Патент USA US2082459код для вставки
ratented June 1, 1937 UNITED STATES. PATENT’ OFFICE ' Joseph B. Nioaoi-rnr'ookiyn, N. v. No Drawing. Application Mai-oh 29, 1933. . Serial- No. 683,427 mm - (01260-110) This invention relates to a‘ method of produc I i " ' phenolic aliphatic acids by reacting‘v an urated aliphatic acid with a phenolic compound ing substituted aliphatic acids, and more particu larly to a method of producing phenolic aliphatic i in the presence of a kationoid} condensingagent, acids either by reacting an unsaturated ‘aliphatic. ' ~ _1Another ‘object of this invention is to produce _ 5 acid with a phenolin the presence of a kationoid "phenolic aliphatic'acids ‘by intramolecularrear- ' condensing agent or by intramolecular rearrange rangementiof a phenoxy aliphatic acid to'the ment of the isomeric vpher'ioxy aliphatic .acid; in vcorresponding isomeric‘ phen'olic aliphatic acid the presence of a kationoid catalyst. ' , _--in they presence of .a kationoid catalysti - ' I? " ‘ "v Hitherto it wasv not possible to produce vphenolic ~ A further object of _ this invention is the useof'. _ aliphatic acids by either of the ‘above -methods.-.'_ a. mixture or glacial ‘acetic ; acid.‘ and c'oncen-. 10 It has been found that'phenolic aliphaticlacids.‘ tratedsulfuric acid ‘as’ kationoidage'nt in which . 10 of the general formula ' . _ RcR."'HcR"-<xoma" are readily obtainedjeither . , a - __ ' _ -_ of‘ glacial acetic acid any-other .' 'may'beused.~ solvent for one or all ‘ of'the ' reacting ' ‘compounds -' ., an un-‘m Still another object of this invention consists saturated aliphatic acid .of thegeneral formula ,‘ ‘_ .' in the preparation of soaps containing a phenolic _ ‘group in their molecule which products . valuable pharmaceutical properties. ' with o. phenol in the presenceof a llationoid'. an: '. very' '. A‘ further object is the production of chaulv -. densing agent or by intra'molecular rearra'nge- ' . ment ofa phenoxy aliphatic acid oi." the general 7 \moogric; acid and its'ihomologues and substitution. 51.20 products containinggajphenolic group‘ in their > molecule-which ‘compounds have very remarkable _ - ' ' -. , , . . , I . , _ - in In thepresence thesev formulas of a kationoid R represents catalyst. hydrogen ' or '1a saturated or unsaturated acyclic oralicylic rad; ical which may contain one orfmore‘substituents such as a hydroxyl, carbonyl‘, 'carboxyli'sulfo- or therapeutical properties.‘ ‘another object of this ‘invention is‘ the use 1.‘ of_ Still the products obtained according to the above ‘described, methods "in _ pharmaceutical prepara '26...‘ i , tions, salves, ointments, creams and thelike, _ thereby including substances in these prepara tions which combine the phenolic characteristics . _ nitro- group or a halogen atom; ‘R'frepresents. .a carboxyl group, R" and R’" hydrogen or a sat; withf'those of the aliphatic acids and esters and 30 urated or unsaturated acyclic'or 'alicyclic radical. . which may contain one or more substituents such‘ so- theirder'ivatives within one and the same mole-' as a hydroxyl, carboxyl, carbonyli' Sl?fo- of _ nitro- group or a halogen atom. with. the above and other objects ‘in view, all -I-. ‘of which will'fully'appear in the following de-‘ ’ X represents or anyaother phenyl, arylnaphthyhtetrahydro'i radical ‘whichjmayfbez scription and claims; the present-invention will ‘ 35 03 Li naphthyl ,jl'i'ereinafter be more fully described in the fol substituted by any aryl, alkyl or 'aralkyl group}. .lowing examples;- ' . = _ _' unsubstituted or substituted by a mum-halogen‘, ' Example 1.'-'-Addition of oleic acid to meta-creed vor hydroxyl, carbonyl, carboxyl, azo, and sulfo. ' Equimolecularmixtures of oleic acid and meta group. 40 40 The terms “kationoid condensing agenti’land. ’ cresol are mixed under cooling with sulfuric acid. “kationoid catalyst” are used-herein audit! the The mixture is allowed to stand for several days until the entire mass has become viscous. The claims appended hereto in the sense of the recent] mass is‘then poured into cold water, washed until electronic postulations of Robert Robinson, com the sulfuric acid is removed, dissolved with alkali, ?ltered, reprecipitated with acid and ?nally dis 45 tilled in vacuo. The product obtained is of a tionen”, Verla'g Ferdinand Enke, Stuttgart, 1932,_ pleasant, thymol-like odor and shows the charac a pare for instance his book on “Versuch einer Elektronentheorie organisch-chemischer Reak especially page 16. Such agents are for instance substances possessing latent valences, such as 50 acids, metal atoms which are able to form co-v ordination systems with. water or ammonia, sulfur from sulfur trioxide; sulfuric ‘acid, acid sodium sul?te, atoms and free; radicals with incomplete electron 55 shells. ' ‘ _ Thus, one objectof this invention is produce teristics oi’ a fatty acid as well as of a phenol. Itsmelting point is about 37° C. In place of the m-cresol shown in this example phenol may be 50 used in which case the product is 10 (p-hydroxy phenyl) stearic acid. ' - _ Example 2.—_Addition of erucic acid to phenol" llquimoiecular amounts of crude acid and 55 a ' v phenol are dissolved in four times their amount Example 8.—Additioa of elaidic acid to pyro of glacial acetic acid.v Then the same amoimt aallol of concentrated sulfuric acid is added to make a Equimolecular amounts :of elaidic acid and sulfuric acid-acetic acid mixture in the propor pyrogallol are dissolved in glacial acetic acid and l 'tion of 1:4, and the mass is heated for several dry hydrochloric acid is introduced into thesolu hours to 120° C. Thereafter, the mixture is cooled tion while boiling under 're?ux. ‘After ‘several and diluted with water while cooling. The acid hours. the reaction product is isolated and puri is puri?ed as described in Example 1 by_dis-' ?ed according to Examples 1 and 2. solving in alkali. reprecipitation and vacuum 10 distillation or it is’ from alcohol. [sample Dee-Addition oluchaahsoocric acid to 10 . ‘mm 3-M%W. to Equimolecular amounts-of elaeoetearic acid . 4 t I 1 "Eauimolecular amounts of chaulmoogric told and guaiacol .are dimolved in glacial acetic acid and heated with zinc chloride imder re?ux. After 15, and phenol are dissolved in ten times their 1. several hours the reaction product is isolated 15 amount of glacial acetic acid and a current of dry. Y and to Examples 1 and 2. ofriclnole'ic acid to tetra hydrochloric acid‘ is introduced into the - temple The temperature is kept at about 100°’ water. 'Ricinoleic acid are 20 2° c. The mixture is then poured into water and the product is isolated and puri?ed according suspended in saturated aliphatic hydrocarbons, to the methods described in Examples 1 and-2. such as hexanesaand, after addition of concen trated sulfuric acid. is heated under reflux while The product obtained contains stillanother tin saturated group and can be‘ subjected to further" stirring vigorously. After several hours the re 25 reaction with phenol in a mixture of glacial acetic action is complete and the reaction product is acid and concentrated sulfuric acid according isolated by distillation with steam to remove the hexanes and puri?ed according to Examples 1 to Example 2. . Y ‘ until a viscous mass is obtained on dilution with Example L-Addition of sorbic acid to :cglenol 30 Sorbic acid and a mixture of xylenols are dis solved in glacial acetic acid and to this solution aluminum chloride is added. The resulting-mi» ture is then heated under a re?ux until'thelcon 35 densation is complete. The product is isolated and puri?ed as described in Examples 14' and 2.. Example say-seamen of chaulmoooric to and 2. _ Example 11.—Addition_of olein to salicylic acid Equimolecular ‘amounts'of olein and salicylic acidaredissolvedwhilecoolinginamixtureof - sulfuric acidand glacial acetic acid (proportion 1:5),_.then heated'gently for ‘several hours at ‘50' to 60° .C. 'lhe reaction product is isolated'and puri?ed in-the- manner described in the preceding -‘examples._- - ,.~ -- EmanipleJfL-dddi?o? oltcaetor oil to paaillin with twice its weight of castor oil is Equimolecular amounts of chaulmoogric acid ‘ 40 and phenol are dissolved in the same amount of dissolved in a mixture of equal parts of acetic concentrated sulfuric acid and care is taken‘ that the temperature does not exceed 80' C. .- After acid anhydride and acetic acid. To this concentrated sulfuric acid is added while vigorously. and keeping the- temperature allowing the mixture‘ to stand for several hours ' 24; to'_ 481 hours standing at at room temperature the condensation is co'm-.~ the reaction mixture is worked ‘5 pleted, the reaction mixture is'diluted with water while cooling and the reaction product is isolated ‘fupa'inqthemanner described in the preceding and puri?ed according to Examples 1 and 2. examplesr-f _ _‘ Example 6.-_Addition of the ethyl ester of had->1 j Erample>13.—iiddttion ol'tiuia oil was to phenol 50 nocarpic acid to resorcinol The ethyl ester of hydnocarpic acid is dissolved ' Tung oil‘ acid and a mixture of 'equimolecular in ?ve times its weight of glacial acetic acid. amounts offormaldehyde, dimolved in acetic acid, To this solution a mixture of the equimolecular ‘and phenol,‘ are heated with a mixture of glacial 55 amount of resorcinol in a mixture of glacial acetic acetic acid and concentrated sulfuric acid and after several hours precipitated by addition of acid and concentrated sulfuric acid in the pro water. The product obtained is a modi?ed portion of 5:1 is added while stirring vigorously. phenol-formaldehyde resin' with very valuable The mixture is then heated under re?ux for glopertitses whichlis soluble in various organic several hours and the reaction product isolated 00 and puri?ed according to the Examples 1 and 2. It is also possible to esterify the acids obtained _E'xample14.—y1teananm't of creamy stearlc u according to these examples with alcohols in the presence of sulfurb'acid, instead of starting with ' tom,» obtained from oleic tom 7 by the addition of :h'ydrobromic acid, is reacted 65 the esters. ' ' ' with pot?siumimeta-creeolaie. The latter is trample 7.—Addittlon of oleic acid to hydro heated at about 100° C(in a mixture of glacial‘ quinone . I ven Equimolecular amounts or oleic acid and hy . - : ' acetic acid and sulfuric acid (0:1) for several hours.’v Thereby a rearrangement takes place drcquinone are introduced gradually into fused ' ' yielding the 10-(2-hydroxy semethyl phenyl) 70 toluene sulfonic acid. The reaction mixturev is diluted with water after cooling, and extracted stearic ‘acid. This acid can also be obtained ac oordingto'hxample ,1. with ether. After evaporation of the ether, the‘ I " phem 15.--Ream1l0ement . in! chaulmoooric ofacid m oleic acid-hydroquinone condensation product is . i Example 75 puri?ed by vacuum distillation. _ The . salt of para-chlorophenol and I. 3 2,082,469 bromo chaulmoogric acid are reacted with each other to form para chlorophenoxy chaulmoogric acid which latter then is rearranged to the cor responding l-hydroxy-?-chlorophenyl chaul moogric acid by heating in glacial acetic acid in the presence of aluminum chloride. The reac tion mixture is worked up in the manner de scribed above. Example 16.—Rearmngement of thymoxy stearic 10 acid _ In a suspension of thymoxy stearic acid, ob tained from bromostearic acid and the sodium salt of thymol, in staurated petroleum hydrocar 15 bons, boiling between 100° and 120° C., a cur rent of dry hydrochloric acid is introduced while stirring vigorously and keeping the temperature at the boiling point of the solvent. After several hours the rearrangement is completed and the 20 reaction mixture is steam distilled in order to remove the petroleum hydrocarbons. The reac tion product may be puri?ed by recrystallization from alcohol. Although specific examples have been given, products of these acids may be employed, for in stance their halogeno, their sulfo, their hydroxy and the like derivatives. The high molecular oxi dation products of petroleum, petroleum wax, brown coal tar and the like which are easily ob tained by catalytic oxidation of the above men tioned raw materials and which possess very re markable disinfecting properties, which is in creased considerably by the combination with 10 the phenolic compounds, are also very useful. The temperature may vary from 0° to 150° C., according to the reactivity of the reactants. The heating may also be carried out under pressure. When sulfuric acid is used, its concentration is preferably 96%; however, monohydrate or any 15 other suitable concentration of the sulfuric acid may be employed. The duration of the reaction depends upon the temperature, the reactivity of the reactants and the kationoid agent selected and can be varied according to the requirements. The methods of isolating the reaction product and purifying them can be varied in accordance with the properties of the reactants and reaction products. These and other changes may be made tions may be made by.those skilled in the art in in the invention within the spirit and scope thereof. accordance with the principles set forth herein. Instead of glacial acetic acid, other liquids may above described methods may be used as such, only one of the'reactants while the other is merely suspended in the solution. 0r liquids 1. A method of producing phenolic aliphatic acids by reacting an unsaturated aliphatic acid 25 the invention is not limited thereto as modi?ca The compounds obtained according to the or in the form of their salts or esters as con be used as solvents for the reactants, such as sul stituents of soap preparations, especially phar furic acid itself, or the homologues of acetic 30 acid, such as propionic or butyric acid, or alkyl maceutical ones, shaving creams, tooth pastes sulfates or mixtures of solvents with each other and various other toilet preparations. Or they and with non-solvents, or other solvents which I may be used in the treatment of diseases, as for are not readily attacked by sulfuric acid such instance the products obtained from chaulmoo gric acid for the treatment of leprosy and the like. Q: Ll as saturated petroleum hydrocarbons, hexane What I claim as my invention is: and the like. The solvent may be a solvent for may be used which are not solvents for the re actants but in which the latter are merely sus pended in very finely comminuted form. Varia tions in the proportion of solvent to reactants and condensing or rearranging agent may also be made. Instead of sulfuric acid and the other mentioned kationoid agents, other compounds may also be used, such as for instance phosphoric acid, benzene sulfonic acids, boron tri?uoride, acid reacting salts,lsuch as acid. sodium sulfate, sodium monophosphate and the like, chlorosul with a phenol in the presence of a mixture of glacial acetic acid and concentrated sulfuric acid. 40 2. As a new product, '10(p-hydroxyphenyl) stearic acid. - 3. As a new product, hydroxy-phenyl dihydro chaulmoogric acid. 4. A method of producing saturated phenolic 45 organic acids containing a free phenolic hydroxyl group in the molecule, by condensing a phenol having an available reactive unsubstituted nu clear position, withan acid of the group consist ing of unsaturated aliphatic acids and singly un fonic acid, alkyi sulionic acids» and many other , 50 acid-reacting agents. A mixture of kationoid saturated alicyclic fatty acids, in the presence of a mixture of concentrated sulfuric acid and gla agents may be employed advantageously. Instead of the phenols mentioned, other phe; cial acetic acid. 5. A process for preparing hydroxyphenyl di nols, such as e. g. xylenols, naphthols, tetra hydronaphthois, hydroxy diphenyls.‘ or phenol derivatives, such as nitrophenols, chlorophenols, the sulfonic acids of these phenolic compounds, the esters of salicylic acid, such as the methyl and the phenyl ester, phenol ethers, phenol alde hydcs, such as salicyclic aldehyde, and many others may be reacted with the aliphatic acids. Instead of the unsaturated aliphatic acids mentioned, other acids. such as linoleic acid, or di~ and tribasic acids, such as muconlc acid, " citrnconic acid. may be added to the phenol, while their corresponding saturated acids may be hydro chaulmoogric acid which comprises con densing phenol with chaulmoogric acid in the presence of concentrated sulfuric acid. 6. A product prepared by the condensation of oleic acid with a phenol in the presence of a mixture of sulphuric acid and glacial acetic acid. 60 7. A saturated hydroxyphenyl carboxylic acid obtainable by condensing a phenol with an acid of the group consisting of unsaturated aliphatic acids and singly unsaturated alicyclic fatty acids in the presence of a mixture of concentrated sul furic acid and glacial acetic acid. used in combination with the phenol for the re arrangement reaction. Likewise the substitution _ _, ' JOSEPH B. NIEDERL.