RU2310650C1 - Method for preparing 2,3,4,5-tetraalkylthiophenols - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 2,3,4,5-tetraalkylthiophenols. Method involves interaction of disubstituted acelylenes with n-BuMgCl and sulfur monochloride (S₂Cl₂) in the presence of zirconacene dichloride as a catalyst, in argon atmosphere, at room temperature in diethyl ether medium for 6-10 h. Proposed method provides preparing the end product with the yield 40-54% by simplified technology and with using easily available and nontoxic raw. Synthesized compounds can be used in food processing industry, as biologically active compounds, dyes, addition agents to oils and hydraulic liquids.

EFFECT: improved method of synthesis.

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):

where R = C ₂ H ₅ , nC ₃ H ₇ , nC ₄ H ₉

Substituted thiophenes can be used 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 the synthesis of tetrasubstituted thiophenes (2 ) with a yield of ~ 55% by the interaction of α, ω-diacetylenes, followed by treatment of the reaction mass with bis-cyclopentadienyl zirconium dichloride 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 reaction of 1,4-dilithio-1,3-dienes obtained 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 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.

, где R=С₂Н₅, н-С₃Н₇, н-С₄H₉, с н-BuMgCl в присутствии катализатора цирконацендихлорида Cp₂ZrCl₂, взятыми в мольном соотношении

:н-BuMgCl:Ср₂ZrCl₂=10:(22-26):(1.0-1.4), предпочтительно 10:24:1.2, с последующим добавлением при 0°С полухлористой серы (S₂Cl₂), взятой в количестве 0.5 мольных эквивалента к BuMgCl. Реакцию проводят в атмосфере аргона при комнатной температуре (~20°С) и атмосферном давлении. Время реакции 6-10 часов, выход целевых продуктов 40-54%. В качестве растворителя необходимо использовать диэтиловый эфир, в других эфирных растворителях (ТГФ, диоксан) выход целевых продуктов (1) значительно снижается.The essence of the method consists in the interaction of disubstituted acetylenes of the formula

where R = C ₂ H ₅ , n-C ₃ H ₇ , n-C ₄ H ₉ , with n-BuMgCl in the presence of a Cp ₂ ZrCl ₂ zirconacene dichloride catalyst, taken in molar ratio

: n-BuMgCl: Cp ₂ ZrCl ₂ = 10: (22-26) :( 1.0-1.4), preferably 10: 24: 1.2, followed by the addition of sulfur chloride (S ₂ Cl ₂ ) at 0 ° C, taken in an amount 0.5 molar equivalent to BuMgCl. The reaction is carried out in an argon atmosphere at room temperature (~ 20 ° C) and atmospheric pressure. The reaction time of 6-10 hours, the yield of target products 40-54%. It is necessary to use diethyl ether as a solvent; in other ethereal solvents (THF, dioxane), the yield of the target products (1) is significantly reduced.

The reaction proceeds according to the scheme:

The target products (1) are formed only with the participation of disubstituted acetylene, n-BuMgCl, sulfur hemichloride (S ₂ Cl ₂ ) 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 , Ra (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 more than 14 mol.% In relation to acetylene does not lead to a significant increase in the yield of the target products (1). The use of Cp ₂ ZrCl ₂ in the reaction of the catalyst less than 10 mol.% Reduces the yield of MOC (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 seal products increases, at a lower temperature (for example, 0 ° C) the reaction rate decreases.

A change in the ratio of the starting reagents toward 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 decreases the yield of MOC (1).

Significant differences of the proposed method:

1. In the proposed method are used as starting compounds disubstituted acetylene, n-BuMgCl and S ₂ Cl ₂ with the participation of the 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 hard-to-reach 1,4-diiodobutadiene, extremely priory 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 24 mmol of n-BuMgCl (2M solution in Et ₂ O). Stirred at room temperature for 3 hours. Next, the reaction mass is cooled to 0 ° C and add 12 mmol of sulfur chloride S ₂ Cl ₂ . The temperature was brought to room temperature and stirred for another 5 hours. An individual 2,3,4,5-tetrapropylthiophene (1) is obtained with a yield of 49%. 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 confirming the method are shown in table 1.

Table 1 №№

The molar ratio of RC≡CR: n-BuMgCl: S ₂ Cl ₂ : Cp ₂ ZrCl ₂ , mmol Reaction time, hour Yield (1),% one hex-3-in 10: 24: 12: 1.2 8 fifty 2 ″ 10: 26: 13: 1.2 8 52 3 ″ 10: 22: 11: 1.2 8 46 four ″ 10: 24: 12: 1.4 8 54 5 ″ 10: 24: 12: 1.0 8 40 6 ″ 10: 24: 12: 1.2 10 53 7 ″ 10: 24: 12: 1.2 6 44 8 oct-4-in 10: 24: 12: 1.2 8 49 9 dec-5-in 10: 24: 12: 1.2 8 47

All experiments were carried out at room temperature (~ 20 ° C) in diethyl ether.

Claims (1)

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

where R = C ₂ H ₅ , nC ₃ H ₇ , nC ₄ H ₉ , characterized in that the disubstituted acetylene of the general formula

where R = C ₂ H ₅ , n-C ₃ H ₇ , H-C ₄ H ₉ , is reacted with n-BuMgCl in the presence of a catalyst of zirconacene dichloride Cp ₂ ZrCl ₂ in a molar ratio

: n-BuMgC: Cp ₂ ZrCl ₂ = 10: 22-26: 1.0-1.4 in argon atmosphere at normal pressure in diethyl ether for 2-4 hours at room temperature, followed by the addition of sulfur chloride S in the reaction mixture at 0 ° С ₂ Cl ₂ in an amount of 0.5 molar equivalents with respect to BuMgCl and subsequent stirring at room temperature for 4-5 hours