CN108676064A

CN108676064A - A method of efficiently synthesizing neotame

Info

Publication number: CN108676064A
Application number: CN201810737564.1A
Authority: CN
Inventors: 庄勇; 王立平; 赵海东; 顾京城
Original assignee: NANTONG CHANGHAI FOOD ADDITIVE CO Ltd
Current assignee: NANTONG CHANGHAI FOOD ADDITIVE CO Ltd
Priority date: 2018-07-06
Filing date: 2018-07-06
Publication date: 2018-10-19
Anticipated expiration: 2038-07-06
Also published as: CN108676064B

Abstract

The present invention provides a kind of process efficiently synthesizing neotame, by Aspartame, 3,3 dimethyl butyraldehydes, the organic solvent synthesizing neotame under catalyst hydrogenation.The invention has the advantages of low raw material cost, and the reaction time is short, and reaction impurities easy to operate are few, and product yield reaches 95% or more, and final product quality meets USP requirement, and profit and industrialized production, prospect of production are good.

Description

A method of efficiently synthesizing neotame

Technical field

The invention belongs to food additives fields, and in particular to a method of efficiently synthesizing neotame.

Background technology

Neotame (Neotame) is a kind of novel non-nutritive high-potency sweetener, entitled N- [N-3, the 3- dimethyl of chemistry Butyl]-L- ɑ-lucid asparagus pacify acyl]-L-phenylalanine 1- methyl esters, structural formula is as follows：

Neotame is the derivative of Aspartame (APM), belongs to novel dipeptide intense sweetener, is universally acknowledged at present The strongest sweetener of sugariness, sugariness is 7000~12000 times of sucrose, is 50 times of Aspartame, and neotame has class It is similar to the pure sweet taste of sucrose and preferable stability, is widely used in bread, beverage, cake, dairy products, ice cream, jelly In the processed foods such as pudding, jam and fruit and vegetable.Neotame can also be used as a kind of flavour enhancer, be applicable not only to include fat, sugar The crowd including patient and cardiovascular disease is urinated, the phenylketonuria patient that cannot be applicable in Aspartame is applied also for.

The synthetic method of neotame both at home and abroad there are many kinds of, these methods have their own advantages, but there is also deficiencies, such as cost It is high, product purity is low, yield is low, complicated for operation etc..It is provided in United States Patent (USP) US5480668 and uses sodium cyanoborohydride as reduction Aspartame and 3, the method for the mixed solution reduction preparation neotame of 3- dimethyl butyraldehydes, sodium cyanoborohydride price are held high in agent It is expensive, and it is acid stronger in reacting when have the danger for generating cyanide, be unfavorable for industrialized production；United States Patent (USP) US5510508, It provides in US7288640 and is hydrogenated the mixture of 3,3- diformazans based precursor and Aspartame with catalyst such as platinum carbon or palladium carbon Carry out synthesizing neotame, yield is low, and product purity is not high to be also not suitable for large-scale production.

Chinese patent CN101270092A is disclosed with formic acid, and by Aspartame and 3,3- dimethyl butyraldehydes carry out N- alkylations Synthetic reaction, but reaction is not thorough, yield is not high, while also will produce the impurity for being difficult to detach；Chinese patent The iridium based catalyst that CN101775066A is used, expensive catalyst are not easy to prepare；Chinese patent CN104177473A purifications are intermediate It is synthesized again after body imines, complex procedures, is unfavorable for production cost control；Chinese patent CN102167722A and CN102863511A Reducing agent is made with acetic acid sodium borohydride and potassium borohydride respectively, wherein acetic acid sodium borohydride is expensive, and the easy moisture absorption is unstable, difficult Operation, post-processing are complicated；Potassium borohydride post-processing needs a large amount of water and is post-processed with acetic acid cumbersome.

Invention content

It is an object of the invention to overcome in the prior art, neotame synthetic method is of high cost, product purity is low, yield is low, behaviour Make the defects of complicated, and provides a kind of simple for process, easy to operate, cost savings, the method for the preparation neotame of Environmental Safety.

The present invention provides a kind of processes efficiently synthesizing neotame, using Raney Ni as catalyst, by Aspartame and Press filtration, vacuum distillation, crystallisation by cooling obtain neotame after 3,3- dimethyl butyraldehyde hydro-reductions, and reaction equation is as follows：

The process provided by the invention for efficiently synthesizing neotame specifically comprises the following steps：

(1) Aspartame, 3,3- dimethyl butyraldehydes and solvent are added in autoclave, catalyst orchid Buddhist nun is added Nickel obtains solution A；

(2) it is passed through hydrogen into reaction solution A, 2~6h of hydrogenation at 50-70 DEG C；

(3) reaction solution that step (2) obtains is obtained into liquor C with nitrogen press filtration；

(4) liquor C for obtaining step (3) is evaporated under reduced pressure, and obtains thick suspension；

(5) the thick suspension crystallisation by cooling for obtaining step (4), centrifugation obtain neotame.

Preferably, organic solvent used in the step (1) is ethyl alcohol or tetrahydrofuran.

Preferably, Ni content >=90% in the step (1) in catalyst Raney Ni.

Preferably, the molar ratio of Aspartame and 3 in the step (1), 3- dimethyl butyraldehydes is 0.9:1~1.2:1；Into One step, the molar ratio of Aspartame and 3 in the step (1), 3- dimethyl butyraldehydes is 1:1~1:1.1.

Preferably, the weight ratio of catalyst Raney Ni and 3 in the step (1), 3- dimethyl butyraldehydes is 0.05:1~ 0.3:1；Further, the weight ratio of catalyst Raney Ni and 3 in the step (1), 3- dimethyl butyraldehydes is 1:9~1:10.

Preferably, Hydrogen Vapor Pressure is 1.0~1.5Mpa in the step (2).Further, hydrogen in the step (2) Pressure is 1.0~1.2Mpa.

Preferably, in the step (5), the temperature of crystallisation by cooling is at -5~10 DEG C.

The beneficial effects of the invention are as follows：The invention has the advantages of low raw material cost, and the reaction time is short, and reaction impurities easy to operate are few, Product yield reaches 95% or more, and final product quality meets USP requirement, and profit and industrialized production, prospect of production are good.

Specific implementation mode

Illustrate technical scheme of the present invention below by way of specific embodiment, but the scope of the present invention is not limited thereto.

The name of compound Chinese and chemical structural formula have conflict in the present invention, are subject to chemical structural formula.

Embodiment 1

It is pumped into ethyl alcohol 100kg, input Aspartame 12.5kg (42.5mol) into 500 liters of autoclaves, then puts into 4.2kg3,3- dimethyl butyraldehyde (41.9mol), stirring and dissolving put into 0.45Kg raney nickel catalysts, close valve, and nitrogen is set Hydrogen displacement system after changing three times, Hydrogen Vapor Pressure is 1.0Mpa in holding system after displacement, opens stirring, and adjusting rotating speed is 30 (phases When in 180r/min), hot water heating, reaction temperature is controlled at 50 DEG C, and heat preservation hydrogenation exhausts hydrogen after 2 hours, and press filtration removing is urged Vacuum distillation removes ethyl alcohol, catalyst recycling after agent, and filtrate is cooled to -5 DEG C of crystallizations, and centrifuge obtains neotame product, with Aspartame rate of collecting 97%, purity (HPLC) 99.83%.

Embodiment 2

Tetrahydrofuran 500kg, input Aspartame 62.5kg (212.4mol) are pumped into 1000 liters of autoclaves, then 23.4kg 3,3- dimethyl butyraldehydes (233.6mol) are put into, stirring and dissolving puts into 2.25Kg raney nickel catalysts, closes valve, Hydrogen replaces system after nitrogen displacement three times, and Hydrogen Vapor Pressure is 1.2Mpa in holding system after displacement, opens stirring, adjusts rotating speed and is 30 (being equivalent to 180r/min), hot water heating, reaction temperature are controlled at 60 DEG C, and heat preservation hydrogenation exhausts hydrogen after 2 hours, and press filtration removes Vacuum distillation removes tetrahydrofuran, catalyst recycling after removing catalyst, and filtrate is cooled to 10 DEG C of crystallizations, and centrifuge obtains neotame Product, with Aspartame rate of collecting 96%, purity (HPLC) 99.63%.

It is enlightenment with above-mentioned desirable embodiment according to the present invention, through the above description, relevant staff is complete Various changes and amendments can be carried out without departing from the scope of the technological thought of the present invention' entirely.The technology of this invention Property range is not limited to the contents of the specification, it is necessary to determine its technical scope according to right.

Claims

1. a kind of process efficiently synthesizing neotame, it is characterised in that：Using Raney Ni as catalyst, by Aspartame and 3,3- Press filtration, vacuum distillation, crystallisation by cooling obtain neotame after dimethyl butyraldehyde hydro-reduction, and reaction equation is as follows：

2. the process as described in claim 1 for efficiently synthesizing neotame, it is characterised in that specifically comprise the following steps：

(1) Aspartame, 3,3- dimethyl butyraldehydes and solvent are added in autoclave, catalyst Raney Ni is added, obtains To solution A；

3. the process as claimed in claim 2 for efficiently synthesizing neotame, which is characterized in that used in the step (1) Organic solvent is ethyl alcohol or tetrahydrofuran.

4. the process as claimed in claim 2 for efficiently synthesizing neotame, which is characterized in that catalyst in the step (1) Ni content >=90% in Raney Ni.

5. the process as claimed in claim 2 for efficiently synthesizing neotame, which is characterized in that A Siba in the step (1) The molar ratio of sweet tea and 3,3- dimethyl butyraldehydes is 0.9:1~1.2:1.

6. the process as claimed in claim 5 for efficiently synthesizing neotame, which is characterized in that A Siba in the step (1) The molar ratio of sweet tea and 3,3- dimethyl butyraldehydes is 1:1~1:1.1.

7. the process as claimed in claim 2 for efficiently synthesizing neotame, which is characterized in that catalyst in the step (1) The weight ratio of Raney Ni and 3,3- dimethyl butyraldehydes is 0.05:1~0.3:1.

8. the process as claimed in claim 7 for efficiently synthesizing neotame, which is characterized in that catalyst in the step (1) The weight ratio of Raney Ni and 3,3- dimethyl butyraldehydes is 1:9~1:10.

9. the process as claimed in claim 2 for efficiently synthesizing neotame, which is characterized in that hydrogen pressure in the step (2) Power is 1.0~1.5Mpa.

10. the process as claimed in claim 2 for efficiently synthesizing neotame, which is characterized in that cooling in the step (5) The temperature of crystallization is at -5~10 DEG C.