Method for continuously preparing 2, 4-dichloro-5-isopropoxy phenylhydrazine hydrochloride

Abstract

The invention belongs to the technical field of preparation of oxadiazon intermediates, and particularly discloses a method for continuously preparing 2, 4-dichloro-5-isopropoxy phenylhydrazine hydrochloride. The method comprises the following steps: respectively precooling a 2, 4-dichloro-5-isopropoxy chlorobenzene diazonium salt solution and a stannous chloride aqueous solution, introducing into a microchannel reactor after precooling, mixing, and reacting to obtain the 2, 4-dichloro-5-isopropoxy phenylhydrazine hydrochloride. The mixing effect of the diazonium salt and the reducing agent stannous chloride is enhanced by utilizing a micro-reaction technology, the reaction speed is increased, the mass transfer and heat transfer effects are improved, and the problems of poor heat and mass transfer effects, low production efficiency, uncontrollable reaction process and accumulation of a large amount of diazonium salt in the existing intermittent reaction are solved; and the existing continuous reaction has the problems of high cost and poor stability.

Description

Technical Field

[0001] This invention relates to the field of oxadiazon intermediate preparation technology, and more particularly to a method for the continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride. Background Technology

[0002] Oxalide is a nitrogen-containing heterocyclic herbicide. Under light conditions, this herbicide exhibits excellent weed control. It is widely used in fields of rice, soybeans, cotton, sugarcane, and other crops, as well as in orchards, to control annual grasses and broadleaf weeds such as barnyard grass and Echinochloa crus-galli. Its structural formula is:

[0003] The synthesis of oxadiazon is complex. Its industrial synthesis route mainly uses 2,4-dichlorophenol as a raw material and proceeds through 10 steps of reaction, including esterification, nitration, hydrolysis, etherification, reduction, diazotization, reduction, alkalization, acylation, and cyclization. Among these steps, 2,4-dichloro-5-isopropoxyaniline as a raw material, which is obtained through diazotization and reduction reactions, is the key intermediate in the synthesis of oxadiazon.

[0004] Chinese patent applications CN120757464A and CN1169423A describe the use of sulfite as a reducing agent to reduce diazonium salts. However, diazonium salts are acidic systems, while sulfite is alkaline. Improper pH control can easily lead to side reactions, generating asphalt-like byproducts and reducing yield. Furthermore, concentrated hydrochloric acid is required for reflux to obtain phenylhydrazine hydrochloride, making the process complex and inefficient. A commonly used method for producing reduced diazonium salts involves using stannous chloride as a reducing agent under acidic conditions. The dropping rate needs to be controlled to maintain the reaction temperature between 0 and 10°C. The resulting stannous chloride is then concentrated for recovery. The reaction steps are as follows:

[0005] A cooled stannous chloride solution was used as the substrate, and a diazonium salt solution was slowly added dropwise under low-temperature conditions to initiate a reduction reaction. After the reaction, solid phenylhydrazine hydrochloride was obtained through centrifugation and other operations. The reduction reaction between diazonium salt and stannous chloride is a rapid reaction occurring within seconds, with a large amount of exothermic reaction. When the stirring efficiency is low and the mass transfer effect is poor, insufficient to disperse the generated phenylhydrazine hydrochloride, the reactive diazonium salt will be encapsulated within the generated phenylhydrazine hydrochloride, causing some side reactions. The generated phenylhydrazine hydrochloride is darker in color and has increased viscosity, further hindering the mass transfer process, ultimately leading to low purity and content, poor product selectivity and yield. The yield of batch process production is approximately 80%. Therefore, the mass transfer effect of batch reaction directly affects the reaction selectivity. Simultaneously, batch reaction requires controlling the dropping rate to control the reaction temperature; if the reaction temperature is too high, the reduction reaction yield will decrease. Therefore, the batch batch process has poor heat and mass transfer effects, resulting in low production yield and low production efficiency. Furthermore, the reaction process is uncontrollable, and the accumulation of large amounts of diazonium salt poses a safety hazard.

[0006] Chinese patent CN107663161B discloses a continuous synthesis process for phenylhydrazine hydrochloride, which can continuously prepare phenylhydrazine hydrochloride. However, the residence time is on the order of minutes, resulting in high costs for scale-up production. Moreover, most of the generated phenylhydrazine hydrochloride is solid, which is highly likely to clog the channels and affect the stability of the device during long-term operation.

[0007] To address the aforementioned problems, this invention proposes a method for producing 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride via a continuous reduction reaction using microchannel technology. By enhancing the mass transfer process of the reduction reaction using microchannel technology, the solid dispersion of phenylhydrazine hydrochloride becomes more uniform, the particle size of phenylhydrazine hydrochloride is reduced, the viscosity of the reduced slurry is decreased, clogging of the reaction channels is avoided, and the reaction can be controlled to improve product selectivity and yield. Summary of the Invention

[0008] In view of this, the present invention provides a method for the continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride, to solve the problems of poor heat and mass transfer, low production efficiency, uncontrollable reaction process and large amount of diazonium salt accumulation in existing batch reactions; and the problems of high cost and poor stability in existing continuous reactions.

[0009] To achieve the above objectives, the present invention adopts the following technical solution: A method for the continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride includes the following steps: The solution of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride and the aqueous solution of stannous chloride were precooled separately, and then mixed in a microchannel reactor to react and obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0010] Preferably, the mass fraction of 2,4-dichloro-5-isopropoxyphenyldiazonium chloride in the 2,4-dichloro-5-isopropoxyphenyldiazonium chloride solution is 10-13%. The mass fraction of stannous chloride in the aqueous solution is 30-40%.

[0011] Preferably, the molar ratio of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride to stannous chloride in the microchannel reactor is 1:2 to 2.6.

[0012] Preferably, the pre-cooled temperatures of the 2,4-dichloro-5-isopropoxyphenyl diazonium chloride solution and the stannous chloride aqueous solution are independently -10 to 0°C.

[0013] Preferably, the reaction pressure is 0.3~0.5MPa and the reaction temperature is 0~15℃; The residence time of the reaction in the microchannel reactor is 0.5~1s.

[0014] Preferably, the internal channel diameter of the microchannel reactor is 0.4~0.6mm, the length of the internal channel is 20~50mm, the internal channel is zigzag-shaped, and the outlet channel diameter is 3~5mm.

[0015] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects: 1. This invention utilizes micro-reaction technology to enhance the mixing effect of diazonium salt and reducing agent stannous chloride, greatly improving the reaction rate. After collision, the diazonium salt can react completely, and the generated 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride solid is uniformly dispersed in the reaction solution, reducing viscosity and having a very short residence time, preventing clogging. The generated solid slurry can be directly filtered by the filtration device. The continuous system has low pressure and can operate continuously for a long time with stable pressure.

[0016] 2. In this invention, the raw materials are pre-cooled, and microchannel technology is used to remove the heat of reaction in a timely manner to control the reaction temperature. Microchannels have a huge specific surface area and an extremely short heat conduction path. Microchannels can be directly attached to the heat exchange surface to ensure that heat can be conducted from the heat source to the channel wall with minimal thermal resistance, thereby removing the heat of reaction in a timely manner. This invention can achieve continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride with a high yield.

[0017] 3. The continuous reduction process of this invention is simple, easy to scale up for production, and has great potential for widespread application. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0019] Figure 1 The process flow diagram for the continuous synthesis of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride; Figure 2 This is a schematic diagram of the structure of a microchannel reactor; Figure 3 This is a schematic diagram of the reaction plate structure of a microchannel reactor. Detailed Implementation

[0020] This invention provides a method for the continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride, comprising the following steps: The solution of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride and the aqueous solution of stannous chloride were precooled separately, and then mixed in a microchannel reactor to react and obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0021] In this invention, a filtration step is further included after the reaction is completed, and the specific process flow is as follows: Figure 1 As shown, the Figure 1 Solution A and solution B are 2,4-dichloro-5-isopropoxyphenyl diazonium chloride solution and stannous chloride aqueous solution, respectively, and solution C is the solution after the mixed reaction.

[0022] In this invention, the structural formula of the 2,4-dichloro-5-isopropoxychlorophenyldiazonium salt is as follows: The structural formula of the 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride is as follows: .

[0023] In this invention, the mass fraction of 2,4-dichloro-5-isopropoxyphenyl diazonium salt in the 2,4-dichloro-5-isopropoxyphenyl diazonium salt solution is 10-13%, specifically 10.5%, 11%, 11.5%, 12%, or 12.5%.

[0024] In this invention, the mass fraction of stannous chloride in the aqueous solution is 30-40%, specifically 32%, 34%, 35%, 36%, or 38%.

[0025] In this invention, the molar ratio of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride to stannous chloride in the microchannel reactor is 1:2 to 2.6, preferably 1:2.1 to 2.5, more preferably 1:2.2 to 2.4, and even more preferably 1:2.3.

[0026] In this invention, the temperature of the 2,4-dichloro-5-isopropoxyphenyl diazonium chloride solution and the stannous chloride aqueous solution after pre-cooling is independently -10~0℃, specifically -8℃, -6℃, -5℃, -4℃, -2℃, and -1℃.

[0027] In this invention, the reaction pressure is 0.3~0.5MPa, specifically 0.32MPa, 0.35MPa, 0.38MPa, 0.4MPa, 0.42MPa, 0.45MPa, or 0.48MPa; the reaction temperature is 0~15℃, specifically 2℃, 4℃, 5℃, 6℃, 8℃, 10℃, 12℃, or 14℃.

[0028] In this invention, the residence time of the reaction in the microchannel reactor is 0.5~1s, specifically 0.6s, 0.7s, 0.8s, or 0.9s.

[0029] like Figure 2 As shown, the microchannel reactor of the present invention consists of a reaction plate, a mirror plate, and a heat exchange plate.

[0030] In this invention, the internal channel diameter of the microchannel reactor is 0.4~0.6mm, specifically 0.42mm, 0.45mm, 0.48mm, 0.5mm, 0.52mm, 0.55mm, or 0.58mm; the length of the internal channel is 20~50mm, specifically 25mm, 30mm, 35mm, 40mm, or 45mm; the internal channel is zigzag-shaped, and the outlet channel diameter is 3~5mm, specifically 3.2mm, 3.5mm, 3.8mm, 4mm, 4.2mm, 4.5mm, or 4.8mm.

[0031] In this invention, the structural schematic diagram of the reaction plate of the microchannel reactor is shown below. Figure 3 As shown, it includes an inlet a, an inlet b, an internal channel, and an outlet. The internal channel is in the shape of a broken line, and the included angle between any two adjacent broken lines is preferably 90°. The length of each broken line is preferably 3~4mm, specifically 3.2mm, 3.4mm, 3.5mm, 3.6mm, or 3.8mm.

[0032] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] Schematic diagrams of the microchannel reactors used in all embodiments of the present invention are shown below. Figures 2-3 As shown, the internal channel diameter of the microchannel reactor is 0.5 mm, the internal channel length is 40 mm, the internal channel is in the shape of a broken line, the included angle between each two adjacent broken line segments is 90°, the length of each broken line segment is 4 mm, and the outlet channel diameter is 4 mm.

[0034] Example 1

[0035] A 30% (w / w) stannous chloride aqueous solution was used as feed solution A, and a 10% (w / w) 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride solution was used as feed solution B. Feed solution A and feed solution B were pumped via a horizontal flow pump, and both were pre-cooled to 0°C after passing through a heat exchanger. The molar ratio of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride to stannous chloride was 1:2.6. Cooled feed solution A was continuously fed into a microchannel reactor through inlet a, and cooled feed solution B was continuously fed into the microchannel reactor through inlet b. The two solutions were mixed to obtain reaction liquid C. The reaction temperature was controlled at 15°C and the reaction pressure at 0.5 MPa using the microchannel reactor. The residence time of reaction liquid C in the microchannel reactor was 1 s. The effluent was filtered to obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0036] The conversion rate of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride in the reduction reaction was 100%, and the yield of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride was 85%.

[0037] Example 2

[0038] A 35% (w / w) stannous chloride aqueous solution was used as feed solution A, and a 12% (w / w) 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride solution was used as feed solution B. Feed solution A and feed solution B were pumped via a horizontal flow pump, and both were pre-cooled to -5°C after passing through a heat exchanger. The molar ratio of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride to stannous chloride was 1:2.4. The cooled feed solution A was continuously fed into a microchannel reactor through inlet a, and the cooled feed solution B was continuously fed into the microchannel reactor through inlet b. The two solutions were mixed to obtain reaction liquid C. The reaction temperature was controlled at 10°C and the reaction pressure at 0.5 MPa using the microchannel reactor. The residence time of reaction liquid C in the microchannel reactor was 1 s. The effluent was filtered to obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0039] The conversion rate of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride in the reduction reaction was 100%, and the reaction yield of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride was 87%.

[0040] Example 3

[0041] A 35% (w / w) stannous chloride aqueous solution was used as feed solution A, and a 12% (w / w) 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride solution was used as feed solution B. Feed solution A and feed solution B were pumped via a horizontal flow pump, and both were pre-cooled to -5°C after passing through a heat exchanger. The molar ratio of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride to stannous chloride was 1:2.0. Cooled feed solution A was continuously fed into a microchannel reactor through inlet a, and cooled feed solution B was continuously fed into the microchannel reactor through inlet b. The two solutions were mixed to obtain reaction liquid C. The reaction temperature was controlled at 10°C and the reaction pressure at 0.5 MPa using the microchannel reactor. The residence time of reaction liquid C in the microchannel reactor was 1 s. The effluent was filtered to obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0042] The conversion rate of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride in the reduction reaction was 100%, and the yield of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride was 85%.

[0043] Example 4

[0044] A 40% (w / w) stannous chloride aqueous solution was used as feed solution A, and a 13% (w / w) 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride solution was used as feed solution B. Feed solution A and feed solution B were pumped by a horizontal flow pump, and both were pre-cooled to -5°C after passing through a heat exchanger; the molar ratio of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride to stannous chloride was 1:2.3. The cooled feed solution A was continuously fed into a microchannel reactor through inlet a, and the cooled feed solution B was continuously fed into the microchannel reactor through inlet b. The two solutions were mixed to obtain reaction liquid C. The reaction temperature was controlled at 12°C and the reaction pressure at 0.5 MPa in the microchannel reactor. The residence time of reaction liquid C in the microchannel reactor was 1 s. The effluent was filtered to obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0045] The conversion rate of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride in the reduction reaction was 100%, and the yield of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride was 86%.

[0046] Example 5

[0047] A 40% (w / w) stannous chloride aqueous solution was used as feed solution A, and a 13% (w / w) 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride solution was used as feed solution B. Feed solution A and feed solution B were pumped via a horizontal flow pump, and both were pre-cooled to -10°C after passing through a heat exchanger. The molar ratio of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride to stannous chloride was 1:2.2. The cooled feed solution A was continuously fed into a microchannel reactor through inlet a, and the cooled feed solution B was continuously fed into the microchannel reactor through inlet b. The two solutions were mixed to obtain reaction liquid C. The reaction temperature was controlled at 5°C and the reaction pressure at 0.5 MPa using the microchannel reactor. The residence time of reaction liquid C in the microchannel reactor was 0.5 s. The effluent was filtered to obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0048] The conversion rate of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride in the reduction reaction was 100%, and the reaction yield of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride was 88%.

[0049] Example 6

[0050] A 40% (w / w) stannous chloride aqueous solution was used as feed solution A, and a 13% (w / w) 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride solution was used as feed solution B. Feed solution A and feed solution B were pumped via a horizontal flow pump, and both were pre-cooled to -10°C after passing through a heat exchanger. The molar ratio of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride to stannous chloride was 1:2.2. The cooled feed solution A was continuously fed into a microchannel reactor through inlet a, and the cooled feed solution B was continuously fed into the microchannel reactor through inlet b. The two solutions were mixed to obtain reaction liquid C. The reaction temperature was controlled at 0°C and the reaction pressure at 0.5 MPa using the microchannel reactor. The residence time of reaction liquid C in the microchannel reactor was 0.5 s. The effluent was filtered to obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0051] The conversion rate of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride in the reduction reaction was 100%, and the yield of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride was 89.9%.

[0052] Example 7

[0053] A 40% (w / w) stannous chloride aqueous solution was used as feed solution A, and a 13% (w / w) 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride solution was used as feed solution B. Feed solution A and feed solution B were pumped via a horizontal flow pump, and both were pre-cooled to -10°C after passing through a heat exchanger. The molar ratio of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride to stannous chloride was 1:2.1. The cooled feed solution A was continuously fed into a microchannel reactor through inlet a, and the cooled feed solution B was continuously fed into the microchannel reactor through inlet b. The two solutions were mixed to obtain reaction liquid C. The reaction temperature was controlled at 0°C and the reaction pressure at 0.5 MPa using the microchannel reactor. The residence time of reaction liquid C in the microchannel reactor was 0.5 s. The effluent was filtered to obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

[0054] The conversion rate of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride in the reduction reaction was 100%, and the yield of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride was 89.8%.

[0055] Examples 1-5 fully verified the feasibility of the continuous reduction process, with the highest reduction yield reaching 89.9%. This continuous reduction process significantly shortens the reaction time, has a high degree of automation, and greatly improves production efficiency and product yield.

[0056] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0057] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for the continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride, characterized in that, Includes the following steps: The solution of 2,4-dichloro-5-isopropoxyphenylhydrazine diazonium chloride and the aqueous solution of stannous chloride were precooled separately, and then mixed in a microchannel reactor to react and obtain 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride.

2. The method for continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride according to claim 1, characterized in that, The mass fraction of 2,4-dichloro-5-isopropoxyphenyldiazonium chloride in the 2,4-dichloro-5-isopropoxyphenyldiazonium chloride solution is 10-13%. The mass fraction of stannous chloride in the aqueous solution is 30-40%.

3. The method for continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride according to claim 2, characterized in that, In the microchannel reactor, the molar ratio of 2,4-dichloro-5-isopropoxyphenyl diazonium chloride to stannous chloride is 1:2~2.

6.

4. A method for the continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride according to any one of claims 1 to 3, characterized in that, The pre-cooled temperatures of the 2,4-dichloro-5-isopropoxyphenyl diazonium chloride solution and the stannous chloride aqueous solution are independently -10 to 0°C.

5. The method for continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride according to claim 4, characterized in that, The reaction pressure is 0.3~0.5MPa, and the reaction temperature is 0~15℃; The residence time of the reaction in the microchannel reactor is 0.5~1s.

6. The method for continuous preparation of 2,4-dichloro-5-isopropoxyphenylhydrazine hydrochloride according to claim 5, characterized in that, The internal channel diameter of the microchannel reactor is 0.4~0.6mm, the length of the internal channel is 20~50mm, the internal channel is zigzag-shaped, and the outlet channel diameter is 3~5mm.

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