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.