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Synthesis method of melatonin

A synthesis method and technology of melatonin, applied in the direction of organic chemistry, etc., can solve the problems of low total yield, long steps, influence on promotion, etc., and achieve the effect of less solvent

Inactive Publication Date: 2015-04-08
湖北金赛药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In the above literature reports, expensive indole ring derivatives are used as raw materials, and at the same time, expensive and dangerous lithium tetrahydrogen aluminum is inevitably used as a reducing agent, and a large amount of organic solvents are also used, which is extremely difficult. restrictions on the industrial production of melatonin, affecting its promotion
[0009] Patent 200910033396.9 provides a synthesis method of melatonin, which mainly uses cheap 4-aminobutyric acid as raw material, undergoes esterification of carboxyl group, acylation of amino group, reduction of ester, oxidation of hydroxyl group, and fischer indole Melatonin is prepared by ring closure and other steps. This method has the disadvantages of long steps, the use of various organic solvents, the need for refining intermediates, and low overall yields.

Method used

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  • Synthesis method of melatonin
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] first step

[0039] Put 300Kg of diethyl malonate and 6Kg of sodium metal into a 500L reactor, add 100Kg of acrylonitrile dropwise below 80°C, and keep the reaction at 80°C for 2 hours after dropping. Cool down, add glacial acetic acid below 40°C to neutralize to pH 7. Transfer to the distillation pot, first recover diethyl malonate under reduced pressure, and when the top temperature reaches 100°C, add the adduct, then connect the fraction before 130°C to obtain 255Kg colorless transparent viscous liquid.

[0040] The second step: hydrogenation reaction

[0041] Add 100Kg of the adduct obtained in the previous step and 300L of absolute ethanol into a 500L autoclave, carefully add 24Kg of catalyst, raise the temperature to 35°C, vacuumize, pass hydrogen to 0.6MPa, and continue to pass hydrogen until the pressure drops. until the hydrogen is absorbed. Lower the temperature, let stand for more than 0.5 hours, pump the supernatant to the ethanol recovery kettle, and rec...

Embodiment 2

[0059] first step

[0060]Put 300Kg of diethyl malonate and 6Kg of sodium metal into a 500L reactor, add 100Kg of acrylonitrile dropwise below 80°C, and keep the reaction at 80°C for 2 hours after dropping. Cool down, add glacial acetic acid below 40°C to neutralize to pH 7. Transfer to the still, first recover diethyl malonate under reduced pressure, and when the top temperature is 100°C, add the adduct, then connect the fraction before 130°C to obtain 256Kg colorless transparent viscous liquid.

[0061] The second step: hydrogenation reaction

[0062] Add 100Kg of the adduct obtained in the previous step and 300L of absolute ethanol into a 500L autoclave, add 24Kg of catalyst, heat up to 30°C, vacuumize, and pass hydrogen until the pressure in the kettle reaches 0.5MPa, and then continue to pass hydrogen after the pressure drops , until no hydrogen is absorbed. Lower the temperature, let stand for more than 0.5 hours, pump the supernatant to the ethanol recovery kettle, a...

Embodiment 3

[0080] first step

[0081] Put 300Kg of diethyl malonate and 6Kg of sodium metal into a 500L reactor, add 100Kg of acrylonitrile dropwise below 80°C, and keep the reaction at 80°C for 2 hours after dropping. Cool down, add glacial acetic acid below 40°C to neutralize to pH 7. Transfer to the distillation pot, first recover diethyl malonate under reduced pressure, and when the top temperature reaches 100°C, add the adduct, then connect the distillate before 130°C to obtain 254Kg colorless transparent viscous liquid.

[0082] The second step: hydrogenation reaction

[0083] Add 100Kg of the adduct obtained in the previous step and 300L of absolute ethanol into a 500L autoclave, carefully add 24Kg of catalyst, raise the temperature to 35°C, vacuumize, and pass hydrogen to 0.5MPa. After the pressure drops, continue to pass hydrogen until it stops. until the hydrogen is absorbed. Cool down, let it stand for more than 0.5 hours, pump the supernatant liquid into an ethanol recover...

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PUM

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Abstract

The invention belongs to the field of chemical synthesis of medicines and specifically relates to a synthesis method of melatonin. The method comprises the following steps: performing addition, ammonolysis of ester, coupling, rearrangement, hydrolysis of amide, decarboxylation, acylation and the like from diethyl malonate and acrylonitrile to obtain melatonin. According to the synthesis method provided by the invention, the starting raw materials are easy to obtain, the reaction in each step is relatively mild, a used solvent is small in amount and can be recovered and applied mechanically, an intermediate can directly enter the next-step reaction without refining and drying, and thus the synthesis method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical synthesis, and in particular relates to a synthesis method of melatonin. Background technique [0002] Melatonin is an indole hormone secreted by the pineal gland of the human brain. Its main function is to maintain the circadian rhythm of the human body's own circadian rhythm, which is conducive to sleep. It has the ability to enhance human immune function, inhibit the growth of tumor cells, Melatonin may also have an inhibitory effect on the central nervous system; it is a more effective peroxide scavenger than vitamin E, and it also regulates production and development, sexual function and many organs. [0003] Its chemical name is: N-acetyl-5-methoxytryptamine [0004] English name: N-Acetyl-5-Methoxytryptamine [0005] Molecular formula: C 13 h 16 N 2 o 2 [0006] Molecular weight: 232.28 [0007] Appearance: white powder [0008] The synthesis method of melatonin has been repo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/14
CPCC07D209/14
Inventor 熊开文赵继舒
Owner 湖北金赛药业有限公司
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