Preparation method of 3-methylthiopropionaldehyde

Abstract

The invention belongs to the technical field of preparation of 3-methylthio-propionaldehyde, and particularly relates to a preparation method of 3-methylthio-propionaldehyde, which comprises the following steps: S1, mixing 3-chlorphenyl-methyl sulfide with an inorganic alkali solution for reaction to obtain an intermediate 1; and S2, putting the intermediate 1 into a reaction kettle, sequentially adding a catalyst and an organic solvent, and oxidizing the intermediate 1 by taking air as an oxygen source to obtain the 3-methylthiopropionaldehyde. The synthesis method is simple and efficient, the reaction system is simple, the yield is high, the selectivity is good, oxygen or air is used as an oxygen source, the cost is low, toxicity is avoided, products obtained after oxidation reaction are few, byproducts difficult to treat cannot be generated, oxidation can be mildly achieved, smelly gas cannot be generated in the reaction process, the pressure in a reaction kettle is low, energy consumption is low, and the method is suitable for industrial production. And the requirements of green, energy-saving and sustainable development are met.

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 by the abbreviation of methionine hydroxy analog MHA).

[0003] Usually, methyl mercaptan and acrolein are reacted under alkaline conditions to obtain the product. However, since this method is a liquid-liquid reaction, the reaction speed is fast and the reaction is exothermic, in the actual production process, it is easy to reduce the purity and yield of the 3-methylmercaptopropionaldehyde product due to excessive local concentration of methyl mercaptan or acrolein or local overheating and excessive by-products. In addition, since methyl mercaptan is a toxic gas with a pungent odor at normal temperature and pressure, it must be pressurized and cooled to be converted into a liquid, which consumes a lot of energy and greatly increases the cost.

[0004] After searching, the patent with the announcement number CN101857560B discloses a method for preparing 3-methylthiopropionaldehyde, which allows acrolein to react with methyl mercaptan in the presence of an organic acid. However, in actual production, continuous distillation is required, 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 as follows:

[0008]

[0009] It specifically includes the following steps:

[0010] S1, mixing 3-chlorophenyl-methyl sulfide with an inorganic base solution to react to obtain an 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, 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 1-2Mpa.

[0022] As a preferred technical solution of the present invention, the oxidation time of step S2 is 8-14h 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 invention is simple and efficient, has a simple reaction system, a high yield, and 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-treat by-products, can mildly achieve oxidation, does not produce unpleasant-smelling gases during the reaction, has a 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 in conjunction with specific embodiments.

[0026] For ease of understanding of the present invention, the present invention will be described more fully below by way of embodiments. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0027] For simplicity, the present invention only explicitly discloses some numerical ranges. However, any lower limit can be combined with any upper limit to form an unambiguous range; and any lower limit can be combined with other lower limits to form an unambiguous range, and any upper limit can be combined with any other upper limit to form an unambiguous range. In addition, although not explicitly stated, each point or single value between the range endpoints is included in the range. Thus, each point or single value can be combined with any other point or single value as its own lower limit or upper limit or with other lower limits or upper limits to form an unambiguous 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 of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention. It should be noted that, unless otherwise specified, the term "and / or" used herein includes any and all combinations of one or more related listed items, and "above", "below" include the number, and the meaning of "multiple" in "one or more" is more than two.

[0029] Embodiment 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. 1 mol of 3-chlorophenyl-methyl sulfide was fully mixed with 5 mol / L 200 ml of sodium hydroxide aqueous solution and reacted at 60°C for 6 h to obtain intermediate 1 with a yield of 95%. Elemental analysis: C4H10OS. Theoretical value: C, 45.25; H, 9.49; O, 15.07; S, 30.19; Found value: C, 45.26; H, 9.50; S, 30.17. HRMS (ESI) m / z (Μ+H)+: Theoretical value: 106.05; Found value: 107.11.

[0034] S2. Place the intermediate 1 (1 mol) in a reactor, add cuprous bromide (1 mmol), 2,2'-dibenzamidodiphenyl disulfide (1 mmol) and dichloromethane (1 L) in sequence, seal the reactor, and oxidize at 90°C for 10 h at a pressure of 1 MPa. After the reaction is completed, cool to room temperature, and gradually release gas and reduce pressure. The organic layer is dried with anhydrous sodium sulfate to remove the solvent, and 3-methylthiopropanal is obtained by silica gel column chromatography with a yield of 92%. Elemental analysis: C4H8OS. Theoretical value: C, 46.12; H, 7.74; O, 15.36; S, 30.78; Measured value: C, 46.13; H, 7.75; S, 30.76. HRMS (ESI) m / z (Μ+H)+: Theoretical value: 104.03; Measured value: 105.16.

[0035] Embodiment 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. 1 mol of 3-chlorophenyl-methyl sulfide was fully mixed with 5 mol / L 200 ml of sodium hydroxide aqueous solution and reacted at 60°C for 6 h to obtain intermediate 1 with a yield of 96%. Elemental analysis: C4H10OS. Theoretical value: C, 45.25; H, 9.49; O, 15.07; S, 30.19; Found value: C, 45.27; H, 9.51; S, 30.15. HRMS (ESI) m / z (Μ+H)+: Theoretical value: 106.05; Found value: 107.14.

[0040] S2. Place the intermediate 1 (1 mol) in a reactor, add pyridinium chlorochromate (2 mmol) and dichloromethane (1 L) in sequence, seal the reactor, and oxidize at 90 ° C for 10 h. After the reaction is completed, cool to room temperature and gradually release the gas and reduce the pressure. The organic layer is dried with anhydrous sodium sulfate to remove the solvent, and 3-methylthiopropionaldehyde is obtained by silica gel column chromatography with a yield of 91%. Elemental analysis: C4H8OS. Theoretical value: C, 46.12; H, 7.74; O, 15.36; S, 30.78; Measured value: C, 46.14; H, 7.76; S, 30.74. HRMS (ESI) m / z (Μ+H) +: theoretical value: 104.03; measured value: 105.19.

[0041] Embodiment 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. 1 mol of 3-chlorophenyl-methyl sulfide was fully mixed with 5 mol / L 200 ml of sodium hydroxide aqueous solution and reacted at 60°C for 6 h to obtain intermediate 1 with a yield of 94%. Elemental analysis: C4H10OS. Theoretical value: C, 45.25; H, 9.49; O, 15.07; S, 30.19; Found value: C, 45.27; H, 9.52; S, 30.14. HRMS (ESI) m / z (Μ+H)+: Theoretical value: 106.05; Found value: 107.19.

[0046] S2. Place the intermediate 1 (1 mol) in a reactor, add cuprous bromide (1 mmol), 2,2'-dibenzamidodiphenyl disulfide (1 mmol) and N,N,N',N'-tetramethylethylenediamine (1 L) in sequence, seal the reactor, and oxidize at 90°C for 10 h at a pressure of 1 MPa. After the reaction is completed, cool to room temperature and gradually release gas and reduce pressure. The organic layer is dried over anhydrous sodium sulfate to remove the solvent, and 3-methylthiopropanal is obtained by silica gel column chromatography with a yield of 95%. Elemental analysis: C4H8OS. Theoretical value: C, 46.12; H, 7.74; O, 15.36; S, 30.78; Measured value: C, 46.14; H, 7.77; S, 30.72. HRMS (ESI) m / z (Μ+H)+: Theoretical value: 104.03; Measured value: 105.22.

[0047] Embodiment 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. 1 mol of 3-chlorophenyl-methyl sulfide was fully mixed with 6 mol / L 200 ml of sodium hydroxide aqueous solution and reacted at 100°C for 8 h to obtain intermediate 1 with a yield of 93%. Elemental analysis: C4H10OS. Theoretical value: C, 45.25; H, 9.49; O, 15.07; S, 30.19; Found value: C, 45.28; H, 9.52; S, 30.13. HRMS (ESI) m / z (Μ+H)+: Theoretical value: 106.05; Found value: 107.21.

[0052] S2. Place the intermediate 1 (1 mol) in a reactor, add cuprous bromide (0.5 mmol), 2,2'-dibenzamidodiphenyl disulfide (0.5 mmol) and dichloromethane (1 L) in sequence, seal the reactor, and oxidize at 90°C for 10 h at a pressure of 1 MPa. After the reaction is completed, cool to room temperature, and gradually release gas and reduce pressure. The organic layer is dried with anhydrous sodium sulfate to remove the solvent, and 3-methylthiopropionaldehyde is obtained by silica gel column chromatography with a yield of 90%. Elemental analysis: C4H8OS. Theoretical value: C, 46.12; H, 7.74; O, 15.36; S, 30.78; Measured value: C, 46.15; H, 7.77; S, 30.73. HRMS (ESI) m / z (Μ+H)+: theoretical value: 104.03; measured value: 105.23.

[0053] Comparative Example 1

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

[0055] Comparative Example 2

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

[0057] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and 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 an intermediate 1; 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.

2. The method for preparing 3-methylthiopropionaldehyde according to claim 1, characterized in that: 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, characterized in that: 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, characterized in that: 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, characterized in that: 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.

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

1.

7. The method for preparing 3-methylthiopropionaldehyde according to claim 1, characterized in that: In step S2, the organic solvent is one or more of dichloromethane, chloroform, 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.

8. The method for preparing 3-methylthiopropionaldehyde according to claim 1, characterized in that: In step S2, the oxygen source is air or oxygen.

9. The method for preparing 3-methylthiopropionaldehyde according to claim 1, characterized in that: In step S2, the pressure of the reactor is 1-2Mpa.

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

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