CN106977524A - 一种菲并呋喃并吡咯类化合物的合成方法 - Google Patents
一种菲并呋喃并吡咯类化合物的合成方法 Download PDFInfo
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Abstract
一种菲并呋喃并吡咯类化合物的合成方法,属于有机合成技术领域。在溶剂和碱性催化剂存在的条件下将菲醌与丙二腈混合进行缩合反应后,再加入3‑芳基氨基‑1‑甲基‑1H‑吡咯‑2,5‑二酮进行环合反应,得到菲并呋喃并吡咯类化合物。本发明的原料简单易得,反应条件温和绿色化,无需无水无氧及金属催化剂的参与,最重要的是,本发明反应条件绿色无污染,无需无水无氧操作及金属催化剂的参与,原料简单易得,产率高。
Description
技术领域
本发明属于有机合成技术领域。
背景技术
呋喃环含有多个潜在的官能团,如双键、二烯、烯醇醚和羰基等,因而是很好的合成砌块,简单的呋喃类化合物是合成复杂呋喃类化合物的基本原料。另外,呋喃杂环化合物是构成天然食品香气特征的重要微量成分之一,几乎存在于所有的食品香料中,如呋喃环硫醇类香料,2-甲基-3 (4) -乙酰巯基呋喃的合成,其以2-甲基呋喃为起始原料经四步反应合成 (刘亚华等. 精细化工, 1995, 12(4):41)。
许多具有并环吡咯结构的衍生物都有显著的生物活性。如:片螺素含有吡咯并异喹琳结构,是片螺素系列化合物中生物活性最强的(Kuza, J.; Gallego,M. A.; et al.Cancer Cell Mitochondria Are Direct Proapoptotic Targets for the MarineAntitumor Drug Lamellarin D[J]. Cancer Res., 2006, 66, 3177)。并环吡咯结构的合成研究得到科研工作者的关注。2010年,Quiroga等人在乙醇作溶剂,醋酸作催化剂的条件下,通过5,5-二甲基-1,3-环己二酮、芳基乙二酮、氨基嘧啶三组分反应得到吡咯并[2,3-d]嘧啶化合物(Quiroga, J.; Cruz,S; et al. Generation of pyrrolo[2,3-d]pyrimidmes. Unexpected products in the multicomponent reaction of 6-aminopyrimidines, dimedone, and arylglyoxal [J]. Tetrahedron Lett., 2010, 51,5443-5447)。由此可见,对于并环吡咯结构的的研究在合成以及医药方面都具有重要的意义。
目前菲并呋喃并吡咯类化合物的合成研究尚未见文献报道,已有报道仅涉及部分并环结构的合成,并且存在一些不足,如底物拓展范围小,结构简单,原料不易获取,反应条件较苛刻,产率过低等。
发明内容
本发明目的在于克服上述问题,提供一种采用新机理、原料简单易得、反应条件温和绿色化、底物拓展范围大的菲并呋喃并吡咯类化合物的合成方法。
本发明技术方案是:在溶剂和碱性催化剂存在的条件下将菲醌与丙二腈混合进行缩合反应后,再加入3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮进行环合反应,得到菲并呋喃并吡咯类化合物,其结构式为:
其中R1为C1~C3苯基、C1~C3苄基、C1~C4烷基取代苯基或C1~C4卤代苯基中的任意一种。
本发明的反应通式为:
本发明反应机理如下:
本发明以菲醌和丙二睛在碱性条件下进行缩合后再与3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮发生迈克尔加成生成中间体,再进行进行分子内脱水环合生成菲并[9',10':4,5]呋喃并[2,3-c]吡咯[3,4-b]吡咯类化合物。
本发明的原料简单易得,反应条件温和绿色化,无需无水无氧及金属催化剂的参与,最重要的是,本发明反应条件绿色无污染,无需无水无氧操作及金属催化剂的参与,原料简单易得,产率高。
进一步地,本发明所述的R1为苯基、4-甲基苯基、4-甲氧基苯基、4-卤代苯基、3-甲基苯基、2-甲基苯基、3-甲氧基苯基、2-甲氧基苯基、3-卤代苯基或2-卤代苯基中的任意一种,其合成产率可达84%~92%。
另外,所述的溶剂为干燥乙腈。采用该具体产品,使合成产率达到84%~92%。
为了保障较高的合成产率,所述的碱性催化剂为三乙胺。
所述三乙胺和3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮的投料摩尔比为0.1∶1。在此种条件下,其合成产率可达84%~92%。
所述菲醌、丙二腈与3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮的投料摩尔比为1∶1∶1。在该投料比下反应产率最高,最高可达92%。
另外,所述的环合反应的温度条件为0~100℃,反应4~8小时。更优选地,反应温度为25℃下反应6小时。因为低温时反应时间过长,反应不彻底;温度过高,产生副产物,影响产率。实验表明在该温度下,反应速率最快,产率最高。
本发明所述3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮为3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(4-叔丁基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(3-甲基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(2-氯苄基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(4-氯苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(3-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(3-氯苯基)氨基-1-甲基-1H-吡咯-2,5-二酮的一种。以上各种原料简单易得,绿色无污染,且参与反应产率高,最高可达92%。
具体实施方式
下面结合实施例对本发明进一步详细说明,但本发明的保护范围不仅限于这些实施例。
实施例1:
以制备结构式如下的5-亚氨基-4-(4-对甲氧基苯基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-二氧六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈为例,其反应式如下:
制备方法如下:
在圆底烧瓶中加入0.2081g(1.0mmol)菲醌,0.0661g(1.0mmol)丙二腈,加10ml干燥乙腈,滴加0.010g(0.1mmol)三乙胺作为催化剂,25℃下搅拌1小时进行缩合反应,然后再加入1.0mmol 3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5 -二酮,通过薄层色谱跟踪反应,25℃搅拌6 h进行环合反应。停止反应后,在旋转蒸发仪上将溶剂浓缩蒸发,用95%乙醇进行洗涤抽滤,得到粗产物再进行柱层析进行提纯分离(乙酸乙酯:石油醚=1:4)即可得到纯5-亚氨基-4-(4-甲氧基苯基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈,其分离收率为92%。
结构表征数据如下:
1H NMR (400 MHz, DMSO) δ: 8.98 (t, J = 8.4Hz, 2H, ArH), 8.91 (d, J =8.4Hz, 1H, ArH), 8.12 (d, J = 8.4Hz, 1H, ArH), 7.91 (t, J = 7.6Hz, 1H, ArH),7.82 (t, J = 7.6Hz, 1H, ArH), 7.74 (t, J = 7.6Hz, 1H, ArH), 7.67 (t, J =8.0Hz, 1H, ArH), 7.33 (s, 1H, NH), 7.32 (t, J = 8.4Hz, 1H, ArH), 6.98 (d, J =9.2Hz, 2H, ArH), 5.45 (s, 1H, CH), 3.75 (s, 3H, OCH3), 3.08 (s, 3H, CH3); 13CNMR (100 MHz, DMSO) δ: 170.3, 169.2, 158.9, 158.7, 154.0, 132.6, 129.8,129.4, 128.8, 128.2, 128.1, 128.1, 127.1, 125.9, 125.5, 124.2, 122.9, 120.3,115.5, 115.2, 109.6, 91.0, 69.1, 58.3, 55.7, 25.9; IR (KBr) υ: 3297, 3070,2942, 2840, 2312, 1801, 1729, 1655, 1609, 1511, 1436, 1380, 1330, 1300, 1247,1172, 1082, 1040, 1010, 910, 838, 751, 719 cm-1; MS (m/z): HRMS (ESI) C29H21N4O4([M+H]+) 理论值489.1485,实测值489.1581。
实施例2:
以制备结构式如下的4-(4-叔丁基苯基)-5-亚氨基-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈为例:
在实施例1中,所用的3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮用等摩尔量的3-(4-叔丁基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮替换,其他步骤方法与实例1相同,得到4-(4-叔丁基苯基)-5-亚氨基-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈,其分离收率为87%。
结构表征数据如下:
1H NMR (400 MHz, DMSO) δ: 8.99-8.91 (m, 3H, ArH), 8.10 (d, J = 8.0Hz, 1H,ArH), 7.91 (t, J = 8.0Hz, 1H, ArH), 7.85 (s, 1H, NH), 7.82 (t, J = 7.6Hz, 1H,ArH), 7.76 (t, J = 8.0Hz, 1H, ArH), 7.68 (t, J = 7.6Hz, 1H, ArH), 7.43 (d, J = 8.4Hz, 2H, ArH), 7.31 (d, J = 8.4Hz, 2H, ArH), 5.57 (s, 1H, CH), 3.09 (s,3H, CH3), 1.24 (s, 9H, 3CH3); 13C NMR (100 MHz, DMSO) δ: 170.6, 169.2, 157.6,154.0, 149.8, 135.0, 132.6, 129.9, 128.3, 128.2, 128.1, 127.0, 126.8, 126.0,125.3, 125.0, 124.8, 124.3, 122.9, 120.2, 115.4, 109.4, 91.0, 69.1, 69.1,58.7, 34.7, 31.4, 25.9; IR (KBr) υ: 3567, 3287, 2954, 2313, 1800, 1756, 1608,1488, 1395, 1269, 1102, 1035, 1005, 837, 799, 751, 719 cm-1; MS (m/z): HRMS(ESI) C32H27N4O3 ([M+H]+) 理论值515.2064,实测值515.2096。
实施例3:
以制备结构式如下的5-亚氨基-4-(3-甲基苯基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈为例:
在实施例1中,所用的3-(4-甲基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮用等摩尔量的3-(3-甲基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮替换,其他步骤方法与实例1相同,得到5-亚氨基-4-(3-甲基苯基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈,其分离收率为86%。
结构表征数据如下:
1H NMR (400 MHz, DMSO) δ: 8.99-8.91 (m, 3H, ArH), 8.11 (d, J = 7.6Hz,1H, ArH), 7.91 (t, J = 7.6Hz, 1H, ArH), 7.83 (s, 1H, NH), 7.79 (t, J = 7.2Hz,1H, ArH), 7.75 (t, J = 7.6Hz, 1H, ArH), 7.68 (t, J = 7.6Hz, 1H, ArH), 7.32(t, J = 8.0Hz, 1H, ArH), 7.22 (s, 2H, ArH) 7.11, (d, J = 7.2Hz, 1H, ArH),5.60 (s, 1H, CH), 3.10 (s, 3H, CH3), 2.26 (s, 3H, CH3); 13C NMR (100 MHz,DMSO) δ: 170.4, 169.2, 157.6, 154.1, 139.6, 137.3, 132.6, 129.9, 128.2,128.1, 128.1, 127.0, 126.0, 125.3, 124.2, 122.9, 120.2, 115.4, 109.4, 91.1,69.0, 58.6, 25.9, 21.2; IR (KBr) υ: 3293, 3066, 2926, 2319, 1800, 1725, 1660,1604, 1486, 1376, 1267, 1083, 1043, 1004, 826, 800, 755, 719 cm-1; MS (m/z):HRMS (ESI) C29H21N4O3 ([M+H]+) 理论值473.1535,实测值473.1618。
实施例4:
以制备结构式如下的5-亚氨基-4-(2-氯苄基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈为例:
在实施例1中,所用的3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮用等摩尔量的3-(2-氯苄基)氨基-1-甲基-1H-吡咯-2,5-二酮替换,其他步骤方法与实例1相同,得到5-亚氨基-4-(2-氯苄基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈,其分离收率为85%。
结构表征数据如下:
1H NMR (400 MHz, DMSO) δ: 8.97 (t, J = 8.8Hz, 2H, ArH), 8.90 (d, J =8.4Hz, 1H, ArH), 8.09 (s, 1H, NH), 8.03 (d, J = 7.6Hz, 1H, ArH), 7.90 (t, J =7.6Hz, 1H, ArH), 7.82-7.73 (m, 2H, ArH), 7.68 (t, J = 8.0Hz, 1H, ArH), 7.33(d, J = 8.0Hz, 1H, ArH), 7.23 (t, J = 7.6Hz, 1H, ArH), 7.13-7.09 (m, 2H,ArH), 5.01-4.97(m, 1H, CH), 4.80 (s, 1H, CH), 4.66-4.62 (m, 1H, CH), 3.06 (s,3H, CH3); 13C NMR (100 MHz, DMSO) δ: 171.0, 169.3, 157.7, 153.7, 132.9, 132.5,130.1, 129.9, 129.8, 129.8, 128.2, 128.0, 127.6, 127.0, 126.0, 125.4, 124.3,124.2, 122.6, 120.0, 115.4, 109.7, 91.1, 66.2, 66.1, 58.7, 45.1, 25.7; IR(KBr) υ: 3286, 3068, 2320, 1800, 1727, 1662, 1494, 1377, 1331, 1299, 1273,1247, 1170, 1043, 1012, 967, 911, 874, 836, 789, 753, 718 cm-1; IR (KBr) υ:3305, 2915, 2313, 1725, 1666, 1430, 1377, 1333, 1263, 1172, 1083, 1045, 1003,825, 798, 754, 720 cm-1; MS (m/z): HRMS (ESI) C29H20ClN4O3 ([M+H]+) 理论值507.1146,实测值507.1228。
实施例5:
以制备结构式如下的4-(4-氯苯基)-5-亚氨基-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈为例:
在实施例1中,所用的3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮用等摩尔量的3-(4-氯苯基)氨基-1-甲基-1H-吡咯-2,5-二酮替换,其他步骤方法与实例1相同,得到5-亚氨基-4-(4-氯苯基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈,其分离收率为90%。
结构表征数据如下:
1H NMR (400 MHz, DMSO) δ: 8.97 (t, J = 7.6Hz, 2H, ArH), 8.91 (d, J =8.4Hz, 1H, ArH), 8.11 (d, J = 8.0Hz, 1H, ArH), 8.04 ( s, 1H, NH), 7.91 (t, J = 8.0Hz, 1H, ArH), 7.82 (t, J = 7.6Hz, 1H, ArH), 7.76 (t, J = 7.6Hz, 1H,ArH), 7.68 (t, J = 7.6Hz, 1H, ArH), 7.50-7.43 (m, 4H, ArH), 5.60 (s, 1H, CH),3.08 (s, 3H, CH3); 13C NMR (100 MHz, DMSO) δ: 170.5, 169.1, 157.2, 154.0,136.5, 132.6, 131.6, 130.0, 129.9, 128.2, 128.2, 128.1, 128.1, 127.7, 127.0,126.0, 125.3, 124.2, 122.9, 120.2, 115.3, 109.4, 90.9, 68.9, 58.6, 25.9; IR(KBr) υ: 3286, 3068, 2320, 1800, 1727, 1662, 1494, 1377, 1331, 1299, 1273,1247, 1170, 1043, 1012, 967, 911, 874, 836, 789, 753, 718 cm-1; MS (m/z): HRMS(ESI) C28H18ClN4O3 ([M+H]+) 理论值 493.0989. 实测值 493.1070。
实施例6:
以制备结构式如下的4-(3-甲基苯基)-5-亚氨基-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈为例:
在实施例1中,所用的3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮用等摩尔量的3-(3-甲基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮替换,其他步骤方法与实例1相同,得到5-亚氨基-4-(3-甲基苯基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈,其分离收率为86%。
结构表征数据如下:
1H NMR (400 MHz, DMSO) δ: 8.99-8.91 (m, 3H, ArH), 8.11 (d, J = 7.6Hz, 1H,ArH), 7.91 (t, J = 7.6Hz, 1H, ArH), 7.83 (s, 1H, NH), 7.79 (t, J = 7.2Hz, 1H,ArH), 7.75 (t, J = 7.6Hz, 1H, ArH), 7.68 (t, J = 7.6Hz, 1H, ArH), 7.32 (t, J = 8.0Hz, 1H, ArH), 7.22 (s, 2H, ArH) 7.11, (d, J = 7.2Hz, 1H, ArH), 5.60 (s,1H, CH), 3.10 (s, 3H, CH3), 2.26 (s, 3H, CH3); 13C NMR (100 MHz, DMSO) δ:170.4, 169.2, 157.6, 154.1, 139.6, 137.3, 132.6, 129.9, 128.2, 128.1, 128.1,127.0, 126.0, 125.3, 124.2, 122.9, 120.2, 115.4, 109.4, 91.1, 69.0, 58.6,25.9, 21.2; IR (KBr) υ: 3293, 3066, 2926, 2319, 1800, 1725, 1660, 1604, 1486,1376, 1267, 1083, 1043, 1004, 826, 800, 755, 719 cm-1; MS (m/z): HRMS (ESI)C29H21N4O3 ([M+H]+) 理论值 473.1535. 实测值473.1618。
实施例7:
以制备结构式如下的4-(3-甲氧基苯基)-5-亚氨基-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈为例:
在实施例1中,所用的3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮用等摩尔量的3-(3-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮替换,其他步骤方法与实例1相同,得到5-亚氨基-4-(3-甲氧基苯基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈,其分离收率为85%。
结构表征数据如下:
1H NMR (400 MHz, DMSO) δ: 8.97 (d, J = 8.4Hz, 2H, ArH), 8.91 (d, J =8.4Hz, 1H, ArH), 8.11 (d, J = 8.4Hz, 1H, ArH), 7.95 (s, 1H, NH), 7.91 (t, J =8.0Hz, 1H, ArH), 7.82 (t, J = 7.6Hz, 1H, ArH), 7.68 (t, J = 7.6Hz, 1H, ArH),7.31 (t, J = 8.0Hz, 1H, ArH), 7.08 (s, 1H, ArH), 6.93 (d, J = 8.4Hz, 1H,ArH), 6.88-6.86 (m, 1H, ArH), 5.63 (s, 1H, CH), 3.72 (s, 3H, OCH3), 3.09 (s,3H, CH3); 13C NMR (100 MHz, DMSO) δ: 170.4, 169.2, 160.5, 157.3, 154.0, 138.6,132.6, 130.8, 129.8, 128.2, 128.1, 127.0, 126.0, 125.3, 124.2, 122.9, 120.2,117.4, 115.4, 113.1, 111.3, 109.4, 91.0, 69.0, 58.7, 55.6, 25.9; IR (KBr) υ:3300, 3094, 2311, 1798, 1725, 1069, 1585, 1510, 1433, 1333, 1249, 1168, 1083,1039, 914, 881, 839, 799, 746, 718 cm-1; MS (m/z): HRMS (ESI) C29H21N4O4 ([M+H]+) 理论值 489.1485. 实测值 489.1581。
实施例8:
以制备结构式如下的4-(3-氯苯基)-5-亚氨基-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈为例:
在实施例1中,所用的3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮用等摩尔量的3-(3-氯苯基)氨基-1-甲基-1H-吡咯-2,5-二酮替换,其他步骤方法与实例1相同,得到5-亚氨基-4-(3-氯苯基)-2-甲基-1,3-二氧-2,3,3a,4,5,5a-六氢-1H-菲并[9',10':4,5]呋喃[2,3-c]吡咯[3,4-b]吡咯-5a-甲腈,其分离收率为84%。
结构表征数据如下:
1H NMR (400 MHz, DMSO) δ: 8.97 (d, J = 8.4Hz, 2H, ArH), 8.91 (d, J =8.4Hz, 1H, ArH), 8.98 (s, 1H, NH), 8.11 (d, J = 8.4Hz, 1H, ArH), 7.91 (t, J =7.6Hz, 1H, ArH), 7.82 (t, J = 7.2Hz, 1H, ArH), 7.77 (t, J = 7.6Hz, 1H, ArH),7.68 (t, J = 7.6Hz, 1H, ArH), 7.60 (s, 1H, ArH), 7.44 (t, J = 8.8Hz, 1H,ArH), 7.35 (d, J = 8.4Hz, 2H, ArH), 5.65 (s, 1H, CH), 3.09 (s, 3H, CH3); 13CNMR (100 MHz, DMSO) δ: 170.5, 169.1, 156.9, 154.1, 139.1, 134.1, 132.6,131.5, 129.8, 128.2, 128.1, 127.2, 127.0, 126.0, 125.6, 125.3, 124.3, 124.2,122.9, 120.2, 115.3, 109.4, 90.8, 68.9, 58.6, 26.0; IR (KBr) υ: 3302, 3068,2312, 1801, 1726, 1658, 1577, 1485, 1435, 1381, 1271, 1224, 1169, 1054, 1011,869, 810, 767, 725 cm-1; MS (m/z): HRMS (ESI) C28H18ClN4O3 ([M+H]+) 理论值493.0989. 实测值493.1067。
Claims (9)
1.一种菲并呋喃并吡咯类化合物的合成方法,其特征在于:在溶剂和碱性催化剂存在的条件下将菲醌与丙二腈混合进行缩合反应后,再加入3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮进行环合反应,得到菲并呋喃并吡咯类化合物,结构式为:
其中R1为C1~C3烷基、C1~C3苯基、C1~C3苄基、C1~C4烷基取代苯基或C1~C4卤代苯基中的任意一种。
2.根据权利要求1所述的合成方法,其特征在于:所述的R1为苯基、4-甲基苯基、4-甲氧基苯基、4-卤代苯基、3-甲基苯基、2-甲基苯基、3-甲氧基苯基、2-甲氧基苯基、3-卤代苯基或2-卤代苯基中的任意一种。
3.根据权利要求1所述的合成方法,其特征在于:所述的溶剂为干燥乙腈。
4.根据权利要求1所述的合成方法,其特征在于:所述的碱性催化剂为三乙胺。
5.根据权利要求4所述的合成方法,其特征在于:所述三乙胺和3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮的投料摩尔比为0.1∶1。
6.根据权利要求1所述的合成方法,其特征在于所述菲醌、丙二腈与3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮的投料摩尔比为1∶1∶1。
7.根据权利要求1或2或3或4或5或6所述的合成方法,其特征在于:所述的环合反应的温度条件为0~100℃,反应4~8小时。
8.根据权利要求7所述的合成方法,其特征在于:所述的环合反应的反应温度为25℃,反应6小时。
9.根据权利要求1所述的合成方法,其特征在于:所述3-芳基氨基-1-甲基-1H-吡咯-2,5-二酮为3-(4-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(4-叔丁基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(3-甲基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(2-氯苄基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(4-氯苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(3-甲氧基苯基)氨基-1-甲基-1H-吡咯-2,5-二酮、3-(3-氯苯基)氨基-1-甲基-1H-吡咯-2,5-二酮的一种。
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CN108017637A (zh) * | 2017-12-21 | 2018-05-11 | 扬州大学 | 一种吲哚并吡咯并喹啉类化合物及其合成方法 |
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-
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Non-Patent Citations (2)
Title |
---|
CHAO WANG ET AL.: "Convenient synthesis of spiro[indoline-3,40-pyrano[2,3-c]pyrazole] and spiro[acenaphthyl-3,40-pyrano[2,3-c]pyrazoles] via four component", 《CHINESE CHEMICAL LETTERS》 * |
YAN-HONG JIANG ET AL.: "Convenient synthesis of functionalized pyrrolo[3,4-b]pyridines and pyrrolo[3,4-b]quinolines via three component", 《RSC ADVANCES》 * |
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CN108017637A (zh) * | 2017-12-21 | 2018-05-11 | 扬州大学 | 一种吲哚并吡咯并喹啉类化合物及其合成方法 |
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