CS274351B1 - Method of ethylamine and 2-aminoethanol or 2-methoxyethylamine preparation by electroreduction of oximes - Google Patents

Abstract

The solution concerns a preparation of ethylamine and 2-aminoethanol or 2-methoxyethylamine by reaction of free solutions of glycolaldehyde or its 0-alkyl substituted derivates with hydroxylamine or its salt with subsequent electroreduction of the solution of the related oximes. The principle of the solution consists in the fact that the related oxime is prepared by reaction of water solutions of reaction components. The electroreduction of the water solution of oxime is performed in presence of at least 50 percent of hydroxylamine surplus. The substances react in potentiostatic and pH-static conditions, with discontinuous pH-static monitoring of circulating or pulsing part of the electrolyzed solution, positioned in the measuring time out of the electric field of the reaction environment, at a pH value ranging from 1 to 5. The working electrode potential ranges from -1.0 to -1.6 V with regards to the saturated calomel electrode. The obtained mixture of amines is subsequently separated. The advantage of the solution consists mainly in the ability to proceed in the preparation of amines from water reaction solutions of oximes. This means that it is not necessary to isolate pure oxime. Another advantage of this method are almost theoretical yields of target amines.

Description

The invention relates to a process for the preparation of ethylamine and 2-aminoethanol or 2-methoxyethylamine by electroreduction of oximes prepared by reaction of glycol aldehyde or its O-substituted derivatives with hydroxylamine.

In the reaction of carbonyl compounds with hydroxylamine, the rate and equilibrium of the oximes formed depend on the pH-values of the environment and the acid-base properties of the reactants. While the reaction rate of oxime formation goes through the rate maximum in an acidic medium, the equilibrium constant values for oxime formation increase with increasing pH-medium values and reach a maximum in alkaline environments / lencks W. P .: Amer. Chem. Soc. B1, (1959) 475; lencks W.P .: Progr. Phys. Org. Chem. 2, (1964) 63]. Only the protonated form of oximes is subject to electrochemical reduction / Lund H .: Acta Chem. Scand. 13, (1959) 249; Haas, J. W. Ir., Kadunce, R. E., l. Chem. Soc. 84, (1962) 4910; Haas 3.W., Ir. Storey 3. D .: Anal. Chem. 34, (1962) 145], it is necessary to select compromise the pH-environment of the electroreduction so as to achieve an optimum between the rate of formation, the equilibrium value and the degree of protonation of the oxime.

Based on a polarographic study of the reaction of glycol aldehyde, glyceraldehyde, dihydroxyacetone and their O-methylated derivatives with hydroxylamine, it was found that in an acidic environment at pH less than 5, it is optimum for the rate of formation and electroruction of the respective oximes. In very strong acidic environments, oxime concentrations are lower and are caused by their hydrolysis to the starting compounds. At pH greater than 5, the polarographic wave heights decrease due to a decrease in their reducibility of the protonated forms. In the case of higher monosaccharides, i. pentoses and hexoses, the rates of oxime formation and their equilibrium constants decrease due to the existence of an equilibrium between the cyclic and acyclic forms of the monosaccharides.

The overall yields of the products depend on the working potential of the working mercury electrode and the pH of the environment. For example, it has been found that, even under optimal reaction conditions, about 20% of the aldehyde oxime component is released in the process of preparative electroreduction of the oxo oxides of glycol aldehyde and its O-methyl derivative, allowing products to be obtained in a maximum of 80% yields. We have shown that at least 50% excess of hydroxylamine must be added at the beginning of the reaction to completely suppress the recovery of the respective aldehydes from the starting oximes.

Analysis of the reaction products of the oxo-glycol aldehyde and its O-methyl derivative revealed that the electroreduction proceeds in an unusual way, since in each case two amines are formed as the final products, i.e. the. not only the predicted 2-aminoethanol and the like. 2-methoxyethylamine, but in both cases unexpected ethylamine. This is the discovery of a new type of electroreduction of oximes.

The principle of the process for the preparation of ethylamine and 2-aminoethanol or 2-methoxyethylamine by electroreduction of oximes according to the invention is to react an aqueous solution of glycol aldehyde or its O-methyl substituted derivative with an aqueous solution of hydroxylamine or its salt present in at least 50% excess. to form a solution of the corresponding oxime. Subsequent electrorecoration of the aqueous oxime solution is carried out in aqueous buffer at pH 1-5, in the presence of at least 50% excess hydroxylamine under potentiostatic and pHstatic conditions by continuous pH static control of the circulating or pulsating portion of the electrolyzed solution present at the time of measurement. reaction environment. The working electrode potential is in the range of -1.0 V to -1.6 V relative to the saturated calomel electrode. The resulting amine mixture is separated by chromatography, fractional distillation of the free amines, or fractional crystallization of their salts.

In the reaction of an aqueous solution of glycol aldehyde and its O-methyl derivative with hydroxylamine added in the form of its salt, the electroreduction of the oximes formed is carried out at a pH of 2 to 5, preferably a pH of 3.6 and a potential. a working electrode in the range of -1.3 to -1.4 V, preferably -1.4 V,

CS 274 351 B1 with respect to a saturated calomel electrode; The 2-aminoethanol and ethylamine in the case of the glycol aldehyde oxime and the mixture of 2-methoxy-ethylamine and the ethylamine in the case of the 2-methoxyacetaldehyde oxime are separated chromatographically respectively. by fractional distillation of the free amines or by fractional crystallization of their salts.

The advantage of the proposed method of electroreduction of oximes is that it is not necessary to start from pure oximes, but aqueous solutions of the reaction components, ie. an aqueous solution of the carbonyl compound and an aqueous solution of the hydroxylamine salt with at least 50% excess thereof, and after reaction, the solution is added to a buffer of the desired pH, whereby the oxime formed solution is prepared for preparative electroruction. A further advantage of the new process is that the use of potentiostatic and pH static conditions allows the products to be obtained practically in theoretical yields and allows not only the expected four-electron reduction product to be obtained in one stage. Due to the general validity of the discovered laws of electroreduction of oximes, it can be used for the preparation of analogous amino derivatives. In contrast to hydrogenation methods, this method also allows the cleavage of a single C-O bond. Hydrogenation cannot provide such unusual amines as are formed after the electro-reductive cleavage of a single C-O bond at -position to the azomethine group of said type of oximes.

The device in which the electroreduction was carried out is described in more detail in MS. AO 248 208, which allows electroreduction to take place in a separate cathodic space on a mercury working electrode at a selected potential relative to a reference saturated calomel electrode maintained by a potentiostat and ensures control and maintenance of the desired pH value by means of a pH-stat.

Example 1

An aqueous solution (50 mL) of 0.2 M glycol aldehyde (0.6 g) and 0.3 M hydroxylammonium sulfate (1.23 g) was allowed to react at room temperature for 30 min. 50 ml of 0.2 M formate buffer, pH 3.6, and the necessary amount of aqueous 1M sodium hydroxide solution are then added to the solution to adjust the said pH. The reaction solution is poured into the cathodic space of the electrolyzer, where it is electroreduced on the mercury working electrode, with vigorous stirring of its surface and cooling of the electrolyzer with water, at a potentiostatically maintained potential of -1.4V relative to the saturated calomel electrode. The pH value of 3.6 was maintained pH-statically by adding the required amount of aqueous 1M sulfuric acid. The anodic compartment of the electrolyzer is filled with an aqueous solution of 0.1 M sulfuric acid.

The course of the oxime electroreduction, the formation of the appropriate amines and glycol aldehyde generation was monitored polarographically, with polarographic curves being recorded at selected time intervals, from the potentials measured relative to the saturated calomel electrode. The decrease in oxime concentration during reduction was monitored by registering its polarographic curves from -0.6V in 0.04 M formate buffer at pH 3.6 (0.1 ml sample in 9.9 ml buffer). Polarographic curves of their condensation products with benzaldehyde in an alkaline medium (0.5 ml sample in 9 ml 0.1 M phosphate buffer and 0.5 ml 0.1 M benzaldehyde) were used to monitor the formation of the amines formed. Glycol aldehyde regeneration was determined by registering its polarographic curves from -1.2 V after adding 0.5 ml of the reaction sample to 9.5 ml of an aqueous solution saturated with calcium hydroxide.

Upon completion of the electroreduction (3 h), crude product showed < ³ > C NMR spectroscopy analysis of the formation of 2-aminoethanol and ethylamine as the final products of the electroreduction at a ratio of 1: 2. The reaction solution was matured with barium formate and the resulting precipitate was filtered off. The vacuum-concentrated small volume water bath filtrate is applied to a cellulose column (1 m / 0 5 cm) and separated in a butanol: formic acid: water = 8: 1: 1 system at a flow rate of 13 ml / h. The individual fractions were combined by chromatography on Whatmann 3M paper in the system and detection with 0.1% ninhydrin in butanol at 105 ° C. 2 first

The fraction gave a fraction of ethyl ammonium formate (0.57 g) which was converted with picric acid to ethylamine picrate of m.p. t. 167-168 ° C; lit. / M itchell J., 3r., Bryant W. M. 0: 3. Amer.

Chem. Soc. 65 (1943) 128 / t. t. 170 ° C, respectively. lit. / Jacobs W.A., Elderfield R.C .:

J. Amer. Chem. Soc. 58 (1936) 1059 / t. t. Mp 166 ° C. From the second fraction 2-hydroxyethylammonium formate (0.2 g) was obtained, which was converted with picric acid to 2-hydroxyethylamine picrate with m.p. t. 158-159 [deg.] C .; lit. / Adkins H., Billica H. R., J. Amer. Chem. Soc. 70 (1948) 3121; t. 159.5-160 ° C.

Example 2

An aqueous solution (50 mL) of 0.2 M 2-methoxyacetaldehyde (0.74 g) and 0.3 M hydroxylammonium sulfate (1.23 g) was allowed to react at room temperature for 30 min. After completion of the reaction, 50 ml of 0.2 M formate buffer, pH 3.6, and the necessary amount of aqueous 1M sodium hydroxide solution are added to the solution to adjust the said pH value carefully. The reaction solution is electroreduced in the cathodic space of the electrolyzer on the orthodox working electrode, with vigorous mixing of its surface and cooling of the electrolyzer with water, at a potentiostatically maintained potential. -1.4V relative to saturated calomel electrode. The set pH of 3.6 is maintained pH-statically by adding the required amount of 1M sulfuric acid. The course of electroreduction of the oxime, formation of the corresponding amines and generation of 2-methoxyacetaldehyde was followed by the polarographic method described in Example 1.

After completion of the electroreduction (3 h), the reaction solution was concentrated in vacuo and the residue analyzed by C NMR spectrometry. The formation of 2-methoxyethylamine and ethylamine in a 1: 1 ratio was shown. 2.3 g of sodium hydroxide were gradually added to the reaction residue with stirring and cooling. The liberated amines were extracted into ether from which, after drying with sodium sulfate, they were obtained by fractional distillation. Ethylamine (0.21 g) with m.p. t. 166 ° C of its picrate and in the second fraction 2-methoxyethylamine (0.36 g) was obtained with m.p. t. 145-147 ° C of its picrate; lit. (Lambert, A., Scaife, CW, Wilde-Smith, A.E .: Chem. Soc. 1947, 1474; t. 148-150 ° C.

The solution may also find application in organic electrosynthesis of analogous amino derivatives.

Claims (4)

A process for the preparation of ethylamine and 2-aminoethanol or 2-methoxyethylamine by electro-reduction of oximes, characterized in that an aqueous solution of glycol aldehyde or an O-methyl substituted derivative thereof is reacted with an aqueous solution of hydroxylamine or a salt thereof present in at least 50% excess, the formation of a solution of the appropriate oxime, which is subjected to electroreduction in an aqueous buffer at pH 1-5, with the potentiostatic conditions, at a working electrode potential in the range of -1.1V to -1.6V with respect to the saturated calomel electrode under pH-static conditions by continuous The pH-stable control of the circulating or pulsating portion of the electrolysed solution, found at the time of measurement outside the influence of the electrical pole of the reaction medium, and then the resulting mixture of two amines is separated. 4 CS 274 351 B1 The fraction was obtained with ethylammonium formate (0.57 g), which was converted with picric acid on ethylamine each time with m.p. 167-168 ° C; lit. / M itchell J., 3r, Bryant W.M. 0: 0. Amer. Chem. Soc. 65 (1943) 128 / mp 170 ° C, respectively. lit. / Jacobs W.A., Elderfield R.C. 2. Preparation according to claim 1, characterized in that the aqueous solution of glycol aldehyde is reacted with hydroxylamine added in the form of its salts, whereby the electroreaction of the aqueous solution of glycol aldehyde oxime is carried out at a pH of 2 to 5, preferably pH 3.6 and apotentials. a working orthose electrode in the range of -1.3 V to -1.5 V, preferably -1.4 V, relative to the saturated calomel electrode, the resulting mixture of amines being separated. 3. A process according to claim 1, wherein 2-methoxyacetaldehyde is reacted with hydroxylamine added in the form of its salt. 3. Amer. Chem. Soc. 58 (1936) 1059 / mp 166 ° C. From the second fraction, 2-hydroxyethylammonium formate (0.2 g) was obtained, which was converted with picric acid to 2-hydroxyethylamine picrate with m.p. 158-159 ° C; lit. / Adkins H., Billica R, J. Amer. Chem. Soc. 70 (1948) 3121 (m.p. 159.5-160 ° C). Example 2 An aqueous solution (50 mL) of 0.2 M 2-methoxyacetaldehyde (0.74 g) and 0.3 M hydroxylammonium sulfate (1.23 g) was reacted at room temperature for 30 min. After completion of the reaction, 50 ml of 0.2 M formate buffer pH 3.6 and the required amount of aqueous 1M sodium hydroxide solution were added to the solution to adjust the pH value again. The reaction solution is electroregulated in the cathodic space of the electrolyzer at the orthose working electrode, intensively mixing its surface and cooling the electrolyzer with water, at a potentiostatically maintained potential of -1.4V relative to the saturated calomel electrode. The adjusted pH of 3.6 is maintained by static addition of 1M sulfuric acid. The course of the electro-reduction of the oxime, the formation of the corresponding amines and the generation of 2-methoxyacetaldehyde was followed by the polarographic method described in Example 1. After the electro-reduction (3 h), the reaction solution was concentrated in vacuo and the residue was analyzed by C NMR spectrometry. The formation of 2-methoxyethylamine and ethylamine in a ratio of 1: 1 was demonstrated. Sodium hydroxide (2.3 g) was gradually added to the reaction residue with stirring and cooling. The liberated amines were extracted into ether and dried over sodium sulfate to give fractional distillation. In the first fraction, ethylamine (0.21 g) was obtained with a m.p. of 166 ° C, and the second fraction gave 2-methoxyethylamine (0.36 g) with m.p. 145-147 ° C of its picrate; lit. (Lambert, A., Scaife, C.W., Wilde-Smith, A.E .: Chem. Soc. 1947, 1474, reported t.148-150 ° C. The solution of the can also find application in the organic electrosynthesis of analogous aminodivatives. SUBJECT MATTER 4. A process according to claim 1, wherein the mixture of two amine derivatives is separated by chromatography, fractional distillation of the free amines or fractional crystallization of their salts.