Method for preparing nitro-iodophenol nitrile in one-pot manner

Abstract

The invention provides a one-pot preparation method of nitro-iodo-phenolate nitrile, which comprises the following steps: nitration reaction: adding dichloroethane and p-hydroxybenzonitrile into a reactor, dropwise adding nitric acid into the reactor at a first temperature, and carrying out heat preservation reaction for 2-2.5 hours to obtain a solution A; 2) iodination reaction: adding ethanol, water and iodine into the solution A, heating to a second temperature, dropwise adding hydrogen peroxide into the solution A, and carrying out heat preservation reaction for 2-2.5 hours to obtain a solution B; 3) distillation: adding water into the solution B, distilling at normal pressure to recover dichloroethane and ethanol, cooling to 15-25 DEG C, preserving heat for 0.5 h, performing suction filtration, and washing a filter cake with water to obtain a nitro-iodo-phenol nitrile crude product; in the distillation step, the volume weight ratio of water to p-hydroxybenzonitrile is 50mL: 25g; and 4) solvent recycling: recycling the dichloroethane and ethanol mixed solution obtained in the distillation step, and applying the dichloroethane and ethanol mixed solution to nitration reaction and iodination reaction. According to the invention, efficient preparation of the nitro-iodo-phenolate nitrile is realized.

Description

Technical Field

[0001] The present application relates to the technical field of chemical synthesis, and in particular to a method for preparing nitroiodine phenol nitrile in one pot. Background Art

[0002] Nitroxynil (4-hydroxy-3-iodo-5-nitrobenzonitrile) is a drug used to prevent and treat Fasciola hepatica infection in cattle and sheep. It was successfully developed by the Rhone-Merieux Institute in France in the 1980s. Since 1987, my country has been relying on imports. Fasciola hepatica is widely distributed throughout the world, causing serious economic losses to many countries. Japan alone loses 33 billion yuan each year. Fasciola hepatica is even more rampant in Inner Mongolia, Ningxia, Qinghai, Gansu, Xinjiang and other provinces with developed animal husbandry in my country, causing hundreds of millions of yuan in economic losses to animal husbandry each year. Therefore, innovation in the synthesis technology of this drug can create good economic and social benefits.

[0003] In foreign countries, nitroiodine phenol nitrile is mostly synthesized by nitration followed by iodination using p-hydroxybenzonitrile as raw material. Among them, nitration reaction uses glacial acetic acid and dichloroethane as solvents, and the amount of waste acid is large and difficult to handle; iodination uses sodium periodate, potassium iodide, and glacial acetic acid as iodination reagents (as shown in Formula 1) or iodine, hydrogen peroxide, and sulfuric acid as iodination reagents (as shown in Formula 2), which has the problems of high cost, low yield, and serious environmental pollution.

[0004]

[0005] Patent CN100500648C uses p-hydroxybenzaldehyde and hydroxylamine hydrochloride as raw materials, formic acid and acetic acid as solvents, sodium nitrite as nitrating agent, sodium periodate, potassium iodide and sodium chloride as iodizing agents (as shown in Formula 3 and Formula 4). This synthetic route has the problems of using a lot of materials, a large amount of waste acid, expensive iodizing agents, high pollution, and high energy consumption.

[0006]

[0007] In view of the various shortcomings of the above synthetic routes, the purpose of the present invention is to provide a preparation method for producing nitroiodine phenol nitrile with mild reaction conditions, simple process operation, low energy consumption, high yield and green environment. Summary of the invention

[0008] The present application provides a one-pot method for preparing nitroiodine nitrile, so as to solve the above-mentioned problems mentioned in the background technology.

[0009] The present application provides a method for preparing nitroiodine nitrile in one pot, comprising the following steps:

[0010] Nitration reaction: add dichloroethane and p-hydroxybenzonitrile to a reactor, raise the temperature to a first temperature, drop nitric acid into the reactor at the first temperature, and after the dropwise addition is completed, keep the temperature for reaction for 2-2.5 hours to obtain solution A;

[0011] 2) Iodination reaction: add ethanol, water and iodine to solution A, raise the temperature to a second temperature, drop hydrogen peroxide into solution A at the second temperature, and after the dropwise addition is completed, keep the temperature for reaction for 2-2.5 hours to obtain solution B;

[0012] 3) Distillation: Add water to solution B, raise the temperature, recover dichloroethane and ethanol by atmospheric distillation, then cool to 15-25°C and keep warm for 0.5h, filter with suction, wash the filter cake with water, and obtain a crude product of nitroiodine phenolnitrile;

[0013] In the distillation step, the volume weight ratio of water to p-hydroxybenzonitrile is 50 mL:25 g;

[0014] 4) solvent recycling: the mixed solution of dichloroethane and ethanol obtained in the distillation step is subjected to a first static stratification to obtain an upper layer of ethanol and a lower layer of dichloroethane, which are separated, and the lower layer of dichloroethane is washed with water, subjected to a second static stratification to obtain an upper layer of water and a lower layer of dichloroethane, the lower layer of dichloroethane is used as recovered dichloroethane in the nitration reaction, the upper layer of water obtained in the second static stratification is combined with the ethanol obtained in the first static stratification to obtain recovered ethanol and recovered water, and the recovered water is used in the iodination reaction;

[0015] In the nitration reaction, ethylene dichloride comes from the recovered ethylene dichloride and / or new ethylene dichloride in the solvent recycling step, in the iodination reaction, ethanol comes from the recovered ethanol and / or new ethanol, and water comes from the recovered water and / or new water.

[0016] Optionally, in the nitration reaction step, the weight volume ratio of p-hydroxybenzonitrile to dichloroethane is 25 g:80 mL, and the feeding molar ratio of nitric acid to p-hydroxybenzonitrile is 1.36-1.50:1.

[0017] Optionally, in the iodination reaction step, the molar ratio of iodine to p-hydroxybenzonitrile is 0.53-0.55:1; and the molar ratio of hydrogen peroxide to p-hydroxybenzonitrile is 1.14-1.16:1.

[0018] Optionally, during the nitration reaction, the dripping rate of nitric acid is 9-9.75 g / h.

[0019] Optionally, during the iodination reaction, the dropping rate of hydrogen peroxide is 14.5-14.75 g / h.

[0020] Optionally, the first temperature is 38-40°C, and the nitration reaction temperature is 38-43°C.

[0021] Optionally, the second temperature is 58-60°C, and the iodination reaction temperature is 60-63°C.

[0022] Optionally, in the iodination reaction, the volume weight ratio of ethanol, water and p-hydroxybenzonitrile is 50 mL: 50 mL: 25 g.

[0023] Optionally, in the distillation step, the terminal temperature for recovering ethylene dichloride and ethanol is 90-95°C.

[0024] Optionally, the method for preparing nitroiodine phenol nitrile further comprises a refining step: adding ethanol to the crude nitroiodine phenol nitrile, stirring and refluxing at a temperature of 75-80° C. for 0.5-1 h, cooling to 15-25° C. after the reflux, and keeping warm for 0.5 h, filtering, washing the obtained filter cake containing nitroiodine phenol nitrile with ethanol, and finally drying to obtain nitroiodine phenol nitrile;

[0025] The volume ratio of the added ethanol to the weight ratio of the crude nitroiodine nitrile was 2:1 mL / g.

[0026] The one-pot method for preparing nitroiodine nitrile provided in the present application realizes the efficient preparation of nitroiodine nitrile and has the following beneficial effects compared with the prior art:

[0027] (1) A nitration reaction is carried out using dichloroethane as a solvent and p-hydroxybenzonitrile and nitric acid as raw materials to introduce a nitro group into a benzene ring to generate 3-nitro-4-hydroxybenzonitrile, thereby obtaining a solution A containing the nitrated product 3-nitro-4-hydroxybenzonitrile. The solution A is not treated and directly subjected to an iodination reaction, and ethanol and water are added to the solution A, together with the dichloroethane in the solution A, as solvents for the iodination reaction, to carry out an iodination reaction, thereby obtaining a solution B containing the product nitroiodine phenol nitrile. The solution B is then subjected to atmospheric distillation to obtain nitroiodine phenol nitrile. By not treating the solution A and directly carrying out a subsequent iodination reaction, wherein the solution A still contains nitric acid that has not been completely reacted, the nitric acid can act as an acid catalyst in the iodination reaction, which helps to enhance the oxidizability of hydrogen peroxide in an acidic medium, thereby facilitating the conversion of hydrogen iodide into elemental iodine, thereby further promoting the iodination reaction. At the same time, the raw materials of the iodination reaction are directly added to the solution A without treatment in a "one-pot" manner, which not only promotes the efficient iodination reaction, but also simplifies the production steps, reduces the use of equipment, thereby reducing the equipment footprint, making the production process of nitroiodine phenol nitrile more convenient and faster, and reducing energy consumption. The dichloroethane and ethanol obtained by atmospheric distillation are recovered and applied to the nitration reaction and iodination reaction, avoiding the waste of solvents, and greatly reducing the treatment load of the wastewater treatment station for the directly discharged dichloroethane and ethanol, which is not only conducive to the construction of the surrounding green environment, but also reduces the production cost, and has good economic and environmental benefits.

[0028] (2) The solvent obtained by atmospheric distillation is recovered and reused, the mixed solution of dichloroethane and ethanol obtained in the distillation step is subjected to a first static stratification to obtain an upper layer of ethanol and a lower layer of dichloroethane, which are separated, and the lower layer of dichloroethane is washed with water, subjected to a second static stratification to obtain an upper layer of water and a lower layer of dichloroethane, the lower layer of dichloroethane is used as recovered dichloroethane in the nitration reaction, the upper layer of water obtained by the second static stratification is combined with the ethanol obtained by the first static stratification to obtain recovered ethanol and recovered water, and the recovered ethanol and recovered water are used in the iodination reaction; in the nitration reaction, the dichloroethane comes from the recovered dichloroethane and / or the new dichloroethane in the solvent recycling step, in the iodination reaction, the ethanol comes from the recovered ethanol and / or the new ethanol, and the water comes from the recovered water and / or the new water.

[0029] (3) The one-pot method for preparing nitroiodine phenol nitrile provided in the present application has a simple process, avoids solvent waste, and improves the utilization rate of the iodination reagent, thereby having good economic and environmental benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, a brief introduction will be given below to the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0031] Figure 1 A process diagram of a method for preparing nitroiodine nitrile in one pot provided in one embodiment of the present application;

[0032] Figure 2 A process diagram of a method for preparing nitroiodine nitrile in one pot provided by another embodiment of the present application;

[0033] Figure 3 This is the HPLC spectrum of nitroiodine nitrile prepared in Example 1 of the present application;

[0034] Figure 4 This is the HPLC spectrum of nitroiodine nitrile prepared in Example 2 of the present application;

[0035] Figure 5 This is the HPLC spectrum of nitroiodine prepared in Example 3 of the present application. DETAILED DESCRIPTION

[0036] In order to make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the technical scheme in the embodiments of the present application is clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work also fall within the scope of protection of the present application.

[0037] like Figure 1 As shown, the present application provides a method for preparing nitroiodine nitrile in one pot, the method comprising the following steps:

[0038] (1) Nitration reaction: adding dichloroethane and p-hydroxybenzonitrile to a reactor, heating to a first temperature, and dropping nitric acid into the reactor at the first temperature. After the dropping is completed, the reaction is kept warm for 2-2.5 hours to obtain a solution A;

[0039] (2) iodination reaction: add ethanol, water and iodine to solution A, raise the temperature to a second temperature, dropwise add hydrogen peroxide to solution A at the second temperature, and after the dropwise addition is complete, keep the temperature for reaction for 2-2.5 hours to obtain solution B;

[0040] (3) Distillation: Add water to solution B, raise the temperature, and distill under normal pressure to recover dichloroethane and ethanol, then cool to 15-25° C. and keep warm for 0.5 h, filter with suction, and wash the filter cake with water to obtain a crude product of nitroiodine phenolnitrile;

[0041] In the distillation step, the volume weight ratio of water to p-hydroxybenzonitrile is 50 mL:25 g;

[0042] (4) solvent recycling: the mixed solution of dichloroethane and ethanol obtained in the distillation step is subjected to a first static decomposition to obtain an upper layer of ethanol and a lower layer of dichloroethane, which are separated, and the lower layer of dichloroethane is washed with water, subjected to a second static decomposition to obtain an upper layer of water and a lower layer of dichloroethane, the lower layer of dichloroethane is used as recovered dichloroethane in the nitration reaction, the upper layer of water obtained in the second static decomposition is combined with the ethanol obtained in the first static decomposition to obtain recovered ethanol and recovered water, and the recovered water is used in the iodination reaction;

[0043] In the nitration reaction, ethylene dichloride comes from the recovered ethylene dichloride and / or new ethylene dichloride in the solvent recycling step, in the iodination reaction, ethanol comes from the recovered ethanol and / or new ethanol, and water comes from the recovered water and / or new water.

[0044] Specifically, in the present application, nitroiodine phenol nitrile is prepared by a one-pot method, and the specific synthesis equation is shown below:

[0045]

[0046] Using dichloroethane as a solvent, nitric acid and p-hydroxybenzonitrile are mixed to carry out a nitration reaction. The solution A containing the nitrate obtained after the nitration does not need to be separated and treated. Ethanol and water are continuously added to the solution A together with the dichloroethane in the nitration reaction as an iodination reaction solvent. Iodine is used as an iodination agent and hydrogen peroxide is used as an oxidant to carry out an iodination reaction to generate a solution B containing nitroiodine phenol nitrile. After the iodination reaction is completed, dichloroethane and ethanol are recovered from the solution B by distillation. The dichloroethane is used in the nitration reaction and the ethanol is used in the iodination reaction, so that the raw materials are recycled, the cost is reduced, and the problems of large wastewater treatment load and environmental pollution caused by large-scale discharge of solvents are avoided.

[0047] In the specific operation, firstly, dichloroethane is used as a solvent, and p-hydroxybenzonitrile and nitric acid are used as raw materials for nitration reaction, and a nitro group is introduced into the benzene ring to generate 3-nitro-4-hydroxybenzonitrile, and the nitrating agent is concentrated nitric acid or fuming nitric acid, wherein the mass fraction of concentrated nitric acid is 68%, and the mass fraction of fuming nitric acid is 98%. Dichloroethane is used as a solvent, so that p-hydroxybenzonitrile molecules are evenly dispersed therein to form a homogeneous system, thereby facilitating the nitration reaction, and obtaining solution A. When the nitration reaction is carried out, the temperature is first raised to a first temperature, and nitric acid is dripped into the reactor at the first temperature, wherein the first temperature is less than the nitration reaction temperature. Raising the temperature can increase the solubility of the reactant p-hydroxybenzonitrile in the acid, reduce the viscosity of the reaction solution, and facilitate diffusion, thereby facilitating the nitration reaction; on the other hand, the nitration reaction is an exothermic reaction, and while dripping nitric acid for the nitration reaction, heat is released, so that the temperature of the reaction system is increased. Therefore, the temperature is first raised to a first temperature, and then the temperature of the reaction system is controlled by dripping nitric acid to avoid excessively high reaction temperature and increase in side reactions, thereby affecting the yield of 3-nitro-4-hydroxybenzonitrile, and then affecting the yield of nitroiodine phenol nitrile. Hydrogen peroxide is dripped in the iodination reaction, and the addition is completed and the heat is kept until the material is clear, and then the reaction is completed.

[0048] After the nitration reaction is completed, a solution A containing nitrate 3-nitro-4-hydroxybenzonitrile is obtained. In this application, solution A is not treated, and solution A is directly subjected to iodination reaction. Ethanol and water are added to solution A, and together with dichloroethane in solution A, as a solvent for iodination reaction, iodination reaction is carried out to obtain solution B containing product nitroiodine phenol nitrile. The iodination reaction is that the iodine molecule itself polarizes as an electrophilic reagent to attack the aromatic ring, and an electrophilic substitution reaction occurs. The hydrogen iodide generated in the iodination reaction has reducing properties, and the iodine introduced into the benzene ring can be replaced by hydrogen again. In order to avoid this phenomenon, hydrogen peroxide is added dropwise to the iodination reaction to convert the hydrogen iodide generated by the reaction into elemental iodine and then carry out the iodination reaction, which not only makes the iodination reaction stable, but also makes full use of the raw material iodine, avoids the waste of raw materials, and improves the generation rate of nitroiodine phenol nitrile. The mass concentration of hydrogen peroxide is 27.5-30%.

[0049] Among them, solution A is not treated and the subsequent iodination reaction is directly carried out, wherein solution A also contains nitric acid that has not been completely reacted. In the iodination reaction, nitric acid can be used as an acid catalyst, which helps to enhance the oxidizability of hydrogen peroxide in an acidic medium, thereby facilitating the conversion of hydrogen iodide into elemental iodine, and further promoting the iodination reaction. At the same time, solution A is not treated and the raw materials for the iodination reaction are directly added in a "one-pot" manner, which not only promotes the efficient iodination reaction, but also simplifies the production steps, reduces the use of equipment, thereby reducing the equipment footprint, making the production process of nitroiodine phenol nitrile more convenient and faster, and reducing energy consumption.

[0050] Solution B containing the product nitroiodine phenol nitrile is purified by atmospheric distillation, dichloroethane and ethanol in solution B are removed, and dichloroethane and ethanol are recovered and applied to nitration reaction and iodination reaction, thereby avoiding waste of solvent and greatly reducing the processing load of dichloroethane and ethanol directly discharged by the wastewater treatment station, which is not only beneficial to the construction of the surrounding green environment, but also reduces the production cost, and has good economic and environmental benefits. The solution after atmospheric distillation of solution B is cooled to reduce the solubility of the product, cooled to 15-25° C. and kept warm for 0.5 h, solid nitroiodine phenol nitrile is precipitated, and then suction filtration is performed, and the filter cake is washed with water for multiple times (at least three times) to remove impurities, so as to obtain a crude nitroiodine phenol nitrile.

[0051] The solvent obtained by atmospheric distillation is recovered and applied, specifically, the following steps are performed: the mixed solution of dichloroethane and ethanol obtained in the distillation step is subjected to a first static stratification to obtain an upper layer of ethanol and a lower layer of dichloroethane, which are separated, and the lower layer of dichloroethane is washed with water, subjected to a second static stratification to obtain an upper layer of water and a lower layer of dichloroethane, the lower layer of dichloroethane is used as recovered dichloroethane in the nitration reaction, the upper layer of water obtained by the second static stratification is combined with the ethanol obtained by the first static stratification to obtain recovered ethanol and recovered water, and the recovered ethanol and recovered water are used in the iodination reaction;

[0052] In the nitration reaction, ethylene dichloride comes from the recycled ethylene dichloride and / or new ethylene dichloride in the solvent recycling step, in the iodination reaction, ethanol comes from the recycled ethanol and / or new ethanol, and water comes from the recycled water and / or new water. New ethylene dichloride refers to newly prepared or commercially available ethylene dichloride with a purity of more than 99.8%, new ethanol refers to newly prepared and / or commercially available anhydrous ethanol, ethanol with a purity of more than 95%, and new water refers to deionized water. By reusing the solvent in the reaction process, the waste of solvent is reduced, the solvent treatment load is reduced, and the production cost is reduced.

[0053] The present application realizes the efficient preparation of nitroiodine phenol nitrile by the above scheme, by using dichloroethane as solvent, using p-hydroxybenzonitrile and nitric acid as raw materials for nitration reaction, introducing nitro group into benzene ring, generating 3-nitro-4-hydroxybenzonitrile, and obtaining solution A containing nitrate 3-nitro-4-hydroxybenzonitrile. And solution A is not treated, and iodination reaction is directly carried out, ethanol and water are added to solution A, and together with dichloroethane in solution A, iodination reaction is carried out as the solvent of iodination reaction, and solution B containing product nitroiodine phenol nitrile is obtained. Solution B is then subjected to atmospheric distillation to obtain nitroiodine phenol nitrile. By not treating solution A and directly carrying out subsequent iodination reaction, wherein solution A also contains nitric acid that is not completely reacted, in iodination reaction, nitric acid can be used as an acid catalyst, which helps to enhance the oxidizability of hydrogen peroxide in acidic medium, and then is conducive to converting hydrogen iodide into elemental iodine, further promoting the progress of iodination reaction. At the same time, the raw materials of the iodination reaction are directly added to the solution A without treatment in a "one-pot" manner, which not only promotes the efficient iodination reaction, but also simplifies the production steps, reduces the use of equipment, thereby reducing the equipment footprint, making the production process of nitroiodine phenol nitrile more convenient and faster, and reducing energy consumption. The dichloroethane and ethanol obtained by atmospheric distillation are recovered and applied to the nitration reaction and iodination reaction, avoiding the waste of solvents, and greatly reducing the treatment load of the wastewater treatment station for the directly discharged dichloroethane and ethanol, which is not only conducive to the construction of the surrounding green environment, but also reduces the production cost, and has good economic and environmental benefits.

[0054] Optionally, in the nitration reaction step, the weight volume ratio of p-hydroxybenzonitrile to dichloroethane is 25 g:80 mL, and the feeding molar ratio of nitric acid to p-hydroxybenzonitrile is 1.36-1.50:1.

[0055] Specifically, in the nitration reaction, ethylene dichloride is used as a solvent and nitric acid is used as a nitrating agent for the reaction. In the nitration reaction, nitric acid can form a mixed solution with ethylene dichloride to form a nitration system. The raw material p-hydroxybenzonitrile has a large solubility in ethylene dichloride and can form a homogeneous system. At the same time, the system can prevent hydrolysis from occurring, which is conducive to the efficient conduct of the reaction. At the same time, if ethylene dichloride is excessive, it will cause solvent waste and reduce the reaction rate. If ethylene dichloride is added too little, it is also not conducive to the formation of a homogeneous system.

[0056] Optionally, in the iodination reaction step, the molar ratio of iodine to p-hydroxybenzonitrile is 0.53-0.55:1; and the molar ratio of hydrogen peroxide to p-hydroxybenzonitrile is 1.14-1.16:1.

[0057] Optionally, during the nitration reaction, the dripping rate of nitric acid is 9-9.75 g / h.

[0058] Specifically, controlling the dripping speed of nitric acid can control the temperature of the nitration reaction, avoiding too fast dripping speed, which leads to violent local reaction and temperature rise, which is not conducive to the stable reaction, and avoiding the generation of side reactions caused by excessively high temperature.

[0059] Optionally, during the iodination reaction, the dropping rate of hydrogen peroxide is 14.5-14.75 g / h.

[0060] Specifically, hydrogen peroxide is added dropwise during the iodination reaction, and the mixture is kept warm until the material becomes clear.

[0061] Optionally, the first temperature is 38-40°C, and the nitration reaction temperature is 38-43°C.

[0062] Specifically, the temperature is first raised to a first temperature, and nitric acid is added dropwise to the reactor at the first temperature. Raising the temperature can accelerate the reaction speed and shorten the reaction time, thereby facilitating the nitration reaction. Meanwhile, heat is released during the nitration reaction, so that the temperature of the reaction system is raised. Therefore, the temperature is first raised to the first temperature, and then the temperature of the reaction system is controlled by adding nitric acid dropwise, so as to avoid an increase in side reactions due to excessively high reaction temperature, such as the production of a by-product dinitration product, thereby affecting the yield of 3-nitro-4-hydroxybenzonitrile, and further affecting the yield of nitroiodine phenolnitrile.

[0063] Optionally, the second temperature is 58-60°C, and the iodination reaction temperature is 60-63°C.

[0064] Specifically, maintaining a suitable reaction temperature is conducive to the efficient progress of the iodination reaction. When the temperature is too low, the solubility of 3-nitro-4-hydroxybenzonitrile in ethanol is poor, which is not conducive to the progress of the reaction.

[0065] Optionally, in the iodination reaction, the volume weight ratio of ethanol, water and p-hydroxybenzonitrile is 50 mL: 50 mL: 25 g.

[0066] Specifically, too much solvent will complicate the subsequent solvent recovery or treatment process, while too little solvent will result in poor dispersion of the reaction raw materials in the solvent, which is not conducive to the efficient completion of the reaction. Therefore, it is necessary to control the amount of solvent added to the nitration reaction and iodination reaction, which is conducive to rapid and efficient completion of the reaction, and thus conducive to increasing the yield of nitroiodine phenol nitrile.

[0067] Optionally, in the distillation step, the terminal temperature for recovering ethylene dichloride and ethanol is 90-95°C.

[0068] Specifically, in the distillation step, the terminal temperature is 90-95° C. to ensure the maximum recovery of ethylene dichloride and ethanol. At the same time, since ethylene dichloride and ethanol are commonly used solvents in chemical production, those skilled in the art can control the temperature during the distillation process according to the different boiling points of ethylene dichloride and ethanol. This process is well known to those skilled in the art and can be achieved through conventional operations to ensure the stable operation of the distillation system, so the distillation temperature control is not described in detail here.

[0069] like Figure 2 As shown, optionally, the method for preparing nitroiodine phenol nitrile further comprises a refining step: adding ethanol to the crude nitroiodine phenol nitrile, stirring and refluxing at a temperature of 75-80° C. for 0.5-1 h, cooling to 15-25° C. after the reflux, and keeping warm for 0.5 h, filtering, washing the obtained filter cake containing nitroiodine phenol nitrile with ethanol, and finally drying to obtain nitroiodine phenol nitrile;

[0070] The weight ratio of ethanol to crude nitroiodine nitrile added was 2:1 mL / g.

[0071] Specifically, in the purification step of nitroiodine phenol nitrile, ethanol is first added to dissolve impurities in the nitroiodine phenol nitrile by ethanol, heating and refluxing can improve the solubility of the impurities, and cooling is performed after the reflux is completed to reduce the solubility of the nitroiodine phenol nitrile, so that solid nitroiodine phenol nitrile is precipitated, and the solid product is separated from the solvent by suction filtration, and finally washed with ethanol to achieve the effect of refining nitroiodine phenol nitrile.

[0072] The technical solution of the present application is described in detail below with reference to specific embodiments.

[0073] Example 1

[0074] A method for preparing nitroiodine nitrile in one pot, comprising the following steps:

[0075] (1) Nitration reaction: add 80 mL of dichloroethane and 25.0 g (0.21 mol) of p-hydroxybenzonitrile to a 250 mL reaction bottle, raise the temperature to a first temperature (38-40° C.) under stirring, add 18 g of fuming nitric acid dropwise at a rate of 9 g / h at the first temperature, and after the addition is complete, keep the temperature at 40-42° C. for 2 h to obtain solution A;

[0076] (2) Iodination reaction: add 50 mL of ethanol, 50 mL of water, 28 g of iodine, and 1.5 g of nitric acid to solution A, raise the temperature to a second temperature (58-60° C.), and dropwise add 29.2 g of hydrogen peroxide (hydrogen peroxide concentration is 27.5%) to solution A at a rate of 14.5 g / h at the second temperature. After the dropwise addition is completed, keep the temperature at 60-63° C. for 2 h to obtain solution B;

[0077] (3) Distillation: Add 50 mL of water to solution B, and recover dichloroethane and ethanol by atmospheric distillation. The end point temperature of atmospheric distillation is 90-95° C., then cool to 15-25° C., keep warm for 0.5 h, filter with suction, and wash the filter cake with 50 mL of water to obtain 71 g of crude nitroiodine phenol nitrile;

[0078] (4) Solvent recycling: The mixed solution of dichloroethane and ethanol obtained in the distillation step is subjected to a first static decomposition to obtain an upper layer of ethanol and a lower layer of dichloroethane, which are separated, and the lower layer of dichloroethane is washed with 20 mL of water, and then subjected to a second static decomposition to obtain an upper layer of water and a lower layer of dichloroethane. 60 mL of the lower layer of dichloroethane is used as a set for recovering dichloroethane. The upper layer of water obtained by the second static decomposition is combined with the ethanol obtained by the first static decomposition, and the specific gravity is measured to obtain an ethanol content of 47.5% (V / V) as recovered ethanol and recovered water. After adding new ethanol, the sets are used in the iodination reaction;

[0079] (5) Purification step: 142 mL of ethanol was added to 71 g of crude nitroiodine phenol nitrile, and the mixture was stirred and refluxed at 75-80° C. for 0.5 h. After the reflux, the mixture was cooled to 17° C. and kept warm for 0.5 h. The mixture was filtered and the filter cake containing nitroiodine phenol nitrile was washed with 50 mL of ethanol and finally dried at 80° C. for 8 h to obtain 55.5 g of yellow powder nitroiodine phenol nitrile. MP. 137-138.5° C. (literature value 137-138° C.), HPLC purity 99.54%, yield 91.20%.

[0080] Example 2

[0081] A method for preparing nitroiodine nitrile in one pot, comprising the following steps:

[0082] (1) Nitration reaction: 60 mL of the recovered dichloroethane, 20 mL of new dichloroethane and 25.0 g (0.21 mol) of p-hydroxybenzonitrile were added to a 250 mL reaction bottle. The mixture was heated to a first temperature (38-40° C.) under stirring. 19.5 g of fuming nitric acid was added dropwise at a rate of 9.5 g / h at the first temperature. After the addition was complete, the mixture was kept at 40-42° C. for 2 h to obtain a solution A.

[0083] (2) Iodination reaction: 80 mL of the 47.5% (V / V) recovered ethanol in Example 1, 12 mL of new ethanol, 8 mL of new water, and 28 g of iodine were added to solution A, and the temperature was raised to a second temperature (58-60° C.). At the second temperature, 29.5 g of hydrogen peroxide (hydrogen peroxide concentration was 27.5%) was added dropwise to solution A at a rate of 14.6 / h. After the addition was completed, the mixture was kept warm at 60-63° C. for 2 h to obtain solution B.

[0084] (3) Distillation: Add 20 mL of the 47.5% (V / V) recovered ethanol and 30 mL of fresh water in Example 1 to Solution B, and recover dichloroethane and ethanol by atmospheric distillation. The endpoint temperature of atmospheric distillation is 90-95° C., then cool to 17° C., keep warm for 0.5 h, filter with suction, and wash the filter cake with 50 mL of water to obtain 73 g of crude nitrophenolnitrile;

[0085] (4) Solvent recycling: The dichloroethane and ethanol mixed solution obtained in the distillation step is subjected to a first static decomposition to obtain an upper layer of ethanol and a lower layer of dichloroethane, which are separated, and the lower layer of dichloroethane is washed with 20 mL of water, and then subjected to a second static decomposition to obtain an upper layer of water and a lower layer of dichloroethane. 63 mL of the lower layer of dichloroethane is used as a set for recovering dichloroethane. The upper layer of water obtained by the second static decomposition and 110 mL of ethanol obtained by the first static decomposition are combined, and the specific gravity is measured to obtain an ethanol content of 45% (V / V) as recovered ethanol and recovered water. New ethanol is added and then used in the iodination reaction;

[0086] (5) Purification step: 146 mL of ethanol was added to 73 g of crude nitroiodine phenol nitrile, and the mixture was stirred and refluxed at 75-80° C. for 0.5 h. After the reflux, the mixture was cooled to 17° C. and kept warm for 0.5 h. The mixture was filtered and the filter cake containing nitroiodine phenol nitrile was washed with 50 mL of ethanol and finally dried at 80° C. for 8 h to obtain 56 g of yellow powder nitroiodine phenol nitrile. MP. 137-138.5° C. (literature value 137-138° C.), HPLC purity 99.47%, yield 92.01%.

[0087] Example 3

[0088] A method for preparing nitroiodine nitrile in one pot, comprising the following steps:

[0089] (1) Nitration reaction: 63 mL of the recovered dichloroethane, 20 mL of new dichloroethane and 25.0 g (0.21 mol) of p-hydroxybenzonitrile were added to a 250 mL reaction bottle. The temperature was raised to a first temperature (38-40° C.) under stirring. 19.5 g of fuming nitric acid was added dropwise at a rate of 9.75 g / h at the first temperature. After the addition was completed, the reaction was carried out at 40-42° C. for 2 h to obtain a solution A.

[0090] (2) Iodination reaction: 80 mL of the 47.% (V / V) recovered ethanol in Example 2, 14 mL of new ethanol, 6 mL of new water, and 28 g of iodine were added to solution A, and the temperature was raised to a second temperature (58-60° C.). At the second temperature, 29.0 g of hydrogen peroxide (hydrogen peroxide concentration was 27.5%) was added dropwise to solution A at a rate of 14.75 g / h. After the addition was completed, the mixture was kept at 60-63° C. for 2 h to obtain solution B.

[0091] (3) Distillation: Add 30 mL of the 45% (V / V) recovered ethanol and 20 mL of fresh water in Example 2 to Solution B, and recover dichloroethane and ethanol by atmospheric distillation. The endpoint temperature of atmospheric distillation is 90-95° C., then cool to 15° C., keep warm for 0.5 h, filter with suction, and wash the filter cake with 50 mL of water to obtain 72 g of crude nitroiodine phenol nitrile;

[0092] (4) Solvent recycling: The dichloroethane and ethanol mixed solution obtained in the distillation step is subjected to a first static decomposition to obtain an upper layer of ethanol and a lower layer of dichloroethane, which are separated, and the lower layer of dichloroethane is washed with 20 mL of water, and then subjected to a second static decomposition to obtain an upper layer of water and a lower layer of dichloroethane. 65 mL of the lower layer of dichloroethane is used as a set for recovering dichloroethane. The upper layer of water obtained by the second static decomposition and 108 mL of ethanol obtained by the first static decomposition are combined, and the specific gravity is measured to obtain an ethanol content of 46.5% (V / V) as recovered ethanol and recovered water. New ethanol is added and then used in the iodination reaction;

[0093] (5) Purification step: 144 mL of ethanol was added to 72 g of crude nitroiodine phenol nitrile, and the mixture was stirred and refluxed at 75-80° C. for 0.5 h. After the reflux, the mixture was cooled to 15° C. and kept at this temperature for 0.5 h. The mixture was filtered and the filter cake containing nitroiodine phenol nitrile was washed with 50 mL of ethanol and finally dried at 80° C. for 8 h to obtain 55.8 g of yellow powder nitroiodine phenol nitrile. MP. 137-138.5° C. (literature value 137-138° C.), HPLC purity 99.43%, yield 91.68%.

[0094] Experimental example

[0095] The nitroiodine phenol nitrile obtained in Example 1 to Example 3 was subjected to high performance liquid chromatography analysis, and the results were as follows: Figures 3 to 5 shown.

[0096] Detection method:

[0097] Chromatographic conditions: Agilent Zorbax SB-C18 column, (4.6 mm x 250 mm, 5 μm).

[0098] Mobile phase: A:B=80:20;

[0099] A: 0.01 mol / L phosphate, pH 6.5, mobile phase preparation: dissolve 7.9 g sodium chloride, 0.2 g potassium chloride, 1.44 g disodium hydrogen phosphate, and 1.8 g dipotassium hydrogen phosphate in 800 ml water, dissolve by ultrasonic, add phosphoric acid to adjust the pH to 6.5, and add water to 1000 ml.

[0100] B: Acetonitrile.

[0101] Column temperature: 25°C, flow rate: 1.0 mL / min, detection wavelength: 273 nm, injection volume: 10 μL.

[0102] Preparation of sample solution: Weigh 20 mg of sample into a 100 ml brown volumetric flask, add 2 ml of acetonitrile to dissolve, and then make up to volume with diluent (mobile phase A:B=80:20).

[0103] The HPLC purity of the nitroiodine phenol nitrile obtained in Examples 1 to 3 was all above 99%, and the yield was all greater than 91%, indicating that the use of the nitroiodine phenol nitrile provided by the present application not only achieved the synthesis of nitroiodine phenol nitrile, but also obtained nitroiodine phenol nitrile with higher purity.

[0104] Experimental Example 2

[0105] Comparing the method for preparing nitroiodine phenol nitrile in one pot provided by the present application with the cost of the prior art provided by Formula 2 in the background technology (the nitration reaction and the iodination reaction are carried out separately), the following is obtained:

[0106] The results are shown in Table 1.

[0107]

[0108] As shown in Table 1, the one-pot method for preparing nitroiodine phthalate provided in the present application is not only low in cost, but also has a better quality than the nitroiodine phthalate product obtained by separate nitration and iodination, and the yield is significantly improved.

[0109] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit it. Although the present application has been described in detail with reference to the aforementioned embodiments, ordinary technicians in the field should understand that they can still modify the technical solutions recorded in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for preparing nitroiodine nitrile in one pot, characterized in that: The steps include: (1) Nitration reaction: adding dichloroethane and p-hydroxybenzonitrile to a reactor, heating to a first temperature, and dripping nitric acid into the reactor at the first temperature. After the dripping is completed, the reaction is kept warm for 2-2.5 hours to obtain a solution A; (2) iodination reaction: adding ethanol, water and iodine to the solution A, raising the temperature to a second temperature, and dropping hydrogen peroxide into the solution A at the second temperature. After the dropping is completed, keeping the temperature for reaction for 2-2.5 hours to obtain a solution B; (3) Distillation: adding water to the solution B, raising the temperature, recovering dichloroethane and ethanol by atmospheric distillation, then cooling to 15-25° C. and keeping the temperature for 0.5 h, filtering with suction, washing the filter cake with water, and obtaining a crude product of nitroiodine phenolnitrile; In the distillation step, the volume weight ratio of the water to the p-hydroxybenzonitrile is 50 mL:25 g; (4) solvent recycling: the mixed solution of dichloroethane and ethanol obtained in the distillation step is subjected to a first static stratification to obtain an upper layer of ethanol and a lower layer of dichloroethane, which are separated, and the lower layer of dichloroethane is washed with water, subjected to a second static stratification to obtain an upper layer of water and a lower layer of dichloroethane, the lower layer of dichloroethane is used as recovered dichloroethane in the nitration reaction, the upper layer of water obtained in the second static stratification is combined with the ethanol obtained in the first static stratification to obtain recovered ethanol and recovered water, and the recovered water is used in the iodination reaction; In the nitration reaction, the ethylene dichloride comes from the recovered ethylene dichloride and / or new ethylene dichloride in the solvent recycling step; in the iodination reaction, the ethanol comes from the recovered ethanol and / or new ethanol; and the water comes from the recovered water and / or new water.

2. The method for preparing nitroiodine nitrile from a one-pot cooking method according to claim 1, characterized in that: In the nitration reaction step, the weight volume ratio of the p-hydroxybenzonitrile to the dichloroethane is 25 g:80 mL, and the feeding molar ratio of the nitric acid to the p-hydroxybenzonitrile is 1.36-1.50:

1.

3. The method for preparing nitroiodine nitrile from a one-pot cooking method according to claim 1, characterized in that: In the iodination reaction step, the molar ratio of the iodine to the p-hydroxybenzonitrile is 0.53-0.55:1; the molar ratio of the hydrogen peroxide to the p-hydroxybenzonitrile is 1.14-1.16:

1.

4. The method for preparing nitroiodine nitrile from a one-pot cooking method according to claim 2, characterized in that: In the nitration reaction, the dropping rate of the nitric acid is 9-9.75 g / h.

5. The method for preparing nitroiodine nitrile from one pot according to claim 3, characterized in that: In the iodination reaction, the dropping rate of the hydrogen peroxide solution is 14.5-14.75 g / h.

6. The method for preparing nitroiodine nitrile from a one-pot cooking method according to claim 1, characterized in that: The first temperature is 38-40°C, and the nitration reaction temperature is 38-43°C.

7. The method for preparing nitroiodine nitrile from a one-pot cooking method according to claim 1, characterized in that: The second temperature is 58-60°C, and the iodination reaction temperature is 60-63°C.

8. The method for preparing nitroiodine nitrile from one pot according to claim 1, characterized in that: In the iodination reaction, the volume weight ratio of the ethanol, the water and the p-hydroxybenzonitrile is 50 mL:50 mL:25 g.

9. The method for preparing nitroiodine nitrile from a one-pot cooking method according to claim 1, characterized in that: In the distillation step, the terminal temperature for recovering ethylene dichloride and ethanol is 90-95°C.

10. The method for preparing nitroiodine nitrile in one pot according to any one of claims 1 to 9, characterized in that: The method for preparing nitroiodine phenol nitrile also includes a refining step: adding ethanol to the crude nitroiodine phenol nitrile, stirring and refluxing at a temperature of 75-80° C. for 0.5-1 h, cooling to 15-25° C. and keeping warm for 0.5 h after the reflux, filtering, washing the obtained filter cake containing nitroiodine phenol nitrile with ethanol, and finally drying to obtain nitroiodine phenol nitrile; The volume ratio of the added ethanol to the weight ratio of the crude nitroiodine nitrate is 2:1 mL / g.

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