CN107043344B - Preparation, structure and the purposes of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base - Google Patents

Preparation, structure and the purposes of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base Download PDF

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CN107043344B
CN107043344B CN201710468263.9A CN201710468263A CN107043344B CN 107043344 B CN107043344 B CN 107043344B CN 201710468263 A CN201710468263 A CN 201710468263A CN 107043344 B CN107043344 B CN 107043344B
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methyl
compound
indolecarboxaldehyde
follows
schiff base
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CN201710468263.9A
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CN107043344A (en
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谭学杰
王超
邢殿香
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齐鲁工业大学
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/10Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13Crystalline forms, e.g. polymorphs
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10Non-macromolecular compounds
    • C09K2211/1003Carbocyclic compounds
    • C09K2211/1007Non-condensed systems
    • CCHEMISTRY; METALLURGY
    • C09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09KMATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10Non-macromolecular compounds
    • C09K2211/1018Heterocyclic compounds
    • C09K2211/1025Heterocyclic compounds characterised by ligands
    • C09K2211/1029Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom

Abstract

The present invention relates to structure, preparation method and some properties of a kind of Schiff base compound.The compound appearance is in golden yellow bulk crystals, and 168.5-169.0 DEG C of fusing point, molecular formula C24H21N3, chemical name are as follows: 3- ((E)-((E)-(1- (biphenyl-4- base) ethylidene)-hydrazine fork)-methyl)-1- methyl-1-H indoles, structure are as follows:It is monoclinic system, P2 that it, which is crystallized,1/ c space group, β=90.252 (2) °,

Description

Preparation, structure and the purposes of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base
Technical field:
The present invention relates to organic synthesis, optical material and field of medicinal chemistry, have used better simply raw material and method one Step synthesis target product.
Background technique:
Schiff base is a kind of compound that structure is more special, can be synthesized according to the difference for introducing group different types of Schiff base.Schiff base has important application in medicine, catalysis, analytical chemistry, corrosion and the fields such as photochromic.For example, Medical domain, Schiff base have antibacterial, sterilization, antitumor, antiviral bioactivity;In optical material field, due to its richness The characteristics of electronics and rigid plane, makes it have good fluorescence property and nonlinear optical property.
4-acetylbiphenyl hydrazone class Schiff base report is less, but such compound has biggish conjugated system, holds that it more Special property is easily generated in optical material field;In drug design field, the cyclohexyl biphenyl stable system fragrance of drug molecule Hydrophobic interaction, therefore it is commonly used for the building of drug molecule.
Summary of the invention
The contents of the present invention are to have synthesized a kind of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base compound, the change It closes beyond the region of objective existence to see in golden yellow bulk crystals, 168.5-169.0 DEG C of fusing point, molecular formula C24H21N3, chemical name are as follows: 3- ((E)-((E)- (1- (biphenyl-4- base) ethylidene)-hydrazine fork)-methyl)-1- methyl-1-H indoles, [english system name are as follows: 3- ((E)-((E)- (1- (biphenyl-4-yl) ethylidene) hydrazono) methyl) -1-methyl-1H-indole], it is abbreviated as 3- BEHMI;Structure is as follows.
1, Structural Identification.
Elemental analysis shows that the percentage composition of its C, H, N are respectively 82.08%, 6.06% and 11.98% (based on molecule Formula C24H21N3Theoretical value be respectively 82.02%, 6.02% and 11.96%);Single crystal structure analysis shows that its crystallization is monocline Crystallographic system, P21/ c space group,β=90.252 (2) °,Z=4, it is related1HNMR spectrum,13CNMR spectrum is shown in attached drawing 1 and attached drawing 2 respectively;Attached drawing 3 and attached drawing 4 be the hot ellipsoid crystal structure figure and crystal structure accumulation graph of the compound respectively.
2, synthetic method.
It is characterized in that in the compound synthesis method: using 4-acetylbiphenyl hydrazone and N- methyl -3- indolecarboxaldehyde as raw material, adopting With solution synthesis or solid-phase synthesis.Steps are as follows:
1) 4-acetylbiphenyl hydrazone and N- methyl -3- indolecarboxaldehyde are dissolved in respectively in suitable organic solvent, then by certain Molar ratio mixing, be stirred to react certain time at a certain temperature;It can also not have to organic solvent, directly mix two kinds instead Answer object, griding reaction.
2) when liquid phase reactor, obtained solution is removed into most of solvent using certain method, powder or knot can be obtained Crystalline object, as target product;When solid phase reaction, grinding certain time can obtain target product.
3) target product can recrystallize in suitable organic solvent with purified product.
Preferably, above-mentioned reaction dissolvent or recrystallization are selected from organic solvent: methanol, ethyl acetate, methylene chloride, second Alcohol, acetonitrile, acetone, chloroform, tetrahydrofuran.
Preferably, the reaction molar ratio of 4-acetylbiphenyl hydrazone and N- methyl -3- indolecarboxaldehyde is 1:4 to 4:1.
Preferably, the reaction temperature is room temperature to being heated to reflux.
Preferably, the reaction time are as follows: 0.5-12 hours.
Preferably, the method for removing solvent is nature volatilization or often/vacuum distillation.
The beneficial effects of the present invention are: function that can be more complicated with fairly simple step and reactant one-step synthesis Molecular material, and separation method is simple.
3, ultraviolet and photoluminescent property.
10-6The ultraviolet spectra that this compound is tested in mol/L ethanol solution, find its in 203nm, 222nm, 282nm, There are four main ultraviolet absorption peak at 348nm, ultraviolet spectrogram is shown in attached drawing 5.
10-5In mol/L ethanol solution, the photoluminescent property of this compound is tested, it is found that it has within the scope of 300-500nm Strong fluorescent emission, fluorescence spectrum are shown in attached drawing 6.
4, anti tumor activity in vitro:
By A549 lung carcinoma cell or 4T1 mouse mastopathy cell in logarithmic phase growth, digested with 0.25% pancreatin thin Born of the same parents, become it is unicellular, with containing 10% fetal calf serum F12K culture solution be made concentration be 1.25 × 107A/L's is unicellular Suspension, by cell inoculation in 96 well culture plates, (the every hole 2.5 × 10 every 200 μ L of hole3A cell).By 96 porocyte culture plates It is placed in CO2In incubator, at 37 DEG C, 5%CO2Under the conditions of, cultivate 48h.
When inner cell covers with (90% is full) when hole, this Schiff base solution (200 of various dose is added by experimental group The hole μ L/), making the final concentration of untested compound is respectively 5 μM, 10 μM, 30 μM, 50 μM, 100 μM, 150 μM, 200 μM, and every group sets 3 A multiple holes cultivate 96h.
It is separately added into the MTT that 20 μ L concentration are 0.5g/L in each hole, continues to cultivate 4h, MTT is made to be reduced to first a ceremonial jade-ladle, used in libation (Formazan).After whole supernatants are sucked out, the DMSO of 200 μ L is added in every hole, is shaked 15min, is made first a ceremonial jade-ladle, used in libation after completely dissolution, is transported With the absorbance (OD value) at enzyme-linked immunosorbent assay instrument measurement 490nm.Then it is calculated according to the following formula:
Cell inhibitory rate %=(control group OD value-experimental group OD value)/control group OD value × 100%
Test result shows that the Schiff base is 108.5 μ to the IC50 (half-inhibitory concentration of drug) of lung cell A549 M, the IC50 (half-inhibitory concentration of drug) to breast cancer cell 4T1 are 112.0 μM, this shows the compound to both cancers Cell has certain inhibitory effect.
Specific embodiment
Content in order to better understand the present invention further illustrates technology of the invention below by two specific embodiments Scheme:
Embodiment 1.
It weighs 4-acetylbiphenyl hydrazone 0.20g (0.95mmol) to be dissolved in 30mL anhydrous methanol, heating stirring adds to whole dissolutions Enter N- methyl -3- indolecarboxaldehyde 0.15g (0.95mmol), is heated to reflux stirring 6 hours, filtrate is then obtained by filtration, is placed in burning Standing volatilization in cup can obtain a large amount of lenticulars precipitatings, will obtain head product (yield is about 70%) after gained precipitating filtering, this primiparity Product can use ethyl alcohol recrystallization, obtain golden yellow bulk crystals, as 3-BEHMI Schiff base.
Embodiment 2.
It weighs 4-acetylbiphenyl hydrazone 0.40g (1.9mmol) to be put into mortar, N- methyl -3- indolecarboxaldehyde 0.30g is added (1.9mmol) grinds 3 hours, obtains target product crude product;By gained powder ethyl alcohol recrystallization, golden yellow bulk crystals are obtained, As 3-BEHMI Schiff base.
Detailed description of the invention
Attached drawing 1 is 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base1H NMR spectra.
Attached drawing 2 is 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base13CNMR spectrogram.
Attached drawing 3 is the crystal structure figure of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base, ellipsoid probability 30%.
Attached drawing 4 is the crystal structure accumulation graph of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base, ellipsoid probability 5%.
Attached drawing 5 is the ultraviolet spectrogram (10 of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base-6Mol/L ethyl alcohol is molten Liquid).
Attached drawing 6 is the fluorescence spectra (10 of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base-5Mol/L ethyl alcohol is molten Liquid).

Claims (5)

1. a kind of compound, appearance is in golden yellow bulk crystals, 168.5-169.0 DEG C of fusing point, molecular formula C24H21N3, chemical name Are as follows: 3- ((E)-((E)-(1- (biphenyl-4- base) ethylidene)-hydrazine fork)-methyl)-1- methyl-1-H indoles, structure are as follows:
It is monoclinic system, P2 that it, which is crystallized,1/ c space group, β=90.252 (2) °,Z=4.
2. the preparation method of compound crystal as described in the appended claim 1, it is characterised in that: with 4-acetylbiphenyl hydrazone and N- methyl- 3- indolecarboxaldehyde is raw material, and using solution synthetic method, steps are as follows:
1) 4-acetylbiphenyl hydrazone and N- methyl -3- indolecarboxaldehyde are dissolved in methanol, ethyl acetate, methylene chloride, ethyl alcohol, second respectively It in nitrile, acetone, chloroform or tetrahydrofuran organic solvent, is then mixed by 1:4 to 4:1 molar ratio, in room temperature to being heated to reflux temperature It is stirred to react under degree 0.5-12 hours;
2) obtained solution is volatilized using nature or often/vacuum distillation method removes most of solvent, powder or knot can be obtained Crystalline object, as target product;
3) target product can be organic in methanol, ethyl acetate, methylene chloride, ethyl alcohol, acetonitrile, acetone, chloroform or tetrahydrofuran Recrystallization with purified product and cultivates monocrystalline in solvent.
3. the preparation method of compound crystal as described in the appended claim 1, it is characterised in that: with 4-acetylbiphenyl hydrazone and N- methyl- 3- indolecarboxaldehyde is raw material, and using solid-phase synthesis, steps are as follows:
1) 4-acetylbiphenyl hydrazone and N- methyl -3- indolecarboxaldehyde are mixed by 1:4 to 4:1 molar ratio, at room temperature griding reaction 0.5-12 hours, gained powder was target product head product;
2) target product head product can be in methanol, ethyl acetate, methylene chloride, ethyl alcohol, acetonitrile, acetone, chloroform or tetrahydro furan Recrystallization mutter in organic solvent with purified product and cultivates monocrystalline.
4. compound as described in claim 1 is in organic pigment, Optical Bleaching Agent, photooxidant, coating, chemistry and biochemical point It analyses, the purposes of solar energy trap, anti-fake mark, pharmaceutical indications and laser field, which is based on its photoluminescent property.
5. as described in the appended claim 1 compound or its pharmaceutically acceptable salt preparation prevention and/or treatment tumour medicine Application in object, it is characterised in that: the tumour is lung cancer or breast cancer.
CN201710468263.9A 2017-06-20 2017-06-20 Preparation, structure and the purposes of 4-acetylbiphenyl hydrazone-N- methyl -3- indolecarboxaldehyde Schiff base CN107043344B (en)

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Citations (5)

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WO1987006133A1 (en) * 1986-04-07 1987-10-22 The Upjohn Company Anthelmintic acylhydrazones, method of use and compositions
CN1598698A (en) * 2003-09-16 2005-03-23 三星电子株式会社 Organophotoreceptor with charge transport compound with an azine group
WO2009155362A1 (en) * 2008-06-19 2009-12-23 Ligand Pharmaceuticals Inc. Small molecule hematopoietic growth factor mimetic compounds and their uses
CN104193650A (en) * 2014-08-12 2014-12-10 齐鲁工业大学 Structure, preparation and application of benzildihydrazone-N,N'-bis(1-formacylnaphthalene)
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987006133A1 (en) * 1986-04-07 1987-10-22 The Upjohn Company Anthelmintic acylhydrazones, method of use and compositions
CN1598698A (en) * 2003-09-16 2005-03-23 三星电子株式会社 Organophotoreceptor with charge transport compound with an azine group
WO2009155362A1 (en) * 2008-06-19 2009-12-23 Ligand Pharmaceuticals Inc. Small molecule hematopoietic growth factor mimetic compounds and their uses
CN104193650A (en) * 2014-08-12 2014-12-10 齐鲁工业大学 Structure, preparation and application of benzildihydrazone-N,N'-bis(1-formacylnaphthalene)
CN104945302A (en) * 2015-06-12 2015-09-30 齐鲁工业大学 Structure, preparation and application of benzil dihydrazone-indole-3-carboxaldehyde dual-Schiff base

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Analytics of nonpeptidic erythropoietin mimetic agents in sports drug testing employing high-resolution/high-accuracy liquid chromatography-mass spectrometry;Matthias Vogel,等;《Anal Bioanal Chem》;20160930;第408卷(第23期);第6431-6442页
新型腙类西弗碱的合成、结构表征及产物类型研究;郝秀其;《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》;20160215;全文

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