SU1685907A1 - Method for obtaining aminopropanones - Google Patents

Abstract

The invention relates to amino ketones, in particular the production of amino propanone intermediates for the synthesis of active substances. The goal is to expand the range of target substances and simplify the process. It is carried out by the reaction of secondary amines and ketones in the medium of an organic solvent at the electrochemical anodic oxidative combination in the presence of a catalytic amount of iodine or alkali metal halide at a current density of 2-10 mA / cm2. It is better to use acetonitrile as a solvent, molar ratio of amine and acetone 1.0: 5.1, volume ratio of acetone and acetonitrile 1: 2, sodium iodide as alkali metal halide, glass carbon, graphite as electrode or steel as well as platinum. These conditions increase the yield of the target product from 70 to 82-85% without the formation of impurities that contaminate the product, and provide the ability to reuse unreacted products. 4 hp ff, 7 table. with C

Description

This invention relates to a process for the preparation of aminopropanones which can be used as intermediates in the synthesis of drugs.

The aim of the invention is to simplify the process technology and expand the range of target products.

This goal is achieved by the fact that in the method of producing aminopropanones by the interaction of secondary amines and ketones in an organic solvent medium, the interaction is carried out by an electrochemically anodic oxidative combination of the corresponding

the secondary amine with acetone as a ketone in the medium of acenonitrile as an organic solvent in the presence of a catalytic amount of iodine or an alkali metal halide at a current density of 2-10 mA / cm2.

In addition, the aim of the invention is to increase the yield of the target product, which is achieved with a molar ratio of secondary amine and acetone equal to 1.0: 5.1, respectively, and a volume ratio of acetone and acetonitrile, equal to 1: 2, respectively.

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Preferably sodium iodide is used as the alkali halide.

Platinum, glassy carbon, graphite or steel can be used as an electrode; most preferred results are achieved using platinum.

The examples below illustrate the invention.

Synthesis procedure.

The electrolysis is carried out in a diaphragm-free electrolyzer at 18–22 ° C and a molar ratio of the starting components is diethylamine (piperidine, morpholine): acetone, equal to 1: 1. Platinum plates with a working surface of 9 cm2 (anode) and 4 cm2 (cathode) are used as electrodes. In addition, you can also use graphite, glassy carbon and steel electrodes. The background electrolyte is methyl tetraethylammonium. The volume of electrolyte 30 ml. The electrolysis is carried out in galvanostatic mode at a current density of 2-10 mA / cm2. The potential of the working electrode is measured relative to silver wire in a 0.01 M solution of silver nitrate in acetonitrile. The potential of the working electrode varies from 0.2 to 0.5 V. The catalyst is preferably sodium iodide. At the end of electrosynthesis, the electrolysis products are extracted with diethyl ether (3 x 50 ml), then the ether is distilled off, and the residue is subjected to fractional distillation.

Analysis of the starting and desired products is carried out by gas chromatography. The composition is confirmed by the results of elemental analysis. The structure of the compounds obtained is proved by IR spectroscopy data.

Example 1. Getting N-diethylaminopropion

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Into a mixture of acetone: acetonitrile 1: 2, 2.0 g (0.9 mol) of diethylamine and 0.4 g (0.05 mol) of tetraethylammonium bromide are introduced. Sodium iodide in an amount of 0.05 g is used as a catalyst. The current density is 5 mA / cm2, the temperature is 20 ° C.

The yield of the target product - M-diethylaminopropanol 2.9 g (82.3%). Bp 44 ° C / 5 mm Hg, 20 = 1.4632.

Found: C, 64.71; H, 11.48; N, 10.23.

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Calculated,%: C65.11; H 11.62; N 10.85.

IR spectrum, v. 1710 (). 2885 (C — H), 1025 (CN).

Example 2. Getting piperidinopropane:

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The process is carried out as in Example 1, but 2.3 g (0.9 mol) of piperidine is taken as the starting material. The yield of the target product piperidinopropanol 3.17 g (83.15%). Bp 50 ° C / 1-2 mm Hg till 20 1.4580.

Found %: C 68.43; H 10.35; N 9.69. . CeHisNO.

Calculated,%: C 68.08; H 10.63; N 9.92.

IR Spectrum, V.CM4: 1725 (). 2692 (C-H), 1020 (C-M).

Example 3. Getting morpholinopropane:

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The process is carried out as in Example 1, but 2.35 g (0.9 mol) of morpholine is taken as the starting material.

The yield of the target product is morpholinopropanone 3.3 g (85.25%), b.p. 75 ° C / 2 mmHg. To 20 1,4602.

Found,%: C 58.34; H 9.48; N 9.5.

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Calculated,%: C 58.7; H 9.09; N 9.7.

IR spectrum, v, 1742 (CO); 2970 (C – H); 1023 (C-N).

Example 4. Preparation of morpholinopropanone.

The process is carried out according to Example 3, but glass carbon is used as an anode. Take 2.35 g (0.9 mol) of morpholine. The yield of the desired product morpholinopropanol 1.63 g (62.3%). Bp 75 ° C / 2 mm Hg, 1.4602,

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In tab. 1 shows data showing the effect of the ratio (volume) of acetone and acetonitrile on the yield of the target product.

The same data are given in table. 2, in which the conditions of the method are similar to example 1.

As can be seen from the data table. 1 and 2, the maximum yield is achieved at a volume ratio of acetone: ecetonitrile of 1: 2.

In tab. 3 shows data showing the effect of the catalyst on the yield of the desired product.

The results were obtained with a molar ratio of catalyst to secondary amine of 0.025: 1, respectively.

As can be seen from the table. 3, the yields of the target product using elemental iodine and sodium iodide are almost identical, but it is easier to work under electrolysis conditions with sodium iodide.

Table 4 gives data on the effect of the ratio (molar) of amine and catalyst (Nal) on the yield of the target product.

As can be seen from the table. 4, when using a catalyst less than 0.01 mol per 1 mol of the secondary amine, the yield of the target product decreases, and the use of the catalyst in amounts greater than 0.05 mol per 1 mol of the amine does not affect the yield of the target product.

In tab. Figure 5 shows the data on the study of the effect of the electrode material on the yield of the target product.

From the data table. 5, it follows that the maximum yield of N-diethylaminopropanol is observed when using a platinum anode.

In tab. 6 shows data on the effect of temperature conditions on the yield of the target product.

As can be seen from the table. 6, the temperature is not a significant sign, since it does not affect the yield of the target product.

In tab. 7 shows data on the effect of current density on the yield of the target product.

In addition, it has been established experimentally that the most preferred results are achieved at a current density of 4.6-5.2 mA / cm2.

Thus, the proposed method, compared with the known method, which provides for the interaction of the secondary amine with chloroacetone in the medium of dry ether at (+2) - (-10) ° C, eliminates the use of chloroacetone - toxic, tear reagent and conduct the reaction at a low temperature, and also to exclude the stage of preliminary preparation of chloroaceton by chlorination of acetone. All this leads to a significant simplification of the process technology.

In addition, the proposed method allows to expand the range of target

products, and with f, -. .i (, their reagents and auxiliary substances increase the yield of bulk products from 70 to 82-85%.

The proposed method is electrochemical, environmentally friendly: in addition to the target product (82-85%), after the experiment only unreacted acetone and the secondary amine remain, which is recycled again. It allows the synthesis of industrially available starting compounds synthesized in the USSR: acetone, diethylamine, piperidine and morpholine and can be carried out in the simplest type electrolysis cells of any design.

Claims (5)

1. A method for producing aminopropanone by reacting secondary amines and ketones in an organic solvent medium, characterized in that, in order to simplify the process technology and expand the range of target products, the interaction is carried out by electrochemically anodic oxidative combination of the corresponding secondary amine with acetone as ketone in the medium acetonitrile as an organic solvent in the presence of a catalytic amount of iodine or alkali metal halide at a current density of 2-10 mA / cm2. 2. A method according to claim 1, characterized in that, in order to increase the yield of the target product, the reaction is carried out at a molar ratio of secondary amine and acetone equal to 1.0: 5.1, respectively, and a volume ratio of acetone and acetonitrile equal to 1 : 2 respectively. 3. Method according to paragraphs. 1 and 2, characterized in that sodium iodide is taken as the alkali metal halide, 4. A method according to claim 1, characterized in that the electrochemical interaction is carried out using platinum, glass carbon, graphite or steel as an electrode. 5. A method according to claim 4, characterized in that platinum is taken as the electrode. Table 1 The effect of the ratio of acetone: acetonitrile on the output of N-diethylaminopropanone, dissolve 30 ml, I 5 mA / cm2, t 20 ° C, anode - Pt The influence of the nature of the halide release of aminopropanones at I 5 mA / cm, t 20 ° С, the anode - Pt Continued table. one Table 2 Table 3 Table 4 The effect of the electrode material on the output of N-diethylaminopropanol (acetone: acetonitrile - 1: 2. / 0 to 30 ml; i 5.0 mA / cm2; CNai 2.5 mol; CEIZNH 2 g 1685907 10 a b l and c a 5 Table 6 Table 7