RU2285005C1 - Method for preparing 3,6-diazahomoadamantane - Google Patents

Abstract

FIELD: organic chemistry, chemical technology, virology.

SUBSTANCE: invention relates to a new method for synthesis of a novel compound - 3,6-diazahomoadamantane of the formula:

. Compounds of 3,6-diazahomoadamantane class possess an antiviral effect comparable with antiviral effect of aminoadamantane, elicit strychnine-like activity and show bactericidal, fungicide and algicidal properties and can be used as an antiviral preparation. Method for synthesis of 3,6-diazahomoadamantane involves interaction of 1-phenylthio-3,6-diazahomoadamantane-9-one with 65-66% hydrazine hydrate at boiling to form 1-phenylthio-3,6-diazahomoadamantane-9-one hydrazone that is subjected for reduction in Kizhner-Wolf reaction by alloying with alkali and then 1-phenylthio-3,6-diazahomoadamantane is desulfurized with Raney nickel in isopropyl alcohol at boiling.

EFFECT: improved method of synthesis.

2 cl, 1 ex

Description

The invention relates to the field of organic chemistry, and specifically to a method for producing 3,6-diazagomoadamantane, which has the following structure:

Compounds of the class 3,6-diazagomoadamantane have an antiviral effect comparable to the antiviral effect of aminoadamantane, exhibit strychnine-like activity, and also have bactericidal, fungicidal and algicidal properties.

A known method of producing 1-alkyl- and 1-aryl-3,6-diazagomoadamantane by reduction of the corresponding hydrazone at a temperature of 220-240 ° C in the presence of alkali according to the Kizhner-Wolf reaction [Kuznetsov AI, Vladimirova IA, Serova T .M., Moskovkin A.S. Heteroadamantanes and their derivatives. 17. Recovery of 3,6-diazagomoadamantanones according to Kizhner-Wolf. // HCG. - 1992. - No. 5 - S.653-657.]. However, under the conditions of this reaction, the hydrazone of 3,6-diazagomoadamantane without substituents in the nodal positions is converted to azine. The presence of bulky substituents in the diazagomoadamantane molecule reduces the biological activity of the substance.

The technical task of the invention is to develop an affordable method for the synthesis of 3,6-diazagomoadamantane without substituents in the nodal positions.

The technical result of the proposed achievement is that 1-phenylthio-3,6-diazagomadamantan-9-one, which is obtained by a known method [Kuznetsov AI, Vladimirova IA, Basargin EB and other heteroadamantanes and their

R = Me, Et, Pr, Ph

derivatives. II. Synthesis of 3,6-diazagomoadamantan-9-one and its derivatives with substituents in nodal positions. // HCG. - 1990. - No. 5. - S.675-680.] When heating phenylthioacetone with tetramethylene diethylenetetramine while boiling in isopropyl alcohol in the presence of acetic acid as a catalyst, they turn 1-phenylthio-3,6-diazagomoadamantan-9-one into a hydrazone at a boiling point of 65-66% - hydrazine hydrate, which is then subjected to reduction in 1-phenylthio-3,6-diazagomoadamantane by fusion with alkali, and the obtained 1-phenylthio-3,6-diazagomoadamantane is desulfurized with Raney nickel while boiling in isopropyl alcohol. The yield of 3,6-diazagomoadamantane was 76%. The synthesis is carried out according to the following scheme:

Example 1

1-phenylthio-3,6-diazagomoadamantan-9-one

A solution of 3.66 g (21.78 mmol) of tetramethylene diethylenetetramine and 3.27 ml (54.45 mmol) of acetic acid in 30 ml of isopropyl alcohol was heated to 60 ° C. Then, 3.61 g (21.78 mmol) of phenylthioacetone was added and stirred at room temperature for 1 h. The solvent was evaporated in vacuo. The reaction mass was treated with hot heptane (3 × 100 ml), the extractant was evaporated in vacuo. Recrystallization from heptane gave 2 g of 1-phenylthio-3,6-diazagomoadamantan-9-one. Yield 35%. _Mp 133-134 ° C. IR spectrum, ν, cm ^-1 : 1695 (СО), 1600 (arom). ¹ H-NMR Spectrum, δ, ppm: 3.02 m (4H, NCH ₂ CH ₂ N); 3.55-3.25 m (8H, NCH ₂ C, ² J = 14.0 Hz); 0.80 br s (1H, CH); 7.45 d, 7.12 d (C ₆ H ₅ ). Mass spectrum, m / z (I _rel. ,%): 274 [M ⁺ ]

1-phenylthio-3,6-diazagomoadamantan-9-one hydrazone

A solution of 2.37 g (8.64 mmol) of 1-thiophenyl-3,6-diazagomoadamantan-9-one in 40 ml of a 66% aqueous solution of hydrazine hydrate was heated at the boil for 3 h. Cooled to 0 ° C, the precipitate was filtered off. Recrystallization from isopropyl alcohol gave 2 g of 1-thiophenyl-3,6-diazagomoadamantan-9-one hydrazone. Yield 80%. _Mp 189-190 ° C. IR spectrum, ν, cm ^-1 : 3300, 1560 (NH), 1680 (C = N), 1600 (arom). ¹ H-NMR Spectrum, δ, ppm: 2.98 m (4H, NCH ₂ CH ₂ N); 3.52-2.75 m (8H, NCH ₂ C, ² J = 14.0 Hz); 5.20 br s (NH ₂ ); 1.90 br s (1H, CH) 7.55 d, 7.35 d (C ₆ H ₅ ). Mass spectrum, m / z (I _rel. ,%): 288 [M ⁺ ]

1-phenylthio-3,6-diazagomoadamantane 13

A carefully mixed mixture of 1.90 g (6.59 mmol) of 1-phenylthio-3,6-diazagomoadamantan-9-one hydrazone and 1.75 g of potassium hydroxide powder was alloyed for 2 hours at 220-240 ° C. The cooled alloy was extracted with diethyl ether (2 × 25 ml), the solvent was distilled off in vacuo. Recrystallization from heptane afforded 1.30 g of 1-phenylthio-3,6-diazagomoadamantane. Yield 76%. _Mp 87-89 ° C. IR spectrum, ν, cm ^-1 : 1600 (arom). ¹ H-NMR Spectrum, δ, ppm: 3.00 m (4H, NCH ₂ CH ₂ N); 3.35-2.60 m (8H, NCH ₂ C, ² J = 14.0 Hz); 1.85 ears s (1H, CH); 1.25 s (2 H, CH ₂ ). Mass spectrum, m / z (I _rel. ,%): 260 [M ⁺ ]

3,6-diazagomoadamantane

To a solution of 0.40 g (2.33 mmol) of 1-phenylthio-3,6-diazagomoadamantane in 20 ml of isopropyl alcohol was added 2 g of freshly prepared Raney nickel and the mixture was boiled for 20 h, additionally adding 2 g of Raney nickel every 7 hours. The catalyst was filtered off, washed with isopropyl alcohol, and the filtrate was evaporated in vacuo. Recrystallization from heptane gave 0.18 g of 3,6-diazagomoadamantane. Yield 76% (calculated as 1-phenylthio-3,6-diazagomoadamantane). _Mp 250-251 ° C.

¹ H-NMR Spectrum, δ. ppm: 3.12 m (4H, NCH ₂ CH ₂ N); 3.42 d, 2.80 d (8H, CCH ₂ N ² J = 14.0 Hz); 1.85 broad s (1H, CH), 1.30 s (2H, CH ₂ ). ¹³ C-NMR spectrum, δ, ppm: 29.79 (C-1.8), 34.07 (C-8), 57.27 (C-5, 4), 62.37 (C-2, 7, 10, 11) . Mass spectrum, m / z ( _Irel ,%): 152 [M ⁺ ] (97), 108 (97), 95 (66), 85 (30), 72 (17), 60 (45), 55 (57), 57 (100), 42 (65). Elemental analysis: calculated,% C 71.05, H 10.52, N 18.52, found,% C 71.09, H 10.50, N 18.50.

The individuality of the compounds was confirmed by a combination of mass spectrometry, IR, ¹ H-NMR- ¹³ C-NMR spectroscopy, as well as elemental analysis.

Thus, this method allows to obtain 3,6-diazagomadamantane without substituents in the nodal positions, which can be used as an antiviral drug.

Claims (1)

The method of producing 3,6-diazagomoadamantane, which consists in the interaction of 1-phenylthio-3,6-diazagomoadamantan-9-one with 65-66% hydrazine hydrate at the boil to form 1-phenylthio-3,6-diazagomoadamantan-9-one hydrazone, which subjected to reduction by the Kizner-Wolf reaction by fusion with alkali, and the obtained 1-phenylthio-3,6-diazagomoadamantane is desulfurized with Raney nickel while boiling in isopropyl alcohol.