RU2377239C2 - Method of producing 2,3,4,5-tetraalkylthiophenes - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, specifically to a method of producing 2,3,4,5-tetraalkylthiophenes, which can be used as an intermediate product during synthesis of dyes, biologically active compounds, as well as components of flavour boosters in food, additives to oil and hydraulic fluids. A method is described for producing 2,3,4,5-tetraalkylthiophenes, involving reaction of disubstituted acetylenes with n-BuMgCl in the presence of a zirconocene dichloride catalyst in an argon atmosphere at room temperature in diethyl ether for 2-4 hours with subsequent addition of elemental sulphur S₈ in equimolar amount with respect to BuMgCl and boiling in benzene for 5 hours.

EFFECT: obtaining end product with high selectivity using simple technique due to exclusion of difficult to access 1,4-butadiene diiodide, highly pyrophoric n-butylithium and highly toxic carbon disulphide.

1 cl, 1 tbl, 9 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):

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], RJ. Fagan, WANugent, JCCalabrese. Metallacycle transfer from zirconium to main group elements: A versatile synthesis of heterocycles // JACS, 116, (1994), 1880-1890) for the synthesis of tetrasubstituted thiophenes (2) with a yield of ~ 55% by the interaction of α, ω-diacetylenes with subsequent processing of the reaction mixture with biscyclopentadienyl zirconium dichloride (Cp ₂ ZrCl ₂ ) and butyl lithium (n-BuLi), with sulfur hemichloride (S ₂ Cl ₂ ) for 1 hour 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) synthesis of tetraalkylthiophenes by the interaction of 1,4-dilithio-1,3-dienes obtained by treating 1,2,3,4-tetraalkyl-1,4-diiod-1,3-butadiene with butyllithium (n-BuLi) at a temperature of 78 ° C for 1 hour, with carbon disulfide at -20 ° C for 1 hour with a yield of 52-68% according to the scheme:

The known method for the synthesis of 2,3,4,5-tetraalkylthiophenes (1) involves the use of inaccessible 1,4-diiodo-1,3-butadiene, extremely 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 consists in the interaction of disubstituted acetylenes of the formula R-≡-R, where R = C ₂ H ₅ , n-C ₃ H ₇ , n-C ₄ H ₉ , with n-BuMgCl in the presence of a catalyst of zirconacenedichloride (Cp ₂ ZrCl ₂ ) taken in the molar ratio R-≡-R: n-BuMgCl: Cp ₂ ZrCl ₂ = 10: (22-26) :( 1.0-1.4), preferably 10: 24: 1.2, in diethyl ether for 2-4 h at room temperature (~ 20 ° C), followed by the addition of an equivalent amount of elemental sulfur (S ₈ ) to BuMgCl, benzene and boiling for 5 h. The reaction was carried out in an argon atmosphere and atmospheric pressure. The yield of target products is 44-60%.

The reaction proceeds according to the scheme:

R = C ₂ H ₅ , nC ₃ H ₇ , nC ₄ H ₉

The target products (1) are formed only with the participation of disubstituted acetylene, n-BuMgCl, elemental sulfur (S ₈ ) and the 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.

Carrying out the reaction in the presence of the catalyst Ср ₂ ZrCl ₂ 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 less than 10 mol.% Reduces the yield of thiophenes (1), which is associated with a decrease in catalytically active centers in the reaction mass. The experiments were carried out at room temperature ~ 20 ° C. At a higher temperature (for example, 50 ° C), the content of the seal products increases, at a lower temperature (for example, 0 ° C) the reaction rate decreases.

A change in the ratio of the starting reagents towards an increase in the content of n-BuMgCl 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 n-BuMgCl with respect to acetylene reduces the yield of thiophenes (1).

Significant differences of the proposed method:

In the proposed method, disubstituted acetylene, n-BuMgCl and S ₈ with the participation of the catalyst Cp ₂ ZrCl ₂ are used as starting compounds. In the known method, tetraalkylthiophenes (1) are obtained from 1,4-diiodobutadiene, butyl lithium and carbon disulfide.

The proposed method has the following advantages:

The method allows to obtain with high selectivity 2,3,4,5-tetraalkylthiophenes (1) without the use of hard-to-reach 1,4-diiodobutadiene, extremely high-grade 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, 1.2 mmol of Cp ₂ ZrCl ₂ , 10 mmol of oct-4-in, and at a temperature of ~ 0 ° 24 mmol of n-BuMgCl (2M solution in Et ₂ O). It is stirred at room temperature for 3 hours, then 24 mmol of elemental sulfur S ₈ , 10 ml of benzene are added and boiled for 5 hours. Individual 2,3,4,5-tetrapropylthiophene (1) is obtained in a yield of 54%. Spectral characteristics of 2,3,4,5-tetrapropylthiophene (1).

¹³ C NMR spectrum (δ, ppm): 13.54 (C ^14.17 ), 14.25 (C ^8.11 ), 21.90 (C ^13.16 ), 24.18 (C ^7.10 ), 29.33 (C ^{6, 9} ), 30.17 (C ^12.15 ), 135.25 (C ^2.5 ), 136.78 (C ^3.4 ).

Other examples of the method are shown in the table.

№№ R-≡-R The molar ratio of RC≡CR: n-BuMgCl: S ₈ : Cp ₂ ZrCl ₂ , mmol Reaction time, hour Yield (1),% one hex-3-in 10: 24: 24: 1.2 8 56 2 " 10: 26: 26: 1.2 8 58 3 " 10: 22: 22: 1.2 8 51 four " 10: 24: 24: 1.4 8 60 5 " 10: 24: 24: 1.0 8 44 6 " 10: 24: 24: 1.2 9 59 7 " 10: 24: 24: 1.2 7 52 8 oct-4-in 10: 24: 24: 1.2 8 54 9 dec-5-in 10: 24: 24: 1.2 8 fifty

Claims (1)

The method of obtaining 2,3,4,5-tetraalkylthiophenes of General formula (I)

characterized in that the disubstituted acetylene of the general formula
R - ≡-R,
where R is C ₂ H ₅ , nC ₃ H ₇ , nC ₄ H ₉ ,
subjected to interaction with n-BuMgCl in the presence of a catalyst of zirconacene dichloride (Cp ₂ ZrCl ₂ ) in a molar ratio of R-≡-R: n-BuMgCl: Cp ₂ ZrCl ₂ = 10: 22-26: 1.0-1.4 in an argon atmosphere at normal pressure in diethyl ether for 2-4 hours, followed by the addition of elemental sulfur S ₈ in an amount equimolar to BuMgCl and boiling in benzene for 5 hours