Improved synthesis method of orotic acid

Abstract

The invention discloses an improved synthesis method of orotic acid and belongs to the field of organic chemical synthesis. The improved synthesis method comprises the following steps: heating a watersolution of hydantoin, glyoxylic acid and sodium hydroxide in a specific micro-channel reactor and reacting to obtain an orotic acid crude product; after refining the crude product, obtaining an orotic acid pure product. According to the improved synthesis method, a whole production process is carried out in the micro-channel reactor, so that the reaction conversion rate and the yield are improved and the reaction yield reaches 90 percent or above.

Description

technical field

[0001] The invention belongs to the field of organic chemistry, and in particular relates to an improved synthesis method of orotic acid. Background technique

[0002] Orotic acid, also known as vitamin B13, the ketone name is 1,2,3,4-tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid, and the enol name is 2,6- Dihydroxypyrimidine-4-carboxylic acid, as an effective precursor in the biosynthesis of pyrimidine-based nucleic acids in living organisms, is an important pyrimidine derivative that plays a unique role in biological and medicinal chemistry.

[0003] Orotic acid and its derivatives are widely used in the field of medicine. Orotic acid is used as an important drug in the treatment of liver diseases for the treatment of icteric liver disease and general liver dysfunction. Drug molecules participated in by orotic acid group play an important active role in the treatment of myocardial infarction, gastric ulcer, Mycobacterium tuberculosis and so on. In lif...

Examples

experiment example 1

[0033] A kind of improved synthetic method of orotic acid:

[0034] S1. Control the temperature in the reaction channel at 115-120°C, adjust the flow rate of the double pumps, and pump 1.5 kg of hydantoin, 10 kg of water, 2.5 kg of 50% glyoxylic acid mixed solution and 7.5 liters of 8N sodium hydroxide solution at the same time After 2 hours of heating cycle reaction, stop heating. When the temperature drops to 70-80°C, transfer the reaction solution to a 50-liter purification reactor, maintain the internal temperature at 60-65°C, and add concentrated hydrochloric acid dropwise to adjust the pH to 9 -9.5, centrifuge the precipitated solid to obtain a crude product of off-white sodium orotate, add the crude product to 6 liters of water, keep warm at 60-65°C, add concentrated hydrochloric acid to adjust the pH to 1-2, stir for half an hour, and The centrifugation of the solid that separates out obtains 3 kilograms of orotic acid crude product;

[0035] S2. Add the above crude s...

experiment example 2

[0037] A kind of improved synthetic method of orotic acid:

[0038] S1. Control the temperature in the reaction channel at 100-110°C, adjust the flow rate of the double pumps, and pump 1.5 kg hydantoin, 10 kg water, 2.5 kg 50% glyoxylic acid mixed solution and 7.5 liters of 8N sodium hydroxide at the same time Solution, after heating and circulating for 5 hours, stop heating, and when the temperature drops to 70-80°C, transfer the reaction solution to a 50-liter purification reactor, maintain the internal temperature at 50-60°C, and add concentrated hydrochloric acid dropwise to adjust the pH to 9-9.5, centrifuge the precipitated solid to obtain a crude product of off-white sodium orotate, add the crude product to 5 liters of water, keep it warm at 60-65°C, add concentrated hydrochloric acid dropwise to adjust the pH to 1-2, and stir for half an hour, The precipitated solid is centrifuged to obtain 2.8 kilograms of orotic acid crude product;

[0039]S2. Add the above crude so...

experiment example 3

[0041] A kind of improved synthetic method of orotic acid:

[0042] S1. Control the temperature in the reaction channel at 110-115°C, adjust the flow rate of the double pumps, and pump 1.5 kg of hydantoin, 10 kg of water, 2.5 kg of 50% glyoxylic acid mixed solution and 7.5 liters of 8N sodium hydroxide at the same time Solution, after heating and circulating for 2 hours, stop heating, and when the temperature drops to 70-80°C, transfer the reaction solution to a 50-liter purification reactor, maintain the internal temperature at 60-65°C, and add concentrated hydrochloric acid dropwise to adjust the pH to 9-9.5, centrifuge the precipitated solid to obtain a crude product of off-white sodium orotate, add the crude product to 5 liters of water, keep it warm at 60-65°C, add concentrated hydrochloric acid dropwise to adjust the pH to 1-2, and stir for half an hour, The precipitated solid is centrifuged to obtain 2.95 kilograms of orotic acid crude product;

[0043] S2. Add the abo...

technical field

[0001] The invention belongs to the field of organic chemistry, and in particular relates to an improved synthesis method of orotic acid. Background technique

[0002] Orotic acid, also known as vitamin B13, the ketone name is 1,2,3,4-tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid, and the enol name is 2,6- Dihydroxypyrimidine-4-carboxylic acid, as an effective precursor in the biosynthesis of pyrimidine-based nucleic acids in living organisms, is an important pyrimidine derivative that plays a unique role in biological and medicinal chemistry.

[0003] Orotic acid and its derivatives are widely used in the field of medicine. Orotic acid is used as an important drug in the treatment of liver diseases for the treatment of icteric liver disease and general liver dysfunction. Drug molecules participated in by orotic acid group play an important active role in the treatment of myocardial infarction, gastric ulcer, Mycobacterium tuberculosis and so on. In lif...

Examples

experiment example 1

[0033] A kind of improved synthetic method of orotic acid:

[0034] S1. Control the temperature in the reaction channel at 115-120°C, adjust the flow rate of the double pumps, and pump 1.5 kg of hydantoin, 10 kg of water, 2.5 kg of 50% glyoxylic acid mixed solution and 7.5 liters of 8N sodium hydroxide solution at the same time After 2 hours of heating cycle reaction, stop heating. When the temperature drops to 70-80°C, transfer the reaction solution to a 50-liter purification reactor, maintain the internal temperature at 60-65°C, and add concentrated hydrochloric acid dropwise to adjust the pH to 9 -9.5, centrifuge the precipitated solid to obtain a crude product of off-white sodium orotate, add the crude product to 6 liters of water, keep warm at 60-65°C, add concentrated hydrochloric acid to adjust the pH to 1-2, stir for half an hour, and The centrifugation of the solid that separates out obtains 3 kilograms of orotic acid crude product;

[0035] S2. Add the above crude s...

experiment example 2

[0037] A kind of improved synthetic method of orotic acid:

[0038] S1. Control the temperature in the reaction channel at 100-110°C, adjust the flow rate of the double pumps, and pump 1.5 kg hydantoin, 10 kg water, 2.5 kg 50% glyoxylic acid mixed solution and 7.5 liters of 8N sodium hydroxide at the same time Solution, after heating and circulating for 5 hours, stop heating, and when the temperature drops to 70-80°C, transfer the reaction solution to a 50-liter purification reactor, maintain the internal temperature at 50-60°C, and add concentrated hydrochloric acid dropwise to adjust the pH to 9-9.5, centrifuge the precipitated solid to obtain a crude product of off-white sodium orotate, add the crude product to 5 liters of water, keep it warm at 60-65°C, add concentrated hydrochloric acid dropwise to adjust the pH to 1-2, and stir for half an hour, The precipitated solid is centrifuged to obtain 2.8 kilograms of orotic acid crude product;

[0039]S2. Add the above crude so...

experiment example 3

[0041] A kind of improved synthetic method of orotic acid:

[0042] S1. Control the temperature in the reaction channel at 110-115°C, adjust the flow rate of the double pumps, and pump 1.5 kg of hydantoin, 10 kg of water, 2.5 kg of 50% glyoxylic acid mixed solution and 7.5 liters of 8N sodium hydroxide at the same time Solution, after heating and circulating for 2 hours, stop heating, and when the temperature drops to 70-80°C, transfer the reaction solution to a 50-liter purification reactor, maintain the internal temperature at 60-65°C, and add concentrated hydrochloric acid dropwise to adjust the pH to 9-9.5, centrifuge the precipitated solid to obtain a crude product of off-white sodium orotate, add the crude product to 5 liters of water, keep it warm at 60-65°C, add concentrated hydrochloric acid dropwise to adjust the pH to 1-2, and stir for half an hour, The precipitated solid is centrifuged to obtain 2.95 kilograms of orotic acid crude product;

[0043] S2. Add the abo...

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