Patented Mar. 16, 1948 2,438,091

UNITED STATES PATENT OFFICE 2,438,091 ASPARTICAC DSTERS AND TER PRE PABATON Kathryn L. Lynch, Stamford, Conn., assignor to American Cyanamid Company, New York, N. Y., a corporation of Maine No Drawing. Application September 6, 1943, Serial No. 50117 5 Claims, (C. 260-482) 2 This invention relates to N-substituted aspartic phobic properties sufficiently strong to Orient the acid esters and to their preparation. The inven molecule at an oil-water interface. In order that tion includes the new compounds themselves, the this condition may be met the total number of novel method by which they are prepared and carbon atoms in R2, R3 and R4 should be at least also compositions containing them. twelve. I have found that primary alkyl and primary The compounds vary in physical character from alkoxyalkyl amines may be caused to react with oily liquids to hard wax-like materials. The con certain maleic acid esters to be hereinafter de pounds are in general colorless but some are pale scribed to yield N-alkyl and N-alkoxyalkyl sub yellow to light brown in color. Those compounds stituted aspartic acid esters having the gen O of low molecular weight are soluble in water and eral formula: very readily soluble in aqueous solutions of acids. R. O. As the length of the substituent chains increases, however, the compounds become more difficultly soluble in water but may be dissolved in aqueous 5 acids, mineral spirits, alcohols, and other organic h k, ) Solvents. Although it would be expected in a reaction in in which R and R1 are members of the group con volving a maleic acid ester with a primary amine sisting of hydrogen and alkyl radicals of from 1 that the ester groups would be hydrolyzed with the to 3 carbon atoms, R2 and R3 are alkyl radicals of 20 formation of amides, I have found that by fol from 1 to 18 carbon atoms and R4 is a member of lowing the procedure to be described hereinafter the group consisting of alkyl and alkoxyalkyl rad the primary amine may be caused to react at the icals. The alkyl radicals, R2 and R3, may be in double bond of the maleic acid ester to form N terrupted, terminated or substituted with various substituted aspartic acid esters directly in sub types and kinds of substituent groups. 25 stantially quantitative yield. As a result of my . Many of the compounds of this class, particu studies of the reaction I have discovered that when larly those which have in the R2, R3 and R4 posi a primary amine is mixed with a maleic acid tions a long chain hydrophobe group and a short ester of the type described hereinafter a number chain group are cationically surface active in the of different reactions may occur simultaneously form of their acid salts and possess wetting, foam 30 at different rates depending upon the temperature ing and detergent properties. The hydrophobe of the reaction mass and the relative proportions group may be a long chain alkyl or alkoxyalkyl of the reactants. At temperatures within the group of about six or more carbon atoms and may range of 10-100° C. the principal reaction in be positioned at any of R2, R3 or R4 in the general volves the addition of the primary amine at the formula above. 35 double bond of the maleic acid ester with the Although the compounds of the present inven formation of N-substituted aspartic acid esters. tion may be used in the form of their acid salts A second and concurrent reaction involves the as surface active agents, they are of greatest conversion of unreacted maleic acid ester to the value as intermediates in the preparation of a corresponding fumaric acid ester. The third, a class of Superior Wetting agents and detergents 40 much slower reaction, involves the reaction of the described and claimed in my copending applica primary amine with the fumaric acid ester. A tion, Serial No. 501,851, filed September 10, 1943. fourth reaction involves the reaction of the as When used as intermediates in this process at partic acid ester with itself to form undesirable least one of the groupS R2, R3 or R4 should be a by-products such as diketo piperazine derivatives. hydrophobe alkyl or alkoxyalkyl radical having 5 This latter reaction occurs principally at ele four or more carbon atoms. Of course, One or two wated temperatures and upon heating the reac of the groups R2, R3 or R4 may be a short chain tion mixture for long periods of time. alkyl or alkoxyalkyl radical provided that the During the early stages of the reaction the addi requisite number of carbon atoms is present in the tion of the primary amine to the maleic acid ester molecule to give a portion thereof having hydro- 50 is rapid, an approximately 50% yield of diethyl 2,488,091 3 4. N-Octadecyl aspartate being obtained in 30 min perature of the reaction mixture. The reaction . utes upon reacting octadecyl amine with diethy mixture is then allowed to stand until the reaction maleate at 20° C. At higher temperatures the is substantially complete. Towards the end of the reaction proceeds even faster. The conversion of reaction period the reactants may be heated up the maleate ester to the fumarate ester is also to about 100° C. for a short time to hasten con fairly rapid during the early stages of the reac pletion of the reaction. As stated before, how tion. Since as stated before the reaction of the ever, use of high temperatures for extended pe primary amine with the fumarate ester is quite riods of time is to be avoided if a product of high slow, it will be scen that the evenual completion purity is to be obtained. of the reaction to form N-substituted aspartic O The maleic acid esters which may be employed acid esters depends to a considerable extent upon in the reaction described herein are those having - the amount of fumarate ester formed. As high the general formula: temperatures favor the conversion of the maleic acid ester to the fumaric acid ester more than they favor the reaction of the primary amine with 15 maleic acid ester it is desirable that the reaction be conducted at low temperatures, preferably less than about 50 C., in the early stages of the re in which R and R1 are members of the group action. This is desirable in order to secure the consisting of hydrogen and alkyl radicals of from formation of N-substituted aspartic acid esters 20 from the maleic acid ester in as high yields as 1 to 3 carbon atoms, R2 and R3 are alkyl radicals possible, while the maleic acid ester remains as of from 1 to 18 carbon atoms. The alkyl radicals, Such in the reaction mixture. After holding the R2 and Ra, may be interrupted, terminated or sub reaction mixture at relatively low temperatures stituted with various types and kinds of substit until the maleic acid ester has either reacted with 25 uent groupS. Specific examples of the maleic acid the primary amine or has been converted to the esters that may be employed in my invention are corresponding fumaric acid ester, the tempera diethyl maleate, diamyl maleate, dibutyl maleate, ture may be raised thereby allowing the reaction dicapryl maleate, di (methyl amyl) maleate, di of the primary amine and the fumaric acid ester (ethyl hexyl) maleate, di-n-hexyl maleate, di to proceed more rapidly with the formation of 30 decyl maleate, dioctyl ethyl maleate, di-hexyl N-Substituted aspartic acid esters. citraconate, dicapryl pyrocinchonate, di-ethyl Another important factor which enables me to itaconate, hexyl octyl maleate, diglycol maleate, obtain N-Substituted aspartates of high purity dicyclohexyl maleate, di (2 cyclohexyl ethyl) and in good yield relates to the proportions of maleate, and the like. reactants used. I have found that the use of 35 Primary alkyl and primary alkoxyalkyl amines more than the theoretical quantity of primary which may be employed in my process include alkyl or primary alkoxyalkyl amine necessary to those such as butyl amine, amyl amine, octyl react with the maleic acid esters at the double amine, dodecyl amine, Octadecyl amine, methoxy bond position results in the formation of amides propyl amine, ethoxypropyl amine, amoxypropyl through replacement of the ester groups. Ac 40 amine, dodecoxypropyl amine and others of sim cordingly I employ an equal molecular propor ilar character. tion of the maleic acid ester or a slight excess The invention will now be illustrated in greater thereof with each mole of primary amine. detail by means of the following specific examples. From the foregoing it will be seen that my new It should be understood that although these ex method comprises the steps of reacting a primary 45 amples may describe in detail some of the more alkyl amine or a primary alkoxyalkyl amine with specific features of the present invention they are at least a stoichiometric proportion of maleic given primarily by Way of illustration and the acid ester at temperatures not in excess of about invention in its broader aspects in not to be lim 100° C. Preferably I carry out the first phase of ited thereto. the reaction at temperatures not in excess of 50 EXAMPLE about 50° C. until substantially all of the maleic 145 g. (1 mol) dimethyl maleate was added acid ester has reacted with the primary amine to slowly with stirring to a solution of 265 g. (1 mol) yield the corresponding N-substituted aspartic of octadecyl amine in 500 cc. of tertiary butanol acid ester. I then allow the mixture to react at at 50° C. After standing at 28° C. for 10 hours temperatures not in excess of about 100° C. until 55 the formation of dimethyl N-Octadecyl aspartate substantially all of the primary amine has reacted was 91.2% complete. After standing 43 hours the With the fumarate ester formed from the maleic ester. This procedure avoids the formation of reaction was 94.5% complete and after 65 hours amides and all undesirable by-products which re was 96.2% complete. sult from side reactions when the reaction is at 60 EXAMPLE 2 tempted at high temperature. As a result I ob 900 g. (5 mols--5% excess) of diethyl maleate tain N-Substituted aspartic acid esters of excellent was added slowly with stirring to a solution of 1325 purity with yields as high as theoretical. g. (5 mols) of technical Octadecyl amine in 1500 The reaction may be carried out by simply mix cc. of tertiary butanol. After standing 17 hours ing a suitable primary alkyl or primary alkoxy 65 at room temperature the condensation was 91.2% alkyl amine With a maleic acid ester and allow ing the mixture to stand at room temperatures complete and after standing 50 hours it was 95.5% until reaction is complete. In most cases it is complete. desirable, however, to carry out the reaction with Reaction between diethylmaleate and octadecyl the reactants dissolved in a suitable solvent such to amine to form diethyl N-octadecyl aspartate as an alcohol, mineral spirits, toluene, ethers, was caused to take place at different temperatures dioxane, etc. Since the reaction is exothermic in and the course of the reaction followed by tak character, it is generally advisable to add one of ing samples of the reaction mixture from time to the reactants to the other slowly in Small pro time. The results of this series of experiments portions to prevent an excessive rise in the tem 75 are given in the following table. 2,488,091 5 6 ABLE EOKARE 8 Aspartate formation-percent completion To a solution of 38 g. (0.2 mol) of n-dodecyl

anine in 50 ml. of t-butanol was added 46 g. (0.2 mol) of dibutyl maleate and the mixture Temperature allowed to stand at room temperature. In sev 1 Hour l'Hours 3 Hours enty hours, the reaction was 95% complete, and in ninety hours, it was more than 99% complete. Percent Percent Percent 100------80 69 The t-butanol was removed by heating the reac 67 78 O tion mixture under reduced pressure until the 70.5 87 temperature of the residue rose to 90-100° C. 79.5 89 There was obtained 82 g., a 98% yield of dibutyl N-n-dodecylaspartate, a slightly yellow oil. From the above it will be seen that the reaction proceeds rapidly in the earlier stages but requires 5 EXAMPLE 9 a considerable period of time for completion even To a solution of 23 g (0.2 mol) of n-heptyl at the higher temperatures. At low temperatures, amine in 30 ml. of t-butanol was added 46 g. the reaction will go to approximately 98% of Com (0.2 mol) of dibutyl maleate and the mixture pletion if given sufficient time for reaction. allowed to stand at room temperature. The re EXAMPLE 3 20 action was more than 99% complete in seventy hours. The t-butanol was then removed by heat 50 g. of diglycol maleate was added to 66 g. ing under reduced pressure until the temperature of technical octadecyl amine dissolved in 250 cc. of the residual liquid rose to 90-100° C. There of tertiary butanol. The reaction mixture was was obtained 69 g, a 99% yield of dibutyl N-n- kept at 89.5 C. for 2% hours at the end of which heptylaspartate. time the formation of diglycol n-octadecyl as partate was 82.5% complete. The reaction mix EXAMPLEO ture was allowed to stand at 89.5° C. for 29.5 To a solution of 15 g. (0.2 mol) of n-butylamine hours and then at 25 C. for 48 hours at which in 30 ml. of t-butanol was added 68 g. (0.2 mol) time the reaction was 96% complete. The prod 30 of di-n-octyl maleate and the mixture allowed uct was an almost colorless pasty mass. to stand at room temperature. In seventy-two hours reaction had taken place to the extent of EXAMPLE 4 95% and was more than 99% complete in ninety 51.2 parts of diamyl maleate Was Stirred with hours. The t-butanol was then removed by heat 20.6 parts of ethoxypropyl amine at 26° C. The ing the solution under reduced pressure until the temperature of the reaction maSS rose to 47 C. temperature of the residue rose to 90-100° C. as the mixture was being stirred. Within i0 to The yield was 82 g., a 99% yield of theoretical of 5 ininutes diamyl N-ethoxypropyl asparate had di-n-Octyl N-n-butylaspartate. been formed to such an extent that the product was soluble in dilute hydrochloric acid to give a EXAMPLE 1. foaming and wetting solution. The product was To 34 g. (0.08 mol) of di-undecyl maleate was a colorless oil-like liquid. added 25 ml. of t-butanol solution containing 0.08 mol of methylamine and the mixture was EXAMPLE: 5 allowed to stand at room temperature. The re 20 parts by weight of diisopropyl maleate Was 43 action was more than 99% complete in sixty added slowly with stirring to 28 parts by weight Seven hours. The t-butanol was evaporated by of technical octadecyl amine dissolved in 39 parts heating under reduced pressure until the tem by Weight of tertiary butanol. The mixture Was perature of the residual liquid reached 110° C. allowed to stand at room temperature for 113 After cooling, the yellow oily liquid was filtered hours at the end of which time the formation of to remove a small amount of white solid which diisopropyl n-octadecyl aspartate was 95% COra separated. The yield was 30 g., a 82% yield of plete. di-undecyl N-methylaspartate. EKAPLE 6 EAAPLE 2 14.6 parts by weight of butyl amine was added 55 To 43 g. (0.2 mol) of n-tetradecylamine dis to 68 parts by weight of dioctyl maleate at 24 C. solved in 50 ml. of t-butanol was added 35 g. In less than 2 minutes the temperature of the (0.2 mol) of diethyl maleate and the Solution was reaction mass had risen to 64 C. A clear color allowed to stand at room temperature, the reac less oil was obtained which was slightly soluble tion was more than 99% complete in sixty-eight in dilute hydrochloric acid to give aqueous Solu 60 hours. The t-butanol was evaporated under re tions having wetting and foaming properties. duced pressure with heating until the tempera EAMPLE ture of the liquid residue rose to 90-100° C. There was obtained 77 g., a 98% yield of diethyl 57.6 g. (0.4 mol) of dimethyl maleate was dis N-n-tetradecylaspartate. solved in 150 cc. of ethanol. 51.6 g. (0.4 mol) of 65 octyl amine was then added to the Solution while EXAMPLE 3 keeping the temperature of the reaction mass be To a solution of 18 g. (0.2 mol) of y-methoxy low 49° C. by cooling. After allowing the mix propylamine in 300 ml, of t-butanol was added ture to stand at 28° C. for one hour dimethyl 57 g. (0.2 mol) of di-n-hexyl maleate and the fumarate separated from the liquid as a Solid. The 70 mixture allowed to stand at room temperature. mixture was filtered and 13 g. of dimethyl fu In seventy-two hours, the reaction was more than marate was obtained. The filtrate Containing 99% complete. The t-butanol was evaporated by dimethyl N-octyl aspartate was very soluble in heating under reduced pressure until the temper dilute hydrochloric acid solution to give a slightly ature of the residual liquid rose to 90-100° C. foaming and wetting solution. There was obtained 75 g., a 100% yield, of di-n- 9488,001 7 centrations whereas aqueous solutions of the hexyl N-methoxypropylaspartate, a slightly yel other compounds developed foam when shaken. low oily liquid. This is a continuation-in-part of my applica AMP 14 tion Serial No. 448,650, filed June 26, 1942, now To a solution of 50 g. (0.27 mol) of n-dodecyl abandoned. amine in 40 ml. of t-butanol was added 39 g. claim: (0.27 mol) of dimethyl maleate. The mixture 1. N-substituted aspartic acid esters having was allowed to stand at room temperature. The surface active properties said esters having the addition was found to be more than 99% con general formula: plete in sixty-nine hours. The t-butanol was 0. R O evaporated by heating under reduced pressure H---0-R, until the temperature of the liquid residue rose to 90-100° C. There was obtained 87 g., a 98% R-N-b-c-o-R. yield, of dimethyl N-n-dodecylaspartate. h k, s in which RandR are members of the group con EXAMPLE 15. sisting of hydrogen, and alkyl radicals having To 81 g (0.47 mol) of diethylmaleate was added 1 to 3 carbon atoms, Ra and R3 are alkyl radicals at once 148 m. of a t-butanoi Solution containing of from 1 to 8 carbon atoms and R4 is a member 0.47 mol of methylamine with cooling in a water of the group consisting of alkyl and alkoxyalkyl bath. There was a noticeable heat of reaction. 20 radicals, the total number of carbon atoms in The addition was 91% complete in one hour, and R2, R3 and R4 being at least twelve. in nineteen hours at room temperature, the addi 2. Dialkyl N-alkyl aspartates having surface tion was more than 99% complete. The t-butanol active properties said compounds having at least was evaporated under reduced pressure with heat 12 carbon atoms in the alkyl groups thereof. ing until the residue reached a temperature of 25 3. Dialkyl N-alkoxyalkyl aspartates having sur 100-110° C. There was obtained 93 g., a 98% face active properties said compound having at yield, of diethyl N-methylaspartate. least 12 carbon atoms in the alkyl groups thereof. The surface active characteristics of the prod 4. A method of preparing dialkyl esters of N ucts of the last five examples are given in the Substituted aspartic acid which comprises mixing table below in terms of their wetting power as Substantially equal molecular quantities of a pri measured by the standard Draves test. The wet mary amine of the group consisting of primary ting power is expressed as the number of seconds alkyl amines containing at least 4 carbon atoms required for a 5.5 g. gray cotton skein attached and primary alkoxyalkyl amines containing at to a 1.5 g. hook to sink in a designated concen least 4 carbon atoms with a dialkyl ester of maleic tration of the surface active agent in water. The 35 acid, allowing the mixture to react at tempera tures not in excess of about 50 C. until substan compounds were tested in the form of their hy tially all of the maleic acid present has reacted drochloride salt. with the primary amine, and then heating the Wetting time, in seconds mixture attemperatures of 50-100° C. to complete the reaction between the remaining primary Concentration of Solution annine and the fumarate ester formed from the maleic ester. 5. A method of preparing dialkyl esters of N Substituted aspartic acid which comprises mixing substantially equal molecular quantities of a pri Diethyl N-methylaspartate------Diethyl N-tetradecy aspartate----- mary alkyl amine containing 4 to 18 carbon atoms Dinnethyl N-dodecy aspartate----- and a dialkyl ester of maleic acid, allowing the Di-D-hexyl N-methoxypropyl as mixture to react at temperatures not in excess of about 50 C. until substantially all of the maleic acid ester present has reacted with the primary As will be seen from the above results the con amine and then heating the mixture at tempera pound diethyl N-methyl aspartate has no Wetting tures of 50-100 C. to complete the reaction be power whatever. The reason being that it has no tween the remaining primary amine and the hydrophobe groups as do the other compounds 55 fumarate ester formed from the maleic ester. shown above. As stated before the compounds KAERYN . NCB. must have a total of at least 12 carbon atoms in the groups R2, R3 and R4, if they are to have sure REFERENCES CITED face active properties. The following references are of record in the The last four compounds in the table, that is fle of this patent: the products of Examples 1 to 14, inclusive, also UNITED STATES PATENTS showed a remarkable lowering of the surface ten sion of water when dissolved therein. As meas Number Name Date ured by the Du Nuoy tensioneter at 30 C., these 2,017,537 Hoffmann ------Oct. 15, 1935 four compounds at a concentration of 0.5% low 2,200,220 Reppe ------May 7, 1940 ered the surface tension of distilled water from 7 2,317,378 Harris ------Apr. 27, 1943 dynes per centimeter to an average of about 34 2,324,712 Lynch ------July 20, 1943 dynes whereas diethyl N-methyl aspartate had OTHER REFERENCES no appreciable effect on the surface tension at the same concentration. This latter compound Korner and Menozzi: "Gazetta Chinica Ital also failed to give foaming solutions at all cons 70 iana' vol. 19, pages 422, 426, 431 (1889).