CN117924033A - Novel electron-deficient macrocyclic molecule, and preparation method and application thereof - Google Patents
Novel electron-deficient macrocyclic molecule, and preparation method and application thereof Download PDFInfo
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- CN117924033A CN117924033A CN202211257041.XA CN202211257041A CN117924033A CN 117924033 A CN117924033 A CN 117924033A CN 202211257041 A CN202211257041 A CN 202211257041A CN 117924033 A CN117924033 A CN 117924033A
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- 230000002950 deficient Effects 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000002775 capsule Substances 0.000 claims abstract description 25
- 238000005859 coupling reaction Methods 0.000 claims abstract description 24
- 230000003197 catalytic effect Effects 0.000 claims abstract description 17
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 13
- 238000001308 synthesis method Methods 0.000 claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 8
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 48
- 239000002243 precursor Substances 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 16
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical group FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 11
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- UHHYOKRQTQBKSB-UHFFFAOYSA-N 1,2,3,5-tetrafluorobenzene Chemical compound FC1=CC(F)=C(F)C(F)=C1 UHHYOKRQTQBKSB-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 7
- 150000001450 anions Chemical class 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 238000005893 bromination reaction Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000006722 reduction reaction Methods 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- QFWVNEBRTUUHIE-UHFFFAOYSA-N [3-(hydroxymethyl)-5-methoxyphenyl]methanol Chemical compound COC1=CC(CO)=CC(CO)=C1 QFWVNEBRTUUHIE-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 238000001179 sorption measurement Methods 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims 2
- 239000000539 dimer Substances 0.000 abstract description 12
- 230000008878 coupling Effects 0.000 abstract description 4
- 238000010168 coupling process Methods 0.000 abstract description 4
- 150000002430 hydrocarbons Chemical class 0.000 abstract description 4
- 238000001338 self-assembly Methods 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 239000004215 Carbon black (E152) Substances 0.000 abstract description 2
- 238000010499 C–H functionalization reaction Methods 0.000 abstract description 2
- 229930195733 hydrocarbon Natural products 0.000 abstract description 2
- 239000001257 hydrogen Substances 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 239000000203 mixture Substances 0.000 description 9
- 101710121996 Hexon protein p72 Proteins 0.000 description 7
- 101710125418 Major capsid protein Proteins 0.000 description 7
- 150000002678 macrocyclic compounds Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 238000000914 diffusion-ordered spectroscopy Methods 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- OXHOPZLBSSTTBU-UHFFFAOYSA-N 1,3-bis(bromomethyl)benzene Chemical compound BrCC1=CC=CC(CBr)=C1 OXHOPZLBSSTTBU-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 239000002071 nanotube Substances 0.000 description 1
- 239000002070 nanowire Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940079877 pyrogallol Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/24—Halogenated derivatives
- C07C39/42—Halogenated derivatives containing six-membered aromatic rings and other rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/57—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings being part of condensed ring systems of the carbon skeleton
- C07C211/61—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings being part of condensed ring systems of the carbon skeleton with at least one of the condensed ring systems formed by three or more rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/90—Ring systems containing bridged rings containing more than four rings
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a novel electron-deficient macrocyclic molecule, and a synthesis method and application thereof, wherein the structure of the novel electron-deficient macrocyclic molecule is shown as any one of a, b and C, the synthesis method mainly utilizes palladium catalytic coupling to realize C-H activation/coupling of polyfluoroaromatic hydrocarbon, and adopts a strategy of segment synthesis, thereby synthesizing polyfluoro [1 4 ] m-ring with different functional groups. In addition, the novel electron-deficient macrocyclic molecule with the structure shown as b or c can also form a dimer artificial capsule through hydrogen bonding, expands the novel electron-deficient macrocyclic molecule type for constructing the artificial capsule, and has important significance in the field of supermolecule self-assembly.
Description
Technical Field
The invention relates to the field of supermolecule chemical synthesis, in particular to a novel electron-deficient macrocyclic molecule, and a preparation method and application thereof.
Background
The artificial capsule formed by non-covalent interaction has great interest to scientists because of the large internal cavity which can be applied to the field of supermolecules such as identification, encapsulation and separation, and the construction of the artificial capsule becomes an important research direction in the field of supermolecule self-assembly.
The ring-guava-type macrocyclic compound with the cavity has unique advantages in terms of assembly materials due to unique chemical structures and properties, for example, the ring-guava-type macrocyclic compound can self-assemble to obtain micro-nano structures (nanowires, nanotubes, vesicles and the like) with different skeletons by utilizing various non-covalent bond effects such as pi-pi stacking, van der Waals force, hydrophobic effect and the like. Among them, the [1 n ] meta-ring of cone conformation ([ 1 n ] MCPs) is of great interest in constructing artificial capsules, and the [1 n ] meta-ring mainly comprises macrocycles such as calix [ n ] arene, resorcinol [ n ] arene and pyrogallol [ n ] arene, and at present, the macrocycles are basically electron-rich macrocycles with electron-pushing groups obtained through Friedel-Crafts reaction. The synthesis of electron-deficient [1 n ] MCP is only obtained by post-modification on the basis of the above, and is not used in the construction of artificial capsules.
Therefore, a new way for directly synthesizing electron-deficient [1 n ] MCP is developed, a series of novel electron-deficient [1n ] MCP is provided, and the method has important research significance in the field of supermolecule self-assembly.
Disclosure of Invention
In view of the above, the present invention aims to develop a new way for directly synthesizing electron-deficient [1 n ] MCP, and simultaneously provide a series of novel electron-deficient [1 n ] MCP, so as to lay a foundation for developing artificial capsules with novel properties.
In order to achieve the above purpose, the invention adopts the following technical scheme:
In a first aspect, the present invention provides a novel electron-deficient macrocyclic molecule having the structure shown in a:
Wherein Q 1 is NR 1H,OR2 or R 3;R1 or R 2 is any one of C 1-10 alkyl, C 1-10 acyl and C 6-20 aryl; r 3 is any one of H, C 1-10 alkyl, C 1-10 acyl and C 6-20 aryl.
The invention also provides a novel electron-deficient macrocyclic molecule, the structure of which is shown as b or c:
in a second aspect, the present invention provides a method for synthesizing the novel electron-deficient macrocyclic molecule, wherein the method for synthesizing the novel electron-deficient macrocyclic molecule with a structure a comprises the following steps:
the cyclized precursor compound and 1,2,3, 5-tetrafluorobenzene are subjected to one-time palladium catalytic coupling reaction to obtain the cyclized precursor compound with two fluorobenzene units,
Wherein the structure of the cyclic precursor compound is shown as d:
And carrying out secondary palladium catalytic coupling reaction on the cyclization precursor compound with two fluorobenzene units and the cyclization precursor compound to obtain the novel electron-deficient macrocyclic molecule.
The synthesis method of the novel electron-deficient macrocyclic molecule with the structure b comprises the following steps:
the cyclized precursor compound and 1,2,3, 5-tetrafluorobenzene are subjected to one-time palladium catalytic coupling reaction to obtain the cyclized precursor compound with two fluorobenzene units,
Wherein the precursor compound has a structure as shown in e:
and (3) carrying out secondary palladium catalytic coupling reaction on the ring-forming precursor compound with the two fluorobenzene units and the ring-forming precursor compound, and then carrying out deprotection reaction to remove methyl protecting groups.
The synthesis method of the novel electron-deficient macrocyclic molecule with the structure of c comprises the following steps:
the cyclized precursor compound and 1,2,3, 5-tetrafluorobenzene are subjected to one-time palladium catalytic coupling reaction to obtain the cyclized precursor compound with two fluorobenzene units,
Wherein the precursor compound has a structure as shown in f:
and (3) carrying out a secondary palladium catalytic coupling reaction on the ring-forming precursor compound with the two fluorobenzene units and the ring-forming precursor compound, and then carrying out a deprotection reaction to remove acetyl protecting groups.
Further, in the method for synthesizing the novel electron-deficient macrocyclic molecule with the structure of any one of a-c, the step of adding pivalic acid is further included before the primary palladium catalytic coupling reaction or the secondary palladium catalytic coupling reaction is carried out; the molar ratio of the pivalic acid to the cyclic precursor compound is 2-3:1. Wherein, in the above synthesis method, the yield of the reactant can be further improved by adding pivalic acid.
In the method for synthesizing a novel electron-deficient macrocyclic molecule having the structure of any one of a to c, the catalyst for the primary palladium-catalyzed coupling reaction or the secondary palladium-catalyzed coupling reaction may be selected from palladium trifluoroacetate, palladium chloride, bis (dibenzylideneacetone) palladium, palladium acetate, and the like, and preferably palladium acetate.
Illustratively, in the method for synthesizing the novel electron-deficient macrocyclic molecule of any one of structures a-c, the primary palladium-catalyzed coupling reaction is carried out by stirring at 100-150 ℃ for 10-15 hours; the secondary palladium catalytic coupling reaction is carried out by stirring for 20-30 hours at 100-150 ℃.
Further, in the synthesis method of the novel electron-deficient macrocyclic molecule with the structure of any one of a-c, the molar ratio of the cyclic precursor compound to 1,2,3, 5-tetrafluorobenzene is 1-3:1-10;
the molar ratio of the cyclic precursor compound having two fluorobenzene units to the cyclic precursor compound is 1-2:1.
Further, in the synthesis method of the novel electron-deficient macrocyclic molecule having the structure as described in b, the preparation step of the precursor compound comprises: taking 5-methoxy-1, 3-phthalic acid as a starting material, carrying out a reduction reaction to obtain 5-methoxy-1, 3-benzenedimethanol, and then carrying out a bromination reaction to obtain the catalyst;
The precursor compound of the present invention can be purchased directly or synthesized according to the existing method, and in order to save the cost, the present invention uses cheap and easily available 5-methoxy-1, 3-phthalic acid as a starting material, and obtains the 1, 3-di (bromomethyl) benzene with various functional groups at the 5-position by using a reduction and re-bromination strategy, and it can be understood that the preparation steps of the precursor compound are similar to the above in the synthesis method of the novel electron-deficient macrocyclic molecule with the structure as described in a or c.
In a third aspect, the present invention provides a dimer artificial capsule, which is prepared from the novel electron-deficient macrocyclic molecule with the structure shown in b or c under the action of anions.
Further, the anion is any one of F-、Cl-、Br-、I-、NO3 -、OAc-、BF4 -、PF6 -.
Furthermore, the invention also provides application of the dimer artificial capsule in the fields of adsorption, separation, catalysis, fluorescent identification and the like.
The beneficial effects of the invention are that
The synthesis method of the novel electron-deficient macrocyclic molecule mainly utilizes palladium catalytic coupling conditions to realize C-H activation/coupling of polyfluoroaromatic hydrocarbon, adopts a fragment synthesis strategy to synthesize polyfluoro [1 4 ] meta-cyclic double with different functional groups, has strong universality, and can be used for synthesizing a series of electron-deficient [1 4 ] MCP with different structures.
The multi-fluoro [1 4 ] meta-ring containing hydroxyl or amino provided by the invention forms a dimer artificial capsule through hydrogen bond combination under the induction of anions, further expands the types of novel macrocyclic compounds which can be used for constructing the artificial capsule, and has great research significance for the field of supermolecule self-assembly.
Drawings
FIG. 1 shows 1 H NMR spectrum of compound 4 obtained in example 1.
FIG. 2 shows 1 H NMR spectrum of compound 5 obtained in example 1.
FIG. 3 shows 1 H NMR spectra of novel electron-deficient macrocyclic molecules prepared in example 1.
FIG. 4 shows a schematic of the preparation of dimer artificial capsules in example 3.
Detailed Description
Term interpretation and description
Unless otherwise indicated, the radical and term definitions recited in the description and claims of the present application, including as examples, preferably, the definition of a specific compound in an embodiment, etc., may be arbitrarily combined and coupled with each other. Such combinations and combinations of radical definitions and compound structures should fall within the scope of the application.
Unless otherwise indicated, the superscript of a group in the present application is a group label, and the subscript generally refers to the number of the group.
"C 1-10 alkyl" as used herein alone or as a suffix or prefix, means branched and straight chain saturated aliphatic hydrocarbon radicals having from 1 to 10 carbon atoms (or a specific number of carbon atoms if provided), such as "C 1-6 alkyl". The "C 1-4 alkyl" represents an alkyl group having 1,2, 3, 4, 5, 6 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-ethylpropyl, 1, 2-dimethylpropyl, neopentyl, 1-dimethylpropyl, and the like, as well as all isomeric forms of the foregoing groups.
The term "C 6-20 aryl" is understood to mean a monovalent aromatic or partially aromatic monocyclic, bicyclic or tricyclic hydrocarbon ring having 6 to 20 carbon atoms, for example "C 6-14 aryl". The term "C 6-14 aryl" is understood to mean a monovalent aromatic or partially aromatic mono-, bi-or tricyclic hydrocarbon ring having 6, 7, 8, 9, 10, 11, 12, 13 or 14 carbon atoms ("C 6-14 aryl"), in particular a ring having 6 carbon atoms ("C 6 aryl"), for example phenyl; a ring having 7 carbon atoms ("C 7 aryl"), such as benzyl; or biphenyl, or a ring having 9 carbon atoms ("C 9 aryl"), such as indanyl or indenyl, or a ring having 10 carbon atoms ("C 10 aryl"), such as tetrahydronaphthyl, dihydronaphthyl or naphthyl, or a ring having 13 carbon atoms ("C 13 aryl"), such as fluorenyl, or a ring having 14 carbon atoms ("C 14 aryl"), such as anthracenyl.
The present invention is described in detail below by way of examples, which are necessary to be pointed out herein for further illustration only and are not to be construed as limiting the scope of the invention, as many insubstantial modifications and adaptations can be made by those skilled in the art in light of the foregoing disclosure. Embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Example 1: provides a novel electron-deficient macrocyclic molecular compound
Synthesis of precursor compounds:
1 (1.96 g,10.0mmol,1.0 equiv) and 50ml of anhydrous THF are added to a dry 250ml eggplant-shaped bottle in air. A1 mol/L solution of LAH in THF (65 ml,65.0mmol,6.5 equiv) was slowly added dropwise to the mixture at 0deg.C and transferred to 25℃for 12h.3mL of deionized water and 3mL of 15wt% NaOH aqueous solution were slowly added dropwise to the reaction solution at 0℃respectively, and after transferring to 25℃9mL of deionized water was added dropwise thereto, followed by stirring for 15min. Anhydrous sodium sulfate was added to the reaction solution, dried, filtered through a buchner funnel, and the solvent was removed under reduced pressure, and the obtained colorless liquid was separated by column chromatography to obtain colorless liquid 2 (1.40 g, yield) 82％).1H NMR(400MHz,Chloroform-d)δ6.95(s,1H),6.86(s,2H),4.68(d,J＝6.0Hz,4H),3.83(s,3H),1.67(t,J＝6.0Hz,2H).
2 (1.40 G,8.32mmol,1.00 equiv) and 40ml of dry diethyl ether were added to a dry 250ml eggplant-shaped bottle in air. Phosphorus tribromide (2.40 mL,25.5mmol,3.06 equiv) was slowly added dropwise to the mixture at 0deg.C, and transferred to reaction at 25deg.C for 12h. Deionized water was slowly added dropwise to the reaction solution at 0℃and the aqueous phase was extracted three times with methylene chloride. The organic phases were combined and dried with anhydrous sodium sulfate. The solvent was removed by rotary evaporation, and the obtained transparent yellow oily substance was separated by column chromatography to give pale yellow solid 3 as a precursor compound (1.95 g, yield 80%). 1 H NMR (400 MHz, chloro-d) delta 7.00 (s, 1H), 6.86 (s, 2H), 4.44 (s, 4H), 3.82 (s, 3H).
Synthesizing a novel electron-deficient macrocyclic molecule:
Pd (OAc) 2 (135 mg,0.60mmol,20 mol%), L (244 mg,0.72mmol,24 mol%), anhydrous Cs 2CO3 (4.70 g,14.4mmol,4.80 equiv), and anhydrous toluene (180 ml) were taken in a glove box filled with nitrogen gas. The mixture was stirred in a glove box for 15min.1,2,3, 5-tetrafluorobenzene (2.30 g,15.3mmol,5.10 equiv), 3 (882 mg,3.00mmol,1.00 equiv) and pivalic acid (730 mg,7.20mmol,2.40 equiv) were added sequentially to the mixture. The vessel was capped, taken out of the glove box, and stirred at 120 ℃ for 12 hours. After the mixture was cooled to room temperature, it was filtered through celite and ethyl acetate, and the solvent was removed under reduced pressure. Purification using silica gel column chromatography gave 4 (236 mg, 18% yield, 1 H NMR spectrum as shown in FIG. 1) as a white solid, 1 H NMR (400 MHz, chloroform-d) delta 6.76-6.73 (m, 3H), 6.60 (s, 2H), 3.90 (s, 4H), 3.74 (s, 3H).
Pd (OAc) 2 (22.4 mg,0.10mmol,20 mol%), phJohnPhos (40.6 mg,0.12mmol,24 mol%), anhydrous Cs 2CO3 (780 mg,2.4mmol,4.80 equiv), and anhydrous toluene (30 ml) were taken in a glove box filled with nitrogen gas. The mixture was stirred in a glove box for 15min. 3 (147 mg,0.50mmol,1.00 equiv), 4 (216 mg,0.50mmol,1.00 equiv) and pivalic acid (123 mg,1.20mmol,2.40 equiv) were then added sequentially to the mixture. The vessel was capped, taken out of the glove box, and stirred at 120 ℃ for 24 hours. After the mixture was cooled to room temperature, it was filtered through celite and ethyl acetate, and the solvent was removed under reduced pressure. Purification by silica gel column chromatography gave 5 (31 mg, 11% yield, 1 H NMR spectrum shown in fig. 2) as a white solid. 1 H NMR (400 MHz, chloro-d) delta 6.78 (s, 2H), 6.74 (s, 4H), 3.88 (s, 8H), 3.77 (s, 6H).
In a glove box filled with nitrogen, 5 (40.0 mg,0.071mmol,1.00 equiv) and anhydrous CH 2Cl2 (10 mL) were added to a 40mL glass bottle. And then sealed with a teflon septum cap and transferred out of the glove box. BBr 3 (30 μl,0.31mmol,4.37 equiv) was added to the mixture by syringe at 0deg.C. The reaction mixture was stirred at 0℃for 20 min and then at 25℃for 12 h. The reaction was quenched with deionized water and diluted with ethyl acetate. The aqueous phase was extracted 3 times with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The white solid 6 is obtained by column chromatography and centrifugal separation, namely the novel electron-deficient macrocyclic molecule (36 mg, yield 95%, 1 H NMR spectrum is shown in figure 3). 1 H NMR (400 MHz, chloro-d) delta 8.38 (s, 2H), 6.73 (s, 4H), 6.45 (s, 2H), 3.90 (s, 8H).
Example 2 provides a dimer artificial capsule
The synthesis steps comprise: in air, 6 and n-BuN 4 Cl of example 1 were each prepared as a 20mM stock solution. Then, 250. Mu.L of the solution was mixed together to form a mixed solution of 6 and n-BuN 4 Cl in an equimolar ratio (10 mM), and the mixed solution was sonicated to obtain a dimer artificial capsule ([ 6] 2[Cl–]2) solution.
The dimer artificial capsule was detected by mass spectrometry and the result showed ：HRMS(ESI):[6]2[Cl–]2[n-Bu4N+]C72H68F16Cl2NO4, theoretical value 1384.4275, measured value 1384.4339.
The dimer artificial capsule is detected by using two-dimensional nuclear magnetism, and the result shows that: DOSY (600 mhz, chloroform-D) diffusion coefficient d=1.77×10 -9 of 6 before mixing, diffusion coefficient d=1.32×10 -9 of 6 after mixing, i.e. the hydrodynamic diameter increases from 0.8nm to 1.1nm.
Example 3 provides a dimer artificial capsule
The synthesis steps comprise: diethyl ether was diffused into a solution of example 1 in acetone/acetonitrile (1:1) at 25℃and excess Et 4 NCl to give a chloride-induced dimeric artificial capsule single crystal (see FIG. 4 for schematic).
The dimer artificial capsule size in the crystal matched the diameter values based on DOSY data measured in example 2. The width of the crystalline dimer artificial capsule is(Distance between chlorides), depth/>(Distance between fluorine atoms at the upper edge of the same macrocycle) of height/>(Distance between top and bottom fluorine atoms). The capsules adopt two orthogonal orientations in the crystal structure, and the capsules are piled up through pi-pi interaction.
It should be understood that the foregoing examples of the present invention are provided merely for clearly illustrating the present invention and are not intended to limit the embodiments of the present invention, and that various other changes and modifications may be made therein by one skilled in the art without departing from the spirit and scope of the present invention as defined by the appended claims.
Claims (10)
1. The novel electron-deficient macrocyclic molecule is characterized in that the structure is shown as a:
Wherein Q 1 is NR 1H,OR2 or R 3;R1 or R 2 is any one of C 1-10 alkyl, C 1-10 acyl and C 6-20 aryl; r 3 is any one of H, C 1-10 alkyl, C 1-10 acyl and C 6-20 aryl.
2. A novel electron-deficient macrocyclic molecule, characterized in that the structure is as shown in b or c:
3. A method of synthesizing a novel electron deficient macrocyclic molecule as claimed in claim 1, comprising the steps of:
the cyclized precursor compound and 1,2,3, 5-tetrafluorobenzene are subjected to one-time palladium catalytic coupling reaction to obtain the cyclized precursor compound with two fluorobenzene units,
Wherein the structure of the cyclic precursor compound is shown as d:
And carrying out secondary palladium catalytic coupling reaction on the cyclization precursor compound with two fluorobenzene units and the cyclization precursor compound to obtain the novel electron-deficient macrocyclic molecule.
4. A method of synthesizing a novel electron deficient macrocyclic molecule as claimed in claim 2, wherein the method of synthesizing a novel electron deficient macrocyclic molecule of structure b comprises the steps of:
the cyclized precursor compound and 1,2,3, 5-tetrafluorobenzene are subjected to one-time palladium catalytic coupling reaction to obtain the cyclized precursor compound with two fluorobenzene units,
Wherein the precursor compound has a structure as shown in e:
carrying out secondary palladium catalytic coupling reaction on the ring-forming precursor compound with two fluorobenzene units and the ring-forming precursor compound, and then carrying out deprotection reaction to remove methyl protecting groups to obtain the catalyst;
the synthesis method of the novel electron-deficient macrocyclic molecule with the structure of c comprises the following steps:
the cyclized precursor compound and 1,2,3, 5-tetrafluorobenzene are subjected to one-time palladium catalytic coupling reaction to obtain the cyclized precursor compound with two fluorobenzene units,
Wherein the precursor compound has a structure as shown in f:
and (3) carrying out a secondary palladium catalytic coupling reaction on the ring-forming precursor compound with the two fluorobenzene units and the ring-forming precursor compound, and then carrying out a deprotection reaction to remove acetyl protecting groups.
5. The synthetic method according to claim 3 or 4, further comprising the step of adding pivalic acid before the primary palladium-catalyzed coupling reaction or the secondary palladium-catalyzed coupling reaction; wherein the molar ratio of the pivalic acid to the cyclic precursor compound is 2-3:1.
6. The synthetic method according to claim 3 or 4, wherein the molar ratio of the cyclic precursor compound to 1,2,3, 5-tetrafluorobenzene is 1-3:1-10;
the molar ratio of the cyclic precursor compound having two fluorobenzene units to the cyclic precursor compound is 1-2:1.
7. The method of synthesis according to claim 4, wherein the step of preparing a precursor compound of structure e comprises: taking 5-methoxy-1, 3-phthalic acid as a starting material, carrying out a reduction reaction to obtain 5-methoxy-1, 3-benzenedimethanol, and then carrying out a bromination reaction to obtain the catalyst;
8. A dimeric artificial capsule prepared from the novel electron-deficient macrocyclic molecule of claim 2 under the action of anions.
9. The dimeric artificial capsule of claim 8, wherein the anion is any one of F-、Cl-、Br-、I-、NO3 -、OAc-、BF4 -、PF6 -.
10. Use of a dimeric artificial capsule according to any one of claims 8-9 in the fields of adsorption, separation, catalysis, fluorescent recognition.
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