Synthesis method of deuterated chlorobenzene-D4

Abstract

The invention belongs to the technical field of preparation of deuterated organic compounds, and particularly relates to a synthetic method of deuterated chlorobenzene-D4, which comprises the following steps: reacting deuterated aniline, benzyltriethylammonium chloride and tert-butyl nitrite to prepare the deuterated chlorobenzene-D4. According to the method, the synthesis process is mild and easy to control, the requirement for equipment is low, the raw materials are low in price and high in utilization rate, and the purity and the deuteration rate of the prepared deuterated chlorobenzene-D4 are high.

Description

Technical Field

[0001] This invention belongs to the field of deuterated organic compound preparation technology, specifically relating to a method for synthesizing deuterated chlorobenzene-D4. Background Technology

[0002] The deuteration rate in deuterated compounds is a crucial factor in evaluating the quality of deuterated products. Because deuterated compounds are expensive, a high yield is essential for controlling production costs.

[0003] The industrial synthesis of chlorobenzene uses benzene and chlorine, which has high requirements for equipment and safety. Moreover, polychlorinated benzene is easily generated during the chlorination process, which reduces the utilization of raw materials.

[0004] The most common process for synthesizing chlorobenzene in the laboratory is the Sandmeyer reaction, which converts amino groups into halogens. This process involves using acid and nitrite at low temperatures to convert amino groups into diazonium salts, and then using cuprous halide as a catalyst to synthesize the corresponding haloaromatics. However, this process generates a large amount of nitrogen gas, which can easily cause splashing or even explosions, making it highly dangerous.

[0005] Therefore, existing chlorobenzene synthesis processes are not suitable for the preparation of deuterated chlorobenzene-D4. Summary of the Invention

[0006] The purpose of this invention is to provide a novel method for synthesizing deuterated chlorobenzene-D4. The synthesis process is mild and easy to control, has low requirements for equipment, uses inexpensive raw materials, has high utilization rate, and produces deuterated chlorobenzene-D4 with high purity and deuteration rate.

[0007] Specifically, the present invention provides the following technical solutions: A method for synthesizing deuterated chlorobenzene-D4 involves reacting deuterated aniline, benzyltriethylammonium chloride, and tert-butyl nitrite to prepare deuterated chlorobenzene-D4.

[0008] The reaction formula is as follows:

[0009] In the reaction of this invention, tert-butyl nitrite releases nitrous acid in the solvent, which then slowly forms an N₂O₃ precursor. This precursor then combines with deuterated aniline, undergoing a series of reactions to generate a deuterated benzene diazonium salt. This salt then combines with a chlorine atom provided by benzyltriethylammonium chloride to generate deuterated chlorobenzene-D₄. The above reaction process is mild, and the post-processing is simple. More importantly, the deuteration rate and yield of the obtained product are high.

[0010] Preferably, the amount of benzyltriethylammonium chloride used is 1.55 to 1.65 equivalents of deuterated aniline.

[0011] Preferably, the amount of tert-butyl nitrite used is 1.15 to 1.25 equivalents of deuterated aniline.

[0012] Experiments showed that the yield of the product deuterated chlorobenzene-D4 was the highest under the above dosage ratio.

[0013] As a preferred option, the following steps are included: (1) Dissolve deuterated aniline, benzyltriethylammonium chloride and tert-butyl nitrite in dichloromethane and stir at 20-60℃ for 4-8 hours; (2) The solvent in the reaction solution obtained in step (1) was removed by vacuum distillation, washed with water, extracted with dichloromethane, and the resulting organic phase was removed by vacuum distillation and further distilled to obtain deuterated chlorobenzene-D4.

[0014] More preferably, the reaction temperature is 40~50℃.

[0015] The beneficial effects of this invention are at least as follows: 1) The present invention provides a method for synthesizing deuterated chlorobenzene-D4, which uses inexpensive benzyltriethylammonium chloride and tert-butyl nitrite as raw materials, resulting in low production costs. At the same time, the reaction process is simple, the reaction conditions are mild, and the requirements for equipment are low. 2) The present invention provides a method for synthesizing deuterated chlorobenzene-D4, which has a simple reaction process, mild reaction conditions, and does not require high temperature and high pressure, making it very suitable for industrial production; 3) The present invention provides a method for synthesizing deuterated chlorobenzene-D4, which yields deuterated chlorobenzene-D4 with high purity and deuteration rate. By optimizing the ratio of raw materials, the product yield can be further improved. 4) The present invention provides a method for synthesizing deuterated chlorobenzene-D4, which is simple to process and does not require column chromatography purification to obtain a deuterated chlorobenzene-D4 product with a yield of >70%, purity ≥99.7%, and deuteration rate ≥99%. Attached Figure Description

[0016] Figure 1 The mass spectrum of deuterated chlorobenzene-D4 prepared in Example 1; Figure 2 The gas phase diagram of deuterated chlorobenzene-D4 prepared in Example 1; Figure 3 The image shows the 1H NMR spectrum of deuterated chlorobenzene-D4 prepared in Example 1. Detailed Implementation

[0017] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. The following embodiments are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Where specific techniques or conditions are not specified in the embodiments, they shall be performed in accordance with the techniques or conditions described in the literature in the art, or in accordance with the product manual.

[0018] In Example 1 below, the deuterated aniline used was sourced from Ningbo Cuiying Chemical Technology Co., Ltd.; The benzyltriethylammonium chloride used was sourced from Anaiji Chemical; The tert-butyl nitrite used was sourced from Anaiji Chemical.

[0019] Example 1 In a 500 mL single-necked round-bottom flask equipped with a stirrer, 300 mL of dichloromethane, 50 g (1 eq) of deuterated aniline, 186 g (1.6 eq) of benzyltriethylammonium chloride, and 63 g (1.2 eq) of tert-butyl nitrite were added sequentially. The flask was also equipped with a thermometer and a spherical condenser. The oil bath temperature was adjusted to 60 °C, and the temperature inside the round-bottom flask was adjusted to 45 °C. The reaction was carried out for 7 hours, and then cooled to room temperature.

[0020] Dichloromethane solvent was removed by vacuum distillation. 1 liter of deionized water was added to wash away benzyltriethylammonium chloride salts. Then, dichloromethane was added for extraction. The mixture was separated using a separatory funnel, and the organic phase was collected. The solvent was removed by vacuum distillation. Finally, deuterated chlorobenzene-D4 was obtained by distillation with a yield of 83%, a purity of 99.78%, and a deuteration rate of 99%.

[0021] Figure 1 The mass spectrum of deuterated chlorobenzene-D4 prepared in Example 1; Figure 2 The gas phase diagram of deuterated chlorobenzene-D4 prepared in Example 1; Figure 3 The image shows the 1H NMR spectrum of deuterated chlorobenzene-D4 prepared in Example 1.

[0022] Example 2 In a 500 mL single-necked round-bottom flask equipped with a stirrer, 300 mL of dichloromethane, 50 g of deuterated aniline (1 eq), 139.5 g of benzyltriethylammonium chloride (1.2 eq), and 63 g of tert-butyl nitrite (1.2 eq) were added sequentially. The flask was also equipped with a thermometer and a spherical condenser. The oil bath temperature was adjusted to 60 °C, and the temperature inside the round-bottom flask was adjusted to 45 °C. The reaction was carried out for 7 hours, and then cooled to room temperature.

[0023] Dichloromethane solvent was removed by vacuum distillation. 1 liter of deionized water was added to wash away benzyltriethylammonium chloride salts. Then, dichloromethane was added for extraction. The mixture was separated using a separatory funnel, and the organic phase was collected. The solvent was removed by vacuum distillation. Finally, deuterated chlorobenzene-D4 was obtained by distillation with a yield of 73%, a purity of 99.71%, and a deuteration rate of 99.2%.

[0024] Example 3 In a 500 mL single-necked round-bottom flask equipped with a stirrer, 300 mL of dichloromethane, 50 g (1 eq) of deuterated aniline, 186 g (1.6 eq) of benzyltriethylammonium chloride, and 52.5 g (1 eq) of tert-butyl nitrite were added sequentially. The single-necked round-bottom flask was equipped with a thermometer and a spherical condenser. The oil bath temperature was adjusted to 60 °C, and the temperature inside the round-bottom flask was adjusted to 45 °C. The reaction was carried out for 7 hours, and then cooled to room temperature.

[0025] Dichloromethane solvent was removed by vacuum distillation. 1 liter of deionized water was added to wash away benzyltriethylammonium chloride salts. Then, dichloromethane was added for extraction. The mixture was separated using a separatory funnel, and the organic phase was collected. The solvent was removed by vacuum distillation. Finally, deuterated chlorobenzene-D4 was obtained by distillation with a yield of 71%, a purity of 99.79%, and a deuteration rate of 98.8%.

[0026] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for synthesizing deuterated chlorobenzene-D4, characterized in that, Deuterated chlorobenzene-D4 was prepared by reacting deuterated aniline, benzyl triethylammonium chloride, and tert-butyl nitrite.

2. The method for synthesizing deuterated chlorobenzene-D4 according to claim 1, characterized in that, The amount of benzyltriethylammonium chloride used is 1.55 to 1.65 equivalents of deuterated aniline.

3. The method for synthesizing deuterated chlorobenzene-D4 according to claim 1 or 2, characterized in that, The amount of tert-butyl nitrite used is 1.15 to 1.25 equivalents of deuterated aniline.

4. The method for synthesizing deuterated chlorobenzene-D4 according to claim 1 or 2, characterized in that, Includes the following steps: (1) Dissolve deuterated aniline, benzyltriethylammonium chloride and tert-butyl nitrite in dichloromethane and stir at 20-60℃ for 4-8 hours; (2) The solvent in the reaction solution obtained in step (1) was removed by vacuum distillation, washed with water, extracted with dichloromethane, and the resulting organic phase was removed by vacuum distillation and further distilled to obtain deuterated chlorobenzene-D4.

5. The method for synthesizing deuterated chlorobenzene-D4 according to claim 4, characterized in that, The reaction temperature is 40~50℃.

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