United States Patent Office 2,357,283

Patented Sept. 5, 1944 2,357,283 UNITED STATES PATENT OFFICE 2,357,283. PROCESS FOR THE PRODUCTION OF NALKYLOLAM DES Franklin Traviss Peters, Wilmington, Del, as signor to E. E. du Pont de Nemours & Company, Wilmington, Dei., a corporation of Delaware No Drawing. Application June 2, 1942, Serial No. 445,485 18 Claims. (C. 260-56) This invention relates to improvements in the Although the reaction of alkylene oxides with manufacture of N-alkylolamides, and particu carboxylic acid amides containing at least one larly to the manufacture of N-alkylolamides of amido-hydrogen atom may be carried out under the lower aliphatic acids. elevated or reduced pressures, it is generally pre It is an object of this invention to prepare N 5 ferred to conduct the reaction under normal at alkylolamides of lower aliphatic carboxylic acids. mospheric pressure, since a suitable reaction rate Another object is to prepare lower aliphatic amides is obtained and equipment is thereby simplified. substituted in the N- position by an alkylol group, As hereinbefore stated, this invention contem Without the intermediate use of an amine. A plates the reaction of alkylene oxides with car further object is to prepare N (beta-hydroxyethyl) O boxylic acid amides containing at least one amido amides of formic acid. Yet another object is to hydrogen atom. Suitable alkylene Oxides for re prepare N(beta-hydroxyethyl) formamides by a action include ethylene oxide, propylene oxide, catalytic process. A still further object is to butylene oxide and similar epihydrins contain accomplish a general advance in the art, ing the epoxide linkage, such as glycidol. Ethyl These and other objects hereinafter apparent 5 ene oxide constitutes a preferred alkylene oxide are accomplished according to this invention for use in this invention, and its employment which provides a process for the production of will hereinafter be detailed at greater length. N-alkylolamides Wherein a carboxylic acid amide However, any epihydrin capable of reacting with containing at least one amido-hydrogen atom is an amido-hydrogen atom is within the purview Subjected to reaction with an alkylene oxide. 20 of this invention. A. Preferably, the alkylene oxide is employed in By the expression “carboxylic acid amides con an amount not greater than about that which is taining at least one amido-hydrogen atom,' is chemically equivalent to the amido-hydrogen intended such organic chemical substances as atoms, since it has been found that undesired contain the structural nucleus formation of by-products is thereby suppressed. 2 5 O In one preferred embodiment, the present in Vention comprises admixing an alkylene oxide C-N-E . With a formanide containing at least one amido that is, a hydrogen atom is directly bonded to hydrogen atom, and subjecting the resulting mix a nitrogen atom, which is in turn directly bonded ture to reaction to produce an N-alkylol form 30 to a carbonyl group. amide. Although any carboxylic acid amide contain It has been discovered that when an alkylene ing at east one amido-hydrogen aton may be -oxide is reacted with a carboxylic acid amide at reacted in accordance With this invention, a pre a temperature below that at Which substantial ferred class of carboxylic acid amides comprises formation of polyglycol derivatives takes place, 35 those carboxylic acid amides containing at least extremely high yields of N-alkylol amides, ap One amido-hydrogen aton and Which are derived proaching quantitative proportions, are readily from carboxylic acids of not more than four attained. In general a reaction temperature not carbon atoms. Examples of suitable amides are higher than about 80 C. has been found suit the amides of formic, acetic, glycollic, propionic, able for the production of N-alkylol amides in 40 crotonic, lactic, butyric, isobutyric, and hydroxy the practice of this invention. . On the other isobutyric acids and their mono-N-substitution hand, a reaction temperature sufficiently high to products, such as the N-methyl-, N-ethyl-, N secure a rapid production of N-alkylolamides is propyl-, N-hydroxyethyl-, N-hydroxypropyl-, N usually preferred in the hereindescribed reaction, methoxyethyl-, N-phenoxyethyl-, and N-meth since it has been found that greatly lowering the 45 Oxymethoxyethyl- Substitution products of the reaction temperature retards the chemical reac foregoing amides, as well as other, N-alkyl-, N tion rate to an undesired extent. A temperature aryl-, N-aroyl-, N-hydroxyalkyl- and N-alkoxy of at least about 35° C. provides a practical re alkyl- monosubstitution products thereof, pro action rate in the present invention. Preferably, Wided that the amides contain at least One amido a temperature in the more restricted range of 50 hydrogen atom. Of the preferred class of amides between about 50° C. and about 75° C. is main containing at least one amido-hydrogen atom and tained during the reaction of alkylene oxides derived from a carboxylic acid of not more than with carboxylic acid amides containing at least four carbon atoms, formamide is an outstanding one amido-hydrogen atom in accordance with example, and it has been demonstrated to possess this intertion. w 55 peculiarly advantageous properties, described be 2 2,357,283 low, for reaction with alkylene oxides in the prac is dissolved and simultaneously reacted with the tice of this invention. Formamide is unique in amide or amide-solvent mixture until hydrogen that it reacts rapidly and substantially quanti is no longer evolved. The resulting mixture Con tatively with alkylene oxides, especially ethylene tains alkali metal-amide reaction product which oxide, to produce N-alkylol formamides, such serves as the active catalyst. When an alcohol as N (beta-hydroxyethyl) formanide and N is used as a solvent, Some alkali alcoholate may bis (beta-hydroxyethyl) formamide, the said re be formed. action. With formanide requiring no extraneous After hydrogen evolution has ceased, the al solvent. kylene oxide is passed into the amide-catalyst In the reaction of alkylene oxides with amides 0 solvent mixture above obtained at Such a rate containing at least One amido-hydrogen atom, it that the exothermic heat of reaction maintains has been found that the alkali metals, such as the desired reaction temperature, cooling means Sodium, potassium, and lithium, act as catalysts being employed if necessary. When the reac for the reaction. The alkali catalyst is prefer tion is completed, the alkali metal catalyst is neu ably employed in the form of its reaction product tralized, preferably with dry hydrogen chloride. With an organic acid amide, usually the same The reaction mixture can then be separated into amide as the one to be reacted with the alkylene its components by distillation under reduced pres Oxide, although other amides can be used. The sure or by other means. alkali metal reaction products with alcohols can The following examples, in which parts are by likewise be used as catalysts if desired, in place 20 weight unless otherwise designated, illustrate the of the amide-reaction products. practice of the invention without, however, lim Suitable alkali metal compounds for use as iting it thereto: catalysts embrace the reaction products of me Eacample 1.--Forty-five parts of anhydrous tallic sodium, potassium, lithium and other al formanide are placed at room temperature in a kali metals with amides such as formamide, reaction vessel provided with heating and cooling carbamide, acetamide, propion amide and similar means, means for stirring the reactants, and a amides as well as with alcohols, such as the so reflux condenser which may be cooled to 0° C. dium, potassium and lithium alcoholates de To the formamide, there is added 2.3 parts of rived from methanol, ethanol, propanol, isopro metallic Sodium the addition being in Small pOr panol, butanol, isobutanol, and Similar mono- and 30 tions. Hydrogen is evolved, and after hydrogen polyhydric alcohols. evolution has ceased, ethylene oxide is passed Although the use of an alkali metal catalyst into the reaction mixture by means of an inlet enhances the yield and Speed of reaction as above tube extending under the Surface of the liquid. described it. has been found that foramide, the Stirring is commenced, and the temperature of preferred amide for reaction according to this : the reaction mixture rises to about 60° C. There invention, reacts with an alkylene oxide to pro after, the rate of ethylene oxide addition is ad duce an alkylol formamide in the absence of a justed so that the temperature is maintained in catalyst and also in the absence of extraneous the range of 60-70° C. In all, 22 parts ethylene solvent. This is indeed unexpected since many oxide is added. After refluxing in the condenser other amides are preferably reacted in the pres 40 has ceased, the reaction is completed, and gase ence of both a solvent and a catalyst in order ous hydrogen chloride is bubbled through the to hasten the rate of reaction. reaction mixture until it is neutral. The sodium In carrying out the reaction of an amide with chloride which precipitates is filtered off and the an alkylene oxide in this invention, it has been mixture is then placed in a still having an - found that an organic solvent for the amide to shaped tubulated column. Twenty-six parts of be reacted is desirable when the said amide is not unreacted formamide is recovered by distillation in the liquid state under the reaction conditions. under reduced pressure, and 29 parts N-beta-hy Suitable organic solvents for the amide reactant droxyethyl formamide is obtained by distillation include alcohols, ethers, hydrocarbons and other of the residue at 175° C. to 182° C. under 10 mm. organic compounds capable of dissolving amides absolute pressure. The final residue, consisting under the reaction conditions, such as, for ex O of 9.5 parts, is N-bis(beta-hydroxyethyl)-form ample, dimethyl foramide, methanol, ethanol, amide. - propanol, isobutanol, benzene, dioxane, petroleum Eacample 2.-Metallic sodium (2.3 parts) is dis ether, and the like. Lower aliphatic alcohols, solved in 160 parts of absolute alcohol. To this especially methanol and ethanol, are the preferred 3. 5 is added 59 parts of anhydrous acetamide, and Solvents. While an organic solvent is desirable the resulting solution is placed in a reaction ves in the reaction of amides containing at least one sel of the type described in Example 1. Eighty amido-hydrogen atom with alkylene oxides, the parts of ethylene oxide is bubbled through the reaction of said amides is preferably carried out acetamide-alcohol mixture in a manner Similar in the absence of a solvent when the amides are 60 to that described in Example 1. After the ethyl normally liquid at the reaction temperatures em ene oxide has all been added, the mixture is ployed. Thus, formamide is preferably reacted neutralized with concentrated hydrochloric acid. with alkylene oxides in the absence of extraneous Sodium chloride precipitates and is filtered off. solvent; a decided advantage. Volatile material is removed by distillation, first In general, the reaction of an amide containing at atmospheric pressure, and then at reduced at least one amido-hydrogen atom is preferably pressure. After unreacted acetainide is removed carried out under anhydrous conditions, because by distillation under reduced pressure, 74 parts water has been found to have a detrimental ef of a light-yellow liquid remains as a residue. fect upon yields, and it also reacts with the alkali This comprises a mixture of N-beta-hydroxyethyl catalyst when a catalyst is employed. 70 acetamide and N-bis(beta-hydroxyethyl) acet In carrying out the present invention, when amide in about equal parts by weight. employing an alkali metal catalyst, the metallic Eacample 3-By reacting 44 parts of ethylene catalyst is admixed with the amide to be reacted oxide with 59 parts of N-methyl formamide by (after the amide has been dissolved in an organic the process described in Example 1, N-methyl, solvent if a solvent is used), and the alkali metal 75 N-beta-hydroxyethyl foramide is obtained. 2,357,288 3 Eacample 4-Butylamide (87 parts) is reacted perature between about 50° C. and 75° C. an an with propylene oxide (104 parts) by the process hydrous inixture of formamide with an amount described in Example 2. In this case the alkylene of ethylene oxide not more than about that which oxide is introduced into the alcoholic solution of is chemically equivalent to the amido-hydrogen the butyramide as a 50% solution in alcohol. 5 atoms, in the presence of an alkaline catalyst The reaction product, after remova) of unreacted comprising sodium formamide. alkylene oxide and butyramide by distillation, is 3. The process which comprises adding about a mixture comprising N-propylol butyramide and 2.3 parts by weight of metallic sodium to about N-bis(propylol) butyramide. 45 parts by weight of anhydrous formamide, sep The preferred catalyst is the sodium substitu O arating evolved hydrogen, introducing about 22 tion product of the amide used as a reactant. A parts by weight of ethylene oxide into the reac concentration of catalyst corresponding to about tion mixture thus formed while maintaining the 1 to 10 mole percent based on the amide reac temperature at 60-70° C., neutralizing the reac tant is preferred under anhydrous conditions. tion mixture with dry hydrogen chloride gas, Increase in the concentration of catalyst results separating the precipitated sodium chloride, and in an increase in the rate of reaction. thereafter subjecting the reaction mixture to dis While it is preferred to utilize the alkylene tillation at reduced pressure to recover about 29 oxide in a ratio of not greater than about chemi- . parts by Weight of N-beta-hydroxyethyl forman cally equivalent proportions to the amide, the ide and about 9.5 parts by weight of N-bis (beta proportion of alkylene oxide is subject to some. 20 hydroxyethyl)-formamide. variation. When the amide reactant has two 4. The process which comprises adding about amido-hydrogen atoms, the preferred ratio of 59 parts by weight of anhydrous acetamide to a reactants varies with the degree of substitution Solution of about 2.3 parts by weight of metallic desired; at a ratio of amide reactant to alkylene sodium in about 160 parts by weight of absolute Oxide reactant of 1:1, the amounts of mono alcohol, introducing about 80 parts by weight of and di-substitution are about equal. With ra ethylene oxide into the solution thus formed, tios less than this, di-substitution predominates. neutralizing the reaction mixture with concen If, therefore, it is desired to have the substi trated hydrochloride acid, separating the pre tution of only one amido-hydrogen atom pre cipitated sodium chloride, and thereafter sub dominate, the preferred ratio of reactants is 30 jecting the reaction mixture to distillation at about two mols of amide to one of alkylene ox reduced pressure to recover as a residue a mix ide, that is, about twice the amount of amide ture of N-beta-hydroxyethyl acetamide and N theoretically necessary for the reaction, and the bis (beta-hydroxyethyl) acetamide in about equal excess amide reactant is recovered by distillation parts by weight. after the reaction is completed. - 5. The process which comprises adding about As previously stated, formamide is the pre 87 parts by weight of butyramide to a solution ferred amide for reaction. Formamide not only prepared by dissolving about 2.3 parts by weight requires no solvent for reaction in accordance of metallic sodium in about 160 parts by weight with this invention, but contrary to the annides of of absolute alcohol, introducing into the solu other aliphatic acids, the reaction is highly exo tion thus formed about 104 parts by weight thermic and proceeds at greater speed. propylene oxide dissolved in an equal weight of Preferably, the alkylerae oxide is gradually absolute alcohol, submitting the mixture to re added to the amide reactant rather than the re action at a temperature between about 50° C. verse. This provides an excess of amide reac and about 75 C., neutralizing the reacted mix tant during the addition, which permits the pre ture, and recovering by distillation a mixture domination of mono-substitution of an amide re of N-propylol butyramide and N-bis(propylol) actant containing two amido-hydrogen atoms. butyramide. While the products of the invention may be sep 6. A process for N-alkylol amide production arated by distillation, preferably under reduced which comprises subjecting to reaction in the atmospheric pressure, for many uses it is unnec presence of an alkaline catalyst, under anhydrous essary to separate the N-alkyiol-amides from conditions at a temperature of at least 35° C. but each other, the removal of any unreacted initial below that at which substantial formation of material being sufficient purification. polyglycol derivatives takes place, a mixture of The N-alkylolamides are stable, high-boiling a carboxylic acid amide containing at least one materials which are very soluble in water. They s 5 amido-hydrogen atom with an alkylene oxide. are particularly useful as softeners for regenerat 7. A process for N-alkylol amide production ed cellulose, as described in U. S. Patent No. which comprises subjecting to reaction in the 2,170,845. presence of an alkaline catalyst, under anhydrous It will be apparent from the foregoing descrip conditions at a temperature of at least 35° C. but tion that a novel and convenient method for the not higher than about 80 C., a mixture of a car production of N-alkylol-amides in high yield and 60 boxylic acid amide containing at least one amido with but slight formation of by-products has been hydrogen atom with an amount of an alkylene oxide not more than about that which is 'chemi provided. cally equivalent to the amido-hydrogen atoms. Various changes may be made in the details 8. A process for N-alkylol amide production and practice of the invention without departing which comprises subjecting to reaction, under from the spirit and scope thereof. anhydrous conditions at a temperature between 1.I claim:In a process for the production of N-alkylol about 50 C. and about 75 C., a mixture of a car amides, the steps which comprise admixing an boxylic acid amide containing at least one amido anhydrous formamide containing at least one hydrogen atom with an alkylene oxide in the amido-hydrogen atom with ethylene oxide, and 70 presence of an organic solvent for said amide and subjecting the resulting mixture to reaction un an alkaline catalyst selected from the group con der anhydrous conditions. sisting of the compounds of alkali metals with 2. A process for N-alkylol amide production anides and the compounds of alkali metals with which comprises subjecting to reaction at a ten alcohols.

4 2,357,283 9. A process for N-alkylol amide production consisting of the compounds of alkali metals with which comprises subjecting to reaction, under amides and the compounds of alkali metals with anhydrous conditions at a temperature of at alcohols. least 35° C. but not higher than about 80 C., a 14. A process for N-alkylol amide production mixture of a carboxylic acid amide containing 5 which comprises subjecting to reaction at a tem at least one amido-hydrogen atom . With an perature between about 35° C. and about 75 C. amount of an alkylene oxide not more than an anhydrous mixture of a carboxylic acid amide about that which is chemically equivalent to the containing at least one amido-hydrogen atom amido-hydrogen atoms in the presence of an and not more than four carbon atoms in the organic solvent for said amide and an alkaline 10 carboxylic acid residue with ethylene oxide, in substance Selected from the group consisting of the presence of an alkaline substance selected the compounds of alkali metals with amides and from the group consisting of the compounds of the compounds of alkali metal with alcohols. alkali metals with amides and the compounds of 10. A process for N-alkylol amide production alkali metals with alcohols. which comprises subjecting to reaction an anhy 15. A process for N-alkylol amide production drous mixture of a carboxylic acid amide con which comprises subjecting to reaction at a tem taining at least One amido-hydrogen atom and perature between about 50° C. and about 75° C. not more than four carbon atoms in the car an anhydrous mixture of a carboxylic acid amide boxylic acid residue with an alkylene oxide in containing at least one amido-hydrogen atom the presence of an alkaline substance selected 20 and not more than four carbon atoms in the from the group consisting of the compounds of carboxylic acid residue with an amount of ethyl alkali metals with amides and the compounds of ene oxide not more than about that which is alkali metals with alcohols. chemically equivalent to the amido-hydrogen 11. A process for N-alkylol amide production atoms, in the presence of an organic solvent for which comprises Subjecting to reaction, at a tem 2 5 the Said amide and an alkaline substance selected perature not higher than about 80° C., an anhy from the group consisting of the compounds of drous mixture of a carboxylic acid amide con alkali metals with amides and the compounds of taining at least one amido-hydrogen atom and alkali metals with alcohols. not more than four carbon atoms in the acyl 16. In a process for the production of N-alkylol radical, with an amount of an alkylene oxide not amides, the steps which comprise admixing more than... about that which is chemically equiv formamide with an alkylene oxide, and subject alent to the amido-hydrogen atoms, in the pres ing the resulting mixture to reaction under an ence of an alkaline substance selected from the hydrous conditions at a temperature between 35 group consisting of the compounds of alkali and 75° C. . metals with amides and the compounds of alkali 3. 5 17. A process for N-alkylol amide production metals with alcohols. Which comprises subjecting to reaction at a tem 12. A process for N-alkylol amide production perature not higher than about 80° C. an anhy which comprises subjecting to reaction an anhy drous mixture of a formamide containing at least drous mixture of a carboxylic acid amide con one amido-hydrogen atom with an amount of an taining at least one amido-hydrogen atom and 40 alkylene oxide not more than about that which not more than four carbon atoms in the car is chemically equivalent to the amido-hydrogen boxylic acid residue with an alkylene oxide, in atoms, in the presence of an alkaline substance the presence of an organic solvent for the said Selected from the group consisting of the com amide and an alkaline substance selected from pounds of alkali metals with amides and the com the group consisting of the compounds of alkali pounds of alkali metals with alcohols. metals with amides and the compounds of alkali 18. A process for N-alkylol amide production metals with alcohols. which comprises subjecting to reaction at a tem 13. A process for N-alkylol amide production perature between about 35° C. and about 75° C. which comprises subjecting to reaction at a tem an anhydrous mixture of a formamide contain perature not higher than about 80° C., an anhy ing at least One amido-hydrogen atom with an drous mixture of a carboxylic acid amide con amount of ethylene oxide not more than about taining at least one amido-hydrogen atom and that which is chemically equivalent to the amido not more than four carbon atoms in the acyl hydrogen atoms, in the presence of an alkaline radical with an amount of an alkylene oxide not Substance selected from the group Consisting of more than about that which is chemically equiv the compounds of alkali metals with amides and alent to the amido-hydrogen atoms, in the pres the compounds of alkali metais with alcohols. ence of an organic solvent for the said amide FRANKLIN TRAVISS PETERs. and an alkaline substance selected from the group