Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2001-11-05
2004-04-13
Richter, Johann (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
Reexamination Certificate
active
06720446
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to the field of the production of neotame. More particularly, it relates to the field of processes for producing neotame using a catalyst in the reductive alkylation of aspartame with 3,3-dimethylbutyraldehyde to produce neotame.
2. Description of the Prior Art
The sweetener, N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester (“neotame”) is a highly intense non-nutritive sweetening agent useful to impart sweetness to a wide variety of food, beverage, and other products. This sweetener was disclosed in U.S. Pat. No. 5,480,668. The sweetener is approximately 8,000 times as sweet as sucrose, with variance depending on level of use and specific product to which it is added.
One production process which has been taught to make neotame is detailed in U.S. Pat. No. 5,510,508. Under this process, reductive alkylation of aspartame with 3,3-dimethylbutyraldehyde takes place. U.S. Pat. No. 5,728,862 teaches further improvements to this type of reductive alkylation. In particular, U.S. Pat. No. 5,728,862 teaches the reductive alkylation of aspartame with 3,3-dimethylbutyraldehyde in methanol. The patent recommends use of hydrogenation catalysts based on platinum or palladium, for example, platinum on activated carbon, palladium on activated carbon, platinum black or palladium black. The patent details a number of other catalysts which can be used. The patent recommends a weight ratio of catalyst to aspartame of about 0.01:1 to about 0.25:1.
There are a number of motivations related to making catalyst use more effective. Catalysts are relatively expensive per pound, so low levels of use and successful recycling processes are two important means to reduce costs. Further, proper selection of catalyst can affect the overall purity and yield of the desired product.
Thus, improved catalyst effectiveness would be highly desirable. The present invention details means for providing such an effective catalyst.
SUMMARY OF THE INVENTION
The present invention is directed to the selection of catalysts in a process for manufacturing neotame. A catalyst is initially selected from the group of catalysts conventionally used in hydrogenation processes. The catalyst is then altered by one of the following methods: 1) multiple re-use in the reductive alkylation produces a catalyst which is more selective and results in a decrease of certain impurities. The catalyst on recycle agglomerated at the surface resulting in lower dispersion of palladium; 2) preparing the initial catalyst with same characteristics as found in the re-cycle catalyst (as described in case 1); 3) addition of catalyst modifiers in the preparation of catalyst or addition of the catalyst modifier in the reductive alkylation process; or 4) co-precipitated bi-metallic catalyst in the reductive alkylation process. Advantages of these catalyst will be in higher purity and yield of neotame which will provide significant opportunities for cost reduction.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
In a first preferred embodiment, a modified catalyst is used in the reductive alkylation process to make neotame using aspartame and 3,3-dimethylbutyraldehyde. This catalyst is preferably a modified palladium on activated carbon catalyst. The use of the modified catalyst has been shown to reduce the level of dialkylated aspartame, one of the impurities resulting from conventional processes for manufacturing neotame.
The modified catalyst can be produced by recycling catalyst resulting in the agglomeration of the catalyst. It can also be produced directly in the catalyst manufacturing process. Any catalyst conventionally used in hydrogenation reactions is suitable for use and modification hereunder.
In a conventional process for manufacturing neotame, such as the process set forth in U.S. Pat. Nos. 5,510,508; 5,728,862 and U.S. patent application Ser. No. 09/572,843 filed on May 18, 2000, which are incorporated herein by reference, a catalyst is used in the reductive alkylation step of aspartame with 3,3-dimethylbutyraldehyde. This reductive alkylation step is conventionally carried out in the presence of methanol or aqueous methanol, and under pressure conditions between 5 psig and 100 psig hydrogen and temperature conditions between 25-60° C. The catalysts used include, but are not limited to palladium (in a preferred form of a 5% palladium on a carbon support), platinum, rhodium, ruthenium, and nickel. The resulting product, neotame, is isolated, and conventionally, the catalyst is recovered and recycled.
Typically, there are small amounts of impurities which are produced during the above process. One of these impurities is dialkylated aspartame [N,N-di (3,3-dimethylbutyl)-L-&agr;-aspartyl-L-phenylalanine 1-methyl ester]. This impurity has been found to be produced in amounts between 1.25-2.50% in conventional neotame coupling processes using fresh palladium catalyst.
When recycled catalyst was used, unexpected low levels of the dialkylated aspartame impurity were produced along with the neotame. In a series of five runs of neotame in which the same catalyst was recycled, the level of the impurity decreased consistently through the five runs. In the first run using fresh catalyst, the level of the dialkylated aspartame impurity was 1.24%. Through the next four runs, the level was 0.98% on the second use of the catalyst, 0.66% on the third use, 0.59% on the fourth use, and 0.56% on the fifth use.
Analysis of the recycled catalyst indicates that the palladium in the fresh catalyst was finely distributed consistently throughout the catalyst. The recycled catalyst showed a different pattern. Overall, the recycled catalyst was found to have less dispersed metal where the palladium agglomerated and moved to the catalyst surface.
Initially modified catalysts, as found in the recycle catalyst, also have been found to improve the overall yield of the process and reduce the level of impurities. Another form of modification is the addition of catalyst modifiers to a catalyst such as 5% palladium on a carbon or other conventional support. The modifiers are preferably selected from the group including, but not limited to, carbon dioxide, quinoline, morpholines, piperizine, pyridine, triphenylphosphine, phosphorous acid, thiocyanates, cyanamid, ethylenediamine, amidines, thiourea, ethyl di-isopropylamine, zinc, lead, silver, copper, mercury, tin, vanadium and other metallic salts, sodium hydroxide, ferrous sulfate or other salts, cadmium sulfate or other salts, and lithium trioxide. The supports are selected from the group comprising carbon, aluminum, silicate, clay, calcium, strontium carbonate, barium sulfate or molecular sieve support.
The palladium catalyst is modified as follows: The catalyst is mixed with the desired modifier either in the preparation of catalyst or addition of the catalyst modifier in the reductive alkylation process. The amount of modifier to be added is selected from ppm-5% level.
The resulting modified catalyst is used in the neotame manufacturing process in the same manner as conventional catalyst, and under the same operating conditions. The catalyst is more selective in forming neotame as opposed to other impurities, therefore, product can be crystallized at higher concentrations, thereby resulting in increased neotame yield.
An additional mechanism for modifying catalysts involves the use of co-precipitated bimetallic metal on carbon or other conventional supports. The preferred bimetallic metal catalyst is a hydrogenation catalyst combined via co-precipitation with a metal from the Group VIII-IIB periodic chart of the elements. Preferred hydrogenation catalysts include, but are not limited to palladium, platinum, rhodium, nickel, and ruthenium. Especially preferred mixtures include 3% palladium/2% rhodium on carbon support and 3% palladium/2% copper on carbon support.
The use of this catalyst in a neotame manufacturing process results in less dialkylated aspartame being produced and an overall greater select
Prakash Indra
Scaros Mike G.
Hoster Jeffrey M
Richter Johann
The NutraSweet Company
Zucker Paul A.
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