Synthesis method of carbohydrazide

Abstract

The present invention relates to the technical field of compound synthesis, and in particular to an efficient synthesis method of carbohydrazide, comprising the following steps: (1) preparing a urea aqueous solution, a sodium nitrite aqueous solution, an acid solution, and an alkali solution; (2) simultaneously pumping the urea aqueous solution and the sodium nitrite aqueous solution into a microchannel reactor to mix them uniformly, and then pumping the acid solution into the reactor to carry out a diazotization reaction, wherein the diazotization reaction temperature is lower than 10°C and the reaction residence time is within 5 seconds; (3) then pumping the alkali solution into the reactor below 0°C to make the pH value of the reaction solution alkaline and continuing the reaction in the microchannel reactor, wherein the reaction residence time is within 5 seconds, and collecting a diazonium salt intermediate solution; and (4) adding an alcohol solvent into the diazonium salt intermediate solution, stirring the solution uniformly, adding a metal catalyst, and then introducing hydrogen into the reactor to carry out a hydrogenation catalytic reduction reaction to obtain a crude carbohydrazide product, which is then refined to obtain a pure carbohydrazide product with a yield of more than 90%. The present invention can realize the process of urea diazotization and forming a relatively stable diazonium salt intermediate.

Description

Technical Field

[0001] The present invention relates to the technical field of compound synthesis, and in particular to a high-efficiency synthesis method of carbohydrazide. Background Art

[0002] Carbohydrazide is a white, columnar crystal that absorbs heat when dissolved. It contains 62.18% nitrogen, and its 1% aqueous solution has a pH of 7.4. It is non-hygroscopic and reacts with hydrochloric acid, sulfuric acid, oxalic acid, phosphoric acid, and nitric acid to form salts. At room temperature, carbohydrazide appears as white, short, columnar crystals or a white crystalline powder. It is insoluble in ethanol but highly soluble in water, but absorbs heat when dissolved. It is insoluble in alcohol, ether, and benzene. As a hydrazine derivative, it has strong reducing properties and is non-toxic, making it a suitable alternative to hydrazine hydrate and oximes. It has a wide range of industrial applications, including as a deoxidizer for boiler water in water treatment and as a component of rocket propellant. Because hydrogen atoms attached to nitrogen atoms are easily replaced by other groups, it is also used in the textile industry as a crosslinker for elastic fibers, a formaldehyde scavenger, and an antioxidant for pigments such as carotene. Furthermore, adding an appropriate amount of carbohydrazide to soaps containing phenolic fungicides can prevent discoloration and rancidity.

[0003] As a chemical raw material and chemical intermediate, carbohydrazide is widely used in the pharmaceutical, herbicide, plant growth regulator, dye and other industries, and can be used to synthesize a series of biologically active heterocyclic compounds. The traditional method for synthesizing carbohydrazide is to react phosgene and hydrazine. This method is not only dangerous and pollutes the environment, but also accompanied by the production of an equivalent amount of corrosive byproduct hydrogen chloride. Moreover, the phosgene used is a highly toxic substance that pollutes the environment. The safety operation requirements are very high, which limits the production and development of carbohydrazide products. In the prior art, CN102531970A discloses carbohydrazide and a rapid synthesis method thereof, which is obtained by microwave reaction of dimethyl carbonate, hydrazine hydrate and molecular sieve; CN114031524A discloses a method for synthesizing carbohydrazide, which is synthesized from dimethyl carbonate and excess hydrazine hydrate; CN106674059A discloses a method for synthesizing carbohydrazide, which is obtained by reacting butanone azine and urea at 80-130°C. Summary of the Invention

[0004] The present invention provides an efficient synthesis method of carbohydrazide, and provides a different synthesis strategy for the preparation of carbohydrazide. The present invention uses urea as a raw material, performs a diazotization reaction on the raw material to obtain a diazonium salt intermediate, and then catalytically hydrogenates the raw material to obtain carbohydrazide. The reaction process adopts a microchannel reaction. In the method of the present invention, the raw materials are readily available and inexpensive, and the preparation process is simple and efficient.

[0005] In order to achieve the above objectives, the present invention is implemented through the following technical solutions:

[0006] The efficient synthesis method of carbohydrazide comprises the following steps:

[0007] (1) Prepare urea aqueous solution, sodium nitrite aqueous solution, acid solution, and alkali solution;

[0008] (2) In a microchannel reactor, the urea aqueous solution and the sodium nitrite aqueous solution are simultaneously pumped in and mixed evenly, and then the acid solution is pumped in to carry out a diazotization reaction, wherein the diazotization reaction temperature is lower than 10° C. and the reaction residence time is within 5 s;

[0009] (3) then pumping the alkali solution into the reaction solution at a temperature below 0°C to make the pH of the reaction solution alkaline and continuing the reaction in the microchannel reactor with a reaction residence time of less than 5 seconds, and collecting the diazonium salt intermediate solution;

[0010] (4) Adding an alcohol solvent to the diazonium salt intermediate solution, stirring evenly, adding a metal catalyst, and then introducing hydrogen to carry out a hydrogenation catalytic reduction reaction to obtain a crude carbohydrazide, which is then refined to obtain a pure carbohydrazide.

[0011] Step (2): The equation for generating diazonium salt is as follows,

[0012] CO(NH 2 ) 2 +NaNO 2 +HCl→Cl - N 2 + CON 2 + Cl - +NaCl+H 2 O。

[0013] Step (3): The diazonium salt generated in the above step (2) forms a relatively stable electronic conjugate under alkaline conditions - a diazonium salt intermediate. The diazonium salt intermediate will not decompose to produce nitrogen, carbon dioxide, etc. in a short period of time. The structure of the diazonium salt intermediate is as follows:

[0014] .

[0015] Step (4): The catalytic hydrogenation process is as follows,

[0016] .

[0017] Furthermore, the acid solution is a dilute hydrochloric acid solution, and the concentration of the acid solution is 8-9 mol / L; the alkali solution is one of sodium hydroxide solution, potassium hydroxide solution, sodium carbonate solution, potassium carbonate solution, sodium bicarbonate solution, and potassium bicarbonate solution, and the concentration of the alkali solution is 5-6 mol / L, and the alkali solution is preferably sodium hydroxide solution; the molar concentration of the sodium nitrite aqueous solution is 4.5-5.5 mol / L; the molar concentration of the urea aqueous solution is 2.3-2.8 mol / L.

[0018] Furthermore, the alcohol solvent is methanol and / or ethanol; the metal catalyst is a nickel-based catalyst, preferably activated nickel. Compared with precious metal catalysts such as palladium and platinum, nickel-based catalysts are less expensive and have better catalytic activity.

[0019] Preferably, the temperature of the diazotization reaction in step (2) is 4-6°C, and the reaction residence time is 1-2 seconds; the temperature of the alkali solution when added in step (3) is -2-0°C, and the reaction residence time after adding the alkali solution is less than 1 second; the specific pH value for making the pH of the reaction solution alkaline in step (3) is 7.5-8.5. The diazotization reaction is a highly exothermic reaction and the diazonium salt is unstable. In order to prevent the diazonium salt from decomposing, the present invention provides a relatively stable electron conjugate of the diazonium salt under alkaline conditions and below 0°C to obtain a diazonium salt intermediate.

[0020] Furthermore, the molar ratio of urea in the urea aqueous solution to sodium nitrite in the sodium nitrite aqueous solution is equistochemically equivalent; and a corresponding volume of the alcohol solvent is added to each mole of the diazonium salt intermediate in an amount half the volume of the urea aqueous solution used in the reaction process.

[0021] Furthermore, the flow rate of the urea aqueous solution is 2-3 ml / s, the flow rate of the sodium nitrite aqueous solution is 2-3 ml / s, the flow rate of the acid solution is 2-3 ml / s, and the flow rate of the alkali solution is 2-3 ml / s.

[0022] Furthermore, the temperature of the hydrogenation catalytic reduction reaction in step (4) is 35-40° C., the reaction is carried out under normal pressure, the amount of the metal catalyst used is 14-16% of the molar amount of urea used; and the refining is recrystallization.

[0023] Beneficial technical effects:

[0024] The present invention uses chemical continuous flow intensification technology and a microchannel reactor to obtain a stable carbohydrazide intermediate (diazonium salt intermediate). Specifically, four pumps and three-stage feeding are used to perform a diazotization reaction on urea at low temperature to obtain a diazonium salt. Subsequently, the system is adjusted to be alkaline at a lower temperature so that the diazonium salt forms a stable electron conjugate, thereby obtaining a relatively stable diazonium salt intermediate that does not decompose. The diazonium salt intermediate is then catalytically hydrogenated to obtain a carbohydrazide product. The process of the present invention is simple, and the raw materials are inexpensive and readily available, greatly reducing the manufacturing cost. The present invention can realize the process of urea diazotization and forming a relatively stable diazonium salt intermediate. The product of the present invention has a high carbohydrazide yield of more than 90%, and a high product purity of more than 98.5%. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Schematic diagram of the process for preparing diazonium salt intermediates in a microchannel reactor using four pumps and three-stage feeding. DETAILED DESCRIPTION

[0026] The following will be combined with the embodiments of the present invention and the accompanying drawings to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is in no way intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0027] Unless otherwise specifically stated, the numerical value set forth in these embodiments does not limit the scope of the present invention. Technology and methods known to those of ordinary skill in the relevant art may not be discussed in detail, but in appropriate cases, the technology and methods should be considered as a part of the specification. In all examples shown and discussed here, any specific value should be interpreted as merely exemplary, rather than as a limitation. Therefore, other examples of exemplary embodiments can have different values. Example

[0028] The efficient synthesis method of carbohydrazide comprises the following steps:

[0029] (1) Prepare a 2.5 mol / L urea aqueous solution, a 5 mol / L sodium nitrite aqueous solution, an 8 mol / L dilute hydrochloric acid solution, and a 5 mol / L sodium hydroxide solution;

[0030] (2) In the microchannel reactor, the process is as follows Figure 1As shown, at room temperature, the urea aqueous solution and the sodium nitrite aqueous solution are simultaneously introduced through pump 1 and pump 2 at a rate of 2 ml / s, respectively, and are merged and mixed uniformly; after 2 seconds at 4°C, the dilute hydrochloric acid solution is introduced through pump 3 at a rate of 2.2 ml / s to carry out a diazotization reaction. The diazotization reaction temperature is controlled at 4°C, and the reaction residence time is 1 to 1.5 seconds;

[0031] (3) Then, at 0°C, the dilute sodium hydroxide solution was introduced through pump 4 at a rate of 2.2 ml / s to adjust the pH of the reaction solution to 7.5 and the reaction was continued in the microchannel reactor (the reaction temperature was controlled at 0°C). The reaction residence time was 0.6-1 s, and the diazonium salt intermediate solution was collected;

[0032] The above reaction is a continuous process, and the volume of the collected reaction liquid is calculated at the end;

[0033] (4) Methanol was added to the diazonium salt intermediate solution. A corresponding volume of methanol was added to each mole of diazonium salt intermediate in an amount half the volume of the urea aqueous solution used. After stirring for 5 minutes, the mixture was filtered to remove impurities and transferred to a normal pressure hydrogenation reactor. Raney nickel catalyst was added (the active nickel content in the Raney nickel catalyst was 90 wt%, and a corresponding molar amount of active nickel was added for every 1 mol of urea. The weight of the catalyst used was calculated based on the active nickel. The particle size of the Raney nickel catalyst was <50 μm. If the total amount of urea used in the above diazotization reaction was set to 1 mol, the amount of active nickel used was 0.15 mol, and 9.78 g of Raney nickel catalyst was required). Hydrogen was introduced to replace the air in the reactor. A catalytic hydrogenation reduction reaction was carried out at 40° C. under normal pressure until the reaction stopped absorbing hydrogen. After cooling, the catalyst was filtered out. After removing the solvent (the catalyst and the solvent methanol could be recycled), 82.4 g of pure carbohydrazide was obtained by recrystallization from the aqueous phase with a yield of 90.5 wt%.

[0034] The final product was identified to have a melting point of 153-154°C. The purity of the carbohydrazide product was determined to be 98.9 wt% by perchloric acid titration. Example

[0035] The efficient synthesis method of carbohydrazide comprises the following steps:

[0036] (1) Prepare a 2.5 mol / L urea aqueous solution, a 5 mol / L sodium nitrite aqueous solution, an 8.5 mol / L dilute hydrochloric acid solution, and a 5.5 mol / L sodium hydroxide solution;

[0037] (2) In the microchannel reactor, the process is as follows Figure 1As shown, at room temperature, the urea aqueous solution and the sodium nitrite aqueous solution are simultaneously introduced through pump 1 and pump 2 at a rate of 2 ml / s, respectively, and are merged and mixed uniformly; at 5°C, after 2 seconds, the dilute hydrochloric acid solution is introduced through pump 3 at a rate of 2.4 ml / s to carry out a diazotization reaction. The diazotization reaction temperature is controlled at 5°C, and the reaction residence time is 1-1.5 seconds;

[0038] (3) Then, at -2°C, the dilute sodium hydroxide solution was introduced through pump 4 at a rate of 2.2 ml / s to adjust the pH of the reaction solution to 7.5 and the reaction was continued in the microchannel reactor (the reaction temperature was controlled at -2°C) with a reaction residence time of 0.6 to 1 s, and the diazonium salt intermediate solution was collected;

[0039] The above reaction is a continuous process, and the volume of the collected reaction liquid is calculated at the end;

[0040] (4) Methanol was added to the diazonium salt intermediate solution. A corresponding volume of methanol was added to each mole of diazonium salt intermediate in an amount half the volume of the urea aqueous solution used. After stirring for 5 minutes, the mixture was filtered to remove impurities and transferred to a normal pressure hydrogenation reactor. Raney nickel catalyst was added (the active nickel content in the Raney nickel catalyst was 90 wt%, and a corresponding molar amount of active nickel was added for every 1 mole of urea. The weight of the catalyst used was calculated based on the active nickel. The particle size of the Raney nickel catalyst was <50 μm. If the total amount of urea in the above diazotization reaction was set to 1 mol, the amount of active nickel was 0.155 mol, and 10.1 g of Raney nickel catalyst was required). Hydrogen was introduced to replace the air in the reactor. A catalytic hydrogenation reduction reaction was carried out at 38° C. under normal pressure until the reaction stopped absorbing hydrogen. After cooling, the catalyst was filtered out. After removing the solvent (the catalyst and the solvent methanol could be recycled), 83.5 g of pure carbohydrazide was obtained by recrystallization from the aqueous phase with a yield of 91.9%.

[0041] The final product was identified to have a melting point of 153-154°C; the purity of the carbohydrazide product was determined to be 99.1% by perchloric acid titration. Example

[0042] The efficient synthesis method of carbohydrazide comprises the following steps:

[0043] (1) Prepare a 2.5 mol / L urea aqueous solution, a 5.5 mol / L sodium nitrite aqueous solution, a 9 mol / L dilute hydrochloric acid solution, and a 6 mol / L sodium hydroxide solution;

[0044] (2) In the microchannel reactor, the process is as follows Figure 1As shown, at room temperature, the urea aqueous solution and the sodium nitrite aqueous solution are simultaneously introduced through pump 1 and pump 2 at a rate of 2 ml / s, respectively, and are merged and mixed uniformly; after 2 seconds at 6°C, the dilute hydrochloric acid solution is introduced through pump 3 at a rate of 2.4 ml / s to carry out a diazotization reaction. The diazotization reaction temperature is controlled at 6°C, and the reaction residence time is 1 to 1.5 seconds;

[0045] (3) Then, at -2°C, the dilute sodium hydroxide solution was introduced through pump 4 at a rate of 2.4 ml / s to adjust the pH of the reaction solution to 7.5 and the reaction was continued in the microchannel reactor (the reaction temperature was controlled at -2°C). The reaction residence time was 0.6-1 s, and the diazonium salt intermediate solution was collected. The above reaction was a continuous process, and the volume of the collected reaction solution was finally calculated.

[0046] (4) Ethanol was added to the diazonium salt intermediate solution. A corresponding volume of ethanol was added to each mole of the diazonium salt intermediate in an amount half the volume of the urea aqueous solution used. After stirring for 5 minutes, the mixture was filtered to remove impurities and transferred to a normal pressure hydrogenation reactor. Raney nickel catalyst was added (the active nickel content in the Raney nickel catalyst was 90 wt%, and a corresponding molar amount of active nickel was added for every 1 mole of urea. The weight of the catalyst used was calculated based on the active nickel. The particle size of the Raney nickel catalyst was <50 μm. If the total amount of urea used in the above diazotization reaction was set to 1 mol, the amount of active nickel used was 0.14 mol, and 9.13 g of Raney nickel catalyst was required). Hydrogen was introduced to replace the air in the reactor. A catalytic hydrogenation reduction reaction was carried out at 40° C. under normal pressure until the reaction stopped absorbing hydrogen. After cooling, the catalyst was filtered out. After removing the solvent (the catalyst and the solvent methanol could be recycled), 82.7 g of pure carbohydrazide was obtained by recrystallization from the aqueous phase with a yield of 90.6%.

[0047] The final product was identified to have a melting point of 153-154°C; the purity of the carbohydrazide product was determined to be 98.6% by perchloric acid titration.

[0048] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, who makes equivalent replacements or changes based on the technical solution and inventive concept of the present invention, should be covered by the scope of protection of the present invention.

Claims

1. A method for synthesizing carbohydrazide, characterized in that: The steps include: (1) Prepare urea aqueous solution, sodium nitrite aqueous solution, acid solution, and alkali solution; (2) In a microchannel reactor, the urea aqueous solution and the sodium nitrite aqueous solution are simultaneously pumped in and mixed evenly, and then the acid solution is pumped in to perform a diazotization reaction, wherein the diazotization reaction temperature is lower than 10° C. and the reaction residence time is within 5 s; (3) then pumping the alkali solution into the reaction solution at a temperature below 0° C. to make the pH of the reaction solution alkaline and continuing the reaction in the microchannel reactor with a reaction residence time of less than 5 s, and collecting the obtained diazonium salt intermediate solution; (4) adding an alcohol solvent to the diazonium salt intermediate solution, stirring evenly, adding a metal catalyst, and then introducing hydrogen to carry out a hydrogenation catalytic reduction reaction to obtain a crude carbohydrazide, which is then refined to obtain a pure carbohydrazide.

2. The synthetic method of carbohydrazide according to claim 1, wherein The acid solution is a dilute hydrochloric acid solution, and the concentration of the acid solution is 8-9 mol / L; The alkali solution is one of sodium hydroxide solution, potassium hydroxide solution, sodium carbonate solution, potassium carbonate solution, sodium bicarbonate solution, and potassium bicarbonate solution, and the concentration of the alkali solution is 5-6 mol / L; The molar concentration of the sodium nitrite aqueous solution is 4.5-5.5 mol / L; The molar concentration of the urea aqueous solution is 2.3-2.8 mol / L.

3. The synthetic method of carbohydrazide according to claim 1, wherein The alcohol solvent is methanol and / or ethanol; The metal catalyst is a nickel-based catalyst.

4. The synthetic method of carbohydrazide according to claim 1, wherein The temperature of the diazotization reaction in step (2) is 4-6° C. and the reaction residence time is 1-2 seconds; The temperature of the alkali solution when added in step (3) is -2 to 0°C, and the reaction residence time after adding the alkali solution is within 1 second; The specific pH value for making the pH of the reaction solution alkaline in step (3) is 7.5-8.

5.

5. The synthetic method of carbohydrazide according to claim 1, wherein The molar ratio of urea in the urea aqueous solution to sodium nitrite in the sodium nitrite aqueous solution is equistochemically equivalent; and a corresponding volume of the alcohol solvent is added to each mole of the diazonium salt intermediate in an amount half the volume of the urea aqueous solution used in the reaction process.

6. The synthetic method of carbohydrazide according to claim 1, wherein The flow rate of the urea aqueous solution is 2-3 ml / s, the flow rate of the sodium nitrite aqueous solution is 2-3 ml / s, the flow rate of the acid solution is 2-3 ml / s, and the flow rate of the alkali solution is 2-3 ml / s.

7. The synthetic method of carbohydrazide according to claim 1, wherein The temperature of the hydrogenation catalytic reduction reaction in step (4) is 35-40° C., the reaction is carried out under normal pressure, and the amount of the metal catalyst used is 14-16% of the molar amount of urea used; and the refining is recrystallization.

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