FI67207B - FOERFARANDE FOER FRAMSTAELLNING AV N-ETYLETYLENDIAMIN - Google Patents

Description

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Patent · OCh registerstyralsan AiwMcm ntfefd odl utUkrftw p «Mearad .10.84 (31) (33) (31) PjnM" OT · ο · οΛ · υ · -β · | ΐΜΐ prior ** 30.01.78 15.11.78 USA (US) 873450, 960972 Proven-Styrkt (71) Lederle Piperacillin, Inc., Carolina, Puerto Rico, USA (72) Karel Francis Bernady, Belle Mead, New Jersey,

Paul David Mogolesko, Belle Mead, New Jersey, USA (US) (7 * 0 Oy Kolster Ab (5 **) Process for the preparation of N-ethylethylenediamine -For the preparation of N-ethylethylenediamine

The invention relates to a process for N-ethylethylenediamine

B

To prepare C2H5NCH2CH2NH2 having a purity of about 99%, in which process (a) reacting the ethyl halide and ethylenediamine at a molar ratio of ethylenediamine to ethyl halide of about 1-20: 1 and at a temperature of about -10 to about + 120 ° C under anhydrous conditions under anhydrous reaction. , and (b) about 0.20-30% by weight of a suitable aliphatic hydrocarbon solvent, based on the weight of the reaction mixture, is added to the reaction mixture.

The process is particularly characterized in that (c) fractionating the reaction mixture to remove ethylenediamine as an azeotropic mixture with an aliphatic hydrocarbon solvent, (d) neutralizing the resulting mixture by contacting it with at least 0.9 molar equivalents of a suitable base per mol of ethylene the alkali halide precipitate from the suspension and recovering the resulting mother liquor / (f) washing the separated alkali halide with an aliphatic hydrocarbon solvent, (g) fractionating to remove the mother liquor from step (e) and the aliphatic hydrocarbon wash liquor recovered from step (f), virtually all water and residual (h) fractionally distilling the resulting mixture to remove residual aliphatic hydrocarbon solvent and recovering N-ethylethylenediamine.

N-ethylethylenediamine is hereinafter abbreviated NEED and ethylenediamine is abbreviated EDA.

U.S. Patent 4,061,633 discloses the separation of an azeotropic mixture of water and an amine by the addition of a hydrocarbon.

U.S. Patent No. 2,868,833 describes the preparation of N-ethylethylenediamine by reacting monoacetylethylenediamine with lithium aluminum hydride in a solvent.

GB patent 1,007,343 describes the preparation of octadecylethylenediamine by reacting ethylenediamine with octadecyl bromide in a solvent. The solvent is extracted with heptane and the heptane is removed by evaporation. Crude octadecylethylenediamine is obtained (yield 96%).

DE Patent 2,113,208 describes the reaction of an alkyl halide with a diamine.

In J. of Pharm. Sciences 57 (1968) 2073 describes the preparation of N-C 1 -C 4 -alkylethylenediamines by alkylation of anhydrous ethylenediamine with an alkyl halide in a solvent (yields 57% or less).

J. of the American Chemical Society 73 (1951) 1370 describes the preparation of N-C 1 -C 6 -alkylethylenediamines by reacting N-alkylamine with 2-bromoethylamine hydrobromide. Yields are then 52% or less.

3 67207

J. of the American Chemical Society 67 (1945) 1581 describes a process for the preparation of N-alkylethylenediamines by refluxing for several hours a mixture of alkyl chloride or bromide and a large excess of highly concentrated (95%) ethanol, after which the ethanol is evaporated to leave the remaining liquid is separated into two layers.

The upper layer is separated, diluted with water and extracted with ether. The ether extract is dried over anhydrous sodium sulfate and evaporated to give N-alkylethylenediamine.

The process of the present invention is not previously known in the art, in which N-ethylethylenediamine is prepared by reacting an ethyl halide with ethylenediamine and wherein the unreacted ethylenediamine is removed by azeotropic distillation.

According to the invention, ethylenediamine as an anhydrous liquid is reacted with an ethyl halide as follows:

B

C0H, -X + H_N-CH ~ CH0-NH0- * C «HcN-CH_CH0NH„ + HX,

Z D Z Z Z Z Z O Z Z Z

wherein X is a halogen atom such as chlorine, bromine, fluorine or iodine, preferably chlorine. The reaction is carried out with stirring of the reaction mixture in a suitable reaction vessel at a temperature between about -10-n. + 120 ° C, preferably at about 25-75 ° C, for about 1-24 hours, preferably 2-6 hours. The molar ratio of EDA to ethyl halide used is about 1-20: 1, preferably about 2-5: 1. The total residence time in the reaction vessel depends on the temperature used, with shorter residence times being used in conjunction with higher temperatures.

When the reaction is complete, the reaction mixture is diluted with about 0.2 to 30% by weight, preferably about 0.5 to 1.0% by weight, of a suitable aliphatic hydrocarbon solvent, based on the weight of the reaction mixture. The diluted reaction mixture is then heated to boiling point in the distillation column to remove any remaining EDA by azeotropic distillation. The EDA distillate can possibly be recovered and returned.

The term "suitable aliphatic hydrocarbon solvent" is defined herein as an aliphatic hydrocarbon solvent that is miscible with 67207 NEED, immiscible with EDA, and forms an azeotropic mixture with water and / or EDA at about 20-131 ° C, without that substantial amounts of NEED are present. Suitable aliphatic hydrocarbon solvents include n-heptane, isooctane, cyclohexane, n-hexane, methylcyclohexane, n-pentane, etc., although the most suitable aliphatic hydrocarbon solvent is n-heptane. Aromatic hydrocarbons cannot be used in place of aliphatic hydrocarbons due to their miscibility with both EDA and NEED.

The reaction mixture is then neutralized by contacting it with at least 0.9 molar equivalents of a suitable base per mole of alkyl halide used. The term "suitable alkalizing agent" is defined herein as sodium or potassium hydroxide, either alone or in mixtures. The most suitable base is an aqueous solution of about 50% sodium hydroxide.

The alkali halide precipitate formed is separated from the formed suspension by conventional methods, such as filtration or centrifugation, and washed as an aliphatic hydrocarbon solvent, preferably n-heptane.

The aliphatic hydrocarbon solvent washes are collected and combined with the mother liquor obtained by separating the alkali halide precipitate from the addition of the alkylating agent from the suspension formed in the reaction mixture. The combined liquids are azeotroped at atmospheric pressure through a packed column, preferably returning the heptane distillate to the top of the column until the remaining material is substantially free of EDA and water.

The resulting substantially EDA-free reaction mixture containing the product NEED, higher alkylated ethylenediamines, and an aliphatic hydrocarbon solvent is fractionally distilled using a fractional distillation column containing a sufficient number of theoretical bases to separate the aliphatic hydrocarbon solvent from the product NEED. Using, for example, a column containing 15 theoretical bases, n-heptane is distilled off as a precursor with a boiling point of about 98-100 ° C. The resulting hydrocarbon solvent fraction can be returned to other process steps, such as diluting the reaction mixture or azeotropic distillation of EDA or water from the reaction mixture.

5 67207

After removal of the hydrocarbon solvent precursor, the reaction mixture is clarified to remove any insolubles present and the clarified solution is further distilled to form a NEED (b.p. 130-131 ° C) with a purity greater than 99% and a yield of about 62-65%, based on theoretical addition. the amount of ethyl halide.

It should be noted that this process can also be carried out continuously using suitable vessels, such as continuous flow reactors, separation vessels, distillation columns, etc.

The invention is further illustrated by the following examples in which the temperatures given are in degrees Celsius. Unless otherwise indicated, all parts are by weight. The purity of the product is expressed as a percentage, determined by vaporase chromatography. (VPC).

Example 1 This example illustrates the use of anhydrous EDA 565 g (8.76 moles) of ethyl chloride are added to 1,420 g (23.63 moles) of anhydrous EDA at 30-40 ° C over 5 hours. The reaction mixture is stirred for 2 hours after the addition is complete and 935 ml (17.5 mol) of 50% sodium hydroxide solution are added. The resulting biphasic mixture is stirred for 30 minutes, allowed to stabilize and the aqueous phase is separated and extracted with 2 x 150 ml of n-heptane. The heptane extract is added to the organic phase and the combined solution is heated to remove water and EDA by azeotropic distillation at 88-97 ° C using a fractional distillation column and separator to return the distilled heptane to the distillation vessel and separate the denser EDA-water phase. In this way, the aqueous EDA phase, which consists of 394 g of water and 896 g (14.91 moles) of EDA, is separated. The EDA-free residue is fractionally distilled to form a heptane precursor (b.p. 98-102 ° C) consisting of 3-4% by weight NEED and 484 g NEED (b.p. 130-131 ° C) of greater than 99% purity. .8% according to vapor phase chromatography. The yield is 62.7%, based on the ethyl chloride used.

Example 2 6 67207 This example illustrates the separation of EDA from NEEDt by azeotropic distillation

A mixture of 500 g of EDA and 500 g of NEED is diluted with 200 ml of n-heptane and heated for azeotropic fractional distillation of EDA (boiling point 87-90 ° C) using a distillation column and a device which returns the recovered heptane to a distillation apparatus and allows for a denser EDA phase recovery. The EDA recovered in this way contains less than 1% NEED according to vapor phase chromatography. The EDA-free residue is then fractionally distilled to recover the heptane precursor and pure NEED (b.p. 13-131 ° C).

As described above, but using cyclohexane, n-hexane or isooctane instead of n-heptane, similar results are obtained.

Example 3 This example illustrates the separation of water from NEEDs by azeotropic distillation

To a mixture of 56 g of NEED and 10 g of water is added 50 ml of n-heptane. The mixture is heated to boiling and the water is partitioned azeotropically (boiling point 88-98 ° C) therefrom using a distillation column and a separator which returns the recovered heptane to the still and allows the denser aqueous phase to be removed. At the end of the dewatering, the residue is fractionally distilled to recover the heptane fraction and the NEED (b.p. 130-131 ° C) containing less than 0.2% water by vapor phase chromatography.

As described above, but using cyclohexane, n-hexane or isooctane instead of n-heptane, similar results are obtained.

Example 4 67207 62.4 g (0.967 moles) of ethyl chloride are added with stirring to 146.3 g (2.43 moles) of ethylenediamine over 1 hour, during which time the temperature is allowed to rise to 95 ° C. When the addition of ethyl chloride is complete, 34.2 g of n-heptane are added and the resulting mixture is azeotroped using a fractional distillation column and a Dean Stark apparatus to recover a liquid two-phase distillate consisting of a lower layer of 85.09 g of ethylenediamine and an upper layer of hepane. return to the fractionation column until all of the ethylenediamine has been removed.

The material obtained is cooled to 80 °, neutralized with 77.36 g (0.967 mol) of sodium hydroxide in 50% aqueous solution and the sodium chloride precipitate formed is filtered off to form a filter cake and a flowable two-phase filtrate. The filter cake is then washed with 50 ml of heptane and the washings are added to the original two-phase filtrate.

The resulting biphasic liquid is then azeotroped using a fractional distillation column and a Dean-Stark apparatus to recover a biphasic distillate containing n-heptane and water. After all the water has been removed, the residue is fractionally distilled to remove any heptane and recover 54.5 g of N-ethylethylenediamine having a boiling point of 130-131 ° C, a yield of 64% and a purity of 99%.

Example 5

The experiment according to Example 4 is repeated in every detail until the final distillation. After all the water has been removed by azeotropic distillation, the residue is filtered to separate 4.32 g of a white precipitate. The filter cake is then washed with 16 g of heptane and the washings are combined with the filtrate. The filtrate combined with the washing liquid is then fractionally distilled to remove heptane and recover 53.7 g of N-ethylethylenediamine having a boiling point of 130-131 ° C, a yield of 63% and a purity of 99%.

Example 6 67207

A glass-jacketed reaction vessel is charged with 848 parts of ethylenediamine (98%) followed by 331 parts of liquid ethyl chloride, added through a dropping apparatus at such a rate that the reaction mixture remains at 45-55 ° C. The mixture is stirred for 2 hours and 91 parts of heptane are added. Excess ethylenediamine is azeotroped off through the packed column, returning the heptane distillate to the top of the column. A total of 492 parts of ethylenediamine are recovered from the distillate during the recovery. The reaction mixture is neutralized with 402 parts of sodium hydroxide in a 50% solution cooled to room temperature and centrifuged to remove the sodium chloride by-product. The salt cake is washed with 70 parts of heptane and the washing liquid is combined with the mother liquor in a glass-lined vessel. Water is azeotroped off the combined liquids through the packed column, returning the distilled heptane to the top of the column. After all the water has been removed, the heptane is fractionally distilled through a packed column to form a residue containing the residues obtained in Examples 7, 8 and 9.

Example 7

A glass-jacketed reaction vessel is charged with 492 parts of the ethylenediamine recovered from Example 6 and 375 parts of fresh ethylenediamine (98%). To this mixture is added 331 parts of ethyl chloride at such a rate that the reaction mixture remains at 55-65 ° C. The mixture is stirred for 2 hours and 45 parts of the heptane recovered from Example 7 are added. Excess ethylenediamine is azeotroped off through the packed column, returning the heptane distillate to the top of the column. A total of 501 parts of ethylenediamine are recovered from the distillate for recovery. The reaction mixture is neutralized with 407 parts of sodium chloride in 50% solution, cooled to room temperature and centrifuged to remove the sodium chloride by-product. The salt cake is washed with 78 parts of heptane and the washing liquid is combined with the mother liquor in a glass-jacketed vessel. Water is azeotroped off the combined liquids through the packed column, returning the distilled heptane to the top of the column. After all the water has been removed, the heptane is fractionally distilled through a packed column to form a residue containing 288 parts of N-ethylethylenediamine. This residue is combined with the residues obtained in Examples 2.8 and 9.

Example 8.

67207

A glass-jacketed reaction vessel is charged with 501 parts of the ethylenediamine recovered from Example 7 and 396 parts of fresh ethylenediamine (98%). To this mixture is added 331 parts of ethyl chloride at such a rate that the reaction mixture remains between 65 and 75 ° C. The mixture is stirred for 2 hours and 28 parts of the heptane recovered from Example 7 are added. Excess ethylenediamine is azeotroped off through the packed column, returning the heptane distillate to the top of the column. A total of 504 parts of ethylenediamine are recovered from the distillate for recovery. The reaction mixture is neutralized with 409 parts of sodium hydroxide in 50% solution, cooled to room temperature and centrifuged to remove the sodium chloride by-product. The salt cake is washed with 82 parts of heptane and the washing liquid is combined with the mother liquor in a glass-lined vessel. Water is azeotroped off the combined liquids through the packed column, returning the distilled heptane to the top of the column. After all the water has been removed, the heptane is fractionally distilled through a packed column to form a residue containing 310 parts of N-ethylethylenediamine. This residue is combined with the residues obtained in Examples 6.7 and 9.

Example 9.

A glass-jacketed reaction vessel is charged with 504 parts of the ethylenediamine recovered from Example 8 and 388 parts of fresh ethylenediamine (98%). To this mixture is added 331 parts of ethyl chloride at such a rate that the reaction mixture remains between 55 and 65 ° C. The mixture is stirred for 2 hours and 30 parts of the heptane recovered from Example 8 are added. Excess ethylenediamine is azeotroped off through the packed column, returning the heptane distillate to the top of the column. A total of 523 parts of ethylenediamine are recovered from the distillate for recovery. The reaction mixture is neutralized with 409 parts of sodium hydroxide in 50% solution, cooled to room temperature and evaporated to remove the sodium chloride by-product. The salt cake is washed with 91 parts of heptane and the wash water is combined with the mother liquor in a glass-jacketed vessel. Water is azeotroped away from the combined liquids through the packed column, returning the distilled heptane to the top of the column. After all water has been removed, heptane is fractionally distilled through a packed column to form a residue containing 317 parts of N-ethylethylenediamine, which is combined with the residues from Examples 6, 7 and 8.

The resulting material is fractionally distilled through a packed column at atmospheric pressure to form 1120 parts of N-ethylethylenediamine having a boiling point of 129-131 ° C. The yield is 61.9%, based on the ethyl chloride used, the purity of the product is 99%.

Claims (7)

11 67207 A process for preparing N-ethylethylenediamine having a purity of about 99%, wherein process (a) reacts ethyl halide and ethylenediamine with a molar ratio of ethylenediamine to ethyl halide of about 1-20: 1 and a temperature between about -10 -n. + 120 ° C under anhydrous conditions to form an alkylation reaction mixture, and (b) adding to the reaction mixture about 0.20-30% by weight of a suitable aliphatic hydrocarbon solvent, based on the weight of the reaction mixture, characterized by (c) fractionally distilling the reaction mixture to remove ethylenediamine as an azeotropic aliphatic solvent. , (d) neutralizing the resulting mixture by contacting it with at least 0.9 molar equivalents of a suitable base per mole of ethyl halide to form a suspension of the early halide precipitate, (e) separating the alkali halide precipitate from the suspension and recovering the resulting mother liquor, (f) washing the separated alkali halide with aliphatic g) fractionating the mother liquor from step (e) and recovering from step (f) the combination of aliphatic hydrocarbon scrubbing liquid to remove substantially all of the water and residual ethylenediamine, and (h) fractionating the resulting mixture to remove the remaining aliphatic carbon dioxide. to remove the live solvent and recover N-ethylethylenediamine, Process according to Claim 1, characterized in that the aliphatic hydrocarbon is n-heptane. Process according to Claim 1, characterized in that step (a) is carried out at a temperature in the range from n, 25 to 75 ° C. Process according to Claim 1, characterized in that a molar ratio of 2 to 5: 1 is used between ethylenediamine and ethyl halide in step (a). Process according to Claim 1, characterized in that the aliphatic hydrocarbon in step (b) is added in an amount of about 0.5 to 1.0%, based on the weight of the reaction mixture. Process according to Claim 1, characterized in that n-heptane is added in step (b) in an amount of about 0.5 to 1.0%, based on the weight of the reaction mixture. Process according to Claim 1, characterized in that the base in step (d) is a solution of about 50% of aqueous sodium hydroxide. 12 Patentkrav 6 7 2 0 7