CN117384094A - 一种炔基四氢异喹啉类衍生物的制备方法 - Google Patents
一种炔基四氢异喹啉类衍生物的制备方法 Download PDFInfo
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- CN117384094A CN117384094A CN202311317043.8A CN202311317043A CN117384094A CN 117384094 A CN117384094 A CN 117384094A CN 202311317043 A CN202311317043 A CN 202311317043A CN 117384094 A CN117384094 A CN 117384094A
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- China
- Prior art keywords
- tetrahydroisoquinoline
- reaction
- porphyrin
- insoluble
- alkynyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- -1 alkynyl tetrahydroisoquinoline derivative Chemical class 0.000 title claims abstract description 56
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 238000006243 chemical reaction Methods 0.000 claims abstract description 65
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims abstract description 41
- 150000004032 porphyrins Chemical class 0.000 claims abstract description 32
- YDIYEOMDOWUDTJ-UHFFFAOYSA-N 4-(dimethylamino)benzoic acid Chemical compound CN(C)C1=CC=C(C(O)=O)C=C1 YDIYEOMDOWUDTJ-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000000654 additive Substances 0.000 claims abstract description 14
- 230000000996 additive effect Effects 0.000 claims abstract description 14
- 150000001345 alkine derivatives Chemical class 0.000 claims abstract description 10
- 230000009471 action Effects 0.000 claims abstract description 8
- 238000005859 coupling reaction Methods 0.000 claims abstract description 8
- 238000006356 dehydrogenation reaction Methods 0.000 claims abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 81
- 238000004440 column chromatography Methods 0.000 claims description 26
- 238000001035 drying Methods 0.000 claims description 16
- 239000002244 precipitate Substances 0.000 claims description 16
- KBIAVTUACPKPFJ-UHFFFAOYSA-N 1-ethynyl-4-methoxybenzene Chemical group COC1=CC=C(C#C)C=C1 KBIAVTUACPKPFJ-UHFFFAOYSA-N 0.000 claims description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- ANWXWWSYNQLVED-UHFFFAOYSA-N 5,10,15,20-tetrakis(4-bromophenyl)-21,23-dihydroporphyrin Chemical compound Brc1ccc(cc1)-c1c2ccc(n2)c(-c2ccc(Br)cc2)c2ccc([nH]2)c(-c2ccc(Br)cc2)c2ccc(n2)c(-c2ccc(Br)cc2)c2ccc1[nH]2 ANWXWWSYNQLVED-UHFFFAOYSA-N 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 239000011701 zinc Substances 0.000 claims description 8
- 238000004064 recycling Methods 0.000 claims description 7
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- DXXWCWWIOSXGQZ-UHFFFAOYSA-N 6,7-dimethoxy-2-phenyl-3,4-dihydro-1h-isoquinoline Chemical group C1C=2C=C(OC)C(OC)=CC=2CCN1C1=CC=CC=C1 DXXWCWWIOSXGQZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
- 229940057499 anhydrous zinc acetate Drugs 0.000 claims description 4
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 4
- 229910021641 deionized water Inorganic materials 0.000 claims description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 229910052725 zinc Inorganic materials 0.000 claims description 4
- DJWUNCQRNNEAKC-UHFFFAOYSA-L zinc acetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O DJWUNCQRNNEAKC-UHFFFAOYSA-L 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 238000000703 high-speed centrifugation Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 238000002791 soaking Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 230000001699 photocatalysis Effects 0.000 abstract description 5
- 238000013032 photocatalytic reaction Methods 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 4
- 239000007864 aqueous solution Substances 0.000 abstract description 3
- 238000010276 construction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 description 35
- 238000012512 characterization method Methods 0.000 description 21
- 239000012043 crude product Substances 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- 239000011734 sodium Substances 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 238000005286 illumination Methods 0.000 description 20
- 239000007788 liquid Substances 0.000 description 18
- 238000001228 spectrum Methods 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- ONQBUHWENXKHHP-UHFFFAOYSA-N 2-phenyl-3,4-dihydro-1h-isoquinoline Chemical compound C1CC2=CC=CC=C2CN1C1=CC=CC=C1 ONQBUHWENXKHHP-UHFFFAOYSA-N 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000004896 high resolution mass spectrometry Methods 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 5
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 4
- PUAQLLVFLMYYJJ-UHFFFAOYSA-N 2-aminopropiophenone Chemical compound CC(N)C(=O)C1=CC=CC=C1 PUAQLLVFLMYYJJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- IZGDXVLRMHXOJV-SFHVURJKSA-N (3s)-4-[2-[2-(4-fluoro-3-methylphenyl)-4-methyl-6-propan-2-ylphenyl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=CC(C)=CC(C=2C=C(C)C(F)=CC=2)=C1CCP(O)(=O)C[C@@H](O)CC(O)=O IZGDXVLRMHXOJV-SFHVURJKSA-N 0.000 description 3
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- BOOYHBPHFVNWNH-OAHLLOKOSA-N 1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-5-[(4-fluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C[C@H](C1=CC=C(C=C1)Cl)NC2=NC3=C(C=NN3C(C)(C)C)C(=O)N2CC4=CC=C(C=C4)F BOOYHBPHFVNWNH-OAHLLOKOSA-N 0.000 description 3
- PSWDQTMAUUQILQ-UHFFFAOYSA-N 2-[(6-methoxy-4-methylquinazolin-2-yl)amino]-5,6-dimethyl-1h-pyrimidin-4-one Chemical compound N1=C(C)C2=CC(OC)=CC=C2N=C1NC1=NC(=O)C(C)=C(C)N1 PSWDQTMAUUQILQ-UHFFFAOYSA-N 0.000 description 3
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- 229940126650 Compound 3f Drugs 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 3
- 229940125796 compound 3d Drugs 0.000 description 3
- MUTCAPXLKRYEPR-ITWZMISCSA-N methyl (e,3r,5s)-7-[4-bromo-2,3-bis(4-fluorophenyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyhept-6-enoate Chemical compound COC(=O)C[C@H](O)C[C@H](O)\C=C\N1C(C(C)C)=C(Br)C(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 MUTCAPXLKRYEPR-ITWZMISCSA-N 0.000 description 3
- QMGHHBHPDDAGGO-IIWOMYBWSA-N (2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide Chemical compound CN(CCCNC1=NC(NC2=CC=C(OCCCOCCCCOCCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCC3=CC=C(C=C3)C3=C(C)N=CS3)C(C)(C)C)C=C2)=NC=C1Br)C(=O)C1CCC1 QMGHHBHPDDAGGO-IIWOMYBWSA-N 0.000 description 2
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- AKNNEGZIBPJZJG-MSOLQXFVSA-N (-)-noscapine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-MSOLQXFVSA-N 0.000 description 1
- FPQLMVNLVDVRHA-UHFFFAOYSA-N 1-[2-(4-bromophenyl)ethynyl]-2-phenyl-3,4-dihydro-1h-isoquinoline Chemical compound C1=CC(Br)=CC=C1C#CC1C2=CC=CC=C2CCN1C1=CC=CC=C1 FPQLMVNLVDVRHA-UHFFFAOYSA-N 0.000 description 1
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Abstract
本发明涉及一种炔基四氢异喹啉衍生物的制备方法,包括如下步骤:在20W白光条件下,通过光敏剂和添加剂的作用,让四氢异喹啉与炔烃在水中于室温下发生交叉脱氢偶联反应,反应12h后,得到炔基四氢异喹啉类衍生物。本发明使用四氢异喹啉和炔烃类化合物为原料,使用5mol%不溶性聚卟啉为光敏剂,以4‑二甲氨基苯甲酸为添加剂,在20W白光的作用下,在水溶液中室温反应12个小时,最终以53%‑79%的收率得到了炔基四氢异喹啉类衍生物,反应条件温和,产物收率中等到良好,底物范围广泛;所使用的不溶性聚卟啉基光敏剂展现出优异的光催化活性,在水相中可诱导C(sp3)‑C(sp)键的构建,并且可以重复回收使用,为水相中光催化反应提供了一种绿色和可持续的途径。
Description
技术领域
本发明涉及一种炔基四氢异喹啉类衍生物的制备方法,属于有机合成技术领域。
背景技术
本申请要求了申请日为2022年11月08日,申请号为CN202211392739.2的中国专利申请的优先权,其全部内容通过引用结合在本申请中。
四氢异喹啉(THIQ)类生物碱在自然界广泛存在,并具有抗肿瘤、抗病毒、抗菌、抗凝和抗炎等多种生物活性(Curr.Opin.Chem.Biol.2010,14,347-361;Bioorg.Med.Chem.Lett.2006,16,5285-5289;Eur.J.Med.Chem.2008,43,1160-1170及Bioorg.Med.Chem.Lett.2006,16,5294-5297)。但是天然产物受到产量、内在活性和分离提纯等诸多因素的限制,难以满足人们的需求,需要寻求人工合成的方法来解决。2013年,Zimmermann等人在天然化合物诺斯卡品的四氢异喹啉结构骨架的α位引入炔基基团,发现经炔基化修饰后能提高化合物的抗肿瘤活性(ChemBioChem 2013,14,295-300)。因此,发展绿色、高效的合成方法制备炔基四氢异喹啉类衍生物,具有重要的研究意义。
目前,对于四氢异喹啉类化合物α位炔基化的研究,主要采用交叉脱氢偶联反应的策略。2004年,李朝军等人首次使用铜催化剂,在叔丁基过氧化氢的作用下,实现了四氢异喹啉α位炔基化反应(J.Am.Chem.Soc.2003,125,15312-15313)。此后,各种金属催化的氧化偶联方法被发展,但是大多数交叉脱氢偶联反应需要过渡金属催化剂和化学计量氧化剂(Acc.Chem.Res.2009,42,335-344;J.Am.Chem.Soc.2012,134,5317-5325;Monatsh.Chem.2017,148,91-104及Green Synth.Catal.2020,1,1-11)。近年来,一些过渡金属或有机染料作为光催化剂被应用于以氧气(空气)为氧化剂的交叉脱氢偶联反应(Green Chem.2007,9,1047-1050;Org.Biomol.Chem.2015,13,447-451;Angew.Chem.,Int.Ed.2020,59,15254-15259及ACS Catal.2022,12,126-134)。
然而,目前报道的交叉脱氢偶联反应大多是在有机溶剂中基于均相小分子光敏剂的光催化,缺乏对光敏剂的可重用性和可回收性。因此,需要发展可重用的水相容性非均相高分子量光敏剂,来实现炔基四氢异喹啉类衍生物的绿色合成。
发明内容
本申请要求了申请日为2022年11月08日,申请号为CN202211392739.2的中国专利申请的优先权,其全部内容通过引用结合在本申请中。
本发明的目的在于提供一种光敏剂可循环利用的炔基四氢异喹啉类衍生物的绿色制备方法。
为达到上述目的,本发明提供如下技术方案:
一种炔基四氢异喹啉衍生物的制备方法,包括如下步骤:
在20W白光条件下,通过光敏剂和添加剂的作用,让四氢异喹啉与炔烃在水中于室温下发生交叉脱氢偶联反应,反应12h后,得到炔基四氢异喹啉类衍生物,反应式如下:
其中,R1,R2和R3为氢、烷基或芳基;
所述四氢异喹啉与所述炔烃的摩尔比为1:2.7;
所述添加剂为4-二甲氨基苯甲酸,所述添加剂的用量为所述四氢异喹啉的1倍当量;
所述光敏剂P为不溶性聚卟啉,所述不溶性聚卟啉由摩尔比为1:1的吡咯和4-溴苯甲醛制得,所述不溶性聚卟啉的结构为:
所述不溶性聚卟啉的用量为所述四氢异喹啉的5mol%。
进一步地,所述不溶性聚卟啉的制备方法为:
S1、将所述摩尔比为1:1的吡咯和4-溴苯甲醛溶解在由体积比为3:1的丙酸和乙酸组成的混合溶剂中,在120℃下搅拌2h充分反应,冷却至室温后,离心收集沉淀,沉淀物用甲酸洗涤,干燥,得到5,10,15,20-四(4-溴苯基)-卟啉;
S2、在反应瓶里加入制得的5,10,15,20-四(4-溴苯基)-卟啉、无水醋酸锌和N,N-二甲基甲酰胺,110℃下搅拌3h,反应结束后离心收集沉淀,使用去离子水离心洗涤3次,干燥得到5,10,15,20-四(4-溴苯基)-锌卟啉(1-Zn);
S3、在反应瓶里加入5,10,15,20-四(4-溴苯基)-锌卟啉、双(三苯基膦)二氯化钯、碘化亚铜和1,4-对苯二炔,将所述反应瓶转移到手套箱中,添加溶剂二甲基亚砜,充分溶解后加入三乙胺,100℃下搅拌反应10min,反应结束后使用二氯甲烷离心沉降出产物,干燥后使用三氟乙酸浸泡除锌,得到自聚的所述不溶性聚卟啉。
进一步地,所述制备方法还包括后处理步骤,所述后处理步骤为:将所述炔基四氢异喹啉类衍生物通过乙酸乙酯萃取,无水硫酸钠干燥,旋干后柱层析分离,将柱层析分离后的产物置于真空干燥箱中干燥至恒重。
进一步地,所述制备方法还包括所述不溶性聚卟啉的回收再利用步骤,所述不溶性聚卟啉的回收再利用步骤为:所述炔基四氢异喹啉类衍生物通过乙酸乙酯萃取后,将水相中的固体不溶物高速离心(20000rpm)后收集沉淀,置于真空烘箱中进一步抽干溶剂,作为光敏剂再次加入反应中。
进一步地,所述芳基包括芳烃基、卤代芳烃基、及甲氧基芳基。
进一步地,所述四氢异喹啉为6,7-二甲氧基-2-苯基-1,2,3,4-四氢异喹啉,所述炔烃为4-甲氧基苯乙炔。
本发明的有益效果在于:
本发明使用四氢异喹啉和炔烃类化合物为原料,使用5mol%不溶性聚卟啉P为光敏剂,以4-二甲氨基苯甲酸为添加剂,在20W白光的作用下,在水溶液中室温反应12个小时,最终以53%-79%的收率得到了炔基四氢异喹啉类衍生物,反应条件温和,产物收率中等到良好,底物范围广泛;所使用的不溶性聚卟啉基光敏剂展现出优异的光催化活性,在水相中可诱导C(sp3)-C(sp)键的构建,并且可以重复回收使用,为水相中光催化反应提供了一种绿色和可持续的途径。
上述说明仅是本发明技术方案的概述,为了能够更清楚了解本发明的技术手段,并可依照说明书的内容予以实施,以下以本发明的较佳实施例并配合附图详细说明如后。
附图说明
图1为本发明实施例21中所制得的化合物3s的核磁共振氢谱;
图2为本发明实施例21中所制得的化合物3s的核磁共振碳谱;
图3为本发明实施例1中不溶性聚卟啉P的SEM图;
图4为本发明实施例1中不溶性聚卟啉P的比表面积氮气吸附图;
图5为本发明实施例1中不溶性聚卟啉P的孔径分布图;
图6为本发明实施例1中不溶性聚卟啉P的紫外-可见光谱图(固体紫外)。
具体实施方式
下面结合附图和实施例,对本发明的具体实施方式作进一步详细描述。以下实施例用于说明本发明,但不用来限制本发明的范围。
请参阅图1,本发明提供一种炔基四氢异喹啉衍生物的制备方法,该制备方法底物范围广泛,光敏剂可重复利用。具体地,该制备方法包括如下步骤:
1)制备光敏剂:将摩尔比为1:1的吡咯和4-溴苯甲醛溶解在由体积比为3:1的丙酸和乙酸组成的混合溶剂中,在120℃下搅拌2h充分反应。冷却至室温后,离心收集沉淀,沉淀物用甲酸洗涤,干燥,得到5,10,15,20-四(4-溴苯基)-卟啉。在反应瓶里加入制得的5,10,15,20-四(4-溴苯基)-卟啉、无水醋酸锌和N,N-二甲基甲酰胺,110℃下搅拌3h;反应结束后离心收集沉淀,使用去离子水离心洗涤3次,干燥得到5,10,15,20-四(4-溴苯基)-锌卟啉(1-Zn)。在反应瓶里加入制得的5,10,15,20-四(4-溴苯基)-锌卟啉、双(三苯基膦)二氯化钯、碘化亚铜和1,4-对苯二炔;将反应瓶转移到手套箱中,添加溶剂二甲基亚砜,充分溶解后加入三乙胺,100℃下搅拌反应10min;反应结束后使用二氯甲烷离心沉降出产物,干燥后使用三氟乙酸浸泡除锌,得到自聚的不溶性聚卟啉P。该不溶性聚卟啉P的结构为:
该不溶性聚卟啉具备优异的光催化活性,不溶于几乎所有有机和无机溶剂,包括二氯甲烷、丙酮、甲醇、四氢呋喃、N,N-二甲基甲酰胺、二甲基亚砜、乙腈、丙酮、水等,便于重复回收使用,为水相中光催化反应提供了一种绿色和可持续的途径。
2)合成炔基四氢异喹啉类衍生物:在20W白光条件下,通过光敏剂和添加剂的作用,让摩尔比为1:2.7的四氢异喹啉与炔烃在水中于室温下发生交叉脱氢偶联反应,反应12h后,得到炔基四氢异喹啉类衍生物,反应式如下:
其中,R1,R2和R3为氢、烷基或芳基,芳基包括芳烃基、卤代芳烃基、及甲氧基芳基。关于R1、R2和R3的具体结构,在此不一一列举,可根据实际需要进行选择。
优选地,四氢异喹啉为6,7-二甲氧基-2-苯基-1,2,3,4-四氢异喹啉,炔烃为4-甲氧基苯乙炔,所得6,7-二甲氧基-1-((4-甲氧基苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的产率为79%。
添加剂为4-二甲氨基苯甲酸,添加剂的用量为四氢异喹啉的1倍当量,反应过程中得到的四氢异喹啉亚胺离子中间体,被添加剂苯甲酸阴离子通过离子相互作用稳定得到四氢异喹啉-苯甲酸配合物,从而被亲核试剂炔烃或吲哚进攻得到目标产物炔基四氢异喹啉类衍生物。
光敏剂为上述不溶性聚卟啉,不溶性聚卟啉的用量为所述四氢异喹啉的5mol%,不溶性聚卟啉可循环利用。
3)后处理:将上述炔基四氢异喹啉类衍生物通过乙酸乙酯萃取,无水硫酸钠干燥,旋干后柱层析分离,将柱层析分离后的产物置于真空干燥箱中干燥至恒重。所得炔基四氢异喹啉类衍生物的产率为53%~79%。
4)光敏剂循环利用:炔基四氢异喹啉类衍生物通过乙酸乙酯萃取后,将水相中的固体不溶物高速离心后收集沉淀,将沉淀置于真空烘箱中进一步抽干溶剂,作为光敏剂再次加入反应中。
以下结合具体实施例进一步说明该制备方法。
实施例1,光敏剂不溶性聚卟啉P的制备:
S1、将吡咯(2mL,30mmol)和4-溴苯甲醛(5g,30mmol)溶解在丙酸(45mL)和乙酸(15mL)的混合溶剂中,在120℃下搅拌2h充分反应,冷却至室温后,离心收集沉淀,沉淀物用甲酸洗涤,干燥,得到5,10,15,20-四(4-溴苯基)-卟啉。
S2、在10ml的反应瓶里加入制得的5,10,15,20-四(4-溴苯基)-卟啉(115mg,0.14mmol)、无水醋酸锌(129mg,0.7mmol)和N,N-二甲基甲酰胺(3mL),110℃下搅拌3h,反应结束后使用去离子水离心洗涤3次,干燥得到5,10,15,20-四(4-溴苯基)-锌卟啉(1-Zn)(125mg,90%)。
S3、在反应瓶里加入制得的5,10,15,20-四(4-溴苯基)-锌卟啉(150mg,0.17mmol)、双(三苯基膦)二氯化钯(48mg,0.068mmol)、碘化亚铜(6.5mg,0.034mmol)和1,4-对苯二炔(43mg,0.34mmol)。将反应瓶转移到手套箱中添加溶剂二甲基亚砜(DMSO,2ml),充分溶解后加入三乙胺(0.667ml),100℃下搅拌反应10min。反应结束后使用二氯甲烷(DCM)离心沉降出产物,干燥后使用三氟乙酸浸泡除锌,得到自聚的不溶性聚卟啉P(117mg,85%)。
制备光敏剂不溶性聚卟啉P的反应过程如下:
所得的光敏剂不溶性聚卟啉P的表征结果如下:
13C CP-MAS solid-state NMR:δ163.54,148.97,139.24,130.86,122.04,90.78,83.17,77.36.
IR(KBr)v[cm–1]:3600–3000(br),2200,1596,1481,1344.
P的碳谱见图2,P的SEM图见图3,P的比表面积氮气吸附图见图4,P的孔径分布图见图5,P的紫外-可见光谱图(固体紫外)见图6。
实施例2,1-((4-甲氧基苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3a(26.5mg,产率78%)。
所得化合物3a的结构为:
所得化合物3a的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.36(dd,J=5.2,3.8Hz,1H),7.34–7.28(m,2H),7.25–7.18(m,5H),7.12(d,J=7.9Hz,2H),6.90–6.86(m,1H),6.76–6.72(m,2H),5.63(s,1H),3.84–3.79(m,1H),3.75(s,3H),3.72–3.63(m,1H),3.20–2.93(m,2H).
化合物3a为已知化合物,其谱图与文献报道完全一致(Angew.Chem.Int.Edit.,2020,59,15254-15259)。
实施例3,对于制备化合物3a的光敏剂P的循环实验:
在制备化合物3a时,将萃取后的在水相中的固体不溶物高速离心(20000rpm)后收集沉淀,置于真空烘箱中进一步抽干溶剂(70℃,12h),作为光敏剂再次加入反应中,将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)和H2O(1.0mL)添加到含有磁子和固体沉淀(4.9mg,5mol%)的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3a(25.8mg,产率76%)。重复上述操作,最终3a的产率稳定在75%~78%之间。
实施例4,2-苯基-1-(苯乙炔基)-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、苯乙炔2b(27.5mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3b(20.1mg,产率65%)。
所得化合物3b的结构为:
所得化合物3b的表征结果如下:
1H NMR(600MHz,CDCl3)δ7.38–7.36(m,1H),7.33–7.28(m,4H),7.22(ddd,J=12.1,9.0,4.9Hz,6H),7.12(d,J=8.4Hz,2H),6.89(t,J=7.2Hz,1H),5.64(s,1H),3.78–3.65(m,2H),3.18–2.96(m,2H).
化合物3b为已知化合物,其谱图与文献报道完全一致(ACS Catal.2022,12,126-134)。
实施例5,2-苯基-1-(对甲苯基)-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、4-甲基苯乙炔2c(31.3mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3c(23.2mg,产率72%)。
所得化合物3c的结构为:
所得化合物3c的表征结果如下:
1H NMR(600MHz,CDCl3)δ7.38–7.35(m,1H),7.33–7.30(m,2H),7.24–7.17(m,5H),7.12(d,J=7.9Hz,2H),7.02(d,J=7.9Hz,2H),6.88(t,J=7.3Hz,1H),5.64(s,1H),3.78–3.64(m,2H),3.17–2.95(m,2H),2.29(s,3H).
化合物3c为已知化合物,其谱图与文献报道完全一致(ACS Catal.2022,12,126-134)。
实施例6,1-((4-(叔丁基)苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、4-叔丁基苯乙炔2d(42.7mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色固体3d(21.9mg,产率60%)。
所得化合物3d的结构为:
所得化合物3d的表征结果如下:
1H NMR(600MHz,CDCl3)δ7.37–7.35(m,1H),7.31(t,J=7.9Hz,2H),7.23–7.21(m,5H),7.20–7.17(m,1H),7.12(d,J=8.1Hz,2H),6.96(t,J=9.2Hz,1H),6.88(t,J=7.3Hz,1H),5.63(s,1H),3.78–3.61(m,2H),3.17–2.93(m,2H),1.25(s,9H).
化合物3d为已知化合物,其谱图与文献报道完全一致(Chem.-Eur.J.2012,18,5170-5174)。
实施例7,1-((4-氯苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、4-氯苯乙炔2e(36.7mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色固体3e(24.0mg,产率70%)。
所得化合物3e的结构为:
所得化合物3e的表征结果如下:
1H NMR(600MHz,CDCl3)δ7.36–7.30(m,3H),7.25–7.17(m,7H),7.11(d,J=8.2Hz,2H),6.89(t,J=7.3Hz,1H),5.63(s,1H),3.79–3.61(m,2H),3.19–2.93(m,2H).
化合物3e为已知化合物,其谱图与文献报道完全一致(ACS Catal.2022,12,126-134)。
实施例8,1-((4-溴苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、4-溴苯乙炔2f(48.9mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色固体3f(25.9mg,产率67%)。
所得化合物3f的结构为:
所得化合物3f的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.36–7.29(m,5H),7.25–7.18(m,3H),7.12(dd,J=13.8,8.3Hz,4H),6.89(t,J=7.2Hz,1H),5.62(s,1H),3.79–3.60(m,2H),3.19–2.93(m,2H).
化合物3f为已知化合物,其谱图与文献报道完全一致(Org.Biomol.Chem.2015,13,447-451)。
实施例9,2-苯基-1-(间甲苯基)-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、3-甲基苯乙炔2g(31.3mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3g(22.3mg,产率69%)。
所得化合物3g的结构为:
所得化合物3g的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.37–7.27(m,3H),7.25–7.16(m,3H),7.13–7.07(m,5H),7.02(d,J=4.4Hz,1H),6.87(t,J=7.2Hz,1H),5.62(s,1H),3.80–3.62(m,2H),3.18–2.90(m,2H),2.23(s,3H).
13C NMR(101MHz,CDCl3)δ149.62,137.79,135.56,134.45,132.38,129.20,128.98,128.87,128.05,127.49,127.26,126.33,122.86,119.64,116.72,88.28,85.02,52.33,43.51,28.99,21.18.高分辨质谱(ESI,m/z):C24H22N[M+H]+理论值:324.1746;测量值:324.1752。
实施例10,1-((3-氯苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、3-氯苯乙炔2h(36.7mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3h(25.0mg,产率73%)。
所得化合物3h的结构为:
所得化合物3h的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.41–7.31(m,4H),7.30–7.23(m,4H),7.20–7.13(m,4H),6.94(t,J=7.2Hz,1H),5.68(s,1H),3.84–3.62(m,2H),3.26–2.95(m,2H).
化合物3h为已知化合物,其谱图与文献报道完全一致(Catal.Commun.2017,99,94-99)。
实施例11,1-((2-甲氧基苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、2-甲氧基苯乙炔2i(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3i(18.0mg,产率53%)。
所得化合物3i的结构为:
所得化合物3i的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.41–7.38(m,1H),7.30(t,J=7.8Hz,2H),7.25–7.14(m,7H),6.87(t,J=7.2Hz,1H),6.81–6.76(m,2H),5.68(s,1H),3.76(s,3H),3.75–3.64(m,2H),3.19–2.96(m,2H).
13C NMR(151MHz,CDCl3)δ160.19,149.64,135.64,134.46,133.53,129.41,129.05,128.87,127.52,127.13,126.23,120.22,119.47,116.81,110.79,92.78,81.09,55.78,52.45,43.56,28.95.高分辨质谱(ESI,m/z):C24H22NO[M+H]+理论值:340.1696;测量值:340.1694。
实施例12,1-((2-氯苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、2-氯苯乙炔2j(36.7mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3j(19.2mg,产率56%)。
所得化合物3j的结构为:
所得化合物3j的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.40–7.37(m,1H),7.30(q,J=7.8Hz,4H),7.23–7.17(m,3H),7.15–7.05(m,4H),6.88(t,J=7.2Hz,1H),5.69(s,1H),3.82–3.64(m,2H),3.20–2.94(m,2H).
13C NMR(101MHz,CDCl3)δ149.55,136.09,135.11,134.48,133.35,129.19,129.12,129.07,129.00,127.53,127.35,126.34,126.23,122.98,119.80,116.90,94.11,81.74,52.49,43.56,29.02.高分辨质谱(ESI,m/z):C24H19ClN[M+H]+理论值:344.1201;测量值:344.1202。
实施例13,2-苯基-1-(噻吩-3-乙炔基)-1,2,3,4-四氢异喹啉的制备:
将2-苯基-1,2,3,4-四氢异喹啉1a(20.9mg,0.1mmol)、2-乙炔基噻吩2k(29.2mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3k(16.7mg,产率53%)。
所得化合物3k的结构为:
所得化合物3k的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.37(ddd,J=19.8,8.8,3.7Hz,4H),7.29–7.18(m,4H),7.15(d,J=8.1Hz,2H),7.00(d,J=4.1Hz,1H),6.92(t,J=7.2Hz,1H),5.66(s,1H),3.83–3.65(m,2H),3.24–2.96(m,2H).
化合物3k为已知化合物,其谱图与文献报道完全一致(Monatsh.Chem.2017,148,91-104)。
实施例14,1-((4-甲氧基苯基)乙炔基)-2-(对甲苯基)-1,2,3,4-四氢异喹啉的制备:
将2-(对甲苯基)-1,2,3,4-四氢异喹啉1b(22.3mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到无色液体3l(25.1mg,产率71%)。
所得化合物3l的结构为:
所得化合物3l的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.43–7.35(m,1H),7.29–7.20(m,5H),7.16(d,J=8.3Hz,2H),7.08(d,J=8.4Hz,2H),6.78(d,J=8.7Hz,2H),5.61(s,1H),3.79(s,3H),3.73–3.66(m,2H),3.21–2.95(m,2H),2.33(s,3H).
化合物3l为已知化合物,其谱图与文献报道完全一致(Org.Biomol.Chem.2015,13,447-451)。
实施例15,2-(4-甲氧基苯基)-1-((4-甲氧基苯基)乙炔基)-1,2,3,4-四氢异喹啉的制备:
将2-(4-甲氧基苯基)-1,2,3,4-四氢异喹啉1c(23.9mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到无色液体3m(28.8mg,产率78%)。
所得化合物3m的结构为:
所得化合物3m的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.42–7.35(m,1H),7.28–7.19(m,5H),7.14(d,J=8.9Hz,2H),6.92(d,J=9.0Hz,2H),6.78(d,J=8.8Hz,2H),5.53(s,1H),3.82(s,3H),3.79(s,3H),3.71–3.55(m,2H),3.24–2.92(m,2H).
化合物3m为已知化合物,其谱图与文献报道完全一致(Angew.Chem.,Int.Ed.2020,59,15254-15259)。
实施例16,2-(4-氯苯基)-1-((4-甲氧基苯基)乙炔基)-1,2,3,4-四氢异喹啉的制备:
将2-(4-氯苯基)-1,2,3,4-四氢异喹啉1d(24.3mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到无色液体3n(26.5mg,产率71%)。
所得化合物3n的结构为:
所得化合物3n的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.35(dd,J=5.1,3.7Hz,1H),7.24–7.20(m,7H),7.03(d,J=8.9Hz,2H),6.75(d,J=8.7Hz,2H),5.56(s,1H),3.75(s,3H),3.71–3.59(m,2H),3.15–2.94(m,2H).
化合物3n为已知化合物,其谱图与文献报道完全一致(Angew.Chem.,Int.Ed.2020,59,15254-15259)。
实施例17,2-(4-碘苯基)-1-((4-甲氧苯基)乙炔基)-1,2,3,4-四氢异喹啉的制备:
将2-(4-碘苯基)-1,2,3,4-四氢异喹啉1e(33.5mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到无色液体3o(25.6mg,产率55%)。
所得化合物3o的结构为:
所得化合物3o的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.59(d,J=8.8Hz,2H),7.38(dd,J=5.1,3.6Hz,1H),7.29–7.21(m,5H),6.90(d,J=8.8Hz,2H),6.78(d,J=8.7Hz,2H),5.59(s,1H),3.79(s,3H),3.77–3.61(m,2H),3.19–2.97(m,2H).
13C NMR(151MHz,CDCl3)δ159.51,149.08,137.79,135.25,134.21,133.19,128.85,127.39,127.32,126.40,118.36,114.86,113.76,86.56,80.99,55.27,51.71,43.34,28.79.高分辨质谱(ESI,m/z):C24H21NOI[M+H]+理论值:466.0666;测量值:466.0668。
实施例18,2-(3-甲氧基苯基)-1-((4-甲氧基苯)乙炔基)-1,2,3,4-四氢异喹啉的制备:
将2-(3-甲氧基苯基)-1,2,3,4-四氢异喹啉1f(23.9mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到无色液体3p(24.4mg,产率66%)。
所得化合物3p的结构为:
所得化合物3p的表征结果如下:
1H NMR(600MHz,CDCl3)δ7.37–7.34(m,1H),7.25–7.17(m,6H),6.75–6.67(m,3H),6.67(s,1H),6.44(dd,J=8.1,1.7Hz,1H),5.62(s,1H),3.81(s,3H),3.76(s,3H),3.74–3.64(m,2H),3.16–2.95(m,2H).
13C NMR(151MHz,CDCl3)δ160.65,159.40,150.89,135.64,134.43,133.18,129.79,128.86,127.40,127.17,126.28,115.17,113.70,109.18,104.36,102.76,87.08,84.53,55.24,52.13,43.49,28.86.高分辨质谱(ESI,m/z):C25H24NO2[M+H]+理论值:370.1805;测量值:370.1807。
实施例19,2-(3-氯苯基)-1-((4-甲氧基苯基)乙炔基)-1,2,3,4-四氢异喹啉的制备:
将2-(3-氯苯基)-1,2,3,4-四氢异喹啉1g(24.3mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到无色液体3q(22.4mg,产率60%)。
所得化合物3q的结构为:
所得化合物3q的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.40–7.36(m,1H),7.29–7.21(m,6H),7.10(s,1H),6.99(dd,J=8.3,1.8Hz,1H),6.85(d,J=7.5Hz,1H),6.79(d,J=8.7Hz,2H),5.62(s,1H),3.79(s,3H),3.74–3.66(m,2H),3.20–2.99(m,2H).
13C NMR(151MHz,CDCl3)δ159.52,150.52,135.25,134.95,134.25,133.22,130.07,128.84,127.39,127.34,126.43,118.99,115.99,114.89,114.09,113.77,86.58,84.62,55.27,51.76,43.37,28.80.高分辨质谱(ESI,m/z):C24H21NOCl[M+H]+理论值:374.1317;测量值:374.1312。
实施例20,2-丁基-1-((4-甲氧基苯基)乙炔基)-1,2,3,4-四氢异喹啉的制备:
将2-丁基-1,2,3,4-四氢异喹啉1h(18.9mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3r(17.2mg,产率54%)。
所得化合物3r的结构为:
所得化合物3r的表征结果如下:
1H NMR(600MHz,CDCl3)δ7.33(d,J=8.7Hz,2H),7.31–7.29(m,1H),7.17–7.15(m,2H),7.12–7.10(m,1H),6.79(d,J=8.8Hz,2H),4.87(s,1H),3.79(s,3H),3.06–2.98(m,2H),2.82(dd,J=15.3,8.2Hz,2H),2.73(t,J=7.6Hz,2H),1.66–1.56(m,2H),1.45–1.37(m,2H),0.96(t,J=7.4Hz,3H).
13C NMR(151MHz,CDCl3)δ159.34,135.81,134.02,133.15,128.95,127.83,126.82,125.78,115.46,113.78,86.16,85.95,55.28,54.98,54.74,45.94,29.50,28.94,20.78,14.12.高分辨质谱(ESI,m/z):C22H26NO[M+H]+理论值:320.2020;测量值:320.2014。
实施例21,6,7-二甲氧基-1-((4-甲氧基苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将6,7-二甲氧基-2-苯基-1,2,3,4-四氢异喹啉1i(26.9mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3s(31.5mg,产率79%)。
所得化合物3s的结构为:
所得化合物3s的表征结果如下:
1H NMR(400MHz,CDCl3)δ7.34(t,J=7.9Hz,2H),7.29–7.23(m,2H),7.14(d,J=8.0Hz,2H),6.94–6.87(m,2H),6.78(d,J=8.7Hz,2H),6.69(s,1H),5.58(s,1H),3.92(d,J=9.6Hz,6H),3.79(s,3H),3.73–3.63(m,2H),3.15–2.84(m,2H).
13C NMR(101MHz,CDCl3)δ159.40,149.65,148.24,147.62,133.18,129.11,127.40,126.36,119.61,116.85,115.16,113.72,111.35,110.14,87.19,84.52,56.10,55.93,55.26,52.04,43.41,28.46.高分辨质谱(ESI,m/z):C26H26NO3[M+H]+理论值:400.1910;测量值:400.1913。
实施例22,7-溴-1-((4-甲氧基苯基)乙炔基)-2-苯基-1,2,3,4-四氢异喹啉的制备:
将7-溴-2-苯基-1,2,3,4-四氢异喹啉1i(28.7mg,0.1mmol)、4-甲氧基苯乙炔2a(35.6mg,0.27mmol),4-二甲氨基苯甲酸(16.5mg,0.1mmol)、P(4.9mg,5mol%)和H2O(1.0mL)添加到含有磁子的开放小瓶中,并在室温下在白色LED(20W)的照射下搅拌。反应12小时后,用乙酸乙酯(3×2.0mL)提取粗产物。合并有机层,用无水Na2SO4干燥,然后真空浓缩。残余物通过柱层析分离得到黄色液体3t(31.7mg,产率76%)。
所得化合物3t的结构为:
所得化合物3t的表征结果如下:
1H NMR(600MHz,CDCl3)δ7.35(d,J=6.5Hz,2H),7.31(t,J=7.9Hz,2H),7.24–7.21(m,3H),7.10(d,J=8.3Hz,2H),6.90(t,J=7.2Hz,1H),6.75(d,J=8.7Hz,2H),5.56(s,1H),3.76(s,3H),3.75–3.59(m,2H),3.14–2.90(m,2H).
13C NMR(151MHz,CDCl3)δ159.51,149.39,136.64,134.74,133.17,131.75,129.40,129.18,129.08,120.83,119.94,116.90,114.85,113.75,86.40,85.14,55.26,52.04,43.09,28.75.高分辨质谱(ESI,m/z):C24H21NOBr[M+H]+理论值:418.0807;测量值:418.0807。
综上,本发明使用四氢异喹啉和炔烃类化合物为原料,使用5mol%不溶性聚卟啉P为光敏剂,以4-二甲氨基苯甲酸为添加剂,在20W白光的作用下,在水溶液中室温反应12个小时,最终以53%-79%的收率得到了炔基四氢异喹啉类衍生物,反应条件温和,产物收率中等到良好,底物范围广泛;所使用的不溶性聚卟啉基光敏剂展现出优异的光催化活性,在水相中可诱导C(sp3)-C(sp)键的构建,并且可以重复回收使用,为水相中光催化反应提供了一种绿色和可持续的途径。
以上所述实施例的各技术特征可以进行任意的组合,为使描述简洁,未对上述实施例中的各个技术特征所有可能的组合都进行描述,然而,只要这些技术特征的组合不存在矛盾,都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式,其描述较为具体和详细,但并不能因此而理解为对发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。因此,本发明专利的保护范围应以所附权利要求为准。
Claims (6)
1.一种炔基四氢异喹啉衍生物的制备方法,其特征在于,包括如下步骤:
在20W白光条件下,通过光敏剂和添加剂的作用,让四氢异喹啉与炔烃在水中于室温下发生交叉脱氢偶联反应,反应12h后,得到炔基四氢异喹啉类衍生物,反应式如下:
其中,R1,R2和R3为氢、烷基或芳基;
所述四氢异喹啉与所述炔烃的摩尔比为1:2.7;
所述添加剂为4-二甲氨基苯甲酸,所述添加剂的用量为所述四氢异喹啉的1倍当量;
所述光敏剂P为不溶性聚卟啉,所述不溶性聚卟啉由摩尔比为1:1的吡咯和4-溴苯甲醛制得,所述不溶性聚卟啉的结构为:
所述不溶性聚卟啉的用量为所述四氢异喹啉的5mol%。
2.如权利要求1所述的炔基四氢异喹啉衍生物的制备方法,其特征在于,所述不溶性聚卟啉的制备方法为:
S1、将所述摩尔比为1:1的吡咯和4-溴苯甲醛溶解在由体积比为3:1的丙酸和乙酸组成的混合溶剂中,在120℃下搅拌2h充分反应,冷却至室温后,离心收集沉淀,沉淀物用甲酸洗涤,干燥,得到5,10,15,20-四(4-溴苯基)-卟啉;
S2、在反应瓶里加入制得的5,10,15,20-四(4-溴苯基)-卟啉、无水醋酸锌和N,N-二甲基甲酰胺,110℃下搅拌3h,反应结束后离心收集沉淀,使用去离子水离心洗涤3次,干燥得到5,10,15,20-四(4-溴苯基)-锌卟啉(1-Zn);
S3、在反应瓶里加入5,10,15,20-四(4-溴苯基)-锌卟啉、双(三苯基膦)二氯化钯、碘化亚铜和1,4-对苯二炔,将所述反应瓶转移到手套箱中,添加溶剂二甲基亚砜,充分溶解后加入三乙胺,100℃下搅拌反应10min,反应结束后使用二氯甲烷离心沉降出产物,干燥后使用三氟乙酸浸泡除锌,得到自聚的所述不溶性聚卟啉。
3.如权利要求1所述的炔基四氢异喹啉衍生物的制备方法,其特征在于,所述制备方法还包括后处理步骤,所述后处理步骤为:将所述炔基四氢异喹啉类衍生物通过乙酸乙酯萃取,无水硫酸钠干燥,旋干后柱层析分离,将柱层析分离后的产物置于真空干燥箱中干燥至恒重。
4.如权利要求3所述的炔基四氢异喹啉衍生物的制备方法,其特征在于,所述制备方法还包括所述不溶性聚卟啉的回收再利用步骤,所述不溶性聚卟啉的回收再利用步骤为:所述炔基四氢异喹啉类衍生物通过乙酸乙酯萃取后,将水相中的固体不溶物高速离心(20000rpm)后收集沉淀,置于真空烘箱中进一步抽干溶剂,作为光敏剂再次加入反应中。
5.如权利要求1所述的炔基四氢异喹啉衍生物的制备方法,其特征在于,所述芳基包括芳烃基、卤代芳烃基、及甲氧基芳基。
6.如权利要求5所述的炔基四氢异喹啉衍生物的制备方法,其特征在于,所述四氢异喹啉为6,7-二甲氧基-2-苯基-1,2,3,4-四氢异喹啉,所述炔烃为4-甲氧基苯乙炔。
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