CN114805126A - Preparation method of 2-nitro-4, 5-dibenzyloxy benzyl cyanide - Google Patents
Preparation method of 2-nitro-4, 5-dibenzyloxy benzyl cyanide Download PDFInfo
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- CN114805126A CN114805126A CN202210477188.3A CN202210477188A CN114805126A CN 114805126 A CN114805126 A CN 114805126A CN 202210477188 A CN202210477188 A CN 202210477188A CN 114805126 A CN114805126 A CN 114805126A
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C—CHEMISTRY; METALLURGY
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- C07C253/00—Preparation of carboxylic acid nitriles
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Abstract
The invention discloses a preparation method of 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, belonging to the technical field of compound synthesis, comprising a 3, 4-dibenzyloxy phenylacetonitrile dissolving process, a concentrated nitric acid mixing process, a preheating process, a mixer mixing process, a nitration reaction process, a crystallization process, a filtering and drying process and an acetic acid solution recycling process, wherein the invention uses nitric acid and acetic acid to carry out nitration reaction on the 3, 4-dibenzyloxy phenylacetonitrile in a tubular reactor to obtain the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, the reaction time is short, the reaction heat release is small, the process is safe and controllable, the concentrated nitric acid dosage is small, the acetic acid dosage is small, the cyclic use is realized, the product separation and extraction process is simple, the product purity is more than 98.5 percent, the yield is more than 93 percent, is suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of compound synthesis, and particularly relates to a preparation method of 2-nitro-4, 5-dibenzyloxy benzyl cyanide.
Background
Aniline substances in the traditional hair dye have certain toxicity and irritation, and the safe novel hair dye becomes a product urgently needed by the hair dyeing industry. Among dyeing components of the hair dye, 5, 6-dihydroxyindole is a melanin intermediate, can act on hair keratin dyeing, and has extremely high safety because it can be biologically converted into chemical substances contained in human bodies. For many years, researchers at home and abroad have carried out many researches on the synthesis of 5, 6-dihydroxyindole, wherein the phenylacetonitrile method is one of the main synthetic routes, namely 3, 4-dimethoxyphenylacetonitrile is taken as a raw material, 2-nitro-4, 5-dibenzyloxy phenylacetonitrile is firstly synthesized, and then 5, 6-dihydroxyindole is obtained through reduction and cyclization.
In the synthetic route of the benzyl cyanide method, 3, 4-dimethoxy benzyl cyanide is used as a raw material and is subjected to four-step reaction: the 5, 6-dihydroxyindole is obtained through demethylation reaction, hydroxyl protection reaction, nitration reaction and reduction cyclization reaction, wherein the nitration reaction process has some problems, such as low reaction yield, complex separation and extraction steps in post-treatment, high industrial production cost, safety risk brought by heat release accumulation of nitration reaction and the like. Because 2-nitro-4, 5-dibenzyloxy benzyl cyanide has higher solubility in acetic acid, even if the reaction selectivity is high, raw materials are easy to be completely converted into target products, and a lot of loss is generated in the processes of separating a solvent and extracting the products, so that the yield in the prior art is not high. Therefore, it is necessary to optimize the synthesis method, improve the synthesis efficiency, and make the process amenable to production scale-up.
In the prior art, a Lixiaojun et al (5, 6-dihydroxyindole synthesis [ J ] dye and dyeing, 2007, 44(002): 53-55) design experiment of Hebei industry university studies the influence of the acetic acid dosage in the process conditions of synthesizing 2-nitro-4, 5 dibenzyloxy phenylacetonitrile by nitration reaction, but the nitration yield is 86.9% under the optimized conditions, and the yield is lower. The molar ratio of nitric acid to starting material used in the reaction is much greater than the intrinsic molar ratio of the reaction, increasing the material cost and the risk of uncontrolled exotherms of the reaction during operation.
The Chinese patent with application number 87107372 discloses a method for preparing 5, 6-dihydroxyindole, 3-alkyl derivatives thereof and intermediate compounds, wherein a mixture of 3, 4-dibenzyloxy benzyl cyanide, ethanol and isopropanol is used as a raw material, and a nitration reaction is carried out by concentrated nitric acid or dilute nitric acid, but after the reaction is finished, ethanol is firstly used for washing, and then isopropanol is used for washing, the post-treatment process is complicated, two process devices are needed for washing, and the equipment and solvent cost is increased.
Therefore, how to design a method for synthesizing 2-nitro-4, 5-dibenzyloxy phenylacetonitrile by using 3, 4-dibenzyloxy phenylacetonitrile is an urgent problem to be solved, so that the reaction time is shortened, the reaction heat release is controllable, the treatment process is reduced, the reaction device and process conditions are optimized, the production cost is reduced, and the yield of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile is improved.
Disclosure of Invention
The invention aims to overcome the technical problems of complicated treatment process, complex process conditions, high production cost and the like in the production process of synthesizing 2-nitro-4, 5-dibenzyloxy phenylacetonitrile by using 3, 4-dibenzyloxy phenylacetonitrile in the prior art, and provides the preparation method of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, which has the advantages of short reaction time, controllable reaction heat release, simple reaction device and process conditions, low production cost and high yield of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile.
In order to solve the technical problems, the invention provides a preparation method of 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, which comprises the following steps:
step A: adding acetic acid into a first container, slowly adding 3, 4-dibenzyloxy phenylacetonitrile into the acetic acid, stirring to uniformly mix the 3, 4-dibenzyloxy phenylacetonitrile with the acetic acid, and dissolving the 3, 4-dibenzyloxy phenylacetonitrile into the acetic acid to form a first mixture, wherein the mass ratio of the 3, 4-dibenzyloxy phenylacetonitrile to the acetic acid is set to be 1:1-1:5, and the stirring time is set to be 10-40 minutes;
and B: adding acetic acid into the second container, slowly adding the concentrated nitric acid into the acetic acid, stirring to uniformly mix the concentrated nitric acid and the acetic acid to form a second mixture, wherein the volume ratio of the concentrated nitric acid to the acetic acid is set to be 1:1-1:8, and the stirring time is set to be 10-40 minutes;
and C: the preheating process comprises the steps of introducing a first mixture formed in a first container into a first preheating pipe by using a constant-flow pump to heat the first mixture, carrying out oil bath heating on the first preheating pipe through dimethyl silicone oil, and setting the heating temperature of the first preheating pipe to be 20-40 ℃; a second mixture formed in the second container is introduced into a second preheating pipe by using a second advection pump to heat the second mixture, the second preheating pipe is subjected to oil bath heating by using dimethyl silicone oil, and the heating temperature of the second preheating pipe is set to be 20-40 ℃; the flow ratio of the liquid in the first constant-flow pump to the liquid in the second constant-flow pump is set to be 10:1-1: 3;
step D: respectively introducing the preheated mixture I and the preheated mixture II into a feed inlet I and a feed inlet II of a mixer through the mixing process of the mixer, and fully mixing the mixture I and the mixture II in the mixer to form a mixture III, wherein the mixer is a T-shaped mixer or a Y-shaped mixer;
step E: in the nitration reaction process, introducing the mixture III fully mixed by the T-shaped mixer into a feed inlet of the tubular reactor from a discharge port of the mixer, then entering the tubular reactor, and heating the tubular reactor, wherein the heating mode is oil bath heating, the heating temperature is set to be 50-90 ℃, and the reaction time is set to be 6-30 minutes, so that the 3, 4-dibenzyloxy phenylacetonitrile, the concentrated nitric acid and the acetic acid are subjected to nitration reaction to obtain 2-nitro-4, 5-dibenzyloxy phenylacetonitrile;
step F: in the crystallization process, the mixed liquid of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile and the acetic acid collected from the discharge port of the tubular reactor is introduced into a third container, the third container is kept stand, the temperature of the third container is reduced, so that the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile in the acetic acid is crystallized and separated out to obtain a crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, and the temperature during crystallization is set to be 0-25 ℃;
step G: filtering and drying, namely filtering the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile obtained in the step F, and putting the filtered product into an oven to be dried to obtain the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, wherein the temperature of the oven is set to be 70-80 ℃;
step H: and D, recycling the acetic acid solution, namely adding the acetic acid solution filtered in the step G into the first container and/or the second container in the step A and/or the step B again to participate in the reaction as a raw material.
As a further improvement of the invention, in the preparation method of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, in the step A, the mass ratio of the 3, 4-dibenzyloxy phenylacetonitrile to the acetic acid is set to be 1:3-1:4, and the stirring time is set to be 20-30 minutes.
As a further improvement measure of the invention, in the preparation method of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, the volume ratio of the concentrated nitric acid to the acetic acid in the step B is set to be 1:3-1:5, and the stirring time is set to be 20-40 minutes.
As a further improvement measure of the invention, in the preparation method of the 2-nitro-4, 5-dibenzyloxy benzyl cyanide, in the step C, the flow ratio of the liquids in the first constant-current pump and the second constant-current pump is set to be 7:1-3: 1.
As a further improvement measure of the invention, in the preparation method of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, in the step E, the heating temperature is set to be 60-70 ℃, and the reaction time is set to be 8-10 minutes.
As a further improvement of the invention, in the above-mentioned process for producing 2-nitro-4, 5-dibenzyloxyphenylacetonitrile, in the step F, the temperature during crystallization is set to 5 to 15 ℃.
In order to realize the preparation method of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, the preparation method is carried out by using a tubular reaction device, the reaction device comprises a first container and a second container, the first container is connected with a first preheating pipe through a first advection pump, the second container is connected with a second preheating pipe through a second advection pump, the first preheating pipe is connected with a first feed inlet of a mixer, the second preheating pipe is connected with a second feed inlet of the mixer, a discharge outlet of the mixer is connected with a feed inlet of the tubular reactor, a heating device is arranged around the tubular reactor, a discharge outlet of the tubular reactor is connected with the third container, a cooling device is arranged around the third container, and the reaction device further comprises a drying device.
As a further improvement measure of the invention, the preparation method of the 2-nitro-4, 5-dibenzyloxy benzyl cyanide is characterized in that the mixer is a T-type mixer or a Y-type mixer.
As a further improvement of the present invention, in the above-mentioned process for producing 2-nitro-4, 5-dibenzyloxyphenylacetonitrile, the heating apparatus is set up as an oil bath apparatus.
As a further improvement measure of the invention, in the preparation method of the 2-nitro-4, 5-dibenzyloxy benzyl cyanide, the first container and the second container are respectively arranged into two containers, and a first valve and a second valve are respectively arranged between the first container and the second container and between the first constant-current pump and the second constant-current pump; by arranging the first container and the second container, when one of the first container and the second container is used for conveying raw materials through the advection pump I and the advection pump II to react, the other container and the second container can be used for mixing the raw materials through the step A and the step B, so that the time can be saved, and the production efficiency can be improved.
Compared with the prior art, the invention has the beneficial effects that: 1. the preparation method of the invention has short reaction time, can improve the production efficiency and can save energy.
2. The tubular reactor is used for heating through an oil bath, the reaction heat release is controllable, the risk caused by uncontrolled heat release when the traditional kettle type reactor is used for nitration reaction is avoided, compared with the prior art and the prior art, the method has the advantages that although the reaction raw materials are the same, the consumption of nitric acid is reduced, the large-scale use of nitric acid with toxic risk is avoided, and the process is safe and controllable.
3. The invention can reduce the consumption of acetic acid, recycle the acetic acid and save the production cost.
4. The invention can reduce the loss of products which can not be completely extracted from the solvent, can improve the yield, and the yield is more than 93 percent by applying the method of the invention, thus being suitable for industrial production.
5. The purity of the 2-nitro-4, 5-dibenzyloxy benzyl cyanide product obtained by the invention is more than 98.5%, the product quality can be improved, and the product meets the production requirements.
Drawings
FIG. 1 is a schematic diagram of the preparation process of the present invention.
FIG. 2 is a schematic view of the structure of a reaction apparatus of the present invention.
The reference numbers illustrate: 1-container I, 2-container II, 3-advection pump I, 4-advection pump II, 5-preheating pipe I, 6-preheating pipe II, 7-mixer inlet I, 8-mixer inlet II, 9-mixer, 10-mixer outlet, 11-tubular reactor inlet, 12-tubular reactor, 13-tubular reactor outlet, 14-container III, 15-drying device, 16-valve I, 17-valve II.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
On the contrary, the invention is intended to cover alternatives, modifications, equivalents and alternatives which may be included within the spirit and scope of the invention as defined by the appended claims.
Example 1: as shown in fig. 1 and fig. 2, 255g of acetic acid is added into the first container 1, 63.8g of 3, 4-dibenzyloxy phenylacetonitrile is slowly added into the first container 1, and the mixture is stirred for 20 minutes to uniformly mix the 3, 4-dibenzyloxy phenylacetonitrile and the acetic acid, so that the 3, 4-dibenzyloxy phenylacetonitrile is dissolved in the acetic acid to form a first mixture; 38ml of acetic acid is added into the second container 2, 19ml of concentrated nitric acid is slowly added into the second container 2, and the mixture is stirred for 20 minutes to uniformly mix the concentrated nitric acid and the acetic acid to form a second mixture.
Introducing the first mixture formed in the first container 1 into a first preheating pipe 5 by using a first constant-current pump 3 to heat the first mixture, wherein the flow rate of the first constant-current pump 3 is set to be 24.28ml/min, and the heating temperature is set to be 20 ℃; a second mixture formed in the second container 2 is introduced into a second preheating pipe 6 by using a second constant-current pump 4 to heat the second mixture, the flow rate of the second constant-current pump 4 is set to be 5.74ml/min, and the heating temperature is set to be 20 ℃; respectively introducing the preheated mixture I and the preheated mixture II into a feed inlet I7 of a T-shaped mixer and a feed inlet II 8 of the T-shaped mixer, and fully mixing the mixture I and the mixture II in a T-shaped mixer 9 to form a mixture III; introducing a mixture III fully mixed by a T-shaped mixer 9 into a feed inlet 11 of a tubular reactor from a discharge port 10 of the T-shaped mixer, then introducing the mixture III into the tubular reactor 12, carrying out oil bath heating on the tubular reactor 12, setting the oil bath temperature to be 60 ℃, setting the reaction time to be 10 minutes, and carrying out nitration reaction on 3, 4-dibenzyloxy phenylacetonitrile, concentrated nitric acid and acetic acid to obtain a mixed solution of 2-nitro-4, 5-dibenzyloxy phenylacetonitrile and acetic acid, wherein the chemical reaction formula is as follows:
introducing the mixed solution of 2-nitro-4, 5-dibenzyloxy benzyl cyanide and acetic acid collected from the discharge port 13 of the tubular reactor into a third container 14, standing, cooling the third container 14, and setting the temperature to be 5 ℃ during crystallization; crystallizing and separating out the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile in acetic acid to obtain a crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, filtering the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, putting the filtered product into a drying device 15 for drying, for example, putting the dried product into an oven for drying, wherein the temperature of the oven is set to be 70 ℃, and the residual solvent in the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile is dried to obtain 69.2g of a finished product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, and the purity of the finished product is 98.7 percent through liquid chromatography detection. The yield thereof was found to be 95.4%.
The filtered acetic acid solution was recovered again and used as a raw material for the next reaction.
As shown in FIG. 2, the preparation method of the present invention is carried out using a tubular reaction apparatus comprising a first vessel 1 and a second vessel 2, wherein the first vessel 1 is connected to a first preheating pipe 5 by a first advection pump 3, the second vessel 2 is connected to a second preheating pipe 6 by a second advection pump 4, the first preheating pipe 5 is connected to a first mixer inlet 7, the second preheating pipe 6 is connected to a second mixer inlet 8, a mixer outlet 10 is connected to a tubular reactor inlet 11, the mixer 9 is a T-shaped mixer, a heating apparatus is provided around the tubular reactor 12, the heating apparatus is an oil bath apparatus, an oil bath apparatus is provided for easy temperature control, a tubular reactor outlet 13 is connected to the third vessel 14, a cooling apparatus is provided around the third vessel 14, and the reaction apparatus further comprises a drying apparatus 15, such as an oven, for drying the residual solvent.
In order to further improve the production efficiency, the first container 1 and the second container 2 are respectively provided with two containers, the first valve 16 and the second valve 17 are respectively arranged between the first container 1 and the second container 2 and the advection pump I3 and the advection pump II 4, and as the 3, 4-dibenzyloxy benzyl cyanide dissolving process and the concentrated nitric acid mixing process respectively need to be stirred for 10-40 minutes in the first container 1 and the second container 2, the production efficiency is improved in the actual production process, when one container 1 and the second container 2 carry out raw material conveying reaction through the advection pump I3 and the advection pump II 4, the other container 1 and the second container 2 can carry out raw material mixing through the step A and the step B, and the time can be saved.
Example 2: the acetic acid recovered in example 1 was used as a starting material for the reaction.
The acetic acid filtered from 2-nitro-4, 5-dibenzyloxy phenylacetonitrile in example 1 was recovered, 127g of the recovered acetic acid was added to vessel one 1, 128g of fresh acetic acid was further added to vessel one 1, 63.8g of 3, 4-dibenzyloxy phenylacetonitrile was slowly added to vessel one 1, and the mixture was stirred for 20 minutes to uniformly mix the 3, 4-dibenzyloxy phenylacetonitrile and acetic acid, so that the 3, 4-dibenzyloxy phenylacetonitrile was dissolved in the acetic acid to form mixture one.
The other methods are the same as the embodiment 1, and the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile is dried to obtain 67.4g of the finished product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, the purity of the finished product is 98.5 percent and the yield of the finished product is 93.0 percent through liquid chromatography detection.
Example 2 demonstrates that the purity and yield of the product can still meet the product quality requirements when the recovered acetic acid is used as the raw material for production, and therefore, the production process of the invention can recycle the acetic acid, and the production cost can be saved.
Example 3: adding 162g of acetic acid into the first container 1, slowly adding 80.9g of 3, 4-dibenzyloxy phenylacetonitrile into the first container 1, stirring for 20 minutes to uniformly mix the 3, 4-dibenzyloxy phenylacetonitrile and the acetic acid, and dissolving the 3, 4-dibenzyloxy phenylacetonitrile in the acetic acid to form a first mixture; 117ml of acetic acid was added to the second container 2, 29ml of concentrated nitric acid was slowly added to the second container 2, and the mixture was stirred for 20 minutes to uniformly mix the concentrated nitric acid and the acetic acid, thereby forming a second mixture.
Introducing the first mixture formed in the first container 1 into a first preheating pipe 5 by using a first constant-flow pump 3 to heat the first mixture, wherein the flow rate of the first constant-flow pump 3 is set to be 7.86ml/min, and the heating temperature is set to be 20 ℃; a second mixture formed in the second container 2 is introduced into a second preheating pipe 6 by using a second constant-flow pump 4 to heat the second mixture, the flow rate of the second constant-flow pump 4 is set to be 7.14ml/min, and the heating temperature is set to be 20 ℃; respectively introducing the preheated mixture I and the preheated mixture II into a feed inlet I7 of a T-shaped mixer and a feed inlet II 8 of the T-shaped mixer, and fully mixing the mixture I and the mixture II in a T-shaped mixer 9 to form a mixture III; and introducing the mixture III fully mixed by the T-shaped mixer 9 into a feed inlet 11 of the tubular reactor from a discharge port 10 of the T-shaped mixer, then introducing the mixture III into the tubular reactor 12, carrying out oil bath heating on the tubular reactor 12, setting the oil bath temperature to be 70 ℃, and setting the reaction time to be 20 minutes, so that the 3, 4-dibenzyloxy phenylacetonitrile, the concentrated nitric acid and the acetic acid carry out nitration reaction, and obtaining the mixed solution of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile and the acetic acid.
Introducing the mixed solution of 2-nitro-4, 5-dibenzyloxy benzyl cyanide and acetic acid collected from the discharge port 13 of the tubular reactor into a third container 14, standing, cooling the third container 14, and setting the temperature to 10 ℃ during crystallization; crystallizing and separating out the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile in acetic acid to obtain a crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, filtering the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, putting the filtered product into an oven for drying, setting the temperature of the oven at 80 ℃, and drying the residual solvent in the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile to obtain 86.6g of a finished product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, wherein the purity of the finished product is 98.9 percent and the yield of the finished product is 94.2 percent through liquid chromatography detection.
The filtered acetic acid solution was recovered again and used as a raw material for the next reaction.
Example 4: adding 209g of acetic acid into the first container 1, slowly adding 69.7g of 3, 4-dibenzyloxy phenylacetonitrile into the first container 1, stirring for 30 minutes to uniformly mix the 3, 4-dibenzyloxy phenylacetonitrile and the acetic acid, and dissolving the 3, 4-dibenzyloxy phenylacetonitrile in the acetic acid to form a first mixture; 78ml of acetic acid was added to the second container 2, 22ml of concentrated nitric acid was slowly added to the second container 2, and the mixture was stirred for 30 minutes to uniformly mix the concentrated nitric acid and the acetic acid, thereby forming a second mixture.
Introducing the first mixture formed in the first container 1 into a first preheating pipe 5 by using a first constant-flow pump 3 to heat the first mixture, wherein the flow rate of the first constant-flow pump 3 is set to be 6.65ml/min, and the heating temperature is set to be 30 ℃; a second mixture formed in the second container 2 is introduced into a second preheating pipe 6 by using a second constant-flow pump 4 to heat the second mixture, the flow rate of the second constant-flow pump 4 is set to be 3.36ml/min, and the heating temperature is set to be 30 ℃; respectively introducing the preheated mixture I and the preheated mixture II into a feed inlet I7 of a T-shaped mixer and a feed inlet II 8 of the T-shaped mixer, and fully mixing the mixture I and the mixture II in a T-shaped mixer 9 to form a mixture III; and introducing the mixture III fully mixed by the T-shaped mixer 9 into a feed inlet 11 of the tubular reactor from a discharge port 10 of the T-shaped mixer, then introducing the mixture III into the tubular reactor 12, carrying out oil bath heating on the tubular reactor 12, setting the oil bath temperature to be 70 ℃, and setting the reaction time to be 30 minutes, so that the 3, 4-dibenzyloxy phenylacetonitrile, the concentrated nitric acid and the acetic acid carry out nitration reaction, and obtaining the mixed solution of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile and the acetic acid.
Introducing the mixed solution of 2-nitro-4, 5-dibenzyloxy benzyl cyanide and acetic acid collected from the discharge port 13 of the tubular reactor into a third container 14, standing, cooling the third container 14, and setting the temperature to be 25 ℃ during crystallization; crystallizing and separating out 2-nitro-4, 5-dibenzyloxy phenylacetonitrile in acetic acid to obtain a crude product of 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, filtering the crude product of 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, putting the filtered product into an oven for drying, wherein the temperature of the oven is set to 70 ℃, and drying the residual solvent in the crude product of 2-nitro-4, 5-dibenzyloxy phenylacetonitrile to obtain a finished product of 74.2g of 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, wherein the purity of the finished product is 98.8 percent and the yield of the finished product is 93.7 percent through liquid chromatography detection.
The filtered acetic acid solution was recovered again and used as a raw material for the next reaction.
Example 5: adding 82g of acetic acid into the first container 1, slowly adding 82.3g of 3, 4-dibenzyloxy phenylacetonitrile into the first container 1, stirring for 40 minutes to uniformly mix the 3, 4-dibenzyloxy phenylacetonitrile and the acetic acid, and dissolving the 3, 4-dibenzyloxy phenylacetonitrile in the acetic acid to form a first mixture; 197ml of acetic acid was added to vessel two 2, 25ml of concentrated nitric acid was slowly added to vessel two 2, and stirred for 40 minutes to uniformly mix the concentrated nitric acid and acetic acid to form mixture two.
Introducing the first mixture formed in the first container 1 into a first preheating pipe 5 by using a first constant-flow pump 3 to heat the first mixture, wherein the flow rate of the first constant-flow pump 3 is set to be 12.96ml/min, and the heating temperature is set to be 40 ℃; a second mixture formed in the second container 2 is introduced into a second preheating pipe 6 by using a second constant-flow pump 4 to heat the second mixture, the flow rate of the second constant-flow pump 4 is set to be 37.04ml/min, and the heating temperature is set to be 40 ℃; respectively introducing the preheated mixture I and the preheated mixture II into a feed inlet I7 of a T-shaped mixer and a feed inlet II 8 of the T-shaped mixer, and fully mixing the mixture I and the mixture II in a T-shaped mixer 9 to form a mixture III; and introducing the mixture III fully mixed by the T-shaped mixer 9 into a feed inlet 11 of the tubular reactor from a discharge port 10 of the T-shaped mixer, then introducing the mixture III into the tubular reactor 12, carrying out oil bath heating on the tubular reactor 12, setting the oil bath temperature to be 90 ℃, and setting the reaction time to be 6 minutes, so that the 3, 4-dibenzyloxy phenylacetonitrile, the concentrated nitric acid and the acetic acid carry out nitration reaction, and obtaining the mixed solution of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile and the acetic acid.
Introducing the mixed solution of 2-nitro-4, 5-dibenzyloxy benzyl cyanide and acetic acid collected from the discharge port 13 of the tubular reactor into a third container 14, standing, cooling the third container 14, and setting the temperature to be 0 ℃ during crystallization; crystallizing and separating out the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile in acetic acid to obtain a crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, filtering the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, putting the filtered product into an oven for drying, setting the temperature of the oven at 70 ℃, and drying the residual solvent in the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile to obtain 88.4g of a finished product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, wherein the purity of the finished product is 98.4 percent and the yield of the finished product is 94.5 percent through liquid chromatography detection.
The filtered acetic acid solution was recovered again and used as a raw material for the next reaction.
Example 6: adding 286g of acetic acid into the first container 1, slowly adding 57.2g of 3, 4-dibenzyloxy phenylacetonitrile into the first container 1, stirring for 10 minutes to uniformly mix the 3, 4-dibenzyloxy phenylacetonitrile and the acetic acid, and dissolving the 3, 4-dibenzyloxy phenylacetonitrile in the acetic acid to form a first mixture; adding 14ml of acetic acid into the second container 2, slowly adding 14ml of concentrated nitric acid into the second container 2, and stirring for 10 minutes to uniformly mix the concentrated nitric acid and the acetic acid to form a second mixture.
Introducing the first mixture formed in the first container 1 into a first preheating pipe 5 by using a first constant-flow pump 3 to heat the first mixture, wherein the flow rate of the first constant-flow pump 3 is set to be 45.43ml/min, and the heating temperature is set to be 20 ℃; a second mixture formed in the second container 2 is introduced into a second preheating pipe 6 by using a second constant-flow pump 4 to heat the second mixture, the flow rate of the second constant-flow pump 4 is set to be 4.58ml/min, and the heating temperature is set to be 20 ℃; respectively introducing the preheated mixture I and the preheated mixture II into a first feeding port 7 of a T-shaped mixer and a second feeding port 8 of the T-shaped mixer, and fully mixing the mixture I and the mixture II in a T-shaped mixer 9 to form a mixture III; and introducing the mixture III fully mixed by the T-shaped mixer 9 into a feed inlet 11 of the tubular reactor from a discharge port 10 of the T-shaped mixer, then introducing the mixture III into the tubular reactor 12, carrying out oil bath heating on the tubular reactor 12, setting the oil bath temperature to be 50 ℃, and setting the reaction time to be 6 minutes, so that the 3, 4-dibenzyloxy phenylacetonitrile, the concentrated nitric acid and the acetic acid carry out nitration reaction, and obtaining the mixed solution of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile and the acetic acid.
Introducing the mixed solution of 2-nitro-4, 5-dibenzyloxy benzyl cyanide and acetic acid collected from a discharge port 13 of the tubular reactor into a third container 14, standing, cooling the third container 14, and setting the temperature to 10 ℃ during crystallization; crystallizing and separating out the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile in acetic acid to obtain a crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, filtering the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, putting the filtered product into a drying device 15 for drying, for example, putting the dried product into an oven for drying, wherein the temperature of the oven is set to 80 ℃, and the residual solvent in the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile is dried to obtain 61.9g of a finished product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, and the finished product has the purity of 98.6 percent and the yield of 95.2 percent through liquid chromatography detection.
The filtered acetic acid solution was recovered again and used as a raw material for the next reaction.
Example 7: this example, which is a comparative example to example 3, was tested for product purity and yield using a prior art tank reactor with the same product starting materials using the work-up procedure described herein.
80.9g of 3, 4-dibenzyloxyphenylacetonitrile and 162g of acetic acid were successively charged into a 500-ml flask equipped with a dropping funnel, a condenser and a stirrer. 29ml of concentrated nitric acid and 117ml of acetic acid were mixed well and added to the dropping funnel.
Setting the oil bath temperature at 70 ℃, stirring, beginning to dropwise add the mixed solution of concentrated nitric acid and acetic acid after dissolving the 3, 4-dibenzyloxy phenylacetonitrile, slowly dropwise adding at the speed of 1d/s to ensure that the reaction heat release is controllable, and finishing the reaction after 40 minutes to obtain the mixed solution of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile.
Cooling and standing the mixed solution of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile at 10 ℃ until crystals are not separated out, and filtering to obtain a crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile. Drying the residual solvent in the crude product to obtain 81.1g of finished 2-nitro-4, 5-dibenzyloxy benzyl cyanide product; the purity of the finished product is 98.7 percent and the yield is 88.2 percent by liquid chromatography detection.
As can be seen from the comparative examples, although the product raw materials used in this example are the same as those used in example 3, the reaction time is long, the purity is low, the yield is low, the temperature rise during the reaction is obvious, and the temperature fluctuation is large.
Example 8: this example, which is a comparative example to example 3, was tested for product purity and yield using a prior art tank reactor with the same product starting material and a prior art post-treatment method.
80.9g of 3, 4-dibenzyloxyphenylacetonitrile and 162g of acetic acid were put in this order into a 500ml flask equipped with a dropping funnel, a condenser and a stirrer. 29ml of concentrated nitric acid and 117ml of acetic acid were mixed uniformly and added to a dropping funnel.
Setting the oil bath temperature at 70 ℃, stirring, beginning to dropwise add the mixed solution of concentrated nitric acid and acetic acid after dissolving the 3, 4-dibenzyloxy phenylacetonitrile, slowly dropwise adding at the speed of 1d/s to ensure that the reaction heat release is controllable, and finishing the reaction after 40 minutes to obtain the mixed solution of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile.
Cooling to room temperature, filtering, and washing with acetic acid and isopropyl ether in sequence to obtain a product, namely a crude product of 2-nitro-4, 5-dibenzyloxy benzyl cyanide; and (3) drying the residual solvent in the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile to obtain 77.5g of the finished product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, wherein the purity of the finished product is 98.6 percent and the yield is 84.3 percent through liquid chromatography detection.
As can be seen from the comparative examples, the used product raw materials are the same, the same process conditions as the prior art are used, and the post-treatment method in the prior art is used, so that the process steps are complex, the washing times are many, and the yield is low; the method reduces the consumption of nitric acid, avoids using a large amount of nitric acid with toxic risk, has controllable reaction heat release and safe process, and is suitable for industrial production.
The embodiments of the present invention have been described in detail with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and it will be apparent to those skilled in the art that several modifications and improvements may be made without departing from the present invention, and these should be construed as falling within the scope of the present invention.
Claims (10)
1. A preparation method of 2-nitro-4, 5-dibenzyloxy benzyl cyanide is characterized by comprising the following steps:
step A: the 3, 4-dibenzyloxy phenylacetonitrile dissolving process comprises the steps of adding acetic acid into a first container (1), slowly adding 3, 4-dibenzyloxy phenylacetonitrile into the acetic acid, stirring to uniformly mix the 3, 4-dibenzyloxy phenylacetonitrile with the acetic acid, and dissolving the 3, 4-dibenzyloxy phenylacetonitrile into the acetic acid to form a first mixture, wherein the mass ratio of the 3, 4-dibenzyloxy phenylacetonitrile to the acetic acid is set to be 1:1-1:5, and the stirring time is set to be 10-40 minutes;
and B: adding acetic acid into the second container (2), slowly adding the concentrated nitric acid into the acetic acid, stirring to uniformly mix the concentrated nitric acid and the acetic acid to form a second mixture, wherein the volume ratio of the concentrated nitric acid to the acetic acid is set to be 1:1-1:8, and the stirring time is set to be 10-40 minutes;
and C: in the preheating process, a first mixture formed in the first container (1) is introduced into a first preheating pipe (5) by using a first constant-flow pump (3) to heat the first mixture, and the heating temperature is set to be 20-40 ℃; a second mixture formed in the second container (2) is introduced into a second preheating pipe (6) by using a second advection pump (4) to heat the second mixture, and the heating temperature is set to be 20-40 ℃; the flow ratio of the liquid in the constant-flow pump I (3) to the liquid in the constant-flow pump II (4) is set to be 10:1-1: 3;
step D: the preheated mixture I and the preheated mixture II are respectively introduced into a mixer inlet I (7) and a mixer inlet II (8) through a mixer mixing process, the mixture I and the mixture II are fully mixed in a mixer (9) to form a mixture III, and the mixer (9) is set to be a T-shaped mixer or a Y-shaped mixer;
step E: in the nitration reaction process, the mixture III fully mixed by the T-shaped mixer (9) is introduced into a feed inlet (11) of the tubular reactor from a discharge outlet (10) of the mixer, and then enters the tubular reactor (12) to heat the tubular reactor (12), the heating mode is set as oil bath heating, the heating temperature is set to be 50-90 ℃, the reaction time is set to be 6-30 minutes, so that the 3, 4-dibenzyloxy phenylacetonitrile, the concentrated nitric acid and the acetic acid are subjected to nitration reaction to obtain 2-nitro-4, 5-dibenzyloxy phenylacetonitrile; the chemical reaction formula is as follows:
step F: a crystallization process, namely introducing a mixed solution of 2-nitro-4, 5-dibenzyloxy phenylacetonitrile and acetic acid collected from a discharge port (13) of the tubular reactor into a third container (14), standing, cooling the third container (14) to crystallize and separate out the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile in the acetic acid to obtain a crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, wherein the crystallization temperature is set to be 0-25 ℃;
step G: filtering and drying, namely filtering the crude product of the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile obtained in the step F, and putting the filtered product into an oven to be dried to obtain the 2-nitro-4, 5-dibenzyloxy phenylacetonitrile, wherein the temperature of the oven is set to be 70-80 ℃;
step H: and D, recycling the acetic acid solution, namely adding the acetic acid solution filtered in the step G into the first container (1) and/or the second container (2) in the step A and/or the step B again to participate in the reaction as a raw material.
2. The process for the preparation of 2-nitro-4, 5-dibenzyloxyphenylacetonitrile according to claim 1, wherein: in the step A, the mass ratio of the 3, 4-dibenzyloxy phenylacetonitrile to the acetic acid is set to be 1:3-1:4, and the stirring time is set to be 20-30 minutes.
3. The process for the preparation of 2-nitro-4, 5-dibenzyloxyphenylacetonitrile according to claim 1, wherein: in the step B, the volume ratio of the concentrated nitric acid to the acetic acid is set to be 1:3-1:5, and the stirring time is set to be 20-40 minutes.
4. The process for the preparation of 2-nitro-4, 5-dibenzyloxyphenylacetonitrile according to claim 1, wherein: and in the step C, the flow ratio of the liquid in the constant-flow pump I (3) to the liquid in the constant-flow pump II (4) is set to be 7:1-3: 1.
5. The process for the preparation of 2-nitro-4, 5-dibenzyloxyphenylacetonitrile according to claim 1, wherein: in the step E, the heating temperature is set to be 60-70 ℃, and the reaction time is set to be 8-10 minutes.
6. The process for the preparation of 2-nitro-4, 5-dibenzyloxyphenylacetonitrile according to claim 1, wherein: in the step F, the temperature is set to be 5-15 ℃ during crystallization.
7. The process for the preparation of any 2-nitro-4, 5-dibenzyloxybenzeneacetonitrile according to claims 1 to 6, wherein: the preparation method is carried out by using a tubular reaction device, the reaction device comprises a first container (1) and a second container (2), the first container (1) is connected with a first preheating pipe (5) through a first advection pump (3), the second container (2) is connected with a second preheating pipe (6) through a second advection pump (4), the first preheating pipe (5) is connected with a first mixer feed inlet (7), the second preheating pipe (6) is connected with a second mixer feed inlet (8), a mixer discharge outlet (10) is connected with a tubular reactor feed inlet (11), a heating device is arranged around the tubular reactor (12), a tubular reactor discharge outlet (13) is connected with a third container (14), a cooling device is arranged around the third container (14), and the reaction device further comprises a drying device (15).
8. The process for preparing 2-nitro-4, 5-dibenzyloxyphenylacetonitrile according to claim 7, wherein: the mixer (9) is a T-shaped mixer or a Y-shaped mixer.
9. The method for preparing 2-nitro-4, 5-dibenzyloxy phenylacetonitrile according to claim 7, wherein: the heating device is set as an oil bath device.
10. The process for preparing 2-nitro-4, 5-dibenzyloxyphenylacetonitrile according to claim 7, wherein: the device is characterized in that the number of the first container (1) and the number of the second container (2) are respectively two, and a first valve (16) and a second valve (17) are respectively arranged between the first container (1) and the second container (2) and the advection pump (3) and the advection pump (4).
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