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Home , Cerotic acid, Margaric acid, Melissic acid

Patented June 15, 1943 2,321,594

UNITED STATES PATENT OFFICE 2,321,594 AMNO CARBOXYLIC ACD OF HIGHER MOLECULAR WEGHT CARBOX YLIC MonoESTERs oF GLYcoLs Benjamin R. Harris, Chicago, Ill. No Drawing. Application February 5, 1941, Serial No. 3,489 14 Claims. (C. 260-404) This invention relates to the preparation of O new chemical compounds which are especially (8) ch,-0--Cich, useful for antiseptic, medicinal, preservative, bac CE tericidal, bacteriostatic, germicidal and fungicidal / plpOSes. s H-0--cent, A. At least many of the novel substances of the O C present invention, which, in use, are employed O particularly in the form of salts such as hydro chlorides, as hereinafter set forth, fall within the (4) gh-0--c Eas Scope of the general formula: O C H-0-- -CH O NB o--R O (5) CH-O--Citi, 5 bH, Yo-c-R &H-0-0-ch-c E-C Wherein NH, O O R-3- 20 (6) CB-O- - Cis is an acyl radical, O (E), R-C- Hi-o-c-CH-CH-cooH is the acyl radical of an amino- NH, containing at least one primary amino group, 25 O and X is the residue of a glycol. CH-0--0 ults The novel substances of the present invention, (7) generally used in the form of their salts as indi Ho-b H-O-C-CH-CH-CH-CH cated hereinabove, may be regarded as amino NH, carboxylic acid esters of carboxylic acid mono 30 O esters of glycols, particularly higher molecular weight mono-esters of glycols, espe (8) CI- 0-8-cube cially satisfactory being those derived from fatty acids containing from eight to fourteen carbon ch, atoms. 35 s C In order that the nature of the invention may & H-O- C-C-N./ become, more apparent, there are listed herein N below various of the novel substances which gen C erally are used in the form of salts, especially, O hydrochlorides, and fall within the scope of the 40 invention: (9) CE- 0-8-Citi, O H-0--CH-CH-CH-CH (1) CH-0--0. He NH, NH, &H-0- C-CE-NE 45 O CBI-CE (10) 9.H-0-- H-coh-oh, O (2) CH-O-C-C1s 50 &H-0--it-ch-oh-oh,NE b O bH, () cE-0--0 Has &E-o-o-ch-NE, bi-o-o-c-ch-in-KD OBE 2 2,821,594 The substances are prepared, preferably, by glycol, diethylene glycol, trimethylene glycol, tri converting the amino-carboxylic acid into its acyl ethylene glycol, butylene glycol, tetraethylene chloride or a salt of its acyl chloride, such as the glycol, pentaethylene glycol; hexaethylene glycol hydrochloride, and reacting the same with the and still higher homologues; higher molecular stoichiometric equivalent of the higher molecular weight glycols such as cetene glycol and other weight carboxylic acid mono- of the glycol. vicinal glycols; 1,10 dihydroxyoctadecene; 1,10 The following examples are illustrative of a dihydroxyoctadecane, and the like. method which has been found suitable for pre The carboxylic acid acyl radicals represented paring the various compounds which are dis by closed herein. It will be appreciated that other O . O methods may be utilized, that the proportions of R-3- reacting ingredients, times of reaction, order of in the general formula may be derived from steps, and temperatures may be varied and that various sources. Among such sources may be supplementary processes of purification and the mentioned the straight chain and branched like may be resorted to wherever found desirable chain, Saturated and unsaturated, carboxylic, or convenient. These and other variations and | aliphatic (including cycloaliphatic), fatty, aro modifications will be evident to those skilled in matic, hydroaromatic, and araliphatic acids in the art in the light of the guiding principles cluding , , , which are disclosed herein: , pimelic acid, , capric Ecomple A 20 acid, sebacic acid, , , 22 grams of the acyl chloride of phenyl alanine , , , stearic hydrochloride and 29 grams of the acid, , ricinoleic acid, ricinelaidic acid, mono-ester of diethylene glycol were covered ricinostearolic acid, , linolenic acid, with and the resulting mixture Was lauric acid, , , mixtures heated in an oil bath at 75 degrees C. to 92 de of any two or more of the above mentioned acids grees C. for about one-half hour. Hydrochloric or other acids, mixed higher fatty acids derived acid gas was evolved continuously during the from animal or vegetable sources, for example, heating period. The reaction mixture was then lard, coconut oil, rapeseed oil, sesame oil, palm heated at 100 degrees C., under reduced pres kernel oil, palm oil, , corn oil, cotton sure, to remove the remaining hydrochloric acid. 30 Seed oil, Sardine oil, tallow, soya bean oil, peanut On cooling, the product Solidified. It was then oil, castor oil, seal oils, whale oil, shark oil and ground and washed with hexane and the Col other fish oils, partially or completely hydrogen lected precipitate was melted in an Oven at 100 ated animal and vegetable oils such as those men degrees C. to drive of the hexane. The yield tioned; oxidized hydroxy and alpha-hydroxy was 33 grams of a product having a melting 3. 5 higher carboxylic, aliphatic and fatty and/or point of 96 degrees C. to 97 degrees C., and polymerized triglyceride oils; acyloxy carboxylic which, after grinding, Was a hard, White Solid, acids such as C17H35-CO-O-CH2-COOH: soluble in Water and consisting essentially of the acids such as i-hydroxy , dihydroxy hydrochloride of the ester of phenyl alanine with palmitic acid, di-hydroxy-stearic acid, dihy the lauric acid mono-ester of diethylene glycol, 40 droxybehenic acid, alpha-hydroxy , said compound having the formula. alpha-hydroxy stearic acid, alpha-hydroxy palmitic acid, alpha-hydroxy lauric acid, alpha O hydroxy myristic acid, alpha-hydroxy coconut oil mixed fatty acids, alpha-hydroxy , {D-on-on-o-o-o-eirN.Cl 45 alpha-hydroxy arachidic acid, and the like; fatty Eaccomple B and similar acids derived from various waxes Such as , spermaceti, montan wax, coc 20 grams of the hydrochloride of alpha-amino cerin, and carnauba wax and higher molecular isobutyryl chloride are reacted with 30 grams of Weight carboxylic acids derived, by oxidation and the caprylic acid mono-ester of diethylene glycol other methods, from paraffin wax, petroleum and under the conditions described in Example A. Similar hydrocarbons; resinic and hydroaromatic The product comprises essentially the hydrochlo acids such as hexahydrobenzoic acid, naphthenic ride of the ester of alpha-amino isobutyric acid acid and abietic acid; araliphatic and aromatic with the caprylic acid mono-ester of diethylene acids Such as phthalic acid, benzoic acid, glycol, said compound having the formula: 5 5 Twitchell fatty acids, naphthoic acid, pyridine N.HCl carboxylic acid; hydroxy aromatic acids such as Salicyclic acid, hydroxy benzoic and naphthoic CH-C-O -CH-O-CH-0---c Hs acids, and the like. It will be understood that bH, mixtures of any two or more of said acids may It will be understood that the Substances may, 60 be employed if desired and it will also be ap-. for certain purposes, be employed in the form of preciated that said acids may contain substituent impure reaction mixtures containing substan groups such as sulphate, sulphonic, nitrile, tial proportions of the effective compounds. Cyanogen, carbonyl, amide, amine, halogen, Where the substances are used for bactericidal, ketone and other groups. The acids may be em germicidal and like purposes, however, purifica ployed as such or in the form of their anhydrides, tion procedures may be employed to produce pure esters including mono-, di-, tri-glycerides and or substantially pure products. Those versed in the like, and acyl halides, or, in general, in the the art are familiar with the types of purifica form of any of their acylating compounds. Of tion methods which may be employed with ad particular utility, where the final compounds are vantage herein, particularly in the light of the O used as antiseptics, bactericides, germicides and disclosures made hereinabove. the like, are the unsubstituted fatty acids con The glycols whose derivatives, as set forth taining from eight to fourteen carbon atoms and hereinabove, comprise the subject matter of the their acyl halides, lauric acid or its acyl halide present invention, may be selected from a large or coconut oil mixed fatty acids or their acyl group including, by way of illustration, ethylene s halides being especially satisfactory. 2,821,594 3. The amino-carboxylic acids which are or may Among the bacteria, the metabolism of which be utilized in the preparation of the substances is strongly inhibited by many of the compounds include, among those previously mentioned and of the present invention, are the following: others, alpha-amino acetic acid, alpha-amino Staphylococcus aureus, Staphylococcus' albus, propionic acid, alpha-amino butyric acid, beta Sarcina lutea, Micrococcals tetragenus, Bacili amino butyric acid, alpha-amino-n-, coli, Aerobacter aerogenes, Ps, pyocyaneus, alpha-amino isobutyric acid, alpha-amino iso Proteus vulgaris. Many of the substances are valeric acid, phenyl-alanine, tyrosine, trypto also effective against pneumococcus. In addi phane, cystine, arginine, amino poly-carboxylic tion, the phenol coefficients of many of the com acids such as amino succinic acid, amino glutaric 10 pounds are Substantially higher than that of acid, amino citric acid, amino malonic phenol. acid, amino adipic acid, amino Sebacic acid, and The term "higher,' as used herein and in the the like; the amino-carboxylic acids or mixtures claims to describe carboxylic and fatty acids and thereof obtained by the hydrolysis of proteins or the like, will be understood to mean at least eight protein-containing materials such as gluten, Soya. 5 carbon atoms unless otherwise specifically stated. bean flour and the like, whether by enzymatic Wherever the term "amino-carboxylic acid action, by acids or by an other means. Other esters' or like expression is employed in the amino-carboxylic acids include the Synthetic claims, it will be understood to cover the com polypeptides as well as those resulting from the pounds irrespective of whether they are neutral hydrolysis of proteins or protein-containing ma ized to form salts or are present as the free base. terials. Illustrative examples of such poly While the invention has been described in de peptides are glycl-glycine and leucyl-glycyl tail, it is to be understood that the scope thereof glycine, it will be understood that mixtures of is not to be limited other than is set forth in the any two or more of the foregoing or other amino claims. carboxylic acids may be utilized in the prepara What I claim as new and desire to protect tion of the substances of the present invention. by Letters Patent of the United States is: It will also be understood that any of these 1. Primary amino-carboxylic acid esters of amino-carboxylic acids may be esterified with higher molecular weight carboxylic acid mono any of the glycol esters disclosed hereinabove. esters of glycols. As indicated hereinabove, the compounds are : 2. Aliphatic primary amino-carboxylic acid best used in the form of Salts, preferably in the esters of higher molecular weight fatty acid form of substantially neutral salts or at a pH nono-esters of glycols. of about 6.7. The hydrochlorides are especially 3. Aliphatic primary alpha-amino-carboxylic satisfactory but other salts may be employed, in acid esters of higher molecular weight acid certain instances, such as the Sulphates, phos mono-esters of glycols. phates, nitrates, hydrobromides, hydriodides, 4. Aliphatic primary amino-carboxylic acid propionates, gluconates, Sulphoacetates, Sulpho esters of lauric acid mono-esters of glycols. succinates, lactates, tartrates, citrates, Salts of 5. Aliphatic primary amino-carboxylic acid amino-carboxylic acids, and the like. The free esters of higher molecular weight fatty acid esters of the amino-carboxylic acids generally 40 mono-esters of ethylene glycol. possess limited in water and, for that 6. Aliphatic primary amino-carboxylic acid reason, the esters are used in the form of their esters of higher molecular weight fatty acid salts, the salts possessing substantially greater mono-esters of diethylene glycol. water solubility. It is, however, within the 7. Salts of primary amino-carboxylic acid broaderscope of the invention to employ the free mono-esters of higher molecular weight car esters, using solvent media other than water or boxylic acid mono-esters of glycols. water alone, or by solubilizing the esters in any - 8. Inorganic acid salts of aliphatic primary desired Inanner. amino-carboxylic acid mono-esters of higher It will be understood that the numerous Com molecular weight fatty mono-esters of glycols. pounds disclosed herein will vary somewhat in 50 9. Hydrochlorides of aliphatic primary amino bactericidal, germicidal, bacteriostatic, anti carboxylic acid mono-esters of lauric acid mono septic and fungicidal power or potency and that esters of glycols. the effects will also vary depending upon the 10. Hydrochlorides of aliphatic primary alpha environment in which the compounds are used. amino-carboxylic acid mono-esters of higher The compounds are employed particularly in 5 5 molecular weight fatty mono-esters of ethylene dilute aqueous or modified aqueous solutions, glycol, usually on the order of 0.1% to several thou 11. Hydrochlorides of glycine mono-esters of sandths of 1%. They may be used internally higher molecular weight fatty mono-esters of or externally and either as such or in conjunc glycols. tion with other agents having bactericidal, 60 12. Alpha-amino isobutyric acid mono-esters germicidal, antiseptic or like action. Particular of higher molecular fatty acid mono-esters of ly satisfactory use is in connection with denti glycols. frices such as tooth powders, tooth pastes, liquid 13. Hydrochlorides of alpha-amino isobutyric dentifrices, and mouth washes. In such cases, acid mono-esters of higher molecular fatty acid the proportions of the salts of the esters may, if mono-esters of glycols, desired, be somewhat higher than those set forth 14. Hydrochlorides of alpha-amino isobutyric hereinabove. Their especial utility in dentifrices acid mono-esters of higher molecular fatty acid resides not only in the fact that they possess bac mono-esters of ethylene glycol. tericidal, germicidal, and similar properties but, . in addition, they are innocuous, non-toxic and 70 BENJAMINR, HARRIS. relatively tasteless.