Continuous flow method for synthesizing methyl 3-methyl-4-butyryl-5-nitrobenzoate and reaction device thereof

Abstract

The invention discloses a continuous flow method for synthesizing methyl 3-methyl-4-butyryl-5-nitrobenzoate and a reaction device thereof. The preparation method comprises the following steps: taking3-methyl-4-butyryl methyl benzoate as a raw material and mixed acid (nitric acid and sulfuric acid) as a nitration reagent, continuously inputting the materials into a high-efficiency mixer through ametering pump, mixing, feeding into a temperature-controlled pipeline reactor, carrying out nitration reaction, after the reaction is finished, quenching the reaction liquid in the pipeline reactor, performing continuous liquid separation, neutralizing, drying, concentrating and recrystallizing the obtained organic phase to obtain a pure 3-methyl-4-butyryl-5-methyl nitrobenzoate product. The continuous flow nitration reaction has the advantages of low mixed acid consumption, short reaction time, high conversion rate, fewer byproducts and fewer solid wastes, and conforms to the concept of greenchemistry; the continuous flow synthesis method has the advantages of good safety, convenience in intelligent control, high reaction and post-treatment efficiency and the like, and has industrial production application value.

Description

technical field

[0001] The invention discloses a continuous flow method and a reaction device for synthesizing methyl 3-methyl-4-butyryl-5-nitrobenzoate. Background technique

[0002] 3-methyl-4-butyryl-5-nitrobenzoic acid methyl ester is an important intermediate for the synthesis of antihypertensive drug telmisartan, and its synthesis method is usually based on 3-methyl-4-butyryl benzoic acid methyl Esters are used as raw materials and prepared by nitration with mixed acid.

[0003] In the prior art, the synthesis of 3-methyl-4-butyryl-5-nitrobenzoic acid methyl ester generally takes 3-methyl-4-butyryl benzoic acid methyl ester as raw material and excess mixed acid to obtain by kettle-type nitration reaction (eg Chinese patent applications CN103319415 and CN104610161). There are many disadvantages in the traditional batch-type tank-type nitration reaction: First, because the traditional mixed-acid nitration usually uses fuming nitric acid and concentrated sulfuric acid, ...

Examples

Embodiment 1

[0045] The structure of the special reaction device used in this embodiment is as follows: figure 1 As shown, the length of the reactor pipe is 20m, the diameter is 3mm, and the pipe material is Teflon pipe.

[0046] First open the first semiconductor temperature control box 7 precooling pipelines, the temperature is set at 10°C, open the second semiconductor temperature control box 13, and the set temperature is 25°C; Fuming nitric acid, store a sufficient amount of 98% sulfuric acid in the concentrated sulfuric acid storage tank 2, and store in In the liquid storage tank 8 , sufficient 5° C. ice water is stored in the quenching agent liquid storage tank 15 .

[0047] Start the first metering pump 3 and the second metering pump 5, control the flow of the two pumps so that the molar equivalent ratio of nitric acid and sulfuric acid is 3:1, and control the flow rate to keep the temperature of the mixed acid flowing out of the first pipeline reactor 6 at about 18°C. When the m...

Embodiment 2

[0049] The structure of the special reaction device used in this embodiment is as follows: figure 1 As shown, the length of the reactor pipe is 20m, the diameter is 3mm, and the pipe material is Teflon.

[0050] First open the first semiconductor temperature control box 7 precooling pipelines, the temperature is set at 10°C, open the second semiconductor temperature control box 13, and the set temperature is 25°C; Fuming nitric acid, store a sufficient amount of 98% sulfuric acid in the concentrated sulfuric acid storage tank 2, and store in In the liquid storage tank 8 , sufficient 5° C. ice water is stored in the quenching agent liquid storage tank 15 .

[0051] Start the first metering pump 3 and the second metering pump 5, control the flow of the two pumps so that the molar equivalent ratio of nitric acid and sulfuric acid is 3:1, and control the flow rate to keep the temperature of the mixed acid flowing out of the first pipeline reactor 6 at about 18°C. When the mixed ...

Embodiment 3

[0053] The structure of the special reaction device used in this embodiment is as follows: figure 1 As shown, the length of the reactor pipe is 20m, the diameter is 3mm, and the pipe material is Teflon.

[0054] First open the first semiconductor temperature control box 7 precooling pipelines, the temperature is set at 10°C, open the second semiconductor temperature control box 13, and the set temperature is 25°C; Fuming nitric acid, store a sufficient amount of 98% sulfuric acid in the concentrated sulfuric acid storage tank 2, and store in In the liquid storage tank 8 , sufficient 5° C. ice water is stored in the quenching agent liquid storage tank 15 .

[0055] Start the first metering pump 3 and the second metering pump 5, control the flow of the two pumps so that the molar equivalent ratio of nitric acid and sulfuric acid is 3:1, and control the flow rate to keep the temperature of the mixed acid flowing out of the first pipeline reactor 6 at about 18°C. When the mixed ...

technical field

[0001] The invention discloses a continuous flow method and a reaction device for synthesizing methyl 3-methyl-4-butyryl-5-nitrobenzoate. Background technique

[0002] 3-methyl-4-butyryl-5-nitrobenzoic acid methyl ester is an important intermediate for the synthesis of antihypertensive drug telmisartan, and its synthesis method is usually based on 3-methyl-4-butyryl benzoic acid methyl Esters are used as raw materials and prepared by nitration with mixed acid.

[0003] In the prior art, the synthesis of 3-methyl-4-butyryl-5-nitrobenzoic acid methyl ester generally takes 3-methyl-4-butyryl benzoic acid methyl ester as raw material and excess mixed acid to obtain by kettle-type nitration reaction (eg Chinese patent applications CN103319415 and CN104610161). There are many disadvantages in the traditional batch-type tank-type nitration reaction: First, because the traditional mixed-acid nitration usually uses fuming nitric acid and concentrated sulfuric acid, ...

Examples

Embodiment 1

[0045] The structure of the special reaction device used in this embodiment is as follows: figure 1 As shown, the length of the reactor pipe is 20m, the diameter is 3mm, and the pipe material is Teflon pipe.

[0046] First open the first semiconductor temperature control box 7 precooling pipelines, the temperature is set at 10°C, open the second semiconductor temperature control box 13, and the set temperature is 25°C; Fuming nitric acid, store a sufficient amount of 98% sulfuric acid in the concentrated sulfuric acid storage tank 2, and store in In the liquid storage tank 8 , sufficient 5° C. ice water is stored in the quenching agent liquid storage tank 15 .

[0047] Start the first metering pump 3 and the second metering pump 5, control the flow of the two pumps so that the molar equivalent ratio of nitric acid and sulfuric acid is 3:1, and control the flow rate to keep the temperature of the mixed acid flowing out of the first pipeline reactor 6 at about 18°C. When the m...

Embodiment 2

[0049] The structure of the special reaction device used in this embodiment is as follows: figure 1 As shown, the length of the reactor pipe is 20m, the diameter is 3mm, and the pipe material is Teflon.

[0050] First open the first semiconductor temperature control box 7 precooling pipelines, the temperature is set at 10°C, open the second semiconductor temperature control box 13, and the set temperature is 25°C; Fuming nitric acid, store a sufficient amount of 98% sulfuric acid in the concentrated sulfuric acid storage tank 2, and store in In the liquid storage tank 8 , sufficient 5° C. ice water is stored in the quenching agent liquid storage tank 15 .

[0051] Start the first metering pump 3 and the second metering pump 5, control the flow of the two pumps so that the molar equivalent ratio of nitric acid and sulfuric acid is 3:1, and control the flow rate to keep the temperature of the mixed acid flowing out of the first pipeline reactor 6 at about 18°C. When the mixed ...

Embodiment 3

[0053] The structure of the special reaction device used in this embodiment is as follows: figure 1 As shown, the length of the reactor pipe is 20m, the diameter is 3mm, and the pipe material is Teflon.

[0054] First open the first semiconductor temperature control box 7 precooling pipelines, the temperature is set at 10°C, open the second semiconductor temperature control box 13, and the set temperature is 25°C; Fuming nitric acid, store a sufficient amount of 98% sulfuric acid in the concentrated sulfuric acid storage tank 2, and store in In the liquid storage tank 8 , sufficient 5° C. ice water is stored in the quenching agent liquid storage tank 15 .

[0055] Start the first metering pump 3 and the second metering pump 5, control the flow of the two pumps so that the molar equivalent ratio of nitric acid and sulfuric acid is 3:1, and control the flow rate to keep the temperature of the mixed acid flowing out of the first pipeline reactor 6 at about 18°C. When the mixed ...

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