新型順-1,3-二芳基螺[吡唑-4,2′-吡唑并[1,2-a]吡唑]衍生物的非對映選擇性合成

朱美軍, 張 瑜, 陸玉玲, 孫 晶, 顏朝國*

(1. 江海職業(yè)技術(shù)學(xué)院，江蘇 揚(yáng)州 225101； 2. 揚(yáng)州大學(xué) 化學(xué)化工學(xué)院，江蘇 揚(yáng)州 225002)

新型順-1,3-二芳基螺[吡唑-4,2′-吡唑并[1,2-a]吡唑]衍生物的非對映選擇性合成

朱美軍1, 張 瑜2, 陸玉玲2, 孫 晶2, 顏朝國2*

(1. 江海職業(yè)技術(shù)學(xué)院，江蘇 揚(yáng)州 225101； 2. 揚(yáng)州大學(xué) 化學(xué)化工學(xué)院，江蘇 揚(yáng)州 225002)

在三乙胺催化下，環(huán)偶氮甲亞胺與4-芳亞基-5-甲基-2-苯基吡唑-3-酮在乙腈中回流反應(yīng)，經(jīng)1,3-偶極環(huán)加成反應(yīng)合成了13個(gè)新型的1,3-二芳基取代的螺[吡唑-4,2′-吡唑并[1,2-a]吡唑]衍生物(3a～3m)，其結(jié)構(gòu)經(jīng)1H NMR,13C NMR, IR和HR-MS(ESI)表征。采用X-射線單晶衍射研究了3d,3h,3j和3l的單晶結(jié)構(gòu)。結(jié)果表明：3為特殊的順式-1,3-二芳基構(gòu)型。

偶氮甲亞胺; 吡唑酮; 螺環(huán)化合物; 1,3-偶極環(huán)加成; 非對映選擇性合成

吡唑及其衍生物是多種天然產(chǎn)物和合成化合物的重要結(jié)構(gòu)單元。吡唑類化合物大多具有良好的生物活性，在新藥和農(nóng)藥開發(fā)中有諸多應(yīng)用[1]。其中，吡唑并[1,2-a]吡唑是應(yīng)用最為廣泛的吡唑類化合物之一[2-3]。如吡唑并[1,2-a]吡唑啉酮可用作除草劑，也可用作乙酰輔酶A羧化酶和肌醇(內(nèi)肽)胞質(zhì)Ca2+-ATPase的抑制劑[4-5]。此外，還對有氧和厭氧細(xì)菌有顯著的廣譜殺滅活性[6]。γ-內(nèi)酰胺類抗生素是基于肽模擬物的吡唑并[1,2-α]吡唑啉酮類化合物[7]，藥理性質(zhì)獨(dú)特，藥用價(jià)值較高，其合成方法的研究一直是該領(lǐng)域的熱點(diǎn)之一[8-9]。

Scheme1

1,3-偶極子偶氮甲亞胺和含雙鍵、三鍵的親偶極體的1,3-偶極環(huán)加成反應(yīng)，由于具有底物多樣性，區(qū)域選擇性和立體選擇性，成為合成吡唑并[1,2-a]吡唑啉酮衍生物的高效方法之一[10-19]。本課題組持續(xù)開展了螺雜環(huán)化合物的高效合成方法的研究工作，取得諸多成果[20-23]。但使用環(huán)狀偶氮甲亞胺進(jìn)行1,3-偶極環(huán)加成反應(yīng)合成螺吡唑并[1,2-a]吡唑啉酮衍生物的報(bào)道較少[24-26]。最近，我們成功地通過環(huán)狀偶氮甲亞胺進(jìn)行1,3-偶極環(huán)加成反應(yīng)，合成了螺[茚-2,2′-吡唑并[1,2-a]吡唑]和螺[二氫吲哚-3,2′-吡唑并[1,2-a]吡唑]衍生物[27]。為進(jìn)一步拓展環(huán)狀偶氮甲亞胺在1,3-偶極環(huán)加成反應(yīng)中的應(yīng)用范圍，我們繼續(xù)展開了環(huán)狀偶氮甲亞胺與4-亞芳基-5-甲基-2-苯基吡唑-3-酮的1,3-偶極環(huán)加成反應(yīng)的研究。

本文在三乙胺催化下，環(huán)偶氮甲亞胺(1a,1b,1f,1i,1l)與4-芳亞基-5-甲基-2-苯基吡唑-3-酮(2a～2e,2j,2l,2m)在乙腈中回流反應(yīng)，經(jīng)1,3-偶極環(huán)加成反應(yīng)合成了13個(gè)新型的1,3-二芳基取代的螺[吡唑-4,2′-吡唑并[1,2-a]吡唑]衍生物(3a～3m, Scheme 1)，其結(jié)構(gòu)經(jīng)1H NMR,13C NMR, IR和HR-MS(ESI)表征。采用X-射線單晶衍射研究了3d,3h,3j和3l的單晶結(jié)構(gòu)。

1 實(shí)驗(yàn)部分

1.1 儀器與試劑

XT-4型顯微熔點(diǎn)儀(溫度未校正)；Agilent DD2 400 MHz型核磁共振儀(CDCl3為溶劑，TMS為內(nèi)標(biāo));Bruker Tensor 27型紅外光譜儀(KBr壓片)；Bruker MaXis型超高分辨質(zhì)譜儀；Bruker Smart APEX-2型X-射線單晶衍射儀。

1和2a～2m按文獻(xiàn)[14]方法合成；其余所用試劑和溶劑均為分析純。

1.2 3a～3m的合成通法

在反應(yīng)瓶中依次加入10.5 mmol,20.5 mmol，三乙胺0.1 mmol和乙腈15.0 mL，回流反應(yīng)6 h。旋蒸除溶，殘余物經(jīng)硅膠柱層析(洗脫劑：石油醚/乙酸乙酯=1/1,V/V)純化得3a～3m。

3a: 白色固體,產(chǎn)率56%, m.p.160～162 ℃;1H NMRδ: 7.80～7.77(m, 2H, ArH), 7.44～7.39(m, 4H, ArH), 7.28～7.29(m, 2H, ArH), 7.26～7.25(m, 1H, ArH), 7.24～7.22(m, 3H, ArH), 7.04～7.02(m, 2H, ArH), 5.66(s, 1H, CH), 4.41(s, 1H, CH), 3.95～3.88(m, 1H, CH), 3.27～3.19(m, 1H, CH), 3.08～2.99(m, 1H, CH), 2.97～2.90(m, 1H, CH), 1.56(s, 3H, CH3);13C NMRδ: 173.9, 170.5, 159.1, 137.3, 134.5, 132.0, 131.6, 129.1, 129.0, 128.9, 126.0, 125.8, 122.2, 119.2, 77.3, 72.7, 63.5, 47.8, 31.8, 17.2; IRν: 2 871, 1 702, 1 494, 1 397, 1 320, 1 246, 1 125, 1 081, 1 007, 854, 806, 725 cm-1; HR-MS(ESI)m/z: Calcd for C27H24N4O2Br{[M+H]+}515.107 7, found 515.108 4。

3b: 白色固體,產(chǎn)率60%, m.p.198～200 ℃;1H NMRδ: 7.82～7.79(m, 2H, ArH), 7.41(t,J=8.0 Hz, 2H, ArH), 7.30～7.27(m, 2H, ArH), 7.26～7.22(m, 2H, ArH), 7.14～7.10(m, 4H, ArH), 7.07～7.05(m, 2H, ArH), 5.74(s, 1H, CH), 4.38(s, 1H, CH), 3.93～3.86(m, 1H, CH), 3.24～3.16(m, 1H, CH), 3.07～3.00(m, 1H, CH), 2.96～2.90(m, 1H, CH), 2.27(s, 3H, CH3), 1.57(s, 3H, CH3);13C NMRδ: 173.4, 170.9, 159.6, 138.9, 137.4, 135.3, 129.6, 128.9, 128.8, 128.6, 128.2, 125.9, 125.6, 125.0, 119.3, 77.4, 77.2, 72.9, 63.8, 47.9, 32.1, 21.1, 17.1; IRν: 3 020, 1 713, 1 594, 1 500, 1 455, 1 368, 1 327, 1 246, 1 187, 1 095, 1 016, 857, 816, 753 cm-1; HR-MS(ESI)m/z: Calcd for C28H27N4O2{[M+H]+}451.212 9, found 451.213 4。

3c: 白色固體,產(chǎn)率68%, m.p.184～186 ℃;1H NMRδ: 7.81～7.79(m, 2H, ArH), 7.41(t,J=8.0 Hz, 2H, ArH), 7.23(t,J=7.2 Hz, 1H, ArH), 7.13～7.05(m, 6H, ArH), 7.02～7.00(m, 2H, ArH), 5.70(s, 1H, CH), 4.37(s, 1H, CH), 3.93～3.87(m, 1H, CH), 3.22～3.15(m, 1H, CH), 3.08～3.02(m, 1H, CH), 2.95～2.88(m, 1H, CH), 2.28(s, 3H, CH3), 2.27(s, 3H, CH3), 1.56(s, 3H, CH3);13C NMRδ: 172.9, 170.9, 159.7, 138.8, 137.9, 137.4, 132.2, 129.6, 129.5, 128.9, 128.7, 125.9, 125.6, 124.8, 119.2, 77.3, 72.9, 63.7, 48.2, 32.4, 21.1, 21.0, 17.2; IRν: 1 714, 1 596, 1 502, 1 453, 1 365, 1 322, 1 242, 1 184, 1 090, 1 029, 859, 821, 755 cm-1; HR-MS (ESI)m/z: Calcd for C29H29N4O2{[M+H]+}465.228 5, found 465.229 3。

3d: 白色固體,產(chǎn)率70%, m.p.178～180 ℃;1H NMRδ: 7.80(d,J=8.0 Hz, 2H, ArH), 7.41 (t,J=8.0 Hz, 2H, ArH), 7.23(t,J=7.2 Hz, 1H, ArH), 7.13～7.11(m, 2H, ArH), 7.07～7.00(m, 4H, ArH), 6.82～6.80(m, 2H, ArH), 5.69(s, 1H, CH), 4.37(s, 1H, CH), 3.93～3.87(m, 1H, CH), 3.76(s, 3H, OCH3), 3.22～3.15(m, 1H, CH), 3.08～3.01(m, 1H, CH), 2.95～2.89(m, 1H, CH), 2.27(s, 3H, CH3), 1.57(s, 3H, CH3);13C NMRδ: 172.9, 170.9, 159.8, 159.3, 138.8, 137.4, 129.6, 128.9, 128.7, 127.2, 126.2, 125.9, 125.6, 119.2, 114.2, 77.2, 73.0, 63.5, 55.2, 48.2, 32.3, 21.1, 17.2; IRν: 3 003, 2 834, 1 713, 1 599, 1 505, 1 455, 1 363, 1 318, 1 249, 1 184, 1 122, 1 087, 1 030, 923, 829, 758 cm-1; HR-MS(ESI)m/z: Calcd for C29H29N4O3{[M+H]+}481.223 4, found 481.224 0。

3e: 白色固體,產(chǎn)率75%, m.p.190～192 ℃;1H NMRδ: 7.81～7.79(m, 2H, ArH), 7.44～7.40(m, 4H, ArH), 7.24(t,J=7.6 Hz, 1H, ArH), 7.11～7.01(m, 6H, ArH), 5.65(s, 1H, CH), 4.38(s, 1H, CH), 3.93～3.86(m, 1H, CH), 3.25～3.17(m, 1H, CH), 3.08～2.99(m, 1H, CH), 2.96～2.89(m, 1H, CH), 2.27(s, 3H, CH3), 1.57(s, 3H, CH3);13C NMRδ: 173.8, 170.6, 159.2, 139.0, 137.3, 134.6, 132.0, 129.6, 129.0, 128.4, 126.8, 125.9, 125.7, 122.1, 119.2, 77.3, 72.7, 63.4, 47.9, 31.9, 21.1, 17.3; IRν: 3 037, 2 936, 2 886, 1 709, 1 598, 1 497, 1 406, 1 369, 1 335, 1 290, 1 235, 1 181, 1 083, 1 008, 859, 819, 754 cm-1; HR-MS(ESI)m/z: Calcd for C28H26N4O2Br{[M+H]+}529.123 4, found 529.123 2。

3f: 白色固體,產(chǎn)率68%, m.p.154～156 ℃;1H NMRδ: 7.79～7.78(m, 2H, ArH), 7.43～7.39(m, 2H, ArH), 7.24～7.22(m, 1H, ArH), 7.19～7.11(m, 3H, ArH), 7.06～7.02(m, 1H, ArH), 6.98～6.87(m, 2H, ArH), 6.83～6.78(m, 2H, ArH), 5.69(s, 1H, CH), 4.35(s, 1H, CH), 3.92～3.86(m, 1H, CH), 3.74(s, 3H, OCH3), 3.22～3.15(m, 1H,CH), 3.08～3.00(m, 1H, CH), 2.96～2.89(m, 1H, CH), 2.27(s, 3H, CH3), 1.55(s, 3H, CH3);13C NMRδ: 170.9, 159.8, 159.6, 138.4, 137.4, 135.2, 128.9, 128.8, 128.7, 127.2, 125.6, 125.5, 123.4, 122.0, 119.3, 114.2, 72.8, 63.7, 55.1, 47.8, 32.0, 21.4, 17.2; IRν: 2 945, 2 836, 1 714, 1 601, 1 504, 1 455, 1 362, 1 299, 1 246, 1 176, 1 124, 1 086, 1 030, 847, 757 cm-1; HR-MS(ESI)m/z: Calcd for C29H28N4O3Na{[M+Na]+}503.205 9, found 503.205 7。

3g: 白色固體,產(chǎn)率64%, m.p.156～158 ℃;1H NMRδ: 7.78(d,J=7.6 Hz, 2H, ArH), 7.43～7.40(t,J=6.4 Hz, 2H, ArH), 7.23～7.22(m, 2H, ArH), 7.21～7.17(m, 2H, ArH), 7.16～7.13(m, 2H, ArH), 6.92～6.90(m, 1H, ArH), 6.80～6.78(m, 2H, ArH), 5.66(s, 1H, CH), 4.35(s, 1H, CH), 3.90～3.88(m, 1H, CH), 3.74(s, 3H, OCH3), 3.23～3.20(m, 1H, CH), 2.99～2.94(m, 2H, CH), 1.67～1.60(m, 1H, CH), 1.56(s, 3H, CH3);13C NMRδ: 174.4, 170.6, 159.9, 159.1, 137.7, 134.9, 130.2, 128.9, 128.3, 127.2, 125.7, 125.3, 123.2, 123.2, 119.3, 114.3, 72.6, 63.2, 55.2, 47.3, 31.5, 17.2; IRν: 3 063, 2 995, 2 944, 2 830, 1 713, 1 601, 1 505, 1 460, 1 412, 1 364, 1 302, 1 246, 1 182, 1 089, 1 032, 907, 848, 758 cm-1; HR-MS(ESI)m/z: Calcd for C28H25N4O3ClNa{[M+Na]+} 523.151 3, found 523.151 8。

3h: 白色固體,產(chǎn)率65%, m.p.200～202 ℃;1H NMRδ: 7.81～7.79(m, 2H, ArH), 7.43～7.39(m, 4H, ArH), 7.25～7.22(m, 1H, ArH), 7.16～7.13(m, 2H, ArH), 7.03～7.01(m, 2H, ArH), 6.80～6.77(m, 2H, ArH), 5.64(s, 1H, CH), 4.36(s, 1H, CH), 3.93～3.86(m, 1H, CH), 3.74(s, 3H, OCH3), 3.24～3.17(m, 1H, CH), 3.06～3.00(m, 1H, CH), 2.96～2.89(m, 1H, CH), 1.58(s, 3H, CH3);13C NMRδ: 173.9, 170.6, 160.0, 159.2, 137.3, 134.6, 132.0, 129.0, 127.2, 126.8, 125.7, 123.2, 122.1, 119.1, 114.3, 77.3, 72.7, 63.3, 55.2, 47.8, 31.9, 17.3; IRν: 2 945, 1 707, 1 607, 1 503, 1 408, 1 370, 1 303, 1 248, 1 178, 1 086, 1 041, 826, 771 cm-1; HR-MS(ESI)m/z: Calcd for C28H26N4O3Br{[M+H]+}545.118 3, found 545.118 6。

3i: 白色固體,產(chǎn)率60%, m.p.168～170 ℃;1H NMRδ: 7.81～7.79(m, 2H, ArH), 7.44～7.40(m, 2H, ArH), 7.29～7.27(m, 4H, ArH), 7.25～7.23(m, 2H, ArH), 7.18～7.16(m, 2H, ArH), 7.14～7.12(m, 2H, ArH), 5.74(s, 1H, CH), 4.37(s, 1H, CH), 3.94～3.87(m, 1H, CH), 3.22～3.15(m, 1H, CH), 3.07～3.01(m, 1H, CH), 2.97～2.89(m, 1H, CH), 1.58(s, 3H, CH3);13C NMRδ: 173.5, 170.6, 159.2, 137.3, 135.2, 134.9, 130.4, 129.2, 129.0, 128.9, 128.3, 127.4, 125.8, 125.0, 119.2, 76.8, 72.8, 63.9, 47.9, 31.9, 17.1; IRν: 2 928, 2 843, 1 706, 1 598, 1 496, 1 366, 1 319, 1 245, 1 179, 1 096, 1 017, 847, 782, 708 cm-1; HR-MS(ESI)m/z: Calcd for C27H24N4O2Cl{[M+H]+}471.158 2, found 471.158 6。

3j: 白色固體,產(chǎn)率78%, m.p.204～206 ℃;1H NMRδ: 7.81～7.79(m, 2H, ArH), 7.43(t,J=8.0 Hz, 2H, ArH), 7.28～7.27(m, 3H, ArH), 7.25～7.23(m, 2H, ArH), 7.18～7.16(m, 2H, ArH), 7.09～7.07(m, 2H, ArH), 5.68(s, 1H, CH), 4.36(s, 1H, CH), 3.93～3.86(m, 1H, CH), 3.23～3.16(m, 1H, CH), 3.08～3.02(m, 1H, CH), 2.97～2.90(m, 1H, CH), 1.55(s, 3H, CH3);13C NMRδ: 173.9, 170.3, 158.8, 137.2, 135.0, 134.2, 133.8, 130.1, 129.3, 129.1, 129.0, 127.3, 126.4, 125.9, 119.1, 72.7, 63.4, 47.8, 31.8, 17.2; IRν: 2 942, 2 885, 1 704, 1 494, 1 407, 1 370, 1 336, 1 285, 1 234, 1 184, 1 092, 1 009, 824, 762, 733, 701 cm-1; HR-MS(ESI)m/z: Calcd for C27H23N4O2Cl2{[M+H]+}505.119 3, found 505.119 8。

3k: 白色固體,產(chǎn)率75%, m.p.210～212 ℃;1H NMRδ: 7.79 (d,J=8.0 Hz, 2H, ArH), 7.44～7.40(m, 6H, ArH), 7.25～7.23(m, 1H, ArH), 7.10(d,J=8.0 Hz, 2H, ArH), 7.01(d,J=8.0 Hz, 2H, ArH), 5.65(s, 1H, CH), 4.34(s, 1H, CH), 3.93～3.86(m, 1H, CH), 3.22～3.15(m, 1H, CH), 3.09～2.99(m, 1H, CH), 2.96～2.89(m, 1H, CH), 1.55(s, 3H, CH3);13C NMRδ: 173.9, 170.3, 158.8, 137.1, 134.1, 132.2, 132.0, 130.7, 129.0, 127.6, 126.7, 125.9, 123.2, 122.3, 119.9, 72.5, 63.5, 47.8, 31.8, 17.2; IRν: 2 942, 1 740, 1 655, 1 600, 1 494, 1 406, 1 369, 1 336, 1 288, 1 238, 1 184, 1 082, 1 008, 823, 759 cm-1; HR-MS(ESI)m/z: Calcd for C27H23N4O2Br2{[M+H]+}593.018 2, found 593.018 1。

3l: 白色固體,產(chǎn)率78%, m.p.193～195 ℃;1H NMRδ: 8.19～8.14(m, 2H, ArH), 7.78(d,J=7.2 Hz, 2H, ArH), 7.48～7.42(m, 5H, ArH), 7.34～7.25(m, 2H, ArH), 7.12(d,J=7.6 Hz, 2H, ArH), 5.75(s, 1H, CH), 4.39(s, 1H, CH), 3.99～3.92(m, 1H, CH), 3.28～3.21(m, 1H, CH), 3.07～2.93(m, 2H, CH), 1.51(s, 3H, CH3);13C NMRδ: 175.3, 170.1, 158.2, 148.4, 137.9, 136.9, 132.2, 131.1, 130.4, 130.1, 129.0, 127.6, 126.1, 123.3, 120.3, 119.3, 72.3, 63.4, 47.2, 31.1, 17.2; IRν: 3 072, 2 930, 1 712, 1 596, 1 534, 1 494, 1 403, 1 354, 1 240, 1 180, 1 088, 1 006, 822, 761, 718 cm-1; HR-MS(ESI)m/z: Calcd for C27H22N5O4BrNa{[M+Na]+}582.075 3, found 582.074 7。

3m: 白色固體,產(chǎn)率74%, m.p.158～160 ℃;1H NMRδ: 8.18～8.15(m, 2H, ArH), 7.80～7.78(m, 2H, ArH), 7.42～7.32(m, 7H, ArH), 7.09(d,J=7.6 Hz, 2H, ArH), 5.74(s, 1H, CH), 4.37(s, 1H, CH), 3.94～3.89(m, 1H, CH), 3.25～3.19(m, 1H, CH), 3.01～2.95(m, 2H, CH), 1.25(s, 3H, CH3);13C NMRδ: 174.7, 169.9, 158.1, 147.7, 142.6, 137.0, 132.2, 130.3, 129.1, 127.6, 126.2, 126.0, 124.1, 123.3, 119.0, 72.4, 63.5, 47.5, 31.3, 29.6, 17.2; IRν: 3 072, 2 925, 2 854, 1 714, 1 599, 1 521, 1 495, 1 402, 1 344, 1 241, 1 181, 1 114, 1 011, 846, 757, 719 cm-1; HR-MS(ESI)m/z: Calcd for C27H22N5O4BrNa{[M+Na]+}582.075 3, found 582.075 6。

2 結(jié)果與討論

2.1 合成

[27]方法合成3b，反應(yīng)不完全，產(chǎn)率僅30%左右。延長反應(yīng)時(shí)間，仍然有部分原料不能反應(yīng)。加入酸(或堿)催化劑可以改善反應(yīng)結(jié)果。當(dāng)加入催化量的三乙胺時(shí)，反應(yīng)可快速完成，順利的合成3b，產(chǎn)率大幅提高(約60%)。在此反應(yīng)條件下，可以中等至良好的產(chǎn)率合成預(yù)期產(chǎn)物。初步的構(gòu)效分析表明，兩種反應(yīng)底物上的取代基對產(chǎn)率影響較小。

2.2 表征

(1)1H NMR

由于產(chǎn)物的吡唑環(huán)中存在3個(gè)手性碳原子，反應(yīng)中可能形成多種非對映異構(gòu)體?；衔锏?H NMR譜圖中僅顯示一組特征吸收峰，這表明產(chǎn)物中僅存在一種非對映異構(gòu)體。如3d在δ3.76處的特征峰為甲氧基的單峰，δ2.27和δ1.57處出現(xiàn)了兩個(gè)甲基的單峰，δ5.89和δ4.33處單峰為吡咯環(huán)C—H的特征吸收峰，δ3.93～2.89處的多重峰為吡唑啉酮環(huán)中相鄰的兩個(gè)亞甲基由于非對映特性而出現(xiàn)的4個(gè)H的吸收峰。

(2) X-射線單晶衍射

圖1～圖4為3d,3h,3j和3l的單晶結(jié)構(gòu)圖。由圖1～圖4可見，4個(gè)分子具有相同的相對構(gòu)型。兩個(gè)芳基在新形成的吡唑環(huán)中均位于順式位置。5-甲基-2-苯基吡唑-3-酮單元中的羰基位于兩個(gè)芳基的反式位置，甲基伸向兩個(gè)芳基的同一側(cè)。結(jié)合1H NMR的分析，我們確定3a～3m均具有該相對構(gòu)型，中間吡唑環(huán)中位于1,3-位上的兩個(gè)芳基以順式構(gòu)型存在,這與文獻(xiàn)[24]報(bào)道不同。值得注意的是，我們之前合成的螺[茚-2,2′-吡唑并[1,2-a]吡唑]和螺[二氫吲哚-3,2′-吡唑并[1,2-a]吡唑]也具有順式1,3-二芳基的相對構(gòu)型[27]。

綜上可知，環(huán)狀偶氮甲亞胺與環(huán)狀親1,3-偶極子的環(huán)環(huán)加成反應(yīng)具有非常高的非對映選擇性。

圖1 3d(CCDC: 1538806)的單晶分子結(jié)構(gòu)

圖23h(CCDC: 1538807)的單晶分子結(jié)構(gòu)

Figure2Single crystal structure of3h

圖3 3j(CCDC: 1538808)的單晶分子結(jié)構(gòu)

圖4 3l(CCDC: 1544352)的單晶分子結(jié)構(gòu)

3 結(jié)論

通過環(huán)狀偶氮甲亞胺與4-亞芳基-5-甲基-2-苯基吡唑-3-酮的1,3-偶極環(huán)加成反應(yīng)合成了一系列順-1,3-二芳基取代的螺[吡唑-4,2′-吡唑并[1,2-a]吡唑]。該多環(huán)體系由3個(gè)吡唑環(huán)分別以并環(huán)和螺環(huán)方式連接，結(jié)構(gòu)新穎。該反應(yīng)具有反應(yīng)條件簡單、底物普適性強(qiáng)、反應(yīng)產(chǎn)率高，非對映選擇性好等優(yōu)點(diǎn)。合成的新化合物在藥物研發(fā)中具有潛在的應(yīng)用價(jià)值。

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DiastereoselectiveSynthesisofNovelcis-1,3-Diarylspiro[pyrazole-4,2′-pyrazolo[1,2-a]pyrazoles]

ZHU Mei-jun1, ZHANG Yu2, LU Yu-ling2, SUN Jing2, YAN Chao-guo2*

(1. Jianghai Polytechnic College, Yangzhou 225101, China; 2. College of Chemistry amp; Chemical Engineering, Yangzhou University, Yangzhou 225002, China)

Thirteen novel 1,3-diaryl-substituted spiro[pyrazole-4,2′-pyrazolo[1,2-a]pyrazoles] derivatives(3a～3m) were synthesized by triethylamine catalyzed 1,3-dipolar cycloaddition of cyclic azomethine imines with 4-arylidene-5-methyl-2-phenylpyrazol-3-ones in refluxing acetonitrile. The structures were characterized by1H NMR,13C NMR, IR and HR-MS(ESI). The single crystal structures of3d,3h,3jand3lwere investigated by X-ray single diffraction. The results indicated that3have unusualcis-1,3-diaryl-configuration.

azomethine imine; prazol-3-one; spiro compound; 1,3-dipolar cycloaddition; diastereoselective synthesis

2017-09-07;

2017-11-07

國家自然科學(xué)基金資助項(xiàng)目(21572196)

朱美軍(1975-)，女，漢族，江蘇揚(yáng)州人，碩士，主要從事有機(jī)合成的研究。 E-mail: happyfengjunyang@126.com

顏朝國，教授, E-mail: cgyan@yzu.edu.cn

O626.2

A

10.15952/j.cnki.cjsc.1005-1511.2017.12.17214