1. A3-amino-4-hydroxycarbazole compound is characterized in that the structural formula is as follows:

R＝CH₃and an aryl group.

2. The process for producing 3-amino-4-hydroxycarbazole-based compounds according to claim 1,

the synthesis steps are as follows: adding the raw materials 1 and 2 and potassium carbonate into tetrahydrofuran/n-hexane, heating to 40-60 ℃, reacting for 24-36h, and performing column chromatography separation to obtain the target compound 3.

3. The use of the 3-amino-4-hydroxycarbazole-based compound of claim 1 in organic optoelectronic materials and active pharmaceutical molecules.

Background

Carbazole structural units are present in natural products, drugs and functional materials. For example, 4-hydroxycarbazole is present in the drug carvedilol (j.med. chem.2019,62,5312) for the treatment of hypertension and heart failure, and additionally the family of natural products, carbazomycin, which have antibacterial activity (j.antibiot.1980,33,683) also contains this fragment.

The traditional synthesis method of 4-hydroxy carbazole is palladium-catalyzed dehydroaromatization of tetrahydro-4H-carbazole-4-ketone (Tetrahedron 2003,59,6323), and the reaction has the defects of harsh reaction conditions, incapability of directly obtaining substituted 4-hydroxy carbazole and the like. Since indole has an advantage of being easily available, a method for preparing a 4-hydroxycarbazole derivative using a benzene cyclization strategy of indole from indole as a starting material has also been reported. Among many methods, 3-nitroindole is a more efficient and simple method for synthesizing 4-hydroxy carbazole through benzene cyclization reaction of 3-nitroindole because the preparation method is simple (Synthesis 1999,7, 1117). Substrates that have been reported to react with 3-nitroindole to produce 4-hydroxycarbazoles include: methoxy-substituted 1, 3-cyclohexadienes (Tetrahedron 2009,65,5328), 1-trimethylsiloxy-1, 3-butadiene (lett. org. chem.2012,9,691) and enals (org. chem. front.2020,7,3862). However, these methods have disadvantages such as narrow substrate range, severe reaction conditions, and (or) complicated reaction procedures.

Based on the important application of the 4-hydroxy carbazole derivative and the defects of the existing synthesis method, in order to synthesize the compound efficiently and simply, a method for synthesizing the substituted 4-hydroxy carbazole compound is invented.

Disclosure of Invention

The invention aims to provide a 3-amino-4-hydroxycarbazole compound, a preparation method and application thereof.

A3-amino-4-hydroxycarbazole compound:

according to the invention, the synthesis steps of the 3-amino-4-hydroxycarbazole compound are as follows: synthesizing a target compound by taking a 3-nitroindole compound and an alkylidene azlactone compound as raw materials and tetrahydrofuran/n-hexane (1:2, v/v) as a solvent under the action of potassium carbonate under the protection of nitrogen, wherein the synthesis reaction formula of the target compound is as follows:

in the reaction, the feeding molar ratio of the 3-nitroindole compound 1 to the alkylene azlactone compound 2 is 1:1.2, the feeding molar ratio of the potassium carbonate to the 3-nitroindole compound 1 is 2:1, tetrahydrofuran/n-hexane (1:2, v/v) is used as a solvent, the reaction time is 24-36h under the protection of nitrogen, and the reaction temperature is 40-60 ℃.

After the reaction is finished, after the reaction system is cooled to room temperature, post-treatment is carried out on the reaction system, and column chromatography purification is carried out to obtain the target product 3.

The 3-amino-4-hydroxycarbazole compound can be applied to synthesis of a core structure (EP2894157A1,2015) of a photoelectric material and potential active drug molecules (WO 2014153055A2,2014).

The 3-amino-4-hydroxycarbazole compound is prepared by the method, and the method has the following advantages: the 3-amino-4-hydroxycarbazole compound is synthesized for the first time, the raw materials are easy to prepare, the reaction conditions are mild, the operation is simple and convenient, and a metal catalyst is not needed.

Detailed Description

The present invention will be further described with reference to the following examples, which are only for illustrating the technical solutions of the present invention and are not to be construed as limiting the present invention.

Example 1

Under nitrogen protection, 1a (0.20mmol), 2a (0.24mmol,1.2equiv), and four were added to a 25mL dry reaction tubeHydrofuran/n-hexane (1:2, v/v,4mL) and magnetons. Stirring at room temperature, and adding anhydrous K₂CO₃(0.40mmol,2.0equiv), transferred to a 40 ℃ oil bath and stirred for a further 24 h. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted hydrochloric acid (1M,2mL) was added thereto, stirring was continued for several minutes, and the organic solvent was removed therefrom under reduced pressure. Adding H to the remaining mixture₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtration, removal of the organic solvent under reduced pressure and column chromatography of the residue (DCM: PE ═ 1:1) afforded product 3a in 85% yield.

White solid, 90.2mg, mp 220-.¹H NMR(400MHz,CDCl₃):δ10.34(br s,1H),8.43(d,J＝7.2Hz,1H),8.30(d,J＝8.0Hz,1H),7.99(br s,1H),7.90(s,1H),7.68(d,J＝8.4Hz,2H),7.60-7.46(m,9H),7.42-7.37(m,3H),7.11(d,J＝8.0Hz,2H),2.28(s,3H)ppm.¹³C{¹H}NMR(100MHz,CDCl₃)δ166.7,146.50,145.0,138.2,138.1,137.5,135.1,134.7,132.5,132.2,129.8,129.7,129.2,128.9,128.5,127.2,126.7,126.4,126.1,124.2,123.7,118.7,117.3,114.4,108.2,21.5ppm.HRMS(ESI-TOF)m/z:[M+Na]⁺ Calcd for C₃₂H₂₄N₂NaO₄S⁺ 555.1349；Found 555.1358.

Example 2

To a 25mL dry reaction tube, 1a (0.20mmol), 2b (0.24mmol,1.2equiv), tetrahydrofuran/n-hexane (1:2, v/v,4mL), and magnetite were added under nitrogen. Stirring at room temperature, and adding anhydrous K₂CO₃(0.40mmol,2.0equiv), transferred to a 40 ℃ oil bath and stirred for a further 24 h. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted hydrochloric acid (1M,2mL) was added thereto, stirring was continued for several minutes, and the organic solvent was removed therefrom under reduced pressure. Adding H to the remaining mixture₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtration, removal of the organic solvent under reduced pressure and column chromatography (DCM: PE ═ 1:1) of the residue afforded product 3b in 50% yield.

White solid, 55.0mg, mp ═ 210 ℃ and 211 ℃.¹H NMR(400MHz,CDCl₃)δ10.30(br s,1H),8.41(d,J＝7.6Hz,1H),8.30(d,J＝8.4Hz,1H),8.05(br s,1H),7.87(d,J＝7.8Hz,1H),7.67(d,J＝8.0Hz,2H),7.56(d,J＝7.6Hz,2H),7.53-7.45(m,2H),7.40-7.35(m,7H),7.10(d,J＝8.4Hz,2H),2.48(s,3H),2.27(s,3H)ppm.¹³C{¹H}NMR(100MHz,CDCl₃)δ166.7,146.4,144.9,138.4,138.1,137.5,135.1,134.7,132.5,132.2,129.8,129.7,129.6,128.8,127.2,126.6,126.4,126.2,124.1,123.7,118.8,117.1,114.4,108.2,21.4,21.3ppm.HRMS(ESI-TOF)m/z:[M+Na]⁺ Calcd for C₃₃H₂₆N₂NaO₄S⁺ 569.1505；Found 569.1515.

Example 3

To a 25mL dry reaction tube, 1a (0.20mmol), 2c (0.24mmol,1.2equiv), tetrahydrofuran/n-hexane (1:2, v/v,4mL), and magnetons were added under nitrogen. Stirring at room temperature, and adding anhydrous K₂CO₃(0.40mmol,2.0equiv), transferred to a 40 ℃ oil bath and stirred for a further 24 h. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted hydrochloric acid (1M,2mL) was added thereto, stirring was continued for several minutes, and the organic solvent was removed therefrom under reduced pressure. Adding H to the remaining mixture₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtration, removal of the organic solvent under reduced pressure and column chromatography of the residue (DCM: PE ═ 5:1) afforded product 3c in 84% yield.

White solid, 96.9mg, mp 267-268 ℃.¹H NMR(400MHz,DMSO-d₆)δ10.35(br s,1H),9.73(br s,1H),8.27-8.23(m,4H),7.81-7.56(m,7H),7.60-7.43(m,5H),7.35(d,J＝8.4Hz,2H),2.29(s,3H)ppm.¹³C{¹H}NMR(100MHz,DMSO-d₆)δ166.7,150.6,146.8,146.6,145.9,138.9,137.4,137.3,134.3,133.6,131.4,130.3,130.2,128.1,127.7,127.2,126.3,125.1,124.6,123.2,123.0,118.1,114.8,114.2,106.3,21.1ppm.HRMS(ESI-TOF)m/z:[M+Na]⁺ Calcd for C₃₂H₂₃N₃NaO₆S⁺ 600.1200；Found 600.1204.

Example 4

To a 25mL dry reaction tube, 1a (0.20mmol), 2d (0.24mmol,1.2equiv), tetrahydrofuran/n-hexane (1:2, v/v,4mL), and magnetons were added under nitrogen. Stirring at room temperature, and adding anhydrous K₂CO₃(0.40mmol,2.0equiv), transferred to a 40 ℃ oil bath and stirred for a further 24 h. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted hydrochloric acid (1M,2mL) was added thereto, stirring was continued for several minutes, and the organic solvent was removed therefrom under reduced pressure. Adding H to the remaining mixture₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtration, removal of the organic solvent under reduced pressure and column chromatography of the residue (DCM: PE ═ 1:1) afforded product 3d in 63% yield.

White solid, 73.0mg, mp 212-.¹H NMR(400MHz,CDCl₃)δ10.28(br s,1H),8.46(d,J＝7.2Hz,1H),8.32(d,J＝8.4Hz,1H),8.07(br s,1H),8.03-7.91(m,5H),7.69(d,J＝8.0Hz,2H),7.64-7.59(m,3H),7.54-7.39(m,5H),7.30(t,J＝7.8Hz,2H),7.12(d,J＝8.0Hz,2H),2.29(s,3H)ppm.¹³C{¹H}NMR(100MHz,CDCl₃)δ166.9,146.7,145.0,138.2,137.7,135.5,135.0,134.8,133.4,132.9,132.5,132.2,129.7,129.1,128.9,128.9,128.1,127.9,127.5,127.2,127.0,126.9,126.7,126.5,126.1,124.2,123.8,118.8,117.4,114.5,108.6,21.5ppm.HRMS(ESI-TOF)m/z:[M+Na]⁺ Calcd for C₃₆H₂₆N₂NaO₄S⁺605.1505；Found 605.1520.

Example 5

To a 25mL dry reaction tube, 1a (0.20mmol), 2e (0.24mmol,1.2equiv), tetrahydrofuran/n-hexane (1:2, v/v,4mL), and magnetons were added under nitrogen. Stirring at room temperature, and adding anhydrous K₂CO₃(0.40mmol,2.0equiv), transferred to a 60 ℃ oil bath and stirred for a further 24 h. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted hydrochloric acid (1M,2mL) was added thereto, stirring was continued for several minutes, and the organic solvent was removed therefrom under reduced pressure. Adding H to the remaining mixture₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtration, removal of the organic solvent under reduced pressure and column chromatography of the residue (DCM: PE ═ 1:1) afforded product 3e in 24% yield.

White solid, 25.4mg, mp 189-.¹H NMR(400MHz,CDCl₃)δ10.28(br s,1H),8.44(d,J＝7.2Hz,1H),8.36(br s,1H),8.30(d,J＝8.4Hz,1H),8.03(s,1H),7.70(t,J＝8.2Hz,4H),7.59-7.54(m,2H),7.51-7.45(m,3H),7.40(t,J＝7.6Hz,1H),7.24(m,2H),7.12(d,J＝8.4Hz,2H),2.28(s,3H)ppm.¹³C{¹H}NMR(100MHz,CDCl₃)δ166.7,146.5,145.0,139.3,138.2,137.3,134.6,132.7,132.1,129.7,129.0,128.0,127.9,127.5,127.4,127.2,126.9,126.5,126.0,124.3,123.8,119.1,117.9,114.5,109.1,21.5ppm.HRMS(ESI)m/z:[M+Na]⁺ Calcd for C₃₀H₂₂N₂NaO₄S₂ ⁺ 561.0913；Found 561.0922.

Example 6

To a 25mL dry reaction tube, 1a (0.20mmol), 2f (0.24mmol,1.2equiv), tetrahydrofuran/n-hexane (1:2, v/v,4mL), and magnetons were added under nitrogen. Stirring at room temperature, and adding anhydrous K₂CO₃(0.40mmol,2.0equiv)The mixture was transferred to an oil bath at 40 ℃ and stirred for 36 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted hydrochloric acid (1M,2mL) was added thereto, stirring was continued for several minutes, and the organic solvent was removed therefrom under reduced pressure. Adding H to the remaining mixture₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtration, removal of the organic solvent under reduced pressure and column chromatography (DCM: PE ═ 1:1) of the residue afforded product 3f in 32% yield.

White solid, 29.9mg, mp 247-.¹H NMR(400MHz,CDCl₃)δ9.39(br s,1H),8.35(d,J＝7.2Hz,1H),8.25(d,J＝9.0Hz,1H),7.94-7.92(m,3H),7.80(s,1H),7.66(d,J＝8.4Hz,2H),7.61(t,J＝7.4Hz,1H),7.53(t,J＝7.6Hz,2H),7.43(t,J＝7.6Hz,1H),7.35(t,J＝7.2Hz,1H),7.09(d,J＝8.0Hz,2H),2.55(s,3H),2.26(s,3H)ppm.¹³C{¹H}NMR(100MHz,CDCl₃)δ167.2,146.5,144.9,137.8,137.7,134.8,132.8,132.7,130.2,129.6,129.0,127.3,126.4,126.3,126.2,124.1,123.4,119.9,116.3,114.4,108.5,21.5,19.5ppm.HRMS(ESI-TOF)m/z:[M+Na]⁺ Calcd for C₂₇H₂₂N₂NaO₄S⁺ 493.1192；Found 493.1197.

Example 7

To a 25mL dry reaction tube, 1a (0.20mmol), 2g (0.24mmol,1.2equiv), tetrahydrofuran/n-hexane (1:2, v/v,4mL), and magnetite were added under nitrogen. Stirring at room temperature, and adding anhydrous K₂CO₃(0.40mmol,2.0equiv), transferred to a 40 ℃ oil bath and stirred for a further 24 h. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted hydrochloric acid (1M,2mL) was added thereto, stirring was continued for several minutes, and the organic solvent was removed therefrom under reduced pressure. Adding H to the remaining mixture₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtering, removing the organic solvent under reduced pressure, and subjecting the residue to column chromatography (DCM: P)E ═ 1:1) isolated to give 3g of product in 72% yield.

A white solid, 79.0mg,¹H NMR(400MHz,CDCl₃)δ10.40(br s,1H),8.44(d,J＝7.2Hz,1H),8.30(d,J＝8.0Hz,1H)8.04(br s,1H),7.90(s,1H),7.68(d,J＝8.4Hz,2H),7.57-7.44(m,5H),7.42-7.38(m,3H),7.35-7.29(m,3H),7.11(d,J＝8.0Hz,2H),2.45,2.28ppm.¹³C{¹H}NMR(100MHz,CDCl₃)δ166.7,146.5,144.9,139.1,138.1,138.1,137.6,135.2,134.8,132.6,132.4,130.6,129.7,129.3,129.1,128.9,127.2,126.9,126.7,126.5,126.2,124.2,123.7,118.8,117.2,114.5,108.1,21.49,21.47ppm.HRMS(ESI-TOF)m/z:[M+Na]⁺Calcd for C₃₃H₂₆N₂NaO₄S⁺ 569.1505；Found 569.1514.

example 8

To a 25mL dry reaction tube, 1a (0.20mmol), 2h (0.24mmol,1.2equiv), tetrahydrofuran/n-hexane (1:2, v/v,4mL), and magnetons were added under nitrogen. Stirring at room temperature, and adding anhydrous K₂CO₃(0.40mmol,2.0equiv), transferred to a 40 ℃ oil bath and stirred for a further 24 h. After the reaction was completed, the reaction mixture was cooled to room temperature, diluted hydrochloric acid (1M,2mL) was added thereto, stirring was continued for several minutes, and the organic solvent was removed therefrom under reduced pressure. Adding H to the remaining mixture₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtration, removal of the organic solvent under reduced pressure and column chromatography (DCM: PE ═ 1:1) of the residue afforded the product 3h, yield 20%.

White solid, 22.6mg, mp 226-.¹H NMR(400MHz,CDCl₃)δ10.24,8.43(d,J＝7.6Hz,1H),8.31(d,J＝8.4Hz,1H),7.85(s,1H),7.77(br s,1H),7.68(d,J＝8.4Hz,2H),7.65-7.62(m,2H),7.54-7.35(m,10H),7.10(d,J＝8.4Hz,2H),2.27ppm.¹³C{¹H}NMR(100MHz,CDCl₃)δ167.2,146.4,145.0,138.2,137.4,136.9,134.5,133.9,132.5,132.5,132.3,132.1,130.3,130.0,129.6,128.9,127.7,127.1,126.8,126.5,126.2,124.3,123.8,119.3,118.0,114.6,108.5,21.5ppm.HRMS(ESI-TOF)m/z:[M+Na]⁺ Calcd for C₃₂H₂₃ClN₂NaO₄S⁺ 589.0959；Found 589.0970.

The 3-amino-4-hydroxycarbazole compound is prepared by the method, and the method for synthesizing the compound is not reported at present. The invention has the advantages that: the 3-amino-4-hydroxy carbazole compound is synthesized for the first time, the raw materials are easy to prepare, the reaction conditions are mild, and the operation is simple and convenient.

Application experiments

The photoelectric material core structure 4 and the potential active drug molecules 5 are prepared by simple chemical conversion by utilizing the hydroxyl and amino functional groups at the ortho positions in the compound obtained by the invention. The following is an example of compound 3 a:

the synthetic route for compound 4 is as follows:

to a 25mL dry reaction tube was added 3a (0.10mmol), MeSO₃H (0.30mmol,3.0equiv,28.8mg) and magnetons. Moving the mixture into an oil bath, heating, refluxing and stirring for 18 h. After the reaction is finished, the reaction solution is cooled to room temperature, and H is added into the reaction solution₂O (10mL) with CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtration, removal of the organic solvent under reduced pressure and column chromatography of the residue (DCM: PE ═ 1:2) afforded product 4 in 97% yield.

White solid, 49.7mg, 97% yield. mp 270-272 ℃.¹H NMR(400MHz,CDCl₃)δ8.62(s,1H),8.43(d,J＝8.4Hz,1H),8.37-8.35(m,2H),8.26(d,J＝7.6Hz,1H),8.19(d,J＝7.6Hz,2H),7.73(d,J＝8.4Hz,2H),7.62-7.46(m,8H),7.10(d,J＝8.4Hz,2H),2.24(s,3H)ppm.¹³C{¹H}NMR(100MHz,CDCl₃)δ162.5,145.1144.6,138.8,137.4,137.0,136.9,134.7,131.7,131.3,129.7,129.4,128.8,128.7,128.1,127.6,127.4,127.1,126.5,124.5,123.4,122.1,115.5,110.7,110.4,21.5ppm.HRMS(ESI-TOF)m/z:[M+H]⁺ Calcd for C₃₂H₂₃N₂O₃S⁺515.1424；Found 515.1434.

The synthetic route for compound 5 is as follows:

to a 25mL dry reaction tube were added 3a (0.20mmol), hydrazine hydrate (85%, 1.0mL) and magnetons. Moving to an oil bath for stirring under reflux for 4h. After the reaction is finished, cooling the reaction liquid to room temperature, adjusting the pH of the solution to 6 by using diluted hydrochloric acid (1M), and using CH₂Cl₂(10 mL. times.3) and the combined organic phases were extracted with anhydrous Na₂SO₄Drying, filtering, removing the organic solvent by rotary evaporation under reduced pressure, dissolving the residue with anhydrous tetrahydrofuran, adding N, N' -carbonyldiimidazole (CDI,0.24mmol,1.2equiv,38.9mg), moving the reaction system to an oil bath, heating under reflux, stirring for 4h, cooling the reaction solution to room temperature, removing the organic solvent by rotary evaporation under reduced pressure, and separating the residue with column chromatography (DCM) to obtain the product 5 with a yield of 53%.

White solid, 48.0mg, 53% yield. mp>300℃.¹H NMR(400MHz,DMSO-d₆)δ11.97(br s,1H),8.29(d,J＝8.4Hz,1H),8.07(s,1H),8.01(d,J＝7.6Hz,1H),7.76-7.51(m,9H),7.30(d,J＝7.6Hz,2H),2.25(s,3H)ppm.¹³C{¹H}NMR(100MHz,DMSO-d₆)δ154.9,145.8,138.1,136.8,136.2,134.0,133.3,130.2,129.2,128.4,128.3,126.3,125.0,124.8,123.6,122.2,114.9,109.3,109.0,21.0ppm.HRMS(ESI-TOF)m/z:[M+H]⁺ Calcd for C₂₆H₁₉N₂O₄S⁺455.1060；Found 455.1065。

It should be noted that the above summary and the detailed description are intended to demonstrate the practical application of the technical solutions provided by the present invention, and should not be construed as limiting the scope of the present invention. Various modifications, equivalent substitutions, or improvements may be made by those skilled in the art within the spirit and principles of the invention. The scope of the invention is to be determined by the appended claims.