Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing oxygen-containing organic compound
Reexamination Certificate
2001-10-12
2004-03-16
Lilling, Herbert J. (Department: 1651)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing oxygen-containing organic compound
C435S198000
Reexamination Certificate
active
06706502
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a process for the enzymatic preparation of hydroxy fatty acid esters which are solid at room temperature and have improved melting behavior. More specifically, the inventive enzymatic process comprises reacting hydroxy fatty acids with polyhydric alcohols having at least two primary and, optionally, secondary or tertiary, hydroxyl groups.
BACKGROUND OF THE INVENTION
Hydroxy fatty acid esters of polyols are used widely in applications where their interface-active properties have an effect. Examples which may be mentioned include their use as emulsifiers or dispersants in surface coatings and paints or in cosmetic preparations.
Products which are frequently used are the ricinoleic acid esters and hydroxystearic acid esters of glycerol and of polyglycerols (DE 44 20 516). The glycerol esters of ricinoleic acid or hydrated derivatives thereof, the glycerol esters of 12-hydroxystearic acid, are usually of natural origin.
Furthermore, the use of esters of hydroxystearic acid and gelling agents or gel formers in deodorant sticks or antiperspirant gels is mentioned in WO 98/58623, WO 98/27952 and U.S. Pat. No. 5,744,130.
The preparation of hydroxy fatty acid esters by chemical means such as esterification or transesterification of hydroxy fatty acids or esters thereof with alcohols is possible only at relatively high temperatures in the presence of catalysts such as, for example, organic and inorganic tin compounds, titanium compounds, lead, tin and zinc soaps, sulfuric acids, aryl- and alkylsulfonic acids, and with reaction times up to 20 hours (cf. J. Am. Pharm. Assoc. 32, (1943), p. 115-118; JP-A-79-56063, CA 94:120899; DD 155771; JP-A-78-14970, CA 101:151437).
In the synthesis of ethylene glycol, propylene glycol and trimethylene glycol esters of hydroxystearic acid with p-toluenesulfonic acid in toluene under reflux at 135° to 145° C., it was possible to isolate relatively pure products only by extensive fractionation, for example, in ether. Yields of only 40 to 60% were obtained, with considerable amounts of low-melting, amorphous material (J. Am. Pharm. Assoc. 32, (1943), p. 115-118).
Apart from the fact that these catalysts, in particular those containing heavy metals, can be used only to a limited extent, the catalysts have a series of other disadvantages, such as, insufficient solubility in the starting materials and/or reaction products, and low catalytic activity coupled with low selectivity. In particular, under these conditions, undesired secondary reactions, such as dehydration reactions or esterifications of the hydroxyl groups in the hydroxy fatty acids to polyhydroxy fatty acids cannot be (sufficiently) prevented.
Recently, the literature has increasingly described esterification and transesterification reactions of hydroxy fatty acids with alcohols with co-use of enzyme catalysts. The advantages mentioned have been the more mild reaction conditions as well as the stereo- and regiospecificity, and the higher degree of purity of the reaction products associated therewith.
In JAOCS, Vol.73, No.11 (1996), page 1513 ff., high yields are achieved using the vinyl esters of hydroxystearic acid. Although the use of vinyl esters does produce high conversions due to the irreversible transesterification, it also leads to the formation of the byproduct acetaldehyde, which cannot be removed completely in practice. Acetaldehyde is undesired, particularly in cosmetic products, because of toxicological reasons and because of its odor.
In J. Agric. Food Chem. 1988, 46, 2427 ff., investigations into the reactivity and substrate selectivity during the esterification of various unsaturated fatty acids and, for example, 12-hydroxystearic acid and ricinoleic acid with 1-butanol, are carried out. The degree of conversion for 12-hydroxystearic acid is below 30% after about 160 hours.
According to JAOCS, Vol. 75, No. 8 (1998), 1075 ff., it has-been found that the lipase-catalyzed reaction of 12-hydroxystearic acid with long-chain C
8
- to C
18
-fatty alcohols can be carried out and that the melting points of the pure reaction products are significantly lower than those of the starting mixtures.
In view of the disadvantages in prior art processes of preparing hydroxy fatty acid esters, there is a continued need for providing a new and improved enzymatic process of preparing hydroxy fatty acid esters which overcome the various drawbacks associated with prior art processes.
SUMMARY OF THE INVENTION
Accordingly, one object of the present invention is to provide an improved enzymatic process for the preparation of hydroxy fatty acid esters which are solid at room temperature, which produces products that have improved melting behavior and with increased yields, in particular with regard to criteria which are relevant in industry. The preparation of such esters has not hitherto been satisfactorily solved on an industrial scale. Relatively pure products can be obtained only with considerable expenditure via purification processes, some of which are multistage (see, for example, J. Am. Pharm. Assoc. 32, (1943), p. 115-118).
The aforementioned object is achieved in the present invention by utilizing a process for the enzymatic preparation of hydroxy fatty acid esters which are solid at room temperature and which have improved melting behavior, wherein a reaction mixture of hydroxy fatty acids and/or alkyl esters thereof (i.e., fatty acid component) with C
1
- to C
6
-, preferably C
1
- to C
3
-, monoalcohols and one or more polyols, optionally in a suitable solvent, are reacted in the presence of an enzyme which catalyses the esterification or transesterification reaction. The inventive reaction is typically carried out at a temperature in the range from about 20° to about 110° C., preferably 40° to 90° C., optionally at reduced pressure relative to the atmosphere, preferably less than 400 mbar, in particular less than 100 mbar, and optionally with the continuous removal of water of reaction and/or alcohol of reaction which forms.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
The process according to the present invention permits the preparation of hydroxy fatty acid esters on an industrially acceptable scale with increased purities, relative to the prior art, of often more than 80%, in some cases more than 90%. The reaction mixtures comprise no unacceptable byproducts such as acetaldehyde and only a small amount of condensation products of hydroxystearic acid with itself. The esters prepared according to the present invention generally have an improved melting behavior. The property, improved melting behavior, is to be understood in comparison with the prior art and means a higher melting point, represented, for example, by the dropping point, and the presence of low-melting fractions, which hinder formulation such as, for example, pelleting.
An essential advantage of the esters prepared according to the present invention over the soft and sometimes still tacky or flowable mixtures of the prior art is that the inventive esters are solid at room temperature and can therefore be readily handled in solid form, for example, as powders, flakes or pellets.
The inventive reaction can be carried out, for example, in a stirred-tank reactor or in a fixed-bed reactor.
The stirred-tank reactor is preferably equipped with a device for distilling off any liberated water or alcohol. The reaction of the present invention is typically carried out until the desired conversion is achieved. When the conversion is complete, the enzyme catalyst can be separated off by suitable techniques, such as filtration or decantation, and may, if desired, be reused a number of times.
The fixed-bed reactor can, for example, be equipped with immobilized enzymes, where the reaction mixture is pumped through the reactor filled with the catalyst. In the case of a continuous procedure, the reaction mixture is conveyed only once through the fixed-bed reactor, the flow rate controlling the residence time and thus the desired conversion. It is also possible to pump the reaction mixture
Grüning Burghard
Hills Geoffrey
Lersch Peter
Goldschmidt AG
Lilling Herbert J.
Scully Scott Murphy & Presser
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