2,881,193 United States Patent Office Patented Apr. 7, 1959 2 propionic acid, glutamic acid, aspartic acid and the like. 2,881,193 Particularly satisfactory results are obtained in the PURIFICATION OF N-HIGHER FATTY ACED purification of N-higher fatty acyl sarcosine compounds AMDES OF LOWER MONOAMINOCAR such as salts of N-lauroyl sarcosine, N-myristoyl sarcosine BOXYFLIC ACDS and N-palmitoyl sarcosine, e.g., sodium, potassium salts thereof. Morton Batlan Epstein, Linden, N.J., assignor to Colgate While the present invention is broadly applicable to Palmolive Company, Jersey City, N.J., a corporation mixtures of the amide and higher fatty acid material of Delaware as indicated, it is effective particularly with the reaction No Drawing. Application May 9, 1955 product produced in the following manner and results Serial No. 507,177 in an amide material substantially free from soap and the like. Thus, the amide may be formed by condensing 6 Claims. (C. 260-404) a higher fatty acyl halide with a salt of said amino car boxylic acid, which has a primary or secondary amino The present invention relates to a novel process for 5 group, in an aqueous alkaline medium. purifying N-higher. acyl amide compounds. More This condensation reaction may be performed under specifically the invention is of a method for removing various suitable conditions. The reaction may be con impurities of the fatty acid or soap type from compounds ducted by mixing suitable proportions of the reactants which are N-higher fatty amides of lower monoamino in an aqueous medium. In general, the reaction is effected carboxylic acids or salts thereof. 20 by using substantially stoichiometric ratios of reactants. U.S. Patent No. 2,689,170, issued September 14, 1954, Generally no external heat need be applied, though the discloses that dental preparations containing certain reaction mixture may be cooled below room tempera higher aliphatic amides of amino acids possess caries ture or subjected to elevated temperatures up to the inhibitory properties. Such a dental preparation con refluxing temperature, if desired. It is necessary to taining the specified active ingredients, e.g., a dental cream 25 operate in a non-acidic medium. A suitable alkaline containing sodium N-lauroyl sarcosine, when used to substance is present and acts as acceptor for the hydrogen brush the teeth regularly, reduces dental caries sub halide which is liberated by the condensation reaction stantially and inhibits for a prolonged time the produc and thereby facilitates the completion of reaction. Any tion of acid in the mouth after the intake of sugar. suitable alkaline neutralizing agent may be employed such The said amide compounds used in dentrifices are prefer 30 as an alkali metal hydroxide, e.g., sodium or potassium ably pure or substantially pure and in particular it is hydroxide, as well as organic bases including amines such desirable that they be as free as practicable from higher as pyridine. The resulting reaction mixture from the fatty acid material, such as soap, which interferes with above condensation reaction contains a variable amount their intended function. of impurities and by-products in addition to the desired In acocrdance with the present invention an impure 35 amide salt compounds. There is present a proportion of N-higher fatty amide of lower monoaminocarboxylic. higher fatty acid material, such as soap, which should acid containing fatty acid material is purified by adjust be removed or reduced to a minimum. ing the pH of an aqueous medium containing the said Because such method of making the desired amide impure amide compound to a point at which the fatty compounds results in a mixture of amide salt and soap acid material is present as fatty acid and the said amide 40 suitable for treatment by the process of the invention, compound is present as a water soluble salt and separating the invented process will be described in detail using the the fatty acid from the amide compound. The amide mixture as the starting material. However, it must be compound may then be recovered in purified form. remembered that the process of the invention can be A further embodiment of the invention comprises a used generally to purify the disclosed amide compounds process for separating soap from water soluble salt of of fatty acid material and hence adjustment of pH of N-higher fatty amide of lower monoaminocarboxylic acid 45 an aqueous medium containing amide acid and higher by adjusting the pH of an aqueous solution thereof to fatty acid by addition of an alkaline agent, e.g., sodium a point at which the soap changes to higher fatty acid, hydroxide, alkaline phosphates, is also within the scope the said amide salt being unaltered, and separating the of the invention. The latter processes may be conducted resulting fatty acid from the amide salt solution. in a manner similar to that to be described. In this specification in the interest of conciseness and 50 The impure amide salt may be purified of soap by clarity of expression the term "amide compound” includes adjusting the pH of a solution of impure amide salt N-higher fatty amides of lower monoaminocarboxylic to a point at which soap is converted to fatty acid, the acids and salts thereof. "Amide acid' refers to N-higher amide salt remaining as the water soluble salt, separating fatty amides of lower monoaminocarboxylic acids and 55 the fatty acid from the aqueous solution and recovering "amide salt” to the salts derived from these acids. "Fatty the amide salt. The solutions of amide salt may be acid material” includes the higher fatty acids and soaps process solutions, or may be made up from impure solid made therefrom. amide salts. As has been mentioned, the amide compounds suitable Generally, as a consequence of the usual processes for purification by the process of the invention are the N-higher fatty amides of lower aliphatic monoamino 60 of making amide salts, the soap impurity and the amide carboxylic acid compounds. More particularly the salt will have identical cations. However it is not neces process is used to purify those amides having a saturated sary that such should be the case. fatty acyl radical of about 12 to 16 carbon atoms, al The soap content of the impure amide salt to be purified though amides with other higher fatty acyl radicals such may vary over a wide range. It may be equal to or exceed as decanoyl, stearoyl and oleoyl radicals may also be 65 the weight of the amide salt but generally it will be a minor purified by the present method. The lower amino acid proportion, between about 2 and 20 percent of the weight partion of these compounds is derived preferably from the of the solids (amide salt plus soap). lower aliphatic saturated monoamino carboxylic acids The impure amide salt should preferably be in solution such as those having about 2 to 6 carbon atoms. Among in an aqueous solvent medium before pH adjustment is the amino acids from which suitable amide compounds 70 undertaken. An excess of amide salt and/or soap beyond may be made are sarcosine, glycine, alanine, 3-amino saturation may be utilized satisfactorily provided that such 2,881,198 3. 4. is in finely dispersed form and does not interfere with the from amide salt solution. After standing a short while process separation of fatty acid and amide salt. separations occur and the ether layers are removed. The The aqueous medium in which the amide salt is dis fatty acids will be found in the ether layer and the amide solved (and sometimes partially suspended) is water. salt will be present in the aqueous medium. Miscible solvents and solutes may also be present when Often the degree of removal of soap may be judged desired. visually by observation of the extract residues after sol The concentration of solids in the aqueous medium is vent (ether) evaporation and the preferred pH for the not critical nor is the temperature employed during the pH purification process may be so ascertained, but a quanti adjustment. Of course to promote rapid conversion of tative determination of soap present with the amide salt soap to fatty acid it is desirable that the solution concen O is desirable. Such determination may be made by X-ray tration and temperature should be such as to make the diffraction, chromatographic adsorption or film drainage solution fluid and homogeneous. transition temperature measurements of the purified amide Any suitable agent may be used for adjusting the pH, salt or solutions thereof. Preferably the ether extract either an acid, e.g., a mineral acid such as hydrochloric is also tested for amino acids or nitrogen to determine acid, or solutions of buffer salts, e.g., phosphates or mix 5 whether the adjusted pH was lower than optimum. The tures thereof. optimum process pH to which a specific impure amide salt Gentle agitation of the solution of impure amide sait Solution is adjusted is that at which the purified amide is desirable during the addition of acid or acid buffer to salt contains the least amount of soap impurity and the the said solution. The reaction of soap with acid ions at least amount of amide salt is converted to lower amino the process pH is rapid and hence reaction times are not 20 acids. critical. The processes of purifying salts of N-higher fatty acyl The pH to which an amide salt-soap solution should be sarcosine are preferred embodiments of this invention, adjusted is specific to the particular impure annide salt and the process is particularly advantageously used in the solution being processed. It will usually be in rather purification of impure sodium N-lauroyl sarcosine and narrow selective portions of the pH range 4-10. 25 sodium N-palmitoyl sarcosine. On adjustment of pH of an impure amide salt solution Water solutions of impure sodium N-lauroyl sarcosine to the proper point the soap impurity will be converted containing a minor proportion of soap (sodium laurate) to fatty acid. Such acid may drop out of solution, form thicken appreciably at concentrations of about 35 percent ing a homogeneous continuous liquid phase or a solid in solids by weight and gel at about 40 percent concentra which case it may be drawn off and separated from the 30 tion. Therefore concentrations of solutions thereof to amide salt solution, or the amide solution may be drawn be purified are generally held below 40 percent solids by off. More often, however, either all or part of the gen weight and preferably below 35 percent. erated acid will be present in the aqueous medium in dis Impure sodium N-palmitoyl sarcosine containing a persed or emulsified form and might even be dissolved in minor amount of soap gels at about 15 percent concentra it to some extent. In these latter instances the fatty acid 35 tion Solids by weight, Hence it is preferred that such may be removed by extracting it with a preferential sol solutions to be purified should be of concentrations less vent, or by selectively sorbing it on various adsorbents, than 15 percent. e.g., silica, activated carbon, alumina. Alternatively, In the case of solutions of sodium N-lauroyl sarcosine known emulsion breaking devices or methods may be em containing minor proportions of sodium laurate a pH ployed, e. g., ultrasonic wave generators, raising electro 40 adjustment to 5.5 to 7, preferably 5.5 to 6.5, results in the lyte content of the aqueous medium to break the fatty formation of fatty acid but the sarcosine derivative re acid emulsions, after which the fatty acids will separate mains water soluble. For purification of solutions of so and may be drawn off. dium N-palmitoyl sarconsinate containing minor amounts A preferred method of removing fatty acid from the of Sodium palmitate a pH of 6.5 to 8.5 is preferred. pH-adjusted amide salt solution is by extracting it with 45 In either case the fatty acid may be removed by extrac a preferential solvent, e.g., diethyl ether, petroleum ether. tion with petroleum either or diethyl ether. Such solvent will dissolve the fatty acid and not the amide The following specific examples of the invented proc salt. If desired, the preferential solvent may be dispersed esses are given for purposes of illustration only and are in the aqueous impure amide solution before adjustment not to be regarded as limiting the invention. All parts of pH. After pH adjustment the preferential solvent 50 indicated are by weight. containing fatty acid, being non-miscible with the aqueous phase, will separate from said phase and may be drawn Example I off. A preferential solvent which is substantially non A water solution was made containing 20 parts sodium miscible with the aqueous phase may be used because, N-lauroyl sarcosine, 1 part sodium laurate and 179 parts even though some of the solvent remains in the aqueous 55 water. The pH of the solution was adjusted to 6.1 by phase, the greater part of the fatty acid will dissolve in careful addition, while stirring, of 2-Normal hydrochloric the non-aqueous phase and substantial purification will acid. It was noted that the solution became cloudy as be effected. The solution of purified amide salt may be acid was added, indicating the formation of a fatty acid used directly or the solvent may be driven off to obtain emulsion. After standing 5 minutes diethyl ether was the amide salt in solid form. 60 added to the solution and the mixture was agitated for To determine the optimum pH range to which specific 5 minutes to promote extraction by the ether of the Solutions of impure amide salts should be adjusted one lauric caid. The resulting either-water mixture was al need only employ a relatively simple test procedure such lowed to stand overnight and after this settling period as the following, the heavier phase, the water phase, was drawn off. The mixture of water soluble amide salt and soap is 65 Tests made on the water solution showed it to be a made up to a fluid mixture or solution of about 10 percent solution of sodium N-lauroyl sarcosinate containing less concentration of solids in water (although lesser or greater than 0.5 percent soap on a solids weight basis. The origi concentrations may be employed). The solution is then nal solution had contained 4.8 percent sodium laurate divided into several portions each of which is adjusted in on the same basis. pH by addition of mineral acid, e.g., hydrochloric acid, 70 or suitable buffer to a predetermined value between about Example II 4 and 10 so that a series of solution pH's is obtained. Ten parts of a mixture of sodium N-palmitoyl sarcosine The adjusted solutions are allowed to stand a few minutes and sodium palmitate solids containing about ten per and are then shaken with diethyl ether, petroleum ether cent soap by weight were dissolved in 200 parts water. or other suitable solvent capable of extracting fatty acid 75 The pH of the resulting solution was adjusted to 8.5 by

2,88.98 5 6 addition of dilute hydrochloric acid while stirring. As fatty acid amide of sarcosine having about 12 and 16 the acid was added the solution become cloudy. The carbon atoms in the fatty group which comprises low fatty acid present was extracted with ethyl ether. Tests ering the pH of an aqueous solution of the impure N made on the water solution remaining after removal higher fatty acid sarcosine salt to a pH between 4 of ether showed that it was a solution of sodium N and 10 at which the alkali metal soap of higher fatty palmitoyl sarcosine containing less than one percent acid is converted to higher fatty acid and the N-higher Soap (sodium palmitate) on a solids weight basis. fatty acid sarcosine salt remains water soluble, separat The invention has been described in conjunction with ing the higher fatty acid from the N-higher fatty acid illustrative examples thereof. It will be obvious to those sarcosine salt and recovering said sarcosine salt. skilled in the art, after reading this specification, that 10 5. A process for removing a minor proportion of other variations and modifications of the invention can sodium laurate impurity from sodium N-lauroyl sar be made and various equivalents substituted therein cosine which comprises lowering the pH of an aqueous without departing from the principles disclosed or gping solution containing less than 40% impure sodium N outside the scope of the specification or purview of the auroyl sarcosine solids, of which solids about 2 to 20% claims. 5 thereof is sodium laurate, to between 5.5 and 7, at which What is claimed is: pH the sodium laurate is converted to lauric acid and the 1. A process for removing fatty acid material im sodium N-lauroyl sarcosine remains water soluble, sep purity selected from the group consisting of higher fatty arating the lauric acid from aqueous solution of sodium acid and alkali metal higher fatty acid soap from a cor N-lauroyl sarcosine by contacting said solution with a responding N-higher fatty amide compound selected from substantially water immiscible organic solvent for lauric the group consisting of N-higher fatty amides of lower acid, removing the solvent containing lauric acid from monoaminocarboxylic acids and salts thereof which com the aqueous solution of sodium N-lauroyl sarcosine and prises adjusting the pH of an aqueous medium contain recovering sodium N-lauroyl sarcosine. ing said impure amide compound to a point at which 6. A process for removing a minor proportion of the fatty acid material is present as fatty acid and the 25 sodium palmitate impurity from sodium N-palmitoyl amide compound is present as a water soluble salt and sarcosine which comprises lowering the pH of an aque separating the fatty acid from the amide compound. ous solution containing less than 15% impure sodium 2. A process for removing a minor proportion of al N-palmitoyl sarcosine solids, of which solids about 2 kali metal higher fatty acid soap impurity from alkali to 20% thereof is sodium palmitate, to between 6.5 and metal salt of an amide of higher fatty acid of 10 to 18 30 8.5, at which pH the sodium palmitate is converted to carbon atoms and lower saturated monoaminocarboxylic paimitic acid and the sodium N-palmitoyl sarcosine re acid of 2 to 6 carbon atoms which comprises lowering mains water soluble, separating the palmitic acid from the pH of an aqueous solution of the said impure amide aqueous solution of sodium N-palmitoyl sarcosine by con salt to a pH at which the higher fatty acid soap is con tacting said solution with a substantially water immisci verted to higher fatty acid and the amide salt remains 35 ble organic solvent for palmitic acid, removing the sol water soluble, separating the fatty acid from the amide vent containing palmitic acid from the aqueous solution salt and recovering said amide salt. of sodium N-palmitoyl sarcosine and recovering sodium 3. A process for removing a minor proportion of N-palmitoyl sarcosine. water soluble alkali metal higher fatty acid soap im purity from alkali metal salt of N-higher fatty acid 40 References Cited in the file of this patent sarcosine amide in which the fatty acid group is of 10 UNITED STATES PATENTS to 18 carbon atoms which comprises lowering the pH of an aqueous solution of impure N-higher fatty acid 1,822,016 Daniels ------Sept. 8, 1931 sarcosine salt to a pH at which the higher fatty acid 2,680,753 Masci et al. ------June 8, 1954 soap is converted to higher fatty acid and the N-higher 45 2,684,969 Krems et al. ------July 27, 1954 fatty acid sarcosine salt remains water soluble, separat FOREIGN PATENTS ing the fatty acid from the sarcosine salt and recover 316,703 Great Britain ------Aug. 8, 1929 ing the sarcosine salt. 4. A process for removing a minor proportion of OTHER REFERENCES water soluble alkali metal higher fatty acid soap im 50 Hackh: Chemical Dictionary (3rd ed.), 1944, page purity for a water soluble alkali metal salt of N-higher 18. The Blakiston Co., Philadelphia.