CN109053572B - 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound and preparation method and application thereof - Google Patents
4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound and preparation method and application thereof Download PDFInfo
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- CN109053572B CN109053572B CN201811130987.3A CN201811130987A CN109053572B CN 109053572 B CN109053572 B CN 109053572B CN 201811130987 A CN201811130987 A CN 201811130987A CN 109053572 B CN109053572 B CN 109053572B
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- Prior art keywords
- trifluoromethyl
- bromo
- naphthalimide
- naphthalimide compound
- compound
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- 238000002360 preparation method Methods 0.000 title abstract description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 150000007960 acetonitrile Chemical class 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 238000005893 bromination reaction Methods 0.000 claims abstract description 3
- -1 m-methoxyphenyl Chemical group 0.000 claims description 24
- 239000003054 catalyst Substances 0.000 claims description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 6
- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 4
- 230000009471 action Effects 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 238000001308 synthesis method Methods 0.000 claims description 4
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- APBIDAXJCGEEIS-UHFFFAOYSA-N 6-bromobenzo[de]isoquinoline-1,3-dione Chemical compound O=C1NC(=O)C2=CC=CC3=C2C1=CC=C3Br APBIDAXJCGEEIS-UHFFFAOYSA-N 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 2
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical group [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 abstract description 28
- 239000000523 sample Substances 0.000 abstract description 10
- 239000007850 fluorescent dye Substances 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 238000006692 trifluoromethylation reaction Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 22
- 239000000047 product Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 10
- 239000013078 crystal Substances 0.000 description 9
- 239000011259 mixed solution Substances 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- XJHABGPPCLHLLV-UHFFFAOYSA-N benzo[de]isoquinoline-1,3-dione Chemical class C1=CC(C(=O)NC2=O)=C3C2=CC=CC3=C1 XJHABGPPCLHLLV-UHFFFAOYSA-N 0.000 description 7
- 150000001450 anions Chemical class 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000004611 spectroscopical analysis Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- UKVQBONVSSLJBB-UHFFFAOYSA-N 2-pyridin-2-ylacetonitrile Chemical compound N#CCC1=CC=CC=N1 UKVQBONVSSLJBB-UHFFFAOYSA-N 0.000 description 3
- 229910014263 BrF3 Inorganic materials 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000005870 benzindolyl group Chemical group 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- DTUOTSLAFJCQHN-UHFFFAOYSA-N 4-bromo-1,8-naphthalic anhydride Chemical compound O=C1OC(=O)C2=CC=CC3=C2C1=CC=C3Br DTUOTSLAFJCQHN-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000228 antimanic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229940006460 bromide ion Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006081 fluorescent whitening agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- DTMHTVJOHYTUHE-UHFFFAOYSA-N thiocyanogen Chemical compound N#CSSC#N DTMHTVJOHYTUHE-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N21/643—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" non-biological material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
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- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
Abstract
The invention discloses a 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound, and a preparation method and application thereof. The structural formula of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound is shown as follows:
wherein: r1Is C1‑C10A linear or branched alkyl group; r2Is phenyl, naphthyl, substituted phenyl, 5-or 6-membered heteroaryl or benzo 5-or 6-membered heteroaryl. The invention uses N-R1The (E) -1, 8-naphthalimide compound is used as an initial raw material, and N-R is obtained after trifluoromethylation and bromination1-4-trifluoromethyl-6-bromo-1, 8-naphthalimide, which is reacted with R2The substituted acetonitrile is reacted under the catalysis of alkali to obtain the product. The 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound prepared by the invention can be used for detecting the ratio of cyanide ionsColor probe and fluorescent probe applications.
Description
Technical Field
The invention relates to a 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound, a preparation method and application thereof, and belongs to the technical field of organic photoelectric or fluorescent probes.
Background
Anion recognition, particularly cyanide ion recognition, has important applications in the fields of life, medicine, environment and the like. The cyanide ions with extremely high toxicity have very serious harm to the environment, the cyanide ions absorbed by drinking water can cause serious harm to human bodies, and meanwhile, the detection of the cyanide ions with high toxicity has important application in the environment and biological systems.
The color chemical sensor can convert information identified by molecules into color signals which are easy to perceive, has the characteristics of sensitivity, rapidness, low detection limit and the like, and can be widely applied to the relevant fields of biochemistry, cell biology, analytical chemistry and the like.
The naphthalimide compound is a very excellent chromophore, and can be used as a fluorescent whitening agent and a fluorescent dye and widely applied to the fields of photoelectric sensitive materials, fluorescent probes and the like due to the characteristics of strong fluorescence, bright color, good thermal stability, high fluorescence quantum yield and the like. The naphthalimide derivatives reported at present are mainly derived by amidation of anhydride heads of naphthalimide, and some naphthalimide compounds containing groups such as NH or OH at the 4-position are derived by some substitution reactions of bromine atoms of 4-bromine-1, 8-naphthalimide and corresponding substituted amino or hydroxyl functional groups.
In view of the above, many reports have not been made on the naphthalimide derivative having a CH group at the 2-position, and particularly, no report has been made on the naphthalimide derivative having an arylacetonitrile group at the 2-position. It is necessary to obtain 2-position arylacetonitrile-1, 8-naphthalimide derivative, because the derivative can be used as a color chemical sensor for anion recognition.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide a 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound, and a preparation method and application thereof. The invention enriches the structural library of the 1, 8-naphthalimide compound, and the preparation method has the advantages of mild reaction conditions, no side reaction, high reaction yield and the like; the 2-arylacetonitrile-1, 8-naphthalimide compound can be used as a color probe and a fluorescent probe for detecting cyanide ions.
The technical scheme provided by the invention is specifically introduced as follows.
A4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound has a structural formula shown in formula (I):
wherein: r1Is straight-chain or branched C1-C10An alkyl group; r2Is phenyl, naphthyl, substituted phenyl, 5-or 6-membered heteroaryl or benzo 5-or 6-membered heteroaryl; the 5-or 6-membered heteroaryl has N, O heteroatoms or N and O, and the number of heteroatoms is 1 or 2; the substituted phenyl represents C in which 1 or 2 hydrogen atoms on the phenyl ring are substituted by a straight chain or a branched chain1-C4Alkyl, straight or branched C1-C4Alkoxy or halogen substituted phenyl.
Preferably, R1Is C1-C6A linear alkyl group.
Preferably, the substituted phenyl group is p-fluorophenyl, o-chlorophenyl, o-bromophenyl, p-methoxyphenyl, m-methoxyphenyl, or m-bromophenyl.
Preferably, the 5-membered heteroaryl is furyl, pyrrolyl or imidazolyl.
Preferably, the 6-membered heteroaryl is pyridyl or pyrimidinyl.
Preferably, the benzo 5-membered heteroaryl is benzofuranyl, benzimidazolyl, benzo BOC protected indolyl or benzindolyl.
Preferably, the benzo 6-membered heteroaryl is a benzopyridyl or benzopyrimidinyl.
The invention also provides a synthetic method of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound, wherein the synthetic route is as follows:
the method comprises the following steps:
(1) with N-R14-bromo-1, 8-naphthalimide as a starting material, and reacting N-R1Carrying out substitution reaction on 4-bromo-1, 8-naphthalimide and methyl fluorosulfonyl difluoroacetate in a solvent at the temperature of 85-90 ℃ under the catalytic action of a catalyst cuprous iodide to obtain a 4-trifluoromethyl-1, 8-naphthalimide compound;
(2) carrying out bromination reaction on the obtained 4-trifluoromethyl-1, 8-naphthalimide compound and N-bromosuccinimide NBS in concentrated sulfuric acid under the condition of 0-room temperature to obtain a 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound;
(3) 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound and R at room temperature2The substituted acetonitrile reacts in an organic solvent under the action of an alkali catalyst to obtain the 4-trifluoromethyl-6-bromine-2-substituted acetonitrile-1, 8-naphthalimide compound.
In the step (1), the solvent is N, N-dimethylformamide or N-R1The mass-volume ratio of the-4-bromo-1, 8-naphthalimide to the organic solvent is 1:20-1:30 g/mL; N-R1The molar ratio of the (4-bromo-1, 8) -naphthalimide to the methyl fluorosulfonyl difluoroacetate to the cuprous iodide serving as a catalyst is 1 (2.1-2.3): (1.5-2).
In the step (2), the mass-to-volume ratio of the 4-trifluoromethyl-1, 8-naphthalimide compound to the concentrated sulfuric acid is 1:20-1:30g/mL, and the molar ratio of the 4-trifluoromethyl-1, 8-naphthalimide compound to the N-bromosuccinimide NBS is 1: 1.0-1: 1.1.
In the step (3), the organic solvent is toluene or tetrahydrofuran, and the base catalyst is sodium hydrogen or sodium methoxide; the mass-volume ratio of the 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound to the organic solvent is 1:50-1:60g/mL, the 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound and R2The molar ratio of substituted acetonitrile to base catalyst is 1: (1.1-1.4) and (5.4-6).
The invention further provides application of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound as a color probe or a fluorescent probe for selectively detecting cyanide ions.
The invention further provides an application of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound in detecting cyanide ions by ultraviolet spectrum or naked eyes.
The invention further provides an application of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound in the aspect of being used as a colorimetric reagent for detecting cyanide ions.
Compared with the prior art, the invention has the beneficial effects that:
the synthesis method of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound takes the 4-bromo-1, 8-naphthalimide and the substituted acetonitrile as raw materials, and the raw materials belong to raw materials which are easily obtained by industry, so the synthesis method has the characteristic of low production cost.
Furthermore, the synthetic method of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound has the advantages of simple synthetic route, easily controlled process, high yield of final products and the like because the process only relates to conventional substitution reaction.
Furthermore, because the 1, 8-naphthalimide compounds are widely applied in the fields of dyes, medicines and the like and the aryl acetonitrile groups can effectively transform functional groups, the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compounds obtained by the invention can be transformed by the functional groups, and further can be developed into intermediates for synthesizing antidepressants, anti-tumor drugs, antimanic drugs and complex dye molecules.
Furthermore, the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound of the invention has the function of identifying anions, particularly has ultrahigh sensitivity and selectivity on cyanide ions, and the detection limit of the 4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide compound obtained in example 4 on cyanide ions in 90% acetonitrile solution is 0.815 mu M, so that the compound can be used as a high-selectivity and high-sensitivity detection probe for cyanide ions. Particularly, the probe can provide naked eye detection of 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound solution from colorless to blue, so that the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound can be used as a detection reagent for detecting cyanide ions and further be practically applied.
Drawings
FIG. 1, application example 1, 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-
The naphthalimides are respectively reacted with Cyanide (CN)-) Ion, fluorine ion, dihydrogen phosphate ion, chlorine ion, bromine ion, iodine ion, hydrogen sulfate ion, nitrate ion, tetrafluoroborate ion, perchlorate ion, sulfide ion, and thiocyanate ion3CN/H2O9/1, v/v).
FIG. 2 shows the reaction of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound obtained in example 4 with CN in application example 2-Ion continuous titration to obtain a mixed solution of 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide Compounds (CH)3CN/H2O-9/1, v/v).
FIG. 3 shows the reaction of the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound obtained in example 4 with Cyanide (CN)-) Ions, fluoride ions, dihydrogen phosphate ions, chloride ions, bromide ions, iodide ions, hydrogen sulfate ions, nitrate ions, tetrafluoroborate ions, perchlorate ions, sulfide ions, thiocyanogen ionsIn a mixed solvent (CH) having root action3CN/H2O9/1, v/v).
Detailed Description
The invention is further illustrated, but not limited, by the following specific examples in connection with the accompanying drawings.
The names, specifications and manufacturer information of the various raw materials used in the examples of the present invention are shown in Table 1.
TABLE 1
| Name of raw material | Specification of | Manufacturer information |
| Cuprous iodide | 100g | SHANGHAI TITAN TECHNOLOGY Co.,Ltd. |
| 4-bromo-1, 8-naphthalic anhydride | 500g | Shanghaineri Fine chemicals Co., Ltd |
| Benzyl cyanide | 100ml | SINOPHARM CHEMICAL REAGENT Co.,Ltd. |
| Pyridine-2-acetonitrile | 25g | SHANGHAI TITAN TECHNOLOGY Co.,Ltd. |
| Fluorosulfonyl difluoroacetic acid methyl ester | 25g | SHANGHAI TITAN TECHNOLOGY Co.,Ltd. |
| Alkali catalyst NaH | 60w％、250g | SHANGHAI TITAN TECHNOLOGY Co.,Ltd. |
| N, N-dimethylformamide | AR (Shanghai test), 500ml | SINOPHARM CHEMICAL REAGENT Co.,Ltd. |
| Acetonitrile | AR (Shanghai test), 500ml | SINOPHARM CHEMICAL REAGENT Co.,Ltd. |
| Methanol | AR (Shanghai test), 500ml | SINOPHARM CHEMICAL REAGENT Co.,Ltd. |
| Concentrated sulfuric acid | AR (Shanghai test), 500ml | SINOPHARM CHEMICAL REAGENT Co.,Ltd. |
| Tetrahydrofuran (THF) | AR (Shanghai test), 500ml | SINOPHARM CHEMICAL REAGENT Co.,Ltd. |
The silica gel column used in each example of the present invention was a silica gel column having a length of 45cm and a diameter of 45mm, which was manufactured by Beijing Bihua glass instruments Co., Ltd.
Example 1
A4-trifluoromethyl-1, 8-naphthalimide compound has a structural formula shown as follows:
wherein R is1Is n-butyl;
the reaction equation of the synthesis process is as follows:
the preparation method comprises the following specific steps:
adding 2.0g (6.04mmol) of N-N-butyl-4-bromo-1, 8-naphthalimide and 1.72g (9.04mmol) of CuI iodide into a 50ml single-neck bottle, adding 40ml of organic solvent DMF, and finally adding 2.54g (13.24mmol) of methyl fluorosulfonyl difluoroacetate, and reacting for 20h at 85-90 ℃ under magnetic stirring to obtain the 4-trifluoromethyl-1, 8-naphthalimide compound;
after the reaction is finished, filtering to remove insoluble substances, adding ethyl acetate into the filtrate, washing the organic phase with a large amount of water and saturated saline solution for three times, drying with anhydrous sodium sulfate, performing chromatography treatment by a silica gel column, eluting with an eluent, wherein the eluent is a mixed solution of petroleum ether (boiling range: 60-90 ℃) and ethyl acetate in a volume ratio of 100:1, and collecting RfThe peak was observed at 0.5 (volume ratio of petroleum ether to ethyl acetate: 5: 1) to give 1.16g of a white solid as a powdery product with a yield of 60.1%.
The white solid powder obtained above was subjected to hydrogen spectroscopy by means of a nuclear magnetic resonance instrument (Bruker AVANCE III 500MHz) and the data are as follows:
1H NMR(500MHz,CDCl3),δ8.70(d,J＝7.0Hz,1H),8.65(d,J＝7.5Hz,1H),8.52(d,J＝8.5Hz,1H),8.12(d,J＝7.5Hz,1H),7.95–7.85(m,1H),4.19(t,J＝7.5Hz,2H),1.78–1.66(m,2H),1.52–1.39(m,2H),0.98(t,J＝7.5Hz,3H)；
the white solid powder obtained above was subjected to carbon spectroscopy by means of a nuclear magnetic resonance instrument (Bruker AVANCE III 500MHz) and the data are as follows:
13C NMR(125MHz,CDCl3)δ163.58,163.14,131.70,130.24,129.56,128.66,128.50,127.60,126.26,125.24,125.20,123.28,40.51,30.14,20.35,13.80；
the white solid powder product obtained above was subjected to mass spectrometry by a high-resolution mass spectrometer (solanX 70FT-MS), and the data are as follows: HRMS-ESI (M/z) [ M + H ]]+Calcd.for(C17H15F3NO2),322.10494,Found:322.10506.
Through comprehensive analysis of nuclear magnetic resonance spectrum data and high-resolution mass spectrum data of the obtained white solid powder product, the result shows that the obtained white solid powder product is N-N-butyl-4-trifluoromethyl-1, 8-naphthalimide.
Example 2
A4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound has a structural formula shown as follows:
wherein R is1Is n-butyl;
the reaction formula of the synthesis process is shown as follows:
the preparation method comprises the following specific steps:
into a 50ml single-neck flask were charged 1.0g (3.11mmol) of the 4-trifluoromethyl-1, 8-naphthalimide compound obtained in example 1, i.e., N-N-butyl-4-trifluoromethyl-1, 8-naphthalimide, and 20ml of concentrated sulfuric acid. Adding 0.55g (3.11mmol) of N-bromosuccinimide (NBS) under ice bath, stirring for 10min, removing ice bath, continuing stirring for reaction for 1h at room temperature, and tracking the reaction process by using a TLC point plate until the reaction is complete;
after the reaction, the reaction solution was poured into ice water, extracted with ethyl acetate, and then the organic phase was washed with a saturated solution of sodium hydrogencarbonate, water and saturated brine, respectively, and dried over anhydrous sodium sulfate. Finally separating by silica gel column chromatography, wherein the eluent used in the separation process is a mixed solution of petroleum ether (boiling range: 60-90 ℃) and ethyl acetate with the volume ratio of 120:1, and collecting RfThe peak was observed at 0.4 (15: 1 in terms of the volume ratio of petroleum ether to ethyl acetate), and 1.13g of a white solid product was finally obtained in a yield of 90.8%.
The white solid powder obtained above was subjected to hydrogen spectroscopy by means of a nuclear magnetic resonance instrument (Bruker AVANCE III 500MHz) and the data are as follows:1H NMR(500MHz,CDCl3),δ8.76(d,J＝1.5Hz,1H),8.64(d,J＝3.5Hz,1H),8.63(d,J＝1.5Hz,1H),8.13(d,J＝8.0Hz,1H),4.18(t,J＝7.5Hz,2H),1.74-1.68(m,2H),1.48-1.40(m,2H),0.98(t,J＝7.5Hz,3H)；
the white solid powder obtained above was subjected to carbon spectroscopy by means of a nuclear magnetic resonance instrument (Bruker AVANCE III 500MHz) and the data are as follows:
13C NMR(125MHz,CDCl3)δ162.62,162.44,134.80,132.18,129.71,128.77,127.16,126.36,126.30,126.25,124.63,124.52,123.43,40.69,30.08,20.31,13.78；
the white solid powder product obtained above was subjected to mass spectrometry by a high-resolution mass spectrometer (solanX 70FT-MS), and the data are as follows:
HRMS-ESI(m/z):[M+H]+Calcd.for(C17H14BrF3NO2),400.00818,Found:400.00831.
through comprehensive analysis of nuclear magnetic resonance spectrum data and high-resolution mass spectrum data of the obtained white solid powder product, the result shows that the obtained white solid powder product is N-N-butyl-4-trifluoromethyl-6-bromo-1, 8-naphthalimide.
Example 3
A4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound has a structural formula shown as follows:
wherein: r1Is n-butyl; r2Is phenyl.
The reaction formula of the synthesis process is shown as follows:
the preparation method comprises the following specific steps:
0.17g (1.41mmol) of phenylacetonitrile, 0.28g (7.0mmol) of a basic catalyst NaH (60 w%) and 25ml of tetrahydrofuran are added into a 50ml three-necked flask, nitrogen is replaced three times, after stirring at room temperature for 30min, 0.5g (1.25mmol) of the N-N-butyl-4-trifluoromethyl-6-bromo-1, 8-naphthalimide obtained in example 2 is added, the reaction is continued for 3h at room temperature, and the reaction process is tracked to the completion by a TLC point plate;
after the reaction, the reaction solution was adjusted to pH 1-2 with a saturated citric acid solution, and extracted with ethyl acetate. Washing the obtained organic phase with saturated saline solution for 3 times, drying with anhydrous sodium sulfate, separating by silica gel column chromatography, eluting with mixed solution of petroleum ether (boiling range: 60-90 deg.C) and ethyl acetate at volume ratio of 25:1, collecting RfThe peak was observed at 0.6 (volume ratio of petroleum ether to ethyl acetate: 5: 1), and 0.21g of a pale yellow crystalline product was finally obtained at a yield of 31.3%.
The hydrogen spectra of the product of pale yellow crystals obtained above were measured by means of a nuclear magnetic resonance instrument (Bruker AVANCE III 500MHz) and the data are as follows:
1H NMR(500MHz,CDCl3),δ8.84(d,J＝1.5Hz,1H),8.61(s,1H),8.16(s,1H),7.63(s,1H),7.45(d,J＝7.5Hz,2H),7.43–7.34(m,3H),4.19(m,J＝7.0Hz,2H),1.73–1.67(m,2H),1.47-1.40(m,2H),0.99(t,J＝7.5Hz,3H)；
the carbon spectrum of the product of pale yellow crystals obtained above was measured by means of a nuclear magnetic resonance instrument (Bruker AVANCE III 500MHz) and the data are as follows:
13C NMR(125MHz,CDCl3)δ163.18,161.58,140.87,135.79,134.16,132.28,131.00,130.75,129.52,128.82,128.30,128.27,128.23,128.01,127.85,124.69,124.02,122.37,118.96,41.04,38.16,29.97,20.33,13.79；
the obtained yellowish crystal product was subjected to mass spectrometry by a high-resolution mass spectrometer (solanX 70FT-MS), and the data are as follows:
HRMS-ESI(m/z):[M+Na]+Calcd.for(C25H18BrF3N2NaO2),538.18998,Found:538.18820.
through comprehensive analysis of nuclear magnetic resonance spectrum data and high-resolution mass spectrum data of the obtained light yellow crystal product, the result shows that the obtained light yellow crystal product is N-N-butyl-4-trifluoromethyl-6-bromine-2-phenylacetonitrile-1, 8-naphthalimide.
Example 4
A4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound has a structural formula shown as follows:
wherein: r1Is n-butyl; r2Is a pyridyl group.
The reaction equation of the synthesis process is as follows:
the preparation method comprises the following specific steps:
adding 0.16g (1.41mmol) of pyridine-2-acetonitrile, 0.28g (7.0mmol) of alkali catalyst NaH (60 w%) and 25ml of tetrahydrofuran into a 50ml three-necked flask, replacing nitrogen for three times, stirring at room temperature for 30min, adding 0.5g (1.25mmol) of the 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound obtained in example 2, namely N-N-butyl-4-trifluoromethyl-6-bromo-1, 8-naphthalimide, and continuing to react at room temperature for 3h, wherein the reaction process is tracked by a TLC point plate until the reaction is complete;
after the reaction, the reaction solution was adjusted to pH 1-2 with a saturated citric acid solution, and extracted with ethyl acetate. Washing the obtained organic phase with saturated saline solution for 3 times, drying with anhydrous sodium sulfate, separating by silica gel column chromatography, eluting with mixed solution of petroleum ether (boiling range: 60-90 deg.C) and ethyl acetate at volume ratio of 15:1, collecting RfThe peak was observed at 0.6 (volume ratio of petroleum ether to ethyl acetate: 3: 1), and 0.32g of a pale green crystalline product was finally obtained at a yield of 49.6%. The light green crystal product obtained above was subjected to hydrogen spectroscopy by means of a nuclear magnetic resonance instrument (Bruker AVANCE III 500MHz) and the data are as follows:
1H NMR(500MHz,CDCl3),δ8.74(s,1H),8.56(s,1H),8.47(s,1H),8.37(s,1H),7.74–7.53(m,3H),7.20(s,1H),4.09(d,J＝6.0Hz,2H),1.64–1.58(m,2H),1.40–1.29(m,2H),0.91(t,J＝6.5Hz,3H)；
the light green crystalline product obtained above was subjected to carbon spectroscopy by means of a nuclear magnetic resonance instrument (Bruker AVANCE III 500MHz) and the data are as follows:
13C NMR(125MHz,CDCl3)δ163.24,161.69,153.55,150.24,139.58,137.57,135.56,132.30,129.19,128.45,127.89,124.63,123.84,123.53,123.33,122.56,118.57,40.95,40.87,29.94,20.29,13.77；
the light green crystal product obtained above was subjected to mass spectrometry by a high resolution mass spectrometer (solanX 70FT-MS), and the data are as follows:
HRMS-ESI(m/z):[M+H]+Calcd.for(C24H18BrF3N3O2),516.04562,Found:516.04575.
through comprehensive analysis of nuclear magnetic resonance spectrum data and high-resolution mass spectrum data of the obtained light green crystal product, the result shows that the obtained light green crystal product is N-N-butyl-4-trifluoromethyl-6-bromine-2-pyridine acetonitrile-1, 8-naphthalimide.
Above only with R2By way of example for 2-pyridine, phenyl, the person skilled in the art can obtain R by adjusting the corresponding substrates according to the above examples22-substituted acetonitrile-1, 8-naphthalimide compounds which are p-fluorophenyl, o-chlorophenyl, o-bromophenyl, p-methoxyphenyl, m-methoxyphenyl or m-bromophenyl, furyl, pyrrolyl, imidazolyl, pyrimidinyl, benzofuryl, benzimidazolyl, benzo BOC protected indolyl, benzindolyl, benzopyridyl or benzopyrimidinyl.
Application example 1
25.82mg of N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide obtained in example 4 was weighed into a 10ml volumetric flask, and a 5mmol/L solution was prepared by diluting to a constant volume with acetonitrile solution.
Transferring the 0.5mL solution into a 100mL volumetric flask, adding 10mL deionized water, and diluting acetonitrile to 100mL to obtain a 20 μ M mixed solution (CH)3CN/H2O-9/1, v/v). Accurately weighing 20 μ M of the solution into 14 10mL test tubes, respectively, adding 6.0 equivalents of various anions (from left to right, in sequence: N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + cyanide ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + fluoride ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1 at one time into the test tubes, 8-naphthalimide + dihydrogen phosphate ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + acetate ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + chloride ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + bromide ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + iodide ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + hydrogen sulfate ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + nitrate ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + tetrafluoroborate ion, N-N-butyl-4-trifluoromethyl6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + perchlorate ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + sulfide ion, N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide + thiocyanate ion) are added and mixed uniformly, then the mixture is quickly moved into a quartz cuvette and is subjected to ultraviolet test by taking acetonitrile as a reference solvent, and the test result is shown in figure 1 (the probe in figure 1 is N-N-butyl-4-trifluoromethyl-6-bromo-2-phenylacetonitrile-1, 8-naphthalimide), as can be seen from FIG. 1, only the mixed solution of N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide compound added with cyanide ions has significant spectral red shift change, the wavelength is shifted to 612nm, the addition of other anions can not cause the spectral change of the acetonitrile solution of the N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide compound, and the color change is difficult to detect by naked eyes, thereby showing that the N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide compound can identify the cyanide ions by naked eyes with high selectivity, therefore, the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound can be used as a colorimetric probe of cyanide ions with high selectivity.
FIG. 3 shows the reaction product of 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide obtained in example 4 with a blank compound and Cyanide (CN)-) Mixed solution (CH) with functions of ions, fluorine ions, dihydrogen phosphate ions, chlorine ions, bromine ions, iodine ions, hydrogen sulfate ions, nitrate ions, tetrafluoroborate ions, perchlorate ions, sulfur ions and thiocyanogen3CN/H2O9/1, v/v). The results showed that only 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compounds and Cyanide (CN)-) The ions showed blue color, and the others were almost unchanged and approached colorless.
Application example 2
The N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridineacetonitrile-1, 8-naphthalimide obtained in example 4 was prepared as a 20. mu.M mixed solution (CH)3CN/H2O-9/1, v/v), 5 mul of cyanide ion acetonitrile solution with the concentration of 50000 mul is added dropwise at the same time,after each dripping is finished, the obtained ultraviolet absorption spectrogram is recorded by an ultraviolet spectrophotometer respectively, the obtained spectrums which are dripped for multiple times are superposed to obtain a graph 2, and as can be seen from the graph 2, with the addition of cyanide ions, new absorption peaks exist at the wavelengths of 292nm,348nm, 405nm and 612nm and the absorption intensity is continuously enhanced, which shows that the molecules of the N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridine acetonitrile-1, 8-naphthalimide compound and the cyanide ions have hydrogen bond action to generate a hydrogen bond compound, thereby influencing the color of the probe, namely the N-N-butyl-4-trifluoromethyl-6-bromo-2-pyridine acetonitrile-1, 8-naphthalimide, to be changed from colorless to blue.
Application example 3
Reference is made to examples 3 and 4, with other R2Substituted acetonitrile replaces pyridine-2-acetonitrile to prepare a series of 4-trifluoromethyl-6-bromine-2-substituted acetonitrile-1, 8-naphthalimide compounds; the series of 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compounds are mixed in a mixed solvent (CH)3CN/H2Table 2 shows the results of the color change table with respect to the action of cyanide ion and other anions in O9/1, v/v), and the experimental conditions were tested under the same conditions as in application example 1.
TABLE 2
In summary, the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound provided by the invention can be used as a detection probe for high selection of cyanide ions, and particularly, the probe can provide naked eye detection of a 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound solution from colorless to blue, so that the 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound can be used as a colorimetric reagent for detecting cyanide ions, and further can be practically applied.
The above description is only a basic description of the present invention, and any equivalent changes made according to the technical solution of the present invention should fall within the protection scope of the present invention.
Claims (6)
1. A4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound is characterized in that the structural formula is shown as the following formula (I):
wherein: r1Is straight-chain or branched C1-C10An alkyl group; r2Is phenyl, o-bromophenyl, m-methoxyphenyl, p-methoxyphenyl, 2-pyridyl or 3-indolyl.
2. The 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound of claim 1, wherein: r1Is C1-C6A linear alkyl group.
3. The method for synthesizing a 4-trifluoromethyl-6-bromo-2-substituted acetonitrile-1, 8-naphthalimide compound according to claim 1 or 2, comprising the steps of:
(1) with N-R14-bromo-1, 8-naphthalimide as a starting material, and reacting N-R1Carrying out substitution reaction on 4-bromo-1, 8-naphthalimide and methyl fluorosulfonyl difluoroacetate in a solvent at the temperature of 85-90 ℃ under the catalytic action of a catalyst cuprous iodide to obtain a 4-trifluoromethyl-1, 8-naphthalimide compound;
(2) carrying out bromination reaction on the obtained 4-trifluoromethyl-1, 8-naphthalimide compound and N-bromosuccinimide NBS in concentrated sulfuric acid under the condition of 0-room temperature to obtain a 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound;
(3) 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound and R at room temperature2The substituted acetonitrile reacts in an organic solvent under the action of an alkali catalyst to obtain the 4-trifluoromethyl-6-bromine-2-substituted acetonitrile-1, 8-naphthalimide compound.
4. The method of synthesis of claim 3, whereinIn the step (1), the solvent is N, N-dimethylformamide, N-R1The mass-volume ratio of the-4-bromo-1, 8-naphthalimide to the organic solvent is 1:20-1:30 g/mL; N-R1The molar ratio of the (4-bromo-1, 8) -naphthalimide to the methyl fluorosulfonyl difluoroacetate to the cuprous iodide serving as a catalyst is 1 (2.1-2.3): (1.5-2).
5. The synthesis method according to claim 3, wherein in the step (2), the mass-to-volume ratio of the 4-trifluoromethyl-1, 8-naphthalimide compound to the concentrated sulfuric acid is 1:20-1:30g/mL, and the molar ratio of the 4-trifluoromethyl-1, 8-naphthalimide compound to the N-bromosuccinimide NBS is 1: 1.0-1: 1.1.
6. The synthesis method according to claim 3, wherein in the step (3), the organic solvent is toluene or tetrahydrofuran, and the base catalyst is sodium hydrogen or sodium methoxide; the mass-volume ratio of the 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound to the organic solvent is 1:50-1:60g/mL, the 4-trifluoromethyl-6-bromo-1, 8-naphthalimide compound and R2The molar ratio of substituted acetonitrile to base catalyst is 1: (1.1-1.4) and (5.4-6).
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