CN108929286B - Method for synthesizing propargylamines by multicomponent reaction promoted by functionalized ionic liquid - Google Patents
Method for synthesizing propargylamines by multicomponent reaction promoted by functionalized ionic liquid Download PDFInfo
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- CN108929286B CN108929286B CN201810710303.0A CN201810710303A CN108929286B CN 108929286 B CN108929286 B CN 108929286B CN 201810710303 A CN201810710303 A CN 201810710303A CN 108929286 B CN108929286 B CN 108929286B
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- 239000002608 ionic liquid Substances 0.000 title claims abstract description 67
- 238000000034 method Methods 0.000 title claims abstract description 57
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical class NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 16
- 238000006452 multicomponent reaction Methods 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 89
- 238000003756 stirring Methods 0.000 claims abstract description 55
- 230000008569 process Effects 0.000 claims abstract description 37
- -1 aldehyde compounds Chemical class 0.000 claims abstract description 34
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 15
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 13
- 230000003197 catalytic effect Effects 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 230000035484 reaction time Effects 0.000 claims abstract description 8
- 239000000758 substrate Substances 0.000 claims abstract 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(I) nitrate Inorganic materials [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 93
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 81
- 239000012043 crude product Substances 0.000 claims description 54
- 239000012074 organic phase Substances 0.000 claims description 54
- 239000000047 product Substances 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 27
- 238000012544 monitoring process Methods 0.000 claims description 27
- 238000010898 silica gel chromatography Methods 0.000 claims description 27
- 238000004809 thin layer chromatography Methods 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 238000000605 extraction Methods 0.000 claims description 25
- 238000002390 rotary evaporation Methods 0.000 claims description 24
- 238000004064 recycling Methods 0.000 claims description 5
- HRDVWDQQYABHGH-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-N,N-dimethylaniline hydrochloride Chemical compound Cl.CN(C)c1ccc(cc1)-c1ccc(cc1)N(C)C HRDVWDQQYABHGH-UHFFFAOYSA-N 0.000 claims 1
- 239000003446 ligand Substances 0.000 abstract description 6
- 230000001737 promoting effect Effects 0.000 abstract description 4
- 239000011261 inert gas Substances 0.000 abstract description 3
- 101710134784 Agnoprotein Proteins 0.000 abstract 1
- 239000003426 co-catalyst Substances 0.000 abstract 1
- 230000009972 noncorrosive effect Effects 0.000 abstract 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 72
- 238000002156 mixing Methods 0.000 description 27
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 24
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 23
- 150000001299 aldehydes Chemical class 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 150000001345 alkine derivatives Chemical group 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 229910052709 silver Inorganic materials 0.000 description 4
- 239000004332 silver Substances 0.000 description 4
- ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 238000005580 one pot reaction Methods 0.000 description 3
- 238000010025 steaming Methods 0.000 description 3
- LFZJRTMTKGYJRS-UHFFFAOYSA-N 1-chloro-4-ethynylbenzene Chemical group ClC1=CC=C(C#C)C=C1 LFZJRTMTKGYJRS-UHFFFAOYSA-N 0.000 description 2
- KSZVOXHGCKKOLL-UHFFFAOYSA-N 4-Ethynyltoluene Chemical group CC1=CC=C(C#C)C=C1 KSZVOXHGCKKOLL-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000010499 C–H functionalization reaction Methods 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FINHMKGKINIASC-UHFFFAOYSA-N Tetramethylpyrazine Chemical compound CC1=NC(C)=C(C)N=C1C FINHMKGKINIASC-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 238000010523 cascade reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XZDYFCGKKKSOEY-UHFFFAOYSA-N 1,3-bis[2,6-di(propan-2-yl)phenyl]-4,5-dihydro-2h-imidazol-1-ium-2-ide Chemical compound CC(C)C1=CC=CC(C(C)C)=C1N1CCN(C=2C(=CC=CC=2C(C)C)C(C)C)[C]1 XZDYFCGKKKSOEY-UHFFFAOYSA-N 0.000 description 1
- LTLVZQZDXQWLHU-UHFFFAOYSA-N 1-bromo-4-ethynylbenzene Chemical group BrC1=CC=C(C#C)C=C1 LTLVZQZDXQWLHU-UHFFFAOYSA-N 0.000 description 1
- IQQRAVYLUAZUGX-UHFFFAOYSA-N 1-butyl-3-methylimidazolium Chemical compound CCCCN1C=C[N+](C)=C1 IQQRAVYLUAZUGX-UHFFFAOYSA-N 0.000 description 1
- ZNTJVJSUNSUMPP-UHFFFAOYSA-N 1-ethyl-4-ethynylbenzene Chemical group CCC1=CC=C(C#C)C=C1 ZNTJVJSUNSUMPP-UHFFFAOYSA-N 0.000 description 1
- KBIAVTUACPKPFJ-UHFFFAOYSA-N 1-ethynyl-4-methoxybenzene Chemical group COC1=CC=C(C#C)C=C1 KBIAVTUACPKPFJ-UHFFFAOYSA-N 0.000 description 1
- UVFFOABHOIMLNB-UHFFFAOYSA-N 1-ethynyl-4-propylbenzene Chemical group CCCC1=CC=C(C#C)C=C1 UVFFOABHOIMLNB-UHFFFAOYSA-N 0.000 description 1
- TXSHDUNPZCVHHF-UHFFFAOYSA-N 1-nitro-4-prop-2-ynoxybenzene Chemical compound [O-][N+](=O)C1=CC=C(OCC#C)C=C1 TXSHDUNPZCVHHF-UHFFFAOYSA-N 0.000 description 1
- UNNGUFMVYQJGTD-UHFFFAOYSA-N 2-Ethylbutanal Chemical compound CCC(CC)C=O UNNGUFMVYQJGTD-UHFFFAOYSA-N 0.000 description 1
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 1
- RACCOFGYHHVUQB-UHFFFAOYSA-N 2-prop-2-ynoxynaphthalene Chemical compound C1=CC=CC2=CC(OCC#C)=CC=C21 RACCOFGYHHVUQB-UHFFFAOYSA-N 0.000 description 1
- CLRPXACRDTXENY-UHFFFAOYSA-N 3-ethynylpyridine Chemical compound C#CC1=CC=CN=C1 CLRPXACRDTXENY-UHFFFAOYSA-N 0.000 description 1
- YGCZTXZTJXYWCO-UHFFFAOYSA-N 3-phenylpropanal Chemical compound O=CCCC1=CC=CC=C1 YGCZTXZTJXYWCO-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical class O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- 229910007339 Zn(OAc)2 Inorganic materials 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- ILVDYAGPHFWNQI-UHFFFAOYSA-N deca-1,9-diyne Chemical compound C#CCCCCCCC#C ILVDYAGPHFWNQI-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- ZOMNIUBKTOKEHS-UHFFFAOYSA-L dimercury dichloride Chemical compound Cl[Hg][Hg]Cl ZOMNIUBKTOKEHS-UHFFFAOYSA-L 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002192 fatty aldehydes Chemical class 0.000 description 1
- CBMIPXHVOVTTTL-UHFFFAOYSA-N gold(3+) Chemical compound [Au+3] CBMIPXHVOVTTTL-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N phenyl propionaldehyde Natural products CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- AIQRJSXKXVZCJO-UHFFFAOYSA-N prop-2-ynoxybenzene Chemical group C#CCOC1=CC=CC=C1 AIQRJSXKXVZCJO-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003378 silver Chemical class 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000005829 trimerization reaction Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- DJWUNCQRNNEAKC-UHFFFAOYSA-L zinc acetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O DJWUNCQRNNEAKC-UHFFFAOYSA-L 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了一种功能化离子液体促进多组分反应合成炔丙胺类化合物的方法，属于炔丙胺类化合物的合成技术领域。本发明的技术方案要点为：以醛类化合物、仲胺类化合物和炔类化合物为反应底物，AgNO3为催化剂，功能化离子液体为助催化剂和溶剂，于70℃搅拌反应制得目标产物炔丙胺类化合物，功能化离子液体重复循环使用。本发明的功能化离子液体制备简便，价廉易得且环境友好；功能化离子液体的催化活性较高，并且循环使用多次后仍然保持较好的催化活性；此反应无需配体和溶剂，不需要惰性气体的保护，反应时间较短；该反应体系对设备无腐蚀性，对反应容器无特殊要求，并且此催化体系的操作及后处理过程均较简单。The invention discloses a method for synthesizing propargylamine compounds by promoting multi-component reaction with functionalized ionic liquid, and belongs to the technical field of synthesis of propargylamine compounds. The main points of the technical solution of the present invention are as follows: using aldehyde compounds, secondary amine compounds and alkyne compounds as reaction substrates, AgNO 3 as catalyst, functionalized ionic liquid as co-catalyst and solvent, and stirring the reaction at 70 ° C to obtain the target product Propargylamine compounds, functionalized ionic liquids are used repeatedly. The functionalized ionic liquid of the present invention is easy to prepare, cheap and easy to obtain, and environmentally friendly; the functionalized ionic liquid has high catalytic activity, and can still maintain good catalytic activity after being recycled for many times; the reaction does not require ligands and solvents, and The protection of inert gas is not required, and the reaction time is short; the reaction system is non-corrosive to equipment, has no special requirements for the reaction vessel, and the operation and post-treatment process of the catalytic system are relatively simple.
Description
Technical Field
The invention belongs to the technical field of propargylamine compound synthesis, and particularly relates to a method for synthesizing propargylamine compounds by promoting multi-component reaction of functionalized ionic liquid under the conditions of no ligand, no solvent and no inert gas protection.
Background
Propargylamine is a common structural unit in compounds with biological activity and is an important intermediate for synthesizing complex nitrogen-containing compounds. Such as for the development of beta-lactams, conformationally constrained polypeptides, oxotremorine analogs, certain natural compounds, and clinical drug molecules, among others. Past A3The tandem reaction mostly uses Cu (I) (Park S B, aluminum H. an effective synthesis of partially amides via C-H activation catalyzed by hopper (I) in ionic liquids [ J].Chemical Communication,2005,36(31):1315-1317.)，Au(Zhang X,Corma A.Supported gold(III)catalysts for highly efficient three-component coupling reactions[J].AngewandteChemie International Edition,2008,47(23):4358-4361.)，Fe(Li P,Zhang Y,Wang L.Iron-catalyzed ligand-free three-component coupling reactions of aldehydes，terminal alkynes,and amines[J].Chemistry-A European Journal,2009,15(9):2045-2049.)，In(Zhang Y,Li P,Wang M,et al.Indium-catalyzed highly efficient three-component coupling of aldehyde,alkyne,and amine via C-H bond activation[J].Journal of Organic Chemistry,2009,40(43):4364-4367.)，Zn(Ramu E,Varala R,Sreelatha N,et al.Zn(OAc)2·2H2O:a versatile catalyst for the one-pot synthesis of propargylamines[J].Tetrahedron Letters,2007,48(40):7184-7190.)，Ni(Samai S,Nandi G C,Singh M S.An efficient and facile one-pot synthesis of propargylamines by three-component coupling of aldehydes,amines,and alkynes via C-H activation catalyzed by NiCl2[J].Tetrahedron Letters,2011,42(5):5555-5558.)，Co(Chen W W,Bi H P,Li C J.The First cobalt-catalyzed transformation of alkynyl C-H bond:aldehyde-alkyne-amine(A3)coupling[J].Synlett,2010,2010(3):475-479.)，Hg(Li P,Wang L.Mercurous chloride catalyzed mannich condensation of terminal alkynes with secondary amines and aldehydes[J]Chinese Journal of Chemistry,2005,23,1076-1080.) for the catalytic synthesis of propargylamine, and solid supported metal catalysts (Nakamura S, Ohara M. chip-catalyzed active metal-complex synthesis of optically active precursors from amides, and aliphatic alkylalkylkynylamines [ J]Chemistry 2010,16(8):2360-2O3、AuCl4/LDH, Cu/HAP, etc. In the Cu and Au catalytic system, the yield and the conversion rate of the fatty aldehyde are low. In recent years, silver and silver salts have been widely used as initiators and catalysts in organic synthesis because they exhibit good catalytic activity in all of tandem reactions, addition reactions, rearrangement reactions, and cyclization reactions. For A3A coupling reaction, when the aldehyde is an aliphatic aldehyde, Ag is more significant in catalytic activity than Cu and Au, and a by-product, namely a trimerization product of the aldehyde, is rarely generated. Li and its co-workers (Wei C, Li Z, Li C J. the first silver-catalyzed thread-component coupling of aldehyde, alk)yne,and amine[J]Organic Letters,2003,5(23):4473-4475.) Ag catalyzed A was first reported in 20033The propargylamine is synthesized by reaction. The system requires N2Protection, H2O is used as a solvent. Subsequently, the team (Li Z, Wei C, Chen L, et al, three-component coupling of aldehyde, alkyne, and amine catalyzed by silver in ionic liquid [ J]Tetrahedron Letters,2004,45(26):2443-2446.) use of AgI in IL ([ Bmim ]]PF6) The propargylamine is synthesized by medium catalysis, and N is still needed in the reaction2Protection, high temperature, long reaction time and expensive catalyst AgI. In addition, researchers need additional solubilizers or ligands such as [ Ag (I) (Pc-L) while using Ag metal as a catalyst]+X-(X＝BF4、OTf、N(Tf)2)(Trose M,Dell'Acqua M.[Silver(I)(pyridine-containing ligand)]complexes as unusual catalysts for A(3)-coupling reactions[J].Journal of Organic Chemistry,2014,79(16):7311-7320.)，NHC–Ag(I)(Chen M T,Landers B,Navarro O.Well-defined(N-heterocyclic carbene)-Ag(I)complexes as catalysts for A3reactions[J].Organic&Biomolecular Chemistry,2012,10(11):2206-2208.)，PS–NHC–Ag(I)(He Y,Lv M F,Cai C.A simple procedure for polymer-supported N-heterocyclic carbene silver complex via click chemistry:an efficient and recyclable catalyst for the one-pot synthesis of propargylamines[J].Dalton Transactions,2012,41(40):12428-12433.)，(SIPr)Ag(OAc)(Chen M T,Landers B,Navarro O.Well-defined(heterocyclic carbene)–Ag complexes as catalysts for A reactions[J].Organic&Biomolecular Chemistry,2012,10(11):2206-2208.)，(CyNaph-NHC)AgCl(Li Y,Chen X,Song Y,et al.Well-defined N-heterocyclic carbene silver halides of 1-cyclohexyl-3-arylmethylimidazolylidenes:synthesis,structure and catalysis in A3-reaction of aldehydes,amines and alkynes[J]Dalton transactions 2011 40(9): 2046-. It is noted that the process for synthesizing the ligand is complicated and uses organic solvents, and the methods for producing propargylamine have more or less disadvantages, such as the need for heating to very high reaction temperatures, the need for carrying out under nitrogen, the need for adding solvents, and the need for microwavesLong irradiation and reaction time, etc. Therefore, the technical problem to be solved urgently is to search for an environment-friendly, economic and effective method for promoting the generation of propargylamine by solving the defects of the synthesis method.
In recent decades, with the introduction of green chemistry, ionic liquids have been vigorously developed as a new and green catalyst and solvent, and the research thereof has been more and more active, and the variety thereof has been increasing. Due to the rich variety and designability, people are often endowed with some special functions, and the method can be applied to many fields. Therefore, it has attracted a lot of attention in academia and industry. The ionic liquid has the characteristics of difficult volatilization, designability, high thermal stability and chemical stability, strong catalytic activity, recyclability and the like, and has wide application prospect in the synthesis and catalysis industry. The multi-component reaction puts three or more than three reaction raw materials into one reactor, directly obtains a target product with a relatively complex structure without an intermediate product separation process, and contains all the added raw material segments in the structure of the final target product. The method reduces the steps and time for synthesizing the target product, does not use expensive solvent in the reaction process, saves energy, reduces waste generation, and meets the requirement of green chemistry from the aspects of economy and environment. Therefore, the multi-component reaction system is widely concerned by researchers in organic synthesis.
Disclosure of Invention
The invention solves the technical problem of providing a cheap, easily obtained, convenient and efficient method for synthesizing propargylamine compounds by promoting multi-component reaction by using functional ionic liquid.
The invention adopts the following technical scheme for solving the technical problems, and the method for synthesizing the propargylamine compounds by using the functionalized ionic liquid to promote the multicomponent reaction is characterized by comprising the following specific processes: aldehyde compound, secondary amine compound and alkyne compound are used as reaction substratesSubstance, AgNO3The method is characterized in that the method is a catalyst, the functionalized ionic liquid is a cocatalyst and a solvent, the propargylamine compound as a target product is prepared by stirring and reacting at 70 ℃, the functionalized ionic liquid is recycled, and the reaction equation in the synthesis process is as follows:
the structural formula of the functionalized ionic liquid is as follows:
the aldehyde compound is
Wherein R is H, 4-CH3Or 4-Cl;
the secondary amine compound is as follows:
the alkyne compound is
Preferably, the aldehyde compound, the secondary amine compound, the acetylene compound and AgNO3The feeding molar ratio of the functionalized ionic liquid to the functionalized ionic liquid is 1:1.2:1.2:0.01: 1.
Preferably, the reaction time of the synthesis process is 2-12 h.
The invention relates to a method for synthesizing propargylamine compounds by using functionalized ionic liquid to promote multi-component reaction, which is characterized by comprising the following specific steps: in the reaction vessel, firstlyAdding [ TMG ]][TFA]Functionalized ionic liquids and AgNO3Sequentially adding an aldehyde compound, a secondary amine compound and an alkyne compound, stirring and reacting for 2-12h at 70 ℃, monitoring the whole reaction process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting a mixture of a reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product propargylamine compound, [ TMG (tetramethylpyrazine) compound][TFA]In the process of synthesizing the propargylamine compounds serving as target products by recycling the catalyst system of the functionalized ionic liquid, the catalyst system still maintains higher catalytic activity after repeated recycling, and the yield of the propargylamine compounds serving as the target products is still higher.
Compared with the prior art, the invention has the following advantages:
1. the functionalized ionic liquid is simple and convenient to prepare, low in price, easy to obtain and environment-friendly;
2. the functionalized ionic liquid has higher catalytic activity, and still maintains better catalytic activity after being recycled for multiple times;
3. the reaction does not need ligand and solvent, does not need the protection of inert gas, and has short reaction time;
4. the reaction system has no corrosion to equipment and no special requirement on a reaction vessel, and the operation and the post-treatment process of the catalytic system are simple.
Detailed Description
The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.
Example 1
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenylacetylene (0.72mmol) in sequence, stirring, mixing, stirring at 70 deg.C for 2 hr, monitoring by TLC for the whole experiment process until the reaction is complete, and extracting with ethyl acetate and waterTaking the mixture of the reaction system, extracting for multiple times, combining organic phases, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 90%.
Example 2
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 4-methylphenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using a silica gel column chromatography to obtain a pure target product, wherein the yield is 85%.
Example 3
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 4-methoxyphenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using a silica gel column chromatography to obtain a pure target product with the yield of 92%.
Example 4
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 4-ethyl phenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring at 70 deg.C for 2h, monitoring by TLC in the whole experimental process until the reaction is complete, extracting the mixture of the reaction system with ethyl acetate and water, mixing organic phases after multiple extractions, performing reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by silica gel column chromatography to obtain the final productThe target product was pure with a yield of 87%.
Example 5
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 4-propylphenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using a silica gel column chromatography to obtain a pure target product with the yield of 89%.
Example 6
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 4-fluoroacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 87%.
Example 7
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 4-chlorophenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product, wherein the yield is 80%.
Example 8
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionSub-liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 4-bromophenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using a silica gel column chromatography to obtain a pure target product, wherein the yield is 70%.
Example 9
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 3-ethynylpyridine (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 69%.
Example 10
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 1, 9-decadiyne (0.72mmol) in sequence, stirring and mixing uniformly, stirring at 70 ℃ for reaction for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 70%.
Example 11
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexyl formaldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenoxymethylacetylene (0.72mmol) in sequence, stirring, mixing, and stirring at 70 deg.CStirring for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, finally extracting a mixture of a reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 89%.
Example 12
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 3- (4-nitrophenoxy) -1-propyne (0.72mmol) in sequence, stirring and mixing uniformly, stirring at 70 ℃ for reaction for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product, wherein the yield is 85%.
Example 13
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and 2-naphthol propargyl ether (0.72mmol) in sequence, stirring and mixing uniformly, stirring at 70 ℃ for reaction for 2h, monitoring by TLC in the whole experimental process until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using a silica gel column chromatography to obtain a pure target product with the yield of 90%.
Example 14
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenyl [4- (2-propargyl-oxy) phenyl]Uniformly stirring and mixing 0.72mmol of ketone, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, and finally extracting the mixture of the reaction system by using ethyl acetate and water for multiple timesAfter extraction, the organic phases are combined, the organic phase is subjected to reduced pressure rotary evaporation to obtain a crude product, and the crude product is separated by silica gel column chromatography to obtain a pure target product with the yield of 80%.
Example 15
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), then adding n-hexanal (0.6mmol), pyrrolidine (0.72mmol) and phenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, then stirring and reacting at 70 ℃ for 6h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, finally extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, then carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 75%.
Example 16
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), then sequentially adding phenylpropionaldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenylacetylene (0.72mmol), stirring and mixing uniformly, then stirring and reacting at 70 ℃ for 6h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, finally extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, then decompressing and rotary-steaming the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product, wherein the yield is 85%.
Example 17
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), sequentially adding 2-ethylbutyraldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenylacetylene (0.72mmol), stirring and mixing uniformly, stirring and reacting at 70 ℃ for 6h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product, wherein the yield is 80%.
Example 18
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), then sequentially adding benzaldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenylacetylene (0.72mmol), stirring and mixing uniformly, then stirring and reacting at 70 ℃ for 12h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, finally extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, then carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product, wherein the yield is 54%.
Example 19
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), sequentially adding 4-methylbenzaldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenylacetylene (0.72mmol), stirring and mixing uniformly, stirring and reacting at 70 ℃ for 12h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product, wherein the yield is 66%.
Example 20
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), sequentially adding 4-chlorobenzaldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenylacetylene (0.72mmol), stirring and mixing uniformly, stirring at 70 ℃ for reaction for 12h, monitoring by TLC in the whole experimental process until the reaction is complete, extracting the mixture of the reaction system by ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by silica gel column chromatography to obtain a pure target product with the yield of 50%.
Example 21
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), and cyclohexylformaldehyde (C), (D)0.6mmol), piperidine (0.72mmol) and phenylacetylene (0.72mmol), stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experiment process by adopting TLC until the reaction is complete, finally extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, decompressing and rotary-steaming the organic phase to obtain a crude product, and separating the crude product by using a silica gel column chromatography to obtain a pure target product with the yield of 80%.
Example 22
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), piperidine (0.72mmol) and 4-methylphenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, then stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, finally extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product, wherein the yield is 82%.
Example 23
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), piperidine (0.72mmol) and 4-fluoroacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 72%.
Example 24
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), piperidine (0.72mmol) and 4-chlorophenylacetylene (0.72mmol) in sequence, stirring, mixing, stirring at 70 deg.C for 2 hr, monitoring by TLC for the whole experiment process until the reaction is complete, and extracting with ethyl acetate and waterAnd (3) mixing the organic phases after extracting the mixture of the reaction system for multiple times, carrying out reduced pressure rotary evaporation on the organic phases to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 60%.
Example 25
To a 10mL round bottom flask was added [ TMG ]][TFA]Functionalized ionic liquid (0.6mmol) and AgNO3(0.006mmol), adding cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol) and phenylacetylene (0.72mmol) in sequence, stirring and mixing uniformly, stirring and reacting at 70 ℃ for 2h, monitoring the whole experimental process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, decompressing and rotary-steaming the organic phase to obtain a crude product, and separating the crude product by using silica gel column chromatography to obtain a pure target product with the yield of 90%.
The example 25 is used as a probe reaction to perform an activity repeatability test on the [ TMG ] [ TFA ] functionalized ionic liquid, the [ TMG ] [ TFA ] functionalized ionic liquid is repeatedly used for 4 times, and the yield of the target product is shown in Table 1.
TABLE 1[ TMG ] [ TFA ] functionalized ionic liquids recycle
As can be seen from table 1: [ TMG][TFA]The yield is still high after the catalyst system of the functionalized ionic liquid is recycled for 4 times in the process of preparing the target product by recycling, which indicates that the yield is high [ TMG ]][TFA]Functionalized ionic liquid in catalyzing multicomponent A3The propargylamine compounds can be repeatedly recycled in the reaction synthesis process.
TABLE 2 Effect of the amount of functionalized Ionic liquid added on the promotion of the Synthesis of propargylamine by Multi-component reaction
aReaction conditions are as follows: cyclohexylformaldehyde (0.6 mmo)l), pyrrolidine (0.72mmol), phenylacetylene (0.72mmol), functionalized ionic liquid [ TMG ]][TFA](ii) a The reaction temperature is 70 ℃; the reaction time is 2 h; molar ratio ═ IL: cyclohexyl formaldehyde;bisolated yield.
TABLE 3 Effect of different functionalized ionic liquids on the promotion of the Synthesis of propargylamine by Multi-component reaction
aReaction conditions are as follows: cyclohexylformaldehyde (0.6mmol), pyrrolidine (0.72mmol), phenylacetylene (0.72mmol), AgNO3(5% mol), the reaction temperature is 70 ℃, and the reaction time is 2 h;bcyclohexyl formaldehyde: pyrrolidine: phenylacetylene: AgNO3：IL；cIsolated yield.
The foregoing embodiments illustrate the principles, principal features and advantages of the invention, and it will be understood by those skilled in the art that the invention is not limited to the foregoing embodiments, which are merely illustrative of the principles of the invention, and that various changes and modifications may be made therein without departing from the scope of the principles of the invention.
Claims (4)
1. The method for synthesizing the propargylamine compounds by using the functionalized ionic liquid to promote multi-component reaction is characterized by comprising the following specific steps: the aldehyde compound, the secondary amine compound and the alkyne compound are taken as reaction substrates, and AgNO3The method is characterized in that the method is a catalyst, the functionalized ionic liquid is a cocatalyst and a solvent, the propargylamine compound as a target product is prepared by stirring and reacting at 70 ℃, the functionalized ionic liquid is recycled, and the reaction equation in the synthesis process is as follows:
the structural formula of the functionalized ionic liquid is as follows:
the aldehyde compound is
Wherein R is H, 4-CH3Or 4-Cl;
the secondary amine compound is as follows:
the alkyne compound is
2. The method for synthesizing propargylamine compounds by using functionalized ionic liquids to promote multi-component reactions according to claim 1, wherein: the aldehyde compound, the secondary amine compound, the alkyne compound and AgNO3The feeding molar ratio of the functionalized ionic liquid to the functionalized ionic liquid is 1:1.2:1.2:0.01: 1.
3. The method for synthesizing propargylamine compounds by using functionalized ionic liquids to promote multi-component reactions according to claim 1, wherein: the reaction time of the synthesis process is 2-12 h.
4. The method for synthesizing propargylamine compounds by using functionalized ionic liquid to promote multi-component reaction according to claim 1, comprising the following specific steps: the [ TMG ] is added into the reaction vessel][TFA]Functionalized ionic liquids and AgNO3Then sequentially addAdding aldehyde compound, secondary amine compound and alkyne compound, stirring and reacting for 2-12h at 70 ℃, monitoring the whole reaction process by adopting TLC (thin layer chromatography) until the reaction is complete, extracting the mixture of the reaction system by using ethyl acetate and water, combining organic phases after multiple extractions, carrying out reduced pressure rotary evaporation on the organic phase to obtain a crude product, and separating the crude product by silica gel column chromatography to obtain a pure target product propargylamine compound, [ TMG (tetramethylbenzidine hydrochloride)][TFA]In the process of synthesizing the propargylamine compounds serving as target products by recycling the catalyst system of the functionalized ionic liquid, the catalyst system still maintains higher catalytic activity after repeated recycling, and the yield of the propargylamine compounds serving as the target products is still higher.
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| Ionic liquid assisted silver-catalyzed one-pot A3 the synthesis of propargylamines;Anlian Zhu等;《Journal of Molecular Liquids》;20190128;第279卷;第289-293页 * |
| Three-component coupling of aldehyde, alkyne, and amine catalyzed by silver in ionic liquid;Zigang Li等;《Tetrahedron Letters》;20041231;第45卷;第2444页 Scheme 1，第2445-2446页 通用反应步骤 * |
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