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...

Examples

Embodiment 1

[0025] After evacuating the vacuum tank to -0.7MPa, add 1200g of methanol, 294g of aspartame and 100g of 3,3-dimethylbutyraldehyde, heat in a water bath to 30°C, react for 13h, and then concentrate at 40°C , to obtain a white paste, add 1800g of deionized water to crystallize, the crystallization temperature is controlled at 15°C, and the time is 15h, the obtained white solid is centrifuged to obtain 372 grams of white solid, and the yield of imine is 98.9%;

[0026] Add 372g of the obtained imine to the hydrogenation kettle, add 1500g of methanol, feed hydrogen to a pressure of 0.5MPa, add 85g of palladium-ruthenium / activated carbon catalyst, heat to 40°C in a water bath, react for 15h, remove the catalyst by filtration, and concentrate the filtrate The methanol solution is removed, and neotame is obtained by ethanol recrystallization, with a yield of more than 90% and a purity of more than 99% (HPLC).

[0027] Wherein, the palladium-ruthenium / activated carbon catalyst is a p...

Embodiment 2

[0029] After evacuating the vacuum tank to -0.96MPa, add 1500g of ethanol, 294g of aspartame and 100g of 3,3-dimethylbutyraldehyde, heat in a water bath to 33°C, react for 24h, concentrate and separate at 40°C , to obtain a white paste, add 1800g of deionized water to crystallize, the crystallization temperature is controlled at 20°C, and the time is 10h, the obtained white solid is centrifuged to obtain 373.1 grams of white solid, and the yield of imine is 99.2%;

[0030] Add 373.1g of the obtained imine to the hydrogenation kettle, add 1200g of ethanol, feed hydrogen to a pressure of 0.3MPa, add 30g of palladium-ruthenium / alumina catalyst, heat to 35°C in a water bath, react for 5h, remove the catalyst by filtration, and concentrate Ethanol solution, neotame is obtained by recrystallization with water, the yield is greater than 90%, and the purity is higher than 99% (HPLC).

[0031] Among them, the palladium-ruthenium / alumina catalyst is a palladium-ruthenium alloy that acco...

Embodiment 3

[0033] After evacuating the vacuum tank to -0.85MPa, add 2500g of ethyl acetate, 294g of aspartame and 100g of 3,3-dimethylbutyraldehyde, heat in a water bath to 35°C, the reaction time is 24h, at a temperature of 35°C Concentrate and separate to obtain a white paste, add 1800g of deionized water to crystallize, the crystallization temperature is controlled at 5°C, and the time is 5h. The obtained white solid is centrifuged to obtain 366.7 grams of white solid, and the yield of imine is 97.5 %;

[0034] Add 366.7g of the obtained imine to the hydrogenation kettle, add 1500g of ethyl acetate, feed hydrogen to a pressure of 0.1MPa, add 55g of palladium-nickel / activated carbon catalyst, heat to 35°C in a water bath, react for 5h, and remove the catalyst by filtration , concentrated ethyl acetate solution, and recrystallized with ethanol to obtain neotame, with a yield greater than 90% and a purity greater than 99% (HPLC).

[0035] Wherein, the palladium-nickel / activated carbon c...

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...

Examples

Embodiment 1

[0025] After evacuating the vacuum tank to -0.7MPa, add 1200g of methanol, 294g of aspartame and 100g of 3,3-dimethylbutyraldehyde, heat in a water bath to 30°C, react for 13h, and then concentrate at 40°C , to obtain a white paste, add 1800g of deionized water to crystallize, the crystallization temperature is controlled at 15°C, and the time is 15h, the obtained white solid is centrifuged to obtain 372 grams of white solid, and the yield of imine is 98.9%;

[0026] Add 372g of the obtained imine to the hydrogenation kettle, add 1500g of methanol, feed hydrogen to a pressure of 0.5MPa, add 85g of palladium-ruthenium / activated carbon catalyst, heat to 40°C in a water bath, react for 15h, remove the catalyst by filtration, and concentrate the filtrate The methanol solution is removed, and neotame is obtained by ethanol recrystallization, with a yield of more than 90% and a purity of more than 99% (HPLC).

[0027] Wherein, the palladium-ruthenium / activated carbon catalyst is a p...

Embodiment 2

[0029] After evacuating the vacuum tank to -0.96MPa, add 1500g of ethanol, 294g of aspartame and 100g of 3,3-dimethylbutyraldehyde, heat in a water bath to 33°C, react for 24h, concentrate and separate at 40°C , to obtain a white paste, add 1800g of deionized water to crystallize, the crystallization temperature is controlled at 20°C, and the time is 10h, the obtained white solid is centrifuged to obtain 373.1 grams of white solid, and the yield of imine is 99.2%;

[0030] Add 373.1g of the obtained imine to the hydrogenation kettle, add 1200g of ethanol, feed hydrogen to a pressure of 0.3MPa, add 30g of palladium-ruthenium / alumina catalyst, heat to 35°C in a water bath, react for 5h, remove the catalyst by filtration, and concentrate Ethanol solution, neotame is obtained by recrystallization with water, the yield is greater than 90%, and the purity is higher than 99% (HPLC).

[0031] Among them, the palladium-ruthenium / alumina catalyst is a palladium-ruthenium alloy that acco...

Embodiment 3

[0033] After evacuating the vacuum tank to -0.85MPa, add 2500g of ethyl acetate, 294g of aspartame and 100g of 3,3-dimethylbutyraldehyde, heat in a water bath to 35°C, the reaction time is 24h, at a temperature of 35°C Concentrate and separate to obtain a white paste, add 1800g of deionized water to crystallize, the crystallization temperature is controlled at 5°C, and the time is 5h. The obtained white solid is centrifuged to obtain 366.7 grams of white solid, and the yield of imine is 97.5 %;

[0034] Add 366.7g of the obtained imine to the hydrogenation kettle, add 1500g of ethyl acetate, feed hydrogen to a pressure of 0.1MPa, add 55g of palladium-nickel / activated carbon catalyst, heat to 35°C in a water bath, react for 5h, and remove the catalyst by filtration , concentrated ethyl acetate solution, and recrystallized with ethanol to obtain neotame, with a yield greater than 90% and a purity greater than 99% (HPLC).

[0035] Wherein, the palladium-nickel / activated carbon c...