A bispyrazolopyridine iron (II) complex and a method for synthesizing the same

Abstract

The application discloses a kind of double pyrazolopyridine iron (II) complex and synthesis method thereof, belong to the technical field of coordination chemistry synthesis.The method is with aryl hydrazine and aryl formyl acetonitrile as substrate, iron trichloride hexahydrate is used as accelerator, and double pyrazolopyridine iron (II) complex single crystal is synthesized by solvothermal reaction one-pot method in alcohol solvent.The application realizes the synthesis of double pyrazolopyridine three heterocyclic rings without substituent group at position 4 for the first time, and introduces new substituent group such as benzothiazole-2-yl and benzimidazole-2-yl to position 1 and 7, which expands the substituent group types of the compounds.The method has mild reaction condition, and the raw materials are cheap and easy to obtain, and the operation is simple, with medium to good yield, which provides a new way for the synthesis of double pyrazolopyridine complexes.

Description

Technical Field

[0001] This invention relates to the field of coordination chemistry synthesis technology, specifically to a bispyrazolopyridine iron(II) complex and its synthesis method. Background Technology

[0002] Bispyrazolopyridine tricyclic molecules, due to their rigid planar conjugated structure and abundant coordination sites, hold significant promise for applications in optoelectronic materials, catalysts, and bioactive molecules. However, their development is limited by existing inefficient synthetic methods.

[0003] Currently, the synthesis of this skeleton mainly relies on the cyclization condensation reaction of 5-aminopyrazole and aromatic aldehyde. This method has significant drawbacks: First, the aldehyde carbon forms the 4th position of the pyridine ring, which strictly limits the substituent at this position to aryl or acyl groups, making it difficult to introduce alkyl or hydrogen atoms and limiting the space for structural modification. Second, the introduction of substituents at positions 1 and 7 depends on the pre-modification of the starting material, which is cumbersome and has a limited range of groups that can be introduced, making it difficult to graft functional groups such as benzo[a]heterocyclic rings.

[0004] More importantly, due to coordination configuration limitations, stable metal complexes (especially transition metal complexes) based on this framework have not yet been reported, hindering their application in catalysis and functional materials. Existing synthetic strategies are lengthy and inefficient, and lack an integrated method that can simultaneously achieve framework construction, diverse introduction of substituents, and in-situ generation of metal complexes. Therefore, developing a new synthetic strategy that overcomes these limitations is an urgent need in this field. Summary of the Invention

[0005] The primary objective of this invention is to overcome the shortcomings of existing technologies and provide a simple, inexpensive, and readily available "one-pot" synthetic strategy for preparing a series of novel bispyrazolopyridine iron(II) complexes. This method introduces novel substituents such as benzothiazoles and benzimidazoles into the 1 and 7 positions of the bispyrazolopyridine skeleton, and for the first time achieves the introduction of an alkyl group into the 4 position or maintains it as an unsubstituted hydrogen atom, thereby greatly expanding the structural diversity of such molecules.

[0006] The technical solution of this invention is implemented as follows:

[0007] On one hand, this invention provides a method for synthesizing a bispyrazolopyridine iron(II) complex, comprising the following steps: dissolving arylhydrazine, arylformylacetonitrile, and ferric chloride hexahydrate in an organic solvent, and reacting to obtain the target complex. This complex utilizes arylhydrazine as a substrate and reacts with benzoylacetonitrile in a Fe... 3+ The bispyrazolopyridine organic framework was constructed under facilitated conditions, avoiding the use of highly reactive aromatic aldehydes as substrates. The synthetic reaction formula is shown below:

[0008] .

[0009] Based on the above technical solutions, the preferred synthesis method is to dissolve arylhydrazine, arylformylacetonitrile, and ferric chloride hexahydrate in methanol or ethanol in stoichiometric proportions, react to obtain yellow-brown blocky single crystals, and then filter, wash, and dry to obtain the corresponding bispyrazolopyridine iron(II) complex.

[0010] More preferably, the molar ratio of arylhydrazine, arylformylacetonitrile and ferric chloride hexahydrate is 1:1:(0.5-3).

[0011] More preferably, the molar ratio of the arylhydrazine, arylformylacetonitrile, and ferric chloride hexahydrate is 1:1:1. The reaction involves multi-step cyclization and requires Fe. 3+ It forms an intermediate complex with the reactants. The 1:1:1 ratio ensures that arylhydrazine and arylformylacetonitrile fully participate in the reaction, while Fe... 3+ Excessive but not excessive amounts are used to account for differences in reactivity among different substrates. Fe 3+ Sufficient quantity ensures effective activation of the reactants, promotes condensation and cyclization, provides ample oxidizing power to generate the desired formaldehyde, and avoids side reactions. Simultaneously, Fe... 3+ Reduced to Fe 2+ The process requires an appropriate amount of Fe 3+ To maintain a reducing atmosphere—hydrogen generation—a 1:1:1 ratio balances the oxidation and reduction steps, ensuring the stable formation of the iron(II) complex.

[0012] Further preferred, the reaction temperature is 140 °C and the reaction time is 24 hours.

[0013] Secondly, the present invention provides a bispyrazolopyridine iron(II) complex, the structure of which is shown below:

[0014] .

[0015] Based on the above technical solutions, preferably, in the complex, R is a hydrogen atom or a methyl group. (This is achieved through Fe...) 3+ During oxidation, methanol is converted to formaldehyde, which then participates in the cyclization process, providing a carbon atom at the 4-position of the pyridine ring. When ethanol is used, a methyl group can be introduced at the 4-position, demonstrating the universality of the solvent as a direct alkyl source.

[0016] More preferably, in the complex, Ar is derived from arylhydrazine and is selected from one of pyridin-2-yl, benzimidazole-2-yl, and benzothiazol-2-yl.

[0017] More preferably, in the complex, Ar' is derived from arylformylacetonitrile, and Ar' is selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 3-methoxyphenyl, and thiophen-2-yl.

[0018] More preferably, the complex is in single-crystal form. Its crystal belongs to the monoclinic crystal system, with space group P21 / c.

[0019] The present invention has the following beneficial effects:

[0020] (1) A new strategy for the one-pot synthesis of bispyrazolidine metal complexes was proposed for the first time, which combines the two steps of ligand synthesis and metal coordination into one, simplifies the process, avoids the separation and purification of intermediates, and saves costs.

[0021] (2) For the first time, an alkyl substituent was successfully introduced into the 4 position of the bispyrazolopyridine skeleton or the hydrogen atom was retained, and novel substituents such as benzothiazole and benzimidazole were introduced into the 1 and 7 positions, which greatly expanded the structural library of this type of molecule and provided more possibilities for performance research.

[0022] (3) This invention reveals the multiple roles of iron ions in the reaction, especially by using methanol as a carbon source instead of the active and unstable aldehyde substrates in the traditional method, making the reaction safer and more controllable.

[0023] (4) The reaction conditions are mild and do not require harsh operations such as anhydrous and oxygen-free processes; the raw materials used are all inexpensive and readily available commercial chemicals, which are very suitable for large-scale production.

[0024] (5) The product was directly precipitated in the form of high-purity single crystals. Its structure was fully characterized by a variety of methods such as X-ray single crystal diffraction, X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (PXRD), and high-resolution mass spectrometry, which confirmed its novel coordination mode. Attached Figure Description

[0025] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0026] Figure 1 The molecular structures of the complexes ae and 1-a of this invention are shown below;

[0027] Figure 2 The molecular structure of the complex a of the present invention is shown in (a); the coordination spheres are shown in (b); the weak intermolecular interactions (hydrogen bonds) are shown in (c) and the weak intermolecular interactions (π-π stacking) are shown in (d).

[0028] Figure 3 X-ray photoelectron spectroscopy (a), X-ray powder diffraction pattern (b), thermogravimetric analysis curve (c), and high-resolution mass spectrum (d) of complex a of the present invention.

[0029] Figure 4 This invention relates to time-dependent high-resolution mass spectrometry.

[0030] Figure 5 This is a possible formation mechanism of bispyrazolopyridine in this invention;

[0031] Figure 6 The reaction formula for the synthesis of the bispyrazolopyridine Fe(II) complex of the present invention is shown. Detailed Implementation

[0032] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0033] Material Source Description Table 1:

[0034]

[0035] Example 1

[0036] Complex a: FeLCl2 (L = 2,2'-(3,5-diphenylbispyrazole[3,4-)) b :4',3'- e ]pyridine-1,7-diyl)bis(benzo[ d Synthesis of thiazole.

[0037] 0.5 mmol (83.0 mg) of 2-hydrazinobenzo[ d Thiazole, 0.5 mmol (73.0 mg) of benzoylacetonitrile, and 0.5 mmol (136.0 mg) of FeCl3·6H2O were weighed and placed in a hydrothermal reactor. 10.0 mL of anhydrous methanol was added, and the mixture was stirred at room temperature until a yellow suspension was formed. The reactor was sealed and placed in an oven at 140 °C for 24 hours. Heating was stopped, and the mixture was slowly cooled to room temperature. The solution was filtered, washed three times with 15 mL of anhydrous methanol, and dried to obtain 85.03 mg of yellowish-brown strip-shaped crystals, with a yield of 48%.

[0038] Example 2

[0039] Complex b: FeLCl2 (L = 2,2'-(3,5-bis(4-fluorophenyl)bispyrazolo[3,4-) b :4',3'- e ]pyridine-1,7-diyl)bis(benzo[ d Synthesis of thiazole.

[0040] 0.5 mmol (83.0 mg) of 2-hydrazinobenzo[ d Thiazole, 0.5 mmol (81.6 mg) of 4-fluorobenzoylacetonitrile and 0.5 mmol (136.0 mg) of FeCl3·6H2O were weighed and placed in a hydrothermal reactor. 10.0 mL of anhydrous methanol was added, and the mixture was stirred at room temperature until a yellow suspension was formed. The reactor was sealed and placed in an oven at 140 °C for 24 hours. Heating was stopped, and the mixture was slowly cooled to room temperature. The solution was filtered, washed three times with 15 mL of anhydrous methanol, and dried to obtain 80.3 mg of yellow-brown strip-shaped crystals, with a yield of 43%.

[0041] Example 3

[0042] Complex c: FeLCl2 (L = 2,2'-(3,5-bis(4-chlorophenyl)bispyrazolo[3,4-) b :4',3'- e ]pyridine-1,7-diyl)bis(benzo[ d Synthesis of thiazole.

[0043] 0.5 mmol (83.0 mg) of 2-hydrazinobenzo[ d Thiazole, 0.5 mmol (89.8 mg) of 4-chlorobenzoylacetonitrile and 0.5 mmol (136.0 mg) of FeCl3·6H2O were weighed and placed in a hydrothermal reactor. 10.0 mL of anhydrous methanol was added, and the mixture was stirred at room temperature until a yellow suspension was formed. The reactor was sealed and placed in an oven at 140 °C for 24 hours. Heating was stopped, and the mixture was slowly cooled to room temperature. The solution was filtered, washed three times with 15 mL of anhydrous methanol, and dried to obtain 85.1 mg of yellowish-brown strip-shaped crystals, with a yield of 44%.

[0044] Example 4

[0045] Complex d: FeLCl2 (L = 2,2'-(3,5-bis(3-methoxyphenyl)bispyrazole[3,4- b :4',3'- e ]pyridine-1,7-diyl)bis(benzo[ d Synthesis of thiazole.

[0046] The difference from Example 1 is that 0.5 mmol (73.0 mg) benzoyl acetonitrile was replaced with 0.5 mmol (87.6 mg) 3-methoxybenzoyl acetonitrile. The remaining steps are the same as in Example 1 and will not be repeated here.

[0047] Example 5

[0048] Complex e: FeLCl2 (L = 2,2'-(3,5-bis(thiophen-2-yl)bispyrazole[3,4-) b :4',3'- e ]pyridine-1,7-diyl)bis(benzo[ d Synthesis of thiazole.

[0049] Unlike Example 1, 0.5 mmol (73.0 mg) benzoylacetonitrile was replaced with 0.5 mmol (83.0 mg) 2-hydrazinobenzo[ d The remaining steps are the same as in Example 1, and will not be repeated here.

[0050] Example 6

[0051] Complex 1-a: FeLCl2 (L = 2,2'-(4-methyl-3,5-diphenylbispyrazole[3,4-)) b :4',3'- e ]pyridine-1,7-diyl)bis(benzo[ d Synthesis of thiazole.

[0052] Unlike Example 1, the reaction solvent in Example 6 is ethanol. The remaining steps are the same as in Example 1, and will not be repeated here.

[0053] Comparative Examples 1-4

[0054] Complex a: FeLCl2 (L = 2,2'-(3,5-diphenylbispyrazole[3,4-)) b :4',3'- e ]pyridine-1,7-diyl)bis(benzo[ d Synthesis of thiazole.

[0055] Unlike Example 1, Comparative Examples 1-4 used 2-hydrazinobenzo[ d The molar ratios of thiazole, benzoylacetonitrile, and FeCl3·6H2O were 1:1:0.2, 1:1:0.5, 1:1:3, and 1:1:5, respectively. All comparative examples had 2-hydrazinobenzo[ d The dosage of thiazole was 0.5 mmol (83.0 mg).

[0056] Comparing Comparative Examples 1-4 with Example 1, it can be seen that the yield is 22.03% when the ratio is 1:1:0.2, 23.41% when the ratio is 1:1:0.5, 46.82% when the ratio is 1:1:3, and 48.68% when the ratio is 1:1:5. Considering both yield and cost, a ratio of 1:1:1 is optimal.

[0057] Characterization and structural analysis of coordination compound a:

[0058] Complex a in the monoclinic crystal system P Crystallization in space group 21 / c (Table 2, Figure 1 a, Figure 2 a), its smallest asymmetric unit consists of a tripentate ligand L, a Fe atom (Fe1), and two Cl atoms (Cl1, Cl2). The ligand L contains a 5-6-5 trifused ring structure with a six-membered ring in the middle ( β (ring) and the five-element rings on both sides ( α and γ The lengths of the CC bond (1.372(8) Å-1.452(7) Å), CN bond (1.298(7) Å-1.366(7) Å), and NN bond (1.383(6) Å-1.392(5) Å) on the ring are between the lengths of the corresponding single and double bonds, respectively, indicating that the bond lengths have been averaged. α , β and γ The sums of the interior angles of the ring are 540°, 720°, and 540°, respectively. β Ring and α , γ The dihedral angles of the rings are 0.5° and 0.7°, respectively, indicating that the trifused ring structure has good coplanarity. Therefore, this trifused ring structure can be classified as 1,7-dihydrobispyrazole [3,4- b 4'3'- e Pyridine. The valence state of the central Fe ion, as determined by X-ray photoelectron spectroscopy, is +2 ( Figure 3 a) further supports the view that the six-membered ring in the middle of the trifused ring is a pyridine structure. The central Fe(II) ion is coordinated with the two Cl ions, the pyridine nitrogen atom of the L ligand, and the N atom of the substituent thiazole ring in a trigonal bipyramidal configuration. Figure 2 b). Calculations using SHAPE 2.0 software confirmed the coordination geometry (Table 3). The crystals of coordination compound a exhibit hydrogen bonding (…). Figure 2 c) and the weak molecular interactions of π-π stacking ( Figure 2 d).

[0059] Powder X-ray diffraction (PXRD) experiments were performed on the yellow-brown crystals obtained by solvothermal experiments. The resulting spectra ( Figure 3b) The powder diffraction pattern simulated from single-crystal data of complex a is highly consistent with that of complex a, indicating that the solid sample is also complex a.

[0060] like Figure 3 As shown in Figure c, complex a was heated from room temperature to 700 °C at a rate of 10 °C / min in a N2 atmosphere. No mass loss was observed below 400 °C, indicating the absence of guest molecules such as low-boiling-point solvents.

[0061] Complex a was characterized by high-resolution mass spectrometry. Figure 3 d), where m / z 578.1213 [C 33 H 20 N7S2] + The peak attributed to the generated ligand bispyrazolopyridine (theoretical value m / z 578.1216) indicates that complex a can remove metal ions under mass spectrometry conditions.

[0062] Possible mechanisms of the reaction include Figure 5 As shown. The carbonyl oxygen of benzoylacetonitrile reacts with Fe. 3+ The substance coordinates with the amino group of the aryl nitrile, then undergoes condensation to form intermediate A, followed by intramolecular nucleophilic addition to form intermediate B, and finally, through hydrogen migration and dissociation to release Fe ions, it forms intermediate C. The solvent methanol is reacted with Fe... 3+ Oxidation to formaldehyde, followed by reaction with intermediate C to give intermediate D. D undergoes hydrogen migration and dehydration to give intermediate E. Another molecule of C undergoes aziraMichael addition with E to give intermediate F. F undergoes hydrogen migration to give intermediate G. G undergoes intramolecular cyclization to remove one molecule of NH3 to give intermediate H. H undergoes dehydrogenation aromatization and then coordination with FeCl2 to give the product. Intermediates A, C, D, E, and G were all detected by high-resolution mass spectrometry. Figure 4 Table 4 supports the proposed mechanism. 3+ The reaction with methanol produces formaldehyde and releases hydrogen gas. This reducing atmosphere can reduce Fe. 3+ Reduced to Fe 2+ .

[0063] Table 2: Crystallographic data of coordination compound a

[0064]

[0065] Table 3: CSHM values ​​of Fe(II) ions in complex a

[0066]

[0067] Table 4: Possible composition and structure of mass spectrometry peaks

[0068]

[0069] Table 5: The structure and yield of reactants and products involved in this invention.

[0070] Note: All data listed in this table are from actual experiments. Unless otherwise specified, the reaction conditions are as follows: arylhydrazine:arylformylacetonitrile:FeCl3·6H2O molar ratio = 1:1:1, temperature 140℃, time 24 hours, the reaction solvent for product (1-a) in sequence number 6 is ethanol, and the other products are obtained using methanol as the solvent. Detailed experimental steps and characterization data are provided in the Detailed Implementation section.

[0071]

[0072]

[0073]

[0074] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for synthesizing a bispyrazolopyridine iron(II) complex, characterized in that, The process includes the following steps: dissolving arylhydrazine, arylformylacetonitrile, and ferric chloride hexahydrate in methanol or ethanol, and reacting to obtain the target complex; The structure of the complex is shown below: ； Wherein, R is a hydrogen atom or a methyl group; Ar comes from arylhydrazine, and Ar is selected from one of pyridin-2-yl, benzimidazol-2-yl, and benzothiazol-2-yl; Ar' comes from arylformylacetonitrile, and Ar' is selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 3-methoxyphenyl, and thiophen-2-yl.

2. The synthesis method according to claim 1, characterized in that, The molar ratio of arylhydrazine, arylformylacetonitrile and ferric chloride hexahydrate is 1:1:(0.5-3).

3. The synthesis method as described in claim 2, characterized in that, The molar ratio of arylhydrazine, arylformylacetonitrile, and ferric chloride hexahydrate is 1:1:

1.

4. The synthesis method according to claim 1, characterized in that, The reaction temperature was 140 ℃ and the reaction time was 24 hours.

5. The synthesis method according to claim 1, characterized in that, The complex is in single-crystal form.

Images