CN117126094A - Synthesis method of 2, 5-diaminopyrrole compound - Google Patents

Abstract

The invention discloses a method for synthesizing 2,5-diaminopyrroles compounds. The synthesis method is as follows: in a reactor, N-trifluoroacetanilide compounds, alkyne halides, isonitriles, palladium salt catalysts, bases, additives, and solvents are stirred and reacted at 60°C. The reaction liquid is separated and purified to obtain 2 ,5‑diaminopyrrole compounds. The method of the invention develops a three-component four-molecule series cyclization reaction of N-trifluoroacetanilide, alkyne halide and isonitrile to construct a series of highly functionalized 2,5-diaminopyrroles compounds. Mild reaction conditions, easy availability of raw materials, simple operation, good regioselectivity and wide substrate versatility are the main characteristics of the reaction.

Description

A kind of synthesis method of 2,5-diaminopyrroles compounds

Technical field

The invention belongs to the technical field of organic synthesis, and specifically relates to a method for synthesizing 2,5-diaminopyrrole compounds.

Background technique

Pyrrole and its derivatives, as an important class of five-membered aromatic heterocyclic compounds, are key components of many natural products or biologically active substances. Because of their special chemical properties and biological activities, they are widely used in many fields such as medicine, materials, dyes, etc. Therefore, developing new strategies to synthesize such compounds has also been one of the research hotspots of scientists in recent years. Traditional methods for synthesizing pyrrole compounds such as Knorr reaction, Hantzsch reaction, Paal-Knorr reaction, etc. are mainly realized by condensation of carbonyl compounds and amines (Knorr, L. Ann. 1886, 236, 290; Hantzsch, A. Ber. Dtsch. Chem .Ges.1890,23,1474; Knorr, L.Dtsch.Chem.Ges.1884,17,1635; Paal, C.Ber.Dtsch.Chem.Ges.1885,18,367). However, the above reactions usually require harsh and dangerous conditions such as high temperature and strong acid, so the scope of use is relatively limited.

The synthesis of pyrrole and its derivatives through transition metal-catalyzed cyclization is one of the most popular synthetic strategies favored by scientists in recent decades, such as [4+1], [3+2], [3+1+1 ], [2+1+1+1] cycloaddition reaction, etc. In the reported transition metal catalyzed synthesis of pyrrole and its derivatives (D.Srimani, Y.B.David, D.Milstein, Angew.Chem.Int.Ed.2013, 125, 4104; J.Liu, Z.X.Fang, Q.Zhang, Q Liu, ,Y.Gao,W.Hu,Y.Gao,M.Hu,W.Wu,Y.Ren,H.Jiang,Org.Lett.2016,18,5924;G.Qiu,Q.Wang,J.Zhu ,Org.Lett.2017,19,270;Y.Zhou,L.Zhou,L.T.Jesikiewicz,P.Liu,S.L.B,J.Am.Chem.Soc.2020,142,9908;K.Huang,J.B.Liu,Z.F.Chen, Y.C.Wang, S.Yadav, G.Qiu, Org.Lett.2020,22,5931), in addition to simple pyrrole, the synthesis of multi-substituted pyrrole compounds usually requires the use of some more complex compounds as starting materials, which is cumbersome and Atomic economy is poor. Therefore, it is still of great value to develop new synthetic methods that use simple raw materials to construct multi-substituted pyrrole compounds in one step.

Isonitrile is a type of highly active small molecule containing (-NC) structure. Its special valence bond structure gives it rich chemical properties. In recent decades, isonitrile has been combined with various reagents such as amines, alkenes, etc. through transition metal catalysis. Coupling cyclization reactions of alkynes, diazo compounds, carbonyl compounds, etc., have constructed many nitrogen-containing heterocyclic compounds (Peng, J.; Gao, Yang.; Zhu, C.; Liu, B.; Gao, Y. ;Hu,M.;Wu,W.;Jiang,H.J.Org.Chem.2017,82,3581;Wang,J.;Gao,D.-W.;Huang,J.;Tang,S.;Xiong,Z .;Hu,H.;You,S.-L.;Zhu,Q.ACS Catalysis.2017,7,3832;Wu,W.;Li,M.;Zheng,J.;Hu,W.;Li, C.; Jiang, H. Chem. Commun. 2018, 54, 6855; Yuan, W. K.; Liu, Y. F.; Lan, Z.; Wen, L. R.; Li, M. Org. Lett. 2018, 20, 7158; Collet, J.W.;Van Der Nol,E.A.;Roose,T.R.;Maes,B.U.W.;Ruijter,E.;Orru,R.V.A.J.Org.Chem.2020,85,7378;Zhu,Y.-M.;Fang,Y.;Li,H .; Xu, X.P.; Ji, S.-J.Org.Lett.2021,23,7342; Li, M.; Zhang, R.; Gao, Q.; Jiang, H.; Lei, M.; Wu, W. Angew. Chem. Int. Ed. 2022, 61, e202208203). However, most of the current methods use monoisonitrile to participate in the reaction. Although in recent years, bimolecular or multi-molecular isonitrile reactions have been reported from time to time to synthesize heterocyclic compounds, but in most cases, the reaction site of isonitrile is single. Lack of selectivity. This limits the development of the diversity of isonitrile chemistry to a certain extent; in addition, the simultaneous use of two molecules of simple isonitriles to achieve the synthesis of functionalized 2,5-diaminopyrroles has not yet been reported. In summary, a simple N-trifluoroacetanilide compound, an alkyne halide and two molecules of isonitrile are used to synthesize 2,5-diaminopyrrole compounds, and a new carbon-carbon bond is efficiently constructed in one step through a tandem cyclization process. and carbon-nitrogen bonds. In addition to the novelty of the methodology, its application prospects are also worth looking forward to.

Contents of the invention

The object of the present invention is to provide a synthesis method of 2,5-diaminopyrroles compounds in view of the shortcomings and deficiencies of the prior art. This method uses simple and easily available N-trifluoroacetanilide and alkyne halide as raw materials, a common palladium salt as a catalyst, a cesium salt as a base, lithium bromide as an additive, water and toluene as a mixed solvent, and uses alkali promotion and palladium catalytic ring As a strategy, we selectively constructed pyrrole derivatives substituted with amino groups at the 2- and 5-positions. It has the advantages of high atom economy, single selectivity, simple and safe operation, and wide substrate applicability. It has the advantages of practical production and research. Good application prospects.

The object of the present invention is achieved through the following technical solutions.

A method for synthesizing 2,5-diaminopyrrole compounds, including the following steps:

In the reactor, add the substrate N-trifluoroacetanilide compound, alkyne halide, palladium salt catalyst, alkali, additives, water and solvent, stir the reaction at 40~100°C, cool to room temperature after the reaction is completed, and the product is Separate and purify to obtain the 2,5-diaminopyrroles compound.

Further, the chemical reaction equation of the synthesis process is as follows:

In the formula, R ¹ is a substituent on N-trifluoroacetanilide, selected from hydrogen, 3-fluoro, 3-chloro, 3-methyl, 3-cyano, 4-methoxy, and 4-alkenyl. more than one kind;

R ² is the substituent on the alkyne halide, which is hydrogen, 4-bromo, 4-methyl, 4-methylcarboxylate, or 3-chloro;

R ³ is a substituent on the isonitrile, which is tert-butyl or 1,1,3,3-tetramethylbutyl.

Further, the N-trifluoroacetanilide compound is N-trifluoroacetanilide; the alkyne halide is (bromoethynyl)benzene.

Further, the palladium salt catalyst is one or more of tetrakis(triphenylphosphine)palladium, palladium chloride, and palladium acetate.

Further, the molar ratio of the added amount of the palladium salt catalyst to the N-trifluoroacetanilide compound is 0.05 to 0.1:1.

Further, the molar ratio of the added amount of the alkyne halide to the N-trifluoroacetanilide compound is 1.5 to 3.0:1.

Further, the base is one or more of cesium carbonate, potassium carbonate, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

Further, the molar ratio of the added amount of the base to the N-trifluoroacetanilide compound is 1.0 to 3.0:1.

Further, the additive is one or more of sodium chloride, potassium bromide, and lithium bromide.

Further, the molar ratio of the added amount of the additive to the N-trifluoroacetanilide compound is 0.5 to 2.0:1.

Further, the solvent is one of dichloroethane, dimethyl sulfoxide, 1,4-dioxide, toluene or a mixed solvent of water and toluene in a volume ratio of 1:100.

Further, the stirring reaction time is 4 to 16 hours, preferably 8 to 12 hours.

Further, the separation and purification operation is as follows: extract the reaction solution with ethyl acetate, combine the organic phases, dry with anhydrous magnesium sulfate, filter, and evaporate the organic solvent under reduced pressure to obtain a crude product, which is purified by column chromatography. The 2,5-diaminopyrroles compounds are obtained.

Furthermore, the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20 to 150:1, preferably a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50 to 100:1. .

The reaction principle of the synthesis method of the present invention is that under the promotion of alkali, N-trifluoroacetanilide, alkyne halide and a molecule of isonitrile undergo an addition reaction to form an alkenyl halide intermediate, and then the palladium salt catalyst undergoes oxidative addition with the intermediate. After another molecule of isonitrile migrates and inserts, 2,5-diaminopyrrole compounds are obtained through intramolecular cyclization, reduction elimination and isomerization.

Compared with the existing technology, the present invention has the following advantages and beneficial effects:

(1) The present invention develops a synthetic method for constructing 2,5-diaminopyrrole compounds through the tandem cyclization reaction of N-trifluoroacetanilide, alkyne halide and isonitrile under palladium catalysis, and the basic raw material N-trifluoroacetanilide is Fluoroacetanilide can be synthesized from cheap aniline and trifluoroacetic anhydride, and alkyne halide can be prepared in one step from phenylacetylene and N-halogenated succinimide. The raw materials are easy to obtain, the operation is safe and simple, the conditions are mild, and the atoms are economical. Features of high stability and wide substrate applicability;

(2) The synthesis method of the present invention is easy to operate, has high conversion efficiency, and has good tolerance to functional groups, so it is expected to be applied to actual industrial production and further derivatization.

Description of the drawings

Figures 1 and 2 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 1;

Figures 3 and 4 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 2;

Figure 5 and Figure 6 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 3;

Figures 7 and 8 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 4;

Figures 9 and 10 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 5;

Figures 11 and 12 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 6;

Figures 13 and 14 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 7;

Figures 15 and 16 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 8;

Figures 17 and 18 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 9;

Figures 19 and 20 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 10;

Figures 21 and 22 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 11;

Figures 23 and 24 are respectively the hydrogen spectrum and the carbon spectrum of the target product obtained in Example 12.

Detailed ways

The technical solution of the present invention will be described in further detail below with reference to specific embodiments and drawings, but the scope and implementation of the present invention are not limited thereto.

Example 1

Add 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetrakis (triphenylphosphine) palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene) benzene, 0.3 mmol into the reaction tube. Tert-butyl isonitrile, 1.0 ml of toluene and 0.7 mmol of water were used as solvents, and the reaction was stirred at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL of water, and extract 3 times with ethyl acetate. Combine the organic phases and use 0.5 g of free Dry over magnesium sulfate, filter, concentrate under reduced pressure, and then separate and purify through column chromatography. The column chromatography eluent used is a petroleum ether:ethyl acetate mixed solvent with a volume ratio of 50:1 to obtain the target product with a yield of 92 %.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 1 and Figure 2 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.66 (d, J = 6.8 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.44-7.36 (m, 3H), 7.31-7.21 (m, 3H),6.32(s,1H),2.93(s,1H),1.05(s,9H),0.67(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.2 (q, J = 32.7Hz), 137.2, 136.7, 130.9, 129.1, 128.5, 128.3, 128.0, 127.5, 125.6, 122.6, 118.0, 116.5 (q, J = 288.4 Hz),109.1,63.2,55.5,29.9,26.9.

IR(KBr)ν _max 3388,2972,1703,1598,1527,1497,1371,1195,1154,755,701cm ^-1 ;

HRMS(ESI)Calcd for C ₂₅ H ₃₃ N ₂ Si[M+H] ⁺ :458.2414, Found458.2407.

Based on the above data, the structure of the target product is deduced as follows:

Example 2

Add 0.1 mmol N-(3-fluorophenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, and 0.1 mmol into the reaction tube. Lithium bromide, 0.2 mmol (bromoacetylene) benzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water are used as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, and use acetic acid Extract with ethyl ester three times, combine the organic phases, dry with 0.5g anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and then separate and purify through column chromatography. The column chromatography eluent used is petroleum ether with a volume ratio of 50:1. : Ethyl acetate mixed solvent to obtain the target product with a yield of 90%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 3 and Figure 4 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.54 (d, J＝6.8Hz, 2H), 7.47-7.40 (m, 1H), 7.37 (t, J＝7.6Hz, 2H), 7.23 (t, J＝ 7.6Hz,1H),7.12-7.02(m,3H),6.28(s,1H),2.74(s,1H),1.05(s,9H),0.64(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 162.7 (d, J = 246.2Hz), 158.2 (q, J = 32.9Hz), 138.8 (d, J = 9.7Hz), 136.4, 131.0, 130.1 (d, J ＝9.0Hz),128.4,128.1,125.9,124.2,122.6,118.6,117.9(q,J＝288.2Hz),116.3(d,J＝23.4Hz),114.4,114.6,109.7,63.4,55.6,29.9,27.0 .

IR(KBr)ν _max 3739,2969,1701,1631,1599,1524,1491,1393,1161,861,760,694cm ^-1 ;

HRMS(ESI)Calcd for C ₂₆ H ₃₅ N ₂ Si[M+H] ⁺ :466.3040, Found466.3034.

Based on the above data, the structure of the target product is deduced as follows:

Example 3

Add 0.1 mmol N-(3-chlorophenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, and 0.1 mmol into the reaction tube. Lithium bromide, 0.2 mmol (bromoacetylene) benzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water are used as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, and use acetic acid Extract with ethyl ester three times, combine the organic phases, dry with 0.5g anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and then separate and purify through column chromatography. The column chromatography eluent used is petroleum ether with a volume ratio of 50:1. : Ethyl acetate mixed solvent to obtain the target product with a yield of 78%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 5 and Figure 6 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.52 (d, J = 6.8 Hz, 2H), 7.43-7.32 (m, 5H), 7.25-7.20 (m, 1H), 7.15 (dt, J = 7.8, 2.0 Hz,1H),6.28(s,1H),2.81(s,1H),1.05(s,9H),0.64(s,9H);

¹³ C NMR (100MHz, CDCL ₃ ) Δ158.23 (q, J = 32.8Hz), 138.6,136.3,134.4,131.1,129.0, 1208.4, 128.5, 126.5,122.6,118.7,117 .9 (Q ,J＝288.2Hz),109.8,63.4,55.6,29.9,27.0.

IR(KBr)ν _max 2972,1703,1592,1526,1481,1367,1267,1197,1158,760,699cm ^-1 ;

HRMS(ESI)Calcd for C ₂₆ H ₃₅ N ₂ Si[M+H] ⁺ :492.2024,Found492.2016.

Based on the above data, the structure of the target product is deduced as follows:

Example 4

Add 0.1 mmol N-(3-methylphenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol mol lithium bromide, 0.2 mmol (bromoacetylene) benzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, and use Extract three times with ethyl acetate, combine the organic phases, dry with 0.5g anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and then separate and purify through column chromatography. The column chromatography eluent used is petroleum with a volume ratio of 50:1. Ether:ethyl acetate mixed solvent was used to obtain the target product with a yield of 94%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 7 and Figure 8 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.63 (d, J＝6.8Hz, 2H), 7.35 (td, J＝7.6, 2.0Hz, 3H), 7.22-7.16 (m, 2H), 7.03 (d, J＝8.4Hz,2H),6.27(s,1H),2.75(s,1H),2.41(s,3H),1.01(s,9H),0.65(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.3 (q, J = 32.9 Hz), 139.2, 137.1, 136.8, 130.8, 129.0, 128.3, 128.0, 125.6, 125.5, 122.7, 117.9 ( q, J = 288.1 Hz) ,117.8,109.0,63.2,29.9,26.9,21.4.;

IR(KBr)ν _max 2969,1702,1599,1526,1490,1368,1192,1154,760,699cm ^-1 ;

HRMS(ESI)Calcd for C ₂₅ H ₃₂ FN ₂ Si[M+H] ⁺ :472.2570, Found472.2564.

Based on the above data, the structure of the target product is deduced as follows:

Example 5

Add 0.1 mmol N-(3-cyanophenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol mol lithium bromide, 0.2 mmol (bromoacetylene) benzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, and use Extract three times with ethyl acetate, combine the organic phases, dry with 0.5g anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and then separate and purify through column chromatography. The column chromatography eluent used is petroleum with a volume ratio of 50:1. Ether:ethyl acetate mixed solvent was used to obtain the target product with a yield of 86%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 9 and Figure 10 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.70-7.63(m,2H),7.59(t,J＝8.0Hz,1H),7.50(d,J＝8.0Hz,1H),7.47-7.37(m, 4H),7.29-7.24(m,1H),6.31(s,1H),2.95(s,1H),1.04(s,9H),0.60(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.2 (q, J = 33.2Hz), 138.5, 135.9, 132.7 (d, J = 15.2Hz), 131.1, 130.6, 129.8, 128.6, 128.1, 126.3, 122.4, 119.4 ,117.9,116.3(q,J=288.5Hz),113.0,110.4,63.6,55.8,29.8,27.0.;

IR(KBr)ν _max 3387,2972,2233,1704,1592,1526,1485,1370,1197,1166,762,699cm ^-1 ;

HRMS(ESI)Calcd for C ₂₅ H ₃₂ ClN ₂ Si[M+H] ⁺ ,483.2366,found483.2361.

Based on the above data, the structure of the target product is deduced as follows:

Example 6

Add 0.1 mmol N-(4-alkenylphenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol mol lithium bromide, 0.2 mmol (bromoacetylene) benzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, and use Extract three times with ethyl acetate, combine the organic phases, dry with 0.5g anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and then separate and purify through column chromatography. The column chromatography eluent used is petroleum with a volume ratio of 50:1. Ether:ethyl acetate mixed solvent was used to obtain the target product with a yield of 89%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 11 and Figure 12 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.61 (d, J＝7.2Hz, 2H), 7.35 (t, J＝7.6Hz, 2H), 7.22-7.12 (m, 3H), 6.99 (d, J＝ 8.8Hz,2H),6.26(s,1H),3.85(s,3H),2.65(s,1H),1.03(s,9H),0.65(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.4 (q, J = 32.8Hz), 136.8, 130.9, 129.9, 128.2, 128.0, 125.6, 122.7, 117.6, 116.5 (q, J = 288.1Hz), 114.3, 108.8 ,63.1,55.5,55.5,29.9,27.0;

IR(KBr)ν _max 3739,3615,3365,2922,1700,1634,1516,1465,1393,1250,1188,1032,838,759,700cm ^-1 ;

HRMS(ESI)Calcd for C ₂₅ H ₃₂ ClN ₂ Si[M+H] ⁺ :488.2519,Found488.2512.

Based on the above data, the structure of the target product is deduced as follows:

Example 7

Add 0.1 mmol N-(4-nitrophenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol mol lithium bromide, 0.2 mmol (bromoacetylene) benzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, and use Extract three times with ethyl acetate, combine the organic phases, dry with 0.5g anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and then separate and purify through column chromatography. The column chromatography eluent used is petroleum with a volume ratio of 50:1. Ether:ethyl acetate mixed solvent was used to obtain the target product with a yield of 90%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 13 and Figure 14 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.60 (d, J = 7.2Hz, 2H), 7.51 (d, J = 8.4Hz, 2H), 7.36 (t, J = 7.6Hz, 2H), 7.24-7.17 (m,3H),6.75(dd,J＝17.6,10.8Hz,1H),6.28(s,1H),5.82(d,J＝17.6Hz,1H),5.34(d,J＝10.8Hz,1H) ,2.81(s,1H),1.03(s,9H),0.64(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.3 (q, J = 32.8 Hz), 136.7, 136.6, 136.6, 135.7, 130.8, 128.6, 128.3, 128.0, 126.8, 125.7, 122.7, 118.2, 116.5 (q, J =288.2Hz),115.0,109.3,63.3,55.7,29.9,27.0;

IR(KBr)ν _max 3411,2970,1702,1519,1370,1193,1154,912,848,759,701cm ^-1 ;

HRMS(ESI)Calcd for C ₂₆ H ₃₅ N ₂ Si[M+H] ⁺ :484.2570,Found484.2565.

Based on the above data, the structure of the target product is deduced as follows:

.

Example 8

Add 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, and 0.2 mmol 1-(bromoalkynyl)-4 into the reaction tube. - Bromobenzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, extract 3 times with ethyl acetate, and combine The organic phase was dried with 0.5g anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography. The column chromatography eluent used was a petroleum ether:ethyl acetate mixed solvent with a volume ratio of 50:1. The target product was obtained with a yield of 92%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 15 and Figure 16 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.57 (d, J＝8.4Hz, 2H), 7.52-7.43 (m, 4H), 7.38 (t, J＝7.6Hz, 1H), 7.22 (d, J＝ 7.2Hz,2H),6.27(s,1H),3.00(s,1H),1.01(s,9H),0.65(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.1 (q, J = 32.8 Hz), 136.9, 135.6, 131.2, 130.8, 129.5, 129.3, 128.4, 127.8, 123.0, 119.2, 116.8, 116.4 ( q, J = 288.2 Hz),108.6,63.1,55.6,29.9,26.9;

IR(KBr)ν _max 2970,1703,1595,1525,1491,1370,1195,1152,761,705cm ^-1 ;

HRMS(ESI)Calcd for C ₂₆ H ₃₂ N ₃ Si[M+H] ⁺ :536.1519,Found 536.1511.

Based on the above data, the structure of the target product is deduced as follows:

Example 9

Add 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, and 0.2 mmol 1-(bromoalkynyl)-4 into the reaction tube. - Bromobenzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, extract 3 times with ethyl acetate, and combine The organic phase was dried with 0.5g anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography. The column chromatography eluent used was a petroleum ether:ethyl acetate mixed solvent with a volume ratio of 50:1. The target product was obtained with a yield of 79%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 17 and Figure 18 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.51-7.44(m,4H),7.36(t,J＝7.6Hz,1H),7.23(d,J＝7.2Hz,2H),7.17(d,J＝ 8.0Hz,2H),6.25(s,1H),2.60(s,1H),2.36(s,3H),1.00(s,9H),0.63(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.3 (q, J = 32.9 Hz), 137.3, 135.2, 133.7, 130.7, 129.1, 129.0, 128.6, 127.8, 127.4, 122.5, 117.9, 116.5 ( q, J = 288.1 Hz),109.1,63.2,55.5,29.9,26.9,21.1;

IR(KBr)ν _max 3465,2968,2923,1702,1530,1374,1191,1156,756,706cm ^-1 ;

HRMS(ESI)Calcd for C ₂₅ H ₃₂ FN ₂ Si[M+H] ⁺ :536.1519,Found536.1511.

Based on the above data, the structure of the target product is deduced as follows:

Example 10

Add 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, and 0.2 mmol 4-(bromoynyl)benzoic acid into the reaction tube. Methyl ester, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water as solvent, stir and react at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, extract 3 times with ethyl acetate, and combine the organic acids The phases were dried using 0.5g anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography. The column chromatography eluent used was a petroleum ether:ethyl acetate mixed solvent with a volume ratio of 50:1 to obtain Target product, yield 87%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 19 and Figure 20 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ8.03 (d, J = 8.0Hz, 2H), 7.77 (d, J = 8.4Hz, 2H), 7.51 (t, J = 7.6Hz, 2H), 7.44-7.38 (m,1H),7.23(d,J＝7.2Hz,2H),6.34(s,1H),3.93(s,3H),2.66(s,1H),1.01(s,9H),0.65(s, 9H);

¹³ C NMR (100MHz, CDCL ₃ ) Δ167.2,158.2 (q, J = 32.9Hz), 141.6,136.8,131.5, 129.6, 129.4,128.0, 127.0, 123.0,116.4 (Q, J = J = 288.2 Hz),108.8,63.2,56.0,51.9,29.9,26.9;

IR(KBr)ν _max 3467,3419,2919,1705,1635,1530,1273,1190,1109,756cm ^-1 ;

HRMS(ESI)Calcd for C ₂₅ H ₃₂ ClN ₂ Si[M+H] ⁺ ,516.2469,Found 516.2462.

Based on the above data, the structure of the target product is deduced as follows:

Example 11

Add 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetrakis(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, and 0.2 mmol 1-(bromoalkynyl)-4 into the reaction tube. - Bromobenzene, 0.3 mmol tert-butyl isonitrile, 1.0 ml toluene and 0.7 mmol water as solvents, stir the reaction at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL water, extract 3 times with ethyl acetate, and combine The organic phase was dried with 0.5g anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and then separated and purified by column chromatography. The column chromatography eluent used was a petroleum ether:ethyl acetate mixed solvent with a volume ratio of 50:1. The target product was obtained with a yield of 78%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 21 and Figure 22 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.76-7.70 (m, 1H), 7.56-7.47 (m, 3H), 7.40 (t, J = 7.6Hz, 1H), 7.31-7.26 (m, 1H), 7.22(d,J＝7.2Hz,2H),7.19-7.14(m,1H),6.28(s,1H),2.62(s,1H),1.00(s,9H),0.66(s,9H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.2 (q, J = 32.8 Hz), 138.5, 136.9, 134.1, 131.1, 129.5, 129.4, 128.5, 127.9, 125.9, 125.6, 123.1, 116.7, 116.4 (q, J =288.5Hz),108.7,63.2,55.7,30.0,27.0;

IR(KBr)ν _max 3496,2968,1702,1594,1525,1370,1194,1152,760,702cm ^-1 ;

HRMS(ESI)Calcd for C ₂₅ H ₃₁ Cl ₂ N ₂ Si[M+H] ⁺ ,492.2024,Found492.2018.

Based on the above data, the structure of the target product is deduced as follows:

Example 12

Add 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetrakis (triphenylphosphine) palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene) benzene, 0.3 mmol into the reaction tube. 1,1,3,3-Tetramethylbutyl isonitrile, 1.0 ml of toluene and 0.7 mmol of water as solvents, stir and react at 60°C and 500 rpm for 12 hours; stop stirring, add 5 mL of water, and extract with ethyl acetate 3 times, combine the organic phases and use 0.5g anhydrous magnesium sulfate to dry, filter, concentrate under reduced pressure, and then separate and purify through column chromatography. The column chromatography eluent used is petroleum ether:ethyl acetate with a volume ratio of 50:1. The solvents were mixed to obtain the target product with a yield of 84%.

The hydrogen spectrum and carbon spectrum of the obtained target product are shown in Figure 23 and Figure 24 respectively, and the structural characterization data are as follows:

¹ H NMR (400MHz, CDCl ₃ ) δ7.60-7.56 (m, 2H), 7.48 (t, J = 7.6Hz, 2H), 7.40-7.34 (m, 3H), 7.26-7.19 (m, 3H), 6.31(s,1H),3.01(s,1H),2.07(d,J＝14.8Hz,1H),1.15(s,3H),1.10(s,1H),1.08-0.96(m,2H),0.85 (s,3H),0.83(s,9H),0.80(s,9H),0.64(s,3H),0.55(s,3H);

¹³ C NMR (100MHz, CDCl ₃ ) δ 158.1 (q, J = 32.5Hz), 137.5, 137.0, 130.8, 129.2, 128.3, 127.7, 125.7, 122.5, 118.3, 116.5 (q, J = 288.9Hz), 109.7 ,68.2,59.8,56.5,49.4,31.6,31.4,31.3,29.4,28.5,26.8(d,J=28.5Hz);

IR(KBr)ν _max 2955,1703,1598,1492,1372,1194,1152,756,700cm ^-1 ;

HRMS(ESI)Calcd for C ₂₆ H ₃₅ N ₂ Si[M+H] ⁺ ,570.3666, found 570.3657.

Based on the above data, the structure of the target product is deduced as follows:

The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, etc. may be made without departing from the spirit and principles of the present invention. All simplifications should be equivalent substitutions, and are all included in the protection scope of the present invention.

Claims (10)

1. The synthesis method of the 2, 5-diaminopyrrole compound is characterized by comprising the following steps:

adding a substrate N-trifluoroacetanilide compound, alkyne halogen, isonitrile, palladium salt catalyst, alkali, additive, water and solvent into a reactor, stirring the mixture at 50 to 90 ℃ for reaction, cooling the mixture to room temperature after the reaction is finished, and separating and purifying the product to obtain the 2, 5-diaminopyrrole compound.

2. The method for synthesizing 2, 5-diaminopyrrole compounds according to claim 1, wherein the chemical reaction equation in the synthesis process is as follows:

wherein R is ¹ More than one of hydrogen, 3-fluoro, 3-chloro, 3-methyl, 3-cyano, 4-methoxy and 4-alkenyl;

R ² is a substituent on alkyne halogen, and is hydrogen, 4-bromine, 4-methyl formate or 3-chlorine;

R ³ is substituent on isonitrile and is tert-butyl or 1, 3-tetramethylbutyl.

3. The method for synthesizing 2, 5-diaminopyrrole compound according to claim 1, wherein the N-trifluoroacetanilide compound is N-trifluoroacetanilide; the alkyne halogen is (bromoacetylene) benzene.

4. The method for synthesizing 2, 5-diaminopyrrole compound according to claim 1 or 2, wherein the palladium salt catalyst is one or more of tetrakis (triphenylphosphine) palladium, palladium chloride and palladium acetate; the molar ratio of the addition amount of the palladium salt catalyst to the N-trifluoroacetanilide compound is 0.05-0.1:1.

5. The method for synthesizing 2, 5-diaminopyrrole compound according to claim 1 or 2, wherein the molar ratio of the addition amount of alkyne halogen to the trifluoroacetanilide compound is 1.5-3.0:1.

6. The method for synthesizing 2, 5-diaminopyrrole compound according to claim 1 or 2, wherein the molar ratio of the addition amount of isonitrile to the trifluoroacetanilide compound is 2.0-3.5:1.

7. The method for synthesizing a 2, 5-diaminopyrrole compound according to claim 1 or 2, wherein the base is one or more than two of cesium carbonate, potassium carbonate and 1, 8-diazabicyclo [5.4.0] undec-7-ene; the molar ratio of the addition amount of the alkali to the N-trifluoroacetanilide compound is 1.0-3.0:1.

8. The method for synthesizing 2, 5-diaminopyrrole compound according to claim 1 or 2, wherein the additive is one or more of sodium chloride, potassium bromide and lithium bromide; the molar ratio of the addition of the additive to the N-trifluoroacetanilide compound is 0.5-2.0:1;

the solvent is dichloroethane, dimethyl sulfoxide, 1, 4-hexacyclic dioxide, toluene or water and toluene, and the volume ratio is 1: 100.

9. The method for synthesizing 2, 5-diaminopyrrole compound according to claim 1 or 2, wherein the stirring reaction time is 4 to 16 hours.

10. The method for synthesizing 2, 5-diaminopyrrole compound according to claim 1 or 2, wherein the separation and purification operations are as follows: extracting the reaction liquid with ethyl acetate, combining organic phases, drying with anhydrous magnesium sulfate, filtering, evaporating the organic solvent under reduced pressure to obtain a crude product, and purifying by column chromatography to obtain the 2, 5-diaminopyrrole compound.