US2882286A

US2882286A - Preparation of vitamin a palmitate

Info

Publication number: US2882286A
Application number: US544069A
Authority: US
Inventors: George Y Brokaw
Original assignee: Eastman Kodak Co
Current assignee: Eastman Kodak Co
Priority date: 1955-10-31
Filing date: 1955-10-31
Publication date: 1959-04-14
Anticipated expiration: 1976-04-14

Description

United States Patent PREPARATION OF VITAMIN A PALMITATE George Y. Brokaw, Rochester, N.Y., assignor to Eastman Kodak Company, Rochester, N.Y., a corporation of New Jersey No Drawing. Application October 31, 1955 Serial No. 544,069

1 Claim. (Cl. 260410) This invention relates to the preparation of vitamin A esters, and more particularly, to a process for preparing higher fatty acid esters of vitamin A. Vitamin A is a highly unsaturated compound that is too unstable to esterify directly with higher fatty acids with out substantial destruction or reduction of its vitamin A biological activity. Thus, the usual method used for preparing higher fatty acid esters of vitamin A is to esterify with higher acyl halides in the presence of such substances as pyridine, the pyridine being diflicult to separate from the final product. Further, such higher acyl halides as palmitoyl chloride require special procedures and techniques because of their highly corrosive nature and their instability in the presence of even small amounts of water. Accordingly, it is desirable to have a more convenient means for preparing higher fatty acid esters of vitamin A.

It is thus an object of this invention to prepare higher fatty acid esters of vitamin A by a new and improved process.

It is another object of this invention to prepare vitamin A palmitate from vitamin A by novel means.

It is a further object of this invention to prepare higher fatty acid esters of vitamin A having good color and stability by a new method.

These and other objects are accomplished by interesterifying vitamin A with higher fatty acid esters of lower alkyl monohydric alcohols in the presence of a basic interesterification catalyst.

The vitamin A esterified by the prsent process can be prepared by chemical synthesis, or it can be prepared from natural sources such as from fish liver oils.

The higher fatty acid esters of lower alkyl monohydric alcohols used in the present process comprise a wide range of ester materials. Any ester of a lower alkyl monohydric alcohol having from 1 to 6 carbon atoms, and which is esterified with a higher fatty acid having more than 6, and preferably less than 22 carbon atoms, can be utilized. Esters containing fat-forming fatty acid radicals are preferably employed. Typical of the higher fatty acid esters of lower alkyl monohydric alcohols that can be suitably used are methyl palmitate, ethyl palmitate, butyl stearate, methyl oleate, propyl linoleate, methyl myristate, methyl laurate, and the like. Likewise, mixtures of several higher fatty acid esters of lower alkyl monohydric alcohols, such as methyl esters of fat-forming fatty acids derived from vegetable oils or animal fats,

can also be utilized.

Any of the well-known basic interesterification catalysts can be used in the present interesterification process. The alkali metal lower aliphatic alcoholates containing from 1 to 6 carbon atoms are particularly effective, and include such compounds as sodium methoxide, potassium ethoxidc, lithium isopropoxide and related alcoholates. Such alcoholate catalysts are preferred as they are effective at relatively low temperatures, usually temperatures of about 4090 C. being employed with such catalysts, although some alcoholate catalysts are effective at about room temperature. Likewise, related:

' alkaline earth metal lower aliphatic alcoholates can be used, and include such compounds as calcium methoxide, barium isopropoxide, magnesium ethoxide, and the like. Also, alkali metal and alkaline earth metal hydrides andamides such as sodium hydride, potassium amide can be or oxides, such as, sodium palmitate, lithium palmitate,

barium hydroxide and the like. Only relatively small proportionate amounts of the present catalyst need be employed to effect the present interesterification reaction, the amount of catalyst necessary varying mainly with the type of catalyst and the nature of the reaction composition.. Typical catalytic amounts of sodium methoxide, for example, are about .2%-5% by weight of the reaction composition, larger amounts of sodium methoxide likewise being satisfactory.

In carrying out the invention, the vitamin A is com- 'bined with the higher fatty acid ester of a lower alkyl monohydric alcohol in the presence of a catalytic amount of a basic interesterification catalyst and the mixture reacted until the resulting interesterification is substantially complete. The temperature of the reaction can be widely varied, the temperature depending primarily on the type of catalyst employed. If the higher fatty acid ester of a lower alkyl monohydric alcohol is solid at room temperature, this ester is usually melted prior to being incorporated into the reaction mixture. Likewise, the reaction can be effected in an inert organic solvent media, such solvents as xylene, toluene, benzene, petroleum ether, diethyl ether being suitably employed. Usually a stoichio metric excess of the higher fatty acid ester of a lower alkyl monohydric alcohol is employed, although the present interesterification reaction can be effected with stoichiometric proportions of the reactants. The reaction can be effected under vacuum and the lower alkyl monohydric alcohol resulting from the interesterification reaction removed during the course of the reaction. The reaction time typically varies from about 1 hour to 2 or 3 hours, Or even longer, the reaction time depending on such variants as the catalyst, the reaction temperature, the reactants themselves, and other related variants. The reaction mixture is preferably stirred or agitated to increase the effectiveness of the catalyst. After the re action is completed, the inert organic solvent, unreacted higher fatty acid ester of a lower alkyl monohydric alcohol, and lower alkyl monohydric alcohol resulting from the interesterification reaction can be readily separated from the vitamin A ester product by vacuum distillation. Likewise, the prepared higher fatty acid ester of vitamin A can be separated from the interesterification reaction mixture by any of the other well-known separating means, such as by chromatographic adsorption, for example.

The invention is illustrated by the following example of a preferred embodiment thereof, it being understood that the example is illustrative only and not intended to limit the scope of the invention unless otherwise specifically indicated.

Example To a 120.40 g. sample of vitamin A prepared by chemical synthesis and having Was added 180.6 g. of melted methyl palmitate and 1.5 g. of sodium methoxide. The resulting mixture was thereafter reacted at a temperature of about 60 C. for 60 minutes at a reduced pressure with constant stirring. The resulting reaction mixture was thereafter cooled with Patented Apr. 14, 1959 Y 3 690 of petroleum ether (boiling range 60100 C.) containing a small amount of Dry Ice. The cooled re action mixture was filtered and the resulting filtrate was vacuum distilled to give 296.4 g. of vitamin A palmitate having fofa yield of about 99%. (The yield was calculated fro higher fatty acid esters of a lower alkyl monohydric alcohol'ca'rr be interesterifie'd with vitamin A to produce richer ram} acid esters of'vitath'hl A. Higher fatty acid esters or vitamin A prepared in accordance with the presexit process are particularly characterized as having good color andstabilit y. U I

Thns by means" of this'invention; higher fatty acid esters-ofvitamin A can be readily and conveniently prepared.

. Although the invention has been; described in detail with particular reference to certain preferred embodiments thereof; it-Will beunders'tood that variations and ultra-violet absorption data.) Similarly, other modifications can be eifected within the spirit and scope of the invention as described hereinabove and as defined in the appended claim.

I claim:

The method of preparing vitamin A palmitate having improved stability to oxidative deterioration which comprises subjecting vitamin A alcohol and methyl palmitate to an alcoholy'sis reaction in' the presence of a catalytic amount of sodium methoxide and thereby forming vitamin A palmitate.

References Cited in the file of this patent UNiTED STATES" PATENT Stieg et al. Nov. 2, 1954 OTHER REFERENCES Dean: Utilization of Fats, 1938, page 118. v v amos: Fatty Acids and Their Derivatives; 1948; page 544: g y

Fies er et al.: Organic Chemistry; 1950, pa1ge 1026. Grbg' g'i-iis: Unit Processes in organic syntheses; 4th edition, 1952;15age 616.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent NO. 2,882,286 April 14, 1959 George Yo Brokaw ars in the -printed specification It is herebfi certified that error appe ection and that the said Letters of the above numbered patent requiring corr Patent should read as corrected below.

Column 2 line 19 after "are about, for .2%=-5j%" read w ,2%=-5% Signed and sealed this 1st day of September 1959;

(SEAd 1) Attcst:

KARL Ho AXLINE Attesting Ofiicer ROBERT C. WATSON Commissioner of Patents