Processes for producing citrate esters

Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters

Reexamination Certificate

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C560S176000, C560S185000

Reexamination Certificate

active

06403825

ABSTRACT:

BACKGROUND
This invention relates generally to processes for producing citrate esters, and more particularly to processes useful for preparing citrate esters from partially purified citric acid-containing fermentation broths.
As further background, citric acid is a biologically occurring material which finds use in the food, pharmaceutical, cosmetics and plastics industries. In the plastics industry in particular, citric acid serves as a raw material for the manufacture of citrate ester plasticizers.
Since the early work of C. Wehmer beginning in the 1890's, there has been substantial interest and investment in fermentation processes for producing citric acid. As such, nearly all of the 700 million pounds or more of citric acid produced worldwide yearly are from fermentation processes, for instance by the fermentation of a carbon source such as molasses with the microorganism, Aspergillus Niger. Typically, broths from such fermentations will contain about 10 weight % or more citric acid, as well as about 1000 ppm or more salts, about 1 weight % carbohydrates, and 2 weight % proteins, amino acids and other materials.
Purification of citric acid from such mediums has itself been the subject of substantial attention in the academia and industry. In general, three techniques have been used to date, those being precipitation, solvent extraction and solid-phase polymer adsorption and subsequent desorption. As to the first technique, precipitation, it can be fairly stated that it has been the more preferred technique used on a commercial scale, even though significant endeavors as to the other two techniques have been made. In precipitation, calcium hydroxide (lime) is usually added to the fermented medium to form the slightly soluble tricalcium citrate tetrahydrate. Properly performed, this precipitation leaves most impurities in the solution. Impurities may further be removed by washing the filtered precipitate. To further purify the product, the moist precipitate is reacted with sulfuric acid to yield calcium sulfate (gypsum) and a solution of free acid. The free acid solution is then treated with activated carbon and ion exchange resins before evaporation to the crystalline citric acid product. As is recognized, the efficacy of this precipitation method is highly dependent on properly and carefully performing the various steps involved. It is thus a sensitive process requiring high refinement, especially on a commercial scale.
A second technique which has been used to purify citric acid is solvent extraction. In this technique, citric acid is extracted from the fermentation broth with solvent hydrocarbons, for example, octane, benzene, kerosene, ethers, esters, ketones or amines. Citric acid is then reextracted from the solvent phase into water with either the addition of heat or the formation of a citric acid salt. However, this solvent extraction technique is also expensive and complex. Further, solvent extraction generates a very substantial amount of waste for disposal, which from both cost and environmental standpoints is unattractive.
A third technique which has been suggested involves the use of solid adsorbents to remove citric acid from the medium. The adsorbed citric acid is then recovered from the polymer utilizing a desorbing agent. For example, U.S. Pat. No. 4,323,702 to Kawabata et al. describes a process for recovering carboxylic acids with a material of which the main component is a polymeric compound having a pyridine skeletal structure and a cross-linked structure. The captured carboxylic acids are then desorbed using an aliphatic alcohol, an aliphatic ketone or a carboxylic ester as the desorbing agent. U.S. Pat. No. 4,720,579 to Kulprathipanja describes a process in which citric acid is separated from a fermentation broth using an adsorbent of a neutral, noniogenic, macroreticular, water-insoluble cross-linked styrene-poly(vinyl)benzene, and desorbed with an acetone/water mixture.
In U.S. Pat. No. 4,851,573 to Kulprathipanja et al., another process is described in which an adsorbent of a cross-linked acrylic or styrene resin matrix having attached tertiary amine functional groups or pyridine functional groups is used as an adsorbent for the citric acid, which is desorbed preferably with sulfuric acid. In still another patent, U.S. Pat. No. 4,851,574, Kulprathipanja describes separating citric acid from a fermentation broth using an adsorbent of a cross-linked acrylic or styrene resin matrix having attached aliphatic quaternary amine functional groups.
As will be appreciated, the above-described techniques for purifying citric acid, as well as final crystallization processes generally used in all of them to remove sugars, add significant cost to the final product. In turn, significant costs are added to products downstream of citric acid. For example, as previously indicated, among its other uses, citric acid is an important starting material to citrate esters which have been found to be particularly useful as plasticizers for PVC compositions, see, e.g. U.S. Pat. Nos. 4,870,204; 4,789,700; 4,711,922; and 4,824,893; and biodegradable polymer compositions, see, e.g., U.S. Pat. No. 5,556,905. For the most part, citrate esters have been prepared by esterification of purified citric acid, e.g. technical or USP grade, with the appropriate alcohol and in the presence of an esterification catalyst. However, the cost pressures caused by using such purified grades of citric acid are a significant disadvantage, as the citrate esters are made and used in relatively large quantities.
German Pat. No. 1 041 944 describes a process in which a citric acid ester is said to be prepared from a crude citric acid broth. Specifically, the authors describe a process for producing an ester of citric acid, in which a raw 30% citric acid broth is dehydrated with benzene and ethanol to a syrup. Butanol and butyl acetate, along with a tin catalyst, are added to the syrup and the mixture is heated to a temperature of 140-160° C., whereupon the reaction is halted with potassium hydroxide. The resulting reaction product is washed with sodium carbonate in water, and the crude mixture distilled. The authors report yielding acetyl tributyl citrate in the recovered material.
In light of the above, there remains a need for economic routes to important citrate esters useful as plasticizers. Desirably, such routes would avoid the high costs of purification while yielding citrate ester products suitable for use as industrial plasticizers for PVC and other plastics. The present invention is addressed to these needs.
SUMMARY OF THE INVENTION
One feature of the present invention is the surprising discovery that desirable citrate ester products can be prepared by esterification of relatively impure citric acid-containing fermentation broths, if such broths are treated to remove cations prior to the esterification. Accordingly, one preferred embodiment of the present invention provides a process for preparing a citrate ester which includes (i) providing a citric acid-containing broth from a citric acid-producing fermentation, the broth having been treated to remove cationic impurities; and (ii) reacting the citric acid-containing broth with an alcohol to esterify the citric acid and form a citrate ester. It has been found that the removal of the cations prior to conducting the esterification minimizes the formation of particulate impurities otherwise produced, and significantly improves the reaction rate and the product yield and product purity. This surprising aspect of the invention provides for an economic production of citrate esters while avoiding the costs associated with bringing the citric acid to a purified state such as a technical or USP grade citric acid.
In a particularly preferred aspect, the invention provides processes as described above for preparing a citrate triester composition of Formula I:
wherein
R=H, R
2
—CO— or Ph(—R
2
)
n
—CO— wherein R
2
is a C
1
to C
18
aliphatic group, n is 0 or 1, and Ph is a phenyl group;
each R
1
, which can be the same or different from e

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