CN107936019B - 一种八氢二吡咯并喹啉类化合物的制备方法 - Google Patents

一种八氢二吡咯并喹啉类化合物的制备方法 Download PDF

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CN107936019B
CN107936019B CN201711254567.1A CN201711254567A CN107936019B CN 107936019 B CN107936019 B CN 107936019B CN 201711254567 A CN201711254567 A CN 201711254567A CN 107936019 B CN107936019 B CN 107936019B
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CN107936019A (zh
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肖建
朱帅
李帅帅
王亮
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Qingdao Agricultural University
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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
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Abstract

本发明涉及一种苯基‑2‑吡咯烷基苄醇类化合物在酸性条件下生成八氢二吡咯并喹啉化合物的方法。以苯基‑2‑吡咯烷基苄醇类化合物在酸性条件下脱水生成碳正离子，四氢吡咯邻位碳上的氢以氢负离子的形式迁移到碳正离子，原位上生成亚胺正离子，其中的一部分亚胺正离子通过质子转移转变为烯胺，烯胺分子与含有亚胺正离子的分子发生分子间的[4+2]环加成反应得到八氢二吡咯并喹啉化合物。本发明实现了通过氢迁移策略构建了八氢二吡咯并喹啉化合物，不需要金属催化剂，绿色环保，成本低廉。

Description

一种八氢二吡咯并喹啉类化合物的制备方法
技术领域
本发明涉及化学合成技术领域，特别涉及一种八氢二吡咯并喹啉类化合物的制备方法。
背景技术
八氢二吡咯并喹啉骨架是天然产物Incargranine B和seneciobipyrrolidine基本骨架的非对映体。
目前，生产类似骨架化合物的方法如：
所使用的催化剂为：该方法使用手性磷酸和银催化剂成本高，有污染。
发明内容
针对现有技术中存在的问题，本发明的目的在于提供一种苯基-2-吡咯烷基苄醇类化合物在酸性条件下生成八氢二吡咯并喹啉化合物的方法。
具体反应式如下：
其中，R1，R2，R3均为H、CH3或OCH3。
苯基-2-吡咯烷基苄醇类化合物以PA(联萘酚磷酸)为催化剂，以甲苯为溶剂，在60℃的条件下，反应24小时，制得八氢二吡咯并喹啉化合物；其中苯基-2-吡咯烷基苄醇类化合物与PA的摩尔比为10:2；溶剂甲苯的用量为：每mmol苯基-2-吡咯烷基苄醇类化合物添加10ml。
联萘酚磷酸：
反应原理：
本发明以苯基-2-吡咯烷基苄醇类化合物在酸性条件下脱水生成碳正离子，四氢吡咯邻位碳上的氢以氢负离子的形式迁移到碳正离子，原位上生成亚胺正离子，其中的一部分亚胺正离子通过质子转移转变为烯胺，烯胺分子与含有亚胺正离子的分子发生分子间的[4+2]环加成反应得到八氢二吡咯并喹啉化合物。本发明实现了通过氢迁移策略构建了八氢二吡咯并喹啉化合物，不需要金属催化剂，绿色环保，成本低廉。
附图说明：
图1为本发明实施例2产物的核磁共振1H谱；
图2为本发明实施例2产物的核磁共振13C谱；
图3为本发明实施例3产物的核磁共振1H谱；
图4为本发明实施例3产物的核磁共振13C谱；
图5为本发明实施例4产物的核磁共振1H谱；
图6为本发明实施例4产物的核磁共振13C谱。
具体实施方式
实施例1
以3-甲氧基苯基-2-吡咯烷基-1-基苯基甲醇为例，来制备反应过程如表1所示，
将0.2mmol与催化剂(20mol％)混合后加入到2ml的溶剂中，在60℃的条件下反应，反应时间如表中所示，来检查最终产物的产率，结果如表1所示。
表1：反应条件及结果
催化剂(20mol％) 溶剂 T/℃ Time/h Yield/％<sup>b</sup>
1 CSA DCE 60 72 20
2 TfOH DCE 60 72 42
3 TFA DCE 60 72 58
4 2,4-二硝基苯甲酸 DCE 60 72 52
5 PA DCE 60 48 79
6 PA CHCl<sub>3</sub> 60 24 86
7 PA Toluene 60 24 96
8 PA DMF 60 48 61
9 PA H<sub>2</sub>O 60 24 65
10 PA THF 60 24 69
11 PA DCM 60 24 73
12 PA Dioxane 60 48 65
13 PA EtOH 60 24 67
14 PA CH<sub>3</sub>CN 60 48 52
表1中的17中，DCE先进行干燥，干燥的方法为：在每升DCE中加入CaH2 5g，于130℃下蒸馏；b：柱色谱分离产率。
实施例2
原料：3-甲氧基苯基-2-吡咯烷基-1-基苯基甲醇
反应条件：甲苯，60℃，PA(20％)
产物：化学式：C36H38N2O2
精确分子量：530.2933
分子量：530.7120
结构式：
产率:96％,dr 5:1.
1H NMR(500MHz,CDCl3)δ7.15(dt,J＝14.9,7.7Hz,4H),7.04–6.96(m,2H),6.79–6.62(m,9H),6.50(t,J＝7.5Hz,1H),4.80(d,J＝8.4Hz,1H),4.06(s,2H),3.94–3.81(m,3H),3.74(d,J＝12.0Hz,6H),3.65(dd,J＝10.2,5.4Hz,2H),3.53(dd,J＝16.1,7.9Hz,1H),3.42(td,J＝8.5,4.0Hz,1H),3.20(td,J＝8.7,2.7Hz,1H),2.89(dd,J＝15.8,8.4Hz,1H),2.73(td,J＝10.6,2.9Hz,1H),2.07–2.00(m,1H),1.98–1.74(m,6H)；13C NMR(125MHz,CDCl3)δ159.65,159.56,150.33,145.68,143.65,143.38,137.12,131.00,130.68,129.17,129.09,127.94,127.78,127.16,127.01,123.26,122.30,121.81,121.24,118.45,114.95,114.49,111.09,111.02,63.78,59.70,55.12,55.07,53.67,52.26,42.71,39.90,37.45,29.07,25.84,24.50；HRMS(ESI):calcd for C36H38N2O2[M+H]+:531.3012,found:531.3014.
实施例3
原料：4-甲氧基苯基-2-吡咯烷基-1-基苯基甲醇
反应条件：甲苯，60℃，PA(20％)
产物：化学式：C36H38N2O2
精确分子量：530.2933
分子量：530.7120
结构式：
产率:92％,dr 5:1.
1H NMR(500MHz,CDCl3)δ7.20–7.15(m,1H),7.12(d,J＝7.2Hz,1H),7.01(dd,J＝9.0,5.2Hz,4H),6.99(dd,J＝5.3,2.0Hz,2H),6.80–6.78(m,1H),6.78–6.73(m,4H),6.65(dd,J＝9.1,3.7Hz,1H),6.49(t,J＝7.5Hz,1H),4.79(d,J＝8.5Hz,1H),4.02(d,J＝5.2Hz,2H),3.88(dd,J＝10.6,7.7Hz,1H),3.80–3.76(m,1H),3.74(d,J＝6.0Hz,6H),3.72(d,J＝5.3Hz,1H),3.65–3.60(m,1H),3.52(dd,J＝16.3,7.8Hz,1H),3.42(td,J＝8.6,4.1Hz,1H),3.23–3.18(m,1H),2.89(dt,J＝8.7,6.9Hz,1H),2.72(qd,J＝8.3,3.2Hz,1H),2.06–1.98(m,1H),1.96–1.73(m,6H)；13C NMR(125MHz,CDCl3)δ157.73,157.71,150.23,145.76,137.81,133.98,133.85,130.94,130.62,130.23,129.65,127.72,127.69,127.07,123.27,122.27,118.44,113.72,113.67,63.75,59.84,55.27,55.26,53.75,52.25,42.82,39.06,36.55,29.07,25.86,24.57；HRMS(ESI):calcd for C36H38N2O2[M+H]+:531.3012,found:531.3011.
实施例4
原料：3,5-二甲基苯基-2-吡咯烷基-1-基苯基甲醇
反应条件：甲苯，60℃，PA(20％)
产物：化学式：C38H42N2
精确分子量：526.3348
分子量：526.7680
结构式：
产率:90％,dr 5:1.
1H NMR(500MHz,CDCl3)δ7.33–7.29(m,1H),7.24(d,J＝7.6Hz,1H),7.18–7.07(m,3H),6.93(d,J＝6.2Hz,2H),6.91(d,J＝6.0Hz,3H),6.88(s,2H),6.82–6.80(m,1H),6.64(t,J＝7.5Hz,1H),4.96(d,J＝8.4Hz,1H),4.19(dd,J＝26.1,9.8Hz,2H),4.04(d,J＝15.5Hz,1H),3.90(d,J＝15.5Hz,1H),3.80–3.75(m,1H),3.67(dd,J＝16.1,8.1Hz,1H),3.58(td,J＝8.6,4.3Hz,1H),3.34(td,J＝8.5,3.4Hz,1H),3.07–3.00(m,1H),2.88(ddd,J＝18.3,8.4,3.1Hz,1H),2.37(d,J＝0.6Hz,12H),2.35(s,1H),2.29(s,1H),2.21–2.13(m,1H),2.10–1.95(m,5H),1.95–1.88(m,1H)；13C NMR(125MHz,CDCl3)δ150.21,141.85,141.61,137.73,137.59,137.58,131.07,130.75,127.73,127.44,127.35,127.33,127.03,126.69,123.24,122.28,118.44,63.73,59.92,53.53,52.30,42.81,39.80,37.36,29.16,25.80,24.59,21.41,21.41,21.39,21.32；HRMS(ESI):calcd for C38H42N2[M+H]+:527.3426,found:527.3429.
以上所述，仅是本发明的较佳实施例而已，并非是对本发明作其它形式的限制，任何熟悉本专业的技术人员可能利用上述揭示的技术内容加以变更或改型为等同变化的等效实施例。但是凡是未脱离本发明技术方案内容，依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与改型，仍属于本发明技术方案的保护范围。

Claims (7)

1.一种八氢二吡咯并喹啉类化合物的制备方法，其特征在于，具体的方法是：
其中：
R1＝R2＝H、R3＝OCH3或
R1＝R3＝H、R2＝OCH3或
R1＝R3＝CH3、R2＝H；
苯基-2-吡咯烷基苄醇类化合物在酸性条件下脱水生成碳正离子，四氢吡咯邻位碳上的氢以氢负离子的形式迁移到碳正离子，原位上生成亚胺正离子，其中的一部分亚胺正离子通过质子转移转变为烯胺，烯胺分子与含有亚胺正离子的分子发生分子间的[4+2]环加成反应得到八氢二吡咯并喹啉化合物。
2.根据权利要求1所述的制备方法，其特征在于，所述的酸性条件由联萘酚磷酸提供。
3.根据权利要求2所述的制备方法，其特征在于，所述的苯基-2-吡咯烷基苄醇类化合物与联萘酚磷酸的摩尔比为10:2。
4.根据权利要求1-3任一项所述的制备方法，其特征在于，具体的方法是：制备方法是在溶剂甲苯中进行的，溶剂的用量为每mmol苯基-2-吡咯烷基苄醇类化合物添加10ml甲苯。
5.根据权利要求4所述的制备方法，其特征在于，制备方法是在60℃的条件下进行的。
6.根据权利要求1、2、3、5任一项所述的制备方法，其特征在于，具体步骤如下：苯基-2-吡咯烷基苄醇类化合物以PA(联萘酚磷酸)为催化剂，以甲苯为溶剂，在60℃的条件下，反应24小时，制得八氢二吡咯并喹啉化合物；其中苯基-2-吡咯烷基苄醇类化合物与联萘酚磷酸的摩尔比为10:2；溶剂甲苯的用量为：每mmol苯基-2-吡咯烷基苄醇类化合物添加10ml甲苯。
7.根据权利要求6所述的制备方法，其特征在于，所述苯基-2-吡咯烷基苄醇类化合物为：
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