Preparation method of N-chloroethyl carbazole

Abstract

The invention relates to a preparation method of N-chloroethyl carbazole, which is characterized in that carbazole and vinyl chloride are subjected to nucleophilic addition reaction under alkaline conditions to obtain the N-chloroethyl carbazole. The preparation method of N-chloroethyl carbazole provided by the invention solves the problems of tedious steps, high cost and more byproducts in the traditional synthesis method, and has the characteristics of simple process, cheap and easily available raw materials, mild reaction conditions, high yield of 89% or more and high purity.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, specifically to a method for synthesizing N-chloroethylcarbazole from vinyl chloride and carbazole via a one-step addition reaction. Background Technology

[0002] N-Chloroethylcarbazole is an important organic intermediate widely used in pharmaceuticals, dyes, and optoelectronic materials. Its traditional synthesis methods often involve multi-step reactions, such as using carbazole and chloroethanol (or dichloroethane) as raw materials, followed by a substitution reaction in the presence of a dehydrating agent, or obtaining it through the addition reaction of carbazole with ethylene oxide followed by chlorination. These methods suffer from problems such as cumbersome reaction steps, high raw material costs, numerous byproducts, and low yields, limiting their industrial application.

[0003] Therefore, developing an efficient and simple one-step synthesis process is of great practical significance. Summary of the Invention

[0004] In order to solve the above-mentioned technical problems, the inventors of this invention discovered in their research that N-chloroethylcarbazole can be prepared by a one-step nucleophilic addition reaction of carbazole and vinyl chloride as raw materials. The process is simple, the reaction conditions are mild, and the yield is high. It also avoids the use of highly toxic chlorinating reagents and eliminates the generation of byproducts such as hydrochloric acid gas from the source.

[0005] The technical solution of the present invention is as follows:

[0006] This invention provides a method for preparing N-chloroethylcarbazole. Under alkaline conditions, carbazole undergoes a nucleophilic addition reaction with vinyl chloride to obtain N-chloroethylcarbazole. The reaction equation is as follows:

[0007] .

[0008] Carbazole undergoes deprotonation under alkaline conditions to form an active carbazole anion. The carbazole anion attacks the partially positively charged β-carbon (the carbon bonded to chlorine) in the vinyl chloride molecule, breaking the double bond in vinyl chloride. The chlorine atom remains at the end of the molecular chain as a leaving group, yielding N-chloroethylcarbazole.

[0009] The hydrogen atom in the nitrogen atom of carbazole is acidic. Under alkaline conditions, it generates a carbazole anion, which enhances the nucleophilicity of imidazole.

[0010] The alkaline conditions described in this invention are provided by an alkaline reagent, which can be an organic or inorganic base, as long as it provides alkaline conditions for the reaction environment. Preferably, the alkaline reagent is selected from at least one of potassium carbonate, sodium carbonate, lithium hydroxide, sodium hydroxide, triethylamine, and 1,5-diazabicyclo[4.3.0]non-5-ene. The molar ratio of the alkaline reagent to the carbazole is 4:5 to 6:5.

[0011] The nucleophilic addition reaction described in this invention is carried out in an organic solvent, which only needs to be able to dissolve carbazole and a basic reagent. Preferably, the solvent is selected from at least one of N,N-dimethylaniline and N,N-dimethylformamide. The amount of the organic solvent used is 80-120 mg / 0.1 mol carbazole.

[0012] The nucleophilic addition reaction described in this invention can be carried out at a temperature that allows the reaction to occur. Preferably, the reaction temperature is 40–120°C, and more preferably, the reaction temperature is 60–100°C.

[0013] At the reaction temperature of this invention, vinyl chloride is in the gas phase. To improve the reaction rate and product yield, a phase transfer catalyst is added to the nucleophilic addition reaction. The phase transfer catalyst is selected from at least one of benzyltriethylammonium chloride, tetrabutylammonium bromide, and hexadecyltrimethylammonium bromide. The amount of the phase transfer catalyst is 1% to 5% of the mass of carbazole.

[0014] The vinyl chloride described in this invention can enter the reaction system in either the gas phase or the liquid phase. To match the reaction temperature of this invention, preferably, the vinyl chloride enters the reaction system in the gas phase at a rate of 0.1 to 0.5 L / h, and the reaction time is 2 to 6 hours.

[0015] After the nucleophilic addition reaction described in this invention is completed and cooled to room temperature, the reaction solution is poured into distilled water, filtered to obtain a crude product, and the crude product is recrystallized from ethanol and dried under vacuum to obtain N-chloroethylcarbazole. The amount of ethanol used is 5-10 times the mass of the crude product.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] (1) One-step synthesis with a very simple route: The preparation method provided by the present invention cleverly utilizes the carbazole anion to attack the double bond of vinyl chloride to undergo a nucleophilic addition reaction. N-chloroethylcarbazole can be prepared in just one step, which is completely different from the two-step nucleophilic substitution method used in the field to prepare N-chloroethylcarbazole. The one-step method provided by the present invention shortens the process flow, improves production efficiency, and reduces equipment and operating costs.

[0018] (2) Low raw material cost and environmentally friendly: This invention directly uses vinyl chloride as a chlorinating agent, avoiding the use of commonly used highly toxic and corrosive chlorinating agents such as SOCl2 and POCl3, thus eliminating the generation of byproducts such as hydrochloric acid gas from the source, resulting in less waste and conforming to the principles of green chemistry. Moreover, the vinyl chloride used in this invention is commonly used as a monomer in polymerization, and there are no publicly reported reports of its use as a raw material in nucleophilic addition reactions, nor are there any publicly reported reports of its use as a chlorinating agent.

[0019] (3) The reaction conditions are mild and suitable for industrial application: The preparation method provided by the present invention avoids dangerous operations such as high-temperature chlorination and has high process safety; the reaction conditions are mild, there are few by-products, the operation is simple, and the equipment requirements are not high, making it very suitable for large-scale industrial production.

[0020] (4) High product yield and high purity: The preparation method provided by the present invention can achieve a high yield, with a yield of over 89%, and the product can achieve a purity of over 97% after one recrystallization. Attached Figure Description

[0021] Figure 1 The 1H NMR spectrum of N-chloroethylcarbazole prepared in Example 1 is shown. Detailed Implementation

[0022] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with embodiments, is provided below.

[0023] All reagents and instruments used in this invention embodiment are as follows:

[0024] Reagents: Carbazole, chemically pure; vinyl chloride, industrial grade, purity ≥99%; base (potassium carbonate, lithium hydroxide, triethylamine, 1,5-diazabicyclo[4.3.0]non-5-ene), chemically pure; phase transfer catalyst (benzyltriethylammonium chloride, tetrabutylammonium bromide, hexadecyltrimethylammonium bromide, etc.), chemically pure; solvent (NN dimethylaniline, NN dimethylformamide, etc.), chemically pure; ethanol, chemically pure.

[0025] Apparatus: Three-necked flask, 250 mL.

[0026] Example 1

[0027] Carbazole was dried in a vacuum drying oven at 60℃ and -0.06 to -0.08 MPa for 4 hours for later use. In a three-necked flask equipped with a stirrer, reflux condenser, and thermometer, 16.7 g (0.1 mol) of dried carbazole, 2.4 g (0.1 mol) of potassium hydroxide, 0.5 g of benzyltriethylammonium chloride, and 100 mL of N,N-dimethylaniline were added. The stirrer was turned on, and the temperature was raised to 80℃. Vinyl chloride was continuously introduced at a rate of 0.3 L / h for 4 hours. After the reaction was completed, the introduction of vinyl chloride was stopped, and the mixture was cooled to room temperature. The reaction solution was poured into distilled water, stirred until a solid precipitated, and filtered to obtain the crude product. The crude product was recrystallized from ethanol and dried under vacuum to obtain white crystalline N-chloroethylcarbazole. The product was characterized by ¹H NMR spectroscopy, as shown in the attached figure. Figure 1The purity was determined by high performance liquid chromatography (HPLC). The yield of the product was 90%, the purity was 98.5%, and the melting point was 129-130℃.

[0028] Example 2

[0029] Same as Example 1, except that: 13.8 g (0.1 mol) of potassium carbonate was used instead of 2.4 g (0.1 mol) of lithium hydroxide, and 100 mL of N,N-dimethylformamide was used instead of 100 mL of N,N-dimethylaniline. The product yield was 91.2%, the purity was 97.9%, and the melting point was 128-130 °C.

[0030] Example 3

[0031] Same as Example 1, except that 10.1 g (0.1 mol) of triethylamine was used instead of 2.4 g (0.1 mol) of lithium hydroxide. The product yield was 91.4%, the purity was 96.5%, and the melting point was 127-130 °C.

[0032] Example 4

[0033] Same as Example 1, except that 12.3 g (0.1 mol) of 1,5-diazabicyclo[4.3.0]non-5-ene was used instead of 2.4 g (0.1 mol) of lithium hydroxide, and 100 mL of N,N-dimethylformamide was used instead of 100 mL of N,N-dimethylaniline. The product yield was 90.9%, the purity was 98.2%, and the melting point was 129-131 °C.

[0034] Example 5

[0035] Same as Example 1, except that 0.7 g of tetrabutylammonium bromide was used instead of 0.5 g of benzyltriethylammonium chloride. The measured product yield was 91.9%, the purity was 98.0%, and the melting point was 128-130℃.

[0036] Example 6

[0037] Same as Example 1, except that: 1.0 g of hexadecyltrimethylammonium bromide was used instead of 0.5 g of benzyltriethylammonium chloride, and 100 mL of N,N-dimethylformamide was used instead of 100 mL of N,N-dimethylaniline. The product yield was measured to be 89.9%, the purity was 97.6%, and the melting point was 127-129 °C.

[0038] Example 7

[0039] Same as Example 1, except that: 16.7 g (0.1 mol) of carbazole and 2.88 g (0.12 mol) of lithium hydroxide were used. The measured product yield was 92%, the purity was 98.3%, and the melting point was 128-130 °C.

[0040] Example 8

[0041] Same as Example 1, except that: 16.7 g (0.1 mol) of carbazole and 1.92 g (0.08 mol) of lithium hydroxide were used. The measured product yield was 90.8%, the purity was 97.8%, and the melting point was 127-129 °C.

[0042] Example 9

[0043] Same as Example 1, except that the reaction temperature was 60°C. The measured product yield was 91.2%, the purity was 98.1%, and the melting point was 129-130°C.

[0044] Example 10

[0045] Same as Example 1, except that the reaction temperature was 100°C. The measured product yield was 89.3%, the purity was 97.5%, and the melting point was 127-129°C.

[0046] Example 11

[0047] Same as Example 1, except that the reaction time was 2 hours. The measured product yield was 92.1%, the purity was 98.4%, and the melting point was 128-130℃.

[0048] Example 12

[0049] Same as Example 1, except that the reaction time was 6 hours. The measured product yield was 91.8%, the purity was 98.2%, and the melting point was 128-130℃.

[0050] Example 13

[0051] Same as Example 1, except that the vinyl chloride introduction rate was 0.5 L / h. The measured product yield was 89.8%, the purity was 97.9%, and the melting point was 127-129 °C.

[0052] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for preparing N-chloroethylcarbazole, characterized in that: Under alkaline conditions, carbazole undergoes a nucleophilic addition reaction with vinyl chloride to give N-chloroethylcarbazole, as shown in the following equation: 。 2. The method for preparing N-chloroethylcarbazole according to claim 1, characterized in that: The alkaline conditions are provided by an alkaline reagent, which is selected from at least one of organic bases and inorganic bases.

3. The method for preparing N-chloroethylcarbazole according to claim 2, characterized in that: The organic base is selected from at least one of triethylamine and 1,5-diazabicyclo[4.3.0]non-5-ene; the inorganic base is selected from at least one of potassium carbonate, sodium carbonate, lithium hydroxide, and sodium hydroxide.

4. The method for preparing N-chloroethylcarbazole according to claim 2, characterized in that: The ratio of the molar amount of the alkaline reagent to the molar amount of carbazole is 4:5 to 6:

5.

5. The method for preparing N-chloroethylcarbazole according to claim 1, characterized in that: The nucleophilic addition reaction is carried out in an organic solvent selected from at least one of N,N-dimethylaniline and N,N-dimethylformamide.

6. The method for preparing N-chloroethylcarbazole according to claim 5, characterized in that: The amount of the organic solvent used is 80-120 mg / 0.1 mol carbazole.

7. The method for preparing N-chloroethylcarbazole according to claim 1, characterized in that: The reaction temperature for the nucleophilic addition reaction is 40–120 °C.

8. The method for preparing N-chloroethylcarbazole according to claim 1, characterized in that: A phase transfer catalyst is added to the nucleophilic addition reaction, and the phase transfer catalyst is selected from at least one of benzyltriethylammonium chloride, tetrabutylammonium bromide, and hexadecyltrimethylammonium bromide.

9. The method for preparing N-chloroethylcarbazole according to claim 8, characterized in that: The phase transfer catalyst is used in an amount of 1% to 5% of the carbazole mass.

10. The method for preparing N-chloroethylcarbazole according to claim 1, characterized in that: The vinyl chloride enters the reaction system in the gas phase at a rate of 0.1–0.5 L / h.

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