A process for the synthesis of 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one
The synthesis of 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one by simplifying it to a one-step reaction method solves the problems of low yield and cumbersome operation in the prior art, and realizes a high-yield and simple synthesis process.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- CHANGZHOU UNIV
- Filing Date
- 2024-07-24
- Publication Date
- 2026-05-19
AI Technical Summary
The existing method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one requires six consecutive reaction steps, resulting in low yield and cumbersome operation.
2-Mercapto-N-methylbenzamide, benzaldehyde, and hydroiodic acid were used as raw materials. The reaction was carried out by heating and stirring in a sealed tube. After the reaction was completed, the mixture was purified, simplifying the reaction into a one-step process. Solvents such as acetonitrile were used, and the reaction conditions were optimized.
It achieves a high yield (over 80%) of the target product, is easy to operate, has low equipment requirements, and requires simple post-processing.
Smart Images
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Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one. Background Technology
[0002] 3-Methyl-2-phenyl-2,3-dihydrobenzothiazin-4-one is a sulfur-nitrogen-containing benzo[a] six-membered heterocyclic compound with antifungal activity. This compound exhibits strong inhibitory activity against eight clinically common pathogenic fungi (Rhizopus, Trichophyton rubrum, Aspergillus, Microsporum gypseum, Trichophyton verruciformis, Cryptococcus neoformans, Saccharomyces rubrum, and Candida albicans).
[0003] The common synthetic method for 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one uses o-aminobenzoic acid as a starting material and requires six consecutive reaction steps, resulting in low yield and cumbersome operation, which is not conducive to the large-scale preparation of the target product. Summary of the Invention
[0004] The existing technology has the following problems: conventional methods for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one usually use anthranilic acid as a starting material, requiring six consecutive reaction steps to obtain the product. This process is time-consuming, yields low, and is cumbersome. To address these problems, this invention provides a method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one, the preparation method comprising the following steps:
[0005] 2-Mercapto-N-methylbenzamide, benzaldehyde, hydroiodic acid (HI), and reaction solvent were added sequentially to a sealed tube. The reaction system was heated and stirred to induce a vigorous reaction. After the reaction was completed, the reaction product was purified to obtain 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one. The structural formula of 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one is as follows:
[0006]
[0007] The reaction yield is over 80%, and Me is a methyl group.
[0008] Preferably, the purification method involves sequentially concentrating the reaction solution and separating it by column chromatography.
[0009] Preferably, the ratio of 2-mercapto-N-methylbenzamide to the reaction solvent, benzaldehyde, and hydroiodic acid is 0.4 mmol: 2-6 mL: 0.4-0.8 mmol: 0.01-0.04 mmol.
[0010] Preferably, the ratio of 2-mercapto-N-methylbenzamide to the reaction solvent, benzaldehyde, and hydroiodic acid is 0.4 mmol: 4 mL: 0.6-0.8 mmol: 0.02-0.04 mmol.
[0011] Preferably, the reaction solvent includes acetonitrile, 1,2-dichloromethane, or toluene.
[0012] Preferably, the reaction solvent is acetonitrile.
[0013] Preferably, the reaction temperature is 80-120℃.
[0014] Preferably, the reaction temperature is 100°C.
[0015] Preferably, the reaction time is 30 min to 6 h.
[0016] Preferably, the reaction time is 5 hours.
[0017] The present invention has the following beneficial effects:
[0018] The present invention provides a method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazin-4-one, which uses 2-mercapto-N-methylbenzamide as a starting material and completes the reaction in one step. The raw materials and catalysts are readily available, the operation is simple, the reaction is fast, the equipment requirements are low, the post-processing is simple, and the yield of the target product is high. Detailed implementation method:
[0019] The present invention will be described in detail below with reference to embodiments. However, it should be understood that the following embodiments are merely illustrative examples of implementation of the present invention and are not intended to limit the scope of the present invention.
[0020] Example 1
[0021] 2-Mercapto-N-methylbenzamide (0.4 mmol, 66.89 mg), acetonitrile (4.0 mL), benzaldehyde (0.6 mmol, 63.67 mg), and catalyst HI (5.0 mol%, 0.02 mmol, 2.8 μL) were added sequentially to a 50 mL sealed tube. The mixture was stirred at 100 °C for 1 h. After the reaction was completed, the reaction solution was concentrated under reduced pressure and separated by column chromatography to obtain the target product 3-methyl-2-phenyl-2,3-dihydrobenzothiazin-4-one, with a yield of 98.0 mg and a recovery rate of 96%.
[0022]
[0023] NMR data of the target product: 1H NMR (300MHz, CDCl3) δ8.18-8.12(m,1H),7.31-7.16(m,7H),7.09(dd,J=7.6,1.4Hz,1H),5.64(s,1H),3.24(s,3H). 13 C NMR (75MHz, CDCl3) δ164.26,138.42,132.98,132.03,130.02,128.83,128.65,128.45,127.34,126.24,126.22,63.81,36.03.
[0024] Example 2 is the same as Example 1, except that the amount of HI used in Example 2 is 0.01 mmol. The yield of the target product obtained in Example 2 is 90%.
[0025] Example 3 is the same as Example 1, except that the amount of HI used in Example 3 is 0.04 mmol. The yield of the target product obtained in Example 3 is 96%.
[0026] Example 4 is the same as Example 1, except that the reaction time in Example 4 is 10 minutes. The yield of the target product obtained in Example 4 is 41%.
[0027] Example 5 is the same as Example 1, except that the reaction time in Example 5 is 30 minutes. The yield of the target product obtained in Example 5 is 90%.
[0028] Example 6 is the same as Example 1, except that the reaction time in Example 6 is 6 minutes. The yield of the target product obtained in Example 6 is 96%.
[0029] Example 7 is the same as Example 1, except that the reaction solvent used in Example 7 is 1,2-dichloromethane. The yield of the target product obtained in Example 7 is 92%.
[0030] Example 8 is the same as Example 1, except that the reaction solvent used in Example 8 is 1,2-dichloroethane. The yield of the target product obtained in Example 8 is 87%.
[0031] Example 9 is the same as Example 1, except that toluene was used as the reaction solvent in Example 9. The yield of the target product obtained in Example 9 was 80%.
[0032] Example 10 is the same as Example 1, except that the reaction solvent used in Example 10 is N,N-dimethylformamide. The yield of the target product obtained in Example 10 is 0%.
[0033] Example 11 is the same as Example 1, except that the reaction solvent used in Example 11 is dimethyl sulfoxide. The yield of the target product obtained in Example 11 is 0%.
[0034] Example 12 is the same as Example 1, except that methanol was used as the reaction solvent in Example 12. The yield of the target product obtained in Example 12 was 0%.
[0035] Example 13 is the same as Example 1, except that the reaction solvent used in Example 13 is water. The yield of the target product obtained in Example 13 is 0%.
[0036] Example 14 is the same as Example 1, except that the reaction solvent used in Example 14 is anhydrous ethanol. The yield of the target product obtained in Example 14 is 5%.
[0037] Example 15 is the same as Example 1, except that the amount of acetonitrile used in Example 15 is 2 mL. The yield of the target product obtained in Example 15 is 88%.
[0038] Example 16 is the same as Example 1, except that the amount of acetonitrile used in Example 16 is 6 mL. The yield of the target product obtained in Example 16 is 90%.
[0039] Example 17 is the same as Example 1, except that the amount of benzaldehyde used in Example 17 is 0.4 mmol. The yield of the target product obtained in Example 17 is 82%.
[0040] Example 18 is the same as Example 1, except that the amount of benzaldehyde used in Example 18 is 0.8 mmol. The yield of the target product obtained in Example 18 is 95%.
[0041] Example 19 is the same as Example 1, except that the reaction temperature in Example 19 is 25°C. The yield of the target product obtained in Example 19 is 0%.
[0042] Example 20 is the same as Example 1, except that the reaction temperature in Example 20 is 60°C. The yield of the target product obtained in Example 20 is 0%.
[0043] Example 21 is the same as Example 1, except that the reaction temperature in Example 21 is 60°C. The yield of the target product obtained in Example 21 is 80%.
[0044] Example 22 is the same as Example 1, except that the reaction temperature in Example 22 is 80°C. The yield of the target product obtained in Example 22 is 80%.
[0045] Example 23 is the same as Example 1, except that the reaction temperature in Example 23 is 120°C. The yield of the target product obtained in Example 23 is 93%.
[0046] Example 24 is the same as Example 1, except that the catalyst in Example 24 is concentrated hydrochloric acid with a mass concentration of 36%, the added concentrated hydrochloric acid contains 0.02 mmol of HCl, and the reaction solvent is acetonitrile. The yield of the target product obtained in Example 24 is 0%.
[0047] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.
Claims
1. A method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one, characterized in that, The preparation method includes the following steps: 2-Mercapto-N-methylbenzamide, benzaldehyde, hydroiodic acid, and reaction solvent were added sequentially to a sealed tube. The reaction system was heated and stirred to induce a vigorous reaction. After the reaction was completed, the reaction product was purified to obtain 3-methyl-2-phenyl-2,3-dihydrobenzothiazin-4-one. The structural formula of 3-methyl-2-phenyl-2,3-dihydrobenzothiazin-4-one is as follows: ； The reaction yield is over 80%, and Me is a methyl group; The reaction solvent is selected from acetonitrile, dichloromethane, 1,2-dichloroethane, or toluene; The reaction temperature is 80-120℃.
2. The method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one according to claim 1, characterized in that, The purification method involves sequentially concentrating the reaction solution and separating it by column chromatography.
3. The method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one according to claim 1, characterized in that, The ratio of 2-mercapto-N-methylbenzamide to the reaction solvent, benzaldehyde, and hydroiodic acid is 0.4 mmol: 2-6 mL: 0.4-0.8 mmol: 0.01-0.04 mmol.
4. The method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one according to claim 3, characterized in that, The ratio of 2-mercapto-N-methylbenzamide to the reaction solvent, benzaldehyde, and hydroiodic acid is 0.4 mmol: 4 mL: 0.6-0.8 mmol: 0.02-0.04 mmol.
5. The method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one according to claim 1, characterized in that, The reaction solvent is acetonitrile.
6. The method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one according to claim 1, characterized in that, The reaction temperature is 100℃.
7. The method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one according to claim 1, characterized in that, The reaction time is 30 min to 6 h.
8. The method for synthesizing 3-methyl-2-phenyl-2,3-dihydrobenzothiazine-4-one according to claim 7, characterized in that, The reaction time is 5 hours.