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.