CN105820174A - Polysubstituted thienoindole derivative and preparation method thereof - Google Patents

Abstract

The invention discloses a method for preparing multi-substituted thienoindole derivatives, which belongs to the technical field of organic synthesis. The method is as follows: add o-alkynyl isothiocyanate and isocyanide into the reactor, heat in a solvent under nickel catalysis, cool to room temperature after the reaction is completed, extract the system with ethyl acetate, and then use a rotary evaporator to The filtrate was concentrated to obtain a crude product, which was finally separated by column chromatography. The preparation method of the multi-substituted thienoindole derivative provided by the invention is scientific and reasonable, the yield is high, and the product is easy to purify.

Description

A kind of preparation method of multi-substituted thienoindole derivatives

technical field

The invention belongs to the technical field of organic synthesis, in particular to a preparation method of multi-substituted 2H-thieno[2,3-b]indole derivatives.

Background technique

Thienoindole derivatives are a common class of heterocyclic compounds with biological and pharmacological activities widely present in natural products. Many thienoindole derivatives have biological and pharmacological activities such as bactericidal, antihypertensive, antidepressant, antiallergic, antimalarial, and antitumor, such as 2H-thieno[2,3-b]indole derivatives can be Further transformation produces a compound that controls the activity of rice seedlings.

The synthetic application of thienoindole derivatives has gone beyond the field of medicine and gradually extended to the field of material chemistry, such as electrochemical copolymerization of thienoindole derivatives to prepare high-performance conductive polymers and organic electroluminescent devices.

Thienoindole derivatives have a wide range of applications in these fields, making the synthesis of these compounds particularly important.

The preparation method of thienoindole derivatives has:

1) Peter Langer synthesis method: 3-halogenated chromone, β-ketoamide and 1,3-dihydroindoline-2-thione are reacted to obtain thienoindole derivatives.

2) Takashi Otani synthesis method: 2-alkylphenylisothiocyanate is catalyzed by trifluoromethanesulfonic acid to form a ring to obtain thienoindole derivatives.

3) TakaoSaito synthesis method: o-alkynyl isothiocyanate is catalyzed by cobalt carbonyl or molybdenum carbonyl, and thienoindole derivatives are obtained through Pauson-Khand reaction.

Using the above method to prepare thienoindole derivatives in the laboratory has obvious disadvantages: 1) The synthesis steps are many, the operation is cumbersome, and the catalytic metal is expensive. 2) The reaction is carried out under strong acid or strong alkaline conditions, causing great environmental pollution; 3) Some reagents are highly toxic and the reaction conditions are harsh.

Contents of the invention

In order to overcome the deficiencies of the above-mentioned prior art, the present invention provides a multi-substituted thienoindole derivative and a preparation method thereof.

A multi-substituted thienoindole derivative having the structure shown in formula I:

In formula I, wherein R ¹ is selected from cyclohexyl, n-butyl, tert-butyl, 2,6-dimethylphenyl; R ² is selected from fluorine atom, chlorine atom, bromine atom, saturated three-membered ring, tert-butyl Base, thienyl, phenyl, substituted aryl, wherein the substituting group is a fluorine atom, a chlorine atom, a methyl group, a methoxyl group; ^R3 is selected from a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group, a methoxyl group ; R ⁴ is selected from a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group.

By o-alkynyl isothiocyanate and isocyanide, under nickel catalysis, a kind of multi-substituted thieno indole derivative is obtained after heating reaction in the solvent; The preparation method is represented by the following formula II:

The nickel catalyst selected is nickel acetylacetonate, the amount of nickel acetylacetonate is 0.3% of the amount of ortho-alkynyl isothiocyanate, and the molar ratio of ortho-alkynyl isothiocyanate to isonitrile is 1.0:1.2. The solvent is tetrahydrofuran, the reaction temperature is 80°C, and the reaction time is 5h.

The beneficial effects of the present invention are: the synthesis method of the multi-substituted thienoindole derivatives provided by the present invention is scientific and reasonable, and 2H-thieno[2,3-b]indole derivatives with various substituents can be synthesized; It also has the characteristics of simple synthesis method, high yield, easy purification of products and the like.

Description of drawings

Fig. 1 is the ¹ HNMR, ¹³ CNMR collection of spectra of the compound prepared in Example 5;

Fig. 2 is the ¹ HNMR, ¹³ CNMR collection of spectra of the compound prepared in Example 7;

Fig. 3 is the ¹ HNMR, ¹³ CNMR collection of spectra of the compound prepared in Example 10;

detailed description

Below in conjunction with accompanying drawing and specific embodiment the present invention is described in further detail:

The test methods described in the following examples, unless otherwise specified, are conventional methods; the reagents and materials, unless otherwise specified, can be obtained from commercial sources.

The solvents used in the following examples were subjected to anhydrous and oxygen-free treatment or simple treatment by adding activated molecular sieves before use.

Example 1: (Z)-N-cyclohexyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine (R ¹ = cyclohexyl in structural formula I, R ² = phenyl , R ³ =hydrogen atom, R ⁴ =hydrogen atom)

Add 2-phenylethynyl-phenylisothiocyanate (1.0mmol, 235mg), cyclohexylisonitrile (1.2mmol, 153uL) and nickel acetylacetonate (0.003mmol, 0.88mg) to a 25mL round bottom flask, add 3.0 mL of redistilled tetrahydrofuran, sealed and placed in an oil bath at 80°C for 5 hours. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) The red solid product (Z)-N-cyclohexyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine 336 mg with a purity greater than 99% was obtained. The isolated yield was 96%.

Structural identification of (Z)-N-cyclohexyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine:

¹ HNMR (CDCl ₃ , 500MHz): δ=1.26–1.35(m,1H,CH ₂ ),1.40–1.47(m,2H,CH ₂ ),1.61–1.70(m,4H,2×CH ₂ ),1.82 –1.87(m,4H,2×CH ₂ ),3.40–3.44(m,1H,CH),6.9(t,J=7.5Hz,1H,ArH),7.32(t,J=7.6Hz,1H,ArH ),7.41(d,J=7.6Hz,1H,ArH),7.51–7.55(m,3H,ArH),7.60(d,J=7.5Hz,1H,ArH),7.74–7.76(m,2H,ArH ); ¹³ CNMR (CDCl ₃ , 125MHz): δ=24.1, 25.4, 33.3, 69.5, 119.9, 123.10, 124.3, 125.6, 128.2, 130.1, 130.7, 131.4, 131.6, 142.6, 147.4, 161.1, 161.2, 175 HRMS (ESI-TOF,[M+H] ⁺ ): _{calcdforC22H20FN2S} , _345.1425 , _{found345.1428}

Example 2: (Z)-N-cyclohexyl-3-(4-fluorophenyl)-2H-thieno[2,3-b]indole-2-imine (R ¹ =cyclohexyl in the structural formula I , R ² = p-fluorophenyl, R ³ = hydrogen atom, R ⁴ = hydrogen atom)

To a 25 mL round bottom flask was added (3-fluorophenyl)ethynyl-phenylisothiocyanate (1.0 mmol, 253 mg), cyclohexylisonitrile (1.2 mmol, 153 uL) and nickel acetylacetonate (0.003 mmol, 0.88 mg ), add 3.0 mL redistilled tetrahydrofuran, seal the mouth and put it in an oil bath at 80°C for 5 hours. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) The product (Z)-N-cyclohexyl-3-(4-fluorophenyl)-2H-thieno[2,3-b]indole-2-imine was obtained as a red solid with a purity greater than 99% 294 mg isolated yield 95%.

Structural identification of (Z)-N-cyclohexyl-3-(4-fluorophenyl)-2H-thieno[2,3-b]indole-2-imine:

¹ HNMR (CDCl ₃ , 500MHz): δ=1.23–1.35(m,1H,CH ₂ ),1.38–1.46(m,2H,CH ₂ ),1.58–1.67(m,4H,2×CH ₂ ),1.79 –1.85(m,4H,2×CH ₂ ),3.37–3.42(m,1H,CH),6.98(t,J=7.6Hz,1H,ArH),7.20(t,J=8.7Hz,2H,ArH ), 7.31(t, J=7.6Hz, 1H, ArH), 7.39(d, J=7.7Hz, 1H, ArH), 7.54(d, J=7.5Hz, 1H, ArH), 7.72-7.75(m, 2H, ArH); ¹³ CNMR (CDCl ₃ , _125MHz ); ,147.3,161.2,161.2,163.7(d,J _CF ＝251.4Hz),175.0.HRMS(ESI-TOF,[M+H] ⁺ ):calcdforC ₂₂ H ₂₀ FN ₂ S,363.1331,found363.1342.

Example 3: (Z)-N-cyclohexyl-5-fluoro-3-phenyl-2H-thieno[2,3-b]indol-2-amine (R ¹ = cyclohexyl in the structural formula I, R ² = phenyl group, R ³ = fluorine atom, R ⁴ = hydrogen atom)

Into a 25 mL round bottom flask was added 4-fluoro-2-(phenylethynyl)-phenylisothiocyanate (1.0 mmol, 253 mg), cyclohexylisonitrile (1.2 mmol, 153 uL) and nickel acetylacetonate (0.003 mmol ,0.88mg), add 3.0mL redistilled tetrahydrofuran, seal the mouth and put it in an oil bath at 80°C for 5h. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) The product (Z)-N-cyclohexyl-5-fluoro-3-phenyl-2H-thieno[2,3-b]indol-2-amine 330mg with a purity of more than 99% was obtained. The isolated yield was 93% .

Structural identification of (Z)-N-cyclohexyl-5-fluoro-3-phenyl-2H-thieno[2,3-b]indol-2-amine:

¹ HNMR (CDCl ₃ , 500MHz): δ=1.24–1.35(m,1H,CH ₂ ), 1.39–1.46(m,2H,CH ₂ ), 1.61–1.67(m,4H,2×CH ₂ ), 1.80 –1.86(m,4H,2×CH ₂ ),3.39–3.43(m,1H,CH),7.00(td, ¹ J=8.8Hz, ² J=2.4Hz,1H,ArH),7.28(dd, ¹ J＝8.2Hz, ² J＝2.4Hz,1H,ArH),7.31–7.33(m,1H,ArH),7.52–7.54(m,3H,ArH),7.70–7.71(m,2H,ArH); ¹³ CNMR (CDCl ₃ , 125MHz); δ=24.0, 25.5, 33.4, 69.5, 110.7(d, J _CF ＝26.3Hz), 117.4(d, J _CF ＝22.3Hz), 120.2, 126.8, 128.4, 130.4, 130.6, 131.1, 143.9, 146.8, 157.2, 159.1, 160.1 (d, J _CF ＝244.0Hz), 160.9, 174.7. HRMS (ESI-TOF, [M+H] ⁺ ): calcdforC ₂₂ H ₂₀ FN ₂ S, 363.1331, found363 .1339

Example 4: (Z)-N-cyclohexyl-3-(4-methoxyphenyl)-2H-thieno[2,3-b]indol-2-amine (R ¹ in the structural formula I = ring Hexyl, R ² =p-methoxyphenyl, R ³ =hydrogen atom, R ⁴ =hydrogen atom)

To a 25 mL round bottom flask was added (3-methoxyphenyl)-ethynyl-phenylisothiocyanate (1.0 mmol, 265 mg), cyclohexylisonitrile (1.2 mmol, 153 uL) and nickel acetylacetonate (0.003 mmol ,0.88mg), add 3.0mL redistilled tetrahydrofuran, seal the mouth and put it in an oil bath at 80°C for 5h. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) The red solid product (Z)-N-cyclohexyl-3-(4-methoxyphenyl)-2H-thieno[2,3-b]indole-2-amine 289mg with a purity of more than 99% was obtained. rate of 81%.

Structural identification of (Z)-N-cyclohexyl-3-(4-methoxyphenyl)-2H-thieno[2,3-b]indol-2-amine:

¹ HNMR (CDCl ₃ , 500MHz): δ=1.25–1.35(m,1H,CH ₂ ),1.39–1.47(m,2H,CH ₂ ),1.60–1.67(m,4H,2×CH ₂ ),1.80 –1.87(m,4H,2×CH ₂ ), 2.44(s,3H,OCH ₃ ),3.39-3.43(m,1H,CH),6.98(t,J＝7.6Hz,1H,ArH),7.29– 7.32 (m, 2H, ArH), 7.39–7.42 (m, 2H, ArH), 7.52–7.55 (m, 2H, ArH), 7.58 (d, J=7.4Hz, 1H, ArH); ¹³ CNMR (CDCl ₃ ,125MHz); δ＝21.4,24.1,25.5,33.4,69.4,119.9,123.1,124.3,125.8,127.9,128.1,130.8,131.3,131.5,137.8,142.9,147.3,161.2,175.2.HRMS,(ESI-TOF [M+H] ⁺ ):calcdforC ₂₃ H ₂₃ N ₂ OS,375.1531,found375.1529

Example 5: (Z)-N-cyclohexyl-3-(p-tolyl)-2H-thieno[2,3-b]indol-2-amine (R ¹ =cyclohexyl in structural formula I, R ² = p-methylphenyl, R ³ = hydrogen atom, R ⁴ = hydrogen atom)

To a 25 mL round bottom flask was added (4-tolyl)-ethynyl-phenylisothiocyanate (1.0 mmol, 249 mg), cyclohexylisonitrile (1.2 mmol, 153 uL) and nickel acetylacetonate (0.003 mmol, 0.88 mg ), add 3.0 mL redistilled tetrahydrofuran, seal the mouth and put it in an oil bath at 80°C for 5 hours. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) The red solid product (Z)-N-cyclohexyl-3-(p-tolyl)-2H-thieno[2,3-b]indol-2-amine 302 mg with a purity greater than 99% was obtained. The isolated yield was 84%.

Structural identification of (Z)-N-cyclohexyl-3-(p-tolyl)-2H-thieno[2,3-b]indol-2-amine:

¹ HNMR (CDCl ₃ , 500MHz): δ=1.26–1.34(m,1H,CH ₂ ),1.39–1.46(m,2H,CH ₂ ),1.59–1.67(m,4H,2×CH ₂ ),1.80 –1.86(m,4H,2×CH ₂ ), 2.45(s,3H,CH ₃ ),3.38–3.43(m,1H,CH),6.98(t,J＝7.5Hz,1H,ArH),7.29– 7.33(m,3H,ArH),7.39(d,J=7.7Hz,2H,ArH),7.61(d,J=7.4Hz,1H,ArH),7.65(d,J=8.0Hz,2H,ArH) ; ¹³ CNMR (CDCl ₃ , 125MHz); HRMS (ESI-TOF,[M+H] ⁺ ):calcdforC ₂₃ H ₂₃ N ₂ S,359.1582,found359.1576

Example 6: (Z)-N-cyclohexyl-3-cyclopropyl-2H-thieno[2,3-b]indol-2-amine (R ¹ =cyclohexyl in structural formula I, R ² =cyclo Propyl, R ³ =hydrogen atom, R ⁴ =hydrogen atom)

Add 1-cyclopropyl-phenylisothiocyanate (1.0mmol, 199mg), cyclohexylisonitrile (1.2mmol, 153uL) and nickel acetylacetonate (0.003mmol, 0.88mg) to a 25mL round bottom flask, add 3.0 mL of redistilled tetrahydrofuran, sealed and placed in an oil bath at 80°C for 5 hours. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) The red solid product (Z)-N-cyclohexyl-3-cyclopropyl-2H-thieno[2,3-b]indol-2-amine 294 mg with a purity greater than 99% was obtained. The isolated yield was 95%.

Structural identification of (Z)-N-cyclohexyl-3-cyclopropyl-2H-thieno[2,3-b]indol-2-amine:

¹ HNMR (CDCl ₃ , 500MHz): δ=1.21–1.28(m,2H,CH ₂ ),1.34–1.46(m,3H,CH ₂ ),1.57–1.64(m,4H,2×CH ₂ ),1.71 –1.75(m,2H,CH ₂ ),1.81–1.82(m,4H,2×CH ₂ ),2.42–2.47(m,1H,CH),3.28–3.32(m,1H,CH),7.07(t ,J=7.5Hz,1H,ArH),7.29(t,J=7.7Hz,1H,ArH),7.38(d,J=7.8Hz,1H,ArH),7.62(d,J=7.4Hz,1H, ArH); ¹³ CNMR (CDCl ₃ , 125MHz); TOF,[M+H] ⁺ ):calcdforC ₁₉ H ₂₁ N ₂ S,309.1425,found309.1432

Example 7: (Z)-N-cyclohexyl-3-(trimethylsilyl)-2H-thieno[2,3-b]indol-2-amine (R ¹ =cyclohexyl in formula I , R ² =trimethylsilyl group, R ³ =hydrogen atom, R ⁴ =hydrogen atom)

To a 25 mL round bottom flask was added (2-isothiocyanatophenyl)-ethynyl-trimethylsilane (1.0 mmol, 231 mg), cyclohexylisonitrile (1.2 mmol, 153 uL) and nickel acetylacetonate (0.003 mmol, 0.88mg), add 3.0mL redistilled tetrahydrofuran, seal the mouth and put it in an oil bath at 80°C for 5h. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) A red solid product (Z)-N-cyclohexyl-3-(trimethylsilyl)-2H-thieno[2,3-b]indol-2-amine with a purity greater than 99% was obtained 201 mg isolated yield 59%.

Structural identification of (Z)-N-cyclohexyl-3-(trimethylsilyl)-2H-thieno[2,3-b]indol-2-amine:

¹ HNMR (CDCl ₃ , 500MHz): δ＝0.46(s,9H,3×CH ₃ ),1.38–1.45(m,3H,CH ₂ ),1.61–1.66(m,3H,CH ₂ ),1.82–1.84 (m,4H,2×CH ₂ ),3.37–3.38(m,1H,CH),7.06(t,J=7.4Hz,1H,ArH),7.29–7.36(m,2H,ArH),7.74(d , J＝7.5Hz, 1H, ArH); ¹³ CNMR (CDCl ₃ , 125MHz); 177.8. HRMS (ESI-TOF, [M+H] ⁺ ): calcd for C ₁₉ H ₂₅ SiN ₂ S, 341.1508, found 341.1501.

Example 8: (Z)-N-cyclohexyl-6-methyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine (R ¹ = cyclohexyl in the structural formula I, R ² =phenyl, R ³ =hydrogen atom, R ⁴ =methyl)

Into a 25 mL round bottom flask was added 4-methyl-1-(phenylethyl)-phenylisothiocyanate (1.0 mmol, 249 mg), cyclohexylisonitrile (1.2 mmol, 153 uL) and nickel acetylacetonate (0.003 mmol ,0.88mg), add 3.0mL redistilled tetrahydrofuran, seal the mouth and put it in an oil bath at 80°C for 5h. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) The product (Z)-N-cyclohexyl-6-methyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine as a red solid with a purity greater than 99% was obtained in 334 mg. Isolated yield 91 %.

Structural identification of (Z)-N-cyclohexyl-6-methyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine:

¹ HNMR (CDCl ₃ , 500MHz): δ=1.19–1.28(m,1H,CH ₂ ),1.32–1.39(m,2H,CH ₂ ),1.55–1.60(m,3H,CH ₂ ),1.73–1.79 (m,4H,2×CH ₂ ),2.31(s,3H,CH ₃ ),3.31-3.35(m,1H,CH),6.71(d,J=7.6Hz,1H,ArH),7.14(s, 1H, ArH), 7.20 (s, 1H, ArH), 7.39 (d, J=7.7Hz, 1H, ArH), 7.42-7.45 (m, 3H, ArH), 7.65-7.67 (m, 2H, ArH); ¹³ CNMR (CDCl ₃ , 125MHz); -TOF,[M+H] ⁺ ):calcdforC ₂₃ H ₂₃ N ₂ S,359.1582,found359.1576

Example 9: (Z)-N-n-butyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine (in the structural formula I, R ¹ = n-butyl, R ² =phenyl, R ³ =hydrogen atom, R ⁴ =hydrogen atom)

Add 2-phenylethynyl-phenylisothiocyanate (1.0mmol, 235mg), n-butylisonitrile (1.2mmol, 99.8mg) and nickel acetylacetonate (0.003mmol, 0.88mg) into a 25mL round bottom flask, add 3.0 mL redistilled tetrahydrofuran, seal the mouth and place it in an oil bath at 80°C for 5 hours. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) The red solid product (Z)-N-n-butyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine 290 mg with a purity greater than 99% was obtained. The isolated yield was 94%.

Structural identification of (Z)-N-n-butyl-3-phenyl-2H-thieno[2,3-b]indol-2-amine:

¹ HNMR (CDCl ₃ , 500MHz): δ=0.97 (t, J=7.3Hz, 3H, CH ₃ ), 1.46 (hexa, J=7.6Hz, 2H, CH ₂ ), 1.79 (penta, J=7.2Hz, 2H, CH ₂ ), 3.77(t, J=6.9Hz, 2H, CH ₂ ), 6.98(t, J=7.5Hz, 1H, ArH), 7.31(t, J=7.6Hz, 1H, ArH), 7.40 (d,J=7.7Hz,1H,ArH),7.48–7.54(m,3H,ArH),7.56(d,J=7.5Hz,1H,ArH),7.70–7.72(m,2H, ^ArH ); CNMR (CDCl ₃ , 125MHz); 164.0,175.0.HRMS(ESI-TOF,[M+H] ⁺ ):calcdforC ₂₀ H ₁₉ N ₂ S,319.1269,found319.1258

Example 10: (Z)-N-(2,6-dimethylphenyl)-3-phenyl-2H-thieno[2,3-b]indole-2-imine (in structural formula I, R ¹ =2,5-dimethylphenyl, R ² =phenyl, R ³ =hydrogen atom, R ⁴ =hydrogen atom,)

Into a 25 mL round bottom flask was added 2-phenylethynyl-phenylisothiocyanate (1.0 mmol, 235 mg), 2,5-dimethylphenylisonitrile (1.2 mmol, 113 mg) and nickel acetylacetonate (0.003 mmol ,0.88mg), add 3.0mL redistilled tetrahydrofuran, seal the mouth and put it in an oil bath at 80°C for 5h. After the reaction was complete, cool to room temperature, extract the system with ethyl acetate, then evaporate the solvent with a rotary evaporator, and separate the residue by column chromatography (200-300 mesh silica gel) (petroleum ether/ethyl acetate=20/1) A red solid product (Z)-N-(2,6-dimethylphenyl)-3-phenyl-2H-thieno[2,3-b]indole-2-imine with a purity greater than 99% was obtained 242 mg isolated yield 66%.

Structural identification of (Z)-N-(2,6-dimethylphenyl)-3-phenyl-2H-thieno[2,3-b]indole-2-imine:

¹ HNMR (CDCl ₃ , 500MHz): δ=2.13(s,6H,2×CH ₃ ),6.99–7.04(m,2H,ArH),7.07–7.09(m,2H,ArH),7.32(t,J =7.6Hz,1H,ArH),7.38(d,J=7.6Hz,1H,ArH),7.53–7.61(m,4H,ArH),7.86(d,J=6.9Hz,2H,ArH); ¹³ CNMR (CDCl ₃ , 125MHz); ,[M+H] ⁺ ): calcdforC ₂₄ H ₁₉ N ₂ S, 367.1269, found 367.1258.

Claims (3)

1. a preparation method for polysubstituted thiophene diindyl derivant, described polysubstituted thiophene diindyl derivant has a structure shown in formula I:

In formula I, wherein R¹Selected from cyclohexyl, normal-butyl, the tert-butyl group, 2,6-3,5-dimethylphenyl；R²Selected from fluorine atom, chlorine atom, bromine atoms, saturated three-membered ring, the tert-butyl group, thienyl, phenyl, substituted aryl, substituted radical therein is fluorine atom, chlorine atom, methyl, methoxyl group；R³Selected from hydrogen atom, fluorine atom, chlorine atom, methyl, methoxyl group；R⁴Selected from hydrogen atom, fluorine atom, chlorine atom, methyl；It is characterized in that, by adjacent alkynyl isothiocyanate and isonitrile, under nickel is catalyzed, solvent obtains after reacting by heating the polysubstituted thiophene diindyl derivant shown in formula I；This preparation method below equation represents:

Preparation method the most according to claim 1, it is characterized in that selected Raney nickel is nickel acetylacetonate, the consumption of nickel acetylacetonate is the 0.3% of the amount of adjacent alkynyl isothiocyanate materials, and the molar ratio of adjacent alkynyl isothiocyanate and isonitrile is 1.0:1.2.

Preparation method the most according to claim 1, it is characterised in that selected solvent is oxolane, reaction temperature is 80 DEG C, and the response time is 5h.