Preparation and Use of a Cobalt Complex

Abstract

A cobalt metal complex of 2-amino-4-hydroxy-6-methylpyrimidine, whose structural formula is as follows: #imgabs0# The synthesis method of the 2-amino-4-hydroxy-6-methylpyrimidine cobalt metal complex crystal I is to separately weigh CoCl2·6H2O (0.949 g, 3.99 mmol) and the ligand 2-amino-4-hydroxy-6-methylpyrimidine (1.0 g, 7.9 mmol)), dissolve them in 100 mL of anhydrous methanol and 25 mL of water, and reflux and stir for 30 hours. Perform hot filtration and allow natural evaporation at room temperature. After 3 days, light red crystals appear. The use of the 2-amino-4-hydroxy-6-methylpyrimidine cobalt metal complex crystal I is as an anticancer reagent, showing certain inhibitory activity in liver cancer cell experiments, and its IC 50 value is 21.72 ± 0.78.

Description

Technical Field

[0001] The present invention relates to a preparation and synthesis method of a complex, specifically a preparation and synthesis method of a cobalt complex of 2-amino-4-hydroxy-6-methylpyrimidine. Background Art

[0002] With the development of organic chemistry, metal-organic compounds have been increasingly widely used in organic synthesis, which is one of the most active fields in modern organic chemistry and has been widely applied in organic synthesis reactions and anti-cancer drugs. In recent years, metal complexes have been successively reported, especially cobalt complexes. See Reference [1].

[0003] 1. Bebga G, Nfor EN, Mbiangué YA, Djonwouo PL, Nenwa J. Synthesis and Crystal Structure of the First Example of a Tris-Chelated Co(II) Complex Based on Oxamide Dioxime Ligand. 2015; (May 2017). doi:10.4236 / csta.2015.42002. Summary of the Invention

[0004] The present invention aims to provide a synthesis method for the field of asymmetric synthesis, especially for the preparation of chiral drug compounds. The technical problem to be solved is to select a suitable ligand, 2-amino-4-hydroxy-6-methylpyrimidine, to synthesize a cobalt metal complex in one step.

[0005] (1) The compound referred to in the present invention is a complex represented by the following chemical formula (I):

[0006]

[0007] Its chemical name: cobalt metal complex of 2-amino-4-hydroxy-6-methylpyrimidine, abbreviated as complex (I).

[0008] The synthesis method of the complex (I) includes synthesis, separation, and purification. The synthesis is to separately weigh CoCl2·6H2O (0.949 g, 3.99 mmol) and the ligand 2-amino-4-hydroxy-6-methylpyrimidine (1.0 g, 7.9 mmol), dissolve them in 1**00 mL of anhydrous methanol and 25 mL of water, and reflux and stir for 30 hours. Then, perform hot filtration and allow it to naturally volatilize at room temperature. After 3 days, light red crystals appear. The synthesis route is as follows:

[0009]

[0010] The reaction mechanism of this reaction can be speculated as follows:

[0011] The nitrogen atom in the ligand reacts with cobalt chloride hexahydrate in anhydrous methanol to form a complex in one step. This complex was synthesized using a simple, efficient organic synthesis method, and its structure was confirmed by X-ray diffraction, NMR, IR, and elemental analysis.

[0012] The complex showed a certain catalytic activity in the anti-tumor activity of liver cancer. Its IC 50 The value reached 21.72±0.78. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 It is the crystal structure diagram of target compound I. DETAILED DESCRIPTION

[0014] 1. Preparation of Cobalt Complex 1

[0015] CoCl2·6H2O (0.949 g, 3.99 mmol) and the ligand 2-amino-4-hydroxy-6-methylpyrimidine (1.0 g, 7.9 mmol) were dissolved in 100 mL of anhydrous methanol and 25 mL of water and stirred under reflux for 30 hours. The mixture was filtered and evaporated naturally at room temperature. After 3 days, light red crystals appeared. Yield: 85%; melting point > 250°C; IR peaks at (KBr; ν, cm –1 ): 3520, 3583, 3150, 1650, 1535, 1500, 1415, 1345, 940, 800, 600; HRMS for [C10H14Cl2N6O2Co] calculated: 378.9887found: 379.0922.

[0016] Crystal data of the compound:

[0017] Empirical formula C10H14Cl2N6O2Co

[0018] Molecular weight 380.10

[0019] Temperature 150(0)K

[0020] wavelength

[0021] Crystal system, space group monoclinic, C1 21 / c

[0022] Unit cell parameters alpha=90°.

[0023] beta=106.292(12)°.

[0024] gamma = 90°.

[0025] Volume

[0026] Charge density 8, 1.645 g / m^3

[0027] Absorption correction parameter 8.357 mm^-1

[0028] Number of electrons in the unit cell 1544

[0029] Crystal size 0.10 x 0.02 x 0.02 mm

[0030] Range of Theta angle 3.157 to 48.155°

[0031] Index collection range of HKL -18 <= h <= 18, -8 <= k < 5, -28 <= l <= 28

[0032] Collected / independent diffraction data 12408 / 2169 [R(int) = 0.3634]

[0033] Completeness of data at theta = 30.5 98.2%

[0034] Method of absorption correction Multi-layer scanning

[0035] Method used for refinement Matrix least squares of F^2

[0036] Number of data / number of used restrictions / number of parameters 3893 / 0 / 195

[0037] Method used for refinement 0.939

[0038] Consistency factor of diffraction points R1 = 0.1087, wR2 = 0.2121

[0039] Goodness-of-fit factor for observable diffractions R1 = 0.1762, wR2 = 0.2407

[0040] Maximum peak and valley on the difference Fourier map 0.888 and -0.705 e. 2. Crystal typical bond length and bond angle data:

[0041]

[0042]

[0043] 3. Anticancer activity applications

[0044] The cobalt complex synthesized based on the structure design of active natural products in the present invention shows certain inhibitory activity in cancer cells such as liver cancer tests, and its IC50 value is 21.72 ± 0.78.

[0045] Table 2: Activity of cobalt complex (I) against liver cancer SMMC-7721

[0046] Complex <![CDATA[IC 50 (μM) a > I 21.72±0.78 cis 24.37±0.13

[0047] The test results of its anti-cancer activity are shown in Table 2.

Claims

1. A 2-amino-4-hydroxy-6-methylpyrimidine cobalt metal complex crystal I, whose structural formula is as follows:

2. The 2-amino-4-hydroxy-6-methylpyrimidine cobalt metal crystal complex I according to claim 1, at 150(0) K, on an Oxford X-ray single crystal diffractometer, using MoKα radiation monochromatized by a graphite monochromator Collect diffraction data in the ω-θ scanning mode, characterized in that: Unit cell parameters of the crystal: Monoclinic system, C1 21 / c, alpha = 90°; beta = 106.292(12)°; gamma = 90°.

3. The synthesis method of the 2-amino-4-hydroxy-6-methylpyrimidine cobalt metal crystal complex I described in claim 1, including synthesis and separation. For the synthesis, CoCl2·6H2O (0.949 g, 3.99 mmol) and the ligand 2-amino-4-hydroxy-6-methylpyrimidine (1.0 g, 7.9 mmol) are respectively weighed and dissolved in 100 mL of anhydrous methanol and 25 mL of water, and refluxed and stirred for 30 hours; hot filtered, and naturally volatilized at room temperature. After 3 days, light red crystals appear.

4. Use of the cobalt metal crystal complex I of 2-amino-4-hydroxy-6-methylpyrimidine according to claim 1, characterized in that Prepare anti-hepatocellular carcinoma reagents.

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