CN108659014A - The preparation and use of ethyl chain demethyl Chinese blister beetle acid imide dimer - Google Patents
The preparation and use of ethyl chain demethyl Chinese blister beetle acid imide dimer Download PDFInfo
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- CN108659014A CN108659014A CN201710190513.7A CN201710190513A CN108659014A CN 108659014 A CN108659014 A CN 108659014A CN 201710190513 A CN201710190513 A CN 201710190513A CN 108659014 A CN108659014 A CN 108659014A
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- acid imide
- blister beetle
- chinese blister
- compound
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- 241000623906 Lytta vesicatoria Species 0.000 title claims abstract description 22
- 150000003949 imides Chemical class 0.000 title claims abstract description 20
- 239000002253 acid Substances 0.000 title claims abstract description 19
- 239000000539 dimer Substances 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 20
- 239000000575 pesticide Substances 0.000 claims abstract description 10
- 241000500437 Plutella xylostella Species 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 235000007688 Lycopersicon esculentum Nutrition 0.000 claims abstract description 4
- 241001330975 Magnaporthe oryzae Species 0.000 claims abstract description 4
- 240000003768 Solanum lycopersicum Species 0.000 claims abstract 2
- 239000013078 crystal Substances 0.000 claims description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 19
- 238000001953 recrystallisation Methods 0.000 claims description 19
- 239000007787 solid Substances 0.000 claims description 19
- 239000002994 raw material Substances 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- DHZBEENLJMYSHQ-XCVPVQRUSA-N cantharidin Chemical class C([C@@H]1O2)C[C@@H]2[C@]2(C)[C@@]1(C)C(=O)OC2=O DHZBEENLJMYSHQ-XCVPVQRUSA-N 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 16
- 239000000126 substance Substances 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 13
- 239000000047 product Substances 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 229940095758 cantharidin Drugs 0.000 claims description 12
- 229930008397 cantharidin Natural products 0.000 claims description 12
- DHZBEENLJMYSHQ-UHFFFAOYSA-N cantharidine Natural products O1C2CCC1C1(C)C2(C)C(=O)OC1=O DHZBEENLJMYSHQ-UHFFFAOYSA-N 0.000 claims description 12
- SWWQQSDRUYSMAR-UHFFFAOYSA-N 1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrochloride Chemical group Cl.C1=CC(O)=CC=C1CC1C2=CC(O)=C(O)C=C2CCN1 SWWQQSDRUYSMAR-UHFFFAOYSA-N 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- 239000000376 reactant Substances 0.000 claims description 8
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000007039 two-step reaction Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000003745 diagnosis Methods 0.000 claims description 2
- 239000000975 dye Substances 0.000 claims description 2
- 238000005401 electroluminescence Methods 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000006081 fluorescent whitening agent Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000000990 laser dye Substances 0.000 claims description 2
- 238000005580 one pot reaction Methods 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 239000012860 organic pigment Substances 0.000 claims description 2
- 239000003973 paint Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 230000003068 static effect Effects 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- 239000013067 intermediate product Substances 0.000 claims 3
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical class O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims 1
- 238000012742 biochemical analysis Methods 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 238000003746 solid phase reaction Methods 0.000 claims 1
- 238000006471 dimerization reaction Methods 0.000 abstract description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 239000004593 Epoxy Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 241000233866 Fungi Species 0.000 description 5
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002240 furans Chemical class 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000749 insecticidal effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 231100000111 LD50 Toxicity 0.000 description 2
- 241000227653 Lycopersicon Species 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000001887 anti-feedant effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- JAABVEXCGCXWRR-FBXFSONDSA-N rel-norcantharidin Chemical compound C1C[C@H]2[C@@H]3C(=O)OC(=O)[C@@H]3[C@@H]1O2 JAABVEXCGCXWRR-FBXFSONDSA-N 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000001018 virulence Effects 0.000 description 2
- RABBMOYULJIAFU-UHFFFAOYSA-N 1h-pyrrole;thiophene Chemical class C=1C=CNC=1.C=1C=CSC=1 RABBMOYULJIAFU-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 241000258937 Hemiptera Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000255777 Lepidoptera Species 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 125000000332 coumarinyl group Chemical class O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 150000002171 ethylene diamines Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 150000003219 pyrazolines Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- 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
-
- 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
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
-
- 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
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The present invention relates to a kind of Chinese blister beetle acid imide dimer compound of butyl connection, appearance is in water white transparency crystallite, 234.0 238.3 DEG C of fusing point, molecular formula C20H24N2O6, molecular weight 388.41, structure is as follows：
Description
Technical field：
The present invention relates to fluorescent material and field of pesticide chemistry, specially a kind of system of demethyl Chinese blister beetle acid imide dimer
Preparation Method and in fluorescent material and the purposes of field of pesticide chemistry.
Background technology：
Cantharidin is the active ingredient of Chinese tradition natural drug Chinese blister beetle, can make the DNA firsts and seconds knots of cancer cell
Structure is broken, and then cancer cell is made to enter programmed death, but cantharidin severe toxicity, and synthesis is difficult, limits its clinical application.Go first
Base Chinese blister beetle imide derivative had not only remained the antitumor activity of cantharidin, but also with structure is changeable, be easy to modification, can
The features such as being coordinated with metal is expected to obtain the anti-tumor drug molecule that toxicity is low, activity is high by structure of modification；On the other hand, exist
The dimeric structure being widely present in natural products is generally considered have bioactivity more better than corresponding monomer structure, tool
There is the drug molecule of dimeric structure largely to be synthesized, and for treating cancer, AIDS, Alzheimer disease, malaria and
Various parasitic diseases.But it is considerably less based on the imido dimeric species of Chinese blister beetle, be seen in document report at present is no more than ten
Kind；Applicant seminar always works on research of the cantharidin derivative in anticancer drug field for many years, it has recently found that such spread out
Biology also has special purposes in fluorescent material and field of pesticide chemistry.
Organic fluorescence materials type is various, they carry conjugation heterocycle more and various chromophores, structure are easy to adjust, pass through
The unsaturated groups such as ethylene linkage, phenyl ring and various chromophores are introduced to change its conjugate length, to make compound optoelectronic property send out
Changing.Such as oxadiazoles and its derivative species, triazole and its derivative species, rhodamine and its derivative species, Coumarins derive
Object, 1,8- naphthalimide analog derivative, pyrazoline derivative, triphen amine derivant, porphyrins, carbazole, pyrazine, thiophene
Azole derivative, analog derivative etc..They are widely used in optical electron device, DNA diagnosis, Optochemical sensor, organic
Pigment, dyestuff, fluorescent whitening agent, photooxidant, fluorescent paint, laser dye, organic electroluminescence device (ELD) chemistry and life
Change the fields such as analysis, solar energy trap, anti-fake mark, pharmaceutical indications and laser.But with demethyl Chinese blister beetle acid imide dimerization
Body is that the fluorescent material of skeleton has not been reported.
Research of the cantharidin for pesticide is seldom, and 1974, James E.Carrel and Thomas Eisner existed
It writes articles and points out on Science, 10-5mol.L-1Extremely low concentration under, cantharidin has Antifeedant Effects to various insects.In addition, also
Have stomach toxicity, tag, interior suction the effects that.The insecticidal spectrum of cantharidin is wider, with stronger to Lepidoptera, Homoptera insect effect, simultaneously
There is apparent inhibiting effect to various plants disease fungus.The discoveries such as Chen Yong, Norcantharidin and cantharidin are seemingly, young to diamond-back moth
Worm equally has stronger stomach toxicity and non-selective Antifeedant Effects.But the cytotoxicity of Norcantharidin will be weaker than cantharidin, lead to
Good toxic effect can also be reached by crossing increasing dosage or synergist being added.Demethyl Chinese blister beetle acid imide dimer is used for
The research of pesticide has not been reported.
Invention content
1, structural characterization
Present disclosure is that one kind has been prepared with ethyl (i.e.-(CH by a variety of methods2)2) it is going for connection chain
Methyl Chinese blister beetle acid imide dimer, the structure of the dimer and related characterization parameter are as follows：
The compound appearance is in water white transparency crystallite, 261.2-261.5 DEG C of fusing point, molecular formula C18H20N2O6, molecular weight is
360.36 chemistry is entitled：[- 1,3 (2H)-two of hexahydro -4,7- epoxy -1H- iso-indoles of 2,2'- (ethane -1,2- diyls) two
Ketone], english system is named as：2,2'-(1,2-ethanediyl)bis[hexahydro-4,7-epoxy-1H-isoindole-
1,3 (2H)-dione], structure is as follows：
Elemental analysis show the percentage composition of the dimer C, H, N be respectively 60.12%, 5.65% and 7.79% (by point
Minor C18H20N2O6The theoretical value of calculating is respectively 59.99%, 5.59% and 7.77%)；Pass through1HNMR and13CNMR nuclear-magnetisms are total
Method of slight characterizes its structure, sees attached drawing 1 and attached drawing 2 respectively in relation to spectrogram.
2, synthetic method
There are five types of synthetic methods for the dimer：Method one is the step using unsaturated cantharidin and ethylenediamine as raw material
It is rapid as follows：
After unsaturated cantharidin and ethylenediamine are dissolved in suitable organic solvent respectively, according to certain substance
The mixing of the ratio between amount, is stirred to react certain time at a certain temperature, obtains white powdery solids, concentrate solution of volatilizing, filtering,
Pulverulent solids are washed with suitable solvent, then by suitable solvent recrystallization, obtain white small bulk crystals A, ingredient
For 2,2'- (ethane -1,2- diyls) two (- 1,3 (2H)-diketone of 3a, 4,7,7a- tetrahydrochysene -4,7- epoxy -1H- iso-indoles)；Take this
Crystal is dissolved in suitable organic solvent, and a certain amount of palladium-carbon catalyst is added, and is passed through hydrogen, is stirred to react one at a certain temperature
It fixes time, filters, stand volatilization, it is target product crystal that tiny transparent crystal grain is precipitated after a few days, in solution；It is white preparing
Reaction dissolvent can not also be used in a step of the small bulk crystals A of color, it is directly that two kinds of raw materials are mixed by the ratio between certain amount of substance
It closes, is ground under room temperature, obtain paste, the suitable solvent recrystallization of obtained solid can also obtain crystal A.
Method is second is that with unsaturated demethyl Chinese blister beetle acid imide and 1, and 2- Bromofumes are raw material, and steps are as follows：
By unsaturated demethyl Chinese blister beetle acid imide and 1, after 2- Bromofumes are dissolved in suitable organic solvent, according to certain
The ratio between amount of substance mixes, and is stirred to react certain time at a certain temperature, obtains the small blocks of solid of white, and volatilization concentration is molten
Liquid, filtering, pulverulent solids are washed with suitable solvent, then by suitable solvent recrystallization, obtain white small bulk crystals
A, ingredient 2,2'- (ethane -1,2- diyl) two (3a, 4,7,7a- tetrahydrochysene -4,7- epoxy -1H- iso-indoles -1,3 (2H)-two
Ketone)；It takes the crystal to be dissolved in suitable organic solvent, a certain amount of palladium-carbon catalyst is added, be passed through hydrogen, stir at a certain temperature
It mixes reaction certain time, filtering stands volatilization, and it is target product crystal that tiny transparent crystal grain is precipitated after a few days, in solution；
Reaction dissolvent can not also be used in the step for preparing the small bulk crystals A of white, directly two kinds of raw materials by certain substance
The ratio between amount mixes, and is ground under room temperature, obtains paste, the suitable solvent recrystallization of obtained solid can also obtain crystal A.
Method three is with furans and 1, and 1 '-(ethane -1,2- diyl)-two (1H- pyrroles -2,5- diketone) is raw material, step
It is as follows：
After 1,1 '-(ethane -1,2- diyl)-two (1H- pyrroles -2,5- diketone) is dissolved in suitable organic solvent, according to
Furans is added in the ratio between certain amount of substance, is stirred to react or stands at a certain temperature certain time, obtain white powder
Solid, concentrate solution of volatilizing, filtering, pulverulent solids are washed with suitable solvent, then by suitable solvent recrystallization, are obtained
The small bulk crystals A of white, ingredient 2, (3a, 4,7,7a- tetrahydrochysene -4,7- epoxy -1H- are different by 2'- (ethane -1,2- diyl) two
Indoles -1,3 (2H)-diketone)；It takes the crystal to be dissolved in suitable organic solvent, a certain amount of palladium-carbon catalyst is added, is passed through hydrogen
Gas is stirred to react certain time at a certain temperature, and filtering stands volatilization, tiny transparent crystal grain is precipitated after a few days, in solution
As target product crystal；Reaction dissolvent can not also be used in the step for preparing the small bulk crystals A of white, directly two kinds of originals
Material is ground under room temperature by the mixing of the ratio between certain amount of substance, obtains paste, the suitable solvent recrystallization of obtained solid,
It can also obtain crystal A.
Method one, method two and method three be two-step reaction, they are difference lies in reactant difference, but reactant
Molar ratio is between 4:1 and 1:Between 2.
Method four is using cantharidin and ethylenediamine as raw material, and steps are as follows：
After cantharidin and ethylenediamine are dissolved in suitable organic solvent respectively, according to certain the ratio between amount of substance
Mixing, is stirred to react certain time at a certain temperature, obtains white powdery solids, concentrate solution of volatilizing, and filtering is powdered
Solid is washed with suitable solvent, then by suitable solvent recrystallization to get target product；It can not also use and react molten
Agent is directly mixed two kinds of raw materials by the ratio between certain amount of substance, is ground under room temperature, obtains paste, and obtained solid is closed
Suitable solvent recrystallization can also obtain target product.
Method five is with demethyl Chinese blister beetle acid imide and 1, and 2- Bromofumes are raw material, and steps are as follows：
By demethyl Chinese blister beetle acid imide and 1, after 2- Bromofumes are dissolved in suitable organic solvent, according to certain substance
The mixing of the ratio between amount, is stirred to react certain time at a certain temperature, obtains white powdery solids, concentrate solution of volatilizing, filtering,
Pulverulent solids are washed with suitable solvent, then by suitable solvent recrystallization, obtain target product；Reaction can not also be used
Solvent is directly obtained two kinds of raw materials paste, is ground under room temperature by the mixing of the ratio between certain amount of substance, and obtained solid is used
Suitable solvent recrystallization can also obtain target product.
Method four and method five are one-step reaction, and difference lies in reactant difference, but the molar ratios of reactant for they
Between 4:1 and 1:Between 2.
Organic solvent (including reaction, washing, recrystallization solvent) in above five kinds of methods is selected from：Methanol, ethyl alcohol, second
Nitrile, dichloromethane, chloroform, tetrahydrofuran, ethyl acetate, toluene, acetone, N,N-dimethylformamide (DMF) etc.；It is anti-in solid phase
Solvent is not had in answering.
Preferably, the reaction temperature and recrystallization temperature are room temperature or heating, and reaction method is stirring or stands, and is tied again
Crystal method is to volatilize naturally under static condition.
Preferably, the reaction time and recrystallization time are selected from：- 3 days 2 hours.
The beneficial effects of the invention are as follows：More complicated fluorescent material can be synthesized with fairly simple step and reactant
And pesticide original medicine.
3, ultraviolet and photoluminescent property.
10-5The ultraviolet spectra that this compound is tested in mol/L ethanol solutions finds that it has ultraviolet suction near 233nm
It receives peak (as shown in Fig. 3).
Also in 10-5In mol/L ethanol solutions, swashed respectively with the ultraviolet light that wavelength is 253nm, 273nm and 293nm
Hair, tests the photoluminescent property of this compound, it is found that it has strong fluorescent emission between 325~525nm, ultraviolet with 293nm
The fluorescence that light excitation generates is especially strong, or even naked eyes are as it can be seen that fluorescence spectrum is shown in attached drawing 4.
4, insecticidal test.
Insecticidal test is experimental subjects with diamondback moth larvae, is tested with 75% ethanol solution, using leaching worm immersion method
Measure synthesis virulence of the compound to diamondback moth larvae；According to the minimum full cause for the diamondback moth larvae that preliminary experiment is predicted
Dead concentration and highest are survived concentration entirely, 5-7 gradient concentration are set within this range, by each concentration medicine of 3 instar larvae of diamondback moth immersion
It is placed on blotting paper after 5 seconds in liquid and sucks the upper extra liquid of polypide, be put into cylindricality bottle (diameter 3.5cm, the height for being covered with moisturizing filter paper
In 7.5cm)；And soak cabbage leaves (size about 2cm × 2cm) 2-3 seconds in liquid, extra liquid is sucked, cylindricality bottle is put into
It is middle edible for larva；10 larvas per treatment, each concentration gradient repeat three times, are handled as a contrast with clear water；It will everywhere
Reason is put into weather incubator, controlled at 25 DEG C or so, relative humidity 75%.Photoperiod 14/10 (L/D)；After 24 hours
It checks dead larvae situation, virulence regression equation and lethal concentration of 50 LC50 is found out according to statistical result；Test result shows this
Compound is about 125mg/L to the LC50 values of diamondback moth larvae.
5, inhibit fungi experiment.
Active testing has been carried out using two kinds of phytopathogens of fungus block method pair (Pyricularia oryzae and tomato wilt), has been trained
It is potato agar culture medium (PDA) to support base：Peeled potatoes 200g, sucrose 15g, agar 17g, distilled water 1000ml；Mycelia
Fungus block is made with the sterilizing clamp dog device of a diameter of 0.8cm after length is good, then by fungus block sterilizing tweezers gripping, is put into containing 100mg/
The culture dish center of L compound solutions (solvent is 25% ethanol solution), per one piece of ware, three one group of wares are placed in 27 DEG C of cultures
72h measures bacterial plaque diameter, and is compared with blank assay, and mycelial growth inhibition rate is found out with following formula：
Inhibiting rate=(control group average colony diameter-processing group average colony diameter) ÷ control group average colonies diameter ×
100%
Test result shows that the compound is respectively 89% and 91% to the inhibiting rate of Pyricularia oryzae and tomato wilt.
Specific implementation mode
Content in order to better understand the present invention, the technology further illustrated the present invention below by five specific embodiments
Scheme.
Embodiment 1.
It weighs 3.32g unsaturations cantharidin (0.02mol) to be dissolved in 50mL toluene, be vigorously stirred, be added
0.81mL (0.01mol) 1,2- ethylenediamines, solution become cloudy, are stirred under room temperature for 24 hours, obtain white suspension, wait for that solvent volatilizees
To residue about 10ml, filtering washs precipitation with dichloromethane, then uses recrystallizing methanol, can obtain white small bulk crystals, referred to as
For crystal A, ingredient 2,2'- (ethane -1,2- diyl) two (3a, 4,7,7a- tetrahydrochysene -4,7- epoxy -1H- iso-indoles -1,3
(2H)-diketone)；Crystal A0.50g is weighed, 40mL methanol is added, ultrasonic vibration 10min is added 0.05g palladium-carbon catalysts, is passed through
Hydrogen, 40 DEG C of reaction 8h, after reaction, filtering stands volatilization, after three days, tiny transparent crystal grain is precipitated in solution, as
Target product.
Embodiment 2.
0.33g unsaturation demethyl Chinese blister beetle acid imides are dissolved in 30ml acetone, with the amount ratio 2 of substance:1 is added 1,
2- Bromofume 0.19g, stirring at normal temperature for 24 hours, obtain white suspension, wait for that solvent evaporates into residue about 10ml, and dichloro is used in filtering
Methane wash precipitates, and then uses recrystallizing methanol, can obtain white small bulk crystals, referred to as crystal A, ingredient 2,2'- (second
Alkane -1,2- diyls) two (- 1,3 (2H)-diketone of 3a, 4,7,7a- tetrahydrochysene -4,7- epoxy -1H- iso-indoles)；Weigh crystal
40mL methanol is added in A0.50g, and 0.05g palladium-carbon catalysts are added in ultrasonic vibration 10min, is passed through hydrogen, and 40 DEG C are reacted 8h, instead
After answering, filtering stands volatilization, after three days, tiny transparent crystal grain, as target product is precipitated in solution.
Embodiment 3.
By 0.22g1,1 '-(ethane -1,2- diyl)-two (1H- pyrroles -2,5- diketone) is dissolved in 50ml toluene, with object
The amount ratio 1 of matter:2 are added 0.20g furans, and concentrate solution is to 20ml after being heated to reflux 10h, and filtering, it is heavy to be washed with dichloromethane
It forms sediment, then uses recrystallizing methanol, white small bulk crystals, referred to as crystal A, ingredient 2,2'- (ethane -1,2- bis- can be obtained
Base) two (- 1,3 (2H)-diketone of 3a, 4,7,7a- tetrahydrochysene -4,7- epoxy -1H- iso-indoles)；Crystal A0.50g is weighed, 40mL is added
0.05g palladium-carbon catalysts are added in methanol, ultrasonic vibration 10min, are passed through hydrogen, 40 DEG C of reaction 8h, after reaction, filtering is quiet
Volatilization is set, tiny transparent crystal grain, as target product are precipitated after three days, in solution.
Embodiment 4.
3.36g cantharidins are weighed, are put into mortar, 0.6g ethylenediamines are added, grinds 4h under room temperature, obtains paste
The dissolving of 80ml methanol is added in object, and filtering stands volatilization, after three days, tiny transparent crystal grain is precipitated in solution, as target is produced
Object.
Embodiment 5.
3.34g demethyl Chinese blister beetle acid imides are weighed, are put into mortar, 1.88g1 is added, 2- Bromofumes are ground under room temperature
4h obtains paste, and the dissolving of 80ml methanol is added, and filtering stands volatilization, after three days, tiny transparent crystal grain is precipitated in solution,
As target product.
Description of the drawings
Attached drawing 1 is target compound1HNMR spectrograms.
Attached drawing 2 is target compound13CNMR spectrograms.
Attached drawing 3 is the UV-visible spectrum of target compound.
Attached drawing 4 is the fluorescence spectra of target compound.
Claims (7)
1. a kind of Chinese blister beetle acid imide dimer compound of ethyl connection, appearance is in water white transparency crystallite, fusing point 261.2-261.5
DEG C, molecular formula C18H20N2O6, molecular weight 360.36, structure is as follows：
2. the preparation method of Chinese blister beetle acid imide dimer compound as described in the appended claim 1, it is characterised in that：It is reacted with two kinds
Object is raw material, and one-step or two-step reaction occurs in suitable organic solvent, can not also be directly complete by two kinds of raw materials with solvent
At reaction, steps are as follows for two-step reaction：
1) it after raw material 1 and raw material 2 being dissolved in suitable organic solvent respectively, is mixed according to the ratio between certain amount of substance, one
Determine to be stirred to react certain time at temperature, obtain white powdery solids, be intermediate product, which can not also be with organic molten
Agent, two kinds of direct hybrid reactions of raw material obtain intermediate product；
2) it takes the intermediate product to be dissolved in suitable organic solvent, a certain amount of palladium-carbon catalyst is added, is passed through hydrogen, in a constant temperature
It is stirred to react certain time under degree, filters, stands volatilization, after three days, it is target production that tiny transparent crystal grain is precipitated in solution
Object；
Steps are as follows for single step reaction：
After raw material 1 and raw material 2 are dissolved in suitable organic solvent respectively, mixed according to the ratio between certain amount of substance, certain
At a temperature of be stirred to react certain time, obtain white powdery solids, concentrate solution of volatilizing, filtering, pulverulent solids are with suitable
Solvent washing, then by suitable solvent recrystallization to get target product；Reaction dissolvent can not also be used, directly two
Kind raw material is mixed by the ratio between certain amount of substance, griding reaction certain time under room temperature, obtains paste, and obtained solid is closed
Suitable solvent recrystallization can also obtain target product.
3. the preparation method of compound as stated in claim 2, it is characterised in that：In two-step reaction, two kinds of reactants can
To be selected from：Unsaturated cantharidin and ethylenediamine, or unsaturated demethyl Chinese blister beetle acid imide and 1,2- Bromofumes or furan
It mutters and 1,1 '-(ethane -1,2- diyls)-two (1H- pyrrole-2,5-diones)；In single step reaction, two kinds of reactants can be selected from
Cantharidin and ethylenediamine or demethyl Chinese blister beetle acid imide and 1,2- Bromofumes.
4. the preparation method of compound as stated in claim 2, it is characterised in that：The reaction dissolvent and recrystallization solvent choosing
From：Methanol, ethyl alcohol, acetonitrile, dichloromethane, chloroform, tetrahydrofuran, ethyl acetate, toluene, acetone, n,N-Dimethylformamide,
According to solid phase reaction, then reaction dissolvent is omitted.
5. the preparation method of compound as stated in claim 2, it is characterised in that：The reaction temperature and recrystallization temperature are
Room temperature or heating, reaction method are stirring or stand that recrystallization method is to volatilize naturally under static condition；Two kinds of reactants used
The ratio between the amount of substance be selected from：4:1 to 1:2；The reaction time and recrystallization time are selected from：- 3 days 2 hours.
6. compound crystal as described in claim 1 optical electron device, DNA diagnosis, Optochemical sensor, organic pigment,
Dyestuff, fluorescent whitening agent, photooxidant, fluorescent paint, laser dye, organic electroluminescence device, chemistry and biochemical analysis, too
The purposes of positive energy trap, anti-fake mark, pharmaceutical indications and laser field, the purposes are based on its photoluminescent property.
7. compound as described in claim 1 and its application of the acceptable salt in preparing pesticide in Pesticide Science, feature
It is, the pesticide is for preventing diamondback moth larvae or Pyricularia oryzae or tomato wilt.
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