US2848466A

US2848466A - Removing acyl halide from ester compositions

Info

Publication number: US2848466A
Application number: US404787A
Authority: US
Inventors: George L Fletcher
Original assignee: Eastman Kodak Co
Current assignee: Eastman Kodak Co
Priority date: 1954-01-18
Filing date: 1954-01-18
Publication date: 1958-08-19
Anticipated expiration: 1975-08-19

Description

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2,848,456 Patented Aug. 19, 1958 REMOVING ACYL HALKDE FROM ESTER COMPOSITIDNS George L. Fletcher, Rochester, N. Y., assignor to Eastman Kodak Company, Rochester, N. Y., a corporation of New Jersey No Drawing. Application January 18, 1%54 Serial No. 404,787

'11 Claims. (Cl. 260404) the ester composition. In the esterification of an alcohol with an acyl halide, an excess of one of the reactants is added to upset the equilibrium and to yield relatively more ester in accordance with well-known mass action principles. Thus, for example, in the esterification of an olefinic alcohol with a fatty acid chloride or similar acyl halide, an excess of the least expensive reactant, usually the acyl halide, is added to shift the equilibrium toward a more complete esterification to yield the desired ester.

Unreacted acyl halide thus remains in the ester composition as a major impurity. If stoichiometric amounts of acyl halide and alcohol are esterified, unreacted acyl halide will be present in the ester composition in amounts commensurate with the state of the equilibrium. It is therefore highly desirable to provide an economically feasible method for removing acyl halide from ester compositions.

In the esterification of an acyl halide and an alcohol, the usual method for removing unreacted acyl halide from ester compositions is to hydrolyze the acyl halide with an aqueous alkali, such as aqueous sodium hydroxide. The hydrolysis presumably hydrolyzes the' acyl halide to a free acyl acid, which is converted into an acyl soap to facilitate its removal from the ester composition. When a fatty acid halide is esterified with an alcohol, unreacted halide is not easily removed from the ester composition by hydrolysis. Fatty acid halides do not quantitatively hydrolyze to fatty acid alkali soaps. 'A portion of the unreacted fatty acid halide is converted into undesirable derivatives which are diflicult to remove from the ester composition. A mixture of acidic and non-acidic polymer-like materials is probably formed along with fatty acid alkali soap and free fatty acid. Such impurities make the purification of ester compositions dificult and costly.

Such problems are especially troublesome and economically serious in the manufacture of esters of vitamin A and vitamin E, where it is common to esterify the vitamin alcohol with an acyl halide. Economical and eilicient purification of the vitamin esters is important to successful commercial operation.

It is therefore an object of this invention to provide a new and useful method for removing acyl halides from ester compositions resulting from the csterification of an acyl halide and an alcohol.

t is further the object of this invention to esterify an alcohol and an acyl halide and to remove from the ester composition the ester substantially free of objectionable amounts of acyl halide and acyl halide derivatives.

Another object of this invention is to remove from ester compositions fatty acid halide by a new and simplified method.

Another object of this invention is to esterify vitamin A alcohol with a fatty acid halide, and thereafter separate from the ester composition a vitamin A fatty acid in a form substantially free of fatty acid halide.

Another object of this invention is to prepare a purified vitamin A ester free of objectionable amounts of acyl halide.

Another object of this invention is to esterify a tocopheral with a fatty acid halide, and thereafter separate from the ester composition a tocopherol fatty acid ester in afcrm substantially free of fatty acid halide.

Another object of this invention is to prepare a purified tocopherol ester free of objectionable amounts of unreacted acyl halide.

Another object of this invention is to meet the heretofore difiicult problem of removing higher molecular weight fatty acid halides from ester compositions as exemplified by the difiiculties encountered in using the alkali hydrolysis method to remove palmitoyl chloride from an ester composition.

Another object of this invention is to separate an ester from an ester composition substantially free of polymerlike materials.

Other objects will be apparent from the description and claims which follow.

These and other objects are attained by means of this invention which comprises removing unreacted acyl halide from an ester composition by converting the acyl halide to a nitrogenous derivative by amidating or ammoniating the ester composition, and thereafter separating from the admixture the nitrogenous derivatives.

The invention is applicable for removing objectionable acyl compounds from any of the compositions obtained by esterifying an alcohol with an acyl halide. In effecting the esterification, any of the well-known alcohols can be used, including aliphatic and aromatic alcohols,

Whether saturated or unsaturated. Thus, typical alcohols which are esterified in accordance with this invention include the lower alkyl alcohols as well as the higher molecular weight alcohols and particularly the aralkyl alcohols or olefinically unsaturated alcohols which terminate in a carbocyclic ring. The nature of the alcohol does not affect this invention and it is not intended that the scope of the invention shall be limited thereby, since any of the alcohols which undergo esterification with an acyl halide can be suitably employed.

'Acyl halides in aqueous solutions convert readily into acyl acids which often are bonverted into acyl derivatives. Fatty acids, in particular, convert readily into undesirable derivatives in troublesome amounts in an aqueous alkali ester composition. Higher molecular weight fatty acids, having more than eight carbon atoms, are more easily converted into derivatives than lower molecular weight fatty acids, and thus, the preparation of derivative-free esters of higher molecular weight fatty acids is complicated if the alkali hydrolysis method for removing unreacted acyl halide from an ester composition is used. Although the preferred embodiments of this invention are particularly concerned with removing higher molecular weight fatty acid halides from ester compositions, the invention is applicable to the removal of lower molecular weight fatty acid halides, which form undesirable derivatives to a lesser degree, and other acyl halides in ester compositions. Typical acyl halides which are removed by. means of this invention include stearyl chloride, palrnitoyl bromide, acetyl chloride, benzoyl chloride and related compounds. Acyl chlorides are preferably used as halides in the esterification and are removed by the process embodying this invention. However, acyl bromides,

acyl iodides and acyl fluorides are within the scope of the invention and can be used if desired.

The esterification can be effected by any of the wellknown methods for esterifying an alcohol with an acyl halide. The proportions of esterification reactants can be varied to use an excess of alcohol or of acyl halide. Acyl halide will exist as an impurity in the ester composition in amounts which are largely dependent upon the extent of esterification and on whether a stoichiometric excess of acyl halide is added. Although proportions of the reactants can be varied as desired, in the preferred embodiment, 1 mole of alcohol is combined with approximately 1.2 moles of acyl halide. The reactants are usually heated, but the reaction temperature can be varied with the stability of the reactants, the ease of esterification of the reactants and the desired reaction time. The acyl halide is added in excess to assure the fullest esterification of the alcoholic reactant. Resultingly, acyl halide remains as an impurity to be removed in the purification of the ester product.

Unreacted acyl halide in an ester composition is separated therefrom as an amidated or ammoniated derivative. Amidation or ammoniation of such unreacted acyl derivatives can be effected by any of the methods described hereinafter.

Ammoniation and amidation of an ester composition can be effected with gaseous ammonia. An excess of ammonia gas is usually admixed with the ester composition until substantially all of the unesterified acyl halide has reacted with the ammonia. Such ammoniated derivatives can'be substantially removed from an ester composition by filtration from a suitable solvent.

In a preferred embodiment of this invention, the ester composition is dissolved in a solvent, either before, during or subsequent to the esterification, so that unreacted acyl halide therein can be easily separated from the ester composition as insoluble ammoniated derivatives by filtration. Non-polar solvents such as liquid N-butane, N-pentane, N-hexane, N-heptane and the like are preferably employed although other solvents such as isopropyl ether or the like are entirely suitable. Acyl amides usually separate from the solvent as a flocculent white precipitate. Many secondary amides are appreciably soluble at room temperature in the solvents used in accordance withthis invention. To effect a substantially complete removal of the amides by filtration, it is often desirable to chill the ammoniated ester composition to a temperature where the ammoniated acyl halide derivatives are substantially insoluble. Temperatures below 10 C. are preferably used to effect the removal of substantially all of the ammoniated compounds, although temperatures from -l C. to 20 C. can be used but are usually less desirable. If a further purification step is used thereafter, it may be commercially desirable to chill the ammoniated ester composition to only approximately 20 C., at which temperature most of the ammoniated derivatives are insoluble. Further purification to remove soluble ammoniated derivatives can be effected by distillation, solvent extraction, selective adsorption or the like. In a chilled, nonaqueous, ester composition, ammoniated with gaseous ammonia, primary amides, secondary amides and ammonium chloride constitute a substantial portion of the precipitate that can be easily separated by filtration. There is no substantial formation of troublesome polymerlike materials in an ammoniated ester composition. The ammoniated derivatives can also be separated from the ester composition by distillation, selective adsorption, solvent extraction or the like.

The ammoniation of an ester composition likewise can be effected with ammonia formed in situ in the ester composition as the result of chemical reaction or chemical decomposition as illustrated by the use of such wellknown ammonium salts as ammonium carbonate and ammonium chloride or the like.

The ammoniation of an ester composition can also be effected with aqueous ammonium hydroxide. Ammonium hydroxide hydrolyzes acyl halide to acyl ammonium compounds which can also be removed from an ester composition by filtration, distillation, selective adsorption, solvent extraction, or the like. An aqueous ammonium hydroxide hydrolysis of fatty acid halides does not result in the formation of undesirable polymer-like materials in troublesome amounts as occurs when aqueous alkali metal bases are used. It is suspected that acyl halide reacts more readily with ammonium hydroxide to form ammonium compounds than with itself to form dimers, so that dimer formation is minimized. Because of the soapy, gelatinous nature of many ammonium compounds, it is often desirable to convert the acyl halide to the amide. The use of ammonium hydroxide as an ammoniating agent also introduces waterinto the ester composition as an added impurity to be removed. As a result, it may be more desirable to ammoniate under nonaqueous conditions and to effect the removal of acyl halides as amides rather than as ammonium compounds.

The amidation of unreacted acyl halide in an ester composition can be effected by the use of nitrogen containing compounds, such as amines, having at least one replaceable hydrogen atom on a nitrogen nucleus. Thus, amidation can be effected with primary and secondary amines by aminolysis of the acyl halide to form amides. Related compounds as exemplified by amino acids and combinations thereof, form amides with acyl halides that can be easily separated from an ester composition and can likewise be used. Amides formed by aminolysis can be removed from ester compositions by any of the methods hereinbefore elaborated for the removal of amides and ammonium compounds formed by ammoniation.

The invention will be further described with reference to certain preferred embodiments thereof as illustrated by the following examples.

Example 1 One kilogram of vitamin A alcohol concentrate, 1.5 to 2 million international vitamin A units per gram, was dissolved in 5 liters of isopropyl'ether and .25 kg. of pyridine. One kilogram of palmitoyl chloride was dissolved in 5 liters of isopropyl ether. The isopropyl other solution of palmitoyl chloride was thereafter added to the isopropyl ether solution of vitamin A alcohol and pyridine in small quantities; the temperature kept during the addition below 40 C. The esterification mixture was stirred and held at 40-45 C. for 1 hour. Thereafter the reaction mixture was cooled to 20 C., .30 kg. of ammonium hydroxide (commercial 27% solution) added, and the resulting mixture was agitated for 10 minutes. To the ammoniated mixture was added 1.0 kg. of anhydrous potassium carbonate and .05 kg. of a diatomaceous earth filter aid (Celite) and agitated again for 10 minutes. The temperature during the addition of the ammonium hydroxide and the potassium carbonate was controlled below 30 C. The resulting mixture was chilled 0 to -10 C.) for at least 15 minutes and thereafter filtered. Isopropyl ether solvent was removed by distillation and pyridine was removed by deodorizing techniques. The product showed no free hydroxyl by infrared analysis. Yields of 97% to 100% of ester were achieved which were substantially free of acyl halide and acyl halide derivatives.

Example 2 Seventeen grams of pure vitamin A alcohol were esterified with 17 g. of palmitoyl chloride in the presence of 17 g. of pyridine. Vitamin A alcohol and pyridine were combined and palmitoyl chloride was added drop-wise, keeping the reaction temperature below 45 C. After the palmitoyl chloride had been added, the reactants were allowed to react for one hour at 45 C. The ester composition was thereafter diluted with 200 ml. of N-hexane.

The diluted ester composition was ammoniated by bubbling ammonia gas through the solution for 30 minutes. The ammoniated solution was chilled to 20 C. and insoluble ammoniated derivatives were removed by filtration from the hexane slurry. The resulting filtrate was evaporated to remove free amonia, hexane and pyridine. The ester product at this stage of purification was 96% pure. The product Was redissolved in 500 ml. of hexane and thereafter remaining soluble ammoniated derivatives and other impurities, including colored impurities, were substantially removed by adsorption using 60 g. of mag nesium oxide or an equivalent amount of commercial zeolite. The N-hexane solvent was thereafter evaporated and 30.97 g. of substantially pure vitamin A palmitate was recovered for a yield of 99.2%. The product contained substantially no coloring matter, free acids, nitrogen compounds or polymer-like substances.

Example 3 Fifty grams of vitamin A alcohol concentrate, containing 25.5 grams of pure vitamin A alcohol, was esterified in the presence of 60 grams of pyridine by adding the palmitoyl chloride solution in small aliquots to the vitamin A alcohol solution, keeping the reaction temperature below 45 C. for one hour. The ester composition was diluted with 750 ml. of N-hexane and thereafter grams of morpholine was added. The resulting mixture was agitated for about ten minutes at room temperature, chilled to less than 20 C., filtered and thereafter further purified by adsorption on aluminum oxide. Yields of 98% or better were obtained by this process. The product was highly purified and was substantially free of objectionable amounts of acyl halide derivatives.

Example 4 A 67 gram sample of tocopherol concentrate, comprised of about 50% alpha-tocopherol, was dissolved in 67 grams of pyridine. Sixty-seven grams of palmitoyl chloride were thereafter admixed in small aliquots. The mixture was then heated for two hours at 100 C., thereafter cooled to about 40 C., 670 ml. of N-hexane added, and ammonia gas bubbled through the mixture for about 20 minutes. The ammoniated admixture was then cooled to 5 C. for about 2 hours, the resultant slurry filtered and the filtrate concentrated. A yield of about 99% alpha-tocopherol ester was obtained which was substantially free of nitrogen compounds and polymer-like substances.

Example 5 Ten grams of N-butyl alcohol were esterified with 48.2 g. of palmitoyl chloride (at 30% excess of palmitoyl chloride) in the presence of 48.2 g. of pyridine. The esterification mixture was maintained at 60 C. for about 1 hour. The resulting mixture was cooled to room temperature, 100 ml. of N-hexane added, and ammonia gas bubbled through the cooled esterification mixture for about 30 minutes. Insoluble amides and ammonium chloride were filtered out and the pyridine was evaporated from the filtrate. The filtrate was taken-up with 100 ml. of N-hexane, 10 g. of magnesium oxide added, and the slurry filtered. The N-hexane was evaporated from the resulting filtrate and about 42.5 g. of N-butyl palmitate was obtained for a yield of about 100%. Infrared assay showed a high purity ester. Thus, a large stoichiometric excess of acyl halide was efficiently removed from an ester composition.

The embodiments, as described in the examples, are of particular importance in the preparation of higher molecular weight fatty acid esters substantially free of acyl halide or acyl halide derivatives, although the invention is equally applicable for removing any acyl halide, as disclosed, from an ester composition. Similar results are also obtained by removing an acyl halide from an ester composition resulting from the esterification of an acyl halide and any alcohol, as disclosed.

This invention thus provides a simple, efficient and economically feasible method for removing excess acyl halides from ester compositions. Esters which are substantially free of possible polymer-like materials, acids and acyl halides are easily prepared in accordance with the invention. Esters, such as vitamin A palmitate, which are particularly susceptible to isomerization, decomposition or chemical change, can be readily prepared by this process without substantial change to their chemical structure or properties. This invention also makes the preparation of fatty acid and fatty acid derivative free higher rnolecular weight fatty acid esters a simple and economical process. As described, the embodiments of this invention are also equally applicable for removing other acyl halides from ester compositions. 7

While the invention has been described in considerable detail with reference to certain preferred embodiments thereof, it will be understood that-variations and modifications can be effected within the spirit and scope of the invention as disclosed hereinabove and as defined in the appended claims.

I claim:

1. A method of purifying an ester composition resulting from the esterification of an alcohol with a stoichiometric excess of a high molecular weight fatty acid halide" having more than eight carbon atoms. which comprises diluting said ester composition with a non-polar solvent, reacting said excess fatty acid halide in the resultingdi luted ester composition with gaseous ammonia to form an amide, and thereafter separating said amide from the resulting mixture by filtration.

2. A method for removing unreacted palmitoyl halide from an ester composition resulting from the esterifica tion of vitamin A alcohol with a stoichiometric excess of a palmitoyl halide which comprises treating said ester composition with a member of the group consisting of gaseous ammonia and an amine having at least one rcplaceable hydrogen atom on a nitrogen nucleons in a nonpolar solvent, said treating being effective to convert a substantial portion of unreacted palmitoyl halide in said ester composition to amides, and thereafter removing said amides from the resulting mixture by filtration.

3. A method for removing unreacted palmitoyl chloride from an ester composition resulting from the esterification of vitamin A alcohol with a stoichiometric excess of palmitoyl chloride which comprises treating said ester composition in a nonpolar solvent with gaseous ammonia, said treating being effective to convert a substantial proportion of unreacted palmitoyl chloride in said ester composition to palmitamide, chilling the resulting ammoniated mixture to a temperature at which a substantial proportion of the resulting amide is insoluble in said solvent, and thereafter filtering the resulting insoluble amide from the said chilled mixture.

4. A method of removing unreacted higher molecular weight fatty acid halide from an ester composition re sulting from the esterification of an alcohol and a higher molecular weight fatty acid halide having more than eight carbon atoms which comprises treating said ester composition with a member of the group consisting of ammonium hydroxide, gaseous ammonia and an amine having at least one replacable hydrogen atom on a nitrogen nucleus in a non-polar solvent, said treating being effective to convert a substantial proportion of said unreacted fatty acid halide to a nitrogen-containing fatty acid halide derivative, and there-after removing said derivative from the resulting mixture by filtration.

5. A method of purifying an ester composition resulting from the esterification of an alcohol and a higher molecular weight fatty acid halide having more than eight carbon atoms and containing unreacted higher molecular weight fatty acid halide which comprises ammoniating said unreacted fatty acid halide with ammonium hydroxide in a non-polar solvent, and thereafter separating from the resulting mixture an ammoniated derivative of said unreacted fatty acid halide by filtration.

6. A method of purifying an ester composition resulting from the esterification of an alcohol and a higher molecular weight fatty acid halide having more than eight carbon atoms and containing unreacted portions of said fatty acid halide which comprises amidating said unreacted fatty acid halide with gaseous ammonia in a nonpolar solvent and thereafter separating from the resulting mixture an amidated derivative of said unreacted fatty acid halide by filtration.

7. A method of purifying an ester composition resulting from the esterification of an alcohol and a higher molecular weight fatty acid halide having more than eight carbon atoms and containing unreacted portions of said fatty acid halide which comprises amidating said unreacted fatty halide with an amine having at least one replaceable hydrogen atom on a nitrogen nucleus in a nonpolar solvent, and thereafter separating from the resulting mixture an amidated derivative of said unreacted fatty acid halide by filtration.

8. A method of purifying an ester composition resulting from the esterification of an alcohol with a higher molecular weight fatty acid halide having more than eight carbon atoms and containing unreacted portions of said fatty acid halide which comprises dissolving said ester composition in N-hexane, amidating said unreacted fatty acid halide with morpholine, cooling the resulting reaction mixture below 20 C., and separating from the reaction mixture the resulting fatty acid amide by filtration.

9. The method of removing higher molecular weight fatty acid halide from an ester composition resulting from the esterification of an alcohol and a higher molecular weight fatty acid halide having more than eight carbon atoms and containing unreacted portions of said fatty acid which comprises dissolving said ester composition in N-hexane, amidating said unreacted fatty acid halide with a gaseous ammonia, cooling the resulting reaction mixture below 20 C., and thereafter removing the resulting fatty acid amide by filtration.

10. A method of removing unreacted higher molecular weight fatty acid halide from an ester composition resulting from the esterification of an unsaturated alcohol and a higher molecular weight fatty acid halide having more than eight carbon atoms and containing unreacted portions of said fatty acid halide which comprises treating said unreacted fatty acid halide with a member of the group consisting of ammonium hydroxide, gaseous am monia and an amine having at least one replaceable hydrogen atom on a nitrogen nucleus in a non-polar solvent, chilling the resulting mixture, and thereafter removing from the said chilled mixture resulting insoluble nitrogencontaining derivatives of said fatty acid halide by filtratron.

11. A method of purifying an ester composition resulting from the esterification of a tocopherol and a higher molecular weight fatty acid halide having more than eight carbon atoms and containing unreacted portions of said fatty acid halide which comprises treating said unreacted fatty acid halide with gaseous ammonia in a non-polar solvent, and thereafter removing from the resulting mixture resulting fatty acid amides by filtration.

References Cited in the file of this patent UNITED STATES PATENTS 1,963,968 Burke et al June 26, 1934 2,151,369 Arnold et al Mar. 21, 1939 2,231,125 Karrer Feb. 11, 1941 I 2,575,526 Myers Nov. 20, 1951 2,586,860 Port et al. Feb. 26, 1952 2,712,515 Beutel July 5, 1955 OTHER REFERENCES Taylor et al.: Sidgwicks Organic Chemistry of Nitrogen, 1942, page 138.

Markley: Fatty Acids, 1947, page 358.

Claims

1. A METHOD OF PURIFYING AN ESTER COMPOSITION RESULTING FROM THE ESTERIFICATION OF AN ALCOHOL WITH A STOICHIOMETRIC EXCESS OF A HIGH MOLECULAR WEIGHT FATTY ACID HALIDE HAVING MORE THAN EIGHT CARBON ATOMS, WHICH COMPRISES DILUTING SAID ESTER COMPOSITION WITH A NON-POLAR SOLVENT, REACTING SAID EXCESS FATTY ACID HALIDE IN THE RESULTING DILUTED ESTER COMPOSITION WITH GASEOUS AMMONIA TO FORM AN AMIDE, AND THEREAFTER SEPARATING SAID AMIDE FROM THE RESULTING MIXTURE BY FILTRATION.