Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
1999-12-30
2001-10-02
Killos, Paul J. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
Reexamination Certificate
active
06297396
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates generally to a method of crystallizing and purifying alkyl gallates and, more specifically, to a method of crystallizing and purifying esters of gallic acid or 3,4,5-trihydroxybenzoic acid.
2. Background of the Prior Art
Gallic acid, or 3,4,5-trihydroxybenzoic acid, is often obtained by acid or alkaline hydrolysis of tannins, which are natural substances, widespread and readily available in the environment. White, T.
Of the Science of Food and Agriculture
, 1957, 8, 377. Gallic acid can also be obtained via hydrolysis of spent broths from
Aspergillus niger
or
Penicillium glaucum
. This trihydroxybenzoic acid can be transferred by esterification with alcohol into the methyl, propyl, or lauryl ester, which are all widely used food and feed antioxidant additives.
Some of these esters can also be found as such in nature. Methyl gallate is one of the biologically active components of Galla Rhois. Ahn, Y.-S.; Kmeon, J.-H.
J. of Applied Microbiology
, 1998, 84, 439. In addition to their strong antioxidant effects, gallates also exhibit quite powerful antimicrobial activities. Ahn, Y.-S.; Kmeon, J.-H.
J. of Applied Microbiology
, 1998, 84, 439; Stevens, S. E.
J. of Aquatic Animal Health
, 1997, 9, 309.
This wide range of biological activities of gallates has generated interest in them for commercial application. Unfortunately, the prior art method of synthesis by esterification of gallic acid, including the steps of purification and crystallization, is rather complex and difficult, with the result that the gallates are expensive to produce and to use.
Although several production methods of relatively pure crystals of alkyl gallates are described in the prior art, all methods for the synthesis of higher alkyl gallates (n>5) are rather impractical for large production purposes, result in a product that is difficult to purify, and/or require toxic and expensive solvents to remove the formed water azeotropically. There is, accordingly, a need for a simple and cost effective general synthesis method for the production of a variety of gallates, particularly higher order gallates, with high purity.
SUMMARY OF THE INVENTION
Alkyl gallates are synthesized by reacting gallic acid with an alkyl alcohol in the presence of a catalyst such as hydrochloric acid, sulfuric acid or, preferably, p-toluenesulfonic acid. The reaction is carried out at a temperature of between about 100° C. and 180° C. under atmospheric or reduced pressure to remove the formed water and drive the reaction toward formation of the gallate. The reaction is allowed to proceed to satisfactory completion, whereupon the temperature of the reaction mixture is reduced to an intermediate temperature while stirring and then added to a solvent that is at the approximately the same intermediate temperature. The temperature of the mixture is reduced to ambient. Gallate crystals form in the solvent and are filtered out. The gallate crystals can be washed and recrystallized to remove impurities.
In the preparation of octyl gallate, octyl alcohol is heated in a reactor to 60° C. and gallic acid is added in a molar ratio of 1:3. A small amount of p-toluenesulfonic acid is added as a catalyst. The mixture is submitted to reaction in a Rotavapor at a temperature of 160° C. and a vacuum of −0.4 bar. The azeotrope water/octyl alcohol is distilled for approximately 5 to 6 hours. The remaining reaction mixture is cooled to approximately 55° C. while stirring. In another reactor, petroleum ether (boiling point 40-60° C.) is heated to approximately 55° C. When both the petroleum ether and the reaction mixture have reached the same temperature, the reaction mixture is added to the petroleum ether while stirring. The mixture is allowed to cool to room temperature over a period of approximately 5 hours. The octyl gallate crystallizes and the impure octyl gallate crystals are recovered by filtration. The crystals are washed with room temperature petroleum ether. Drying of the washed octyl gallate crystals for 24 hours at approximately 60° C. under vacuum results in octyl gallate of approximately 95% purity at a yield of approximately 75%.
Purity of the gallate crystals can be improved by washing the crystals with water following the initial washing with petroleum ether, and then washing the crystals with petroleum ether again.
In an alternative embodiment, after the reaction has proceeded to the point where the gallic acid content is less than a desired amount, preferably 1%, the mixture is neutralized by the addition of an aqueous alkaline solution. The neutralized reaction mixture is cooled to approximately 70° C., and then washed with water or, preferably, a solution of water and NaCl. The washed reaction mixture is cooled to approximately 55° C. Petroleum ether in a volume of approximately twice the volume of the reaction mixture heated to 55° C. is added to the reaction mixture. The mixture is then cooled while stirring to crystallize the octyl gallate. The mixture is filtered and the crystals are washed once with water and once with petroleum ether. After filtration, the crystals are dried in vacuo.
The distilled azeotrope water/alkyl alcohol mixture can be separated and the alcohol reused. Also, the petroleum ether can be recovered by vacuum distillation and reused in succeeding syntheses.
It is an object of the invention to provide a simple and economical method for synthesizing alkyl gallates having a high purity.
REFERENCES:
Theodore White, “Tannins-Their Occurrence and Significance”, Read at the Agricultural Group Symposium on Polyphenols in Soils and Plants, Oct. 9, 1956, J. Sci. Food Agric., Jul. 8, 1957, 9 pages.
Y.J. Ahn, C.O. Lee, J.H. Kweon, J.W. Ahn, J.H. Park, “Growth-inhibitory Effects of Galla Rhois-derived Tannins on Intestinal Bacteria”, 1998 The Society for Applied Microbiology, Journal of Applied Microbiology 84, 439-443.
Guojing Zhao, King-Thom Chung, Kimberly Milow, Wenxian Wang, S. Edward Stevens, Jr., “Antibacterial Properties of Tannic Acid and Related Compounds Against the Fish Pathogen Cytophaga Columnaris”, Journal of Aquatic Animal Health 9:309-313, 1997.
Coppens Bruno
Sas Benedikt
Van hemel Johan
Herink Kent A.
Hofmeyer Timothy G.
Killos Paul J.
Rosenberg Daniel A.
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