CN117050010A - 一种2,2’-联喹啉及其衍生物的合成方法 - Google Patents
一种2,2’-联喹啉及其衍生物的合成方法 Download PDFInfo
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- CN117050010A CN117050010A CN202311313140.XA CN202311313140A CN117050010A CN 117050010 A CN117050010 A CN 117050010A CN 202311313140 A CN202311313140 A CN 202311313140A CN 117050010 A CN117050010 A CN 117050010A
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- biquinoline
- iodine
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- aromatic amine
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- WPTCSQBWLUUYDV-UHFFFAOYSA-N 2-quinolin-2-ylquinoline Chemical compound C1=CC=CC2=NC(C3=NC4=CC=CC=C4C=C3)=CC=C21 WPTCSQBWLUUYDV-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 238000001308 synthesis method Methods 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000003054 catalyst Substances 0.000 claims abstract description 20
- 150000004982 aromatic amines Chemical class 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 239000007800 oxidant agent Substances 0.000 claims abstract description 13
- 230000001590 oxidative effect Effects 0.000 claims abstract description 13
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 12
- 239000011630 iodine Substances 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims abstract description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- CZZZABOKJQXEBO-UHFFFAOYSA-N 2,4-dimethylaniline Chemical compound CC1=CC=C(N)C(C)=C1 CZZZABOKJQXEBO-UHFFFAOYSA-N 0.000 claims description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 claims description 4
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 claims description 2
- QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical compound NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 claims description 2
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229940107816 ammonium iodide Drugs 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- CBEQRNSPHCCXSH-UHFFFAOYSA-N iodine monobromide Chemical compound IBr CBEQRNSPHCCXSH-UHFFFAOYSA-N 0.000 claims description 2
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims 2
- 229940071870 hydroiodic acid Drugs 0.000 claims 1
- 229960002317 succinimide Drugs 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 16
- 230000009471 action Effects 0.000 abstract description 5
- 230000002194 synthesizing effect Effects 0.000 abstract description 5
- 229910052751 metal Inorganic materials 0.000 abstract description 4
- 239000002184 metal Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 229910052723 transition metal Inorganic materials 0.000 abstract description 4
- 150000003624 transition metals Chemical class 0.000 abstract description 4
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 3
- -1 2,2' -biquinoline compound Chemical class 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 31
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- UCCQXCFFHYCLEC-UHFFFAOYSA-N 1-quinolin-2-ylethanone Chemical compound C1=CC=CC2=NC(C(=O)C)=CC=C21 UCCQXCFFHYCLEC-UHFFFAOYSA-N 0.000 description 1
- FXWFZIRWWNPPOV-UHFFFAOYSA-N 2-aminobenzaldehyde Chemical compound NC1=CC=CC=C1C=O FXWFZIRWWNPPOV-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- 238000006887 Ullmann reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- AUPXFICLXPLHBB-UHFFFAOYSA-L disodium;2-(4-carboxylatoquinolin-2-yl)quinoline-4-carboxylate Chemical compound [Na+].[Na+].C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)[O-])=CC(C([O-])=O)=C21 AUPXFICLXPLHBB-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- VBSNVDGIHSXRKJ-UHFFFAOYSA-N pyrrolidine-2,5-dione;hydroiodide Chemical compound I.O=C1CCC(=O)N1 VBSNVDGIHSXRKJ-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供了一种2,2’‑联喹啉及其衍生物的合成方法,属于化学合成领域,以芳香胺和1,4‑二氧六环为原料,在催化剂和氧化剂的作用下,于70℃‑140℃反应8h‑48h,将反应混合液纯化处理得到2,2’‑联喹啉类化合物,其中催化剂为含碘化合物或单质碘。这是一种无需过渡金属催化的合成方法,本发明具有反应条件温和、操作简单、反应步骤少,原料来源广泛、价格便宜、产率较高、应用易于扩展等优点;并且克服了现有技术中的成本高,金属催化剂滥用等缺陷;一锅法避免在后处理过程中冗长的分离过程和中间体化合物的纯化过程,从而节省时间与资源并且提高收率。
Description
技术领域
本发明属于化学合成领域,具体涉及一种2,2’-联喹啉及其衍生物的合成方法。
背景技术
2,2’-联喹啉及其衍生物是重要的有机化工原料,在医药、检测和功能材料等领域有着广泛的应用。2,2’-联喹啉与一价铜离子反应显紫色,可用于亚铜的检测;2,2’-联喹啉-4,4’-二甲酸钠是蛋白质检测试剂;另外,2,2’-联喹啉及其衍生物在光电材料、有机催化等方面也有着重要的应用价值,其发展前景广阔。
2,2’-联喹啉类衍生物的合成尽管研究历史悠久,但是仍然具有较大的挑战性,目前报道的2,2’-联喹啉及其衍生物的合成方法主要有以下几种:方法一、喹啉分子间偶联合成2,2’-联喹啉及其衍生物,其主要通过Suzuki-Miyaura偶联、Stille偶联、Ullmann偶联及其改进方法来实现的。该类方法需要过渡金属催化和偶联试剂,有一些偶联试剂是毒性较高的,对环境危害较大;方法二、通过氢化联喹啉还原脱氢来合成2,2’-联喹啉,该方法需要事先制备氢化联喹啉,原材料成本就会较高;方法三、以芳香胺为原料合成2,2’-联喹啉及其衍生物,该类方法中,芳香胺需要事先制备,一般需要在芳香胺的氨基邻位需要取代基参与反应,如邻氨基苯甲醛和2-喹啉基甲基甲酮反应得到目标产物,该方法由于氨基邻位带有取代基的芳香胺价格较高,因此原料成本高;如果芳香胺的结构中氨基邻位没有取代基,则需要多步反应才能合成2,2’-联喹啉及其衍生物,反应步骤长,成本高。
目前合成2,2’-联喹啉及其衍生物的方法,都有不可避免缺陷,存在成本高,或者使用过金属催化剂等问题,因此,有必要开发出一种新的合成2,2’-联喹啉及其衍生物的方法。
发明内容
为了解决上述技术问题,克服高成本,金属催化剂滥用等问题,本发明提供了一种2,2’-联喹啉及其衍生物的合成方法,该方法中无需过渡金属催化剂,为合成该类化合物提供了一条新路径。它还具有反应体系简单、条件温和、原料来源广泛、价格便宜、产率较高、应用易于扩展等优点。
为达到上述目的,本发明提供了一种2,2’-联喹啉及其衍生物的合成方法,包括以下步骤:以式1所示的芳香胺与1,4-二氧六环为原料,加入催化剂和氧化剂,在70℃-140℃混合反应8h-48h,将产物纯化即得到如式2所示的2,2’-联喹啉类衍生物,合成通式如下所示;
;
其中,式1、式2中R选自氢原子、烷基、烷氧基、卤素中的一种,所述催化剂为含碘化合物或单质碘,所述氧化剂为氧气或者空气。
作为优选,所述芳香胺、含碘化合物、1,4-二氧六环的摩尔比为1:0.05-0.6:29-88。
作为优选,所述含碘化合物为碘化钾、碘化钠、碘化铵、55%氢碘酸、氯化碘、溴化碘、碘代丁二酰亚胺中的一种。
作为优选,所述式1所示的芳香胺为苯胺、4-甲氧基苯胺、2-甲基苯胺、4-甲基苯胺、3-氟苯胺、2,4-二甲基苯胺中的一种。
作为优选,所述2,2’-联喹啉及其衍生物为式2-1~式2-6化合物中的一种:
。
本发明的反应机理如下:
反应机理如图1所示,本发明含碘化合物作为催化剂在氧气和加热的情况下,生成碘自由基I·,芳香胺和I·反应生成自由基A,1,4-二氧六环在酸性条件下生成乙烯醇,乙烯醇和自由基A加成得到自由基B,后者异构生成自由基C,它与乙烯醇进一步加成生成自由基D,自由基D对苯环进行分子内加成生成自由基E,自由基E在氧气等氧化剂的作用下,生成中间体F,后者在酸的作用下脱水,生成中间体G,自由基A与中间体G加成生成自由基H,后者异构生成自由基I,1,4-二氧六环经过开环和脱水生成中间体4,自由基I对中间体4进行加成得到自由基J,后者对苯环进行分子内自由基加成生成自由基K,后者在氧气等氧化剂作用下脱去H·得到中间体L,它在酸作用下醚键断裂生成中间体M,中间体M进一步脱水和芳构化生成目标产物联喹啉。
与现有技术相比,本发明具有以下有益效果:
(1)本发明以芳香胺、1,4-二氧六环为原料,在氧化剂、含碘化合物作为催化剂的共同作用下,通过环化反应,在较为温和的条件下,一锅高效合成2,2’-联喹啉及其衍生物,该方法中无需过渡金属催化剂,为合成该类化合物提供了一条新路径。
(2)本发明反应条件温和、操作简单、反应步骤少,原料来源广泛、价格便宜、产率较高、应用易于扩展等优点;克服了现有技术中的成本高,金属催化剂滥用等缺陷。一锅法避免在后处理过程中冗长的分离过程和中间体化合物的纯化过程,从而节省时间与资源并且提高收率。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案,下面将对实施例中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1为本发明制备2,2’-联喹啉及其衍生物的反应机理图;
图2为实施例1产物的核磁氢谱图;
图3为实施例1产物的核磁碳谱图;
图4为实施例19产物的核磁氢谱图;
图5为实施例19产物的核磁碳谱图;
图6为实施例20产物的核磁氢谱图;
图7为实施例20产物的核磁碳谱图;
图8为实施例21产物的核磁氢谱图;
图9为实施例21产物的核磁碳谱图;
图10为实施例22产物的核磁氢谱图;
图11为实施例22产物的核磁碳谱图;
图12为实施例23产物的核磁氢谱图;
图13为实施例23产物的核磁碳谱图。
具体实施方式
为使本发明要解决的技术问题、技术方案和优点更加清楚,下面将结合附图及具体实施例进行详细描述。
以下实施例用于说明本发明,但不用来限制本发明的范围。在不背离本发明精神和实质的情况下,对本发明方法、步骤或条件所作的修改或替换,均属于本发明的范围。
若未特别指明,实施例中所用的技术手段为本领域技术人员所熟知的常规手段;若未特别指明,实施例中所用试剂均为市售。
实施例1-23,制备2,2’-联喹啉类衍生物,
S1、向反应器中加入芳香胺、1,4-二氧六环、催化剂和氧化剂;
S2、将步骤S1中的反应物与催化剂和氧化剂充分混合,然后对反应器进行加热反应,得到混合物;
S3、对步骤S2中的混合物进行纯化:将混合物溶剂蒸干,用硅胶作为吸附剂,柱色谱分离,得到2,2’-联喹啉及其衍生物。
制备过程中的芳香胺、催化剂和氧化剂类型以及芳香胺、含碘化合物、1,4-二氧六环的摩尔比、反应条件如表1所示:
表1 实施例1-23的反应物、催化剂、氧化剂、摩尔比、反应温度、反应时间
,
*为芳香胺、催化剂、1,4-二氧六环的摩尔比。
将实施例1-23反应的反应产物进行产率统计和核磁共振表征,结构式如表2所示:
表2 实施例1-23产物结构式
由表2可知,当反应底物为和1,4-二氧六环时,催化剂为55%氢碘酸,氧化剂为氧气,芳香胺、催化剂、1,4-二氧六环的摩尔比1:0.5: 88,反应条件为110℃,16h时,将混合物溶剂蒸干,用硅胶作为吸附剂,柱色谱分离,得到/>产率最大,为81%。
实施例1产物的核磁氢谱图如图2所示;核磁碳谱图如图3所示,核磁数据:
1H NMR (400 MHz, CDCl3, ppm) δ 8.76 (d, J = 8.8 Hz, 2H), 8.24 (d, J =8.4 Hz, 2H), 8.15 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.67 (t, J =7.6 Hz, 2H), 7.49 (t, J = 7.4 Hz, 2H); 13C NMR (100 MHz, CDCl3, ppm) δ 156.2,147.9, 136.7, 129.9, 129.5, 128.4, 127.6, 126.9, 119.4。
实施例19的产物核磁氢谱图如图4所示;
实施例19的产物核磁碳谱图如图5所示;
实施例19产物的核磁数据:
1H NMR (400 MHz, CDCl3, ppm) δ 8.86 (d, J = 8.4 Hz, 2H), 8.21 (d, J =8.8 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 6.4 Hz, 2H), 7.39 (t, J =7.6 Hz, 2H), 2.90 (s, 6H); 13C NMR (100 MHz, CDCl3, ppm) δ 155.1, 146.8,137.8, 136.8, 129.5, 128.3, 126.6, 125.6, 118.9, 17.9。
实施例20的产物核磁氢谱图如图6所示;
实施例20的产物核磁碳谱图如图7所示;
实施例20产物的核磁数据:
1H NMR (400 MHz, CDCl3, ppm) δ 8.70 (d, J = 8.8 Hz, 2H), 8.15 (d, J =8.4 Hz, 2H), 8.04 (d, J = 8.4 Hz, 2H), 7.56 (s, 2H), 7.51 (d, J = 8.4 Hz,2H), 2.50 (s, 6H); 13C NMR (100 MHz, CDCl3, ppm) δ 155.6, 146.5, 136.8,136.0, 131.8, 129.5, 128.4, 126.5, 119.4, 21.7。
实施例21的产物核磁氢谱图如图8所示;
实施例21的产物核磁碳谱图如图9所示;
实施例21产物的核磁数据:
1H NMR (400 MHz, CDCl3, ppm) δ 8.68 (d, J = 8.8 Hz, 2H), 8.14 (d, J =8.8 Hz, 2H), 8.04 (d, J = 9.2 Hz, 2H), 7.33 (dd, J = 9.2, 2.8 Hz, 2H), 7.08(d, J = 2.4 Hz, 2H), 3.90 (s, 6H); 13C NMR (100 MHz, CDCl3, ppm) δ 158.1,154.2, 144.0, 135.4, 131.3, 129.4, 122.2, 119.5, 105.2, 55.6。
实施例22的产物核磁氢谱图如图10所示;
实施例22的产物核磁碳谱图如图11所示;
实施例22产物的核磁数据:
1H NMR (400 MHz, CDCl3, ppm) δ 8.72 (d, J = 8.4 Hz, 2H), 8.25 (d, J =8.4 Hz, 2H), 7.82-7.76 (m, 4H), 7.31 (t, J = 7.4 Hz, 2H); 13C NMR (100 MHz,CDCl3, ppm) δ 163.3 (d, J = 248.4 Hz), 156.8, 148.9 (d, J = 12.7 Hz), 136.7,128.1 (d, J = 9.8 Hz), 125.5, 118.8 (d, J = 2.5 Hz), 117.5 (d, J = 25.3 Hz),113.5 (d, J = 20.1 Hz)。
实施例23的产物核磁氢谱图如图12所示;
实施例23的产物核磁碳谱图如图13所示;
实施例23产物的核磁数据:
1H NMR (400 MHz, CDCl3, ppm) δ 8.87 (d, J = 8.8 Hz, 2H), 8.17 (d, J =8.8 Hz, 2H), 7.47 (s, 2H), 7.44 (s, 2H), 2.92 (s, 6H), 2.52 (s, 6H); 13C NMR(100 MHz, CDCl3, ppm) δ 154.5, 145.4, 137.3, 136.3, 136.0, 131.8, 128.4,124.5, 118.9, 21.7, 17.8。
Claims (5)
1.一种2,2’-联喹啉及其衍生物的合成方法,其特征在于,包括以下步骤:以式1所示的芳香胺与1,4-二氧六环为原料,加入催化剂和氧化剂,在70℃-140℃混合反应8h-48h,将产物纯化即得到如式2所示的2,2’-联喹啉类衍生物,合成通式如下所示:
,
其中,式1、式2中R选自氢原子、烷基、烷氧基、卤素中的一种,所述催化剂为含碘化合物或单质碘,所述氧化剂为氧气或者空气。
2.根据权利要求1所述的合成方法,其特征在于,所述芳香胺、含碘化合物、1,4-二氧六环的摩尔比为1:0.05-0.6:29-88。
3.根据权利要求1所述的合成方法,其特征在于,所述含碘化合物为碘化钾、碘化钠、碘化铵、55%氢碘酸、氯化碘、溴化碘、碘代丁二酰亚胺中的一种。
4.根据权利要求1所述的合成方法,其特征在于,所述式1所示的芳香胺为苯胺、4-甲氧基苯胺、2-甲基苯胺、4-甲基苯胺、3-氟苯胺、2,4-二甲基苯胺中的一种。
5.根据权利要求1所述的合成方法,其特征在于,所述2,2’-联喹啉及其衍生物为式2-1~式2-6化合物中的一种:
。
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