A connecting heterocyclic benzenesulfonamide derivative and a synthetic method and application thereof

Abstract

The application discloses a sulfonamide derivative containing pyrazole and 1,2,3-triazole, a synthetic method and application. The compound has structures as shown in formula I and formula II. The synthetic method is as follows: taking sulfonamide as a starting material, performing diazotization, azidation, coupling with acetylacetone and ethyl acetoacetate to complete the sulfonamide containing pyrazole and triazole ring, introducing an amide bond in the structure, and then synthesizing a series of novel sulfonamide derivatives containing pyrazole and triazole. The preparation method is simple, and the prepared compound shows excellent bacteriostatic, insecticidal and fungicidal functions on escherichia coli, pseudomonas aeruginosa, salmonella typhi, staphylococcus aureus, bacillus subtilis, and other bacteria, such as candida albicans and aspergillus niger, pests and plant pathogenic fungi in forestry and other fields.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis and pesticide technology, specifically relating to a method for preparing a heterocyclic benzenesulfonamide derivative and its antibacterial, bactericidal, and insecticidal activities. Background Technology

[0002] Over the past few decades, diseases caused by microorganisms have spread rapidly, significantly impacting human health and agricultural development. Therefore, developing effective drugs to prevent and control the spread of diseases and pests is extremely important. One reason for antibiotic resistance in bacteria and fungi is the DNA damage response mechanism, namely the antibiotic-induced SOS response. Developing antibacterial agents that inhibit or block the SOS mechanism is an effective means of combating bacterial and fungal resistance. Currently used antibacterial drugs, such as indolemycin, pyrazinamide, isoniazid, and fluconazole, contain nitrogen-containing heterocyclic systems—indole, pyrazine, pyridine, triazoles, and their fused-ring compounds—which have attracted researchers' attention due to their significant biological activity. Among nitrogen-containing heterocycles, 1,2,3-triazoles, due to unique structural features such as hydrogen bonding, dipole-dipole interactions, and π-π interactions, exhibit good solubility and affinity for biological targets. Studies have found that compounds possessing a 1,2,3-triazole-4-carboxamide scaffold have significant activity in inhibiting the SOS mechanism.

[0003] Sulfonamides possess a variety of effects, including antimicrobial, antitumor, anti-inflammatory, hypoglycemic, antipsychotic, and anticancer properties. Since the introduction of the first sulfonamide drug, Prontosil, an increasing number of researchers have dedicated themselves to the development and screening of sulfonamide drugs. Currently, sulfonamide antibacterial drugs such as sulfamethoxazole (SMZ), sulfamethoxazole (SIZ), sulfadiazine (SG), sulfadimidine (SM2), sulfadiazine (SD), and sulfamethoxypyridazine (SMP) are widely used. Their antibacterial mechanism involves competitively inhibiting the synthesis and metabolism of PABA, which is utilized by bacteria, thereby inhibiting bacterial growth.

[0004] Novel antimicrobial agents are developed by combining two distinct active fragments. These compounds contain two or more independent structural segments within the molecule, enabling them to bind to two or more biological targets and accumulate simultaneously at the target sites. This multi-action approach can significantly overcome current microbial resistance or reduce the likelihood of new resistant strains emerging during drug delivery.

[0005] Given the bioactivity of sulfonamide structures and 1,2,3-triazole fragments, this invention proposes using sulfonamide as a starting material, converting the para-amino group of sulfonamide into a nitrogen-containing heterocycle, and introducing a common antibacterial active group, an amide bond, into the structure of the resulting compound to synthesize a novel compound. The bioactivity of this compound was then determined. Results showed that some compounds exhibited better bioactivity than control compounds, suggesting potential for development in pharmaceuticals and pesticides. Summary of the Invention

[0006] To address the above problems, this invention provides a method for preparing and applying a sulfonamide compound containing pyrazole or triazole. This invention also provides the antibacterial, bactericidal, and insecticidal activities of the above compound and their applications.

[0007] The technical solution of the present invention is as follows:

[0008] I. Compounds containing pyrazole and triazole sulfonamides

[0009] The sulfonamide compounds containing pyrazole and triazole of the present invention have the structure shown in the following general formula:

[0010]

[0011]

[0012] In Formula I, Selected from , , , , , .

[0013] In formula II, Selected from , , , , .

[0014] The structural formulas of typical sulfonamide derivatives of pyrazole and triazole are as follows:

[0015]

[0016] II. Preparation methods of sulfonamide derivatives

[0017] The method for preparing the sulfonamide derivatives of the present invention is as follows:

[0018] (1) The synthetic route of compound I is as follows:

[0019]

[0020] The synthesized compounds 6a-6f have the following specific structural formulas:

[0021]

[0022] Furthermore, the synthesis methods for each step in the above synthetic route are as follows:

[0023] Sulfonamide (compound 1) reacts with nitrous acid to form a diazonium salt (compound 2), which is then reduced with sodium sulfite to give 4-hydrazylbenzenesulfonamide hydrochloride (compound 3). Specifically, 4.5 g of sulfonamide, 18 mL of 36% concentrated hydrochloric acid (v / v), and 10 mL of deionized water are added to a 250 mL round-bottom flask. The flask is placed in an ice-water bath and cooled to -5°C while stirring to dissolve. 1.9 g of sodium nitrite is accurately weighed and dissolved in an appropriate amount of water. While maintaining the low temperature, this solution is added dropwise to the reaction mixture through a constant-pressure funnel. After the addition is complete, stirring continues to yield a pale yellow diazonium salt solution. In a separate 250 mL three-necked flask, add 11.7 g of sodium sulfite and 45 mL of deionized water. Stir at room temperature until the sodium sulfite is completely dissolved. Slowly add the prepared diazonium salt solution to the sodium sulfite solution at room temperature. After the addition is complete, heat the solution system to 95 °C and react for 1 h. After slightly cooling, slowly add 9 mL of concentrated hydrochloric acid (36% by volume). Continue heating to 95 °C and react for 3 h. Stop heating and add another 13.5 mL of concentrated hydrochloric acid. Stop stirring and let stand overnight. A fish-scale-like white-yellow solid precipitates out. Filter, wash the filter cake with a small amount of dilute hydrochloric acid and dry it to obtain compound 3, with a yield of 73%.

[0024] 2) Compound 3 undergoes a condensation reaction with acetylacetone. Utilizing the nucleophilic addition of an amine, compound 4 is formed. Specifically, 1.8722 g (8.4 mmol) of compound 3 was added to a 150 mL round-bottom flask, dissolved by sonication with an appropriate amount of ethanol, followed by the addition of 1.04 mL (10 mmol) of acetylacetone. The mixture was heated to reflux, and the reaction was monitored by thin-layer chromatography. Heating was stopped after the reaction was complete, and the system was allowed to cool slightly before being placed in an ice-cold ethanol bath at 0°C with stirring. During this cooling process, a solid precipitate formed. The system was filtered, and the filter cake was recrystallized with anhydrous ethanol to obtain the target product 4. The optimal yield was 91%.

[0025] 3) Compound 4 reacts with phosphorus oxychloride and dimethylformamide in a Wilsmeer-Hacker reaction to yield compound 5. Specifically, 3 mL of DMF and 0.5 mL of phosphorus oxychloride are added to a 150 mL round-bottom flask. After stirring and mixing at -5°C for 30 min, 0.3 g (1.2 mmol) of compound 4 is weighed and added to the round-bottom flask, and the mixture is heated to 90°C and reacted for 2 h. After the reaction is complete, excess deionized water at 0°C is added, and the system is allowed to stand overnight until a solid precipitates. The precipitate is filtered, dried, and then subjected to column chromatography with petroleum ether:ethyl acetate = 3:1 as the eluent to obtain compound 5. The yield is 60%.

[0026] 4) Using anhydrous ethanol as a solvent, compound 5 was reacted with hydroxylamine hydrochloride or hydrazide to obtain 6a-6f.

[0027] The present invention has the following beneficial effects:

[0028] 1) This invention proposes a research and development approach that combines sulfonamide active fragments and heterocyclic active fragments to develop novel antibacterial agents, thereby enabling the development of novel insecticides and bactericides with multiple targets and functions.

[0029] 2) According to the research and development concept of this invention, various compounds can be synthesized by changing the substituents, and candidate drugs with excellent biological activity can be screened.

[0030] 3) The preparation method of this invention has a simple process flow, saves time and effort, has low equipment requirements, is easy to industrialize, and has a broad market. Attached Figure Description

[0031] Figure 1 The image shows the 1H NMR spectrum of the synthesized compound 3 (the 1H NMR spectrum of hydrazinebenzenesulfonamide hydrochloride).

[0032] Figure 2 The proton NMR spectrum of the synthesized compound 4

[0033] Figure 3 The proton NMR spectrum of the synthesized compound 5

[0034] Figure 4 The proton NMR spectrum of compound 6a synthesized in the example is shown.

[0035] Figure 5 The 1H NMR spectrum of compound 6b synthesized in the example is shown below.

[0036] Figure 6 The 1H NMR spectrum of compound 6c synthesized in the example is shown below.

[0037] Figure 7 The 1H NMR spectrum of compound 6d synthesized in the example is shown below.

[0038] Figure 8 The 1H NMR spectrum of compound 6e synthesized in the example is shown below.

[0039] Figure 9 The 1H NMR spectrum of compound 6f synthesized in the example is shown below.

[0040] Figure 10 The image shows the 1H NMR spectrum of the synthesized compound 7 (4-azidobenzenesulfonamide).

[0041] Figure 11 The proton NMR spectrum of the synthesized compound 8

[0042] Figure 12 The carbon NMR spectrum of the synthesized compound 8.

[0043] Figure 13 The carbon NMR spectrum of compound 9a synthesized in the example is shown.

[0044] Figure 14 The proton NMR spectrum of compound 9b synthesized in the example is shown.

[0045] Figure 15 The 1H NMR spectrum of compound 9c synthesized in the example is shown below.

[0046] Figure 16 The 1H NMR spectrum of compound 9d synthesized in the example is shown below.

[0047] Figure 17 The 1H NMR spectrum of compound 9e synthesized in the example is shown below. Detailed Implementation

[0048] The synthetic route of the compound of formula I of the present invention will be further described in detail below with reference to specific embodiments in order to better understand the content of the present invention, but the present invention is not limited to the following embodiments.

[0049] Example 1: Synthesis of compound 6a

[0050] In a 150 mL round-bottom flask, 0.1 g (0.3 mmol) of compound 5, excess hydroxylamine hydrochloride, and 5 mL of anhydrous ethanol were ultrasonically mixed and dissolved. The mixture was heated to reflux and the reaction was monitored by thin-layer chromatography. After the reaction was completed, the product system was allowed to stand overnight. After solid precipitation, the solid was filtered. The filter cake was washed three times with deionized water, recrystallized with anhydrous ethanol, and dried to give compound 6a in 80% yield.

[0051] 1 H NMR (400 MHz, DMSO- d6) δ 10.92 (s, 1H), 8.26 (s, 1H), 8.12 (s, 1H), 7.92 – 7.87 (m, 2H), 7.72 – 7.66 (m, 2H), 3.34 (s, 3H), 2.94 (s, 3H), 2.44(s, 3H), 2.32 (s, 3H).

[0052] Example 2: Synthesis of compound 6b

[0053] 0.1 g (0.3 mmol) of compound 5 was added to a 150 mL round-bottom flask, along with octanoyl hydrazine and an appropriate amount of anhydrous ethanol to dissolve it completely. The mixture was heated to reflux, and the reaction was monitored by thin-layer chromatography. After the reaction was complete, the mixture was cooled, filtered, and the filter cake was dried. The pure target product 6b was obtained by column chromatography with petroleum ether:ethyl acetate = 3:1 as the eluent, with a yield of 81%.

[0054] 1 H NMR (400 MHz, DMSO- d 6) δ 10.90 (s, 1H), 8.27 (s, 1H), 8.01 (s, 1H), 7.93 – 7.87 (m, 2H), 7.73 – 7.67 (m, 2H), 3.34 (s, 3H), 2.94 (s, 3H), 2.55(d, J = 7.4 Hz, 2H), 2.35 (s, 3H), 1.58 (p, J = 7.1 Hz, 2H), 1.33 – 1.22 (m,8H), 0.85 (t, J = 6.6 Hz, 3H).

[0055] Example 3: Synthesis of compound 6c

[0056] 0.1 g (0.3 mmol) of compound 5 was added to a 150 mL round-bottom flask, along with isoniazid and an appropriate amount of anhydrous ethanol to dissolve it completely. The mixture was heated to reflux, and the reaction was monitored by thin-layer chromatography. After the reaction was complete, the mixture was cooled, filtered, and the filter cake was dried. The pure target product 6c was obtained by column chromatography with petroleum ether:ethyl acetate = 3:1 as the eluent, in 80% yield.

[0057] 1 H NMR (400 MHz, DMSO- d6) δ 12.45 (s, 1H), 9.04 – 8.99 (m, 2H), 8.73(s, 1H), 8.33 – 8.29 (m, 2H), 8.28 (s, 1H), 7.95 – 7.90 (m, 2H), 7.77 – 7.71(m, 2H), 3.18 (s, 3H), 2.94 (s, 3H), 2.55 (s, 3H), 2.42 (s, 3H).

[0058] Example 4: Synthesis of compound 6d

[0059] 0.1 g (0.3 mmol) of compound 5 was added to a 150 mL round-bottom flask, along with nicotinic acid hydrazide, and dissolved completely in an appropriate amount of anhydrous ethanol. The mixture was heated to reflux, and the reaction was monitored by thin-layer chromatography. After the reaction was complete, the mixture was cooled, filtered, and the filter cake was dried. The pure target product 6d was obtained by column chromatography with petroleum ether:ethyl acetate = 3:1 as the eluent, with a yield of 85%.

[0060] 1 H NMR (400 MHz, DMSO- d 6) δ 11.76 (s, 1H), 9.06 (d, J = 2.2 Hz, 1H), 8.76 (dd, J = 4.8, 1.6 Hz, 1H), 8.48 (s, 1H), 8.28 – 8.22 (m, 2H), 7.95 –7.89 (m, 2H), 7.76 – 7.71 (m, 2H), 7.57 (dd, J = 7.9, 4.8 Hz, 1H), 3.17 (d, J = 3.7 Hz, 3H), 2.93 (d, J = 4.7 Hz, 3H), 2.55 (s, 3H), 2.41 (s, 3H).

[0061] Example 5: Synthesis of compound 6e

[0062] 0.1 g (0.3 mmol) of compound 5 was added to a 150 mL round-bottom flask, along with 4-methylbenzenesulfonyl hydrazine, and dissolved completely in an appropriate amount of anhydrous ethanol. The mixture was heated to reflux, and the reaction was monitored by thin-layer chromatography. After the reaction was complete, the mixture was cooled, filtered, and the filter cake was dried. The pure target product 6e was obtained by column chromatography with petroleum ether:ethyl acetate = 3:1 as the eluent, in 88% yield.

[0063] 1 H NMR (400 MHz, DMSO- d 6) δ 11.02 (s, 1H), 8.26 (s, 1H), 7.91 – 7.86 (m, 3H), 7.77 – 7.72 (m, 2H), 7.68 – 7.63 (m, 2H), 7.41 (d, J = 8.1 Hz, 2H), 3.16 (s, 3H), 2.93 (s, 3H), 2.37 (s, 3H), 2.35 (s, 3H), 2.22 (s, 3H).

[0064] Example 6: Synthesis of compound 6f

[0065] 0.1 g (0.3 mmol) of compound 5 was added to a 150 mL round-bottom flask, along with 2,4,6-trimethylbenzenesulfonylhydrazine, and dissolved completely in an appropriate amount of anhydrous ethanol. The mixture was heated to reflux, and the reaction was monitored by thin-layer chromatography. After the reaction was complete, the mixture was cooled, filtered, and the filter cake was dried. The purified target product 6f was obtained by column chromatography with petroleum ether:ethyl acetate = 3:1 as the eluent, in 85% yield.

[0066] 1 H NMR (400 MHz, DMSO- d 6) δ 11.12 (s, 1H), 8.25 (s, 1H), 7.64 (d, J =8.2 Hz, 2H), 7.04 (s, 2H), 3.16 (s, 3H), 2.93 (s, 3H), 2.51 (s, 6H), 2.28 (d, J = 23.3 Hz, 6H), 2.16 (s, 3H).

[0067] (2) The synthetic route for compound II is as follows:

[0068]

[0069] The specific structures of the synthesized compounds 9a-9e are as follows:

[0070]

[0071] Furthermore, the synthesis methods for each step in the above synthetic route are as follows:

[0072] 1) After diazotization with sodium nitrite in hydrochloric acid solution, sulfonamide reacts with sodium azide. Under acidic conditions, the azide group and the diazo group undergo substitution, thereby converting the amino group into an azide compound. Specifically, 1.36 g (7.9 mmol) of sulfonamide was added to a 250 mL three-necked flask, along with 48 mL of 2 mol / L hydrochloric acid. After sonication to dissolve, the mixture was placed in a -5°C reaction bath and stirred to cool. 0.69 g (10 mmol) of sodium nitrite was weighed into a beaker, dissolved in 10 mL of deionized water, and then added dropwise to the cooled three-necked flask using a constant pressure funnel. The reaction was carried out under low temperature and stirring for 30 min. Weigh 0.65 g (10 mmol) of sodium azide into a beaker, add 4 mL of deionized water and stir slowly to dissolve. Under low temperature and stirring conditions, add the solution dropwise into a three-necked flask. After reacting at low temperature for 30 min, remove the flask and stir at room temperature for 2 h. Filter the solution, wash the filter cake three times with dilute hydrochloric acid, and dry it to obtain the target product 4-azidobenzenesulfonamide (compound 7) with a yield of 94%.

[0073] 2) 4-Azidebenzenesulfonamide (compound 7) undergoes a 1,3-dipolar cycloaddition reaction with acetylacetone under alkaline conditions to give a sulfonamide compound containing a 1,2,3-triazole ring. Specifically, 0.1 mL (0.98 mmol) of acetylacetone, 50 μL (0.5 mmol) of piperidine, and an appropriate amount of anhydrous ethanol were placed in a 150 mL round-bottom flask and stirred at 70 °C for 10 min. Then, 0.2 g (1 mmol) of 4-azidobenzenesulfonamide was accurately weighed and slowly added to the round-bottom flask. The mixture was heated to reflux, and the reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was removed under vacuum, followed by the addition of ice water and repeated washing with 10% hydrochloric acid. After washing, the solid was filtered off and dried to give 4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)benzenesulfonamide (compound 8) in 90% yield.

[0074] 3) Compound 8 undergoes a nucleophilic addition reaction with hydroxylamine hydrochloride or the corresponding hydrazide under acetic acid catalysis to give products 9a-9e.

[0075] The synthetic route of the compound of formula II of the present invention will be further described in detail below with reference to specific embodiments in order to better understand the content of the present invention, but the present invention is not limited to the following embodiments.

[0076] Example 7: Synthesis of compound 9a

[0077] 0.1 g (0.357 mmol) of compound 8 and 0.3 g (4.3 mmol) of excess hydroxylamine hydrochloride were placed in a 150 mL round-bottom flask. An appropriate amount of methanol was added, and the mixture was heated under reflux. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the heating was stopped, the mixture was cooled, and the product system was left overnight. The solid was filtered, and the filter cake was washed three times with deionized water. The mixture was recrystallized with anhydrous ethanol and dried to give compound 9a in 75% yield.

[0078] 1 H NMR (400 MHz, DMSO-d6) δ 11.28 (s, 1H), 8.09 – 8.01 (m, 2H), 7.90– 7.82 (m, 2H), 7.58 (s, 2H), 2.30 (s, 3H).

[0079] Example 8: Synthesis of compound 9b

[0080] 0.2 g (0.7 mmol) of compound 8 and 0.7 mmol of octanohydrazide were placed in a 150 mL round-bottom flask. An appropriate amount of anhydrous ethanol was added and stirred to dissolve the compounds. Then, 1 mL (17.5 mmol) of excess acetic acid was added and the mixture was heated to reflux. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the heating was stopped, and the mixture was cooled and allowed to stand overnight. The precipitated solid was filtered, dried, and recrystallized with anhydrous ethanol to give product 9b, with a yield of 72%.

[0081] 1 H NMR (400 MHz, DMSO-d6) δ 10.47 (s, 1H), 8.06 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.59 (s, 2H), 2.63 – 2.53 (m, 5H), 2.41 (d, J = 3.8Hz, 3H), 1.58 (t, J = 7.2 Hz, 2H), 1.27 (dd, J = 14.8, 6.4 Hz, 8H), 0.87 –0.83 (m, 3H).

[0082] Example 9: Synthesis of compound 9c

[0083] 0.2 g (0.7 mmol) of compound 8 and 0.7 mmol of isoniazid were placed in a 150 mL round-bottom flask. An appropriate amount of anhydrous ethanol was added and stirred to dissolve the compounds. Then, 1 mL (17.5 mmol) of excess acetic acid was added and the mixture was heated to reflux. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the heating was stopped, and the mixture was cooled and allowed to stand overnight. The precipitated solid was filtered, dried, and recrystallized with anhydrous ethanol to give product 9c, with a yield of 76%.

[0084] 1 H NMR (400 MHz, DMSO-d6) δ 11.11 (s, 1H), 8.78 (d, J = 4.8 Hz, 2H), 8.07 (d, J = 8.2 Hz, 2H), 7.90 (d, J = 8.1 Hz, 2H), 7.82 (d, J = 5.1 Hz, 2H), 7.60 (s, 3H), 2.68 (s, 3H), 2.56 (s, 3H).

[0085] Example 10: Synthesis of compound 9d

[0086] 0.2 g (0.7 mmol) of compound 8 and 0.7 mmol of nicotinic acid hydrazide were placed in a 150 mL round-bottom flask. An appropriate amount of anhydrous ethanol was added and stirred to dissolve the compounds. Then, 1 mL (17.5 mmol) of excess acetic acid was added and the mixture was heated to reflux. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the heating was stopped, and the mixture was cooled and allowed to stand overnight. The precipitated solid was filtered, dried, and recrystallized with anhydrous ethanol to give product 9d, with a yield of 80%.

[0087] 1 H NMR (400 MHz, DMSO-d6) δ 11.07 (s, 1H), 9.06 (s, 1H), 8.77 (s,1H), 8.25 (d, J = 7.9 Hz, 1H), 8.07 (d, J = 8.2 Hz, 3H), 7.90 (d, J = 8.0 Hz,2H), 7.60 (s, 2H), 3.33 (s, 3H), 2.67 (d, J = 11.9 Hz, 3H), 2.57 (d, J = 2.6Hz, 3H).

[0088] Example 11: Synthesis of compound 9e

[0089] 0.2 g (0.7 mmol) of compound 8, 4-methylbenzenesulfonylhydrazine and 0.7 mmol were placed in a 150 mL round-bottom flask, and an appropriate amount of anhydrous ethanol was added and stirred to dissolve. Then, 1 mL (17.5 mmol) of excess acetic acid was added, and the mixture was heated to reflux. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the heating was stopped, and the mixture was cooled and allowed to stand overnight. The precipitated solid was filtered, dried, and recrystallized with anhydrous ethanol to give product 9e, with a yield of 82%.

[0090] 1 H NMR (400 MHz, DMSO-d6) δ 10.68 (s, 1H), 8.05 – 8.01 (m, 2H), 7.85– 7.77 (m, 5H), 7.59 (s, 2H), 7.41 (d, J = 8.1 Hz, 2H), 2.36 (s, 3H), 2.35(s, 3H), 2.30(s, 3H).

[0091] (3) Antibacterial and bactericidal test

[0092] Example 12: Evaluation of antibacterial effect

[0093] The in vitro antibacterial activity of the synthesized compounds was determined using the perforation method. Sulfamethoxazole (SMZ) was used as a positive control for Gram-negative and Gram-positive bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus, and Bacillus subtilis); fluconazole (FLUCZ) was used as a positive control for fungi (Candida albicans and Aspergillus niger). The synthesized compounds and the two positive control drugs were dissolved in DMSO to prepare concentrations of 512 μg / mL, which were then successively diluted with DMSO to 256, 128, 64, 32, 16, 8, 4, 2, and 1 μg / mL. The diameter of the inhibition zone at each of the ten concentrations was measured. A concentration of 1×10⁻⁶ was selected. 6 The experiment was conducted using pathogenic bacteria at CFU / mL (determined by McFarland turbidimetric assay). Sterilized TSB was used as the solid culture medium. A layer of solid culture medium approximately 5 mm high was poured into each petri dish and allowed to solidify. Then, 100 μL of bacterial solution was pipetted onto the surface of the solid culture medium and spread evenly. Sterilized tweezers were used to hold Oxford cups in the solid culture medium and punch holes. Approximately 50 μL of each drug solution was pipetted into the holes. The petri dishes were placed in a constant temperature incubator and incubated for 18-25 h, with the temperature adjusted according to the optimal temperature for each bacterial species. After incubation, the petri dishes were removed, and the size of the inhibition zone was measured using calipers. The antibacterial results of the 1,2,3-triazole benzyl derivatives are shown in Table 1. The benzyl derivatives of this invention containing pyrazole and 1,2,3-triazole exhibit good antibacterial activity against a variety of bacterial species.

[0094] Table 1. Minimum inhibitory concentrations of synthetic compounds and positive control drugs

[0095] Table 1 Minimum inhibitory concentrations of synthetic compounds and positive control drugs

[0096]

Claims

1. A sulfonamide derivative containing pyrazole or triazole, characterized in that, The sulfonamide derivatives have the structure shown in Formula I or Formula II: ， In the formula: -R1 is selected from -OH, ， -R2 is selected from -OH, 。 2. The method for preparing the sulfonamide derivative according to claim 1, characterized in that, The following synthetic routes are included: Synthesis Route 1: ， Synthesis Route 2: 。 3. The application of the sulfonamide derivative according to claim 1, characterized in that, Used in the preparation of antibacterial and bactericidal agents; The bacteria include Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus, Bacillus subtilis, and Candida albicans.

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