CN107021968B - 多取代bodipy有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法 - Google Patents
多取代bodipy有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法 Download PDFInfo
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- 239000003054 catalyst Substances 0.000 title claims abstract description 23
- -1 indole quinoline class compound Chemical class 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000003647 oxidation Effects 0.000 title claims abstract description 12
- 238000007254 oxidation reaction Methods 0.000 title claims abstract description 12
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 11
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 11
- 238000006356 dehydrogenation reaction Methods 0.000 title claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 12
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
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- 239000001257 hydrogen Substances 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
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- 150000001875 compounds Chemical class 0.000 claims description 6
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- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical group [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 3
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- 125000003865 brosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)S(*)(=O)=O 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
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- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
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- GJBRNHKUVLOCEB-UHFFFAOYSA-N tert-butyl benzenecarboperoxoate Chemical compound CC(C)(C)OOC(=O)C1=CC=CC=C1 GJBRNHKUVLOCEB-UHFFFAOYSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- MFFMQGGZCLEMCI-UHFFFAOYSA-N 2,4-dimethyl-1h-pyrrole Chemical compound CC1=CNC(C)=C1 MFFMQGGZCLEMCI-UHFFFAOYSA-N 0.000 description 1
- NKZKFWYEXDBOTP-UHFFFAOYSA-N 2-(2,5-dibromophenyl)acetic acid Chemical compound OC(=O)CC1=CC(Br)=CC=C1Br NKZKFWYEXDBOTP-UHFFFAOYSA-N 0.000 description 1
- VFUGUWZYXGNQHR-UHFFFAOYSA-N 2h-1,2-benzoxazine;2,3-dihydro-1h-indole Chemical compound C1=CC=C2NCCC2=C1.C1=CC=C2C=CNOC2=C1 VFUGUWZYXGNQHR-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
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- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
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- 241000790917 Dioxys <bee> Species 0.000 description 1
- 241001411320 Eriogonum inflatum Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
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- 229910052786 argon Inorganic materials 0.000 description 1
- XJUFGFWUKUCNKA-UHFFFAOYSA-N butyl hydroxy carbonate Chemical compound CCCCOC(=O)OO XJUFGFWUKUCNKA-UHFFFAOYSA-N 0.000 description 1
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- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
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- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
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- OBMNJSNZOWALQB-NCQNOWPTSA-N grazoprevir Chemical compound O=C([C@@H]1C[C@@H]2CN1C(=O)[C@@H](NC(=O)O[C@@H]1C[C@H]1CCCCCC1=NC3=CC=C(C=C3N=C1O2)OC)C(C)(C)C)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C OBMNJSNZOWALQB-NCQNOWPTSA-N 0.000 description 1
- 229960002914 grazoprevir Drugs 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
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- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
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- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0272—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255
- B01J31/0275—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing elements other than those covered by B01J31/0201 - B01J31/0255 also containing elements or functional groups covered by B01J31/0201 - B01J31/0269
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/30—Catalysts, in general, characterised by their form or physical properties characterised by their physical properties
- B01J35/39—Photocatalytic properties
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/70—Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
- B01J2231/76—Dehydrogenation
- B01J2231/766—Dehydrogenation of -CH-CH- or -C=C- to -C=C- or -C-C- triple bond species
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Indole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了一种多取代BODIPY有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法,该方法利用空气或氧气替代过氧化物作为氧化剂,在反应中使用无金属光催化剂多取代BODIPY有机化合物,催化剂用量少,催化效率高,且反应条件温和,操作简单,环境友好,产物转化率高,选择性好,可用于合成治疗丙肝病毒的药物elbasvir的核心分子。
Description
技术领域
本发明涉及一种在可见光照射下,空气或氧气作为氧化剂,多取代BODIPY有机光催化剂高效催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法。
背景技术
自从20世纪60年代发现第一例抗病毒药物以来,人们持续寻找新的有效的抗病毒药物,治疗丙肝病毒的药物elbasvir在2016年1月被美国食品药品监督管理局批准上市,它是由默克公司开发,并完成了第三期临床试验,与NS3/4A蛋白酶抑制剂grazoprevir联合使用来治疗丙型肝炎病毒。
默克研究实验室首次对elbasvir进行了合成报道(ChemMedChem,2013,8:1930-1940.),其中核心的苯并恶嗪吲哚结构是通过外消旋法来合成,9步合成实现了3.9%的总产率。以间溴苯酚为起始原料,通过Fries重排,以70%的收率得到乙酰基取代的间溴苯酚2,再与对溴苯肼通过传统的Fisher吲哚合成方法来合成吲哚衍生物3,α,α-二溴甲苯与3双烷基化反应得到外消旋的核心骨架结构4,再经过Suzuki偶联和Radziszewski咪唑合成法得到5,经过手性拆分得到最终产物elbasvir。
该研究实验室对elbasvir进行了逆合成分析(Organic Letters,2014,16:2310-2313.),其结构可拆解成两部分合成子:核心苯并恶嗪吲哚结构和侧链5。该合成方法主要是手性苯并恶嗪吲哚片段的构建,避免了手性色谱柱在合成中的使用。构建核心合成子13主要从2,5-二溴苯乙酸作为起始原料,合成吲哚啉类化合物11并构建立体中心,此手性中心的构建可诱导并控制苯并恶嗪吲哚啉的手性中心的产生,避免了苯甲醛与3直接反应生成3位取代环化吲哚的产物。进一步利用高锰酸钾氧化可以83%的收率得到核心合成子13。
Elbasvir核心结构的合成反应中由吲哚啉类衍生物氧化脱氢形成苯并恶嗪吲哚结构需要用到1.6当量的高锰酸钾,副产物为大量不易溶解且有害的二氧化锰(TheJournal of Organic Chemistry,2014,79:8533-8540.)。针对这一反应过程,科研工作者发展了不同类型的氧化脱氢体系,提高产品产率的同时,最大限度地减少环境污染。
2016年,Knowles报道了可见光条件下elbasvir核心结构吲哚啉衍生物氧化脱氢反应(Chemical Science,2016,7:2066-2073.),多组平行反应实验确定了[Ir(dF-CF3-ppy)2(dtbpy)](PF6)为光催化剂,过氧化苯甲酸叔丁酯(tBPB)为氧化剂,反应产物产率高且无光学纯度的损失。
同年,默克研究实验室报道了利用铜催化剂([Cu(MeCN)4]BF4)氧化脱氢吲哚啉到吲哚的反应(The Journal of Organic Chemistry,2016,81:10009-10015.),氧化剂为叔丁基过氧化碳酸-2-乙基己酯(TBPC),对elbasvir核心结构吲哚啉衍生物进行氧化脱氢,其产率为92%和99.9%ee值。此方法可进行克级反应并应用于药物分子的合成步骤中。
发明内容
本发明所要解决的技术问题在于提供一种在可见光照射下,采用多取代BODIPY有机光催化剂高效催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法。
解决上述技术问题所采用的技术方案是:在空气或氧气气氛下,将式I所示的吲哚啉类化合物、多取代BODIPY有机光催化剂、助催化剂溶于有机溶剂中,在可见光照射下室温搅拌反应,分离纯化,得到式II所示吲哚类化合物;
式I和II中,X1、X2各自独立的代表氢、氟、氯、溴、碘、三氟甲磺基、对甲苯磺基、甲基磺酰基、对溴苯磺酰基中的任意一种,R1、R2、R3各自独立的代表氢、硝基、卤素、类卤素、三氟甲基、C1~C10烷基、C1~C10烷氧基、羟基、羧基、醛基、苯基、C1~C4烷基取代苯基、C1~C4烷氧基取代苯基、卤代苯基、萘基中的任意一种。
上述的多取代BODIPY有机光催化剂的结构式如下所示:
式中R4代表F、Cl、苯基、C1~C4烷基取代苯基、C1~C4烷氧基取代苯基、卤代苯基、萘基中的任意一种,R5、R6、R7各自独立的代表氢、C1~C6烷基、C1~C6烷氧基、苯基、C1~C4烷基取代苯基、C1~C4烷氧基取代苯基、卤代苯基、萘基中的任意一种,X代表H、F、Cl、Br、I中的任意一种;优选R4代表F、苯基、C1~C4烷基取代苯基、C1~C4烷氧基取代苯基、卤代苯基中的任意一种,R5、R6、R7各自独立的代表氢、C1~C6烷基、C1~C6烷氧基中的任意一种,X代表Br或I。
上述的助催化剂为四正丁基碘化铵、NaI、KI、I2中的任意一种,优选四正丁基碘化铵。
上述多取代BODIPY有机光催化剂的加入量优选为吲哚啉类化合物摩尔量的0.05%~0.2%,助催化剂的加入量优选为吲哚啉类化合物摩尔量的1%~3%。
上述制备方法中,优选室温搅拌反应的时间为20~72小时。
上述的有机溶剂为N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、四氢呋喃、1,4-二氧六环、乙酸乙酯、乙腈中的任意一种。
本发明利用空气或氧气替代过氧化物作为氧化剂,在反应中使用无金属光催化剂,催化剂用量少,催化效率高,且反应条件温和,操作简单,环境友好,产物转化率高,选择性好。
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并不仅限于这些实施例。
实施例1
合成结构式如下的(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪
将多取代BODIPY有机光催化剂(0.035mg,0.00005mmol)、四正丁基碘化铵(0.37mg,0.001mmol)、(6S,12aR)-6H-3,10-二溴-12,12a-二氢-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪(23mg,0.05mmol)、N,N-二甲基甲酰胺(2mL)加入到光平行反应管中,插入氧气球鼓泡1分钟,旋紧瓶塞,打开5W蓝光LED灯,室温条件下搅拌20小时,待反应结束,向混合物中加入20mL饱和食盐水,然后用20mL乙酸乙酯分三次萃取,收集有机相,用无水Na2SO4干燥,抽滤,用旋转蒸发仪除去溶剂,柱层析分离得到白色固体(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪22.5mg,其产率为98%,ee值为98.9%。
所得产物的波谱数据为:1H NMR(400MHz,CDCl3)δ7.79(d,J=1.6Hz,1H),7.52(d,J=8.8Hz,1H),7.38-7.27(m,3H),7.22-7.15(m,3H),7.13-7.05(m,3H),6.85(s,1H),6.70(d,J=8.8Hz,1H);13C NMR(101MHz,CDCl3)δ150.07,136.26,134.02,132.19,130.80,130.02,129.03,126.92,126.46,125.63,125.15,123.47,122.47,121.42,117.06,114.22,111.24,96.88,84.60。
本实施例中所用的多取代BODIPY有机光催化剂为结构式如下的BODIPY-4:
其根据下述方法制备得到:
步骤1、在500mL烧瓶中加入2,4-二甲基吡咯(1163mg,12.5mmol),再加入新蒸二氯甲烷(250mL),搅拌下滴入苯甲醛(530mg,5mmol),再缓慢滴加三氟乙酸(50μL,0.67mmol),室温反应3小时后,冰浴下加入2,3-二氯-5,6-二氰基-1,4-苯醌(1135mg,5mmol),10分钟后升至室温,搅拌1小时后,加入三乙胺(10mL,72mmol),10分钟后,加入三氟化硼乙醚(10mL,81mmol),继续室温反应2小时,反应混合液经减压蒸除溶剂、二氯甲烷与饱和食盐水萃取,取有机层经无水硫酸钠干燥,粗产物通过硅胶柱层析分离,得红棕色固体中间体1(486mg),产率为30%。
步骤2、取100mL烧瓶于100℃干燥箱中烘干2小时,对烧瓶抽真空状态下使其冷却至室温,加入中间体1(318mg,1mmol),并在氩气条件下加入现蒸四氢呋喃(40mL),搅拌条件下逐滴加入苯基锂(2.0mL,4mmol),室温条件下搅拌5分钟后,用饱和食盐水淬灭反应,用乙酸乙酯萃取三次(50mL×3),合并有机相并用无水硫酸钠干燥,旋转蒸发除去溶剂,粗产物通过硅胶柱层析分离,得到红棕色固体中间体2(110mg),产率为25%。
步骤3、在50mL烧瓶中加入中间体2(100mg,0.23mmol)和新蒸二氯甲烷(12mL),搅拌下加入N-碘代丁二酰亚胺(207mg,0.92mmol),室温反应12小时后,反应混合液经减压蒸除溶剂,粗产物通过硅胶柱层析分离,得到红棕色固体BODIPY-4(110mg),产率为64%,其波谱数据为:1H NMR(400MHz,CDCl3)δ(ppm):7.55-7.50(m,3H),7.43-7.38(m,4H),7.34-7.30(m,2H),7.30-7.20(m,6H),1.93(s,6H),1.43(s,6H);13C NMR(101MHz,CDCl3)δ(ppm):155.33,142.87,141.88,135.96,133.83,131.14,129.30,129.28,128.40,127.57,126.23,87.12,18.46,17.64;HRMS(m/z,ESI)理论值C31H27BI2N2Na+[M+Na]+:715.0254,实测值715.0257。
实施例2
本实施例中,将实施例1中的BODIPY-4用结构式如下的BODIPY-1替换,其它步骤与实施例1相同,得到(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪,其产率为50%。
实施例3
本实施例中,将实施例1中的BODIPY-4用结构式如下的BODIPY-2替换,其它步骤与实施例1相同,得到(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪,其产率为77%。
实施例4
本实施例中,将实施例1中的BODIPY-4用结构式如下的BODIPY-3替换,其它步骤与实施例1相同,得到(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪,其产率为76%。
实施例5
本实施例中,将实施例1中的BODIPY-4用结构式如下的BODIPY-5(其合成方法参考BODIPY-4)替换,其它步骤与实施例1相同,得到(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪,其产率为73%。
实施例6
本实施例中,将实施例1中的BODIPY-4用结构式如下的BODIPY-6(其合成方法参考BODIPY-4)替换,其它步骤与实施例1相同,得到(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪,其产率为83%。
实施例7
本实施例中,将实施例1中的BODIPY-4用结构式如下的BODIPY-7(其合成方法参考BODIPY-4)替换,其它步骤与实施例1相同,得到(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪,其产率为74%。
实施例8
本实施例中,将实施例1中的BODIPY-4用结构式如下的BODIPY-8(其合成方法参考BODIPY-4)替换,其它步骤与实施例1相同,得到(6S)-6H-3,10-二溴-6-苯基-吲哚并[1,2-c][1,3]苯并恶嗪,其产率为84%。
Claims (6)
1.一种多取代BODIPY有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法,其特征在于:在空气或氧气气氛下,将式I所示的吲哚啉类化合物、多取代BODIPY有机光催化剂、助催化剂溶于有机溶剂中,在可见光照射下室温搅拌反应,分离纯化,得到式II所示吲哚类化合物;
式I和II中,X1、X2各自独立的代表氢、氟、氯、溴、碘、三氟甲磺基、对甲苯磺基、甲基磺酰基、对溴苯磺酰基中的任意一种,R1、R2、R3各自独立的代表氢、硝基、卤素、类卤素、三氟甲基、C1~C10烷基、C1~C10烷氧基、羟基、羧基、醛基、苯基、C1~C4烷基取代苯基、C1~C4烷氧基取代苯基、卤代苯基、萘基中的任意一种;
上述的多取代BODIPY有机光催化剂的结构式如下所示:
式中R4代表F、Cl、苯基、C1~C4烷基取代苯基、C1~C4烷氧基取代苯基、卤代苯基、萘基中的任意一种,R5、R6、R7各自独立的代表氢、C1~C6烷基、C1~C6烷氧基、苯基、C1~C4烷基取代苯基、C1~C4烷氧基取代苯基、卤代苯基、萘基中的任意一种,X代表H、F、Cl、Br、I中的任意一种;
上述的助催化剂为四正丁基碘化铵。
2.根据权利要求1所述的多取代BODIPY有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法,其特征在于:所述的R4代表F、苯基、C1~C4烷基取代苯基、C1~C4烷氧基取代苯基、卤代苯基中的任意一种,R5、R6、R7各自独立的代表氢、C1~C6烷基、C1~C6烷氧基中的任意一种,X代表Br或I。
3.根据权利要求1或2所述的多取代BODIPY有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法,其特征在于:所述多取代BODIPY有机光催化剂的加入量为吲哚啉类化合物摩尔量的0.05%~0.2%。
4.根据权利要求1所述的多取代BODIPY有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法,其特征在于:所述助催化剂的加入量为吲哚啉类化合物摩尔量的1%~3%。
5.根据权利要求1所述的多取代BODIPY有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法,其特征在于:所述的室温搅拌反应的时间为20~72小时。
6.根据权利要求1所述的多取代BODIPY有机光催化剂催化吲哚啉类化合物氧化脱氢合成吲哚类化合物的方法,其特征在于:所述的有机溶剂为N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、四氢呋喃、1,4-二氧六环、乙酸乙酯、乙腈中的任意一种。
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