CN108299296B - 一种菲啶类杂环化合物的制备方法 - Google Patents
一种菲啶类杂环化合物的制备方法 Download PDFInfo
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- CN108299296B CN108299296B CN201710872338.XA CN201710872338A CN108299296B CN 108299296 B CN108299296 B CN 108299296B CN 201710872338 A CN201710872338 A CN 201710872338A CN 108299296 B CN108299296 B CN 108299296B
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- isonitrile
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- phthalimide
- acyloxy
- phenanthridine
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- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthrridine Natural products C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- -1 phenanthridine heterocyclic compound Chemical class 0.000 title abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 54
- 150000002527 isonitriles Chemical class 0.000 claims abstract description 33
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 32
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims abstract description 32
- 230000009467 reduction Effects 0.000 claims abstract description 11
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- 238000000034 method Methods 0.000 claims abstract description 10
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- 238000010791 quenching Methods 0.000 claims abstract description 8
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- 239000003513 alkali Substances 0.000 claims abstract description 7
- 230000009471 action Effects 0.000 claims abstract description 5
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 44
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 44
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了一种菲啶类杂环化合物的制备方法。以异腈和N‑(酰氧基)邻苯二甲酰亚胺为原料,在有机小分子催化剂的作用下,加入还原淬灭剂和碱,在白光照射下反应20‑24小时制得菲啶类杂环化合物。本发明制备方法为可见光诱导的光化学反应,摆脱了传统紫外光化学反应对设备的苛刻要求,其采用便宜的家用荧光灯、LED灯和“取之不竭”的清洁能源(太阳光)就可以有效实现。此外,可见光诱导的光化学反应通常反应条件温和、易于控制、高效且产物收率高,因此近年来引起了合成化学家们的广泛关注,并发展成为当前研究的重点和热点。
Description
技术领域
本发明属于化学合成领域,涉及一种菲啶类杂环化合物的制备方法。
背景技术
含氮杂环骨架结构(例如,菲啶,吲哚,喹啉和异喹啉等)广泛存在于天然产物、生物活 性分子、材料、农药和医药分子中。其中,菲啶类化合物在有机化学和药物化学领域是一类重 要的化合物,它们具有很多生物和药物活性,例如抗肿瘤、抗白血病、抗病毒和抗真菌等活性。 NK109是一种含有菲啶类结构的生物碱,它在医学上具有显著的抗肿瘤活性(Bioorg.Med. Chem.Lett.2000,10,2321),石蒜碱内铵盐(lycobetaine)可以用于治疗消化道癌、肝癌、卵巢 癌、肺癌、头颈部癌、恶性淋巴瘤等,特备是对胃癌和卵巢癌疗效不错。类似的还有 trisphaeridine、fagaronine、5-HT receptor等。
由于菲啶衍生物的重要性,近年来有关这类化合物的合成及活性研究引起了有机化学家和 药物化学家的进一步关注。尽管一些合成方法可以用于菲啶类化合物的合成,但有关6位烷基 取代的菲啶衍生物的制备方法却不多,且这些方法都使用了非常昂贵且有毒的过渡金属铱催化 剂,有的方法底物范围非常窄,官能团容忍度不好,仅限于某些含溴的烷基化试剂,而溴代物 往往对环境不友好,不符合环保绿色的要求,有些方法还需要使用价格较贵且具有爆炸危险的 高价碘试剂(Angew.Chem.Int.Ed.2013,52,13289;Angew.Chem.Int.Ed.2014,53,14451)。 因此,从新的反应机制入手,设计并实现廉价、绿色环保、操作安全简单、高效、避免采用价 格昂贵且有毒的过渡金属催化剂、底物范围广且官能团容忍度高的新合成方法,并以此制备一 系列结构多样的菲啶类衍生物显得非常重要。
发明内容
本发明的目的是克服了现有合成方法中普遍存在的难点和缺点,设计一种温和环保的方法 高效合成了菲啶类化合物。
本发明所述的菲啶类杂环化合物,结构如下所示:
其中,R1=3-甲基,2,4-二甲基,2-甲基,3-三氟甲基,2-氯,3-氟,2,4-二氟;R2=8-三氟 甲基,8-甲氧基;R=甲基,乙基,异丙基,叔丁基,十五碳烷基,环己基,含氮或者含氧杂 环的烷基,含氮烷基,含甲氧羰基的烷基,含羰基的烷基,含双键的烷基(具体如下所示)。
本发明所述化合物往往表现出抗肿瘤,抗白血病,抗病毒和抗真菌等生物活性,广泛应用 于医药化学和化工领域。
本发明所述的菲啶类衍生物优选以下任意一种化合物:
本发明提供了所述菲啶衍生物的合成方法,以异腈和N-(酰氧基)邻苯二甲酰亚胺为原 料,在有机小分子催化剂的作用下,加入还原淬灭剂和碱,在白光照射下反应20-24小时;所 述的有机小分子催化剂选自曙红Y、罗丹明B、曙红B、孟加拉玫瑰红、荧光素、亚甲基蓝、 曙红Y二钠盐、核黄素中的任意一种,反应路线如下:
其中,上述材料的投料量摩尔比优选异腈:N-(酰氧基)邻苯二甲酰亚胺:碱:还原淬灭 剂的摩尔比为1:1.5-2.5:1-1.5:1.5-2.5,进一步优选1:2:1.2:2;所述有机小分子催化剂的用 量优选原料异腈的5mol%。
所述还原淬灭剂优选自N,N-二异丙基乙胺、三乙胺、N,N-二甲基苯胺。
所述碱优选自碳酸钾、碳酸氢钠、磷酸氢二钾、碳酸铯。
所述溶剂优选自N,N-二甲基甲酰胺、四氢呋喃、乙腈、二氯甲烷、二甲亚砜、1,2-二氯乙 烷、1,4-二氧六环。
所述有机小分子催化剂优选曙红Y。
本发明使用的异腈原料1(1a-1i)优选如下所示的任意一种化合物:
本发明使用的原料N-(酰氧基)邻苯二甲酰亚胺2(2a-2l)优选如下所示的任意一种化合 物:
本发明制备的菲啶类衍生物(3aa-3id)如下所示:
本发明所涉及的反应机理如图1所示:有机小分子光催化剂曙红Y(此处以曙红Y为例) 在白光照射下形成激发态,激发态经由单电子转移从还原淬灭剂N,N-二异丙基乙基胺得到一个 电子,形成曙红Y自由基负离子中间体,此中间体通过单电子转移将一个电子转移给N-(酰 氧基)邻苯二甲酰亚胺2,从而产生另一自由基负离子I,这一自由基负离子经由包括脱羧等 步骤得到相应的烷基自由基IV,接下来与异腈发生加成反应产生碳中心自由基V,此自由基发 生分子内关环形成中间体VI,然后中间体VI失去一个电子产生碳正离子中间体VII,最后在碱 的作用下失去一个质子得到菲啶类衍生物3。
本发明首次以有机小分子作为光催化剂,采用N-(酰氧基)邻苯二甲酰亚胺还原脱羧的 策略,实现了高效合成6-烷基取代的菲啶类衍生物的新制备方法。
本发明有益的效果是:
本发明制备方法为可见光诱导的光化学反应,摆脱了传统紫外光化学反应对设备的苛刻要 求,其采用便宜的家用荧光灯、LED灯和“取之不竭”的清洁能源(太阳光)就可以有效实现。 此外,可见光诱导的光化学反应通常反应条件温和、易于控制、高效且产物收率高,因此近年 来引起了合成化学家们的广泛关注,并发展成为当前研究的重点和热点。
本发明克服了现有合成方法中普遍存在的难点和缺点,设计一种温和环保的方法高效合成 了菲啶类化合物。即用异腈和N-(酰氧基)邻苯二甲酰亚胺作为原料,在有机小分子光催化 剂的作用下发生反应,从而高效一步合成菲啶类杂环化合物。本发明所涉及的制备方法优势明 显,包括条件温和,操作安全简单,后处理方便,产率高,以廉价环保的有机小分子为光催化 剂,避免采用价格昂贵且有毒的过渡金属,原料便宜易得,底物适用范围广,官能团容忍性好 (例如三氟甲基、卤素、酯基、酮羰基、杂环、氨基、碳碳双键等),因此具有重要的商业价 值和工业应用前景。
附图说明
图1本发明所涉及的反应机理
具体实施方式
下面结合具体实施例对本发明作进一步叙述
实施例1:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2a(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压旋蒸除去溶剂,得到粗产物,粗产物经层析硅胶柱(乙 酸乙酯:石油醚=1:40)纯化得到48.1mg黄色固体产物3aa,收率为83%。
数据表征:1H NMR(400MHz,CDCl3)δ8.61(d,J=8.4Hz,1H),8.53(d,J=8.0Hz,1H),8.21(d, J=8.0Hz,1H),8.10(d,J=8.0Hz,1H),7.83(t,J=7.6Hz,1H),7.70(q,J=8.1Hz,2H),7.61(t,J =7.5Hz,1H),3.04(s,3H);13C NMR(100MHz,CDCl3)δ158.8,143.6,132.5,130.4,129.3,128.6, 127.3,126.5,126.3,125.9,123.7,122.3,121.9,23.4.
实施例2:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2b(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压旋蒸除去溶剂,得到粗产物,粗产物经层析硅胶柱(乙 酸乙酯:石油醚=1:40)纯化得到53.5mg白色固体产物3ab,收率为86%。
数据表征:1H NMR(400MHz,CDCl3)δ8.62(d,J=8.3Hz,1H),8.52(d,J=8.2Hz,1H),8.25(d, J=8.2Hz,1H),8.14(d,J=8.1Hz,1H),7.81(t,J=7.6Hz,1H),7.69(dt,J=8.0,7.2Hz,2H),7.61 (t,J=7.5Hz,1H),3.41(q,J=7.6Hz,2H),1.51(t,J=7.6Hz,3H);13C NMR(100MHz,CDCl3)δ 163.2,143.7,132.9,130.2,129.5,128.5,127.2,126.22,126.17,124.9,123.6,122.4,121.9,29.3, 13.6.
实施例3:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2c(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压旋蒸除去溶剂,得到粗产物,粗产物经层析硅胶柱(乙 酸乙酯:石油醚=1:40)纯化得到98.2mg白色固体产物3ac,收率为86%。
数据表征:1H NMR(400MHz,CDCl3)δ8.61(d,J=8.0Hz,1H),8.51(d,J=8.0Hz,1H),8.23(d, J=8.0Hz,1H),8.14(d,J=8.0Hz,1H),7.80(t,J=7.6Hz,1H),7.69(dt,J=15.2,7.4Hz,2H), 7.60(t,J=7.5Hz,1H),3.44–3.30(m,2H),1.92(dt,J=15.7,7.9Hz,2H),1.59–1.47(m,2H), 1.26(s,22H),0.89(t,J=6.7Hz,3H);13C NMR(100MHz,CDCl3)δ162.4,143.7,132.9,130.2, 129.5,128.5,127.1,126.3,126.2,125.1,123.6,122.4,121.8,36.5,31.9,30.0,29.7,29.64,29.63, 29.58,29.5,29.3,22.7,14.1.
实施例4:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射4小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有机 层,用无水硫酸钠干燥,水泵上减压旋蒸除去溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸 乙酯:石油醚=1:40)纯化得到61.6mg黄色油产物3ad,收率为93%。
数据表征:1H NMR(400MHz,CDCl3)δ8.66(d,J=8.4Hz,1H),8.54(d,J=8.0Hz,1H),8.33(d, J=8.4Hz,1H),8.17(d,J=8.0Hz,1H),7.82(t,J=7.6Hz,1H),7.71(dt,J=9.9,7.6Hz,2H),7.62 (t,J=7.6Hz,1H),4.00(hept,J=6.8Hz,1H),1.54(d,J=6.8Hz,6H);13CNMR(100MHz, CDCl3)δ165.8,143.7,132.9,129.87,129.86,128.3,127.0,126.1,125.6,124.7,123.4,122.5,121.8, 31.4,21.9.
实施例5:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2e(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压旋蒸除去溶剂,得到粗产物,粗产物经层析硅胶柱(乙 酸乙酯:石油醚=1:40)纯化得到65.8mg黄色固体产物3ae,收率为84%。
数据表征:1H NMR(400MHz,CDCl3)δ8.65(d,J=8.4Hz,1H),8.56–8.51(m,1H),8.32(d,J= 8.4Hz,1H),8.16(dd,J=8.1,0.8Hz,1H),7.84–7.77(m,1H),7.74–7.65(m,2H),7.64–7.57(m, 1H),3.63(tt,J=11.2,3.1Hz,1H),2.10(d,J=11.5Hz,2H),2.03–1.93(m,4H),1.86(d,J=12.5 Hz,1H),1.66–1.53(m,2H),1.50–1.38(m,1H);13C NMR(100MHz,CDCl3)δ165.2,143.8, 132.9,129.9,128.3,127.0,126.1,125.6,124.7,123.3,122.5,121.8,41.9,32.3,26.8,26.3.
实施例6:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2f(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸乙 酯:石油醚=1:80~1:60)纯化得到52.9mg白色固体产物3af,收率为75%。
数据表征:1H NMR(400MHz,CDCl3)δ8.69(d,J=8.0Hz,1H),8.65(d,J=8.4Hz,1H),8.53(d, J=8.0Hz,1H),8.15(d,J=8.0Hz,1H),7.79(t,J=7.6Hz,1H),7.71(dd,J=11.1,4.0Hz,1H), 7.68–7.59(m,2H),1.76(s,9H);13C NMR(100MHz,CDCl3)δ166.6,142.9,134.0,130.2,129.2, 128.3,128.2,126.4,125.9,124.3,123.4,122.9,121.6,40.2,31.2.
实施例7:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2g(0.6 0mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸乙 酯:石油醚=1:20)纯化得到50.1mg白色固体产物3ag,收率为67%。
数据表征:1H NMR(400MHz,CDCl3)δ8.65(d,J=8.3Hz,1H),8.55(d,J=8.1Hz,1H),8.45(d, J=8.3Hz,1H),8.20(d,J=8.1Hz,1H),7.83(t,J=7.6Hz,1H),7.71(q,J=7.9Hz,2H),7.65(t,J =7.6Hz,1H),5.78(t,J=6.9Hz,1H),4.22(dd,J=14.6,7.3Hz,1H),4.08(dd,J=14.5,7.4Hz, 1H),2.78-2.68(m,1H),2.48-2.37(m,1H),2.27–2.07(m,2H);13C NMR(100MHz,CDCl3)δ 159.2,143.2,133.2,130.4,130.2,128.4,127.1,126.8,126.4,124.7,124.0,122.3,121.8,79.5,68.9, 30.0,25.9,21.0.
实施例8:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2h(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(石油醚) 纯化得到88.1mg白色固体产物3ah,收率为81%。
数据表征:1H NMR(400MHz,CDCl3)δ8.65(d,J=8.4Hz,1H),8.52(d,J=8.0Hz,1H),8.27(d,J= 8.4Hz,1H),8.12(d,J=8.0Hz,1H),7.82(t,J=7.6Hz,1H),7.73-7.66(m,2H),7.61(t,J=7.4Hz,1H), 4.36(s,2H),3.74(ddd,J=14.7,11.2,3.6Hz,1H),3.02(s,2H),2.06(dd,J=29.2,25.3Hz,4H),1.51(s, 9H);13C NMR(100MHz,CDCl3)δ163.1,154.8,143.7,133.1,130.1,130.0,128.5,127.2,126.4,125.1, 124.5,123.4,122.7,121.8,79.4,44.1,40.0,31.2,28.5;
实施例9:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2i(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(石油醚) 纯化得到65.7mg黄色油产物3ai,收率为71%。
数据表征:1H NMR(400MHz,CDCl3)δ8.62(d,J=8.4Hz,1H),8.53(d,J=8.0Hz,1H),8.14(dd,J= 8.0,4.0Hz,2H),7.85(t,J=7.7Hz,1H),7.71(dd,J=16.4,8.4Hz,2H),7.65(t,J=7.6Hz,1H),6.64(s, 1H),5.02(d,J=3.6Hz,2H),1.55(s,9H);13C NMR(100MHz,CDCl3)δ156.1,154.7,142.8,132.7, 130.8,129.6,128.7,127.7,126.9,124.6,124.0,123.9,122.5,122.0,79.4,43.6,28.5
实施例10:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2j(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(石油醚) 纯化得到81.0mg黄色固体产物3aj,收率为92%。
数据表征:1H NMR(400MHz,CDCl3)δ8.62(d,J=8.0Hz,1H),8.52(d,J=8.4Hz,1H),8.22(d,J= 8.0Hz,1H),8.11(dd,J=8.4,1.0Hz,1H),7.81(dd,J=8.2,7.1Hz,1H),7.73–7.65(m,2H),7.61(t,J =7.6Hz,1H),3.66(s,3H),3.43–3.33(m,2H),2.42(t,J=7.3Hz,2H),2.03–1.93(m,2H),1.93– 1.82(m,2H);13C NMR(100MHz,CDCl3)δ174.0,161.6,143.6,132.9,130.3,129.5,128.5,127.2, 126.3,126.1,125.1,123.6,122.4,121.9,51.5,35.7,33.9,28.7,25.1.
实施例11:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2k(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(石油醚) 纯化得到64.8mg黄色固体产物3ak,收率为82%。
数据表征:1H NMR(400MHz,CDCl3)δ8.57(d,J=8.2Hz,1H),8.49(d,J=7.4Hz,1H),8.31(d, J=8.0Hz,1H),8.10(dd,J=8.1,0.9Hz,1H),7.83–7.74(m,1H),7.68(qd,J=7.2,1.2Hz,2H), 7.62–7.52(m,1H),3.40–3.29(m,2H),2.63(t,J=7.0Hz,2H),2.21(dd,J=15.0,7.3Hz,2H), 2.15(d,J=8.1Hz,3H);13C NMR(100MHz,CDCl3)δ208.8,161.2,143.5,132.7,130.3,129.4, 128.5,127.3,126.3,126.2,125.1,123.6,122.3,121.8,43.0,35.1,30.0,22.9.
实施例12:
将异腈1a(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2l(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(石油醚) 纯化得到51.8mg黄色油产物3al,收率为74%。
数据表征:1H NMR(400MHz,CDCl3)δ8.62(d,J=8.4Hz,1H),8.52(d,J=7.6Hz,1H),8.23(d, J=8.4Hz,1H),8.14(dd,J=8.0,0.8Hz,1H),7.85–7.77(m,1H),7.70(ddd,J=15.9,7.7,1.1Hz, 2H),7.65–7.58(m,1H),6.06(ddt,J=16.8,10.2,6.5Hz,1H),5.22–5.13(m,1H),5.05(dd,J= 10.0,1.6Hz,1H),3.53–3.39(m,2H),2.72(dt,J=7.8,6.6Hz,2H);13CNMR(100MHz,CDCl3)δ 161.2,143.6,138.0,132.8,130.3,129.5,128.5,127.2,126.3,126.1,125.1,123.6,122.4,121.9, 115.0,35.4,33.1.
实施例13:
将异腈1b(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(石油醚) 纯化得到56.3mg黄色固体产物3bd,收率为80%。
数据表征:1H NMR(400MHz,CDCl3)δ8.61(d,J=8.4Hz,1H),8.42(d,J=8.4Hz,1H),8.30(d,J= 8.4Hz,1H),7.99(s,1H),7.79(t,J=7.6Hz,1H),7.65(t,J=7.6Hz,1H),7.44(d,J=8.4Hz,1H),4.00 (hept,J=6.8Hz,1H),2.60(s,3H),1.54(d,J=6.8Hz,6H);13C NMR(100MHz,CDCl3)δ165.8,143.8, 138.4,133.0,129.8,129.4,127.8,126.6,125.6,124.4,122.3,121.6,121.0,31.4,21.9,21.4.
实施例14:
将异腈1c(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(石油醚) 纯化得到61.1mg无色油产物3cd,收率为82%。
数据表征:1H NMR(400MHz,CDCl3)δ8.65(d,J=8.3Hz,1H),8.31(d,J=8.3Hz,1H),8.20(s,1H), 7.78(dd,J=8.0,7.2Hz,1H),7.77(dd,J=8.0,7.2Hz,1H),7.44(s,1H),4.00(hept,J=6.8Hz,1H), 2.90(s,3H),2.60(s,3H),1.56(d,J=6.8Hz,6H);13C NMR(100MHz,CDCl3)δ162.9,140.5,137.5, 135.2,133.0,130.8,129.3,126.6,125.4,124.4,122.9,122.7,119.2,31.6,22.2,21.9,18.0.
实施例15:
将异腈1d(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸乙 酯:石油醚=1:80)纯化得到62.3mg黄色固体产物3dd,收率为72%。
数据表征:1H NMR(400MHz,CDCl3)δ8.66(d,J=8.4Hz,1H),8.61(d,J=8.4Hz,1H),8.45(s,1H), 8.36(d,J=8.4Hz,1H),7.87(t,J=7.6Hz,1H),7.81–7.74(m,2H),4.00(hept,J=6.8Hz,1H),1.52(d, J=6.8Hz,6H);13C NMR(100MHz,CDCl3)δ167.5,143.1,132.2,130.5,130.2(q,J=33.0Hz,),128.3, 127.5(q,J=4.0Hz,),126.2,125.9,125.7,125.6,125.3,123.4(q,J=276.0Hz,),122.9,122.8,122.0 (q,J=3.0Hz,),31.8,21.9.
实施例16:
将异腈1e(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下反应24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸乙 酯:石油醚=1:80)纯化得到65.9mg黄色固体产物3ed,收率为86%。
数据表征:1H NMR(400MHz,CDCl3)δ8.51(d,J=8.4Hz,1H),8.45(s,1H),8.29(d,J=8.0Hz, 1H),8.06(d,J=8.8Hz,1H),7.80(t,J=7.6Hz,1H),7.70(dd,J=8.0,7.2Hz,1H),7.63(dd,J= 8.7,2.1Hz,1H),4.00(hept,J=6.8Hz,1H),1.51(d,J=6.8Hz,6H);13CNMR(100MHz,CDCl3) δ166.1,142.1,131.92,131.85,131.4,130.1,128.8,127.7,125.7,124.8,124.4,122.5,121.4,31.5, 21.9.
实施例17:
将异腈1f(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸乙 酯:石油醚=1:60)纯化得到58.8mg黄色固体产物3fd,收率为82%。
数据表征:1H NMR(400MHz,CDCl3)δ8.55(d,J=8.4Hz,1H),8.48(dd,J=8.4,6.0Hz,1H),8.31(d, J=8.4Hz,1H),7.84–7.77(m,2H),7.68(m,1H),7.35(td,J=8.8,2.7Hz,1H),4.00(hept,J=6.8Hz, 1H),1.51(d,J=6.8Hz,6H);13C NMR(100MHz,CDCl3)δ167.3,162.6(d,J=245.7Hz,),145.1(d,J= 11.8Hz,),132.7,130.3,126.9,125.8,124.2,123.6(d,J=9.0Hz,),122.3,120.0(d,J=2.0Hz,), 115.0(d,J=23.0Hz,),114.4(d,J=20.0Hz,),31.5,21.9.
实施例18:将异腈1g(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y (5mol%)、碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸乙酯:石油醚=1:60)纯化得到72.6mg白色固体产物3gd,收率为94%。
数据表征:1H NMR(400MHz,CDCl3)δ8.47(d,J=8.4Hz,1H),8.34(d,J=8.4Hz,1H),7.95–7.89 (m,1H),7.86–7.81(m,1H),7.78–7.72(m,1H),7.20(ddd,J=10.1,8.7,2.7Hz,1H),4.00(hept,J= 6.8Hz,1H),1.52(d,J=6.8Hz,6H);13C NMR(100MHz,CDCl3)δ165.4,160.7(dd,J=12.2Hz,245.0 Hz,),159.0(dd,J=13.3Hz,255.9Hz,),131.9(dd,J=3.3Hz,4.3Hz,),130.6(dd,J=2.2Hz,10.0Hz,), 130.4,128.3,125.9,125.9(dd,J=2.9Hz,10.3Hz,),125.2,123.0,103.8(dd,J=23.4Hz,27.8Hz,), 102.5(dd,J=4.5Hz,22.6Hz,),31.8,21.9.
实施例19:
将异腈1h(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸乙 酯:石油醚=1:60)纯化得到48.5mg黄色固体产物3hd,收率为56%。
数据表征:1H NMR(400MHz,CDCl3)δ8.73(d,J=8.8Hz,1H),8.58(s,1H),8.52(d,J=8.0Hz,1H), 8.22–8.14(m,1H),8.00(dd,J=8.6,1.3Hz,1H),7.82–7.73(m,1H),7.70–7.60(m,1H),4.07– 3.94(m,1H),1.54(d,J=6.8Hz,6H);13C NMR(100MHz,CDCl3)δ165.6,144.4,135.2,130.1,129.6, 128.8(q,J=32.42Hz,),126.7,125.7(q,J=3.1Hz,),124.2(q,J=270.7Hz,),124.0,123.6,123.1(q,J =4.1Hz,),122.4,122.1,31.5,21.9.
实施例20:
将异腈1i(0.30mmol)、N-(酰氧基)邻苯二甲酰亚胺2d(0.60mmol)、曙红Y(5mol%)、 碳酸氢钠(0.36mmol)、N,N-二异丙基乙胺(0.60mmol)溶于二甲亚砜(3.0mL)中,放置在18W 白灯下照射24小时。反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相三次,合并有 机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经层析硅胶柱(乙酸乙 酯:石油醚=1:60)纯化得到64.1mg白色固体产物3id,收率为85%。
数据表征:1H NMR(400MHz,CDCl3)δ8.54(d,J=9.0Hz,1H),8.48–8.40(m,1H),8.15(d,J= 8.1Hz,1H),7.66(ddd,J=6.9,6.0,1.8Hz,2H),7.58(ddd,J=8.2,7.1,1.4Hz,1H),7.44(dd,J= 9.0,2.6Hz,1H),3.99(s,3H),3.92(hept,J=13.5,6.8Hz,1H),1.55(d,J=6.8Hz,6H);13C NMR (100MHz,CDCl3)δ164.8,158.5,142.9,129.8,127.4,127.2,126.2,125.9,124.2,123.5,121.3, 119.9,106.3,55.4,31.6,21.8.
Claims (3)
1.一种菲啶类化合物3的制备方法,其特征在于以异腈1和N-(酰氧基)邻苯二甲酰亚胺2为原料,在有机小分子催化剂的作用下,加入还原淬灭剂和碱,在白光照射下反应20-24小时;所述有机小分子催化剂为曙红Y,所述还原淬灭剂选自N,N-二异丙基乙胺,所述碱选自碳酸钾、碳酸氢钠、磷酸氢二钾或碳酸铯,反应的溶剂选自N,N-二甲基甲酰胺、四氢呋喃、乙腈、二氯甲烷、二甲亚砜、1,2-二氯乙烷或1,4-二氧六环;其中异腈1:N-(酰氧基)邻苯二甲酰亚胺2:碱:还原淬灭剂的摩尔比为1:1.5-2.5:1-1.5:1.5-2.5,所述有机小分子催化剂曙红Y的用量为原料异腈1的5mol%,反应路线如下:
其中,所述的异腈1选自以下化合物:
所述的N-(酰氧基)邻苯二甲酰亚胺2选自以下化合物:
所述的菲啶类化合物3选自以下化合物:
2.根据权利要求1所述的菲啶类化合物3的制备方法,其特征在于,将异腈1、N-(酰氧基)邻苯二甲酰亚胺2、有机小分子光催化剂、碱、还原淬灭剂溶于溶剂中,放置在18W白灯下照射24小时;反应完毕后,将反应体系用水稀释,用乙酸乙酯萃取水相,合并有机层,用无水硫酸钠干燥,水泵上减压蒸除溶剂,得到粗产物,粗产物经纯化得到相应的纯产品菲啶类化合物3;所述的柱层析固定相为层析硅胶,流动相为乙酸乙酯:石油醚=1:40~1:10。
3.根据权利要求2所述的菲啶类化合物3的制备方法,其特征在于,异腈1:N-(酰氧基)邻苯二甲酰亚胺2:碱:还原淬灭剂的摩尔比为1:2:1.2:2。
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A cascade alkylarylation reaction of 2-isocyanobiphenyls with simple alkanes for 6-alkyl phenanthridines via dual C(sp3)–H/C(sp2)–H functionalizations;Zhi-Qiang Zhu et al.;《Org. Biomol. Chem.》;20140704;第12卷;第5840页Table2 * |
Asymmetric radical alkylation of N-sulfinimines under visible light photocatalytic conditions;Alberto F. Garrido-Castro et al.;《Chem. Commun.》;20170621;第53卷;第7765页Table1; 第7766页Scheme2 * |
Installing amino acids and peptides on N-heterocycles under visiblelight assistance;Yunhe Jin et al.;《Scientific reports》;20160202;第6卷;第20068-4页Figure2; 第20068-5页Figure4; 第20068-3页Table1 * |
Mani Ramanathan et al..Preparation of Substituted Phenanthridines from the Coupling of Aryldiazonium Salts with Nitriles: A Metal Free Approach.《J. Org. Chem.》.2015,第80卷第5331页Scheme3;第5330页Table2;第5329页第1段和第5331页Scheme3;第5329页摘要. * |
Ni-Catalyzed Reductive Addition of Alkyl Halides to Isocyanides;Bo Wang et al.;《Org. Biomol. Chem.》;20151022;第13卷;第11420页Table2 * |
Photodecarboxylation of unmodified carboxylic acids with use of aza aromatic compounds;Keiji Okada et al.;《Tetrahedron Letters》;19891231;第30卷(第48期);第6734页Table1 * |
Preparation of Substituted Phenanthridines from the Coupling of Aryldiazonium Salts with Nitriles: A Metal Free Approach;Mani Ramanathan et al.;《J. Org. Chem.》;20150429;第80卷;第5331页Scheme3; 第5330页Table2; 第5329页第1段和第5331页Scheme3; 第5329页摘要 * |
Synthese dans La chinie des phenanthridines. II. Preparation D'une nouvelle serie D'ω-(Phenanthridinyl-6) alcanoates de methyl ou D'Ethyle;C. Lion et al.;《Bull. Soc. Chim. Belg》;19891231;第98卷(第8期);第569页TableII * |
Transition Metal-Free Oxidative Radical Decarboxylation/Cyclization for the C-onstruction of 6‑Alkyl/Aryl Phenanthridines;Shichao Lu et al.;《J. Org. Chem.》;20150824;第80卷;第9338页Table2 * |
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