A continuous preparation method of 3-nitro-4-cyanotrifluorotoluene

Abstract

The present invention belongs to the technical field of organic fluorine compounds, and specifically provides a continuous preparation method of 3-nitro-4-cyanobenzotrifluoride, S1: 3-nitro-4-methylbenzotrifluoride, bromine and free radical initiator are passed into the first continuous reactor containing bromination anhydrous solvent to generate 3-nitro-4-bromomethylbenzotrifluoride; S2: 3-nitro-4-bromomethylbenzotrifluoride obtained by S1 and cuprous cyanide are passed into the second continuous reactor containing cyanide anhydrous solvent to generate 3-nitro-4-cyanobenzotrifluoride crude product, and filtered to separate the copper-containing filter cake, and the obtained filtrate is distilled to obtain 3-nitro-4-cyanobenzotrifluoride crude product; S3: copper-containing filter cake regeneration cycle; S4: the crude product obtained in S2 is subjected to reduced pressure distillation to obtain high-purity 3-nitro-4-cyanobenzotrifluoride. Cuprous cyanide regeneration can be achieved by the above steps, and efficient utilization of resources is achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of organic fluorine compounds, and in particular to a continuous preparation method of 3-nitro-4-cyanotrifluorotoluene. Background Art

[0002] 3-Nitro-4-cyanobenzotrifluoride is an important pharmaceutical and pesticide intermediate, widely used in the synthesis of a variety of highly active compounds. Currently, the compound is mainly prepared through the nucleophilic substitution reaction of 3-nitro-4-fluorobenzotrifluoride with cyanide.

[0003] The preparation of 3-nitro-4-cyanobenzotrifluoride typically uses cuprous cyanide as a catalyst and operates at high temperatures. However, the cuprous cyanide catalyst used in conventional processes suffers from severe agglomeration, resulting in a small effective surface area and low catalytic efficiency. This not only reduces reaction yield but also requires the use of excess catalyst to maintain reaction efficiency, increasing production costs and environmental impact.

[0004] Secondly, the cuprous cyanide catalyst in the prior art is usually used once, which not only wastes precious metal resources but also generates a large amount of copper-containing hazardous waste, resulting in high treatment costs and great environmental risks. Summary of the Invention

[0005] In view of the above-mentioned defects, the present invention provides a continuous preparation method of 3-nitro-4-cyanotrifluorotoluene, which can realize the regeneration of cuprous cyanide and achieve efficient utilization of resources.

[0006] To achieve the above object, the present invention provides the following technical solution: a continuous preparation method of 3-nitro-4-cyanotrifluorotoluene, comprising the following steps:

[0007] The following steps are involved:

[0008] S1: 3-nitro-4-methylbenzotrifluoride, bromine and a free radical initiator are reacted in a first continuous reactor containing an anhydrous bromine solvent at 60–80°C to generate 3-nitro-4-bromomethylbenzotrifluoride;

[0009] S2: The 3-nitro-4-bromomethylbenzotrifluoride obtained in S1 and cuprous cyanide are introduced into a second continuous reactor containing an anhydrous cyanide solvent, and reacted at 130-160° C. to produce a crude 3-nitro-4-cyanobenzotrifluoride product, which is then filtered to separate a copper-containing filter cake. The resulting filtrate is then distilled to obtain a viscous oily crude 3-nitro-4-cyanobenzotrifluoride product;

[0010] S3: Copper filter cake regeneration cycle:

[0011] S300: dissolving the copper-containing filter cake produced in S2 in an acid solution to obtain a copper salt solution;

[0012] S301: adding sodium fluoride to the copper salt solution to precipitate copper fluoride;

[0013] S302: Under a CO2 atmosphere, copper fluoride is reacted with 4-cyanopyridine N-oxide at a pH of 8-9 and a temperature of 50-60°C to regenerate cuprous cyanide and produce a sodium fluoride solution as a by-product;

[0014] S303: The regenerated cuprous cyanide is returned to step S2 for recycling;

[0015] S4: The crude product obtained in S2 is subjected to reduced pressure distillation to obtain high-purity 3-nitro-4-cyanotrifluorotoluene.

[0016] As a further improvement of the present invention, the S1 is specifically:

[0017] S100: introducing 3-nitro-4-methylbenzotrifluoride and a free radical initiator into a first continuous reactor containing a brominated anhydrous solvent, mixing and heating to 60-80° C., then adding bromine dropwise and continuing stirring until the bromine fades;

[0018] S101: Cool the decolorized solution to 10°C, add a 10% by mass aqueous solution of Na2SO3, and then separate the organic layer through a separation device. Wash the organic layer with a 5% by mass aqueous solution of NaHSO3, and then concentrate under reduced pressure to obtain 3-nitro-4-bromomethyltrifluorotoluene.

[0019] As a further improvement of the present invention, the S1 comprises, by mass, 1 part of 3-nitro-4-methylbenzotrifluoride, 0.52-0.57 parts of bromine, 0.0008-0.0015 parts of a free radical initiator, 4-6 parts of a brominated anhydrous solvent, 1.2-1.5 parts of a 10% aqueous solution of Na2SO3, and 0.8-1.0 parts of a 5% aqueous solution of NaHSO3.

[0020] As a further improvement of the present invention, the anhydrous bromide solvent is any one of carbon tetrachloride, chloroform or dichloromethane; and the free radical initiator is any one of azobisisobutyronitrile or benzoyl peroxide.

[0021] As a further improvement of the present invention, the S2 comprises, by mass, 1 part of 3-nitro-4-bromomethylbenzotrifluoride, 0.35-0.4 parts of cuprous cyanide, and 4-5 parts of anhydrous cyanide solvent.

[0022] As a further improvement of the present invention, the anhydrous cyanide solvent is any one of N,N-dimethylformamide or N-methylpyrrolidone.

[0023] As a further improvement of the present invention, S3: copper-containing filter cake regeneration cycle further comprises:

[0024] S304: The generated (CN)2 is passed into an alkaline absorption tower and converted into NaCN by NaOH for reuse.

[0025] Beneficial effects of the present invention:

[0026] By dissolving the copper-containing filter cake with dilute acid, precipitating sodium fluoride, and converting copper fluoride into cuprous cyanide, the cuprous cyanide regeneration cycle is achieved, the utilization rate of cuprous cyanide is improved, and the performance is stable within 7 cycles, with little impact on the cyanidation reaction time, the activity decay rate is <5%, and the yield is ≥90%, meeting the needs of industrial continuous production.

[0027] The generated (CN)2 gas is absorbed by NaOH and converted into NaCN for reuse, eliminating the emission of highly toxic gases and reducing raw material costs and environmental risks. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0029] A continuous preparation method of 3-nitro-4-cyanotrifluorotoluene comprises the following steps:

[0030] S1: Preparation of 3-nitro-4-(bromomethyl)trifluorotoluene by bromination.

[0031] S100: Bromine anhydrous solvent is introduced into a first continuous reactor equipped with a stirrer, a reflux condenser, a thermometer and a constant pressure dropping funnel, and 3-nitro-4-methylbenzotrifluoride and a free radical initiator are added at the same time. The mixture is stirred and heated to 60-80°C and maintained. Bromine is added dropwise to the reactor through a dropping funnel, and the reaction is continuously stirred until the bromine color completely fades.

[0032] S101: Cool the coolant to 10°C, add a 10% by mass aqueous solution of Na2SO3 to quench the mixture, separate the organic layer using a liquid separator, wash the organic layer with a 5% by mass aqueous solution of NaHSO3, and then concentrate under reduced pressure to obtain light yellow crystals of 3-nitro-4-(bromomethyl)trifluorotoluene.

[0033] In parts by mass, the following ingredients include 1 part of 3-nitro-4-methylbenzotrifluoride, 0.52-0.57 parts of bromine, 0.0008-0.0015 parts of a free radical initiator, 4-6 parts of anhydrous solvent, 1.2-1.5 parts of a 10% aqueous solution of Na2SO3 by mass, and 0.8-1.0 parts of a 5% aqueous solution of NaHSO3 by mass.

[0034] The anhydrous bromination solvent can be carbon tetrachloride (CCl4), chloroform (CHCl3), or dichloromethane (CH2Cl2). The free radical initiator can be azobisisobutyronitrile (AIBN) or benzoyl peroxide (BPO), which can promote the bromination reaction to proceed according to free radical excitation.

[0035] S2: Preparation of 3-nitro-4-cyanotrifluorotoluene by cyanation.

[0036] In a second continuous reactor equipped with a stirrer, a reflux condenser, and a thermometer, cuprous cyanide (CuCN) and anhydrous cyanide solvent are added and stirred thoroughly. 3-nitro-4-(bromomethyl)benzotrifluoride obtained in S1 is added and the 3-nitro-4-(bromomethyl)benzotrifluoride is detected by GC at 130-160°C. When the GC detection shows that the residual 3-nitro-4-(bromomethyl)benzotrifluoride substrate is less than or equal to 1%, the mixture is filtered through a hot filter to obtain a copper-containing filter cake and a filtrate. The filtrate is distilled to obtain a viscous, oily crude 3-nitro-4-cyanobenzotrifluoride.

[0037] In parts by mass, 1 part of 3-nitro-4-(bromomethyl)trifluorotoluene, 0.35-0.4 parts of cuprous cyanide (CuCN), and 4-5 parts of anhydrous cyanide solvent.

[0038] The anhydrous cyanide solvent may be either N,N-dimethylformamide (DMF) or N-methylpyrrolidone (NMP).

[0039] S3: copper-containing filter cake regeneration cycle;

[0040] S300: dissolving the copper-containing filter cake produced in S2 in dilute acid H2SO4 to obtain a CuSO4 solution.

[0041] S301: Sodium fluoride NaF is added to the CuSO4 solution to precipitate copper fluoride CuF2.

[0042] S302: Under a CO2 atmosphere, copper fluoride is reacted with 4-cyanopyridine N-oxide at a pH of 8-9 and a temperature of 50-60°C to regenerate cuprous cyanide and produce a sodium fluoride solution as a by-product.

[0043] The reaction principle is: 2CuF2+4NaCN→ 2CuCN + 4NaF + (CN)2, where CuCN is a precipitate and (CN)2 is a gas.

[0044] S303: The regenerated cuprous cyanide is returned to step S2 for recycling;

[0045] S304: The generated (CN)2 is passed into an alkaline absorption tower and converted into NaCN by NaOH for reuse;

[0046] The reaction principle is: (CN)2+2NaOH→NaCN+NaOCN+H2O.

[0047] S4: The crude 3-nitro-4-cyanobenzotrifluoride obtained in S2 is subjected to reduced pressure distillation to obtain high-purity 3-nitro-4-cyanobenzotrifluoride.

[0048] Example 1

[0049] A continuous preparation method of 3-nitro-4-cyanotrifluorotoluene comprises the following steps:

[0050] S1: Preparation of 3-nitro-4-(bromomethyl)trifluorotoluene by bromination.

[0051] S100: Into a first continuous reactor equipped with a stirrer, a reflux condenser, a thermometer and a constant pressure dropping funnel, 4 parts of dichloromethane solvent were introduced, and at the same time, 1 part of 3-nitro-4-methyltrifluorotoluene and 0.0008 parts of azobisisobutyronitrile were added. The mixture was stirred and heated to 70°C and maintained. 0.52 parts of bromine was added dropwise to the reactor through a dropping funnel, and the reaction was continued by stirring until the color of the bromine completely faded.

[0052] S101: Cool the coolant to 10°C, add 1.2 parts of 10% Na2SO3 aqueous solution to quench, then separate the organic layer through a liquid separator, wash the organic layer with 0.8 parts of 5% NaHSO3 aqueous solution, and then concentrate under reduced pressure to obtain light yellow crystals of 3-nitro-4-(bromomethyl)trifluorotoluene.

[0053] S2: Preparation of 3-nitro-4-cyanotrifluorotoluene by cyanation.

[0054] In a second continuous reactor equipped with a stirrer, reflux condenser, and thermometer, 0.35 parts of cuprous cyanide (CuCN) and 4 parts of N,N-dimethylformamide were added and stirred thoroughly. 1 part of 3-nitro-4-(bromomethyl)benzotrifluoride obtained in S1 was added and reacted at 130°C. The 3-nitro-4-(bromomethyl)benzotrifluoride was detected by GC. When the GC detection of 3-nitro-4-(bromomethyl)benzotrifluoride was less than or equal to 1%, the mixture was filtered through a hot filter to obtain a copper-containing filter cake and a filtrate. The filtrate was distilled to obtain a viscous oily crude 3-nitro-4-cyanobenzotrifluoride.

[0055] S3: copper-containing filter cake regeneration cycle;

[0056] S300: Dissolve the copper-containing filter cake produced in S2 in 10% dilute acid H2SO4 to obtain a CuSO4 solution.

[0057] S301: Sodium fluoride NaF is added to the CuSO4 solution to precipitate copper fluoride CuF2.

[0058] S302: Under a CO2 atmosphere, copper fluoride is reacted with 4-cyanopyridine N-oxide at a pH of 8 and a temperature of 50°C to regenerate cuprous cyanide and produce a sodium fluoride solution as a by-product.

[0059] S303: The regenerated cuprous cyanide is returned to step S2 for recycling. The process steps and the mass fraction of the raw materials used are the same as those in this embodiment.

[0060] Then the cuprous cyanide activity decay rate and cyanide yield are calculated:

[0061]

[0062] The cyanidation reaction time is also monitored.

[0063] The experimental data table of Example 1 is as follows:

[0064]

[0065] Example 2

[0066] A continuous preparation method of 3-nitro-4-cyanotrifluorotoluene comprises the following steps:

[0067] S1: Preparation of 3-nitro-4-(bromomethyl)trifluorotoluene by bromination.

[0068] S100: Into a first continuous reactor equipped with a stirrer, a reflux condenser, a thermometer and a constant pressure dropping funnel, 5 parts of dichloromethane solvent were introduced, and 1 part of 3-nitro-4-methyltrifluorotoluene and 0.00115 parts of azobisisobutyronitrile were added at the same time. The mixture was stirred and heated to 70°C and maintained thereat. 0.545 parts of bromine was added dropwise to the reactor through a dropping funnel, and the reaction was continued by stirring until the color of the bromine completely faded.

[0069] S101: Cool the coolant to 10°C, add 1.35 parts of 10% Na2SO3 aqueous solution to quench, then separate the organic layer through a liquid separator, wash the organic layer with 0.9 parts of 5% NaHSO3 aqueous solution, and then concentrate under reduced pressure to obtain light yellow crystals of 3-nitro-4-(bromomethyl)trifluorotoluene.

[0070] S2: Preparation of 3-nitro-4-cyanotrifluorotoluene by cyanation.

[0071] In a second continuous reactor equipped with a stirrer, reflux condenser, and thermometer, 0.375 parts of cuprous cyanide (CuCN) and 4.5 parts of N,N-dimethylformamide were added and stirred thoroughly. 1 part of 3-nitro-4-(bromomethyl)benzotrifluoride obtained in S1 was added and reacted at 145°C. 3-nitro-4-(bromomethyl)benzotrifluoride was detected by GC. When the GC detection of 3-nitro-4-(bromomethyl)benzotrifluoride was less than or equal to 1%, the mixture was filtered through a hot filter to obtain a copper-containing filter cake and a filtrate. The filtrate was distilled to obtain a viscous oily crude 3-nitro-4-cyanobenzotrifluoride.

[0072] S3: copper-containing filter cake regeneration cycle;

[0073] S300: Dissolve the copper-containing filter cake produced in S2 in 10% dilute acid H2SO4 to obtain a CuSO4 solution.

[0074] S301: Sodium fluoride NaF is added to the CuSO4 solution to precipitate copper fluoride CuF2.

[0075] S302: Under a CO2 atmosphere, copper fluoride is reacted with 4-cyanopyridine N-oxide at a pH of 8.5 and a temperature of 55°C to regenerate cuprous cyanide and produce a sodium fluoride solution as a by-product.

[0076] S303: The regenerated cuprous cyanide is returned to step S2 for recycling. The process steps and the mass fraction of the raw materials used are the same as those in this embodiment.

[0077] The cuprous cyanide activity decay rate, cyanidation yield, and cyanidation reaction time of this embodiment were calculated according to the calculation method of Example 1.

[0078] The experimental data table of Example 2 is as follows:

[0079]

[0080] Example 3

[0081] A continuous preparation method of 3-nitro-4-cyanotrifluorotoluene comprises the following steps:

[0082] S1: Preparation of 3-nitro-4-(bromomethyl)trifluorotoluene by bromination.

[0083] S100: Into a first continuous reactor equipped with a stirrer, a reflux condenser, a thermometer and a constant pressure dropping funnel, 6 parts of dichloromethane solvent were introduced, and 1 part of 3-nitro-4-methyltrifluorotoluene and 0.0015 parts of azobisisobutyronitrile were added at the same time. The mixture was stirred and heated to 80°C and maintained thereat. 0.57 parts of bromine was added dropwise to the reactor through a dropping funnel, and the reaction was continued by stirring until the color of the bromine completely faded.

[0084] S101: Cool the coolant to 10°C, add 1.5 parts of 10% Na2SO3 aqueous solution to quench, then separate the organic layer through a liquid separator, wash the organic layer with 1 part of 5% NaHSO3 aqueous solution, and then concentrate under reduced pressure to obtain light yellow crystals of 3-nitro-4-(bromomethyl)trifluorotoluene.

[0085] S2: Preparation of 3-nitro-4-cyanotrifluorotoluene by cyanation.

[0086] In a second continuous reactor equipped with a stirrer, reflux condenser, and thermometer, add 0.4 parts of cuprous cyanide (CuCN) and 5 parts of N,N-dimethylformamide and stir thoroughly. Then, add 1 part of 3-nitro-4-(bromomethyl)benzotrifluoride obtained in S1 and react at 160°C. Detect the 3-nitro-4-(bromomethyl)benzotrifluoride by GC. When the GC detection shows that the 3-nitro-4-(bromomethyl)benzotrifluoride is less than or equal to 1%, filter through a hot filter to obtain a copper-containing filter cake and a filtrate. Distill the filtrate to obtain a viscous, oily crude 3-nitro-4-cyanobenzotrifluoride.

[0087] S3: copper-containing filter cake regeneration cycle;

[0088] S300: Dissolve the copper-containing filter cake produced in S2 in 10% dilute acid H2SO4 to obtain a CuSO4 solution.

[0089] S301: Sodium fluoride NaF is added to the CuSO4 solution to precipitate copper fluoride CuF2.

[0090] S302: Under a CO2 atmosphere, copper fluoride is reacted with 4-cyanopyridine N-oxide at a pH of 8.5 and a temperature of 55°C to regenerate cuprous cyanide and produce a sodium fluoride solution as a by-product.

[0091] S303: The regenerated cuprous cyanide is returned to step S2 for recycling. The process steps and the mass fraction of the raw materials used are the same as those in this embodiment.

[0092] The cuprous cyanide activity decay rate, cyanidation yield, and cyanidation reaction time of this embodiment were calculated according to the calculation method of Example 1.

[0093] The experimental data table of Example 3 is as follows:

[0094]

[0095] It can be seen from the above Examples 1-3 that the copper filter cake after use is regenerated and recycled to cuprous cyanide and returned to step S2 for reuse. The catalyst activity decay rate is less than 5% within 7 times, and can be used normally. The yield in the cyanidation process can be maintained at more than 90%. When the number of uses is greater than 8 times, the cuprous cyanide activity decay rate and the cyanidation yield will be affected, and the cyanidation reaction time will be greatly increased.

[0096] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A continuous preparation method of 3-nitro-4-cyanotrifluorotoluene, characterized in that: The following steps are involved: S1: 3-nitro-4-methylbenzotrifluoride, bromine and a free radical initiator are reacted in a first continuous reactor containing an anhydrous bromine solvent at 60–80°C to generate 3-nitro-4-bromomethylbenzotrifluoride; The anhydrous bromide solvent is any one of carbon tetrachloride, chloroform or dichloromethane; the free radical initiator is any one of azobisisobutyronitrile or benzoyl peroxide; S2: Passing the 3-nitro-4-bromomethylbenzotrifluoride obtained in S1 and cuprous cyanide into a second continuous reactor containing an anhydrous cyanide solvent, reacting at 130-160° C. to produce a crude 3-nitro-4-cyanobenzotrifluoride product, which is then filtered to separate a copper-containing filter cake. The resulting filtrate is then distilled to obtain a viscous oily crude 3-nitro-4-cyanobenzotrifluoride product; The anhydrous cyanide solvent is any one of N,N-dimethylformamide or N-methylpyrrolidone; S3: Copper filter cake regeneration cycle: S300: dissolving the copper-containing filter cake produced in S2 in an acid solution to obtain a copper salt solution; S301: adding sodium fluoride to the copper salt solution to precipitate copper fluoride; S302: Under a CO2 atmosphere, copper fluoride is reacted with 4-cyanopyridine N-oxide at a pH of 8-9 and a temperature of 50-60°C to regenerate cuprous cyanide and produce a sodium fluoride solution as a by-product; S303: The regenerated cuprous cyanide is returned to step S2 for recycling; S4: The crude product obtained in S2 is distilled under reduced pressure to obtain 3-nitro-4-cyanotrifluorotoluene.

2. The continuous preparation method of 3-nitro-4-cyanotrifluorotoluene according to claim 1, characterized in that: The S1 is specifically: S100: introducing 3-nitro-4-methylbenzotrifluoride and a free radical initiator into a first continuous reactor containing a brominated anhydrous solvent, mixing and heating to 60-80° C., then adding bromine dropwise and continuing stirring until the bromine fades; S101: Cool the decolorized solution to 10°C, add a 10% by mass aqueous solution of Na2SO3, and then separate the organic layer through a separation device. Wash the organic layer with a 5% by mass aqueous solution of NaHSO3, and then concentrate under reduced pressure to obtain 3-nitro-4-bromomethyltrifluorotoluene.

3. The continuous preparation method of 3-nitro-4-cyanotrifluorotoluene according to claim 2, characterized in that: In the S1, in parts by mass, the following components are present: 1 part of 3-nitro-4-methylbenzotrifluoride, 0.52-0.57 parts of bromine, 0.0008-0.0015 parts of a free radical initiator, 4-6 parts of anhydrous bromide solvent, 1.2-1.5 parts of a 10% aqueous solution of Na2SO3, and 0.8-1.0 parts of a 5% aqueous solution of NaHSO3.

4. The continuous preparation method of 3-nitro-4-cyanotrifluorotoluene according to claim 1, characterized in that: In the S2, by mass, 1 part of 3-nitro-4-bromomethylbenzotrifluoride, 0.35-0.4 parts of cuprous cyanide, and 4-5 parts of anhydrous cyanide solvent are included.

5. The continuous preparation method of 3-nitro-4-cyanotrifluorotoluene according to claim 1, characterized in that: S3: The copper-containing filter cake regeneration cycle also includes: S304: The generated (CN)2 is passed into an alkaline absorption tower and converted into NaCN by NaOH for reuse.

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