Method for synthesizing deuterated iodobenzene by taking iodine elementary substance as raw material
The preparation of deuterated iodobenzene by reacting sodium chlorite with elemental iodine solves the problems of numerous byproducts, difficult separation, and poor safety in the synthesis of deuterated iodobenzene, and achieves high-yield and low-cost production of deuterated iodobenzene.
Patent Information
- Application Number
- CN202512030258.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-30
- Publication Date
- 2026-04-24
AI Technical Summary
The existing technology for the synthesis of deuterated iodobenzene involves numerous byproducts, difficult separation, poor safety, and low deuteration rate, resulting in high production costs.
Deuterated iodobenzene was prepared by reacting sodium chlorite as an oxidant and elemental iodine as an iodizing agent with deuterated benzene. By controlling the ratio and conditions of the reactants and optimizing the post-treatment process, no by-products were generated and the yield was high.
This improved the conversion rate and deuterium source utilization of deuterated iodobenzene, reduced production costs, simplified the post-processing, and enabled the safe and efficient synthesis of deuterated iodobenzene.
Smart Images
Figure CN121913863A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of deuterated organic compound preparation technology, specifically relating to a method for synthesizing deuterated iodobenzene using elemental iodine as a raw material. Background Technology
[0002] Deuterated iodobenzene is an important intermediate in the fields of medicine and materials, but its synthesis faces the following technical bottlenecks: Impurity separation is difficult: Traditional methods (such as concentrated nitric acid oxidation and iodine chloride method) easily generate byproducts such as deuterated nitrobenzene and deuterated chlorobenzene, whose boiling points are close to those of the target product, resulting in high separation costs.
[0003] Low safety: The diazotization of aniline carries an explosion risk, and the release of nitrogen gas can easily cause splashing.
[0004] High cost: The use of toxic reagents such as thallium trioxide or the low utilization rate of deuterated raw materials leads to high production costs.
[0005] Therefore, there is an urgent need for a safe, efficient and low-cost synthesis method. Summary of the Invention
[0006] This invention aims to solve the technical problems of numerous byproducts, difficult separation, poor safety, and low deuteration rate in the synthesis of deuterated iodobenzene. It provides a method for synthesizing deuterated iodobenzene using elemental iodine as a raw material, which improves the conversion rate of expensive deuterated benzene, eliminates the generation of byproducts, has low equipment requirements, and allows the heavy water generated in the reaction to be recovered, thereby improving the utilization rate of the deuterium source.
[0007] Specifically, the present invention provides the following technical solutions: A method for synthesizing deuterated iodobenzene using elemental iodine as a raw material includes the following steps: Deuterated iodobenzene was prepared by reacting sodium chlorite as an oxidant and elemental iodine as an iodizing agent with deuterated benzene.
[0008] The synthesis of deuterated iodobenzene in this invention mainly involves two reactions: First, deuterated benzene reacts with iodine to produce deuterated iodobenzene and deuterium iodide. Deuterium iodide has reducing properties and inhibits the generation of iodide ions.
[0009] The reaction equation is:
[0010] Secondly, sodium chlorite is the oxidant and deuterium iodide is the reducing agent. The two undergo a redox reaction, and the generated elemental iodine continues to react with deuterated benzene. Therefore, the theoretical amount of iodine input is equal to the molar amount of deuterated benzene. The generated heavy water can be recovered and obtained through simple distillation.
[0011] The reaction equation is:
[0012] The two reactions mentioned above occur simultaneously.
[0013] Preferably, the mass ratio of deuterated benzene to elemental iodine is 1:1.4 to 1:1.6. In this invention, if the amount of elemental iodine used is lower than the above ratio, the yield of deuterated iodobenzene will decrease significantly.
[0014] Preferably, the ratio of sodium chlorite to deuterated benzene is 30-35:100. Too much sodium chlorite will cause solid sodium chlorite to precipitate from the reaction solution, increasing the burden on the stirring paddle, without increasing the yield of deuterated benzene; too little sodium chlorite cannot effectively limit the content of deuterium iodide in the system.
[0015] More preferably, the ratio of sodium chlorite to deuterated benzene is 1:3. Experiments have shown that the yield of the product deuterated iodobenzene is the highest under the above ratio.
[0016] Preferably, the sodium chlorite is added dropwise to the reaction system in the form of an aqueous sodium chlorite solution, with the temperature of the reaction system at 75~85℃ and the addition time at 4~6h.
[0017] More preferably, the concentration of sodium chlorite in the sodium chlorite aqueous solution is 80~120g / L.
[0018] Preferably, the reaction temperature is 75-85°C, and the reaction time is 2-4 hours. The reaction time is the time after all sodium chlorite has been added.
[0019] Preferably, the reaction also includes a step of purifying the deuterated iodobenzene obtained from the reaction: The reaction system after the reaction was cooled to room temperature, and the upper liquid was removed by separation (to remove heavy water) to obtain the primary processed liquid. The primary treatment solution was washed with water, and then sodium sulfite was added until the solution became colorless (to remove unreacted iodine). It was then washed with water again until neutral, the aqueous layer was separated, and the solution was dried to obtain the secondary treatment solution. The secondary treatment solution was distilled under reduced pressure to obtain pure deuterated iodobenzene.
[0020] The beneficial effects of this invention are at least as follows: (1) The present invention provides a method for synthesizing deuterated iodobenzene using iodine as raw material, which improves the conversion rate of expensive deuterated benzene, does not generate by-products, has low requirements for equipment, and the heavy water or semi-deuterium water generated in the reaction can be recovered, thus improving the utilization rate of deuterium source. (2) The method for preparing deuterated iodobenzene provided by the present invention further improves the yield of the product deuterated iodobenzene by optimizing the ratio of raw materials and reaction conditions; (3) The present invention provides a method for synthesizing deuterated iodobenzene using iodine as a raw material. The post-processing of deuterated iodobenzene is relatively simple. The crude deuterated iodobenzene can be separated by simple liquid-liquid separation. The unreacted deuterated benzene (content of more than 2%) can be separated by simple vacuum distillation since the boiling points of the two are about 100°C apart. (4) The present invention provides a method for synthesizing deuterated iodobenzene using iodine as raw material, and uses inexpensive sodium chlorite as an oxidant, which greatly reduces the synthesis cost. Attached Figure Description
[0021] Figure 1 The gas chromatogram of deuterated iodobenzene-D4 prepared in Example 1; Figure 2 The gas chromatography-mass spectrometry (GC-MS) image of deuterated iodobenzene-D4 prepared in Example 1 is shown below. Figure 3 The image shows the 1H NMR spectrum of the deuterated iodobenzene-D4 prepared in Example 1. Detailed Implementation
[0022] 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.
[0023] Example 1 300g of deuterated benzene and 450g of elemental iodine were added sequentially to a 2L four-necked round-bottom flask. The round-bottom flask was equipped with a thermometer, a constant-pressure dropping funnel, a mechanical stirrer, and a spherical condenser. The condenser was equipped with a tail gas absorption device to absorb the escaped deuterium iodide. The oil bath temperature was adjusted to 80℃, and the temperature inside the round-bottom flask was adjusted to 77℃. 1000mL of deionized solution containing 100g of sodium chlorite was added dropwise over 5 hours. The reaction was then allowed to proceed for another 3 hours to obtain crude deuterated iodobenzene. The solution was cooled to room temperature, and the supernatant was removed by separation. After washing twice with water, sodium sulfite was added until the solution became colorless. The solution was then washed with water until neutral, separated, dried, and distilled under reduced pressure to obtain pure deuterated iodobenzene with a purity of 99.39%, a deuteration rate of 99.15%, and a yield of 77%.
[0024] Figure 1 The image shows the gas chromatogram of deuterated iodobenzene-D4 prepared in Example 1; the purity is 99.39%.
[0025] Figure 2 The gas chromatography-mass spectrometry (GC-MS) chromatogram of deuterated iodobenzene-D4 prepared in Example 1 (i.e., Figure 1 The mass spectrum of the molecular ion peak corresponding to the elution position in the image shows that the compound is deuterated iodobenzene.
[0026] Figure 3 The 1H NMR spectrum of the deuterated iodobenzene-D4 prepared in Example 1 shows a deuteration rate of 99.15%.
[0027] Test method: The principle is that the ratio of the number of hydrogen atoms is equal to the ratio of the peak areas of the hydrogen NMR spectrum.
[0028] 1. Purchase deuterated iodobenzene with a known deuteration rate from the market, whose deuteration rate is Ds (standard sample).
[0029] 2. The deuteration rate of the tested sample is D, and Dx is the content of non-deuterium sample in the tested sample (i.e., hydrogenation rate).
[0030] Take two identical NMR tubes, weigh out the same mass of deuterated iodobenzene standard and the sample to be tested, and perform NMR tests to obtain the peak areas As and Ax. The calculation formula is as follows: D=1-Dx=1-[(1-Ds)*Ax / As].
[0031] Example 2 300g of deuterated benzene and 450g of elemental iodine were added sequentially to a 2L four-necked round-bottom flask. The round-bottom flask was equipped with a thermometer, a constant-pressure dropping funnel, a mechanical stirrer, and a spherical condenser. The condenser was equipped with a tail gas absorption device to absorb the escaped deuterium iodide. The oil bath temperature was adjusted to 80℃, and the temperature inside the round-bottom flask was adjusted to 77℃. 1000mL of deionized solution containing 90g of sodium chlorite was added dropwise over 5 hours. The reaction was then carried out for another 3 hours to obtain crude deuterated iodobenzene. After cooling to room temperature, the supernatant was removed by separation. The solution was washed twice with water and sodium sulfite was added until it became colorless. The solution was then washed with water until neutral, separated, dried, and distilled under reduced pressure to obtain pure deuterated iodobenzene with a purity of 99.29%, a deuteration rate of 99.13%, and a yield of 67%.
[0032] Example 3 300g of deuterated benzene and 400g of elemental iodine were added sequentially to a 2L four-necked round-bottom flask. The round-bottom flask was equipped with a thermometer, a constant-pressure dropping funnel, a mechanical stirrer, and a spherical condenser. The condenser was equipped with a tail gas absorption device to absorb the escaped deuterium iodide. The oil bath temperature was adjusted to 80℃, and the temperature inside the round-bottom flask was adjusted to 77℃. 1000mL of deionized solution containing 100g of sodium chlorite was added dropwise over 5 hours. The reaction was then allowed to proceed for another 3 hours to obtain crude deuterated iodobenzene. The solution was cooled to room temperature, and the supernatant was removed by separation. After washing twice with water, sodium sulfite was added until the solution became colorless. The solution was then washed with water until neutral, separated, dried, and distilled under reduced pressure to obtain pure deuterated iodobenzene with a purity of 99.37%, a deuteration rate of 99.14%, and a yield of 59%.
[0033] Example 4 300g of deuterated benzene and 450g of elemental iodine were added sequentially to a 2L four-necked round-bottom flask. The round-bottom flask was equipped with a thermometer, a constant-pressure dropping funnel, a mechanical stirrer, and a spherical condenser. The condenser was equipped with a tail gas absorption device to absorb the escaped deuterium iodide. The oil bath temperature was adjusted to 80℃, and the temperature inside the round-bottom flask was adjusted to 77℃. 1000mL of deionized solution containing 100g of sodium chlorite was added dropwise over 2 hours. The reaction was then allowed to proceed for another 3 hours to obtain crude deuterated iodobenzene. The solution was cooled to room temperature, and the supernatant was removed by separation. After washing twice with water, sodium sulfite was added until the solution became colorless. The solution was then washed with water until neutral, separated, dried, and distilled under reduced pressure to obtain pure deuterated iodobenzene with a purity of 99.36%, a deuteration rate of 99.11%, and a yield of 63%.
[0034] 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 iodobenzene using elemental iodine as a raw material, characterized in that, Includes the following steps: Deuterated iodobenzene was prepared by reacting sodium chlorite as an oxidant and elemental iodine as an iodizing agent with deuterated benzene.
2. The method for synthesizing deuterated iodobenzene using elemental iodine as a raw material according to claim 1, characterized in that, The mass ratio of the deuterated benzene to iodine is 1:1.4 to 1:1.
6.
3. A method for synthesizing deuterated iodobenzene using elemental iodine as a raw material according to claim 1 or 2, characterized in that, The ratio of sodium chlorite to deuterated benzene is 30-35:
100.
4. The method for synthesizing deuterated iodobenzene using elemental iodine as a raw material according to claim 3, characterized in that, The ratio of sodium chlorite to deuterated benzene is 1:
3.
5. A method for synthesizing deuterated iodobenzene using elemental iodine as a raw material according to claim 1 or 2, characterized in that, The sodium chlorite is added dropwise to the reaction system in the form of an aqueous sodium chlorite solution. The temperature of the reaction system during the dropwise addition process is 75~85℃, and the dropwise addition time is 4~6h.
6. The method for synthesizing deuterated iodobenzene using elemental iodine as a raw material according to claim 5, characterized in that, The sodium chlorite aqueous solution has a sodium chlorite concentration of 80~120 g / L.
7. A method for synthesizing deuterated iodobenzene using elemental iodine as a raw material according to claim 1 or 2, characterized in that, The reaction temperature is 75~85℃, and the reaction time is 2~4h.
8. A method for synthesizing deuterated iodobenzene using elemental iodine as a raw material according to claim 1 or 2, characterized in that, It also includes a step of purifying the deuterated iodobenzene obtained from the reaction: The reaction system after the reaction was cooled to room temperature, and the upper liquid was removed by separation to obtain the primary processed liquid. The primary treatment solution was washed with water, then sodium sulfite was added until the solution became colorless. The solution was washed further with water until neutral, the aqueous layer was removed by separation, and the solution was dried to obtain the secondary treatment solution. The secondary treatment solution was distilled under reduced pressure to obtain pure deuterated iodobenzene.