US3001997A

US3001997A - Carboxylic acid amides of n-aminoalkylene-heterocyclic amines

Info

Publication number: US3001997A
Application number: US20258A
Authority: US
Inventors: Hans S Mannheimer
Original assignee: JOHN J MCCABE JR
Current assignee: JOHN J MCCABE JR
Priority date: 1960-04-06
Filing date: 1960-04-06
Publication date: 1961-09-26
Anticipated expiration: 1978-09-26

Description

Uite

This invention relates to novel'compounds and to methods for preparing them. In one of its more specific aspects the invention is directed to a class of novel surface active agents which are acyl ('RCO') derivatives of heterocyclic polyamines, with said ,acyl radical in each of such derivatives having replaced a hydrogen of an amine group of the polyamine' employed and said surface active agents being finther characterized by having at least one R -COOM group (hereinafter defined) attached directly to another amine nitrogen of said polyamine employed.

Said novel surface active agents have been found useful because they have good detergent, foaming, wetting, emulgating, emulsifying, dispersing, bacteriastatic, bacteriacidal, fungicidal, and deodorizing characteristics. They are highly water-soluble, stable in aqueous solutions in the pH range of 1-14 and are not precipitated out of solution by the salts normally present in hard Water. They are non-vesicant and non-toxic to human and animal life. They serve as excellent synthetic detergents, softeners and dye assistants in the textile and related fields. They may also be employed as therapeutic States 1 Patent agents because they possess germicidal and fungicidal qualities.

They find application in the pharmaceutical field because they appear to be compatible with many pharmaceutical agents of similar ring structures. Moreover they are compatible with anionic as well as cationic compounds because of their amphoteric structure, and are compatible with anionic and cationic compounds having such ring structures similar to those of said amphoterics. It has generally been known that non-ionic surface agents,

although compatible with cationic agents, usually dirninsimilar to the ring structures of the novel compounds of this invention, good compatibility and possibly even enhancement of said pharmaceutical agents should be expected by combining said novel compounds therewith.

The compounds of the present invention are especially useful as surface active agents in the pharmaceutical field, such as in ointments, salves, sprays and oral preparations in which surface active agents are desirable.

The novel amphoteric compounds of this invention are partially or completely saturated and/or unsubstituted or OH, alkyl and/or hydroxy alkyl substituted amino alkyl morpholine, amino alkyl piperidine, amino alkyl pyrrole, pyrrolamine, polyamino pyridine, amino pyridine, amino alkyl pyrroline, amino alkyl pyrrolidine, pyridyl alkyl amine, piperazine and amino alkyl piperazine which have been acylated, that is an RCO radical of 5-19 carbon atoms is attached directly to an amine nitrogen thereof and at least one -R -COOM radical is attached to another amine nitrogen thereof, R and M being hereinafter described.

Said novel water-soluble, surface active, amphoteric 3,001,997 Patented Sept. 26, 1961 a 2 7 compounds may be broadly represented by the following structural formula:

R-r-CO-W in which w either of the following radicalsz 16) caloni nl oooM (12) said radicals (1)-( ll) having one or more of the hydrogens of the hydrocarbon groups in the rings thereof being substituted or replaced by one or more hydroxy and/ or alkyl radicals of 14 carbon atoms and/or alkylol radicals of 1-4 carbon atoms, and any of the foregoing in which the rings thereof are unsaturated and unsubstituted or substituted as aforesaid, but being partially or completely saturated with hydrogen: in which R is an organic radical, which, if connected to a carboxyl group, provides a monocarboxylic acid, and said radical contains at least 4 carbon atoms and is a hydrocarbon radical of 4-48 carbon atoms; R; is hydrogen or an alkyl hydrocarbon radical having 1-4 carbon atoms, such as CH --C H -C H and --C H R is a hydrocarbon group having 1-4 carbon atoms, such as -CH -C H C H and --C H or any one of the aforesaid groups, but of 2-4 carbon atoms, one or more of whose hydrogens has been hydroxy substituted, illustrative examples of which are -CH CHOHCH CH CHOH CHOHCH or any one of said groups, but of 3-4 carbon atoms and whose hydrogens have been either unsustituted or hydroxy substituted and having a single ether (-O--) oxygen linkage therein (by the terms ether group having a single oxygen linkage therein and being alkylene or hydroxy alkylene as used, I mean that the ether group contains a single oxygen therein and otherwise, the group is alkylene or hydroxy alkylene); R is an alkyl group of 1-4 carbon atoms; B is either hydrogen or R -COOM and M is either an alkali metal or hydrogen.

One of the methods which may be employed to produce said novel amphoteric compounds is to react a polyamine with an organic monocarboxylic acid in the molecular proportion of 1 to 1 thereby to acylate, whereby the RCO- group of the R-COOH is substituted for the hydrogen attached to the nitrogen of one of the amine groups of the polyamine employed. When approximately 1 mole proportion of water of reaction has been formed and the acid number of the mass is about zero, the reaction is terminated and the resulting reaction mass is reacted with one or more of various compounds to provide the novel amphoterics of this invention.

The organic acid reacted with a polyamine is one containing a single COOH group or any of the available anhydrides of said acids and by the term monocarboxylic organic acid as used herein, I mean to include both the acid and the anhydride thereof which I regard as the equivalent of the acid. These acids may be: the aliphatic open chain saturated or unsaturated fatty acids as well as said fatty acids containing other substituents, such as aryl radicals, as for example, acids of the type of Twitchell fatty acids, cycloaliphatic carboxylic acids preferably containing no more than 4 condensed nuclei and examples of which are hexahydrobenzoic, resinic, and naphthenic acids.

While carboxylic acids having any number of carbon atoms may be employed, I prefer to employ those having at least 5 carbon atoms and preferably 5-19 carbon atoms in straight chain relationship. The acids which I employ may be derived from a number of difierent sources. Among some of them are the acid components chosen from oil or fats of animal, marine or vegetable origin and these include; the acids of cocoanut, palm kernel and palm oil, also from soy bean, linseed olive, rapeseed, cottonseed, peanut and castor oil which contain large proportions of unsaturated hydroxy fatty acids and also the acids derived from tallow, fish and seal oils, whale or shark oils and the hydrogenated acids from these sources. Moreover, the synthetic high molecular weight fatty acids, obtained by the oxidation of paraflin wax and similar high molecular weight hydrocarbons by means of gaseous oxidizing agents may be employed. In addition the acid may be one of the resinic acids, such as abietic acid, or the naphthenic acids and long chain fatty acids having an aromatic hydrocarbon radical connected directly with the aliphatic chain (Twitchell fatty acids) as are obtainable from oleic, ricinoleic linoleic and similar unsaturated fatty acids. Instead of employing mixture of acids from oil, fats and resins, single acids may be used,

- for example, caproic,=myristic, heptylic, caprylic, undecylic, lauric, palmitic, stearic, behenic, arachic, cerotic, oleic, erucic, linoleic, linolenic, ricinoleic and hydrOXY- stearic acids.

Examples of some of the specific polyamines which may be employed in the practice of this invention are:

Amino ethyl morpholine CHI-CHI N HrCzH4N O C HnC E1 Amino ethyl pip eridine 0 HPO H2 N Hr-C :Hr-N C H;

o H,--o Amino ethyl pyrrole CH=O H z- C aH4N Pyyrolamine GH-O H Diamino pyridine NE, Amino pyridine I Q Amino ethyl pyrroline o Er -0H,

NHr-C ZHA-N C H: C H

Amino ethyl pyrrolidine tr- C zHr-N Pyridyl ethylidene amine NHa- C H Pip erazine o H,- o H,

HN NH C H 2"0 H2 Amino ethyl piperazine NH -O lL-N Diethylol amino pyridine CzH OH Amino ethyl hydroxy hydroxy-methyl pyridine Ethyl amino pyridine The foregoing specific amines are respectively reactants A-O.

Other examples of specific amines which may be employed in the practice of this invention are said reactants A-O which have had one or more of the hydrogens of the hydrocarbon groups in the rings thereof substituted with one or more hydroxy, alkyl and/or alkyl groups, and also any of such reactants either so substituted or unsubstituted and having an unsaturated ring, being partially or completely saturated with hydrogen. Said hydrogenation may be effected by treating the compound with hydrogen in the presence of platinum or in any other manner known to the art and the hydroxylation, alkylation and alkylolation also may be efiected in any manner known to the art. For example, the alkylation may be achieved by the use of an alkyl iodide with carbon as a catalyst. Also the various amino alkyl derivatives, some examples of which are reactants A-C, G, H and K may be prepared by reacting morpholine, piperidine, pyrrole, pyrroline, etc. with alkylene oxide, such as ethylene oxide, for example, and ammonia, and of course in like manner the amino alkyl derivatives of the hydrogenated or unhydrogenated and/or alkyl and/or alkylol derivatives of the various other reactants may be prepared. When R is hydrocarbon, such compounds in which R is hydrogen may be reacted with an alkyl chloride, such as ethyl chloride for example, and treated with NaOH thereby to substitute a hydrocarbon group for said nitrogen or if desired such compounds may be reacted with R OH, where R is hydrocarbon, under pressure for that purpose.

Among some of the salts of the halo acids which may be employed are the sodium and potassium salts of monochloracetic acid, monochlorpropionic acid, monochlorlactic acid, monochlorhydroxyacetic acid obtainable from di-chloracetic acid, monochloracetoacetic acid, monochlorethoxyacetic acid, etc.

One of the general types of method which may be employed for the production of some of the compounds of the present invention consists in first reacting one mol of a monocarboxylic acid (R-COOH) having at least 4 carbon atoms in its radical connected to its COOH group with one mol of one of said polyamines, some examples of which are reactants A-O, until only approximately 1 mol of water has been removed thereby to replace a hydrogen of an amine group with RCO- of the acid. In carrying out this reaction the mixture is first heated to about 1l0180 C. in vacuum of -430 mm. of mercury pressure until one mol of water of reaction has been produced and removed. (All of the terms mm. and mm. pressure as used in this entire description are intended to mean mm. of mercury pressure.) The reaction mass is then allowed to cool to room temperature and consists essentially of an acylated (RCO) polyamine used.

This reaction product in turn is reacted with one of said monohalomonocarboxylic acids in the presence of caustic soda in aqueous solution. In one of its preferred forms one mole of said reaction mass is added to an aqueous solution containing for each amine nitrogen therein one mole of the monohalomonocarboxylic and 2 moles of caustic soda, which solution prior to the addition has been prepared and maintained at a temperature no greater than 20 C. The mix is heated to a temperature of C. until the pH has been reduced from about 13 to 8-8.5 and there is no further change in pH upon continued heating at said temperature. The resultant reaction product is of the general formula:

The following are specific examples of some of the novel amphoteric surface active agents of the present invention'given by way of illustration and not limitation, and methods for preparing them, all parts being given by weight unless otherwise specified.

Example 1 1 mole, 200 parts of lauric acid and 1 mole, 131 parts of amino ethyl morpholine are placed in a reacting vessel and are heated sufliciently to melt the lauric acid whereupon an agitator located therein is started and mixes and maintains these components in mixed condition. While being constantly agitated the mix is heated under vacuum of about mm. pressure for about 3 hours While gradually raising the temperature to'about C. During this period 18 parts'of water have been formed and distilled oil, leaving behind a reaction mass having an acid number of approximately zero. Then this reaction mass containing about 1 mole, 313 parts of acylated amino ethyl morpholine is allowed to cool to room temperature and the entire mass is added to ,a previously prepared solution produced by adding 96 parts of mouochloracetic acid and 80 parts of caustic soda to 300 parts of Water. This solution was prepared and maintained at a temperature below 20 C. before the addition of said reaction mass. This mixture is heated to 95 C. and maintained at this temperature for 2 hours. During this period the pH of the mix is reduced from approximately 13 to 8-8.5. At the end of this period the pH ofthis mass is no longer subject to change by continued heating at said temperature and a sample ofthe resulting product is water soluble to a sparkling clear solution. At the end of this period the .mass consists chiefly of a water solution of one of my novelproducts having the following formula and known as Product. 1:

CHz-CH HzOO ONa Example 2 propionic acid and 80 parts of caustic soda in 300 parts of water prepared and maintained below 20 C. The resulting mixture is then heated under the same conditions as outlined in Example 1 until the resulting product forms sparkling. clear aqueous solutions and is no longer subject to pH change in continued heating. At the end of this period the mass consists chiefly of an aqueous solution of one of my novel products, hereinafter known as Product 2, and having the formula:

Example 3 1 mole, 282 parts of linseed fatty acid and 1 mole, 129 parts of amino ethyl piperazine are condensed in the manner as described in Example 1. The entire reaction mass containing about '1 mole, 391 parts of the acyl derivative of said amine is subsequently processed in the same manner as that set forth in Example 1 except for the 1 mole of monochloracetic acid there is employed 3 moles, 369 parts of monochlorlactic acid and the amounts of caustic and water are increased to 240 and 900 parts respectively. The resulting mass is an aqueous solution of another novel product, known as Product 3, and of the following general formula:

GHz-OHOH-C O ONa 1 mole, 116 parts of caproic acid and 1 mole, 112 parts of amino ethyl pyrroline are condensed in the manner as described in Example 1. The entire reaction mass containing about 1 mole, 210 parts of the acylated derivative of said diamine is then processed in the same manner as that set forth in Example 1, except that for the 1 mole of monochloracetic acid, there is employed 1 mole, 139 parts of monochlorethoxyacetic acid. The resulting mass is an aqueous solution of a novel product, Product 4, and of the following formula:

Example 5 1 mole, 284 parts of stearic acid and 1 mole, 114 parts of amino ethyl pyrrolidine are condensed in the manner described in Example 1. The entire reaction mass containing about 1 mole, 381 parts of said acylated diarnine is then added to a solution prepared by adding 1 mole, 40 parts of caustic soda and 1 mole, 124 parts of ethylene chlorhydrin in water maintained at 5-10 C. After the addition at said low temperature, the mass is continuously agitated and while in such state, the temperature thereof is increased over about a one-hour period to about 95 C. and then maintained at 95 C. for three hours, all of the aforesaid being done under a reflux condenser. During said four hours, the pH of the mass decreases. At the end of said four hours the mass is cooled to room temperature and then processed in the same manner as that of Example 1 except that for the 1 mole of monochloracetic acid, there is substituted 1 mole of lactie acid. The resulting mass in an aqueous solution of novel product, Product 5, of the following formula:

Example 6-14 I1ICO-O11H23 /OHz-OOONa an 7. C Hr-C 0 ONE CH=CH onus-o o-nhn 8. C Hr-C 0 ON a CH: CH= BH CuHaa-C O-NHC:H4

41H: hHl

9. CHr-COONa H H-CH:

HN-CO-CuHn 10. CHr-GH,

CuHzr-C O-N N-CHr-C 0 DNA CHr-C 5 11. CH -CH] CnHgr-C O-NH-CzHt-N N-CHg-C O 0 N8 OHr-C g OH CuHas-C O-NH NCH:-COON8 13. CHzOH OH 0 me-c o-nn N H CHI-C 0 ONE.

CHEW C O N CHr-COOND Example 15 1 mole of Product 7 is further reacted with 1 mole of chloracetic acid and 2 moles of caustic soda in waterin the manner of Example 1 to produce, Product 15, of the following formula:

GHQ-000m CH=CH NaOOO-HzG-N OH oH=o C11H23CONH Example 16 1 mole of Product 10 is reacted with 1 mole of monochloracetic acid and 2 moles of caustic soda in water in the manner of Example 1 to provide Product 16 of the following formula:

CHz-CH: CHr-COONa N-OH GHQ-CH2 lHz-COONB Example 17 1 mole of Product 11 is reacted with 2 moles of monochloracetic acid and 4 moles of caustic soda in water in the manner of Example 1 to provide Product 17 of the following formula:

OH CHr-C O ONa 2 OHz-C O ONa t iHr-C O ONa Examples 180n Various other polyamines, similar to those employed in the foregoing examples wherein the R group is C H or C H instead of C H and/ or the R thereof may be CH or C H instead of hydrogen for example to provide still other specific novel reaction products the same as those herein set forth except for the foregoing changes.

For example, instead of the polyamine reactants of Examples 1-5, 7, and 11 there may be substituted therefore the following respective specific reactants: ethyl amino propyl morpholine, methyl amino ethyl piper-idine, butyl amino ethyl piperazine, ethyl amino ethyl pyrroline, ethyl amino propyl pyrrolidine, ethyl amino pyrrolamine, ethyl amino ethyl piperazine. Also instead of the polyamine reactant used in Example 1, there may be substituted therefor amino ethyl hydroxy-morpholine, amino ethyl methyl-morpholine or amino ethyl ethylol-morpholine whereby there are produced amphoterics the same as Product 1, except that they respectively have an OH, CH and C H OH substituents connected to the carbon atoms in the ring thereof. Also for the amino ethyl piperidine of Example 2, there may be substituted as the polyamine reactant therein a compound the same as that specific reactant except that the ring thereof has the ethylol, methyl or hydroxy substituents in the same positions as those in the polyamine reactants of Examples 13 and 14 thereby to provide amphoterics of such substituted piperidines, the same of Product 2 except for the presence of said substituents. Also for thepyrrolamine of Example 7 there may be substituted therein any of the following as the polyamine reactant, namely amino hydroxy-pyn'ole or amino ethylol-pyrrole thereby to provide compounds the same as Product 7 except that one of the hydrogens of the hydrocarbon groups in the ring thereof is substituted by an OH or a C H OH radical. There may be used polyamines the same as those used in Examples 4 and 5 except that a hydrogen of a hydrocarbon group in the ring is substituted by an hydroxy, ethylol or ethyl radical whereby there are produced novel compounds the same as those of said examples except that the ring of each has an 0H, C H OH or C H substituent for ,a

hydrogen of a hydrocarbongroup in the ring thereof.

It is to be understood that all of the foregoing examples are given by Way of illustration and not limitation, also that instead of Na, potassium may be substituted therefore, and in fact hydrogen may be substituted therefore, the alkali metal being replaced thereby under acidic conditions.

Besides serving the purposes hereinbefore set forth all of the various compounds herein may be reacted with a detergent sulfonic acid salt or sulfate salt examples of which are embodied in my U.S. Patent 2,781,349 of February 12, 1957 and in my copending U.S. application 638,904 of February 8, 1957 and inthe manner therein set forth to provide corresponding sulfonic and sulfate salts. 'I'hisrap'plicationis a continuation-in-part of said application 638,904.

I claim:

1. A compound of the following formula:

Rs-COOM Rr-COOM OH=CH RiCOOM GET-CH \RPCOOM lkr-COOM (12) said (1)-(11) respectively in which at least one of the hydrogens in the hydrocarbon portions of the rings thereof are substituted by a member selected from the group consisting of hydroxy, alkyl, and hydroxy alkyl, with said alkyl and hydroxy alkyl radicals being of 1-4 carbon atoms; in which R is hydrocarbon of 4-18 carbon atoms, R; is selected from the group consisting of hydrogen and alkyl radicals of 1-4 carbon atom-s, R is an alkylene group of 2-4 carbon atoms, R is selected from the group consisting of alkylene groups of 1-4 carbon atoms, hydroxy alkylene groups of 2-4 carbon atoms,

ether groups, each of said ether groups having a single oxygen linkage and being alkylene of 3-4 carbon atoms, ether groups, each of said mentioned ether groups having a single oxygen linkage therein and being hydroxy alkylene of 3-4 carbon atoms; B is selected from the group consisting of hydrogen and R CO0M, M is selected from the group consisting of hydrogen and alkali metals, m is selected from the group consisting of zero and one.

2. A compound of the following formula:

in which R is hydrocarbon of 4-18 carbon atoms.

3. A compound of the following formula:

in which R is hydrocarbon of 4-18 carbon atoms. 4. A compound of the following formula:

/N CHzGOONa in which R is hydrocarbon of 4-18 carbon atoms.

No references cited.

Claims

1. A COMPOUND OF THE FOLLOWING FORMULA:

2. A COMPOUND OF THE FOLLOWING FORMULA