RU2408599C2 - METHOD OF PRODUCING exo-TRICYCLO[4,2,1,02,5]NONANE-3-SPIRO-1'-(3'-SELENIUM)CYCLOPENTANE - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing exo-tricyclo[4,2,1,0^2.5]nonane-3-spiro-1'-(3'-selenium)cyclopentane, which can be used in fine organic synthesis, as well as in synthesis of biologically active heterocyclic compounds. The method involves reaction of 3-methylene-exo-tricyclo[4,2,1,0^2.5]nonane with triethylaluminium in the presence of a zirconocene dichloride catalyst (Cp₂ZrCl₂) in an argon atmosphere at room temperature and atmospheric pressure in hexane for 4 hours and then addition of selenium (Se) to the reaction mass, where selenium is taken in amount which is equimolar to ALEt₃ and stirring at temperature 80°C for 5-7 hours. Output of the end product after hydrolysis of the reaction mass is between 70% and 84%.

EFFECT: high yield.

1 ex, 1 tbl

Description

The present invention relates to organic chemistry, in particular to a method for producing exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane of the formula (1):

The specified compound can find application in fine organic synthesis, as well as in the preparation of heterocyclic compounds with biological activity.

The known method (U. M. Dzhemilev, A. G. Ibragimov, A. P. Zolotarev, G. A. Tolstikov. An unconventional approach to the synthesis of 3-substituted tetrahydrothiophenes and tetrahydroselenofen. Izv. AN. Chem. Series, 1989, No. 6 , 1444) for the preparation of 3-alkylselenofen (2) by the interaction of α-olefin with AlEt ₃ in a benzene solution under the influence of a Cp ₂ ZrCl ₂ catalyst at a temperature of 25 ° C for 8 hours, followed by a three-fold excess of selenium AlEt ₃ and holding the reaction mass for 6 hours at a temperature of ~ 80 ° C. The reaction proceeds according to the scheme:

In a known manner, exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane of the formula (1) cannot be obtained.

There is a method (Y.Vallee, M.Worrell. First Examples of Seleno-Claisen Rearrangements of Allil Vinyl Selenides. JCS, Chem. Commun. 1992, No. 22, 1680-1681) for producing bicyclic selenophanes (3) using Kleisen rearrangement of vinylallyl selenide with the subsequent Diels-Alder reaction according to the scheme:

In a known manner, exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane of the formula (1) cannot be obtained.

A new method is proposed for producing exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane (1).

The essence of the method consists in the interaction of 3-methylene-exo-tricyclo [4.2.1.0 ^2,5 ] nonane (4) with triethylaluminium (Et ₃ Al) in the presence of a catalyst of zirconacenedichloride (Cp ₂ ZrCl ₂ ), taken in a molar ratio of 3-methylene exo-tricyclo [4.2.1.0 ^2.5 ] nonane: Et ₃ Al: Cp ₂ ZrCl ₂ = 10: (10-14) :( 0.4-0.6), preferably 10: 12: 0.5, in an argon atmosphere at room temperature ( 20-21 ° C) and atmospheric pressure in an aliphatic solvent (hexane) for 4 hours, followed by the addition of 10 ml of benzene and selenium (Se) taken in an amount equimolar to AlEt ₃ and stirring at a temperature round 80 ° C for 5-7 hours, preferably 6 hours. The yield of exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane is 70-84%. The reaction proceeds according to the scheme:

exo-Tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane (1) is formed only with the participation of AlEt ₃ , 3-methylene-exo-tricyclo [4.2.1.0 ^{2 , 5} ] nonane and zirconium catalyst Cp ₂ ZrCl ₂ . In the presence of other aluminum compounds (e.g., Bu ₂ ⁱ AlCl, Bu ₃ ⁱ Al, Bu ₂ ⁱ AlH, EtAlCl ₂ , Et ₂ AlCl), other unsaturated compounds (α-olefins, dienes, acetylenes) or other catalysts (e.g. Zr (acac) ₄ , ZrCl ₄ , Cp ₂ TiCl ₂ , Pd (acac) ₂ , Ni (acac) ₂ , NiCl ₂ , Fe (acac) ₂ ) the target product (1) is not formed.

Carrying out this reaction in the presence of a Cp ₂ ZrCl ₂ catalyst _of more than 6 mol% with respect to 3-methylene-exo-tricyclo [4.2.1.0 ^2,5 ] nonane does not lead to a significant increase in the yield of the target product (1). The use of the catalyst Cp ₂ ZrCl ₂ less than 4 mol.% Reduces the yield of tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro (2'-thiophan) (1), which is possibly associated with a decrease in catalytically active centers in the reaction mass .

Carrying out the process (after adding Se) at a higher temperature (for example, 100 ° C) increases the energy consumption of the reaction. Carrying out the process at a lower temperature (for example, 60 ° C) reduces the reaction rate. Changing the ratio of the starting reagents in the direction of increasing their content relative to the starting 3-methylene-exo-tricyclo [4.2.1.0 ^2,5 ] nonane does not lead to a significant increase in the yield of the target product (1).

Reactions were carried out using aliphatic solvents (hexane). In other solvents (e.g., ethereal), the reaction does not proceed.

Significant differences of the proposed method.

In the known method, bicyclic selenophan (3) is obtained by the Kleisen rearrangement of vinylallyl selenide followed by the reaction with dicyclopentadiene according to Diels-Alder.

In the proposed method, exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane (1) is obtained from 3-methylene-exo-tricyclo [4.2.1.0 ^2,5 ] nonane and Et ₃ Al with the participation of Cp ₂ ZrCl ₂ as a catalyst, followed by treatment of the reaction mass with Se.

The proposed method has the following advantages.

1. The method allows to obtain with high selectivity exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane of the general formula (1).

The method is illustrated by the following examples.

EXAMPLE 1. In a 50 ml glass reactor mounted on a magnetic stirrer, 2 ml of hexane, 10 mmol of 3-methylene-exo-tricyclo [4.2.1.0 ^2,5 ] nonane, 0.5 mmol of catalyst Cp ₂ ZrCl ₂ , are placed in an argon atmosphere. at a temperature of ~ 0 ° C, 12 mmoles of AtEt ₃ are stirred for 4 hours at room temperature (20-21 ° C), then the reaction mass is cooled to ~ 0 ° C, 12 mmoles of selenium (Se) are added and stirred at this temperature for 6 hours. At the end of the reaction, the reaction mixture is treated with 5% HCl, exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane (1) is isolated in 76% yield.

Spectral characteristics of exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane (1):

¹³ C NMR spectrum (δ, ppm) of exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane (1): 50.2 (С-3), 49.6 (C-2), 46.7 (C-13), 38.6 (C-6), 36.7 (C-5), 36.6 (C-1), 34.2 (C-9), 33.5 (C-4), 29.0 (C-10), 28.8 (C-7), 28.1 (C-8), 20.3 (C-12).

Other examples confirming the method are given in table 1.

Table 1 No. p / p The molar ratio of 3-methylene-exo-tricyclo [4.2.1.0 ^2.5 ] nonane: AlEt ₃ : Cp ₂ ZrCl ₂ : Se, mmol Total reaction time, hour The yield of exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1 '- (3'-selenium) cyclopentane (1),% one 2 3 four one. 10: 12: 0.5: 12 10 76 2. 10: 14: 0.5: 14 10 78 3. 10: 10: 0.5: 10 10 74 four. 10: 12: 0.6: 12 10 84 5. 10: 12: 0.4: 12 10 70 6. 10: 12: 0.5: 12 eleven 82 7. 10: 12: 0.5: 12 9 71

The experiments were carried out in hexane at room temperature (20-21 ° C). The reaction with selenium was carried out in benzene at a temperature of 80 ° C.

Claims (1)

The method of producing exo-tricyclo [4.2.1.0 ^2,5 ] nonan-3-spiro-1'-3'-selenium) cyclopentane of the general formula (1),

,
characterized in that 3-methylene-exo-tricyclo [4.2.1.0 ^2,5 ] nonane is reacted with triethylaluminium (AlEt ₃ ) in the presence of a catalyst of zirconacene dichloride (Cp ₂ ZrCl ₂ ) at a molar ratio of 3-methylene-exo-tricyclo [4.2 .1.0 ^2.5 ] nonane: AlEt ₃ : Cp ₂ ZrCl ₂ = 10: (10-14) :( 0.4-0.6) in an argon atmosphere at room temperature and atmospheric pressure in hexane for 4 hours, followed by addition to the reaction the mass of selenium (Se) taken in an amount equimolar to AlEt ₃ , and stirring at a temperature of 80 ° C for 5-7 hours