RU2316552C1 - Method for preparing 2,3,4,5-tetraalkylthiophenes - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 2,3,4,5-tetraalkylthiophenes. Method involves interaction of disubstituted acetylenes with R'-AlCl₂ and SOCl₂ in the presence of metallic Mg and zirconacene dichloride as a catalyst in argon atmosphere in tetrahydrofuran medium for 11-15 h. Proposed method shows the simplified technology and uses easily available and nontoxic raw and provides preparing the end product with the yield about 47-54%. Synthesized compounds can be used in food industry, as biologically active compounds, dyes, addition agents to oils and hydraulic liquids.

EFFECT: improved method of synthesis, valuable properties of compounds.

1 tbl, 10 ex

Description

The present invention relates to organic chemistry, specifically to an improved method for producing 2,3,4,5-tetraalkylthiophenes of the general formula (1):

where R = C ₂ H ₃ , nC ₃ H ₇ , nC ₄ H ₉

Substituted thiophenes can find application in the food industry as components of food flavor enhancers, biologically active compounds, dyes, additives to oils and hydraulic fluids.

A known method ([1], RJFagan, WANugent, JCCalabrese. Metallacycle transfer from zirconium to main group elements: A versatile synthesis of heterocycles // JACS, V.116, 5, (1994), 1880-1890) for producing tetrasubstituted thiophenes (2 ) with a yield of ~ 55% by the interaction of α, ω-diacetylenes with bis-cyclopentadienyl zirconium dichloride and butyllithium (n-BuLi), followed by treatment of the reaction mixture with sulfur chloride (S ₂ Cl ₂ ) for 1 h according to the scheme:

In a known manner, 2,3,4,5-tetraalkylthiophenes (1) cannot be obtained.

The known method ([2], J. Chen, Q.Song, Z. Xi. Novel reaction patterns of carbon disulfide with organolithium compounds via cleavage of C = S bonds or via cycloaddition reactions // Tetrahedron Lett., 43 (2002), 3533-3535) for the production of tetraalkylthiophenes by the reaction of 1,4-dilithio-1,3-dienes prepared by treating 1,2,3,4-tetraalkyl-1,4-diiod-1,3-butadiene with butyl lithium (n-BuLi) at a temperature -78 ° C for 1 h, with carbon disulfide at -20 ° C for 1 h with a yield of 52-68% according to the scheme:

A known method for the synthesis of 2,3,4,5-tetraalkylthiophenes (1) involves the use of inaccessible 1,4-diiodo-1,3-butadiene, pyrophoric n-BuLi and carbon disulfide (CS ₂ ), which is a highly flammable, volatile and highly toxic liquid In addition, during the reaction it is necessary to maintain a low temperature of -78 ° C.

An improved method for the synthesis of 2,3,4,5-tetraalkylthiophenes (1) is proposed.

The essence of the method is the interaction of disubstituted acetylenes of the formula R-≡-R, where R = C ₂ H ₅ , nC ₃ H ₇ , nC ₄ H ₉ , with R'AlCl ₂ (R '= C ₂ H ₅ , Cl) and metallic Mg in the presence of a catalyst of zirconacene dichloride Cp ₂ ZrCl ₂ , taken in the molar ratio R-≡-R: R'AlCl ₂ : Mg: Cp ₂ ZrCl ₂ = 10: (6-10) :( 6-10): (1.0-1.4), preferably 10: 8: 8: 1.2, for 8 hours, followed by the addition of thionyl chloride (SOCl ₂ ) at -40 ° C in an equimolar amount with respect to R'AlCl ₂ and stirring the reaction mixture for 1 hours. Then the temperature was brought to room temperature and stirred for another 2-6 hours. The reaction is carried out in an atmosphere Feret argon and atmospheric pressure. The total reaction time of 11-15 hours, the yield of target products 39-54%. As a solvent, tetrahydrofuran must be used; in other ether solvents (ether, dioxane), the yield of the target products (1) is significantly reduced.

The reaction proceeds according to the scheme:

R = C ₂ H ₅ , n-C ₃ H ₇ , n-C ₄ H ₉ ; R '= C ₂ H ₅ , Cl

The target products (1) are formed only with the participation of disubstituted acetylene, R'AlCl ₂ , thionyl chloride (SOCl ₂ ) and a catalyst Cp ₂ ZrCl ₂ . In the presence of other catalysts based on transition metal complexes (for example, Zr (acac) ₄ , Cp ₂ TiCl ₂ , Pd (acac) ₂ , Ni (acac) ₂ , Fe (acac) ₃ ), the target products (1) are not formed.

The reaction in the presence of a catalyst Cp ₂ ZrCl ₂ taken in an amount of more than 14 mol. % with respect to acetylene, does not lead to a significant increase in the yield of the target products (1). Using in the reaction of the catalyst Cp ₂ ZrCl ₂ in an amount of less than 10 mol.% Reduces the yield (1), which is associated with a decrease in catalytically active centers in the reaction mass.

A change in the ratio of the starting reagents towards an increase in the content of R'AlCl ₂ with respect to acetylene does not lead to a significant increase in the yield of the target products (1). A decrease in the amount of R'AlCl ₂ with respect to acetylene reduces the yield (1).

Significant differences of the proposed method:

1. In the proposed method are used as starting compounds disubstituted acetylene, R'AlCl ₂ , SOCl ₂ and a catalyst Cp ₂ ZrCl ₂ . In the known method, tetraalkylthiophenes (1) are obtained from 1,4-diiodobutadiene, butyl lithium and carbon disulfide.

The proposed method has the following advantages:

1. The method allows to obtain with high selectivity 2,3,4,5-tetraalkylthiophenes (1) without the use of inaccessible 1,4-diiodobutadiene, pyrophoric n-BuLi and highly toxic carbon disulfide CS ₂ .

The method is illustrated by the following examples:

EXAMPLE 1. In a 50 ml glass reactor mounted on a magnetic stirrer, 10 ml of THF, 1.2 mmol of Cp ₂ ZrCl ₂ , 10 mmol of hex-3-in, 8 mg-at. Mg metal and at a temperature of ~ 0 ° C 8 mmol R'AlCl ₂ . The temperature was brought to room temperature and stirred for 8 hours. Then the reaction mass was cooled to -40 ° C, 8 mmol of thionyl chloride SOCl _{2 was} added and stirred for 1 hour. Then the temperature was brought to room temperature, stirred for another 4 hours. An individual 2,3,4,5 was obtained -tetraethylthiophene (1) with a yield of 48%. Spectral characteristics of 2,3,4,5-tetrapropylthiophene (1).

¹³ C NMR spectrum (δ, ppm): 13.56 (C ^11.13 ), 14.24 (C ^7.9 ), 29.36 (C ^6.8 ), 30.18 (C ^10.12 ), 135.23 (C ^{2, 5} ), 136.75 (C ^3.4 ).

Other examples confirming the method are shown in table 1.

Table 1 №№ R-≡-R R'AlCl ₂ The molar ratio of RC :CR: R'AlCl ₂ : Mg: SOCl ₂ : Cp ₂ ZrCl ₂ , mmol Total reaction time, hour Yield (1),% one hex-3-in R '= Cl 10: 8: 8: 8: 1.2 13 48 2 " " 10: 10: 10: 10: 1.2 13 52 3 " " 10: 6: 6: 6: 1.2 13 45 four " " 10: 8: 8: 8: 1.4 13 54 5 " " 10: 8: 8: 8: 1.0 13 39 6 " " 10: 8: 8: 8: 1.2 fifteen 51 7 " " 10: 8: 8: 8: 1.2 eleven 43 8 oct-4-in " 10: 8: 8: 8: 1.2 13 44 9 dec-5-in " 10: 8: 8: 8: 1.2 13 42 10 hex-3-in R '= C ₂ H ₅ 10: 8: 8: 8: 1.2 13 47

All experiments were carried out in tetrahydrofuran.

Claims (1)

The method of obtaining 2,3,4,5-tetraalkylthiophenes of the general formula (1)

, where R = C ₂ H ₅ , nC ₃ H ₇ , nC ₄ H ₉ , characterized in that the disubstituted acetylene of the general formula R-≡-R, where R = C ₂ H ₅ , nC ₃ H ₇ , nC ₄ H ₉ , is reacted with R'AlCl ₂ , where R '= C ₂ H ₅ , Cl, in the presence of metallic Mg and a catalyst of zirconacenedichloride Cp ₂ ZrCl ₂ in a molar ratio R-≡-R: R'AlCl ₂ : Mg: Cp ₂ ZrCl ₂ = 10: 6-10: 6: 10: 1.0 -1.4 in tetrahydrofuran in an argon atmosphere at normal pressure and room temperature for 8 hours, followed by the addition of thionyl chloride SOCl ₂ at -40 ° C, taken in an equimolar amount with respect to R'AlCl ₂ and stirring for 1 h, then bringing temperament ry to room temperature and subsequent stirring for another 2-6 hours