Synthesis method of iodobenzonitrile octanoate
The synthesis process of octanoyl iodine benzonitrile is simplified by reacting cyanophenolic with iodide reagent in water to form intermediates and esterified with octanoyl chloride in alkali metal saline solution, and the synthesis complex and cost in the prior art is solved. The problem of high quality achieves industrial production with high purity, high yield and low cost.
Patent Information
- Application Number
- CN202411295012.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-14
- Publication Date
- 2025-01-10
AI Technical Summary
In the prior art, the synthesis method of octanyl iodine benzonitrile is relatively complex and costly, and the intermediate is unstable, making it difficult to achieve industrial production.
The reaction of paracyanophen and iodide reagent in water was used to form 3,5-diiodine-4-hydroxybenzonitrile, and then esterified with octanoyl chloride in an alkali metal saline aqueous solution to form octanoyl iodine benzonitrile. This method simplifies the reaction steps, reduces the use of organic solvents, and improves the reaction yield and purity.
High purity synthesis of octanyl iodine benzonitrile is achieved, with short reaction steps, high yield, low raw material cost, suitable for industrial production, and reducing production costs through solvent recycling.
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of organic synthesis, and more specifically to a method for synthesizing octanoyl iodobenzonitrile. Background Art
[0002] Iodobenzonitrile is a post-emergence contact herbicide with systemic activity. It is a series of hydroxybenzonitrile herbicides developed by May & Baker in 1963, including bromoxynil, ioxynil, octanoyl bromoxynil, octanoyl ioxynil, etc. It is mainly used for the prevention and control of broadleaf weeds that germinate in winter. It can be quickly absorbed by the stems and leaves of plants when used during the growth period of plants, and exhibits herbicidal activity by inhibiting the electron transfer, photosynthesis and respiration of plants. It has almost no absorption effect on the roots of plants, and the half-life is generally about 10 days, with no residual effect. It can effectively prevent and control annual broadleaf weeds in corn fields. Applicable crops are cereal crops, beets, and onions.
[0003] At present, there are few manufacturers producing octanoyl iodobenzonitrile in China, and there is basically no patent literature reporting its synthesis method. According to the original patent Fr1375311A, there are two synthesis methods. One method uses p-cyanophenol as the starting material, and undergoes an iodination reaction with an iodination reagent to generate an intermediate 3,5-diiodo-4-hydroxybenzonitrile, and then undergoes an esterification reaction with octanoyl chloride to generate octanoyl iodobenzonitrile; the other synthesis method is to use p-hydroxybenzaldehyde as the starting material, and undergo an iodination reaction with an iodination reagent to generate an intermediate 3,5-diiodo-4-hydroxybenzaldehyde, and then undergo an oximation reaction with hydroxylamine hydrochloride or hydroxylamine sulfate. The generated intermediate oxime is then dehydrated to obtain 3,5-diiodo-4-hydroxybenzonitrile, and then undergoes an esterification reaction with octanoyl chloride to generate octanoyl iodobenzonitrile.
[0004] Route 1: Iodination reaction:
[0005] Esterification reaction:
[0006] Route 2: Iodination reaction:
[0007] Oximation reaction:
[0008] Hydrolysis reaction:
[0009] Esterification reaction:
[0010] The synthesis method of route 1 is more likely to be industrialized, but the specific synthesis method is not found in the patent. The synthesis method of route 2 uses expensive raw material p-hydroxybenzaldehyde, and the synthesis route is longer, requiring four steps of reaction to synthesize octanoyl iodobenzonitrile. In addition, the generated intermediate oxime is unstable and easily hydrogenated to amine, so the degree of industrialization is low. Summary of the invention
[0011] The present invention aims at a synthesis method which has not been reported so far, adopts the above route 1 as a preparation method, and provides a synthesis method of octanoyl iodobenzonitrile, wherein p-cyanophenol is selected as a raw material to react with an iodination reagent to generate an iodide, and then the iodide is esterified with octanoyl chloride to generate octanoyl iodobenzonitrile.
[0012] In order to achieve the above-mentioned purpose, the present invention specifically adopts the following technical solutions: The present invention provides a method for synthesizing octanoyl iodobenzonitrile, comprising: Step 1: Iodination reaction In water, p-cyanophenol, an iodination reagent, an acid solution and a catalyst are mixed to carry out reaction I, and then hydrogen peroxide is added dropwise to carry out reaction II to obtain 3,5-diiodo-4-hydroxybenzonitrile; Step 2: Esterification reaction An alkali metal salt aqueous solution and octanoyl chloride are added dropwise to a mixed solution of 3,5-diiodo-4-hydroxybenzonitrile and a solvent to carry out reaction III to obtain octanoyl iodobenzonitrile.
[0013] In the synthesis method of octanoyl iodobenzonitrile of the present invention, the reaction mechanism is as follows: .
[0014] Furthermore, the iodination reagent is selected from at least one of potassium iodide, sodium iodide, and elemental iodine; in the present invention, the iodination reagent may also be hydrogen iodide. When hydrogen iodide is selected, the iodination reaction does not need to add an acid solution; the iodination reagent may also be NIS (N-iodosuccinimide). When NIS (N-iodosuccinimide) is selected, the iodination reaction does not need to add hydrogen peroxide, and after reaction II, no reducing agent is required to reduce the unreacted hydrogen peroxide; And / or, the acid solution is selected from at least one of hydrochloric acid and dilute sulfuric acid; And / or, the catalyst is selected from quaternary ammonium salt compounds, preferably at least one of tetrabutylammonium bromide, tetrabutylammonium chloride and benzyltriethylammonium chloride.
[0015] Further, the molar ratio of the p-cyanophenol, the iodination reagent, the hydrochloric acid and the hydrogen peroxide is 1:(1-3):(0.5-1.2):(1.2-2); And / or, the usage ratio of p-cyanophenol to water is 0.1 mol: 80-100 g; the usage ratio of p-cyanophenol to catalyst is 0.1 mol: 0.1-1 g.
[0016] Further, the conditions of the reaction I include: temperature of 30°C to 40°C, time of 1 hour to 3 hours; And / or, the conditions for dropping hydrogen peroxide include: temperature of 60°C to 70°C, and dropping time of 4 hours to 8 hours; And / or, the conditions of the reaction II include: temperature of 80°C to 85°C, time of 6 hours to 10 hours; And / or, after the reaction II, the step of adding a reducing agent to reduce the unreacted hydrogen peroxide and cooling the temperature to 10°C to 15°C is further included; preferably, the reducing agent is selected from at least one of sodium thiosulfate and sodium sulfite; further preferably, the amount ratio of the p-cyanophenol to the reducing agent is 0.1 mol: 0.4-0.5 g; More preferably, the cooling further includes filtering, washing and drying steps.
[0017] Further, the solvent is selected from at least one of toluene, o-xylene, p-xylene and trimethylbenzene; And / or, the acid binding agent is selected from an alkali metal salt aqueous solution, preferably at least one selected from a sodium hydroxide aqueous solution, a potassium hydroxide aqueous solution, and a sodium carbonate aqueous solution.
[0018] Further, the conditions of the reaction III include: pH 9-10, insulation time 1 hour to 3 hours; Preferably, the reaction III further comprises separation, drying and recrystallization; Further preferably, the solvent used for the recrystallization is an alcohol, preferably at least one of methanol, ethanol and isopropanol.
[0019] Furthermore, before the alkali metal salt aqueous solution and octanoyl chloride are added dropwise, the mixed solution of 3,5-diiodo-4-hydroxybenzonitrile and the solvent is cooled to 0°C to 15°C.
[0020] Further, the molar ratio of the 3,5-diiodo-4-hydroxybenzonitrile, octanoyl chloride, and alkali metal salt aqueous solution is 1:(1-1.6):(1-1.6); And / or, the usage ratio of the 3,5-diiodo-4-hydroxybenzonitrile and the solvent is (0.19-0.475) mol: (150-400) g.
[0021] Beneficial effects: The invention provides a synthesis process of octanoyl iodobenzonitrile. The starting material is selected as p-cyanophenol, which is subjected to iodination reaction with an iodination agent, a catalyst and the like in a water reaction system to obtain an intermediate 3,5-diiodo-4-hydroxybenzonitrile. The obtained intermediate 3,5-diiodo-4-hydroxybenzonitrile is subjected to esterification reaction with octanoyl chloride in an organic solvent by using an alkali metal salt aqueous solution as an acid-binding agent to obtain a product octanoyl iodobenzonitrile. The synthesis method has short reaction steps, high yield, low raw material cost and can achieve a high degree of industrialization.
[0022] In the synthesis method of the present invention, water is used as a reaction solvent during the iodination reaction, and the use of organic solvents is avoided, the use of organic solvents is reduced, and the environment is friendly. At the same time, the cost is reduced, and the reaction system is mild and easy to realize industrial production; during the esterification reaction, benzene, an aromatic solvent commonly used in industry, is used, which is easy to recycle and remove water, and can be recycled through simple water washing, liquid separation, and water treatment; secondly, since the addition of aromatic hydrocarbon solvents in the esterification reaction system can effectively protect the hydrolysis of octanoyl chloride and improve the reaction yield, the content can be increased to more than 95% by using solvent recrystallization in the later stage.
[0023] The synthesis method of the present invention can obtain high-purity iodobenzonitrile after the above process. During the synthesis process, a large amount of organic solvent will be generated after recrystallization. This part of organic solvent is called mother liquor. The obtained mother liquor is fully applied to the crystallization process of the next batch of production, which greatly saves production costs and allows the solvent to be recycled.
[0024] The octanoyl iodobenzonitrile synthesized by the process has a purity of more than 95%, and the yield of the two-step reaction reaches more than 85%. The invention has the advantages of simple and easy operation, high yield, high content, low investment and easy industrial production. DETAILED DESCRIPTION
[0025] The present invention will be further explained below in conjunction with the embodiments.
[0026] Example 1 This embodiment provides a method for synthesizing octanoyl iodobenzonitrile, which is as follows: Step 1: Iodination reaction In a 500mL flask, add 23.8g (0.2mol) of p-cyanophenol, 200g of water, 55.8g (0.22mol) of iodine, 10.4g (0.1mol, 35% by mass) of hydrochloric acid, and 1g of tetrabutylammonium bromide. Stir and keep at 30℃ for 1h, then heat to 60℃ at a rate of 5℃ / min, start to drip 32.6g (0.24mol, 25% by mass) of hydrogen peroxide, and add for 4h. After the addition is completed, heat to 80℃ and keep for 8h. Take samples to detect the normalized content of p-cyanophenol in the liquid phase of 0.8%, and perform post-treatment. After the test is qualified, add 1g of sodium thiosulfate. The temperature was lowered to 12°C at a rate of 5°C / min, filtered, 100 g of water was added to the filter cake for washing, and the filter cake was dried to obtain 72.6 g of intermediate 3,5-diiodo-4-hydroxybenzonitrile (content 97%, yield 94.9%, wherein the yield was calculated as follows: the theoretical input molar number of p-cyanophenol was 0.2 mol, the molar number of intermediate 3,5-diiodo-4-hydroxybenzonitrile = 72.6 g * 97% / 370.91 = 0.18986 mol; yield = 0.18986 / 0.2 = 94.9%).
[0027] Step 2: Esterification reaction Put 150g toluene and 72.6g (0.19mol, content 97%) of 3,5-diiodo-4-hydroxybenzonitrile in the reactor, cool to 2°C, first add 5g of sodium hydroxide aqueous solution to adjust the pH value to 7 to prevent hydrolysis of octanoyl chloride when double addition is unreacted, then add 39g (0.24mol) of octanoyl chloride and 29.7g (0.22mol, mass content 30%) of sodium hydroxide aqueous solution at the same time, control the pH value to 10 during the double addition process, keep warm at 5°C for 2h after the addition is completed, take samples to detect the remaining content of 3,5-diiodo-4-hydroxybenzonitrile, and detect the content of 3,5-diiodo-4-hydroxybenzonitrile in the central control. The amount was 0.8%, and post-treatment was carried out. The organic phase was separated to obtain the organic phase, and the solvent was evaporated. The product was recrystallized with methanol to obtain 95.4 g of iodobenzonitrile (content 95.3%, yield 96.3%, wherein the yield was calculated as follows: the number of moles of the intermediate 3,5-diiodo-4-hydroxybenzonitrile = 72.6 g * 97% / 370.09 = 0.18986 mol, which is approximately equal to 0.19 mol, the molecular weight of the product iodobenzonitrile is 497.11 g / mol, the number of moles of the product iodobenzonitrile = 95.4 g * 95.3% / 497.11 = 0.183; yield = 0.183 / 0.19 = 96.3%).
[0028] Example 2 This embodiment provides a method for synthesizing octanoyl iodobenzonitrile, which is as follows: Step 1: Iodination reaction In a 500mL flask, add 23.8g (0.2mol) of p-cyanophenol, 200g of water, 74.7g (0.45mol) of potassium iodide, 12.5g (0.12mol, mass content 35%) of hydrochloric acid, and 2g of tetrabutylammonium chloride. Stirring, keep the temperature at 35℃ for 1h, then heat to 60℃ at a rate of 5℃ / min, start to drip 32.6g (0.24mol, mass content 25%) of hydrogen peroxide, the dripping time is 6h, after the dripping is completed, heat to 85℃ and keep for 6h, take samples to detect the normalized content of p-cyanophenol liquid phase 0.7%, and perform post-treatment. After the test is qualified, add 1g of sodium thiosulfate. The temperature was lowered to 12°C at a rate of 5°C / min, filtered, 150 g of water was added to the filter cake for washing, and the filter cake was dried to obtain 72.9 g of the intermediate 3,5-diiodo-4-hydroxybenzonitrile (content 96.8%, yield 95.1%).
[0029] Step 2: Esterification reaction 150 g of toluene and 72.9 g (0.19 mol, content 96.8%) of 3,5-diiodo-4-hydroxybenzonitrile were added into the reactor, and the temperature was lowered to 0°C. 3 g of sodium hydroxide aqueous solution was first added dropwise to adjust the pH value to 7 to prevent hydrolysis of octanoyl chloride when double addition was not reacted. Then 39 g (0.3 mol) of octanoyl chloride and 33.3 g (0.25 mol, mass content 30%) of sodium hydroxide aqueous solution were added dropwise at the same time. The pH value was controlled to be 10 during the double addition process. After the addition was completed, the temperature was kept at 5°C for 2 h, and the residual content of 3,5-diiodo-4-hydroxybenzonitrile was detected by sampling. The content of 3,5-diiodo-4-hydroxybenzonitrile was 1% in the central control. After post-treatment, the organic phase was separated to obtain the solvent, and the product was recrystallized using methanol to obtain 95.8 g (content 95.5%, yield 96.7%) of octanoyl iodobenzonitrile.
[0030] Example 3 This embodiment provides a method for synthesizing octanoyl iodobenzonitrile, which is as follows: Step 1: Iodination reaction In a 1000mL flask, add 59.5g (0.5mol) of p-cyanophenol, 500g of water, 157.4g (1.05mol) of sodium iodide, 62.6g (0.6mol, 35% by mass) of hydrochloric acid, and 5g of tetrabutylammonium chloride. Stirring was started, the temperature was kept at 40℃ for 3h, then the temperature was raised to 60℃ at a rate of 5℃ / min, and 102g (0.75mol, 25% by mass) of hydrogen peroxide was added dropwise for 8h. After the addition was completed, the temperature was raised to 80℃ and kept for 10h. Samples were taken to detect the normalized content of p-cyanophenol in the liquid phase of 0.6%, and post-treatment was performed. After the test was qualified, 2g of sodium thiosulfate was added. The temperature was lowered to 10°C at a rate of 5°C / min, filtered, 300 g of water was added to the filter cake for washing, and the filter cake was dried to obtain 180.68 g of the intermediate 3,5-diiodo-4-hydroxybenzonitrile (content 97.1%, yield 94.6%).
[0031] Step 2: Esterification reaction 400 g of o-xylene and 180.68 g (0.473 mol, content 97.1%) of 3,5-diiodo-4-hydroxybenzonitrile were added into the reactor, and the temperature was lowered to 5°C. 5 g of sodium hydroxide aqueous solution was first added dropwise to adjust the pH value to 7 to prevent hydrolysis of octanoyl chloride when double addition was not reacted. Then 105.7 g (0.65 mol) of octanoyl chloride and 82.7 g (0.62 mol, mass content 30%) of sodium hydroxide aqueous solution were added dropwise at the same time. The pH value was controlled to be 9 during the double addition process. After the addition was completed, the mixture was kept at 5°C for 2 h, and the residual content of 3,5-diiodo-4-hydroxybenzonitrile was detected by sampling. The content of 3,5-diiodo-4-hydroxybenzonitrile was 0.9% when detected by central control. After post-treatment, the organic phase was separated to obtain the solvent, and the product was recrystallized using methanol to obtain 237.8 g (content 95%, yield 96.1%) of octanoyl iodobenzonitrile.
[0032] Example 4 This embodiment provides a method for synthesizing octanoyl iodobenzonitrile, which is as follows: Step 1: Iodination reaction In a 1000mL flask, add 59.5g (0.5mol) of p-cyanophenol, 450g of water, 252.5g of NIS (98% by mass) (1.1mol), 52.1g of hydrochloric acid (0.5mol, 35% by mass), and 0.5g of benzyltriethylammonium chloride. Stirring was started, the temperature was kept at 30℃ for 3h, then the temperature was raised to 80℃ at a rate of 5℃ / min, and the temperature was kept for 10h. The sample was taken to detect the normalized content of p-cyanophenol in the liquid phase of 1%, and post-processing was performed. After the test was qualified, the temperature was lowered to 10℃ at a rate of 5℃ / min, filtered, 300g of water was added to the filter cake for washing, and the filter cake was dried to obtain 174g of the intermediate 3,5-diiodo-4-hydroxybenzonitrile (content 97.2%, yield 91.2%).
[0033] Step 2: Esterification reaction 400 g of o-xylene and 174 g (0.456 mol, content 97.2%) of 3,5-diiodo-4-hydroxybenzonitrile were added into the reactor, and the temperature was lowered to 1°C. 2 g of potassium hydroxide aqueous solution was first added dropwise to adjust the pH value to 7 to prevent hydrolysis of octanoyl chloride when double addition was not reacted. Then 105.7 g (0.65 mol) of octanoyl chloride and 68.3 g (0.61 mol, mass content 50%) of potassium hydroxide aqueous solution were added dropwise at the same time. The pH value was controlled to be 10 during the double addition process. After the addition was completed, the mixture was kept at 5°C for 2 h, and the residual content of 3,5-diiodo-4-hydroxybenzonitrile was detected by sampling. The content of 3,5-diiodo-4-hydroxybenzonitrile was 1% in the central control. After post-treatment, the organic phase was separated to obtain the solvent, and the product was recrystallized using methanol to obtain 216.5 g (content 95.3%, yield 91%) of octanoyl iodobenzonitrile.
[0034] Example 5 This embodiment provides a method for synthesizing octanoyl iodobenzonitrile, which is as follows: Step 1: Iodination reaction In a 1000mL flask, add 59.5g (0.5mol) of p-cyanophenol, 400g of water, 285.8g of hydrogen iodide (1.05mol, mass content 47%), and 1g of PEG400. Stirring was started, the temperature was kept at 40℃ for 2h, and then the temperature was raised to 60℃ at a rate of 5℃ / min, and 102g of hydrogen peroxide (0.75mol, mass content 25%) was added dropwise for 6h. After the addition was completed, the temperature was raised to 82℃ and kept for 10h. The sample was taken to detect the normalized content of p-cyanophenol liquid phase of 0.8%, and post-treatment was performed. After the test was qualified, 2g of sodium sulfite was added. The temperature was lowered to 10℃ at a rate of 5℃ / min, filtered, the filter cake was washed with 400g of water, and the filter cake was dried to obtain 182.4g of the intermediate 3,5-diiodo-4-hydroxybenzonitrile (content 96.5%, yield 94.9%).
[0035] Step 2: Esterification reaction 300 g of toluene and 182.4 g (0.475 mol, content 96.5%) of 3,5-diiodo-4-hydroxybenzonitrile were added into the reactor, and the temperature was lowered to 0°C. 2 g of potassium hydroxide aqueous solution was first added dropwise to adjust the pH value to 7 to prevent hydrolysis of octanoyl chloride when double addition was not reacted. Then 105.7 g (0.65 mol) of octanoyl chloride and 69.44 g (0.62 mol, mass content 50%) of potassium hydroxide aqueous solution were added dropwise at the same time. The pH value was controlled to be 10 during the double addition process. After the addition was completed, the mixture was kept at 5°C for 3 h, and the residual content of 3,5-diiodo-4-hydroxybenzonitrile was detected by sampling. The content of 3,5-diiodo-4-hydroxybenzonitrile was 0.9% when detected by central control. After post-treatment, the organic phase was separated to obtain the solvent, and the product was recrystallized using methanol to obtain 222.5 g (content 95.5%, yield 90%) of octanoyl iodobenzonitrile.
[0036] Comparative Example 1 This comparative example provides a method for synthesizing octanoyl iodobenzonitrile, which is as follows: Step 1: Iodination reaction In a 500mL flask, add 23.8g (0.2mol) of p-cyanophenol, 200g of water, 55.8g (0.22mol) of iodine, 10.4g (0.1mol, 35% by mass) of hydrochloric acid, and 1g of tetrabutylammonium bromide. Stir and keep at 30℃ for 1h, then heat to 60℃ at a rate of 5℃ / min, start to drip 32.6g (0.24mol, 25% by mass) of hydrogen peroxide, the dripping time is 4h, after the dripping is completed, heat to 85℃ and keep for 10h, take samples to detect the normalized content of p-cyanophenol liquid phase 1%, and perform post-treatment. After the test is qualified, add 1g of sodium thiosulfate. Cool to 10℃ at a rate of 5℃ / min, filter, add 100g of water to the filter cake for washing, and dry the filter cake to obtain 71.7g (content 97.2%, yield 94%) of the intermediate 3,5-diiodo-4-hydroxybenzonitrile.
[0037] Step 2: Esterification reaction 150 g of water and 71.7 g (0.188 mol, content 97.2%) of 3,5-diiodo-4-hydroxybenzonitrile were added into the reactor, and the temperature was lowered to 0°C. 5 g of sodium hydroxide aqueous solution was first added dropwise to adjust the pH value to 7 to prevent hydrolysis of octanoyl chloride when double addition was not reacted. Then 39 g (0.24 mol) of octanoyl chloride and 29.7 g (0.22 mol, mass content 30%) of sodium hydroxide aqueous solution were added dropwise at the same time. The pH value was controlled at 9 during the double addition process. After the addition was completed, the mixture was kept at 5°C for 3 h. The sample was tested for the residual content of 3,5-diiodo-4-hydroxybenzonitrile, and the central control tested the content of 3,5-diiodo-4-hydroxybenzonitrile to be 4%, which was unqualified. 5g (0.03mol) of octanoyl chloride and 3g (0.02mol, mass content 30%) of sodium hydroxide aqueous solution were added, and the reaction was kept warm for 2h. The central control tested the content of 3,5-diiodo-4-hydroxybenzonitrile to be 1%, and post-processed and filtered. The filter cake was recrystallized with methanol to obtain 81.6g of octanoyl iodobenzonitrile (content 92%, yield 80.3%).
[0038] Comparative Example 2 This comparative example provides a method for synthesizing octanoyl iodobenzonitrile, which is as follows: Step 1: Iodination reaction The same amount of feed and operation as in Comparative Example 1 were used to obtain 72 g of the intermediate 3,5-diiodo-4-hydroxybenzonitrile (content 97.5%, yield 94.6%).
[0039] Step 2: Esterification reaction 300 g of cyclohexane and 72 g (0.19 mol, content 97.5%) of 3,5-diiodo-4-hydroxybenzonitrile were added into the reactor, and the temperature was lowered to 0°C. 5 g of sodium hydroxide aqueous solution was first added dropwise to adjust the pH value to 7 to prevent hydrolysis of octanoyl chloride when double addition was not reacted. Then 39 g (0.24 mol) of octanoyl chloride and 32 g (0.24 mol, mass content 30%) of sodium hydroxide aqueous solution were added dropwise at the same time. The pH value was controlled to be 10 during the double addition process. After the addition was completed, the mixture was kept at 5°C for 6 h, and the residual content of 3,5-diiodo-4-hydroxybenzonitrile was detected by sampling. The content of 3,5-diiodo-4-hydroxybenzonitrile was 1% in the central control. After post-treatment, filtration was performed, and the filter cake was recrystallized using methanol to obtain 83.5 g (content 93.3%, yield 82.5%) of octanoyl iodobenzonitrile.
[0040] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited by the description of the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.
[0041] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
Claims
1. A method for synthesizing octanoyl iodobenzonitrile, characterized in that: The synthesis method comprises: Step 1: Iodination reaction In water, p-cyanophenol, an iodination reagent, an acid solution and a catalyst are mixed to carry out reaction I, and then hydrogen peroxide is added dropwise to carry out reaction II to obtain 3,5-diiodo-4-hydroxybenzonitrile; Step 2: Esterification reaction In a mixed solution of 3,5-diiodo-4-hydroxybenzonitrile and a solvent, an acid-binding agent and octanoyl chloride are added dropwise to carry out reaction III to obtain octanoyl iodobenzonitrile.
2. The synthesis method according to claim 1, characterized in that The iodination agent is selected from at least one of potassium iodide, sodium iodide, and elemental iodine; And / or, the acid solution is selected from at least one of hydrochloric acid and dilute sulfuric acid; And / or, the catalyst is selected from quaternary ammonium salt compounds, preferably at least one of tetrabutylammonium bromide, tetrabutylammonium chloride and benzyltriethylammonium chloride.
3. The synthesis method according to claim 1, characterized in that The molar ratio of the p-cyanophenol, iodination reagent, hydrochloric acid and hydrogen peroxide is 1:(1-3):(0.5-1.2):(1.2-2); And / or, the usage ratio of p-cyanophenol to water is 0.1 mol: 80-100 g; the usage ratio of p-cyanophenol to catalyst is 0.1 mol: 0.1-1 g.
4. The synthesis method according to claim 1, characterized in that The conditions of the reaction I include: a temperature of 30°C to 40°C and a time of 1 hour to 3 hours; And / or, the conditions for dropping hydrogen peroxide include: temperature of 60°C to 70°C, and dropping time of 4 hours to 8 hours; And / or, the conditions of the reaction II include: temperature of 80°C to 85°C, time of 6 hours to 10 hours; And / or, after the reaction II, the step of adding a reducing agent and cooling the temperature to 10°C to 15°C is further included; preferably, the reducing agent is selected from at least one of sodium thiosulfate and sodium sulfite; further preferably, the amount ratio of the p-cyanophenol to the reducing agent is 0.1 mol: 0.4-0.5 g; More preferably, the cooling further includes filtering, washing and drying steps.
5. The synthesis method according to claim 1, characterized in that The solvent is selected from at least one of toluene, o-xylene, p-xylene and trimethylbenzene; And / or, the acid binding agent is selected from an alkali metal salt aqueous solution, preferably at least one selected from a sodium hydroxide aqueous solution, a potassium hydroxide aqueous solution, and a sodium carbonate aqueous solution.
6. The synthesis method according to claim 1, characterized in that The conditions of reaction III include: pH 9-10, insulation time 1 hour to 3 hours; Preferably, the reaction III further comprises separation, drying and recrystallization; Further preferably, the solvent used for the recrystallization is an alcohol, preferably at least one of methanol, ethanol and isopropanol.
7. The synthesis method according to claim 1, characterized in that Before the alkali metal salt aqueous solution and octanoyl chloride are added dropwise, the mixed solution of 3,5-diiodo-4-hydroxybenzonitrile and the solvent is cooled to 0°C to 15°C.
8. The synthesis method according to claim 1, characterized in that The molar ratio of the 3,5-diiodo-4-hydroxybenzonitrile, octanoyl chloride and alkali metal salt aqueous solution is 1:(1-1.6):(1-1.6); And / or, the usage ratio of the 3,5-diiodo-4-hydroxybenzonitrile and the solvent is (0.19-0.475) mol: (150-400) g.