CN104788479B - N-pyrimidine-cantharidin amic acid lanthanum (III) complex and preparation method thereof - Google Patents
N-pyrimidine-cantharidin amic acid lanthanum (III) complex and preparation method thereof Download PDFInfo
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- 229940095758 cantharidin Drugs 0.000 title claims abstract description 58
- 239000002253 acid Substances 0.000 title claims abstract description 36
- CZMAIROVPAYCMU-UHFFFAOYSA-N lanthanum(3+) Chemical compound [La+3] CZMAIROVPAYCMU-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000010668 complexation reaction Methods 0.000 title abstract description 4
- 229910052746 lanthanum Inorganic materials 0.000 claims abstract description 10
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims abstract description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- DHZBEENLJMYSHQ-XCVPVQRUSA-N cantharidin Chemical compound 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 29
- 229930008397 cantharidin Natural products 0.000 claims description 27
- DHZBEENLJMYSHQ-UHFFFAOYSA-N cantharidine Natural products O1C2CCC1C1(C)C2(C)C(=O)OC1=O DHZBEENLJMYSHQ-UHFFFAOYSA-N 0.000 claims description 27
- 229910052761 rare earth metal Inorganic materials 0.000 claims description 20
- 150000002910 rare earth metals Chemical class 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 238000012360 testing method Methods 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- 230000006837 decompression Effects 0.000 claims description 6
- 238000004821 distillation Methods 0.000 claims description 5
- 239000013078 crystal Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 238000013459 approach Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- LVESORJKBSOVJG-UHFFFAOYSA-N 2-amino-1H-pyrimidine-2-carbonitrile Chemical compound N#CC1(N)NC=CC=N1 LVESORJKBSOVJG-UHFFFAOYSA-N 0.000 claims description 2
- 238000005352 clarification Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 229910002651 NO3 Inorganic materials 0.000 description 14
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 14
- 238000010521 absorption reaction Methods 0.000 description 7
- 238000002329 infrared spectrum Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- JAABVEXCGCXWRR-UHFFFAOYSA-N norcantharidin Chemical compound C1CC2C3C(=O)OC(=O)C3C1O2 JAABVEXCGCXWRR-UHFFFAOYSA-N 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000013329 compounding Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 4
- -1 rare-earth ion Chemical class 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000001965 diffuse reflectance infrared spectroscopy Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 229910001404 rare earth metal oxide Inorganic materials 0.000 description 3
- 238000002411 thermogravimetry Methods 0.000 description 3
- 241000623906 Lytta vesicatoria Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 150000005005 aminopyrimidines Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000124079 Mylabris Species 0.000 description 1
- 229910052779 Neodymium Inorganic materials 0.000 description 1
- 0 OC(C(C(CC1)OC1*1)C1C(Nc1ncccn1)=O)=O Chemical compound OC(C(C(CC1)OC1*1)C1C(Nc1ncccn1)=O)=O 0.000 description 1
- 241000270666 Testudines Species 0.000 description 1
- JZLUWZPEJDRDEO-UHFFFAOYSA-N [N].C1=CN=CN=C1 Chemical compound [N].C1=CN=CN=C1 JZLUWZPEJDRDEO-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 150000003948 formamides Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- FUXJMHXHGDAHPD-UHFFFAOYSA-N pyrimidine-2-carboxamide Chemical compound NC(=O)C1=NC=CC=N1 FUXJMHXHGDAHPD-UHFFFAOYSA-N 0.000 description 1
- 239000012495 reaction gas Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic Table without C-Metal linkages
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of N-pyrimidine-cantharidin amic acid lanthanum (III) complex and preparation method thereof, its chemical formula is [Ln (HL2)(NO3)(H2O)2](NO3)·2H2O, wherein Ln represents lanthanum, HL2Represent N-pyrimidine-cantharidin amic acid part. N-pyrimidine-cantharidin amic acid lanthanum (III) complex of the application's synthesized has stronger physiologically active and antioxygen stability.
Description
Technical field
The invention belongs to chemosynthesis technical field, specifically refer to a kind of N-pyrimidine-demethyl spotChinese blister beetle element amic acid lanthanum (III) complex and preparation method thereof.
Background technology
Cantharidin (cantharidin, CA) is a kind of day in being extensively present in more than 1500 kind of Chinese blister beetle bodyRight defensive toxin. Mylabris Meloidae insect, taste cold in nature is pungent, is hypertoxic Chinese medicine, except toolHave outside active anticancer, still have the various active such as antiviral, establishing-Yang, increasing leukocyte. ClinicalUpper, cantharidin is demonstrating its unique curative effect aspect treatment cancer and some difficult and complicated cases. ButBecause toxicity is very large, heart kidney organ is had to substantive damage, cantharidin is subject in application very largeRestriction, therefore the more synthetic selective inhibition tumor cells of design, toxicity are little and to bodyImmune response does not have influential cantharidin derivative to be significant.
Recent decades, various countries scholar has synthesized a large amount of cantharidin derivatives and it has been carried outAntitumor activity screening, wherein has this analog derivative of minority to have stronger physiologically active,Drop into clinical use. Compared with cantharidin, in cantharidin (NCTD), lack 1,2Two methyl, stereochemical structure is identical. NCTD not only kept stronger antitumor activity andUnique function of increasing leukocyte, and toxicity reduces greatly, substantially eliminated cantharidin pairUrinary system stimulates side effect. To Normal Bone Marrow Cells DNA, unrestraint even has NCTDCertain promotion, this is that other most of anticancer chemotherapeutic agent are without compared great advantage.
But cantharidin (NCTD) occurs not in the time that clinical practice dosage is slightly largeGood reaction, as excitant of urinary system etc. Animal experiment surface, increases at dosageTo a certain degree time, there is pathological change in kidney and liver. Therefore, for cantharidin(NCTD) using dosage will strictly limit, and this serious cantharidin that hinders(NCTD) performance of drug effect. For this reason, educational circles carries out cantharidin (NCTD)The trial of a lot of architecture advances.
Amide groups is prevalent in the basic structure of protein of nature, and to coordinationIt is also the important composition unit of part for scholar.
Rare earth is a kind of element of not also being familiar with completely by people, along with superconduction, computer, lightThe develop rapidly of the high-technology fields such as fiber communication, Aero-Space, atomic energy, rare earth element andIts compound plays a part more and more important in these fields, make people for these " rareness "Element is regarded with special esteem. But, because rare earth material has certain physiology toxicity, therefore, directlyScoop out for medicine and need to overcome this physiology toxicity.
By retrieval, at present, also there is no document both at home and abroad by amide groups, rare earth and demethylThe direction of cantharidin combination is improved cantharidin.
Summary of the invention
The object of the invention is the shortcoming and defect existing in order to overcome prior art, and provide onePlant and there is brand-new cantharidin transformation product N-pyrimidine-cantharidin amic acidLanthanum (III) complex, it has stronger physiologically active and antioxygen stability.
Another object of the present invention is to provide a kind of above-mentioned N-pyrimidine-cantharidin acid amidesThe preparation method of acid lanthanum (III) complex.
For realizing first object of the present invention, technical scheme of the present invention is it is characterized in that:Its chemical formula is: [Ln (HL2)(NO3)(H2O)2](NO3)·2H2O, its chemical structural formula is:
Wherein Ln represents lanthanum, HL2Represent N-pyrimidine-cantharidin amic acid part,The chemical structural formula of this N-pyrimidine-cantharidin amic acid part is:
For realizing second object of the present invention, its technical scheme is to comprise the following steps:
(1) N-pyrimidine-cantharidin amic acid part is synthetic
Take 1.7g cantharidin in 100ml reaction vessel, the acetonitrile that measures 5ml fallsEnter in l reaction vessel, stirring and dissolving, takes 0.95g2-aminopyrimidine in addition in 50ml beakerIn, the acetonitrile that measures 10ml is dissolved, under stirring at normal temperature, by the second of 2-aminopyrimidineNitrile solution is slowly added drop-wise in the acetonitrile solution of cantharidin, obtains colourless clarification moltenLiquid, builds reflux and temperature is risen to 40 DEG C after mixing, backflow 1.5h, has refluxedBi Hou, decompression distillation goes out the acetonitrile solution of part, reduces the volume of mixed liquor, then will mixLiquid is filled in measuring cup, place more than two days, waits for and has crystal to separate out, then by gainedCrystal is washed for several times with acetonitrile and oxolane, is put at 40 DEG C, baking oven and dries, and obtains yellow brilliantShape material N-pyrimidine-cantharidin amic acid part;
(2) N-pyrimidine-cantharidin amic acid lanthanum complex is synthetic
Taking N-pyrimidine-cantharidin amic acid part 0.5g is dissolved in 4ml methyl alcohol and stirsDissolve, test pH value, close to 5, takes La (NO3)3·nH2O0.4g is dissolved in 2ml methyl alcoholIn, test pH value, for approaching 5, is slowly added drop-wise to rare-earth salts methanol solution under stirring at normal temperatureIn N-pyrimidine-cantharidin amic acid part methanol solution, test pH value approaches 4, dripsAdd 0.1MKOH solution and regulate between PH to 5～6, continue return stirring at 40 DEG C of temperature10h, after backflow, decompression distillation at 40 DEG C, obtains powder, washes for several times with methyl alcohol, places 1～2h,Filter, will remain in material on filter paper place in baking oven and dry at 50 DEG C, obtain N-pyrimidine-Cantharidin amic acid lanthanum complex.
Design considerations of the present invention and Innovation Mechanism are:
(1) amide ligands that the aminopyrimidine of introducing forms is that a class contains the multiple tooth of amide groupsPart. Wherein, can identify the work in cancer cell containing the cantharidin amic acid part of aminopyrimidineProperty position, and be embedded in whole complex, thereby it is lost activity. And the applicationTo have after the part and rare-earth ion coordination of specific physiologically active, both strengthened its physiology and livedProperty, has reduced again the toxicity of rare earth element, is the new drug of the combination of rare earth and cantharidinThing Application and Development provides new reference and trial.
(2) introducing that the application has quoted pyrimidine ring has three effects: the one, improve partNon-oxidizability (improving stability); The 2nd, by the lone electron pair of pyrimidine N, can be directly with inHeart metal-complexing, meanwhile, the π on pyrimidine*Track is accepted central metal ion d electronics and is occurredd-π*Interact, thereby improve the CHARGE DISTRIBUTION of central metal, make it for finding cancer cellAll there is better selection active; The 3rd, pyrimidine nitrogen and ketonic oxygen (or amide nitrogen) can while and metalsCoordination forms five Yuans stable huge legendary turtle cyclizations or the complex of multiple tooth coordination, thereby it is thin to identify cancerActivity site in born of the same parents, and be embedded in whole complex, thereby it is lost activity.
(3) the synthetic N-pyrimidine-cantharidin amic acid lanthanum (III) of the application coordinatesThing, has retained cantharidin and has had oxo bridge structure complete of anticancer function, does not destroyThe active anticancer of cantharidin itself.
(4) the application's synthesis technique cost of material is lower, and reaction is easy to carry out, applicableIn large-scale production.
Below in conjunction with specification drawings and specific embodiments, the present invention is described further.
Brief description of the drawings
The diffuse reflectance infrared spectroscopy frequency diagram of the synthetic part of Fig. 1 the present invention.
Detailed description of the invention
Below by embodiment, the present invention is specifically described, only for the present invention is carried outFurther illustrate, can not be interpreted as limiting the scope of the present invention, the technical staff in this fieldCheng Shike makes some nonessential improvement and adjustment according to the content of foregoing invention to the present invention.
Embodiment
1.1 instrument
Elementary analysis VarioELIII elemental analyser
NEXUS-670 type Fourier transformation infrared spectrometer for infrared spectrum analysis
Thermogravimetric analysis TGA/SDTA851eType thermal analyzer
UV-2501PC ultraviolet-visible photometer for ultraviolet spectral analysis
Molar conductance DDS-12 digital conductivity meter
Hydrogen nuclear magnetic resonance analysis of spectrum BrukerAvanze400MHz NMR
PHS-3C type acidometer
R201D-II rotary evaporator
Melting point apparatus: the WRS-1B of Shanghai Precision Scientific Apparatus Co., Ltd numeral melting point instrument
1.2 reagent
Cantharidin (traditional Chinese medicines group, chemical pure .); 2-aminopyrimidine (AJohnsonMattheyCompany, analyzes pure); Rare earth oxide M2O3(content > 99.9%, Chinese Medicine collectionSolution on Chemical Reagents in Shanghai company of group); Lanthanum La (NO3)3·nH2O; Acetonitrile; Absolute ethyl alcohol; FirstAlcohol; THF; Distilled water; It is pure that other reagent such as DMF are analysis, and water is redistilled water.
The preparation of 2.2 rare earth nitrades
Take a certain amount of rare earth oxide and add a small amount of water, drip while stirring appropriate dense nitreAcid, reaction makes rare earth nitrate solution, and solution obtains rare earth nitrades through evaporative crystallizationLa(NO3)3·nH2The pressed powder of O.
Synthesizing of 2.3N-pyrimidine cantharidin amic acid part
2.3.1N-pyrimidine-cantharidin amic acid part (HL2) synthetic
Take 1.7g (10mmol) cantharidin and, in 100ml round-bottomed flask, measure 5mlAcetonitrile pour in flask, stirring and dissolving. Take in addition 0.95g (10mmol) 2-aminopyrimidineIn 50ml beaker, the acetonitrile that measures 10ml is dissolved. Under stirring at normal temperature, by 2-The acetonitrile solution of aminopyrimidine is slowly added drop-wise in the acetonitrile solution of cantharidin, obtains nothingThe settled solution of look. After mixing, build reflux and temperature is risen to 40 DEG C, refluxAbout 1.5h. After backflow, decompression distillation goes out the acetonitrile solution of part, reduces the body of mixed liquorLong-pending, then mixed liquor is filled in measuring cup, place more than two days, wait for and have crystal to separate out.After a couple of days, the crystal of gained is washed for several times with acetonitrile and THF, is put at 40 DEG C, baking oven and dries,Obtain yellow crystalline material N-pyrimidine-cantharidin amic acid part, the following institute of structural formulaShow:
Productive rate 48%.
This part is slightly soluble in water, and THF is soluble in absolute ethyl alcohol, methyl alcohol, and DMF, in acetonitrile,Be insoluble to chloroform, in ether equal solvent.
Synthesizing of 2.4 complexs
2.4.1N-pyrimidine-cantharidin amic acid rare earth compounding is synthetic
Take HL2Part 0.5 (2mmol) is dissolved in 4ml methyl alcohol stirring and dissolving, test PHValue, close to 5, takes Ln (NO3)3·nH2O0.4 (1mmol) is dissolved in 2ml methyl alcohol, surveysExamination pH value, for approaching 5, is slowly added drop-wise to HL by rare-earth salts methanol solution under stirring at normal temperature2JoinIn body methanol solution, test pH value approaches 4, drips 0.1MKOH solution and regulates PH extremelyBetween 5～6[11], continue return stirring 10h at 40 DEG C of temperature, decompression at 40 DEG C after backflowDistillation, obtains powder, washes for several times with methyl alcohol, places 1～2h, filters, and will remain in filter paperOn material place in baking oven and dry at 50 DEG C, obtain N-pyrimidine-cantharidin amic acidRare earth compounding. The complex of product La is white powdery solid, and the complex of Nd is purplePowdery solid.
3 results and discussion
The composition of 3.1 parts and complex and character
This series complex is more stable in air, is difficult for oxidized. N-pyrimidine-demethyl Chinese blister beetleElement amic acid rare earth compounding is slightly soluble in water, and absolute ethyl alcohol, in DMF, is insoluble in chloroform,Ether, in THF. The color of complex is the characteristic color of rare earth ion: the complex of lanthanumFor white.
Table 1 is elementary analysis and the molar conductance value of part and complex, at 27 DEG C, 1 ×10-3mol.L-1In DMF solution, the molar conductance value that records complex for65-90s.cm2.mol-1Between, be speculated as 1: 1 type dielectric, measure rare earth compounding and consist of[In(HL2)(NO3)(H2O)2](NO3)·2H2O
The results of elemental analyses of table 1 ligands and complexes and molar conductance value
(note: be calculated value in bracket)
The infrared spectrum of 3.2 complexs
3.2.1 the infrared spectrum of part
The diffuse reflectance infrared spectroscopy frequency of part is shown in the infrared spectrum pair of Fig. 1 and part and complexAccording in table 2.
Part HL2Infrared spectrum in there is 3260cm-1Near (vN-H)，1716cm-1Neighbouring is strong peak, has the carbonyl v in carboxylic acidC＝O，1668cm-1Strong absorption is vC＝OAcid amides IBand, 1236cm-1，932cm-1For the infrared signature absworption peak of ether-oxygen bond (C-O-C), 1540cm-1Near absorption belongs to pyrimidine ring skeleton stretching vibration absorption etc.
3.2.2 the infrared spectrum of complex
Complex is at 3000～3450cm-1There is wide and stronger absworption peak in place, may be crystallizationThe antisymmetry of the OH of water and symmetrical stretching vibration peak, and by the v of partN-HPeak is covered. ?The v of carboxylic acid in complexC＝OTo lower wave number red shift 32～40cm-1, shown the hydroxyl in carboxylic acidThe coordination of base oxygen and rare earth ion. 1540cm-1After forming complex, be split into approximately 1598And 1569cm-1Two peaks, illustrate that pyrimidine N atom has also participated in coordination, and each complex all exists1384cm-1Near have the absworption peak of the last one, be free NO3 -Absorption, represent outside complexThere is NO in boundary3 -Ion. Complex infrared spectrum is at 1474cm-1，1297cm-1，1033cm-1，817cm-1，753cm-1Near have some peaks, what have may be capped or strengthen, stillStill there is absworption peak in them, can judge that in complex, boundary exists the NO that makes part3 -Ion.
The main diffuse reflectance infrared spectroscopy peak (cm of table 2. ligands and complexes-1)
The uv-vis spectra of 3.3 parts and complex
Within the scope of 200～400nm, measured the ultraviolet light of 2-aminopyrimidine using water as solventSpectrum. Record two ultraviolets appear in 2-aminopyrimidine absworption peak at 223nm and 283nm, whenAfter it reacts with cantharidin, the part HL recording2Go out at 223nm and 292nmShow two ultraviolet absorption peaks, correspond respectively to two π of pyrimidine ring-π*Transition absorption band,1La(π-π*) and1Lb(π-π*), from 283nm to 292nm1Lb(π-π*) locate to have occurred red shift. Thus canInfer that cantharidin and 2-aminopyrimidine may form amide groups, produce joining of our needsBody HL2. Form after complex, can record the complex of La and Nd respectively at 287nmThere is absworption peak with 291nm place, known HL2Middle 292nm absworption peak is sent out after formation complexRaw violet shift (Δ λ=2～5nm), this is on the 5d unoccupied orbital and pyrimidine ring due to rare earth ionN coordination after, strengthened conjugation, make maximum system energy reduce. The absorption at 223nm placePeak is because and NO3 -Ion is overlapping, and intensity increases, and has become broad peak by spike, and cooperation is describedIn thing, there is free NO3 -, and complex exists1La(π-π*) locate still to have absworption peak.
The mensuration of 3.4 part fusing points
The fusing point of part is measured with melting point detector. Intensification scope is at 90 DEG C-300 DEG C, through surveyingAmount part HL1In the time of 145.9 DEG C, start fusing, during to 147.6 DEG C, melt its melting range completelyScope is 145.9 DEG C-147.6 DEG C; Part HL2Melting range scope be 103.3 DEG C-104.9 DEG C.
The thermogravimetric analysis of 3.5 complexs
At 20 DEG C of .min of heating rate-1, 28 DEG C～900 DEG C of ranges, taking nitrogen as protection gas, skyGas is reaction gas, measures the thermogravimetric curve of complex. From the TG curve map of complex,La complex lost 2 molecular crystalline water in the past at 150 DEG C,, this can find out, in complex4 molecular waters, wherein 2 molecules are the crystallization water, 2 molecules are water of coordination. Analyze TG curveKnown, several places Weight lose on curve, for the step-by-step oxidation of complex decomposes, complex dividesThe first stage of separating, be speculated as the crystallization water that loses 2 molecules; Second stage, is speculated as and losesThe water of coordination of the nitrate anion of 1 molecule and 2 molecules; Phase III, be speculated as the nitre that loses interior boundaryAcid group and pyrimidine amide ligands; Final residue thing is rare earth oxide Ln2O3。
The thermogravimetric analysis result of two kinds of rare earth compoundings of table 3.
(in bracket, being theoretical value)
The structure of 3.6 complexs
The application is by the design of above-mentioned synthesis technique, synthesized that to have no the N-of bibliographical information phoneticPyridine-cantharidin amic acid lanthanum complex, measures consisting of of this complex by sign[La(HL2)(NO3)(H2O)2](NO3)·2H2O, its chemical structural formula is:
Claims (1)
1. a preparation method for N-pyrimidine-cantharidin amic acid lanthanum (III) complex,It is characterized in that:
The chemical formula of this N-pyrimidine-cantharidin amic acid lanthanum (III) complex is:[Ln(HL2)(NO3)(H2O)2](NO3)·2H2O, its chemical structural formula is:
Wherein Ln represents lanthanum, HL2Represent N-pyrimidine-cantharidin amic acid part,The chemical structural formula of this N-pyrimidine-cantharidin amic acid part is:
This preparation method comprises the following steps:
(1) N-pyrimidine-cantharidin amic acid part is synthetic
Take 1.7g cantharidin in 100ml reaction vessel, the acetonitrile that measures 5ml fallsEnter in l reaction vessel, stirring and dissolving, takes 0.95g2-aminopyrimidine in addition in 50ml beakerIn, the acetonitrile that measures 10ml is dissolved, under stirring at normal temperature, by the second of 2-aminopyrimidineNitrile solution is slowly added drop-wise in the acetonitrile solution of cantharidin, obtains colourless clarification moltenLiquid, builds reflux and temperature is risen to 40 DEG C after mixing, backflow 1.5h, has refluxedBi Hou, decompression distillation goes out the acetonitrile solution of part, reduces the volume of mixed liquor, then will mixLiquid is filled in measuring cup, place more than two days, waits for and has crystal to separate out, then by gainedCrystal is washed for several times with acetonitrile and oxolane, is put at 40 DEG C, baking oven and dries, and obtains yellow brilliantShape material N-pyrimidine-cantharidin amic acid part;
(2) N-pyrimidine-cantharidin amic acid lanthanum complex is synthetic
Taking N-pyrimidine-cantharidin amic acid part 0.5g is dissolved in 4ml methyl alcohol and stirsDissolve, test pH value, close to 5, takes La (NO3)3·nH2O0.4g is dissolved in 2ml methyl alcoholIn, test pH value, for approaching 5, is slowly added drop-wise to rare-earth salts methanol solution under stirring at normal temperatureIn N-pyrimidine-cantharidin amic acid part methanol solution, test pH value approaches 4, dripsAdd 0.1MKOH solution and regulate between PH to 5～6, continue return stirring at 40 DEG C of temperature10h, after backflow, decompression distillation at 40 DEG C, obtains powder, washes for several times with methyl alcohol, places 1～2h,Filter, will remain in material on filter paper place in baking oven and dry at 50 DEG C, obtain N-pyrimidine-Cantharidin amic acid lanthanum complex.
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| Synthesis, Characterization, DNA-Binding Studies of Rare Earth Complexes With N-Phenyl Norcantharidin Acylamide Acid;Wen-Zhong Zhu等;《Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metatal Chemistry》;20121231;第42卷;692-697 * |
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Denomination of invention: N-pyrimidinyl-norcantharidin amic acid lanthanum (III) complex and preparation method thereof Effective date of registration: 20191219 Granted publication date: 20160504 Pledgee: Bank of Communications Ltd Lu'an branch Pledgor: Anhui Benma Pioneer Technology Co., Ltd. Registration number: Y2019980001130 |