RU2625449C1 - Method of obtaining salt 9-amino-10-methylacridinium - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely the method of obtaining salt 9-amino-10-methylacridinium of the overall formula I

,

where X=PF₆ (connection a) X=ClO₄ (connection b) X=BF₄ (connection c), R=H, alkyl, interaction derived from dimedone aminering agent in a solvent that is different that as aminering agent using primary amine, solvent use acetonitrile, the reaction is carried out at room temperature and oxidation in electrochemically galvanostatic mode when current density 3 mA/cm².

EFFECT: simple and secure way of getting salts 9-amino-10-methylacridinium, useful as raw material for the synthesis of a variety of compounds.

1 cl

Description

The invention relates to a new method for producing 9-amino-10-methylacridinium salts of the general formula (I), useful commercial products, which are also raw materials for the synthesis of various compounds.

A known method of producing 9-aminoacridine (III) from 9-chloroacridine (II) and ammonium carbonate or gaseous ammonia in a phenol solution [Albert and Ritchie. J. Soc. Chem. Industr., 60, 120 (1941)]. Subsequent alkylation with methyl iodide in boiling methanol leads to 9-amino-10-methylacridinium iodide (IV) (Scheme 1) [Albert and Ritchie. J. Chem. Soc., 458-462 (1943)]. The first stage of this process is carried out for 1 hour at a temperature of 120 ° C. Alkylation is carried out at 4-hour boiling in methanol.

Scheme 1

Despite the good total yield of the product (76%), the method has significant drawbacks, associated primarily with the need for additional production of 9-chloracridine (II). In addition, the use of poisonous phenol as a solvent can significantly increase the technogenic load on the environment.

Another known method for producing 9-aminoacridine (III) is based on the reaction of acridine (V) with urea (VI) in a solution of dimethyl sulfoxide (DMSO) (Scheme 2) [I.V. Borovlev, O.P. Demidov, G.A. Amangasieva, E.K. Avakyan Tetrahedron Lett., 57, 3608 (2016)]. The reaction is carried out at room temperature in the presence of sodium hydride (NaH) for 24 hours.

Despite the good yield of the product, the method has significant disadvantages associated with the need to use hazardous sodium hydride and an unacceptable reaction time. And the evolution of hydrogen during the reaction increases the flammability of the process.

Scheme 2

, I.S. Kashparov, Z.I. Sokolov, M.M. Medvedeva, Chem. Heterocycl. Compd., 1976, 304-311] - прототип. Реакцию проводят в жидком аммиаке при - 70°С в присутствии эквивалентного количества нитрата железа в качестве окислителя.A known method for producing 9-amino-10-methylacridinium perchlorate nitrate (IX), in which N-methylacridinium iodide (VIII) is used as the starting compound, and potassium amide is used as an aminating agent [AF Pozharskii,

, IS Kashparov, ZI Sokolov, MM Medvedeva, Chem. Heterocycl. Compd., 1976, 304-311] - prototype. The reaction is carried out in liquid ammonia at - 70 ° C in the presence of an equivalent amount of iron nitrate as an oxidizing agent.

Scheme 3

The disadvantages of this method are the need to create a low temperature and low yield.

The objective of the invention is the development of a simple, safe, affordable, environmentally friendly and effective method for producing salts of 9-amino-10-methylacridinium.

The problem is solved by using one of the salts of N-methylacridinium (X) as a feedstock, which reacts at room temperature with one of the primary amines (III) in dehydrated acetonitrile to form a colorless solution. Subsequent electrochemical oxidation leads to the formation of product (I) (Scheme 4). For electrolysis, a background electrolyte is added to the resulting solution, which contains acetonitrile or methanol and the corresponding electroactive salt (for example, ammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetrabutylammonium perchlorate or tetrabutylammonium hexafluorophosphate) as a solvent. Electrolysis is carried out on a platinum electrode in galvanostatic mode at a current density of 3 mA / cm ² . Upon completion of the electrolysis, the solvent was distilled off under reduced pressure, and the residue was recrystallized from water and dried in air.

Scheme 4

The use of the salt of N-methylacridinium (X) and primary amine (XI) avoids the exhausting preliminary preparation of reagents and additional stages of synthesis, as well as the reaction at room temperature and significantly reduces the synthesis time of compound I. Moreover, the yield of the target products is significantly increased compared to prototype. The use of electrolysis allows you to fully control the oxidation process and abandon the use of chemical oxidizing agents. This leads to an increase in the efficiency of the process, the prevention of losses, makes it possible to avoid a large number of reagents, auxiliary materials and, most importantly, by-products. All this together allows to reduce the technogenic load on the environment.

The structure of the obtained compound I is determined by NMR spectroscopy and elemental analysis using an AVANCE-500 spectrometer and a Eurovektor EA 3000 analyzer.

The production method is simple to implement and is illustrated by the following examples.

Example 1

To a solution of 1 g (3.56 mmol) of N-methylacridinium tetrafluoroborate (XB) in 10 ml of anhydrous acetonitrile, stirred in the anode space of the electrochemical cell, 1.06 ml (10.68 mmol) of n-butylamine are added at room temperature. After the formation of a colorless solution, the anodic and cathodic regions of the cell, separated by a tracing membrane, are filled with background electrolyte. The background electrolyte is prepared from 50 ml of acetonitrile and 3.86 g (17.8 mmol) of tetraethylammonium tetrafluoroborate. The electrolysis is carried out in galvanostatic mode at a current density of 3 mA / cm ² . After passing the required amount of electricity (2.1 F / mol based on the two-electrode process), electrolysis is stopped. The solvent is distilled off, the residue is recrystallized from water and dried in air. The product yield (Ib, R = Butyl) 0.56 g (45%). ¹ H NMR (DMSO-d ₆ , δ, ppm, J / Hz): 0.91 (t, 3H, J = 7.4), 1.34-1.41 (m, 2H), 1.83-1.89 (m, 2H), 4.02 (t, 2H, J = 7.4), 4.12 (s, 3H), 7.60 (m, 2H), 8.03-8.10 (m, 4H), 8.47 (m, 2H), 10.05 (s, 1H). Found,%: C 61.45; H 6.18; N, 7.79; F 21.68. Calculated,%: C 61.38; H, 6.02; N, 7.95; F 21.58.

Example 2

Ammonia is passed through a solution of 1 g (3.56 mmol) of N-methylacridinium tetrafluoroborate (Hv) tetrafluoroborate (Hv) in 10 ml of dehydrated acetonitrile at room temperature until the solution becomes completely discolored. After that, the anodic and cathodic regions of the cell, separated by a tracing membrane, are filled with background electrolyte. The background electrolyte is prepared from 50 ml of acetonitrile and 3.86 g (17.8 mmol) of tetraethylammonium tetrafluoroborate. The electrolysis is carried out in galvanostatic mode at a current density of 3 mA / cm ² . After passing the required amount of electricity (2.1 F / mol based on the two-electrode process), electrolysis is stopped. The solvent is distilled off, the residue is recrystallized from water and dried in air. The product yield (Ib, R = H) 0.85 g (81%). ¹ H NMR (DMSO-d ₆ , δ, ppm, J / Hz): 4.22 (s, 3H), 7.67 (m, 2H), 8.10-8.14 (m, 2H), 8.22 (m, 2H) 8.67 (m, 2H); 10.05 (s, 2H). Found,%: C 56.67; H 4.48; N, 9.36; F 25.60. Calculated,%: C 56.79; H 4.43; N, 9.46; F 25.67.

Example 3

Methylamine is passed through a solution of 1 g (2.95 mmol) of N-methylacridinium (Xa) hexafluorophosphate in 10 ml of dehydrated acetonitrile at room temperature through a solution stirred in the anode space of the electrochemical cell at room temperature until the solution becomes completely discolored. After that, the anode and cathode regions of the cell, separated by a tracing membrane, are filled with background electrolyte. The background electrolyte is prepared from 50 ml of acetonitrile and 4.66 g (12.05 mmol) of tetrabutylammonium hexafluorophosphate. The electrolysis is carried out in galvanostatic mode at a current density of 3 mA / cm ² . After passing the required amount of electricity (2.1 F / mol based on the two-electrode process), electrolysis is stopped. The solvent is distilled off, the residue is recrystallized from water and dried in air. Yield (Ia, R = Methyl) 0.70 g (65%). ¹ H NMR (DMSO-d ₆ , δ, ppm, J / Hz): 3.64 (s, 3H), 4.11 (s, 3H), 7.59 (m, 2H), 8.04-8.09 (m, 4H) 8.49 (m, 2H); 10.46 (s, 1H). Found,%: C 48.85; H, 4.21; N, 7.69; F 30.79. Calculated,%: C 48.92; H 4.11; N, 7.61; F 30.96.

The use of salts of N-methylacridinium (X), primary amines and acetonitrile as a solvent allows the synthesis to be carried out under mild conditions at room temperature and to significantly reduce its time. Electrolysis is a fully controlled process, which leads to an increase in the efficiency of synthesis and, consequently, to a reduction in the reagents and solvents used. The method allows to abandon the use of toxic and aggressive substances, which helps to reduce anthropogenic pressure on the environment.

Claims (3)

A method of obtaining a salt of 9-amino-10-methylacridinium of the General formula (I)

the interaction of the acridine derivative with an aminating agent in a solvent, characterized in that a primary amine is used as an aminating agent, acetonitrile is used as a solvent, the reaction is carried out at room temperature, and the oxidation is carried out electrochemically in a galvanostatic mode at a current density of 3 mA / cm ² .