RU2294928C2 - Method for preparing 1-[1-hydroxy-1-(pyrid-4-yl)methyl]-1,2-dihydro[60]fullerenes - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 1-[1-hydroxy-1-(pyrid-4-yl)methyl]-1,2-dihydro[60]fullerene. Method involves interaction of C₆₀ with ethylaluminum dichloride and magnesium in the presence of catalyst, in argon atmosphere, at room temperature and under atmosphere pressure in medium of mixed solvent tetrahydrofuran-toluene for 8 h followed by addition nickel-containing catalyst and 4-pyridinecarbaldehyde to the reaction mass at -15°C. Then the reaction mass is stirred at room temperature for 6-10 h followed by its hydrolysis. The total yield of end substances after hydrolysis of the reaction mass is 33-52%. Invention provides the development of a method for synthesis of novel fullerene-containing alcohols. Synthesized compound can be used in fine organic synthesis, manufacture of drugs and biologically active substances.

EFFECT: improved method of synthesis.

1 tbl, 1 ex

Description

The present invention relates to organic chemistry, specifically to a method for producing 1- [1-hydroxy-1- (pyrid-4-yl) methyl] -1,2-dihydro [60] fullerenes of the general formula (1):

Fullerene-containing alcohols and their derivatives can be used in fine organic synthesis, in the production of drugs, biologically active substances.

The known method (Dzhemilev U.M., Ibragimov A.G., Hafizova L.O., Borisova A.L., Tuktarov R.F., Abzalimov PP, Halilov L.M. RF patent №2238263. No. 29 (2004)) for the preparation of 1- [1'-hydroxy-1'-alkyl (1 ', 1'-dialkyl)] methyl-2-hydro [60] fullerenes (3) by reaction of fullerene [60] with EtAlCl ₂ - Mg under the action of the catalyst Cp ₂ TiCl ₂ followed by the addition of ketone in the presence of a CuCl catalyst according to the scheme:

The known method does not allow to obtain fullerene-containing alcohols of the general formula (1).

A new method is proposed for the preparation of 1- [1-hydroxy-1- (pyrid-4-yl) methyl] -1,2-dihydro [60] fullerenes of the formula (1).

The essence of the method consists in the interaction of fullerene C ₆₀ with ethyl aluminum dichloride (EtAlCl ₂ ) and magnesium (Mg, powder) taken in a molar ratio of C ₆₀ : EtAlCl ₂ : Mg = 1: (25-35) :( 25-35), preferably 1 : 30: 30, in the presence of a catalyst of titanocene dichloride (Cp ₂ TiCl ₂ ) in an amount of 15-25 mol. % with respect to C ₆₀ , preferably 20 mol. %, in an argon atmosphere at room temperature (20-21 ° С) and atmospheric pressure in a mixed solvent tetrahydrofuran-toluene (~ 1: 5 volume) for 8 hours, followed by the addition of a catalyst to the reaction mass at a temperature of -15 ° С, consisting of from nickel acetylacetonate (Ni (acac) ₂ ) and triphenylphosphine (Ph ₃ P), taken in a molar ratio of 1: 2, respectively, in an amount of 15-25 mol. % based on Ni (acac) ₂ with respect to the starting fullerene C ₆₀ , preferably 20 mol. %, and 4-pyridinecarbaldehyde in an amount equimolar to EtAlCl ₂ , followed by stirring of the reaction mixture at room temperature (20-21 ° C) for 6-10 hours, preferably 8 hours. The total yield of 1- [1-hydroxy-1- (pyrid-4-yl) methyl] -1,2-dihydro [60] fullerenes of the formula (1) after hydrolysis of the reaction mass is 33-52%.

The reaction proceeds according to the scheme:

Significant differences of the proposed method

In the proposed method, pyridinecarbaldehyde is used as a carbonyl compound, the reaction is carried out in the presence of a two-component catalyst consisting of nickel acetylacetonate (Ni (acac) ₂ ) and triphenylphosphine (Ph ₃ P), taken in a 1: 2 molar ratio, respectively, in a mixed solvent (tetrahydrofuran -toluene). In the known method, alkyl substituted ketones and a CuCl catalyst are used as carbonyl compounds. The proposed method, unlike the known one, allows the preparation of 1- [1-hydroxy-1- (pyrid-4-yl) methyl] -1,2-dihydro [60] fullerenes of the formula (1), the synthesis of which is not described in the literature.

The method is illustrated by the following examples.

EXAMPLE 1. 140 ml of dry toluene and 30 ml of THF, 0.14 mmol of C ₆₀ , 0.028 mmol of catalyst Cp ₂ TiCl ₂ , 4.2 mmol of Mg (powder) and at a temperature of ~ are placed in a 250 ml glass reactor mounted on a magnetic stirrer in an argon atmosphere. 0 ° C 4.2 mmol EtAlCl ₂ , stirred for 8 hours at room temperature (20-21 ° C), then at a temperature of -15 ° C add a two-component catalyst consisting of 0.028 mmol Ni (acac) ₂ , 0.056 mmol Ph ₃ P and 4 , 2 mmol of 4-naphthalene carbaldehyde, stirred for 8 hours at a temperature of 20-21 ° C. The reaction mass is hydrolyzed with a saturated solution of NH ₄ Cl. 1- [1-hydroxy-1- (pyrid-4-yl) methyl] -1,2-dihydro [60] fullerene (1) is isolated from the organic layer in 45% yield.

Spectral characteristics of 1- [1-hydroxy-1- (pyrid-4-yl) methyl] -1,2-dihydro [60] fullerene (1):

IR spectrum (ν / cm ^-1 ): 3350, 2910, 2850, 1450, 1380, 1090, 1020, 750, 730, 580, 520. ¹ H NMR spectrum (δ, ppm): 3.80 (m, H, CH-OH); 6.53 (s, H, HC ₆₀ ); 7.05-7.25 (m, 4H, arom.).

¹³ C NMR spectrum (CDCl ₃ , CS ₂ , δ, ppm): 81.06 (C ¹ ), 120.22 (C ^3.7 ), 148.44 (C ^4.6 ), 152.73 (C ² ).

The signals of the carbon atoms of the sp ² -hybridized fullerene fragment are located in the region of 126.13-161.22 ppm. The signals of sp ³ -hybridized carbon atoms of the fullerene fragment correspond to signals at δ = 59.48 and 69.18 ppm.

Other examples confirming the method are shown in table 1.

Table 1 №№

:Ni(acac)₂:Ph₃P, ммольThe ratio of C ₆₀ : EtAlCl ₂ : Cp ₂ ZrCl ₂ :

: Ni (acac) ₂ : Ph ₃ P, mmol Total reaction time, hour Yield of 1- [1-hydroxy-1- (pyrid-4-yl) methyl] -1,2-dihydro [60] fullerene (1),% one 0.14: 4.2: 0.028: 4.2: 0.028: 0.056 16 45 2 0.14: 4.9: 0.028: 4.9: 0.028: 0.056 16 49 3 0.14: 3.5: 0.028: 3.5: 0.028: 0.056 16 37 four 0.14: 4.2: 0.035: 4.2: 0.035: 0.070 16 52 5 0.14: 4.2: 0.021: 4.2: 0.021: 0.042 16 33 6 0.14: 4.2: 0.028: 4.2: 0.028: 0.056 eighteen fifty 7 0.14: 4.2: 0.028: 4.2: 0.028: 0.056 fourteen 43

The reactions were carried out at room temperature (20-21 ° C) in a solution of toluene-tetrahydrofuran in an argon atmosphere without access of light. In all experiments, the number of substituents in the fullerene molecule [60] varies from 1 to 2.

Claims (1)

The method of obtaining 1- [1-hydroxy-1- (pyrid-4-yl) methyl] -1,2-dihydro [60] fullerenes of the General formula (1)

characterized in that the fullerene C ₆₀ is reacted with ethyl aluminum dichloride (EtAlCl ₂ ) and magnesium (Mg) at a molar ratio of C ₆₀ : EtAlCl ₂ : Mg = 1: (25-35) :( 25-35) in the presence of a titanium-cenadichloride catalyst (Cp ₂ TiCl ₂ ), taken in an amount of 15-25 mol.% With respect to C ₆₀ , in an argon atmosphere at room temperature (20-21 ° C) and atmospheric pressure in a mixed solvent of tetrahydrofuran-toluene for 8 hours, followed by addition to the reaction mass at a temperature of -15 ° C of a catalyst consisting of nickel acetylacetonate (Ni (acac) ₂ ) and triphenylphosphine (Ph ₃ P) taken in a molar ratio of 1: 2, respectively, in an amount of 15-25 mol.% Calculated on Ni (acac) ₂ with respect to C ₆₀ and 4-pyridinecarbaldehyde in an amount equimolar with respect to EtAlCl ₂ , after which the reaction the mass is stirred at room temperature for 6-10 hours and hydrolyzed.