1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl) indole and a preparation method thereof

Abstract

This invention relates to the field of organic synthesis technology, specifically, providing a 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole with the following structural formula: It also provides a method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole, comprising the following steps: using 1-methyl-3-(1,4-naphthoquinone-2-yl)indole as a raw material, adding a solvent, adding a nitrate after temperature control, then slowly adding an acid anhydride solution, reacting at controlled temperature for a period of time, and then processing to obtain 1-methyl-2-nitro-3-... (1,4-Naphthoquinone-2-yl)indole crude product, purified to obtain pure 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole; This invention uses 1-methyl-3-(1,4-naphthoquinone-2-yl)indole as the starting material to prepare the target product. A one-step electrophilic nitration reaction efficiently and safely prepares 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole. The synthesis method is easy to operate, environmentally friendly, low in cost, high in yield, and produces few byproducts, making it suitable for large-scale commercial preparation and production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and more specifically, to a 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole and its preparation method. Background Technology

[0002] 1-Methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole is an important chemical raw material, the core skeleton of carbazole drugs, and a crucial intermediate for other pharmaceuticals. It can be used to produce sulfur dyes (such as Haichang Blue), naphthol AS-IB, anthraquinone vat dyes, oxazine dyes, and the insecticide tetranitrocarbazole. It can also be used to produce ultraviolet-sensitive photographic films and as a reagent for lignin, sugars, and formaldehyde. It has wide applications in the preparation of fluorescent materials, dye synthesis, optoelectronic materials, hole transport materials, photocatalysts, and molecular markers.

[0003] Currently, there are no literature reports on the synthesis of 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole, and its structure is also a new compound. Therefore, it is necessary to fill the gap in the research on this compound and its preparation method. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole, which uses 1-methyl-3-(1,4-naphthoquinone-2-yl)indole as a starting material to prepare the target product. The method involves a one-step electrophilic nitration reaction to efficiently and safely prepare 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole.

[0005] The synthesis process of this invention is simple, easy to operate, environmentally friendly, low-cost, and has a high yield. It can be commercially prepared and produced on a large scale to meet the ever-growing market demand.

[0006] The embodiments of the present invention are achieved through the following technical solutions:

[0007]

[0008] Using 1-methyl-3-(1,4-naphthoquinone-2-yl)indole as a raw material, a solvent was added, and nitrate was added after temperature control. Then, an acid anhydride solution was slowly added dropwise. After reacting at a controlled temperature for a period of time, crude 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole was obtained through treatment. The crude product was purified to obtain pure 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole.

[0009] Furthermore, the molar ratio of the nitrate to 1-methyl-3-(1,4-naphthoquinone-2-yl)indole is 1:1 to 4:1.

[0010] Furthermore, the molar ratio of 1-methyl-3-(1,4-naphthoquinone-2-yl)indole to acid anhydride is 1:1 to 1:8.

[0011] Furthermore, after adding the solvent, the temperature is controlled at -20 to -25°C; after adding the acid anhydride solution, the temperature is controlled at -20 to -25°C, and the reaction time is 4 to 12 hours.

[0012] Furthermore, the nitrate is one or more of potassium nitrate, sodium nitrate, tetramethylammonium nitrate, or tetrabutylammonium nitrate.

[0013] Furthermore, the solvent is one or more of tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, 1,2-dichloroethane, ethyl acetate, or xylene.

[0014] Furthermore, the acid anhydride is one or more of trifluoroacetic anhydride, trifluoromethanesulfonic anhydride, or acetic anhydride.

[0015] Furthermore, the extraction solvent is one or more of ethyl acetate, dichloromethane, or 1,2-dichloroethane.

[0016] Further purification of the crude product involves multiple extractions with an organic solvent, discarding the aqueous phase, washing, drying, filtering, and removing the solvent under reduced pressure to obtain an oily liquid product, which is then further purified to obtain the pure product.

[0017] The technical solutions of the embodiments of the present invention have at least the following advantages and beneficial effects:

[0018] This invention provides a highly efficient and safe one-step electrophilic nitration reaction to prepare 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole with few byproducts, inexpensive and readily available raw materials, mild reaction conditions, environmental friendliness, low cost, and high yield. It can be commercially prepared and produced on a large scale to meet the growing market demand. Attached Figure Description

[0019] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 The hydrogen spectrum of 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole provided in Example 2 of the present invention. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0022] Example 1: Preparation of 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole

[0023] 287 mg of 1-methyl-3-(1,4-naphthoquinone-2-yl)indole and 140 mg of tetramethylammonium nitrate were added sequentially to the reaction vessel, followed by the addition of 1 mL of acetonitrile. The temperature was controlled at -20 to 25 °C, and trifluoroacetic anhydride solution (220 mg dissolved in 1 mL of acetonitrile) was slowly added dropwise. The reaction was carried out for 4 to 12 hours. After the reaction was complete, ethyl acetate was added for extraction three times. The aqueous phase was discarded, and the organic phase was washed with saturated sodium carbonate and saturated brine. The mixture was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by vacuum evaporation to obtain a red solid product. The target product was purified by column chromatography to obtain 285 mg, with a yield of 86%.

[0024] Example 2: Preparation of 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole

[0025] 5.6 g of 1-methyl-3-(1,4-naphthoquinone-2-yl)indole and 3.2 g of tetramethylammonium nitrate were added sequentially to a reaction vessel, followed by 20 mL of dichloromethane. The temperature was controlled at -20 to 25 °C, and a trifluoroacetic anhydride solution (5.3 g dissolved in 20 mL of dichloromethane) was slowly added dropwise. The reaction was carried out for 4 to 12 hours under controlled temperature. After the reaction was complete, the product was extracted three times with dichloromethane. The aqueous phase was discarded, and the organic phase was washed with saturated sodium carbonate and saturated brine. The product was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed by vacuum evaporation to obtain a red solid product. The product was recrystallized from ethanol to obtain 5.4 g of the target product, with a yield of 83%.

[0026] 1 H NMR(400MHz, CDCl3)δ8.24(dt,J=7.2,1.9Hz,2H),7.90-7.81(m,2H),7.55(s,1H) ),7.51(d,J=8.1Hz,1H),7.42-7.30(m,2H),7.25(t,J=7.5Hz,1H),3.88(s,3H).

[0027] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A process for the preparation of 1-methyl-2-nitro-3-(1,4-naphthoquinone-2- yl)indole, characterized in that, The structural formula of 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole is: Its preparation method includes the following steps: Using 1-methyl-3-(1,4-naphthoquinone-2-yl)indole as a raw material, a solvent was added, and nitrate was added after temperature control. Then, an acid anhydride solution was slowly added dropwise. After reacting at a controlled temperature for a period of time, crude 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole was obtained through treatment. The crude product was purified to obtain pure 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole.

2. The method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole according to claim 1, characterized in that, The molar ratio of the nitrate to 1-methyl-3-(1,4-naphthoquinone-2-yl)indole is 1:1 to 4:

1.

3. The method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole according to claim 1, characterized in that, The molar ratio of 1-methyl-3-(1,4-naphthoquinone-2-yl)indole to acid anhydride is 1:1 to 1:

8.

4. The method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole according to claim 1, characterized in that, After adding the solvent, control the temperature to -20 to -25℃; after adding the acid anhydride solution, control the temperature to -20 to -25℃, and the reaction time is 4 to 12 h.

5. The method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole according to claim 1, characterized in that, The nitrate is one or more of potassium nitrate, sodium nitrate, tetramethylammonium nitrate, or tetrabutylammonium nitrate.

6. The method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole according to claim 1, characterized in that, The solvent is one or more of tetrahydrofuran, 1,4-dioxane, acetonitrile, dichloromethane, 1,2-dichloroethane, ethyl acetate, or xylene.

7. The method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole according to claim 1, characterized in that, The acid anhydride is one or more of trifluoroacetic anhydride, trifluoromethanesulfonic anhydride, or acetic anhydride.

8. The method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole according to claim 1, characterized in that, For crude product purification: extract multiple times with organic solvent, discard the aqueous phase, wash, dry, filter, and remove the solvent under reduced pressure to obtain an oily liquid product, which is then further purified to obtain the pure product.

9. The method for preparing 1-methyl-2-nitro-3-(1,4-naphthoquinone-2-yl)indole according to claim 8, characterized in that, The extraction solvent is one or more of ethyl acetate, dichloromethane, or 1,2-dichloroethane.

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