ℃;1H NMRδ:10.17(s,1H),8.04(d,J=8.4 Hz,1H),7.69～7.62(m,2H),7.50～7.47(dd,J=1.8 Hz,8.7 Hz,1H),7.30(d,J=8.4 Hz,1H),7.06(dt,J=1.2 Hz,7.5 Hz,1H),6.88(d,J=6.9 Hz,1H),6.77(t,J=7.3 Hz,1H),6.65(d,J=7.5 Hz,1H),6.3(s,1H),3.48(d,J=13.5 Hz,1H),3.31(d,J=13.5 Hz,1H),2.45(s,3H);13C NMRδ:179.1,156.6,145.8,142.2,135.8,135.2,131.8,131.6,129.2,128.6,126.8,126.8,123.1,109.7,76.0,45.9,21.5;IRν:1 724,1 619,1 595,1 500,746 cm-1。

3-[(6-溴喹啉-2-)甲基]-3-羥基吲哚-2-酮(3t)：黃色固體,收率74%,m.p.198～200 ℃;1H NMRδ:10.18(s,1H),8.17～7.13(m,2H),7.78(dd,J=2.1 Hz,9.0 Hz,1H),7.69(d,J=9.0 Hz,1H),7.40(d,J=8.4 Hz,1H),7.07(t,J=7.5 Hz,1H),6.90(d,J=6.9 Hz,1H),6.78(t,J=7.3 Hz,1H),6.65(d,J=7.8 Hz,1H),6.3(s,1H),3.50(d,J=13.5 Hz,1H),3.34(d,J=13.5 Hz,1H);13C NMRδ:179.0,158.3,145.8,142.2,135.0,132.7,131.5,131.0,130.1,129.3,128.2,124.9,124.1,121.5,119.2,109.7,75.9,46.1;IRν:1 735,1 618,1 594,1 560,756 cm-1。

3-(苯并噻唑-2-甲基)-3-羥基-1-甲基喹啉-2-酮(3u)：白色固體,收率88%,m.p.130～131 ℃;1H NMRδ：7.99(d,J=4.7 Hz,1H),7.84(d,J=4.8 Hz,1H),7.45～7.36(m,2H),7.26(t,J=4.6 Hz,1H),7.11(d,J=4.3 Hz,1H),6.97～6.93(m,2H),6.62(s,1H),3.69(d,J=8.6 Hz,1H),3.57(d,J=8.6 Hz,1H);13C NMRδ：176.6,165.5,152.3,143.8,135.7,130.0,126.3,125.3,124.4,122.7,122.3,109.0,74.7,42.3,26.4;IRν:1 706,1 615,1 555,1 513 cm-1；HR-MS(ESI)m/z:Calcd for C17H14N2O2SNa {[M+Na]+}333.066 44,found 333.066 82。

3-(苯并噻唑-2-甲基)-3-羥基-5-硝基吲哚-2-酮(3v)：黃色固體,收率96%,m.p.150～152 ℃;1H NMRδ:11.0(s,1H),8.17(d,J=5.1 Hz,1H),8.10(s,1H),8.01(d,J=4.7 Hz,1H),7.83(d,J=4.8 Hz,1H),7.44(t,J=4.5 Hz,1H),7.38(t,J=4.4 Hz,1H),6.94(d,J=5.1 Hz,1H),6.86(s,1H),3.85(d,J=8.5 Hz,1H),3.65(d,J=8.6 Hz,1H);13C NMRδ:178.5,164.9,152.5,149.0,142.5,135.6,131.9,127.2,126.4,125.5,122.7,122.4,120.8,110.4,74.8,41.4;IRν:1 737,1 625,1 559,1 524 cm-1；HR-MS(ESI)m/z:Calcd for C16H12N3O4S {[M+H]+}342.053 95,found 342.054 30。

3-(苯并噻唑-2-甲基)-3-羥基-1-苯基吲哚-2-酮(3w)：白色固體,收率83%,m.p.186～187 ℃;1H NMRδ:7.99(d,J=4.7 Hz,1H),7.84(d,J=4.8 Hz,1H),7.57(t,J=4.6 Hz,2H),7.44～7.47(m,2H),7.38～7.33(m,3H),7.18(t,J=4.5 Hz,1H),7.03(t,J=8.9 Hz,1H),6.80(s,1H),6.60(d,J=4.7 Hz,1H),3.84(d,J=8.5 Hz,1H),2.98(d,J=8.6 Hz,1H);13C NMRδ:176.1,165.3,152.6,143.7,135.5,134.6,130.0,128.4,126.8,126.4,125.0,123.2,122.6,122.4,109.2,75.0,42.3;IRν:1 717,1 615,1 502,769,702 cm-1;HR-MS(ESI)m/z:Calcd for C22H16N2O2SNa {[M+H]+}395.082 47,found 395.082 18。

3-(苯并噻唑-2-甲基)-7-溴-3-羥基吲哚-2-酮(3x)：白色固體,收率93%，m.p 228～229 ℃;1H NMRδ:10.67(s,1H),8.02(d,J=4.6 Hz,1H),7.86(d,J=4.8 Hz,1H),7.47～7.43(m,1H),7.40～7.38(m,2H),7.11(d,J=4.3 Hz,1H),6.87(t,J=4.6 Hz,1H),6.71(s,1H),3.67(d,J=8.5 Hz,1H),3.57(d,J=8.6 Hz,1H);13C NMRδ:178.0,165.3,152.4,141.8,135.8,132.8,132.8,126.3,125.4,124.0,123.8,122.7,122.3,102.6,75.7,42.2;IRν:1 705,1 623,1 559,1 509,1 474 cm-1;HR-MS(ESI)m/z:Calcd for C16H11N2O2SBrNa {[M+Na]+}396.961 68,found 396.961 27。

2 結果與討論

2.1 反應條件優(yōu)化

以2,6-二甲基吡啶(1a)與1-甲基靛紅(2a)的反應為模板，Amberlyst-15為催化劑，考察了溶劑、催化劑用量和反應溫度等因素對反應的影響，結果見表1。由表1可以看出，當DMSO為溶劑時，收率最高(74%,No.5)；當反應在Dioxane，THF，EtOH或DMF中進行時，反應也可以發(fā)生，但是收率有所降低(No.1～4)；以Toluene或H2O作溶劑，反應幾乎不發(fā)生(No.6～7)。當催化劑Amberlyst-15用量減半，收率降至60%(No.8)；當Amberlyst-15用量增加一倍時，收率幾乎不變(No.9)。不同反應溫度影響不同，反應溫度從80 ℃升至100 ℃時，收率提高至88%(No.10)，如反應溫度進一步升至120 ℃，收率沒有變化(No.11)。

綜上所述，最佳反應條件為：溶劑為DMSO，Amberlyst-15 30 mg，反應溫度100 ℃。

表1 不同反應條件對收率的影響a

Table 1 Effects of different conditions on the yield

No.SolventTemprature/℃Yield/%1Dioxane80302THF80133EtOH80204DMF80585DMSO80746Toluene80-7H2O80-8bDMSO80609cDMSO807510DMSO1008811DMSO12087

a2a 0.25 mmol,1a 0.75 mmol,Amberlyst-15 30 mg,DMSO 0.8 mL,reaction for 24 h；bAmberlyst-15 15 mg;cAmberlyst-15 60 mg。

2.2 反應普適性

在最佳反應條件下，對反應的普適性進行了研究，結果見Chart 1。由Chart 1可見,靛紅類化合物苯環(huán)上無論是吸電子基團還是給電子基團都可取得較高的收率。另外，靛紅類化合物的氮原子是否帶有取代基都可與2,6-二甲基吡啶反應，收率較高(3a～3h)。除 2,6-二甲基吡啶以外，2-甲基吡啶和2,4,6-二甲基吡啶也可以很好地參與反應(3i～3n,3q)。值得注意的是，4-甲基吡啶也可以與靛紅類化合物發(fā)生反應(3o～3p)。以較高的收率得到了甲基喹啉類化合物和2-甲基苯并噻唑與2的反應產物(3u～3x)。表明該催化劑對不同的底物均有較好的催化性能。

a反應條件 :1 0.75mmol,2 0.25mmol和 Amberlyst-15 30 mg,于100 ℃，在DMSO(0.8mL)為溶劑中反應24 h。

Chart 1

2.3 催化劑的重復利用

以1a與2a的反應為模板，研究了催化劑的回收利用情況。反應結束后，催化劑經過濾后分別用丙酮和乙醚淋洗。于40 ℃干燥3 h，可直接投入使用無需純化。催化劑可重復使用8次，催化活性無明顯降低。

表2 Amberlyst-15的回收利用

a反應條件：2a 0.25 mmol,1a 0.75 mmol,Amberlyst-15 30 mg,DMSO 0.8 mL,反應 24 h。

報道了一種Amberlyst-15催化的C(sp3)—H鍵對靛紅類化合物的加成反應合成3-羥基-2-吲哚酮類化合物的新方法。此反應所使用的催化劑穩(wěn)定，經過濾后可回收和重復使用八次且產率沒有明顯的降低。該方法操作簡單、底物適用范圍廣且產物收率高，符合“綠色化學” 的基本要求，具有較好的應用前景和科研價值。

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The Nucleophilic Addition Reactions of C(sp3)—H to Isatins Catalyed by Amberlyst-15

DONG Dao-qing,HU Dong-yue,XUN Zhi-yu,LI Zong-hui, SHI Da-peng,YANG Jia-qi,WANG Zu-li*

(College of Chemistry and Pharmaceutical Sciences,Qingdao Agricultural University,Qingdao 266109,China)

Twenty four 3-hydroxy-2-oxindoles(3a～3x) were synthesized by the nucleophilic addition reactions of C(sp3)—H bond in methyl pyridine compounds to isatins,using Amberlyst-15 as catalyst.Among them,3u～3x were novel compounds and the structures were characterized by1H NMR,13C NMR,IR and HR-MS(ESI).The catalyst can be reused for eight times without significant loss of its catalytic activity.

C(sp3)—H bond;amberlyst-15;green chemistry;isatin;synthesis;oxindole

2016-04-14；

2016-09-23

國家自然科學基金資助項目( 21402103)；山東省優(yōu)秀中青年基金資助項目(BS2013YY024)；中國博士后基金資助項目(150030)

董道青(1982-)，女，漢族，山東青島人，碩士，主要從事有機化學的研究。 E-mail:why20062002@163.com

王祖利，副教授，Tel.0532-86080895，E-mail:wangzulichem@163.com

O621.25；O621.3

A

10.15952/j.cnki.cjsc.1005-1511.2016.12.16104