US2595221A - Esters of polyhydroxy-benzoic acids and method for their preparation - Google Patents

Description

Patented May 6, 1952 ESTERS OF POLYHYDROXY-BENZOIC ACIDS AND METHOD FOR THEIR PREPARATION Waldo C. Ault, Philadelphia, George C. Nutting, Abington, and James K. Weil, Lansd-ale, Pa., assignors to the. United States of America as represented by the Secretary of Agriculture No Drawing. Application April 22, 1947, SerialNo. 743,210

(Granted under the act of March 3, 1883, as amended April'30, 1928; 370 O. G. 757) 18 Claims.

This application is made under the act of March 3, l883, as amended by the act of April 30, 1928., and the invention herein described, if patented, may be manufactured and used by or for the Government of the United States of America for governmental purposes without the payment to us of any royalty thereon.

This invention relates to esters of polyhydroxybenzoic acids and more particularly to the esters of these acids with aliphatic alcohols containing more than six carbon atoms per molecule and their preparation.

Esters of gallic acids with lower fatty alcohols can be obtained by direct esterification, frequently on heating the reactants in the presence of suitable esterification catalysts. When this procedure is followed in an attempt to esterify gallic acid with higher fatty alcohols containing more than six carbon atoms per molecule, the esterification either does not take place, or the corresponding esters are formed in such small amount that it is not feasible to isolate them from the reaction products. Similar results are obtained on heating the reactants with inert non-polar solvents such as benzene, toluene, cumene, or

other non-polar organic solvents commonly utltheir application for Patent Serial No. 678,188,

filed June 21, 1546, that alkyl esters of gallic acid and of some other polyhydroxy-benzoic acids can be prepared by esterification-of the correspond ing benzyloXy-derivatives of benzoic acid and su sequent debenzylation of the resulting ester by catalytic hydrogenation. Our method, however, is also applicable to the production of polyhydroXy-benzoic acid esters of oleiinic alcohols, since it obviates the hydrogenation step, which causes addition of hydrogen to the double bond of the alcohol radical and thus converts it to the corresponding alkyl group.

An object of this invention is the production of polyhydroxy-hcnzoic acid esters of higher aliphatic alcohols by methods that are simpler and more economical than those used heretofore. A further object is the provision of a method for producing polyhydroXy-benzoic acid esters of aliphatic alcohols containing more than six carbon atoms per molecule, by direct esteriiication. Another object is to provide new compositions of matter which are polyhydroXy-benzoic acid esters. of alcohols containing more. than six. carbo'ns per molecule, in particular, unsaturated a1.-

cohols. Other objects and advantages of the invention will appear hereinafter.

We have found that esters of polyhydroxybenzoic acids with aliphatic alcohols containing more than six carbon atoms per molecule are formed by direct esterification in the presence of a polar organic solvent. In accordance with the method of our invention the polyhydroxy-benzoic acid is heated with the aliphatic alcohol. in the presence of'a polar organic solvent, and preferably in the presence of an esterification catalyst, at a temperature and for the length of time suificient to cause formation of the ester.

The method of this invention is applicable to polyhydroXy-benzoic acids containing hydroxyl groups in para and/or meta positions to. the carboXyl group, such as gallic acid, p-rotocatechuic acid, and alpha-resorcylic acid. Aliphatic alcohols suitable for effecting esterification of these acids include saturated and unsaturated alcohols containing more than six carbon atoms per molecule, for instance n-octyl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, and. oleyl alcohol. Suitable polar organic solvents are polar organic solvents which under the conditions of the process are chemically inert toward the reactants and reaction products. Such polar solvents include for example, nitrobenzene, ortho-dichlorobenzene, anisole and phenetole, which can be used singly or in combination. Addition of esterification catalysts,

such as sulfuri acid, toluene sulfonic acid, naphthalene sulfonic acid, or nitrobenzene sulfonic acid and similar acidic substances increases the reaction rate of the esterification process.

The expression polar solvents is employed here in its widely accepted sense. The following publications indicate the meaning of the term, being the widely accepted manner of defining such solvents:

Liquids, for the sake of convenience are generally divided intotwo classes, polar and nonpolar The dielectric constant of a compound is one of the best measures of polarity." Lewis, Squires and Broughton, Industrial Chemistry of Colloidal and Amorphous Materials. 1942, page 15.

Many organic solvents exhibit this [electrical] conductivity. hose substances are chemically active and are referred to as polar solvents Solvents like alcohols and ketones, have high dielectric constants and this is evidence of strong polarity. Those of low dielectric constants, like the, aliphatic and aromatic hydrocarbons, are classified as nonpolar solvents. Mellan, Industrial Solvents, 1939, page 9.

The dielectric constants of the solvents mentioned in the application and of some common inert, non-polar solvents, boiling within the range claimed are listed in the following table:

Since esterification proceeds more rapidly at higher temperature and is facilitated by removal of water from the reaction mixture it is usually advantageous to utilize polar solvents boiling above 100 C. and to conduct the reaction under reflux with concurrent separation of water. Since the reaction temperature must not, however, be sufliciently high to cause any appreciable decomposition of the polyhydroxy-benzoic acid, the operator should determine the optimum upper limit in each case. Thus for example, esterification of gallic acid in the presence of nitrobenzene is best effected by conducting the reaction under reflux and using a mixture of nitrobenzene with a lower boiling polar solvent thereby maintaining the reaction mixture at a temperature below the decomposition temperature of gallic acid. The ratio of reactants to solvent may be varied within wide limits. We have found, however, that when the polar solvent consists of a mixture of nitrobenzene with another polar organic solvent the highest yields of esters may be obtained if the amounts of polyhydroxy-benzoic acid and nitrobenzene present in the reaction mixture approximate the molar ratio of 1 to 1.

The esters of polyhydroxy-benzoic acids with aliphatic alcohols containing more than six carbon atoms are useful as antioxidants and rancidity inhibitors for fatty and oily materials and as intermediates in production of synthetic chemicals.

As illustrative embodiments of a manner in which our invention may be carried out in practice the following examples are given.

Example I temperature, washed with water to remove the catalyst and unreacted gallic acid, and the solvent evaporated under reduced pressure. Recrystallization of the distillation residue from benzene-petroleum ether gave 8.8 grams (52 percent of theory) of dodecyl gallate melting at 96-97 C.

Example II Cetyl gallate.5.64-. grams of gallic acid, 7.27 grams of cetyl alcohol, 0.5 gram of beta-naphthalene sulfonic acid and cc. of nitrobenzene were refluxed as described in Example I. Since discoloration of the mixture gave reason to be lieve that some decomposition of gallic acid was taking place, 50 cc. of o-dichlorobenzene was added at the end of the first half hour and refluxing was continued for an additional 17 hours.

Three grams (24 percent of theory) of hexadecyl gallate melting at 96-98 C. was recovered from the reaction mixture by the procedure described in Example I. On further recrystallization from benzene-petroleum ether, this product yielded 2.6 grams of ester having a melting point of 98-99 C.

A somewhat lower yield of hexadecyl gallate was obtained on heating a mixture of 5.64 grams gallic acid, 7.27 grams cetyl alcohol, 0.5 gram beta-naphthalene sulfonic acid and 100 cc. nitrobenzene at 170 C. for 24 hours, and treating the resulting reaction mixture as described in Example I. The temperature was kept constant by maintaining a pressure somewhat below at mospheric.

Example III Oleyl gallate.4.71 grams of gallic acid, 8.93 grams of oleyl alcohol, 0.5 gram of p-toluene sulfonic acid and 150 cc. of o-dichlorobenzene were refluxed for 29 hours during which time an additional 0.4 gram of p-toluene sulfonic acid was added by increments.

The mixture was allowed to cool to room temperature and filtered. 2.36 grams of unreacted gallic acid was thus recovered. The filtrate was then washed three times with equal volumes of hot water. The o-dichlorobenzene was removed by distillation under vacuum and the residue taken up in a mixture of benzene and petroleum ether from which the ester was allowed to crystallize. Approximately 1 gram of crystalline octadecenyl gallate melting at 83-85f C. was obtained which after crystallization gave a crystalline material, M. P. 85.f5-86.5 C. Similar results were obtained when a mixture of cc. 0- dichlorobenzene and 5 cc. of nitrobenzene was used as the solvent mixture.

Example IV Lauryl yallate.-A mixture of 3.6 grams of gallic acid, 8 grams n-dodecyl alcohol, 0.2 gram naphthalene beta-sulfonic acid, 45cc. anisole and 2.2 cc. nitrobenzene was refluxedfor 15 hours. The ester was recovered as described" in Example IV and recrystallized from benzene-petroleum ether-mixturez 5.5 grams (7'? percent) of dodecyl gallate, M. P. 96.5-97.0 C; was obtained. An additional 4grams of crude ester (M. P. 85) crystallized from the mother liquor.

Example: VI

Lauryl gaZlate.-A mixture of 51 grams gallic acid, 112 grams. lauryl alcohol, 2.5 grams naphthalene beta-sulfonic acid, 535 cc. anisole and 31 cc. nitrobenzene was refluxed for hours. 67.8 grams (66.8 percent) of dodecyl. gallate, M. P. 96-97 C. was recovered by the procedure given in Example V.

Example VII Myristyl gaZZate;A mixture of 3 grams gallic acid, 7.5 grams myristyli alcohol, 0.2 gram naphthalene-beta-sulfonic acid, cc. phenetole and 2.2 cc. nitrobenzene was refluxed for 9 hours. Thev ester recovered as in Example IV was recrystallized from benzene-petroleum ether yielding 2.6 grams (41 percent) of tetradecyl gallate, M. P. 983 C.

Example VIII Cetyl galleria-A mixture of 3.4 grams gallic acid, 9.6 grams cetyl alcohol, 0.2 gram naphthalene-beta-sulfonic acid, 40 cc. anisole and 2.1 cc. nitrobenzene was refluxed for 15 hours. The ester recovered as in Example IV was recrystallized to yield 2.1 grams (27 percent) of hexadecyl gallate, M. P. 93-94 C.

Example IX Octodecyl gallate was prepared by reacting 3.4 grams of gallic acid with 11.4 grams of l-octadecanol according to the procedure described in Example VIII. The yield was 7.2 grams (86 percent) of crude octadecyl gallate, M. P. 9l93 C. A purified ester melting at 101.5-l03.5 C. was obtained by recrystallization.

Example X Lauryl protocatechuate.A mixture of 0.9 gram protocatechuic acid, 2.6 grams lauryl alcohol, 0.05 gram naphthalene-beta-sulfonic acid, 20 cc. anisole and 0.7 gram nitrobenzene was refluxed for '7 hours. zoate, M. P. 102.'7-103.6 C. was recovered from th reaction mixture by a procedure analogous to those described in the foregoing examples. The yield was 0.9 gram (4'7 percent of the calculated).

Example XI Lauryl alpha-resorcylate, M. P. 8689i C. was obtained by reacting 3,5-dihydroxybenzoic acid with lauryl alcohol, according to the procedure described in Example X.

Example XII Dodecyl-3, 4-dihydroxyben- Having thus described our invention, we claim: 1. A process of producing an ester'of' a. polyhydroxybenzoic' acid of; the general formula:

COOH

in whicha: is an integer from.2.to 3 and in which the positions ortho to the carboxyl group are free of substituents; comprising heating said acid with an alcohol of the formula RCH2OH, in which R is a radical taken from the group consisting of olefine and saturated alkyl radicals having more than five carbon atoms, said heating being in the presence of an acid esterification catalyst and under reflux and return of solvent with concurrent separation of water, thesolvent being a polar organic solvent medium which under the conditions of the process is chemically inert toward the reactants and the reaction products and which boils above C. and not higher than the boiling point of nitrobenzene, andbelow the decomposition temperature of the polyhydroxy-benzoic acid, the solvent medium being a substituted hydrocarbon taken from the group consisting of nitrobenzene, ortho-dichlorbenzen anisole, and phenetole.

2. The process described in claim 1 in which thethe solvent medium is a mixture of nitrobenzene and another solvent of said group, the nitrobenzene being present in the reaction in A minor amount with respect to the said solvent,

and recovering the ester of the acid and the alcohol.

3. The process defined in claim 1 in which the acid is gallic acid.

The process defined in claim 1 in which the acid is protccatechuic acid.

5. The process defined in claim 1 in which the acid is 3,5-dihydroxy benzoic acid.

6. The process defined in claim 1 in which the alcohol is a normal saturated aliphatic alcohol containing from 8 to 18 carbon atoms per molecule.

7. The process defined in claim 1 in which the alcohol is oleyl alcohol.

8. The process defined in claim 1 in which the alcohol is lauryl alcohol.

9. The process defined in claim 1 in which the alcohol is n-cctadecyl alcohol.

10. The process of preparing oleyl gallate com- I prising heating to reflux oleyl alcohol with gallic acid in a medium of ortho-dichlorobenzene in the presence of minor amounts of nitrobenzene with respect to the weight of the gallic acid.

11. The process described in claim 10 in which the reaction is in the presence of p-toluene sulfonic acid.

12. A process comprising refluxing a mixture of protocatechuic acid, lauryl alcohol, anisole and nitrobenzene, and recovering lauryl protocatechuate from the reaction mixture, the anisole being in molar excess with respect to the protocatechuic acid, the nitrobenzene being in minor amount with respect to the anisole.

13. A process of producing an ester of a polyhydroxy-benzoic acid of the formula:

(IJOOH in which x is an integer from 2 to 3 and in which the positions ortho to the carbcxyl group are free of substituents; comprising heating said acid with an alcohol of the formula RCH2OH, in which R is a radical taken from the group consisting of olefine and saturated alkyl radicals having more than five carbon atoms, said heating being under reflux in a mixture of nitrobenacne and anisole.

14. The process described in claim 1 in which the solvent medium is a mixture of nitrobenzene and another solvent of said group having a boiling point below nitrobenzene, the molar ratio of polyhydroxybenzoic acid to nitrobenzene being about 1 to 1.

15. The process described in claim 1 in which the solvent medium is a mixture of nitrobenzene and another solvent of said group having a boiling point below nitrobenzene.

16. The process described in c1aim l in which the solvent is a mixture of nitrobenzene and anisole.

17. The process described in claim 1 in which the polyhydroxybenzoic acid is taken from the group consisting of gallic acid, protocatechuic acid, and 3,5-dihydroxy benzoic acid, the alcohol being taken from the group consisting of oleyl, lauryl, n-octyl, myristyl, cetyl, and stearyl.

18. The process of claim 1 in which the alcohol is monohydric.

WALDO C. AULT. GEORGE C. NUTTING. JAMES K. WEIL.

8 REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS OTHER REFERENCES Steward G. Morris et al.: J. Am. Chem. Soc., vol. 68, pp. 500-501.

Fishery Market News, Vol. 7, N0. '7, pp. 18, 19 (July 1945) Alfred Russell et al.: J. Am. Chem. Soc., vol. 64, pp. 2274-2276, 1942.

Dielectric Constant and Molecular Structure, Smyth, Pub. Chemical Catalog Co., New York, N. Y., pp. 13, 192-199 (1931).

Bergel: Chemistry and Industry, Apr. 1, 1944, p. 127.

Suter et al.: J. A. C. S., vol. 61, p. 531 (1939).

Kailan: Monatschefte, vol. 48, pp. 405-443 (1927).

Weygand: 170472.

Organic Preparation, 1945, pp.

Claims (1)

1. A PROCESS OF PRODUCING AN ESTER OF A POLYHYDROXYBENZOIC ACID OF THE GENERAL FORMULA: