RU2355676C2 - Method of spiro[3,4]oct-6-ylformiate obtainment - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention concerns organic chemistry, particularly method of obtaining spiro[3,4]oct-6-ylformiate. Method

(1) involves interaction of methylenecyclobutane with triethylaluminium (AlEt₃) in the presence of zirconocene dichloride catalyst (Cp₂ZrCl₂) at molar ratio of methylenecyclobutane: AlEt₃:Cp₂ZrCl₂=10:(11-15):(0.5-0.7) in argon atmosphere at room temperature and atmospheric pressure in hexane for 7 hours, with further addition of copper chloride catalyst (CuCl) in amount equimolar to Cp₂ZrCl₂, and alkylformiate of the general formula HCO₂R (where R=Et, n-Pr, n-Bu) thrice exceeding amount of AlEt₃, to reaction mass at -15°C, further stirring at room temperature for 8-10 hours, and acid hydrolysis of reaction mass. Total output of end product after acid hydrolysis of reaction mass reaches 73-89%.

EFFECT: possible application in fine organic synthesis and production of paint coating materials and bioactive substances.

1 ex, 1 tbl

Description

The present invention relates to organic chemistry, in particular to a method for producing spiro [3,4] oct-6-yl formate of the formula (I):

Esters of carboxylic acids can be used in fine organic synthesis, in particular in the preparation of spiro [3.4] octa-5,7-diene ([1] I. Erden, EMSorenson, A convenient synthesis ofspiro [3.4] oct-5,7- diene, Tet. Lett., V.27, 1983, 2731-2732) and the dispiro [2.1.3.2.] dean ([2] JE Baldwin and R. ShukIa, Two synthesis of dispiro [2.1.3.2.] decane, Org .Lett, 1999, VI, No. 7) in the manufacture of paints and varnishes, biologically active substances ([3] Pradhan R. Et al. "A synthon approach to spiro compounds", Tetrahedron 62 (2006) 779-828, [4] Rice LM, Grogan CH "Spiranes. II. Spiro [3.3] heptane derivatives).

The known method ([5] Dzhemilev U.M., Ibragimov AG, Vostrikova OS, Vasilieva EV, Tolstikov GA Regio-selective hydroalumination of unsaturated hydrocarbons catalyzed by zirconium complexes with alkylalans Izv. AN SSSR. Ser. Chem., 1987, p.1089) for the preparation of 1,3-dimethylcyclopentyl) methyl acetate by reacting 2,5-dimethyl-1,5-hexadiene with di (isobutyl) aluminum chloride (i-Bu ₂ AlCl) in the presence of a Cp ₂ ZrCl ₂ catalyst with subsequent oxidation of the reaction mass with oxygen, then hydrolysis and treatment after isolation of the resulting dimethylcyclopene ylmethyl alcohol with acetic anhydride according to the scheme

In a known manner can not be obtained spiro [3,4] oct-6-ylformate of the formula (1):

The known method ([6] Dzhemilev U.M., Ibragimov AG, Vostrikova OS, Vasilieva EV, Tolstikov GA Regio-selective hydroalumination of unsaturated hydrocarbons catalyzed by zirconium complexes with alkylalans Izv. AN SSSR. Ser. Chem., 1987, p.1089) for the preparation of (cyclopentyl) methyl acetate by the interaction of 1,5-hexadiene with di (isobutyl) aluminum chloride in the presence of a Cp ₂ ZrCl ₂ catalyst, followed by oxidation of the reaction mass with oxygen, then hydrolysis and treatment after isolation of the resulting cyclopentyl methyl alcohol using vinegar meat anhydride according to the scheme

The known method does not allow to obtain spiro [3,4] oct-6-yl formate of the formula (1):

A new method is proposed for producing spiro [3,4] oct-6-yl formate (1).

The essence of the method consists in the interaction of methylene cyclobutane with triethylaluminum (Et ₃ Al) in the presence of a catalyst of zirconacenedichloride

(Cp ₂ ZrCl ₂ ) taken in a molar ratio of methylene cyclobutane: Et ₃ Al: Cp ₂ ZrCl ₂ = 10: (11-15) :( 0.5-0.7), preferably 10: 13: 0.6, in an argon atmosphere at room temperature ( 20-21 ° C) and atmospheric pressure in an aliphatic solvent (hexane) for 7 hours, followed by adding to the reaction mass at a temperature of -15 ° C a catalyst of copper chloride (CuCl), taken in an amount equivalent to Cp ₂ ZrCl ₂ , and alkyl formate of the formula HCO ₂ R, where R = Et, n-Pr, n-Bu, taken in threefold excess relative to AlEt _3, followed by stirring the reaction mixture at room temperature (20-21 ° C) for 8-10 hours, preferably 9 hours. After processing the reaction mixture with an 8-10% aqueous HCl solution, spiro [3,4] oct-6-ylformate (1) is obtained with a total yield of 73-89 % The reaction proceeds according to the scheme.

Spiro [3,4] oct-6-ylformate (1) is formed only with the participation of AlEt ₃ , methylene cyclobutane and a 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) 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 catalyst Cp ₂ ZrCl ₂ or CuCl greater than 0.7 mmol per 10 mmol of methylene cyclobutane does not significantly increase the yield of the target product (1). The use of the catalyst Cp ₂ ZrCl ₂ and CuCl less than 0.5 mmol per 10 mmol of methylene cyclobutane reduces the yield of spiro [3,4] oct-6-yl formate (1), which is possibly associated with a decrease in catalytically active centers in the reaction mass. The reactions were carried out at room temperature (20-21 ° C). At a higher temperature (for example, 60 ° C), there is no significant increase in the yield of the target product, and at a lower temperature (for example, 0 ° C), the reaction rate decreases.

Changing the ratio of the starting reagents in the direction of increasing their content relative to the starting methylene cyclobutane 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., ether), the reaction does not proceed.

Significant differences of the proposed method

In the known method, 1,5-hexadiene, di (isobutyl) aluminum chloride, gaseous oxygen and acetic anhydride are used as starting materials, and in the proposed method, methylenecyclobutane, tertylaluminium, alkyl formates are used as starting compounds, the reaction mixture is hydrolyzed with an aqueous HCl solution.

The proposed method has the following advantages

The method allows to obtain with high regioselectivity spiro [3,4] oct-6-yl formate of the general formula (1), the synthesis of which is not described in the literature.

The method is illustrated by the following examples.

EXAMPLE 1. In a glass reactor mounted on a magnetic stirrer, in an argon atmosphere, 5 ml of hexane, 10 mmol of methylenecyclobutane, 0.6 mmol of catalyst Cp ₂ ZrCl _{2 are} placed, at a temperature of ~ 0 ° C 13 mmol of AlEt ₃ are stirred for 7 hours at room temperature 20 -21 ° C, then 0.6 mmol of CuCl catalyst and 39 mmol of ethyl formate are added at a temperature of -15 ° C, stirred for 9 hours at a temperature of 20-21 ° C, the reaction mass is hydrolyzed with an aqueous solution (8-10%) of HCl. Spiro [3,4] oct-6-ylformate is isolated from the organic layer in 81% yield.

Spectral characteristics of spiro [3,4] oct-6-ylformate (1):

¹³ C NMR spectrum (δ, ppm) of spiro [3,4] oct-6-ylformate (1): 16.24, 31.35, 33.82, 33.89, 37.41, 39.55, 45.87, 76.02, 160.84

Other examples confirming the method are given in the table.

Table №№ HCO ₂ R The molar ratio of methylene cyclobutane: AlEt ₃ : Cp ₂ ZrCl ₂ : HCO ₂ R: CuCl, mmol Total reaction time, h The output of spiro [3,4] oct-6-ylformate (1),% one. 2 3 four 5 one. R = Et 10: 13: 0.6: 39: 0.6 16 81 2. - "- 10: 15: 0.6: 45: 0.6 16 84 3. - "- 10: 11: 0.6: 33: 0.6 16 75 four. - "- 10: 13: 0.7: 39: 0.7 16 89 5. - "- 10: 13: 0.5: 39: 0.5 16 73 6. - "- 10: 13: 0.6: 39: 0.6 17 83 7. - "- 10: 13: 0.6: 39: 0.6 fifteen 77 8. R = n-Pr 10: 13: 0.6: 39: 0.6 16 80 9. R = n-Bu 10: 13: 0.6: 39: 0.6 16 76

The experiments were carried out in hexane at room temperature (20-21 ° C).

Claims (1)

The method of obtaining spiro [3,4] oct-6-ylformate (1)

,
characterized in that methylene cyclobutane is reacted with triethylaluminium (AlEt ₃ ) in the presence of a zirconacene dichloride catalyst
(Cp ₂ ZrCl ₂ ) at a molar ratio of methylene cyclobutane: AlEt ₃ : Cp ₂ ZrCl ₂ = 10: (11-15) :( 0.5-0.7) in an argon atmosphere at room temperature and atmospheric pressure in hexane for 7 h, followed by adding to the reaction mass at a temperature of -15 ° C a catalyst of copper chloride (CuCl) in an amount equilibrium with Cp ₂ ZrCl ₂ and an alkyl formate of the general formula HCO ₂ R (where R = Et, n-Pr, n-Bu) a three-fold excess with respect to AlEt ₃ , stirring at room temperature for 8-10 hours, and acid hydrolysis of the reaction mixture.