Method for preparing 2-(benzyl sulfenyl)-2-oxo ethyl acetate

Abstract

The invention relates to the technical field of fine chemical engineering, in particular to a method for preparing 2-(benzylthio)-2-ethyl oxoacetate. The synthesis method of the 2-(benzyl sulfenyl)-2-oxo ethyl acetate is rarely reported. In order to solve the technical problem, the invention provides the method for preparing 2-(benzylthio)-2-oxo ethyl acetate, the target product is successfully synthesized by taking NCS as a key additive for reaction, 2-(benzylthio) ethyl acetate as a reaction raw material and N, N-dimethylformamide as a reaction solvent, the method is simple, the yield is high, and the method is suitable for industrial production. Good application prospects are realized.

Description

Technical Field

[0001] The invention relates to the technical field of fine chemicals, and in particular to a method for preparing ethyl 2-(benzylthio)-2-oxoacetate. Background Art

[0002] Ethyl 2-(benzylthio)-2-oxoacetate and its derivatives are a class of important biologically active sulfur-containing oxalate compounds. Relevant literature reports that this class of compounds can quickly bind to cysteine ​​or cysteamine in the human body, regulate the catalytic activity of enzymes in the human body, and thus affect the normal life activities of the human body (Bioorg. Chem., 1987, 15, 81-91). It is worth noting that, at present, there are few reports on the synthesis methods of this compound and its derivatives.

[0003] Based on the above problems, the present invention designs and synthesizes a method for synthesizing ethyl 2-(benzylthio)-2-oxoacetate using N-chlorosuccinimide (NCS). The reaction uses ethyl 2-(benzylthio)acetate as a raw material and N-chlorosuccinimide (NCS) as a key additive, and obtains ethyl 2-(benzylthio)-2-oxoacetate through a one-step reaction. Summary of the invention

[0004] The problem in the prior art is that there are few reports on the synthesis method of ethyl 2-(benzylthio)-2-oxoacetate. In view of the above technical problems, the present invention provides a method for preparing ethyl 2-(benzylthio)-2-oxoacetate, which comprises the following preparation steps:

[0005] Ethyl 2-(benzylthio)acetate and N-chlorosuccinimide (NCS) are added to N,N-dimethylformamide, and the reaction system reacts violently. After the reaction solution is purified, ethyl 2-(benzylthio)-2-oxoacetate is obtained. The structural formula of ethyl 2-(benzylthio)-2-oxoacetate is as follows:

[0006]

[0007] Preferably, the purification method is to sequentially concentrate the reaction solution and separate it by column chromatography.

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

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

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

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

[0012] Preferably, the usage 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 usage 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] The invention provides a new method for synthesizing ethyl 2-(benzylthio)-2-oxoacetate. The method uses NCS as a key additive for the reaction, uses ethyl 2-(benzylthio)acetate as a reaction raw material, and uses N,N-dimethylformamide as a reaction solvent to successfully synthesize a target product. The method is simple, has a high yield, and has good application prospects. DETAILED DESCRIPTION

[0016] The present invention is described in detail below with reference to the examples. However, it should be understood that the following examples are only illustrative of the embodiments 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 in sequence, and then stirred at 100°C for 12 hours to complete the reaction. After the reaction, the reaction solution was concentrated and separated by column chromatography to obtain ethyl 2-(benzylthio)-2-oxoacetate with a yield of 65%. The reaction formula of the above reaction is as follows:

[0019]

[0020] The NMR data of ethyl 2-(benzylthio)-2-oxoacetate 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 screened 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 solvent was selected as follows:

[0028] Example 6 is the same as Example 1, except that the reaction solvent in Example 6 is ethyl acetate.

[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 screening of NCS dosage 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] Reaction time screening:

[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 ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A method for preparing ethyl 2-(benzylthio)-2-oxoacetate, characterized in that: The method comprises the following preparation steps: Ethyl 2-(benzylthio)acetate and N-chlorosuccinimide are added to N,N-dimethylformamide, and the reaction system reacts violently. After the reaction solution is purified, ethyl 2-(benzylthio)-2-oxoacetate is obtained. The structural formula of ethyl 2-(benzylthio)-2-oxoacetate is as follows:

2. A method for preparing ethyl 2-(benzylthio)-2-oxoacetate according to claim 1, characterized in that: The purification method is to concentrate the reaction solution and separate it by column chromatography in sequence.

3. A method for preparing ethyl 2-(benzylthio)-2-oxoacetate according to claim 1, characterized in that: The reaction temperature is 100-140°C.

4. A method for preparing ethyl 2-(benzylthio)-2-oxoacetate according to claim 3, characterized in that: The reaction temperature was 100°C.

5. A method for preparing ethyl 2-(benzylthio)-2-oxoacetate according to claim 1, characterized in that: The reaction time is greater than 1h.

6. A method for preparing ethyl 2-(benzylthio)-2-oxoacetate according to claim 5, characterized in that: The reaction time is 12h.

7. A method for preparing ethyl 2-(benzylthio)-2-oxoacetate according to claim 1, characterized in that: The usage ratio of ethyl 2-(benzylthio)acetate to N-chlorosuccinimide and N,N-dimethylformamide is 0.2mmol:0.4-0.6mmol:1-3mL.

8. A method for preparing ethyl 2-(benzylthio)-2-oxoacetate according to claim 7, characterized in that: The usage ratio of ethyl 2-(benzylthio)acetate to N-chlorosuccinimide and N,N-dimethylformamide is 0.2mmol:0.4mmol:2mL.

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