Preparation method and application of imidazoline metal complex

Abstract

A synthetic method of a tetraimidazoline copper chloride complex I, a hexa-imidazoline nickel complex II, a hexa-imidazoline copper perchlorate complex III, a tetraimidazoline zinc nitrate complex IV and a tetraimidazoline copper nitrate complex V shown in the following chemical formulas I-V comprises the following steps: respectively weighing 0.1622 g, 0.2673 g, 0.1622 g, 0.1622 g and 0.1622 g of N, N '-carbonyldiimidazole, putting the weighed materials into a 100mL round-bottom flask, then respectively adding 0.0853 g of copper chloride dihydrate, uniformly stirring the materials, and carrying out vacuum drying to obtain the tetraimidazoline copper chloride complex I, the hexa-imidazoline nickel complex II, the hexa-imidazoline copper perchlorate complex III, the tetraimidazoline zinc nitrate complex IV and the tetraimidazoline copper nitrate complex V; the preparation method comprises the following steps: respectively dissolving 0.1829 g of nickel perchlorate hexahydrate, 0.1853 g of copper perchlorate hexahydrate, 0.1488 g of zinc nitrate hexahydrate and 0.1208 g of copper nitrate trihydrate with 30 mL of absolute ethyl alcohol and 10 mL of distilled water; heating and refluxing for 5 hours, carrying out hot filtration, and naturally volatilizing for several days to separate out crystals; the chemical formula of the tetraimidazoline copper nitrate complex V is as follows: # imgabs0 #, and the application of the tetraimidazoline copper nitrate complex V is as follows: the crystal copper complex V shows certain inhibitory activity in cancer cell resistance tests such as lung cancer A-549, and the anti-cancer inhibition rate is 54.84 + / -0.75%.

Description

Technical Field

[0001] The invention relates to a method for preparing a metal organic coordination compound, in particular to a method for synthesizing a metal organic complex containing imidazoline and its application, more specifically to a method for synthesizing an imidazoline nickel nitrate complex and a monohydrate imidazoline zinc chloride complex and its application. Background Art

[0002] With the development of organic chemistry, the application of metal organic compounds in organic synthesis is becoming more and more extensive. It is one of the most active fields in organic chemistry and has been widely used in organic synthesis reactions. The synthesis reaction catalyzed by imidazoline ligands and transition metal complexes has greatly accelerated the research of drugs. In recent years, the synthesis and application research of imidazoline and metal zinc and nickel complexes have appeared one after another, see references [1-2].

[0003] References:

[0004] (1)Lee, HM; Chiu, PL; Hu, C.-H.; Lai, C.-L.; Chou, Y.-C.Synthesis and structural characterization of metal complexes based on pyrazole / imidazoliumchlorides.J.Organomet.Chem.2005,690(2),403-414.DOI:10.1016 / j.jorganchem.2004.09.053.

[0005] (2) Soayed, AA; Refaat, HM; El-Din, DANMetal complexes of moxifloxacin–imidazole mixed ligands: characterization and biological studies. Inorg. Chim. Acta 2013, 406, 230-240. DOI: 10.1016 / j.ica.2013.04.040.

[0006] (3) K.; Várnagy, K.; Süli-Vargha, H.; Sanna, D.; Micera, G.; I.Transition metal complexes of bis(imidazol-2-yl)derivatives ofdipeptides.In Dalton Trans.,2003;p 2009-2016.Slater,JW;D'Alessandro,DM;Keene,FR;Steel,PJMetal-metal interactions in dinuclear rutheniumcomplexes containing bridging 4,5-di(2-pyridyl)imidazolates and relatedligands.In Dalton Trans.,2006 / 04 / 13ed.; 2006; p 1954-1962.

[0007] (4) Hindi, KM; Panzner, MJ; Tessier, CA; Cannon, CL; Youngs, WJ. Summary of the invention

[0008] The present invention aims to provide a Ni-N metal organic complex for application in the field of catalysis. The technical problem to be solved is to select N,N'-thiocarbonyldiimidazole as a ligand to synthesize an imidazoline metal complex in one step.

[0009] The copper complex referred to in the present invention is a complex shown in the following chemical formula prepared by heating N,N'-thiocarbonyldiimidazole and nickel nitrate hexahydrate in 30 mL of anhydrous methanol under reflux for 24 hours:

[0010]

[0011] Chemical name: Copper tetraimidazoline complex, referred to as complex (I).

[0012] Weigh 0.1622g N,N'-carbonyldiimidazole into a 100mL round-bottom flask, add 20mL anhydrous ethanol and 10mL distilled water and stir to dissolve; dissolve 0.0853g cupric chloride dihydrate in 10mL anhydrous ethanol and add the above solution, heat and reflux for 5h; after the reaction is completed, filter the reaction solution while hot, the filtrate evaporates naturally, and crystals precipitate after a few days. The reaction equation is as follows:

[0013]

[0014] The nickel complex referred to in the present invention is a complex shown in the following chemical formula prepared by heating N,N'-thiocarbonyldiimidazole and nickel nitrate hexahydrate in 30 mL of anhydrous methanol under reflux for 24 hours:

[0015]

[0016] Chemical name: Hexaimidazole nickel perchlorate complex, referred to as complex (II).

[0017] The synthesis method of the complex I is as follows: 0.2673 g of N,N'-carbonyldiimidazole is weighed and placed in a 100 mL round-bottom flask, 20 mL of anhydrous ethanol and 10 mL of distilled water are added and stirred to dissolve; 0.1829 g of nickel perchlorate hexahydrate is dissolved in 10 mL of anhydrous ethanol and the above solution is added, and heated.

[0018] Reflux for 5 hours; filter the reaction solution while hot after the reaction is completed, and the filtrate evaporates naturally. Crystals precipitate after a few days. The reaction equation is as follows:

[0019] The copper complex referred to in the present invention is a complex shown in the following chemical formula prepared by heating N,N'-thiocarbonyldiimidazole and nickel nitrate hexahydrate in 30 mL of anhydrous methanol under reflux for 24 hours:

[0020]

[0021] Chemical name: tetraimidazoline copper perchlorate complex, referred to as complex (III).

[0022] The synthesis method of the complex (III) is as follows: 0.1622 g of N,N'-carbonyldiimidazole is weighed and placed in a 100 mL round-bottom flask, 20 mL of anhydrous ethanol and 10 mL of distilled water are added and stirred to dissolve; 0.1853 g of copper perchlorate hexahydrate is dissolved in 10 mL of anhydrous ethanol and added to the above solution, and heated to reflux for 5 h; after the reaction is completed, the reaction solution is filtered while hot, the filtrate evaporates naturally, and crystals precipitate after a few days. The reaction equation is as follows:

[0023]

[0024] The zinc complex referred to in the present invention is a complex shown in the following chemical formula prepared by heating N,N'-thiocarbonyldiimidazole and zinc nitrate hexahydrate in 30 mL of anhydrous methanol under reflux for 24 hours:

[0025]

[0026]

[0027] Chemical name: Tetraimidazoline zinc nitrate complex, referred to as complex (IV).

[0028] The synthesis method of the complex IV is as follows: weigh 0.1622g N,N'-carbonyldiimidazole and put it into a 100mL round-bottom flask, add 20mL anhydrous ethanol and 10mL distilled water and stir to dissolve it; dissolve 0.1488g zinc nitrate hexahydrate in 10mL anhydrous ethanol and add the above solution, heat and reflux for 5h; after the reaction is completed, filter the reaction solution while hot, and the filtrate evaporates naturally. After a few days, crystals precipitate. The chemical equation is as follows:

[0029]

[0030] The copper complex referred to in the present invention is a complex shown in the following chemical formula prepared by heating N,N'-thiocarbonyldiimidazole and zinc nitrate hexahydrate in 30 mL of anhydrous methanol under reflux for 24 hours:

[0031]

[0032] Chemical name: Tetraimidazoline copper nitrate complex, referred to as complex (V).

[0033] The synthesis method of the complex V is as follows: 0.1622g of N,N'-carbonyldiimidazole is weighed and placed in a 100mL round-bottom flask, 20mL of anhydrous ethanol and 10mL of distilled water are added and stirred to dissolve; 0.1488g of zinc nitrate hexahydrate is dissolved in 10mL of anhydrous ethanol and added to the above solution, and heated to reflux for 5h; after the reaction is completed, the reaction solution is filtered while hot, and the filtrate evaporates naturally. After a few days, crystals are precipitated. The chemical formula is as follows:

[0034]

[0035] The crystal data of copper complex I are as follows:

[0036]

[0037] Typical bond length data for crystals:

[0038]

[0039]

[0040] Typical bond angle data of crystals:

[0041]

[0042]

[0043]

[0044] The crystal data of nickel complex II are as follows:

[0045]

[0046]

[0047] Typical bond length data for crystals:

[0048]

[0049]

[0050] Typical bond angle data of crystals:

[0051]

[0052]

[0053] The crystal data of copper complex III are as follows:

[0054]

[0055]

[0056] Typical bond length data for crystals:

[0057]

[0058]

[0059] Typical bond angle data of crystal: C(2)-C(1)-N(1)109.7(2)

[0060]

[0061]

[0062] The crystal data of zinc complex IV are as follows:

[0063]

[0064]

[0065] Typical bond length data for crystals:

[0066]

[0067]

[0068] Typical bond angle data of crystals:

[0069]

[0070]

[0071] The crystal data of copper complex V are as follows:

[0072]

[0073]

[0074] Typical bond length data for crystals:

[0075]

[0076]

[0077] Typical bond angle data of crystals:

[0078]

[0079]

[0080] BRIEF DESCRIPTION OF THE DRAWINGS

[0081] Figure 1 X-ray diffraction analysis of copper chloride complex I.

[0082] Figure 2 X-ray diffraction analysis of nickel perchlorate complex II.

[0083] Figure 3 X-ray diffraction analysis of copper perchlorate complex III.

[0084] Figure 4 X-diffraction analysis of zinc nitrate complex IV.

[0085] Figure 5 X-ray diffraction analysis of copper nitrate complex V. DETAILED DESCRIPTION

[0086] 1. Preparation of tetraimidazoline copper complex I

[0087] Weigh 0.1622g N,N'-carbonyldiimidazole into a 100mL round-bottom flask, add 20mL anhydrous ethanol and 10mL distilled water and stir to dissolve; dissolve 0.0853g cupric chloride dihydrate in 10mL anhydrous ethanol and add the above solution, heat and reflux for 5h; filter the reaction solution while hot after the reaction is completed, the filtrate evaporates naturally, and crystals precipitate after a few days; rinse the crystals with petroleum ether and n-hexane for 3 times, vacuum dry for 30min, and obtain the target product with a yield of 93% and a melting point of 205-208℃. Elemental analysis data C12 H16 Cu Cl2 N8, theoretical value: C: 35.4%; H: 3.9%; N: 27.5%; measured value: C: 35.9%; H: 3.9%; N: 27.9%; infrared spectrum data (KBr, cm -1 ):3301;3121;1535;1335;1069;860;777;664;611.

[0088] 2. Preparation of Hexaimidazoline Nickel Perchlorate Complex II

[0089] Weigh 0.2673g N,N'-carbonyldiimidazole into a 100mL round-bottom flask, add 20mL anhydrous ethanol and 10mL distilled water and stir to dissolve; dissolve 0.1829g nickel perchlorate hexahydrate in 10mL anhydrous ethanol and add the above solution, heat and reflux for 5h; filter the reaction solution while hot after the reaction is completed, the filtrate evaporates naturally, and crystals precipitate after a few days; rinse the crystals with petroleum ether and n-hexane for 3 times, vacuum dry for 30min, and obtain the target product with a yield of 88% and a melting point of 228-231℃. Elemental analysis data C18 H24 Cl2 Ni N12 O4, theoretical value: C: 32.4%; H: 3.6%; N: 25.3%; measured value: C: 32.1%; H: 3.5%; N: 25.8%; infrared spectrum data (KBr, cm -1 ): 3365; 3151; 1538; 1327; 1063; 847; 755; 663; 623;

[0090] 3. Preparation of tetraimidazoline copper perchlorate complex III

[0091] Weigh 0.1622g N,N'-carbonyldiimidazole into a 100mL round-bottom flask, add 20mL anhydrous ethanol and 10mL distilled water and stir to dissolve; dissolve 0.1853g copper perchlorate hexahydrate in 10mL anhydrous ethanol and add the above solution, heat and reflux for 5h; filter the reaction solution while hot after the reaction is completed, the filtrate evaporates naturally, and crystals precipitate after a few days; rinse the crystals with petroleum ether and n-hexane for 3 times, vacuum dry for 30min, and obtain the target product with a yield of 90% and a melting point of 229-234℃. Elemental analysis data C12 H16 Cu Cl2 N8 O8, theoretical value: C: 26.9%; H: 3.0%; N: 20.9%; measured value: C: 26.8%; H: 2.9%; N: 21.4%; infrared spectrum data (KBr, cm -1 ): 3384; 3143; 1544; 1433; 1330; 1069; 847; 756; 664; 627.

[0092] 4. Preparation of zinc nitrate complex IV

[0093] Weigh 0.1622 g of N,N'-carbonyldiimidazole and put it into a 100 mL round-bottom flask, add 20 mL of anhydrous ethanol and 10 mL of distilled water and stir to dissolve it; dissolve 0.1488 g of zinc nitrate hexahydrate in 10 mL of anhydrous ethanol and add the above solution, heat and reflux for 5 hours; after the reaction is completed, filter the reaction solution while it is hot, and the filtrate evaporates naturally. Crystals precipitate after a few days.

[0094] The crystals were rinsed with petroleum ether and n-hexane for 3 times and vacuum dried for 30 min to obtain the target product with a yield of 70% and a melting point of 110-114°C. Elemental analysis data C12 H16 Zn N10 O6, theoretical value: C: 31.2%; H: 3.5%; N: 30.3%; measured value: C: 31.6%; H: 3.7%; N: 30.7%; infrared spectrum data (KBr, cm -1 ): 3134; 1582; ​​1385; 1330; 1071; 936; 833; 766; 661; 617.

[0095] 5. Preparation of Copper Nitrate Complex V

[0096] Weigh 0.1622g N,N'-carbonyldiimidazole into a 100mL round-bottom flask, add 20mL anhydrous ethanol and 10mL distilled water and stir to dissolve; dissolve 0.1208g copper nitrate trihydrate in 10mL anhydrous ethanol and add the above solution, heat and reflux for 5h; filter the reaction solution while hot after the reaction is completed, the filtrate evaporates naturally, and crystals precipitate after a few days; rinse the crystals with petroleum ether and n-hexane for 3 times, vacuum dry for 30min, and obtain the target product with a yield of 95% and a melting point of 182-187℃. Elemental analysis data C12 H16 Cu N10 O6, theoretical value: C: 31.4%; H: 3.5%; N: 30.5%; measured value: C: 31.0%; H: 3.6%; N: 30.6%; infrared spectrum data (KBr, cm -1 ): 3137; 1538; 1385; 1321; 1071; 944; 664; 609.

[0097] 6. Anticancer activity of complex IV

[0098] The complex I synthesized according to the structure of the active natural product shows certain inhibitory activity in tests on cancer cells such as lung cancer A-549, liver cancer (SMMC-7721) and colon cancer SW480 (uM). The inhibition rate is shown in Table 1:

[0099] Table 1. Anticancer inhibition rate data of complexes I-IV)

[0100]

Claims

1. A tetraimidazoline copper chloride complex having the following chemical formula I and unit cell parameters, characterized in that: The synthesis is as follows: 0.1622g of N,N'-carbonyldiimidazole is placed in a 100mL round-bottom flask, 20mL of anhydrous ethanol and 10mL of distilled water are added and stirred to dissolve; 0.0853g of cupric chloride dihydrate is dissolved in 10mL of anhydrous ethanol and added to the above solution, and heated to reflux for 5h; after the reaction is completed, the reaction solution is filtered while hot, the filtrate evaporates naturally, and crystals precipitate after a few days; the chemical formula of the complex is as follows: The unit cell parameters of the complex I are as follows: orthorhombic system, Pmn21; unit cell parameters: α=90°, β=90°; γ=90°.

2. A nickel hexaimidazoline complex having the following chemical formula II and unit cell parameters, characterized in that: Weigh 0.2673g N,N'-carbonyldiimidazole into a 100mL round-bottom flask, add 20mL anhydrous ethanol and 10mL distilled water and stir to dissolve; dissolve 0.1829g nickel perchlorate hexahydrate in 10mL anhydrous ethanol and add the above solution, heat and reflux for 5h, filter the reaction solution, and the filtrate evaporates naturally. After a few days, crystals precipitate; the chemical formula of the complex is as follows: The unit cell parameters of the complex II are: monoclinic, P21 / n, α=90°; β=90.214(2)°; γ=90°.

3. A hexaimidazole copper perchlorate complex represented by the following chemical formula III and unit cell parameters, characterized in that: The synthesis method of the complex III is as follows: 0.1622g of N,N'-carbonyldiimidazole is weighed and placed in a 100mL round-bottom flask, 20mL of anhydrous ethanol and 10mL of distilled water are added and stirred to dissolve; 0.1853g of copper perchlorate hexahydrate is dissolved in 10mL of anhydrous ethanol and added to the above solution, and heated to reflux for 5h; after the reaction is completed, the reaction solution is filtered while hot, the filtrate evaporates naturally, and crystals precipitate after a few days; the chemical formula of the complex is as follows: The unit cell parameters of the complex III are: monoclinic system, P21 / n; its unit cell parameters are: α=90°; β=90.214(2)°; γ=90°.

4. A tetraimidazoline zinc nitrate complex represented by the following chemical formula IV and unit cell parameters, characterized in that: The synthesis method of the complex IV is as follows: 0.1622g of N,N'-carbonyldiimidazole is weighed and placed in a 100mL round-bottom flask, 20mL of anhydrous ethanol and 10mL of distilled water are added and stirred to dissolve; 0.1488g of zinc nitrate hexahydrate is dissolved in 10mL of anhydrous ethanol and added to the above solution, and heated to reflux for 5h; after the reaction is completed, the reaction solution is filtered while hot, the filtrate evaporates naturally, and crystals precipitate after a few days; the chemical formula of the complex is as follows:

5. A tetraimidazoline copper nitrate complex represented by the following chemical formula V and unit cell parameters, characterized in that: Weigh 0.1622g N,N'-carbonyldiimidazole into a 100mL round-bottom flask, add 20mL anhydrous ethanol and 10mL distilled water and stir to dissolve; dissolve 0.1208g copper nitrate trihydrate in 10mL anhydrous ethanol and add the above solution, heat and reflux for 5h; after the reaction is completed, filter the reaction solution while hot, and the filtrate evaporates naturally. After a few days, crystals precipitate; The unit cell parameters of the complex V are: orthorhombic system, Pbcn; unit cell parameters: α=90°; β=90°; γ=90°.

6. The purpose of the tetraimidazoline nitrate copper complex V according to claim 5 is that the crystalline copper complex V shows certain inhibitory activity in anticancer cells such as lung cancer A-549 test, and its anticancer inhibition rate is 54.84±0.75%.

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