A preparation method of 3-methylthiopropionaldehyde

Abstract

The invention belongs to the technical field of preparation of 3 methylthiopropionaldehyde, specifically a kind of preparation method of 3 methylthiopropionaldehyde, comprising the following steps: S1, making 3 chlorophenyl methyl sulfide and inorganic alkaline solution carry out mixed reaction to obtain intermediate 1; S2, intermediate 1 is placed in a reactor, and catalyst and organic solvent are added sequentially, and intermediate 1 is oxidized using air as an oxygen source to obtain 3 methylthiopropionaldehyde. Synthesis method of the present invention is simple and efficient, reaction system is simple, yield is high, selectivity is good, using oxygen or air as an oxygen source, cost is low, non-toxic, the product after oxidation reaction is less, difficult to handle by-products will not be produced, oxidation can be achieved gently, no unpleasant gas will be produced during the reaction, the pressure in the reactor is low, energy consumption is less, and it meets the requirements of green, energy-saving and sustainable development.

Description

Technical Field

[0001] The invention belongs to the technical field of 3-methylmercaptopropionaldehyde preparation, and specifically relates to a method for preparing 3-methylmercaptopropionaldehyde. Background Art

[0002] 3-Methylthiopropionaldehyde, also known as methylmercaptopropionaldehyde (abbreviated as MMP) or 4-thiopentanal (UN No. 2785), is known to be an important intermediate in the preparation of D,L-methionine and its hydroxy analog 2-hydroxy-4-methylthiobutyric acid (also known as the abbreviation of methionine hydroxy analog MHA).

[0003] Methyl mercaptan and acrolein are typically reacted under alkaline conditions to produce the product. However, due to the liquid-liquid reaction method, the reaction speed is relatively fast and the reaction is exothermic. This can lead to excessive local concentrations of methyl mercaptan or acrolein, local overheating, and excessive by-products in actual production processes, thereby reducing the purity and yield of the 3-methylmercaptopropionaldehyde product. Furthermore, since methyl mercaptan is a toxic gas with a pungent odor at normal temperatures and pressures, pressurization and cooling are necessary to convert it into a liquid, consuming a large amount of energy and significantly increasing costs.

[0004] A search revealed patent publication number CN101857560B, which discloses a method for preparing 3-methylthiopropionaldehyde. This method involves reacting acrolein with methyl mercaptan in the presence of an organic acid. However, actual production requires continuous distillation, which is time-consuming and energy-intensive. Summary of the Invention

[0005] The object of the present invention is to provide a method for preparing 3-methylthiopropionaldehyde to solve the defects pointed out in the above background technology.

[0006] The technical solution of the present invention is:

[0007] A method for preparing 3-methylthiopropionaldehyde, the general synthesis formula of which is shown below:

[0008]

[0009] It specifically includes the following steps:

[0010] S1, mixing 3-chlorophenyl-methyl sulfide with an inorganic base solution to react to obtain intermediate 1;

[0011] S2. placing the intermediate 1 in a reaction kettle, and sequentially adding a catalyst and an organic solvent, and oxidizing the intermediate 1 with air as an oxygen source to obtain 3-methylthiopropionaldehyde.

[0012] As a preferred technical solution of the present invention, in step S1, the inorganic alkaline solution is one or more of a sodium hydroxide aqueous solution, a potassium hydroxide aqueous solution, and a calcium hydroxide aqueous solution.

[0013] As a preferred technical solution of the present invention, in step S1, the inorganic alkaline solution is a sodium hydroxide aqueous solution.

[0014] As a preferred technical solution of the present invention, in step S1, the molar ratio between the 3-chlorophenyl-methyl sulfide and the inorganic base solution is 1:(1-1.5).

[0015] As a preferred technical solution of the present invention, in step S1, the molar ratio between the 3-chlorophenyl-methyl sulfide and the inorganic base solution is 1:(1-1.2).

[0016] As a preferred technical solution of the present invention, the reaction time of step S1 is 2-10 hours, and the reaction temperature is 40-100°C.

[0017] As a preferred technical solution of the present invention, in step S2, the catalyst is one or more of cuprous bromide, 2,2'-dibenzamidodiphenyl disulfide, dimethyl sulfoxide, chromium trioxide acetic anhydride, pyridinium chlorochromate, and pyridinium dichromate.

[0018] As a preferred technical solution of the present invention, in step S2, the molar ratio between the catalyst and the intermediate 1 is (100-200):1.

[0019] As a preferred technical solution of the present invention, in step S2, the organic solvent is one or more of dichloromethane, chloroform, and N,N,N',N'-tetramethylethylenediamine, and the amount of the organic solvent added is such that the molar concentration of the intermediate 1 is 2.0-3.0 mol / L.

[0020] As a preferred technical solution of the present invention, in step S2, the oxygen source is air or oxygen.

[0021] As a preferred technical solution of the present invention, in step S2, the pressure of the reactor is 1-2 MPa.

[0022] As a preferred technical solution of the present invention, the oxidation time of step S2 is 8-14 hours, and the oxidation temperature is 60-100°C.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] The synthesis method of the present invention is simple and efficient, has a simple reaction system, high yield, good selectivity, uses oxygen or air as an oxygen source, has low cost, is non-toxic, produces fewer products after the oxidation reaction, does not produce difficult-to-handle by-products, can mildly achieve oxidation, does not produce unpleasant gases during the reaction, has low pressure in the reactor, consumes less energy, and meets the requirements of green, energy-saving and sustainable development. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention is described in detail below with reference to specific embodiments.

[0026] To facilitate understanding of the present invention, the present invention will be described more fully below by way of examples. However, the present invention can be implemented in many different forms and is not limited to the examples described herein. Rather, the purpose of providing these examples is to provide a more thorough and comprehensive understanding of the disclosure of the present invention.

[0027] For simplicity, this disclosure only explicitly discloses certain numerical ranges. However, any lower limit may be combined with any upper limit to form an unspecified range; and any lower limit may be combined with other lower limits to form an unspecified range, and similarly, any upper limit may be combined with any other upper limit to form an unspecified range. In addition, even if not explicitly stated, each point or individual value between the endpoints of a range is included in the range. Thus, each point or individual value may serve as its own lower limit or upper limit and be combined with any other point or individual value, or with other lower limits or upper limits, to form an unspecified range.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the present invention pertains. The terms used herein in the specification of the present invention are for the purpose of describing specific embodiments only and are not intended to limit the present invention. It should be noted that, unless otherwise stated, the term "and / or" used herein includes any and all combinations of one or more of the listed items, and "above" and "below" include the number itself, and the meaning of "a variety" in "one or more" is more than two.

[0029] Example 1

[0030] This embodiment provides a method for preparing 3-methylthiopropionaldehyde, and its general synthesis formula is as follows:

[0031]

[0032] It specifically includes the following steps:

[0033] S1. Thoroughly mix 1 mol of 3-chlorophenyl methyl sulfide with 200 ml of 5 mol / L aqueous sodium hydroxide solution and react at 60°C for 6 h to obtain intermediate 1 in 95% yield. Elemental analysis: C₄H₁₁₀OS. Calculated: C, 45.25; H, 9.49; O, 15.07; S, 30.19; Found: C, 45.26; H, 9.50; S, 30.17. HRMS (ESI) m / z (M+H)+: Calculated: 106.05; Found: 107.11.

[0034] S2. Intermediate 1 (1 mol) was placed in a reaction vessel. Cuprous bromide (1 mmol), 2,2'-dibenzamidodiphenyl disulfide (1 mmol), and dichloromethane (1 L) were added sequentially. The reaction vessel was sealed and oxidized at 90°C for 10 h at a pressure of 1 MPa. After the reaction, the mixture was cooled to room temperature and the pressure was gradually vented. The organic layer was dried over anhydrous sodium sulfate to remove the solvent. 3-methylthiopropanal was obtained by silica gel column chromatography in a 92% yield. Elemental analysis: C₄H₄OS. Calculated: C, 46.12; H, 7.74; O, 15.36; S, 30.78; Found: C, 46.13; H, 7.75; S, 30.76. HRMS (ESI) m / z (M+H)+: Calculated: 104.03; Found: 105.16.

[0035] Example 2

[0036] This embodiment provides a method for preparing 3-methylthiopropionaldehyde, and its general synthesis formula is as follows:

[0037]

[0038] It specifically includes the following steps:

[0039] S1. Thoroughly mix 1 mol of 3-chlorophenyl methyl sulfide with 200 ml of 5 mol / L aqueous sodium hydroxide solution and react at 60°C for 6 h to obtain intermediate 1 in 96% yield. Elemental analysis: C₄H₁₁₀OS. Calculated: C, 45.25; H, 9.49; O, 15.07; S, 30.19; Found: C, 45.27; H, 9.51; S, 30.15. HRMS (ESI) m / z (M+H)+: Calculated: 106.05; Found: 107.14.

[0040] S2. Intermediate 1 (1 mol) was placed in a reaction vessel. Pyridinium chlorochromate (2 mmol) and dichloromethane (1 L) were added sequentially. The vessel was sealed and oxidized at 90°C for 10 h at a pressure of 1 MPa. After completion of the reaction, the reaction mixture was cooled to room temperature and the pressure was gradually vented. The organic layer was dried over anhydrous sodium sulfate to remove the solvent. 3-methylthiopropanal was obtained by silica gel column chromatography in a 91% yield. Elemental analysis: C₄H₄OS. Calculated: C, 46.12; H, 7.74; O, 15.36; S, 30.78; Found: C, 46.14; H, 7.76; S, 30.74. HRMS (ESI) m / z (M+H)+: Calculated: 104.03; Found: 105.19.

[0041] Example 3

[0042] This embodiment provides a method for preparing 3-methylthiopropionaldehyde, and its general synthesis formula is as follows:

[0043]

[0044] It specifically includes the following steps:

[0045] S1. Thoroughly mix 1 mol of 3-chlorophenyl methyl sulfide with 200 ml of 5 mol / L aqueous sodium hydroxide solution and react at 60°C for 6 h to obtain intermediate 1 in 94% yield. Elemental analysis: C₄H₁₁₀OS. Calculated: C, 45.25; H, 9.49; O, 15.07; S, 30.19; Found: C, 45.27; H, 9.52; S, 30.14. HRMS (ESI) m / z (M+H)+: Calculated: 106.05; Found: 107.19.

[0046] S2. Intermediate 1 (1 mol) was placed in a reaction vessel. Cuprous bromide (1 mmol), 2,2'-dibenzamidodiphenyl disulfide (1 mmol), and N,N,N',N'-tetramethylethylenediamine (1 L) were added sequentially. The reaction vessel was sealed and oxidized at 90°C at a pressure of 1 MPa for 10 h. After the reaction, the mixture was cooled to room temperature and the pressure was gradually vented. The organic layer was dried over anhydrous sodium sulfate to remove the solvent. 3-methylthiopropanal was obtained by silica gel column chromatography in a 95% yield. Elemental analysis: C₄H₄OS. Calculated: C, 46.12; H, 7.74; O, 15.36; S, 30.78; Found: C, 46.14; H, 7.77; S, 30.72. HRMS (ESI) m / z (M+H)+: Calculated: 104.03; Found: 105.22.

[0047] Example 4

[0048] This embodiment provides a method for preparing 3-methylthiopropionaldehyde, and its general synthesis formula is as follows:

[0049]

[0050] It specifically includes the following steps:

[0051] S1. Thoroughly mix 1 mol of 3-chlorophenyl methyl sulfide with 200 ml of 6 mol / L aqueous sodium hydroxide solution and react at 100°C for 8 h to obtain intermediate 1 in 93% yield. Elemental analysis: C₄H₁₁₁₁₁₂OS. Calculated: C, 45.25; H, 9.49; O, 15.07; S, 30.19; Found: C, 45.28; H, 9.52; S, 30.13. HRMS (ESI) m / z (M+H)+: Calculated: 106.05; Found: 107.21.

[0052] S2. Intermediate 1 (1 mol) was placed in a reaction vessel. Cuprous bromide (0.5 mmol), 2,2'-dibenzamidodiphenyl disulfide (0.5 mmol), and dichloromethane (1 L) were added sequentially. The reaction vessel was sealed and oxidized at 90°C at a pressure of 1 MPa for 10 h. After the reaction, the mixture was cooled to room temperature and the pressure was gradually vented. The organic layer was dried over anhydrous sodium sulfate to remove the solvent. 3-methylthiopropanal was obtained by silica gel column chromatography in a 90% yield. Elemental analysis: C₄H₄OS. Calculated: C, 46.12; H, 7.74; O, 15.36; S, 30.78; Found: C, 46.15; H, 7.77; S, 30.73. HRMS (ESI) m / z (M+H)+: Calculated: 104.03; Found: 105.23.

[0053] Comparative Example 1

[0054] 3-Methylthiopropionaldehyde was prepared by the method described in patent publication number CN101857560B with a yield of 80%. In addition, there were many by-products (specifically multiple reaction substrates) and continuous distillation was required. The reaction continuity was poor, which was not conducive to large-scale production.

[0055] Comparative Example 2

[0056] 3-Methylthiopropionaldehyde was prepared by the method described in patent publication number CN108884027B with a yield of 78%. Furthermore, the method produced a large number of by-products and required continuous distillation. Furthermore, it was also necessary to add an excess of methyl mercaptan and N,N-dimethylbenzylamine dissolved in acetic acid, which was not conducive to large-scale production.

[0057] The above description of the embodiments is intended to facilitate understanding and use of the invention by those skilled in the art. It will be apparent that those skilled in the art can readily make various modifications to these embodiments and apply the general principles described herein to other embodiments without requiring inventive effort. Therefore, the present invention is not limited to the above-described embodiments. Improvements and modifications made by those skilled in the art based on the disclosure of the present invention, without departing from the scope of the present invention, should be within the scope of protection of the present invention.

Claims

1. A method for preparing 3-methylthiopropionaldehyde, characterized in that: The following steps are involved: S1, mixing 3-chlorophenyl-methyl sulfide with an inorganic base solution to react to obtain intermediate 1; S2, placing the intermediate 1 in a reactor, and sequentially adding a catalyst and an organic solvent, and oxidizing the intermediate 1 with air as an oxygen source to obtain 3-methylthiopropionaldehyde; In step S2, the catalyst is composed of cuprous bromide and 2,2'-dibenzamidodiphenyl disulfide; In step S2, the organic solvent is N,N,N',N'-tetramethylethylenediamine, and the amount of the organic solvent added is such that the molar concentration of the intermediate 1 is 2.0-3.0 mol / L.

2. The method for preparing 3-methylthiopropionaldehyde according to claim 1, wherein In step S1, the inorganic alkaline solution is one or more of a sodium hydroxide aqueous solution, a potassium hydroxide aqueous solution, and a calcium hydroxide aqueous solution.

3. The method for preparing 3-methylthiopropionaldehyde according to claim 1, wherein In step S1, the molar ratio between the 3-chlorophenyl-methyl sulfide and the inorganic base solution is 1:(1-1.5).

4. The method for preparing 3-methylthiopropionaldehyde according to claim 1, wherein The reaction time of step S1 is 2-10 hours, and the reaction temperature is 40-100°C.

5. The method for preparing 3-methylthiopropionaldehyde according to claim 1, wherein In step S2, the molar ratio between the catalyst and the intermediate 1 is (100-200):

1.

6. The method for preparing 3-methylthiopropionaldehyde according to claim 1, wherein In step S2, the oxygen source is air or oxygen.

7. The method for preparing 3-methylthiopropionaldehyde according to claim 1, wherein In step S2, the pressure of the reactor is 1-2 MPa.

8. The method for preparing 3-methylthiopropionaldehyde according to claim 1, wherein The oxidation time of step S2 is 8-14 hours, and the oxidation temperature is 60-100°C.

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