Acridine derivative as well as preparation method and application thereof

Abstract

The invention relates to acridine derivatives as well as a preparation method and application thereof, and belongs to the technical field of nitrogen heterocyclic compounds. The acridine derivative is a compound as shown in the specification or a pharmaceutically acceptable salt thereof. R1 is selected from H, a C1-3 alkyl group and a C1-3 alkoxy group; r2 is selected from H, C1-3 alkyl groups and C1-3 alkoxy groups; a is selected from nitrogen heterocycle and derivative groups thereof. According to the acridine derivative provided by the invention, in the aspect of metal corrosion resistance, the corrosion inhibition efficiency can reach more than 80% under the concentration of 0.0625 mmol / L, which is 1.25 times of the corrosion inhibition effect of the existing 1, 2, 3-triazolyl-acridine derivative, and the acridine derivative has an excellent metal corrosion inhibition effect.

Description

Technical Field

[0001] This invention belongs to the field of nitrogen heterocyclic compound technology, specifically relating to an acridine derivative, its preparation method, and its application. Background Technology

[0002] Nitrogen heterocyclic corrosion inhibitors, as important chemical additives, play a crucial role in suppressing equipment corrosion and ensuring the long-term operation of oil refining units. Nitrogen heterocyclic compounds contain nitrogen atoms with lone pairs of electrons in their structure, which can adsorb onto metal surfaces to form a protective layer and inhibit corrosion. Compared with acid corrosion inhibitors such as plant extracts, amino acids, natural polymers, ionic liquids, and pharmaceuticals, nitrogen heterocyclic compounds have better solubility and adsorption behavior, and are considered safer and more economical corrosion inhibitors.

[0003] Currently, nitrogen heterocyclic corrosion inhibitors are mostly small molecule compounds of five-membered heterocycles, six-membered heterocycles, and benzo[a][b][c ...

[0004] Hassane Lgaz's research group has disclosed three acridine triazole derivatives with anti-corrosion effects. These derivatives are prepared by reacting 6,9-dichloro-2-methoxyacridine with an azide, followed by a reaction with the corresponding alkyne under ultrasonic conditions, yielding acridine triazole derivatives in 48%-61% yield. However, this preparation method suffers from the instability of the intermediate 9-azido-6-chloro-2-methoxyacridine and low yield, making large-scale production difficult. . Summary of the Invention

[0005] The first objective of this invention is to provide a method for preparing acridine derivatives to solve the technical problem that existing acridine derivatives have low yields and are difficult to mass-produce.

[0006] A second objective of this invention is to provide an acridine derivative.

[0007] A third objective of this invention is to provide an application of acridine derivatives.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows: An acridine derivative, characterized in that it is a compound of formula (1) or a pharmaceutically acceptable salt thereof: Equation (1) In equation (1), R 1 Selected from H, C1-C3 alkyl, C1-C3 alkoxy; R 2 Selected from H, C1-C3 alkyl, C1-C3 alkoxy; A is selected from nitrogen heterocycles and their derivatives.

[0009] Furthermore, in the formula (1), A is selected from six-membered nitrogen heterocycles and benzo[a]aza ...

[0010] Furthermore, in formula (1), A is selected from pyrazine, pyrimidine, quinoline, and acridine groups.

[0011] Furthermore, when A is a pyrazine group, the structures of acridine derivatives are shown in formulas (2) to (9); Equation (2); Equation (3); Equation (4); Equation (5); , Equation (6); Equation (7); Equation (8); Equation (9).

[0012] Furthermore, when A is a pyrimidine group, the structure of the acridine derivative is shown in formulas (10) to (14); Equation (10); , Equation (11); Equation (12); Equation (13); Equation (14).

[0013] Furthermore, when A is a quinoline group, the structure of the acridine derivative is shown in formulas (15)-(18); Equation (15); , Equation (16); , Equation (17); Equation (18).

[0014] Furthermore, when A is an acridine group, the structure of the acridine derivative is shown in formulas (19)-(21); , Equation (19); Equation (20); Equation (21).

[0015] A method for preparing an acridine derivative includes the following steps: adding a 9-ethynyl acridine derivative, an azide-azo heterocyclic compound, a copper catalyst, and sodium ascorbate to N,N-dimethylformamide, and heating to 50-80 °C. o The reaction at C takes 8-16 hours to yield the product. The structure of the 9-ethynyl acridine derivative is as follows: ; The azide-azo heterocyclic compound is , , , Any one of them; Where R 1 Selected from H, C1-C3 alkyl, C1-C3 alkoxy; R 2 Selected from H, C1-C3 alkyl, C1-C3 alkoxy; R 3 Selected from H, halogens, phenyl; R 4 Selected from H, C1-C3 alkoxy groups.

[0016] Application of an acridine derivative in metal corrosion inhibitors.

[0017] The beneficial effects of this invention are: This invention introduces a triazole and nitrogen heterocyclic structure into the original acridine structure. On the one hand, it increases the number of nitrogen atoms with lone pairs of electrons in acridine, thereby improving the chemical adsorption capacity of the target compound to the metal, thus improving the adsorption rate and stability. On the other hand, by introducing a planar conjugated structure, it increases the surface area covered by the target compound, achieving a low dosage and high corrosion inhibition effect.

[0018] This invention uses a stable 9-acetylenyl acridine derivative as a starting material and constructs a triazole ring by reacting it with an azide-azo heterocyclic compound. The reaction is carried out in the polar solvent N,N-dimethylformamide, which improves the solubility and contact area of ​​the starting material and avoids the use of unstable 9-azido-acridine derivatives. This invention can achieve a yield of 80-90% at a relatively low temperature (50-80 °C), and the reaction conditions are mild and easy to scale up industrially.

[0019] The acridine derivatives provided by this invention exhibit a corrosion inhibition efficiency of over 80% at a concentration of 0.0625 mmol / L, which is 1.25 times that of existing 1,2,3-triazolyl-acridine derivatives, demonstrating excellent metal corrosion inhibition performance. Attached Figure Description

[0020] Figure 1 The image shows the hydrogen NMR spectrum of compound 2c from Example 3. Detailed Implementation

[0021] The present invention will be further described below with reference to the embodiments and accompanying drawings.

[0022] The structural formulas of the acridine derivatives prepared in Examples 1-8 are shown in Table 1.

[0023] Table 1. Structural formulas of acridine derivatives prepared in Examples 1-8

[0024] Example 1 The preparation method of the acridine derivative in Example 1 includes the following steps: 9-ethynylacridin (1 eq.), 5-azido-2,3-diphenylpyrazine (1.2 eq.), copper sulfate pentahydrate (0.1 eq.), and sodium ascorbate (0.1 eq.) are sequentially added to 10 mL of N,N-dimethylformamide solvent, and reacted at 50 °C for 16 h to obtain 370 mg of compound 2a, with a yield of 77.35%. The mass of 9-ethynylacridin added is 204 mg (1 mmol); the amount of 5-azido-2,3-diphenylpyrazine added is 329 mg (1.2 mmol).

[0025] Elemental analysis of compound 2a: theoretical values: C, 78.13; H, 4.23; N, 17.64. Measured values: C, 78.25; H, 4.11; N, 17.60. Compound 2a 1 H NMR (400MHz, Chloroform-d): δ=9.69(s,1H),9.01(s,1H),8.31(d,2H),8.03(d,2H),7.88-7.74(m,2H),7.53(m,6H),7.42-7.27(m, 6H)ppm. 5-Azide-2,3-diphenylpyrazine References J. Heterocycl. Chem. , 1983, 20 , 1277 Preparation method.

[0026] Example 2 The preparation method of the acridine derivative in Example 2 includes the following steps: 9-ethynyl-2-methoxy-7-methylacridinium (1 eq.), 5-azido-2,3-diphenylpyrazine (1.2 eq.), copper sulfate pentahydrate (0.1 eq.), and sodium ascorbate (0.1 eq.) are sequentially added to 10 mL of N,N-dimethylformamide solvent, and reacted at 80 °C for 8 h to obtain 438 mg of compound 2b, with a yield of 83.90%. The amount of 9-ethynyl-2-methoxy-7-methylacridinium added was 248 mg (1 mmol); the amount of 5-azido-2,3-diphenylpyrazine added was 329 mg (1.2 mmol).

[0027] Elemental analysis of compound 2b: theoretical values: C, 76.14; H, 4.65; N, 16.14; O, 3.07. Measured values: C, 76.21; H, 4.57; N, 16.12; O, 3.11. Compound 2b 1 H NMR (400MHz, Dimethyl Sulfoxide- d ): δ= 8.91(s, 1H), 8.11-8.01(m, 4H), 7.87(m, 1H), 7.60-7.51(m, 4H), 7.36-7.24(m, 8H), 3.84(s, 3H),2.53(s, 3H)ppm. 5-Azide-2,3-diphenylpyrazine References J. Heterocycl. Chem. , 1983, 20 , 1277 Preparation method.

[0028] Example 3 The preparation method of the acridine derivative in Example 3 includes the following steps: 9-ethynylacridin (1 eq.), 5-azido-2-methoxypyrimidine (1.2 eq.), copper sulfate pentahydrate (0.1 eq.), and sodium ascorbate (0.1 eq.) are sequentially added to 10 mL of N,N-dimethylformamide solvent, and reacted at 70 °C for 14 h to obtain 298 mg of compound 2c, with a yield of 83.78%. The amount of 9-ethynylacridin used is 204 mg (1 mmol); the amount of 5-azido-2-methoxypyrimidine used is 182 mg (1.2 mmol).

[0029] Elemental analysis of compound 2c: theoretical values: C, 67.79; H, 3.98; N, 23.72; O, 4.51. Measured values: C, 67.82; H, 3.89; N, 23.81; O, 4.55. Compound 2c 1H NMR (400MHz, Chloroform- d ): δ= 9.42 (s, 1H), 9.35 (s, 2H), 8.28 (d, 2H), 8.22-8.07 (m, 2H), 7.92 (m, 2H), 7.76-7.55 (m, 2H), 4.07 (s, 3H)ppm. Figure 1 This is the 1H NMR spectrum of compound 2c.

[0030] 5-Azide-2-methoxypyrimidine References Org. Biomol. Chem. , 2023, 21 , 6134 was prepared by the preparation method.

[0031] Example 4 The preparation method of the acridine derivative in Example 4 includes the following steps: 9-ethynyl-2-methoxy-7-methylacridine (1 eq.), 5-azido-2-methoxypyrimidine (1.2 eq.), copper sulfate pentahydrate (0.1 eq.), and sodium ascorbate (0.1 eq.) are sequentially added to 10 mL of N,N-dimethylformamide solvent, and 70 mL is added to the solvent. o The reaction was carried out at C for 14 h, yielding 347 mg of compound 2d, with a yield of 86.85%. The amount of 9-ethynyl-2-methoxy-7-methylacridine was 248 mg (1 mmol), and the amount of 5-azido-2-methoxypyrimidine was 182 mg (1.2 mmol).

[0032] Elemental analysis of compound 2d: theoretical values: C, 66.32; H, 4.55; N, 21.09; O, 8.03. Measured values: C, 66.21; H, 4.61; N, 21.12; O, 7.99. Compound 2d 1 H NMR (400MHz, Chloroform- d ): δ= 8.85(s, 2H), 8.10-8.05(m,2H), 7.96(m, 1H), 7.61-7.55(m, 3H), 7.32(m, 1H), 3.86(s, 3H), 3.81(s, 3H),2.55(s, 3H) ppm. 5-Azide-2-methoxypyrimidine References Org. Biomol. Chem. , 2023, 21 , 6134 was prepared by the preparation method.

[0033] Example 5 The preparation method of the acridine derivative in Example 5 includes the following steps: 9-ethynyl-2-methoxy-7-methylacridine (1 eq.), 4-azidoquinoline (1.2 eq.), copper sulfate pentahydrate (0.1 eq.), and sodium ascorbate (0.1 eq.) are sequentially added to 10 mL of N,N-dimethylformamide solvent, and reacted at 80 °C for 10 h to obtain 373 mg of compound 2e, with a yield of 89.09%. The amount of 9-ethynyl-2-methoxy-7-methylacridine used was 248 mg (1 mmol); the amount of 4-azidoquinoline used was 205 mg (1.2 mmol).

[0034] Elemental analysis of compound 2e: Theoretical values: C, 74.80; H, 4.59; N, 16.78; O, 3.83. Measured values: C, 74.69; H, 4.57; N, 16.82; O, 3.85. compound 2e 1 H NMR (400MHz, Chloroform-d): δ= 8.95(m, 1H), 8.38(m, 1H),8.17-8.10(m, 2H), 7.88-7.81(m, 2H), 7.65-7.59(m, 4H), 7.31-7.27(m, 3H), 3.95(s, 3H), 2.57(s, 3H)ppm. 4-Azidequinoline References Eur. J. Med. Chem., 2019 , 181, 111520 was prepared using the preparation method.

[0035] Example 6 The preparation method of the acridine derivative in Example 6 includes the following steps: 9-ethynyl-2-methoxy-7-methylacridine (1 eq.), 2-chloro-4-azidoquinoline (1.2 eq.), copper sulfate pentahydrate (0.05 eq.), and sodium ascorbate (0.05 eq.) are sequentially added to 10 mL of N,N-dimethylformamide solvent, and reacted at 80 °C for 11 h to obtain 377 mg of compound 2f, with a yield of 83.19%. The amount of 9-ethynyl-2-methoxy-7-methylacridine used was 248 mg (1 mmol); the amount of 2-chloro-4-azidoquinoline used was 247 mg (1.2 mmol).

[0036] Elemental analysis of compound 2f: Theoretical values: C, 69.10; H, 4.01; N, 15.50; O, 3.54; Cl, ​​7.84. Measured values: C, 69.04; H, 3.97; N, 15.56; O, 3.58. Compound 2f1 H NMR (400MHz, Chloroform-d): δ= 8.31(m, 1H), 8.13-8.08(m,2H), 7.81-7.75(m, 2H), 7.64-7.60(m, 4H), 7.38(s, 1H), 7.25(m, 2H), 3.87(s,3H), 2.61(s,3H)ppm. 4-Azidequinoline References Eur. J. Med. Chem., 2019 , 181, 111520 was prepared using the preparation method.

[0037] Example 7 The preparation method of the acridine derivative in Example 7 includes the following steps: 9-ethynylacridin (1 eq.), 9-azidomethylacridin (1.2 eq.), copper sulfate pentahydrate (0.05 eq.), and sodium ascorbate (0.05 eq.) are sequentially added to 10 mL of N,N-dimethylformamide solvent, and reacted at 60 °C for 10 h to obtain 2 g of 378 mg compound, with a yield of 86.08%. The amount of 9-ethynylacridin used was 204 mg (1 mmol); the amount of 9-azidomethylacridin used was 282 mg (1.2 mmol).

[0038] Elemental analysis of 2g of compound: theoretical values: C, 79.61; H, 4.38; N, 16.01. Measured values: C, 79.55; H, 4.41; N, 15.97. 2g of compound 1 H NMR (400MHz, Dimethyl Sulfoxide-d): δ= 8.91 (s, 1H), 8.80(d, 2H), 8.26 (d, 2H), 8.19 (d, 2H), 7.99 – 7.89 (m, 2H), 7.89 – 7.76 (m,6H), 7.60 – 7.51 (m, 2H), 6.97 (s, 2H)ppm. 9-Azide-methylacridine References Eur. J. Org. chem ., 2015, 2015 , 2157 Preparation method.

[0039] Example 8 The preparation method of the acridine derivative in Example 8 includes the following steps: 9-ethynyl-2-methoxy-7-methylacridinium (1 eq.), 9-azidomethylacridinium (1.2 eq.), copper sulfate pentahydrate (0.15 eq.), and sodium ascorbate (0.15 eq.) are sequentially added to 10 mL of N,N-dimethylformamide solvent, and reacted at 60 °C for 12 h to obtain 415 mg of the compound over 2 h, with a yield of 85.93%. The amount of 9-ethynyl-2-methoxy-7-methylacridinium added is 248 mg (1 mmol); the amount of 9-azidomethylacridinium used is 282 mg (1.2 mmol).

[0040] Elemental analysis of compound 2h: theoretical values: C, 77.32; H, 4.81; N, 14.54; O, 3.32. Measured values: C, 77.41; H, 4.77; N, 14.59; O, 3.24. Compound 2h 1 H NMR (400MHz, Dimethyl Sulfoxide-d): δ 8.54(d, 2H), 8.11-7.89(m, 7H), 7.71(t, 2H), 7.57(m, 2H), 7.37-7.34(m, 2H), 6.37(s, 2H), 3.95(s,3H), 2.56(s,3H)ppm. 9-Azide-methylacridine References Eur. J. Org. chem., 2015, 2015 , 2157 Preparation method.

[0041] References for the preparation methods of 9-ethynyl acridine derivatives Synthetic Commun., 2013, 43 , 2809; Inorg. Chem., 2021, 60 Prepared by method 8990.

[0042] The preparation method of 9-ethynylacridine is as follows: Step 1: 9-chloroacridine derivatives (20 mmol), trimethylsilylacetylene (3 eq.), bis(triphenylphosphine)palladium dichloride (0.1 eq), cuprous bromide (0.23 eq), and triethylamine (19 eq.) were added sequentially to tetrahydrofuran and reacted for 48 h to obtain 9-[(trimethylsilyl)acetylene]acridine derivatives.

[0043] Step 2: Add 9-[(trimethylsilyl)ethynyl]acridine derivative, potassium hydroxide (1 eq.), and potassium phosphate (1 eq.) to toluene and react until the 9-[(trimethylsilyl)ethynyl]acridine derivative has completely reacted.

[0044] The preparation method of 9-ethynyl-2-methoxy-7-methylacridine differs from that of 9-ethynylacridine in that trimethylsilylacetylene is replaced with 2-methyl-3-butyn-2-ol.

[0045] Table 2. Structural formulas of the 9-alkynylacridine derivatives used in Examples 1-8

[0046] Example 9 The sustained-release effect of the acridine derivatives of the present invention was detected by the weight loss method. The effect of the acridine derivatives at concentrations of 0.0625 mmol / L, 0.25 mmol / L, and 1.00 mmol / L on the corrosion rate of (13 mm × 13 mm × 2 mm) carbon steel in 1M HCl solution at 25 °C was tested. The relevant data are shown in Table 3.

[0047] Table 3. Sustained-release effect of the acridine derivatives of the present invention

[0048] The structural formula of compound TTA in Comparative Example 1 is as follows: TTA was prepared according to the preparation method described in the document "Experimental and theoretical evaluation of the anticorrosive properties of new 1,2,3-triazolyl-acridine derivatives".

[0049] As shown in Table 3, the corrosion inhibition effect of compound 2a-2h prepared in this invention compared with that of Comparative Example 1 is as follows: at a concentration of 0.0625 mmol / L, compound 2a-2h prepared in this invention has a 10% higher corrosion inhibition effect than Comparative Example 1, achieving a better corrosion inhibition effect at a lower concentration. This invention increases the adsorption area of ​​individual corrosion inhibitor molecules, thereby increasing stability and making it less prone to decomposition. The addition of electron-donating groups and heteroatoms in the structure further enhances the corrosion inhibition effect. When electron-withdrawing groups are introduced into the structure, the corrosion inhibition effect is slightly reduced.

[0050] Other embodiments of this disclosure will readily occur to those skilled in the art upon consideration of the specification and practice of the disclosure herein. This disclosure is intended to cover any variations, uses, or adaptations of this disclosure that follow the general principles of this disclosure and include common knowledge or customary techniques in the art not disclosed herein. The specification and examples are to be considered exemplary only, and the true scope and spirit of this disclosure are indicated by the claims.

[0051] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. The scope of patent protection of the present invention shall be determined by the claims. Similarly, any equivalent structural changes made based on the content of the present invention's specification shall also be included within the scope of protection of the present invention.

Claims

1. An acridine derivative, characterized in that, A compound represented by formula (1) or a pharmaceutically acceptable salt thereof: , formula (1), In formula (1), R 1 is selected from H, C1-C3 alkyl, C1-C3 alkoxy; R 2 is selected from H, C1-C3 alkyl, C1-C3 alkoxy; A is selected from an azacycle and a derivative thereof.

2. The acridine derivative according to claim 1, characterized in that, In the formula (1), A is selected from a six-membered nitrogen heterocyclic ring, a benzazepine group.

3. The acridine derivative according to claim 1, characterized in that, In the formula (1), A is selected from a pyrazine, a pyrimidine, a quinoline, an acridine group.

4. The acridine derivative according to claim 3, characterized in that, When A is a pyrazine group, the structure of the acridine derivative is shown in formula (2) to formula (9); , formula (2); , formula (3); , formula (4); , formula (5); , formula (6); , formula (7); , formula (8); , formula (9).

5. The acridine derivative according to claim 3, wherein When A is a pyrimidine group, the structure of the acridine derivative is shown in formula (10) to formula (14); , formula (10); , formula (11); , formula (12); , formula (13); , formula (14).

6. The acridine derivative according to claim 3, wherein When A is a quinoline group, the structure of the acridine derivative is shown in formula (15) to formula (18); , formula (15); , formula (16); , formula (17); , formula (18).

7. The acridine derivative according to claim 3, characterized in that, When A is an acridine group, the structure of the acridine derivative is shown in formula (19) to formula (21); , formula (19); , formula (20); , formula (21).

8. A process for the preparation of an acridine derivative according to any one of claims 1 to 7, characterized in that, comprising the following steps: 9-ethynylacridine derivative, azide heterocyclic compound, copper-based catalyst, sodium ascorbate were added into N,N-dimethylformamide, 50-80 o C reacted for 8-16 h, and the product was obtained. The 9-ethynyl acridine derivative structure is ; The azido azaheterocyclic compound is any one of , , , any one of Where R 1 Selected from H, C1-C3 alkyl, C1-C3 alkoxy; R 2 Selected from H, C1-C3 alkyl, C1-C3 alkoxy; R 3 Selected from H, halogens, phenyl; R 4 Selected from H, C1-C3 alkoxy groups.

9. Use of an acridine derivative according to any one of claims 1 to 7 as a metal corrosion inhibitor.

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