CN106866618B - The preparation and use of two (thiophene -2- methylene) butane -1,4- diamines - Google Patents
The preparation and use of two (thiophene -2- methylene) butane -1,4- diamines Download PDFInfo
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- CN106866618B CN106866618B CN201710195054.1A CN201710195054A CN106866618B CN 106866618 B CN106866618 B CN 106866618B CN 201710195054 A CN201710195054 A CN 201710195054A CN 106866618 B CN106866618 B CN 106866618B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
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- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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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
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1092—Heterocyclic compounds characterised by ligands containing sulfur as the only heteroatom
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Abstract
The present invention relates to a kind of butyl connection thiophene Schiff base dimer crystal, appearance be in colorless and transparent bulk, 68.9-69.6 DEG C of fusing point, molecular formula C14H16N2S2, molecular weight 276.42, chemical name are as follows: (N1E,N4E)‑N1,N4- two (thiophene -2- methylene) butane-Isosorbide-5-Nitrae-diamines, structure are as follows:The crystal category rhombic system, P212121Space group,α=β=γ=90 °,
Description
Technical field:
The present invention relates to organic synthesis, optical material and field of medicinal chemistry, use one step of better simply raw material and method
Synthesize target product.
Background technique:
Symmetry plays important role in vital movement, therefore dimer is that one kind is generally deposited in natural products
Structure type.In technical field of material chemistry, dimeric structure be often used in photoelectric material, supramolecular materials, functional dye,
In the building of the new materials such as fluorescent material；Fluorescent material based on organic dimeric structure is widely used in optics electricity
Sub- device, DNA diagnosis, Optochemical sensor, organic pigment, dyestuff, fluorescent whitening agent, photooxidant, fluorescent paint, laser dye
Material, organic electroluminescence device (ELD) chemistry and biochemical analysis, solar energy trap, anti-fake mark, pharmaceutical indications and laser etc.
Field；In field of medicinal chemistry, dimer often shows better activity than corresponding monomer；With the novel of excellent properties
The design and synthesis of dimer material are always material scholar and the direction that Pharmaceutical Chemist is made great efforts.
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；In view of Schiff base dimerization
Connection chain of body itself can have variation abundant, before optical material and field of medicinal chemistry also have good application
Scape.
Summary of the invention
1, structural characterization
The contents of the present invention are one kind to be prepared by a variety of methods with butyl (i.e.-(CH2)4) be connection chain west
Not alkali conjugated dimmer crystal, the structure of the dimer crystal and related characterization parameter are as follows:
The compound appearance be in colorless and transparent bulk crystals, 68.9-69.6 DEG C of fusing point, molecular formula C14H16N2S2, molecular weight
It is 276.42, chemical name are as follows: (N1E,N4E)-N1,N4- two (thiophene -2- methylene) butane-Isosorbide-5-Nitrae-diamines, english system name
Are as follows: (N1E,N4E)-N1,N4- bis (thiophen-2-ylmethylene) butane-1,4-diamine, structure are as follows:
Elemental analysis shows that the percentage composition of the dimer C, H, N are respectively 60.98%, 5.96% and 10.27% (to press
Molecular formula C14H16N2S2The theoretical value of calculating is respectively 60.83%, 5.83% and 10.13%)；Single crystal structure analysis shows it
Crystallization is rhombic system, P212121Space group,α=β=
γ=90 °,Z=4, attached drawing 1, attached drawing 2 are the hot ellipsoid crystal structure figure and crystalline substance of the compound respectively
Body structure accumulation graph, it is related1HNMR spectrum,13CNMR spectrum is shown in attached drawing 3 and attached drawing 4 respectively.
2, synthetic method
It is characterized in that in the compound synthesis method: using 2 thiophene carboxaldehyde and butanediamine as raw material, being synthesized using solution
Or solid-phase synthesis.Steps are as follows:
1) 2 thiophene carboxaldehyde and butanediamine are dissolved in respectively in suitable organic solvent, it is then mixed by certain molar ratio
It closes, is stirred to react certain time at a certain temperature；It can also not have to organic solvent, directly mix two kinds of reactants, grinding
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 solvent: methanol, ethyl acetate, methylene chloride, ethyl alcohol, second
Nitrile, acetone, chloroform, tetrahydrofuran, toluene, N,N-dimethylformamide.
Preferably, the reaction molar ratio of 2 thiophene carboxaldehyde and butanediamine is 1:2 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.
10-5The ultraviolet spectra that this compound is tested in mol/L ethanol solution finds that it has purple at 261nm and 279nm
Outer absorption peak, as shown in Fig. 5；It is square in b3lyp/6-311+g (d, p) with TD-DFT theory by Gaussian03 software
The ultraviolet spectra of the compound is calculated under method/base group, calculated result is listed in attached drawing 6；It can be found that calculating gained spectrogram and reality
It tests result and coincide fine, such as calculate two main strong absworption peaks of gained and be located at 249nm and 279nm, one of absorption
Peak and experimental result differ only by 12nm, another absorption peak is then identical；Found by orbit analysis, the two absorption peaks be by
What π → π * transition generated.
10-5In mol/L ethanol solution, it is respectively the ultraviolet excitation of 361nm and 379nm with wavelength, tests this chemical combination
The photoluminescent property of object finds that it has strong fluorescent emission between 400~500nm, and fluorescence spectrum is shown in attached drawing 7；It is shone with ultraviolet lamp
It penetrates, naked eyes visible blue fluorescence.
Synthesis, such as following documents it is worth noting that, the dimer compound is reported in more documents:
L.N.Khokhlova,S.Germane,N.P.Erchak,_E.Lukevits,Chem.Heterocycl.Com.30(1994)
279-282 (report fusing point be 75 DEG C), but so far there are no that someone obtains the high purity single crystal of the compound, therefore reported in the literature
The crystal that fusing point is obtained with us is different from；We compared non-crystallization purifying head product and the crystal after recrystallization it is glimmering
Light property finds that the fluorescence intensity difference of the two is very big, tests the solid fluorescence of same quality, the fluorescence intensity of crystal is probably
Twice or more of head product；With ultraviolet light irradiation, head product can not observe with the naked eye apparent fluorescence, use even if increasing solid
Amount, fluorescence intensity are also nothing like crystal state.
4, anti tumor activity in vitro.
A549 lung carcinoma cell in logarithmic phase growth is become into unicellular, use with 0.25% trypsin digestion cell
It is 1.25 × 10 that concentration, which is made, in F12K culture solution containing 10% fetal calf serum7The single cell suspension of a/L, by cell inoculation in 96
In well culture plate, (the every hole 2.5 × 10 every 200 μ L of hole3A cell).96 porocyte culture plates are placed in CO2In incubator, 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, 50 μM, 100 μM, 200 μM, and every group sets 3 multiple holes, culture
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 182.0 μ to the IC50 (half-inhibitory concentration of drug) of lung cell A549
M, this shows that the compound has mild inhibitory effect to lung carcinoma cell.
5, specific embodiment
Content in order to better understand the present invention further illustrates technology of the invention below by a specific embodiment
Scheme:
Embodiment 1.
It weighs 2 thiophene carboxaldehyde 1.12g (0.01mol) to be dissolved in 30mL dehydrated alcohol, heating stirring adds to whole dissolutions
Enter butanediamine 0.44g (0.005mol), is heated to reflux under stirring 6 hours, is filtered after being cooled to room temperature, filtrate is placed in a beaker standing
Volatilization can obtain a large amount of lenticular precipitatings, will obtain head product after gained precipitating filtering, this head product can use recrystallizing methanol, obtain nothing
Color bulk crystals, as target product.
Embodiment 2.
It weighs 2 thiophene carboxaldehyde 1.12g (0.01mol), is added butanediamine 0.44g (0.005mol), grinding 8 is small under room temperature
When, paste is obtained, 20ml dehydrated alcohol is then added, is dissolved by heating, obtains colourless bulk crystals, as target product after cooling,
Recrystallization can make purifying products.
6, Detailed description of the invention
Attached drawing 1 is the crystal structure figure of target compound, ellipsoid probability 30%.
Attached drawing 2 is the crystal structure accumulation graph of target compound, is observed along b axis direction.
Attached drawing 3 is target compound1H NMR spectra.
Attached drawing 4 is target compound13CNMR spectrogram.
Attached drawing 5 is the ultraviolet spectrogram (experimental result) of target compound.
Attached drawing 6 is the ultraviolet spectrogram (03 calculated result of Gaussian) of target compound.
Attached drawing 7 is the fluorescence spectra (experimental result) of target compound.
Claims (1)
1. the thiophene Schiff base dimer crystal of a kind of butyl connection or it is swollen in preparation treatment in pharmaceutically acceptable salt
Application in tumor medicine, it is characterised in that: the tumour is lung cancer；The crystal appearance is in colorless and transparent bulk, fusing point 68.9-
69.6 DEG C, molecular formula C14H16N2S2, molecular weight 276.42, chemical name are as follows: (N1E,N4E)-N1,N4- two (thiophene -2- methylenes
Base) butane-Isosorbide-5-Nitrae-diamines, structure is as follows:
The crystal category rhombic system, P212121Space group,α=β=γ=90 °,
Z=4.
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| CN109824647B (en) * | 2019-04-08 | 2021-04-06 | 齐鲁工业大学 | Preparation and application of 4-hydroxybenzophenone hydrazone-2-acetylthiophene Schiff base |
| CN110590763B (en) * | 2019-09-30 | 2022-09-30 | 齐鲁工业大学 | Structure, preparation and application of 2-thiazole formaldehyde-thiophene Schiff base |
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Non-Patent Citations (2)
| Title |
|---|
| Synthesis and evaluation of certain symmetrical Schiff bases as inhibitors of MDA-MB-241 human breast cancer cell proliferaton;Smaail Radi等;《Letters in Drug Design & Discovery》;20160229;第13卷;第205-209页 |
| Two families of bis(imido) symmetrical Schiff bases: X-ray crystal structure and optical properties;Xiao-Na Ma等;《Journal of Molecular Structure》;20170224;第1137卷;第681-691页 |
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