RU2551683C1 - Method of producing 1-azidoadamantane - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: method includes reacting an adamantane derivative with an inorganic azide in a solvent. The adamantane derivative used is 1,3-dehydroadamantane and the inorganic azide is an anhydrous hydrogen azide solution in diethyl ether obtained in advance. The process takes place in diethyl ether at 20-40°C and molar ratio of 1,3-dehydroadamantane:hydrogen azide of 1:2-2.7, for 10-20 minutes.

EFFECT: method enables to obtain a 1-azidoadamantane in mild conditions with high output.

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Description

The invention relates to a method for producing derivatives of adamantane, in particular to a new method for producing 1-azidoadamantane of the formula

which is used as intermediates in the synthesis of adamantyl-containing amines and heterocyclic compounds, is used in metal complex catalysis.

A known method of producing 1-azidoadamantane by the reaction of 1-haloadamantanes with trimethylsilyl azide in the presence of Lewis acids [Sasaki, T. Synthesis of Adamantane Derivatives. 56. Reaction of 1-Adamantyl Chloride with Trimethylsilyl Pseudohalide / T. Sasaki, A. Nakanishi, M. Ohno // J. Org. Chem. - 1981. - V. 46, No. 26. -P. 5445-5447]. The disadvantage of this method is the use of inaccessible trimethylsilyl azide, a low yield of the reaction product.

A known method of producing 1-azidoadamantane by the interaction of 1-haloadamantanes with alkali metal azides [Preparation of Secondary and Tertiary Cyclic and Polycyclic Hydrocarbon Azides / G.K. Surya Prakash, M.A. Stephenson, J.G. Shih, G.A. Olah // J. Org. Chem. - 1986, V. 51, No. 16. - P. 3215-3217]. The disadvantage of this method is the duration of the reaction (up to 12 hours) and a low yield of the reaction product.

The closest analogue of the invention is a method for producing 1-azidoadamantane by the reaction of 1-adamantanol with sodium azide in sulfuric acid [Synthesis of Adamantane Derivatives, 37. A Convenient and Efficient Synthesis of 1-Azidoadamantane and Related Bridgehead Azides, and Some of Their Reactions / T. Sasaki, Sh. Eguchi, T. Katada, O. Hiroaki // J. Org. Chem. - 1977. - V. 41, No. 23. - P. 3741-3743]. The disadvantage of this method is the use of acids of a strictly defined concentration, the process is accompanied by the formation of by-products and requires accurate aging of the synthesis.

The objective of the proposed method is to develop a technologically advanced method for the synthesis of 1-azidoadamantane in mild conditions with a high yield.

The technical result is to simplify the method of producing 1-azidoadamantane.

The stated result is achieved in the method for producing 1-azidoadamantane, which consists in reacting an adamantane derivative with an inorganic azide in a solvent, using 1,3-dehydroadamantane as an adamantane derivative, and a previously prepared solution of anhydrous hydrogen azide in diethyl ether as an inorganic azide and the process proceeds in diethyl ether at 20-40 ° C and a molar ratio of 1,3-dehydroadamantane: hydrogen azide, equal to 1: 2-2.7, for 10-20 minutes.

The essence of the invention is to obtain 1-azidoadamantane by the alkylation reaction of hydrogen azide with 1,3-dehydroadamantane. The need to use anhydrous hydrogen azide is caused by the possibility of a side reaction of 1,3-dehydroadamantane with water with the formation of 1-hydroxyadamantane. Anhydrous hydrogen azide is obtained in diethyl ether by reaction of dry sodium azide with concentrated sulfuric acid. The resulting hydrogen azide is immediately dissolved in diethyl ether, which ensures the safety of the further synthesis process, while diethyl ether further serves as a reaction medium.

The method is as follows. To a mixture of sodium azide and diethyl ether (ratio 1: 10-15), the required amount of concentrated (96-98%) sulfuric acid is added dropwise with stirring or shaking. Then the mixture was allowed to settle and the solution of hydrogen azide in diethyl ether was decanted into the reaction flask. Then, a solution of 1,3-dehydroadamantane in diethyl ether (ratio of 1,3-dehydroadamantane: calculated amount of hydrogen azide 1: 1.5-2) is added to it at a rate that does not allow intensive boiling of the mixture. The reaction mass is kept for 10-20 minutes at a temperature of 20-40 ° C, after which the solvent and excess hydrogen azide are removed by vacuum distillation of the water-jet pump or the excess hydrogen azide is removed by shaking the reaction mixture with aqueous solutions of sodium bicarbonate or sodium hydroxide, followed by separation of the organic layer and distillation of the solvent. The residue was recrystallized from 2-propanol to give 1-azidoadamantane in 85-90% yield.

Anhydrous concentrated hydrogen azide is explosive, and the use of its solution in an organic solvent makes working with it convenient and safe. Thus, the proposed method is characterized by simplicity and safety in the synthesis and isolation of products.

The highest yield of the reaction product is achieved when it is carried out with a slight excess of hydrogen azide relative to 1,3-dehydroadamantane. The optimal excess of hydrogen azide is 1: 2-2.7, its further increase does not affect the yield of the target product.

This reaction takes place in the temperature range 20–40 ° C without additional heating. The process begins at room temperature (20-25 ° C), then the mixture is heated due to the exothermic effect (up to 35-40 ° C), which is enough for a quick and complete synthesis in a few minutes. It was found that a sufficient reaction time is 10-15 minutes, a complete conversion of 1,3-dehydroadamantane is achieved in 20 minutes, a further increase in the synthesis time does not affect the yield of the target product.

The invention is illustrated by the following examples:

Пример 1

Example 1

1-azidoadamantane

To a mixture of 5.8 g (0.09 mol) of sodium azide in 20 ml of diethyl ether, 3.9 g (0.04 mol) of conc. H ₂ SO ₄ . The reaction mixture was held for 10-15 minutes, after which the solution of anhydrous hydrogen azide was decanted into a flask under reflux, a solution of 2 g (0.015 mol) of 1,3-dehydroadamantane in 15 ml of diethyl ether was added. The reaction mixture was incubated for 10 minutes, an aqueous solution of NaHCO _{3 was} added until a slightly alkaline reaction. Diethyl ether was distilled off from the organic layer, the residue was recrystallized from propan-2-ol, 2.3 g (0.013 mol, 86%) of 1-azidoadamantane were obtained, so pl. 81-82 ° C (lit. mp. 80-81 ° C). IR spectrum, cm ^-1 : 2115 N ₃ .

Пример 2

Example 2

1-azidoadamantane

To a mixture of 4.5 g (0.07 mol) of sodium azide and 30 ml of diethyl ether, 2.9 g (0.03 mol) of sulfuric acid (concentration 94-96%) are added in portions while shaking. The resulting hydrogen azide solution was separated by decantation and 4 g (0.03 mol) of 1,3-dehydroadamantane in 20 ml of diethyl ether were added to the solution. The reaction mixture was incubated for 20 minutes, then diethyl ether was distilled off in a vacuum of a water-jet pump, the residue was recrystallized from propan-2-ol, 2.4 g (0.0136 mol, 90%) of 1-azidoadamantane were obtained, so pl. 80-81 ° C (lit. mp. 80-81 ° C). IR spectrum, cm ^-1 : 2115 N ₃ .

Thus, a technologically advanced method for the synthesis of 1-azidoadamantane has been developed, consisting in the reaction of 1,3-dehydroadamantane with anhydrous hydrogen azide, proceeding for 10-20 minutes, characterized by simplicity in the synthesis and isolation of products.

Claims (1)

The method of producing 1-azidoadamantane, which consists in reacting an adamantane derivative with an inorganic azide in a solvent, characterized in that 1,3-dehydroadamantane is used as an adamantane derivative, a previously prepared solution of anhydrous hydrogen azide in diethyl ether is used, and the process proceeds in diethyl ether at 20-40 ° C and a molar ratio of 1,3-dehydroadamantane: hydrogen azide, equal to 1: 2-2.7, for 10-20 minutes.