Synthesis method of neotame

Abstract

The invention relates to a synthesis method of neotame. The method comprises the following steps: (1) adding aspartame and 3,3-dimethyl-butyl aldehyde to an organic solvent in a vacuum state, reacting at the reaction temperature of 20-50 DEG C for 5-24 hours, carrying out concentration and separation at 0-50 DEG C after reaction is ended, concentrating to obtain white paste, adding deionized water to devitrify, thus obtaining a neotame intermediate imine in a centrifuging manner; (2) adding imine and an organic solvent to a hydrogenation reactor, introducing hydrogen until the pressure is 0.1-0.5MPa, adding a catalyst, reacting at the temperature of 35-40 DEG C for 5-30 hours, filtering and removing the catalyst, concentrating the filtrate and removing an organic solvent, and recrystallizing and purifying by water, methanol or ethanol, so as to obtain the neotame. According to the synthesis method, the defects in the prior art are overcome, high-purity imine is generated, the activity of the catalyst is reduced, the selectivity of the catalyst on the imine is increased, the service life of the catalyst is prolonged, the reaction impurity is reduced, and the product purity is improved.

Description

technical field [0001] The invention relates to a synthetic method of neotame. Background technique [0002] Neotame is a derivative of aspartame. It was first invented by two French scholars and obtained a patent for substance invention in 1993. It was first approved for use in food in Australia and New Zealand in 2001. In July 2002, it was approved by the US FDA. It is also officially approved for use. The Ministry of Health of the People's Republic of China approved the use of neotame in various foods in April 2003. [0003] Neotame has a pure taste, similar to sucrose, 7,000 to 13,000 times sweeter than sucrose, has good stability, provides almost no calories, is safe and harmless to human body, and is a kind of non-nutritional strong sweetener with excellent performance Flavoring agents are widely used in processed foods such as dairy products, beverages, bread, chewing gum, jelly, candied fruit, pastry biscuits, ice cream, jams and pickles, as well as medicines, healt...

AI Technical Summary

Problems solved by technology

[0004] In the chemical synthesis method of neotame, aspartame can be N-alkylated by using sodium cyanoborohydride as a reducing agent with 3,3-dimethylbutyraldehyde (see US Patent No. 5,480,668), Due to the high price and the impurity that is difficult to separate from the synthetic stone, N,N-[bis(3,3-dimethylbutyl)-L-α-aspartyl]-L-benzene with two alkyl groups Alanine methyl ester, the synthesis cost is too high, not suitable for industrial production

[0005] Chinese patent CN101270092B discloses the use of formic acid to carry out the N-alkylation reaction of aspartame and 3,3-dimethylbutyraldehyde, but the reaction is not complete, and impurities that are difficult to separate will also be produced, and two alkanes are introduced. N, N-[bis(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine methyl ester is not suitable for large-scale production, in U.S. Patent US7288640 Describes the synthesis of neotame by hydrogenating a mixture of 3,3-dimethylbutyraldehyde precursor and aspartame with a catalyst such as platinum carbon or palladium carbon, but the yield is less than 60%, and the product purity is not high , only about 97%, also not suitable for industrial production

In the patents CN1784418A and CN101565451A, a series of single catalysts of platinum group elements such as palladium carbon and palladium black are used. The activity of the elements is relatively high, which leads to the excessive reaction of the benzene ring on the aspartame, resulting in excessive hydrogenation in the hydrogenation reaction. Formation of neotame derivatives, resulting in increased impurities

Although the iridium-based catalyst used in the Chinese patent CN101775066B has improved the selectivity to imines, it has not separated imines, and side reactions will also occur, resulting in impurities that are difficult to separate.