CN102329263A - Preparation method of N-acetyl-5-methoxytryptamine - Google Patents

Abstract

The invention discloses a preparation method of N-acetyl-5-methoxytryptamine. Add the raw material 5-methoxytryptamine into the dichloromethane solvent, add the mixture of acetic anhydride and dichloromethane dropwise for 0.5-1.0 hours at 5-10°C, add the catalyst 4-DMAP, and react at room temperature for 1-2 hours , to collect the target product from the reaction product. After testing, the purity of the product is ≥98%, the yield is ≥94%, and the melting point is 114-117°C. The present invention adopts the catalyst 4-DMAP to carry out N-acylation reaction, and the dosage is small, the speed is fast, the side reaction is less, the reaction condition is mild, the yield is high, the reaction is carried out under normal pressure, the operation is safe and convenient, and it is suitable for industrial production.

Description

A kind of preparation method of N-acetyl-5-methoxytryptamine

technical field

The invention relates to a preparation method of N-acetyl-5-methoxytryptamine, in particular to a method for synthesizing N-acetyl-5-methoxytryptamine by using catalyst 4-dimethylaminopyridine (4-DMAP) method of preparation.

Background technique

N-acetyl-5-methoxytryptamine is also called melatonin, and its English name is Melatonin (MLT). N-acetyl-5-methoxytryptamine is a polypeptide hormone mainly secreted by the pineal gland. Studies have shown that clinically it can regulate biological rhythms, treat insomnia, improve sleep quality, regulate the body's immune function, clear Free radicals in the human body can also prevent the toxic effect of tumor chemotherapy drugs on hematopoietic function, and have broad application prospects in the treatment of various central nervous system diseases.

Its structural formula is as follows:

In the prior art, Cao Huilan reported a method for preparing N-acetyl-5-methoxytryptamine from indole [Synthetic Method of Melatonin, Applied Chemical Industry, 2001, Vol.No.5, 5-6] . It uses indole as a raw material to carry out hydroxylation, aminoethylation, and methylation, and then reacts with acetic anhydride to obtain the target product N-acetyl-5-methoxytryptamine through acylation reaction. But because its technological operation is loaded down with trivial details, and cost is high, and yield is low, and total yield is less than 22%, and therefore, industrialization prospect is unsatisfactory.

Yang Jianwu et al reported a method for the synthesis of N-acetyl-5-methoxytryptamine using 5-methoxytryptamine as a raw material, dichloromethane as a solvent, and acetic anhydride as an acylating reagent [Chemical Research, 2003, 14(4):42-44]. However, since no catalyst is used in this method, the acylation reaction takes about 3 hours, the reaction speed is relatively slow, and the yield is only 80%, so the energy consumption is large and the cost is high.

Contents of the invention

The technical problem to be solved by the present invention is to provide a preparation method of N-acetyl-5-methoxytryptamine, using catalyst 4-dimethylaminopyridine, which overcomes the complicated operation, high cost and low yield in the prior art , slow response and other deficiencies.

Technical concept of the present invention is such:

Using 5-methoxytryptamine as a raw material, react with the acylating agent acetic anhydride in dichloromethane solvent, and carry out N-acylation under the action of catalyst 4-DMAP at room temperature, so that N - Acetyl-5-methoxytryptamine.

The preparation method of N-acetyl-5-methoxytryptamine of the present invention comprises the following steps:

Add 5-methoxytryptamine into the dichloromethane solvent, add the mixture of acetic anhydride and dichloromethane dropwise within 0.5-1.0 hours at 5-10°C, add the catalyst 4-DMAP, and react at room temperature for 1-2 hours, The target product N-acetyl-5-methoxytryptamine was collected from the reaction product.

The reaction formula is as follows:

According to the present invention, the mass volume ratio of the 5-methoxytryptamine to dichloromethane is 1:5-10, g/ml.

The molar ratio of the 5-methoxytryptamine to acetic anhydride is 1:1-1.05, mol/mol.

The mixed solution of acetic anhydride and dichloromethane is prepared at a volume ratio of 1:2-3, ml/ml.

The mass ratio of the 5-methoxytryptamine to the catalyst 4-DMAP is 1:0.03-0.06, g/g.

The present invention collects the target product from the reaction product and comprises the following steps: the reaction solution is neutralized with NaOH solution, washed to neutrality, the obtained organic phase is decolorized with activated carbon, dichloromethane solvent is evaporated under reduced pressure (recycled after recovery), The concentrated solution precipitated white crystals below 4°C, and was filtered and dried to obtain the target product.

Wherein, the molar ratio of 5-methoxytryptamine to NaOH is 1:1-1.05, mol/mol. The mass ratio of the 5-methoxytryptamine to the activated carbon is 1:0.02-0.05, g/g.

The N-acetyl-5-methoxytryptamine obtained by the method of the present invention has a purity of ≥98%, a yield of ≥94%, and a melting point of 114-117°C.

Beneficial effect:

The invention uses 4-DMAP as a catalyst to carry out N-acylation reaction, which has the advantages of less consumption, high speed, less side reactions, mild reaction conditions, high yield, reaction under normal pressure, safe and convenient operation, and is suitable for industrial production.

Detailed ways

The present invention will be further described below by the examples, but the examples do not limit the protection scope of the present invention.

Example 1

Add 38.05g (0.2mol) of 5-methoxytryptamine and 200ml of dichloromethane to a reactor equipped with a low-temperature and constant-temperature reaction bath, stirring, and a thermometer respectively. Under stirring, keep the reaction temperature at 5-10°C and drop in 0.5 hours Add 20.4g (0.2mol) of acetic anhydride and a mixed solution of dichloromethane solvent (prepared according to the volume ratio of acetic anhydride:dichloromethane=1:2), add 1.2g 4-DMAP, and react at room temperature for 2 hours.

Add 200ml of 1mol/L NaOH solution to the reaction solution for neutralization, wash with water until neutral, add 1.0g of activated carbon to the separated organic phase for decolorization, distill out the dichloromethane solvent under reduced pressure (recycled after recovery), concentrate White crystals precipitated from the solution below 4°C, and after filtration and drying, 43.6 g of the target product N-acetyl-5-methoxytryptamine was obtained, with a yield of 94%, a purity of 98.7% (HPLC), and a melting point of 114-117°C .

Example 2

Add 38.05g (0.2mol) of 5-methoxytryptamine and 300ml of dichloromethane to a reactor equipped with a low-temperature and constant-temperature reaction bath, stirring, and a thermometer respectively. Under stirring, keep the reaction temperature at 5-10°C and drop in 0.5 hours Add 21.44g (0.21mol) of acetic anhydride and a mixed solution of dichloromethane solvent (prepared according to the volume ratio of acetic anhydride:dichloromethane=1:3), add 2.0g 4-DMAP, and react at room temperature for 2 hours.

Add 210ml 1mol/L NaOH solution to the reaction solution to neutralize, wash with water to neutrality, add 1.8g gac to decolorize in the separated organic phase, dichloromethane solvent is distilled off under reduced pressure (recycling after recovery), concentrated solution White crystals precipitated below 4°C. After filtration and drying, 44.4 g of the target product N-acetyl-5-methoxytryptamine was obtained, with a yield of 95%, a purity of 98.3% (HPLC), and a melting point of 114-117°C.

It should be noted that the above embodiments are only used to illustrate the technical solution of the present invention and not to limit. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solution of the invention can be modified or equivalently replaced without departing from the scope of the technical solution of the present invention, which should be covered in this within the scope of the claimed invention.

Claims (9)

1. a preparation method of N-acetyl-5-methoxytryptamine, is characterized in that, comprises the following steps: Add 5-methoxytryptamine into dichloromethane solvent, add the mixture of acetic anhydride and dichloromethane dropwise at 5-10°C for 0.5-1.0 hours, add the catalyst 4-DMAP, and react at room temperature for 1-2 hours, Collect the target product from the reaction product. 2. The preparation method according to claim 1, characterized in that, the mass volume ratio of the 5-methoxytryptamine to the dichloromethane solvent is 1: 5-10, g/ml. 3. The preparation method according to claim 1, characterized in that the molar ratio of the 5-methoxytryptamine to acetic anhydride is 1:1-1.05. 4. The preparation method according to claim 1, characterized in that the mass ratio of the 5-methoxytryptamine to the catalyst 4-DMAP is 1:0.03-0.06. 5. The preparation method according to claim 1, characterized in that the mixed solution of acetic anhydride and dichloromethane is prepared according to a volume ratio of 1: 2-3. 6. The preparation method according to claim 1, characterized in that, collecting the target product from the reaction product comprises the following steps: the reaction solution is neutralized with NaOH solution, washed with water to neutrality, and the obtained organic phase is decolorized with activated carbon, The dichloromethane solvent was distilled off under reduced pressure, and the concentrated solution precipitated white crystals below 4°C. After filtering and drying, the target product was obtained. 7. The preparation method according to claim 6, characterized in that the molar ratio of 5-methoxytryptamine to NaOH is 1:1-1.05. 8. The preparation method according to claim 6, characterized in that the mass ratio of the 5-methoxytryptamine to activated carbon is 1:0.02-0.05. 9. preparation method according to claim 6 is characterized in that, the dichloromethane solvent that decompression steams out recycles after recycling.