A process for the preparation of ethyl 2-(benzylthio)-2-oxoacetate

Abstract

The present application relates to the technical field of fine chemical industry, in particular to a method for preparing 2-(benzylthio)-2-oxoethyl acetate. The synthesis method of 2-(benzylthio)-2-oxoethyl acetate is rarely reported. In view of the above technical problems, the present application provides a method for preparing 2-(benzylthio)-2-oxoethyl acetate. The method uses NCS as a key additive for reaction, uses 2-(benzylthio) ethyl acetate as a reaction raw material, and uses N,N-dimethylformamide as a reaction solvent to successfully synthesize the target product. The method is simple, has high yield, and has good application prospect.

Description

Technical Field

[0001] This invention relates to the field of fine chemical technology, specifically to a method for preparing ethyl 2-(benzylthio)-2-oxoethyl acetate. Background Technology

[0002] 2-(benzylthio)-2-oxoethyl acetate and its derivatives are an important class of biologically active sulfur-containing oxalate compounds. Related literature reports that these compounds can rapidly bind to cysteine ​​or cysteamine in the human body, regulating the catalytic activity of enzymes and thus affecting normal bodily functions (Bioorg. Chem., 1987, 15, 81-91). It is noteworthy that currently, there are very few reported synthetic methods for this compound and its derivatives.

[0003] To address the aforementioned issues, this invention designs and synthesizes a method for synthesizing ethyl 2-(benzylthio)-2-oxoethyl ester using N-chlorosuccinimide (NCS) as a starting material. The reaction uses ethyl 2-(benzylthio)ethyl ester as the starting material and N-chlorosuccinimide (NCS) as the key additive, yielding ethyl 2-(benzylthio)-2-oxoethyl ester through a one-step reaction. Summary of the Invention

[0004] A problem with existing technologies is that there are few reported methods for synthesizing ethyl 2-(benzylthio)-2-oxoethyl acetate. To address this problem, this invention provides a method for preparing ethyl 2-(benzylthio)-2-oxoethyl acetate, comprising the following steps:

[0005] Ethyl 2-(benzylthio)ethyl acetate and N-chlorosuccinimide (NCS) were added to N,N-dimethylformamide. The reaction system reacted violently. After purification, the reaction solution yielded ethyl 2-(benzylthio)-2-oxoethyl acetate. The structural formula of ethyl 2-(benzylthio)-2-oxoethyl acetate is as follows:

[0006]

[0007] Preferably, the purification method involves sequentially concentrating the reaction solution and separating it by column chromatography.

[0008] Preferably, the reaction temperature is 100-140℃.

[0009] Preferably, the reaction temperature is 100°C.

[0010] Preferably, the reaction time is greater than 1 hour.

[0011] Preferably, the reaction time is 12 hours.

[0012] Preferably, the ratio of ethyl 2-(benzylthio)acetate to N-chlorosuccinimide and N,N-dimethylformamide is 0.2 mmol:0.4-0.6 mmol:1-3 mL.

[0013] Preferably, the ratio of ethyl 2-(benzylthio)acetate to N-chlorosuccinimide and N,N-dimethylformamide is 0.2 mmol:0.4 mmol:2 mL.

[0014] The present invention has the following beneficial effects:

[0015] This invention provides a novel method for synthesizing ethyl 2-(benzylthio)-2-oxoethyl acetate. This method uses NCS as the key additive in the reaction, ethyl 2-(benzylthio)ethyl acetate as the reactant, and N,N-dimethylformamide as the reaction solvent. The target product was successfully synthesized. The method of this invention is simple, has a high yield, and has good application prospects. Detailed Implementation

[0016] 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.

[0017] Example 1

[0018] In a 25 mL sealed tube, ethyl 2-(benzylthio)acetate (0.2 mmol, 42.02 mg), N,N-dimethylformamide (2.0 mL), and NCS (0.4 mmol, 53.41 mg) were added sequentially. The mixture was then stirred at 100 °C for 12 h. After the reaction was complete, the reaction solution was concentrated and separated by column chromatography to obtain ethyl 2-(benzylthio)-2-oxoacetate in a yield of 65%. The reaction equation is as follows:

[0019]

[0020] The NMR data for ethyl 2-(benzylthio)-2-oxoethyl acetate are as follows: 1 H NMR (300MHz, CDCl3): δ7.35-7.25 (m, 5H), 4.36 (q, J = 7.1Hz, 2H), 4.20 (s, 2H), 1.37 (t, J = 7.1Hz, 3H).

[0021] 13 C NMR (75MHz, CDCl3): δ185.06, 158.95, 136.05, 129.05, 128.80, 127.74, 63.66, 33.71, 13.99.

[0022] The reaction temperature was selected as follows:

[0023] Example 2 is the same as Example 1, except that the reaction temperature in Example 2 is 25°C. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0024] Example 3 is the same as Example 1, except that the reaction temperature in Example 3 is 60°C. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0025] Example 4 is the same as Example 1, except that the reaction temperature in Example 4 is 120°C. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 41%.

[0026] Example 5 is the same as Example 1, except that the reaction temperature in Example 5 is 140°C. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 34%.

[0027] The reaction solvents were selected as follows:

[0028] Example 6 is the same as Example 1, except that the reaction solvent in Example 6 is ethyl acetate. 2-(benzylthio)-2-

[0029] The yield of ethyl oxoacetate was 0%.

[0030] Example 7 is the same as Example 1, except that the reaction solvent in Example 7 is tetrahydrofuran. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0031] Example 8 is the same as Example 1, except that the reaction solvent in Example 8 is toluene. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0032] Example 9 is the same as Example 1, except that the reaction solvent in Example 9 is dichloromethane. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0033] Example 10 is the same as Example 1, except that the reaction solvent in Example 10 is dimethyl sulfoxide. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0034] Example 11 is the same as Example 1, except that the reaction solvent in Example 11 is N,N-dimethylacetamide. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0035] Example 12 is the same as Example 1, except that the reaction solvent in Example 12 is anhydrous methanol. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0036] The NCS usage selection is as follows:

[0037] Example 13 is the same as Example 1, except that the amount of NCS used in Example 13 is 0.2 mmol. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0038] Example 14 is the same as Example 1, except that the amount of NCS used in Example 14 is 0.6 mmol. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 42%.

[0039] Screening for reaction time:

[0040] Example 15 is the same as Example 1, except that the reaction time in Example 15 is 1 hour. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 0%.

[0041] Example 16 is the same as Example 1, except that the reaction time in Example 16 is 6 hours. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 46%.

[0042] Example 17 is the same as Example 1, except that the reaction time in Example 17 is 24 hours. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 20%.

[0043] Screening of reaction solvent dosage:

[0044] Example 18 is the same as Example 1, except that the amount of N,N-dimethylformamide used in Example 18 is 1.0 mL. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 45%.

[0045] Example 19 is the same as Example 1, except that the amount of N,N-dimethylformamide used in Example 19 is 3.0 mL. The yield of ethyl 2-(benzylthio)-2-oxoacetate is 50%.

[0046] 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 process for the preparation of ethyl 2-(benzylthio)-2-oxoacetate, characterized in that, The preparation process comprises the following steps: The ethyl 2-(benzylthio)acetate and N-chlorosuccinimide are added into N,N-dimethylformamide, the reaction system is reacted violently, and the reaction solution is purified to obtain ethyl 2-(benzylthio)-2-oxoacetate, and the structural formula of the ethyl 2-(benzylthio)-2-oxoacetate is as follows: ； The reaction temperature is 100-140 DEG C, the reaction time is greater than 1 h, and the amount ratio between the ethyl 2-(benzylthio)acetate, the N-chlorosuccinimide and the N,N-dimethylformamide is 0.2 mmol:0.4-0.6 mmol:1-3 mL.

2. The method for preparing ethyl 2-(benzylthio)-2-oxoethyl acetate according to claim 1, characterized in that, The purification method is to sequentially concentrate and separate the reaction solution by column chromatography.

3. The method for preparing ethyl 2-(benzylthio)-2-oxoethyl acetate according to claim 1, characterized in that, The reaction temperature is 100 DEG C.

4. The method for preparing ethyl 2-(benzylthio)-2-oxoethyl acetate according to claim 1, characterized in that, The reaction time is 12 h.

5. The method for preparing ethyl 2-(benzylthio)-2-oxoethyl acetate according to claim 1, characterized in that, The amount ratio between the ethyl 2-(benzylthio)acetate, the N-chlorosuccinimide and the N,N-dimethylformamide is 0.2 mmol:0.4 mmol:2 mL.

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