A new process for the preparation of dialkyldipropylamine

Abstract

The application discloses a new preparation method of dialkylpropylenediamine, which comprises the following steps: taking malononitrile as a starting raw material, and performing double alkylation reaction with an alkylating agent in the presence of an alkaline system and an organic solvent to prepare a dialkylmalononitrile intermediate; dissolving the obtained dialkylmalononitrile intermediate in an alcohol solvent, and reducing the cyano group under the conditions of hydrogen pressure and heating with a Raney cobalt as a catalyst; separating the catalyst and removing the solvent after the reaction, and then performing alkaline water vapor distillation purification to obtain the target dialkylpropylenediamine; in the dialkylpropylenediamine molecule, two substituents R1 and R2 on the carbon at position 2 are independently selected from C1-C6 linear alkyl and C5-C6 cycloalkyl. The preparation method of the dialkylpropylenediamine is cheap and easy to obtain raw materials, has few side reactions and low rearrangement impurities, is simple to separate, has low industrialization cost, is green and efficient, and is suitable for large-scale production of various types of dialkylpropylenediamine.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis chemical technology, and in particular to a novel method for preparing dialkylpropylenediamine. Background Technology

[0002] Dialkylpropylenediamine is a high-value organic molecular building block widely used in drug synthesis, agrochemicals, epoxy resin curing agents, and polyamide new materials. Existing industrial preparation routes mainly fall into two categories: 1) high-temperature amination reaction of haloalkanes with propylenediamine; 2) high-temperature reductive amination of polycarbonyl compounds. With continuous technological advancements, the requirements for the preparation methods of dialkylpropylenediamine are becoming increasingly stringent.

[0003] The existing process has significant drawbacks: the reaction temperature is high, the system is prone to carbon chain rearrangement, generating a large number of structurally similar homologous byproducts; isomers and polyalkyl impurities are difficult to separate, the purification process is long and solvent consumption is high; the overall yield is low, the raw material cost is expensive, the investment in high temperature and corrosion resistant equipment is large, the economics of large-scale production are poor, and it is difficult to stably obtain high-purity dialkylpropanediamine products with a purity of over 98%.

[0004] Currently, there is a lack of a synthetic route that uses inexpensive malononitrile as a raw material, has controllable side reactions, is easy to separate, and is suitable for continuous production. Therefore, we propose a new method for preparing dialkylpropanediamine. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a novel method for preparing dialkylpropylenediamine, which is low-cost, low-by-product, easy to purify, suitable for industrial application, and compatible with the synthesis of various target products including symmetrical, asymmetrical, and cycloalkyl-substituted products.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: a novel method for preparing dialkylpropylenediamine, comprising the following steps: S1: Alkylation process: Using malononitrile as the starting material, a dialkylation reaction is carried out with an alkylating agent in an alkaline system and in the presence of an organic solvent to obtain a dialkylmalononitrile intermediate; S2: Hydrogenation reduction process: The dialkyl malononitrile intermediate obtained in S1 is dissolved in an alcohol solvent, and the cyano group is reduced under hydrogen pressure and temperature conditions using Raney cobalt as a catalyst. S3: Purification: After the reaction, the catalyst is separated and the solvent is removed. The product is then purified by alkaline steam distillation to obtain the target dialkylpropanediamine. S4: In the dialkylpropylenediamine molecule, the two substituents R1 and R2 on the 2-carbon position are independently selected from C1~C6 straight-chain alkyl and C5~C6 cycloalkyl.

[0007] As a preferred technical solution of this application, the alkali used in the S1 step alkylation process is selected from at least one of potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, and sodium hydride, and the reaction solvent is acetonitrile.

[0008] As a preferred technical solution of this application, the alkylating agent in the S1 step alkylation process is selected from one of dialkyl sulfate, dialkyl carbonate, and alkyl halide. When preparing asymmetric substitution products, two different alkylating agents are added dropwise in two stages.

[0009] As a preferred technical solution of this application, the process control conditions for the alkylation process in step S1 are as follows: Symmetrical alkyl substitution: Heat the system to 45°C, add the alkylating agent dropwise, and maintain the temperature for 5-6 hours; Cycloalkyl / asymmetric alkyl substitution: First add alkali and reflux for 1 hour to remove hydrogen, then add alkyl halide dropwise, and reflux the reaction for 6-8 hours in total; After the reaction, the inorganic salts of the system were removed by filtration, the acetonitrile was recovered by concentration, the organic phase was extracted with dichloromethane, and the intermediate was obtained by drying and concentration with sodium sulfate.

[0010] As a preferred technical solution of this application, in the S2 step hydrogenation reduction process, ethanol is selected as the alcohol solvent, the amount of solvent added is 8 times the mass of the dialkylmalononitrile intermediate, the amount of Raney cobalt catalyst added is 15% of the mass of the intermediate, the hydrogenation temperature is 50°C, the hydrogen pressure is 1.5 MPa, and the reaction endpoint is monitored by gas chromatography.

[0011] As a preferred technical solution of this application, in the purification step after hydrogenation reduction in step S3, the Raney cobalt catalyst is recovered by filtration, ethanol is removed by vacuum distillation, the concentrated material is added with 5 times the mass of pure water, and the pH of the system is adjusted to ≥13 by 25wt% sodium hydroxide aqueous solution, and then the dialkylpropylenediamine product is collected by steam distillation.

[0012] As a preferred technical solution of this application, the dialkylmalononitrile intermediate obtained in step S1 is first hydrolyzed to prepare dialkylmalonamide, and then the amide is reduced by Raney cobalt catalysis to obtain dialkylmalondiamine.

[0013] As a preferred technical solution of this application, the Raney cobalt catalyst is either Raney cobalt or a cobalt-aluminum alloy dissolved in an alkaline solution.

[0014] Beneficial effects: Compared with the prior art, the present invention provides a new method for preparing dialkylpropylenediamine, which has the following beneficial effects: The new method for preparing dialkylpropylenediamine has the advantage of raw material cost: the starting material malononitrile is a basic chemical product in industrial production, which is inexpensive and significantly reduces production costs compared with traditional carbonyl and halogenated propylenediamine raw materials; Controllable side reactions and high purity: The dialkylation site of malononitrile is fixed at the middle carbon, resulting in very few carbon chain rearrangement side reactions and no large number of isomer impurities; after hydrogenation, only simple alkali treatment and steam distillation are needed to obtain a high-purity product of 98.5%~99.0%, eliminating the need for complex distillation and recrystallization processes. Wide range of substrates: One process is compatible with the synthesis of symmetrical dialkyl, dicyclohexyl, methyl-cyclohexyl asymmetric substitution, and cycloalkane-bridged cyclic malononitrile intermediates, and can prepare a variety of functional diamine products; The hydrogenation conditions are mild and the equipment pressure requirements are low: hydrogenation at medium and low pressures of 1.5MPa and reaction at low temperatures of 50°C reduces the investment in equipment corrosion protection and pressure resistance compared to high-temperature reduction amination; Raney cobalt can be filtered, recycled and reused, resulting in low catalyst consumption; The process is green and easy to industrialize: the solvents acetonitrile and ethanol can be distilled, recovered and recycled, resulting in low emissions of waste, simple operation steps, and suitability for batch reactor-type large-scale production. The single-step yield of intermediates is 80%~93%, and the yield of hydrogenation reduction is 88%~93%. The overall yield is significantly better than the existing high-temperature amination route. Attached Figure Description

[0015] Figure 1 This is a schematic diagram of the overall structure of a novel method for preparing dialkylpropylenediamine according to the present invention. Detailed Implementation

[0016] The technical solution of the present invention will now be clearly and completely described in conjunction with the accompanying drawings and specific embodiments.

[0017] like Figure 1 As shown, a novel method for preparing dialkylpropylenediamine includes the following steps: S1: Alkylation process: Using malononitrile as the starting material, a dialkylation reaction is carried out with an alkylating agent in an alkaline system and in the presence of an organic solvent to obtain a dialkylmalononitrile intermediate; S2: Hydrogenation reduction process: The dialkyl malononitrile intermediate obtained in S1 is dissolved in an alcohol solvent, and the cyano group is reduced under hydrogen pressure and temperature conditions using Raney cobalt as a catalyst. S3: Purification: After the reaction, the catalyst is separated and the solvent is removed. The product is then purified by alkaline steam distillation to obtain the target dialkylpropanediamine. S4: In the dialkylpropylenediamine molecule, the two substituents R1 and R2 on the 2-carbon position are independently selected from C1~C6 straight-chain alkyl and C5~C6 cycloalkyl.

[0018] The alkali used in the S1 step alkylation process is selected from at least one of potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, and sodium hydride, and the reaction solvent is acetonitrile.

[0019] The alkylating agent in the S1 step alkylation process is selected from one of dialkyl sulfate, dialkyl carbonate, or alkyl halide. When preparing asymmetric substitution products, two different alkylating agents are added dropwise in two stages.

[0020] S1 step alkylation process control conditions: Symmetrical alkyl substitution: Heat the system to 45°C, add the alkylating agent dropwise, and maintain the temperature for 5-6 hours; Cycloalkyl / asymmetric alkyl substitution: First add alkali and reflux for 1 hour to remove hydrogen, then add alkyl halide dropwise, and reflux the reaction for 6-8 hours in total; After the reaction, the inorganic salts of the system were removed by filtration, the acetonitrile was recovered by concentration, the organic phase was extracted with dichloromethane, and the intermediate was obtained by drying and concentration with sodium sulfate.

[0021] In the S2 step hydrogenation reduction process, ethanol is selected as the alcohol solvent, and the amount of solvent added is 8 times the mass of the dialkylmalononitrile intermediate. The amount of Raney cobalt catalyst added is 15% of the mass of the intermediate. The hydrogenation temperature is 50°C, the hydrogen pressure is 1.5 MPa, and the reaction endpoint is monitored by gas chromatography.

[0022] In the purification step following hydrogenation reduction in step S3, the Raney cobalt catalyst is recovered by filtration, ethanol is removed by vacuum distillation, the concentrated material is mixed with 5 times its mass of pure water, and the pH of the system is adjusted to ≥13 by 25wt% sodium hydroxide aqueous solution. The dialkylpropylenediamine product is then collected by steam distillation.

[0023] The dialkylmalononitrile intermediate obtained in step S1 is first hydrolyzed to prepare dialkylmalonamide, and then the amide is reduced by hydrogenation using Raney cobalt catalysis to obtain dialkylmalonamide.

[0024] The Raney cobalt catalyst is either Raney cobalt or a cobalt-aluminum alloy dissolved in an alkaline solution.

[0025] A novel method for preparing dialkylpropylenediamine comprises two core steps: Step 1: Dialkylation of malononitrile to prepare dialkylmalononitrile intermediate; Step 2: Dialkylmalononitrile cyano group is hydrogenated to obtain dialkylpropanediamine; Alternatively, a derivative process can be used: the dialkylmalononitrile obtained in step one is first hydrolyzed to generate dialkylmalonamide, and then hydrogenated and reduced to obtain the target dialkylmalondiamine.

[0026] Step 1: Dialkylation Reaction Operation Using malononitrile as the raw material and acetonitrile as the reaction solvent, an inorganic / organic base was added to construct a dehydrogenation system. The alkylating agent was added dropwise under controlled temperature, and the reaction was maintained at this temperature to complete the di-substitution. After the reaction was completed, the mixture was filtered to remove salt, concentrated to recover the solvent, extracted with dichloromethane, washed with water, dried, and concentrated to obtain a high-purity dialkylmalononitrile oily intermediate.

[0027] The substituents R1 and R2 are independently selected from C1-C6 straight-chain alkyl and C5-C6 cycloalkyl, and R1 and R2 may be the same or different; dialkyl, bicycloalkyl, and alkyl-cycloalkyl asymmetric substitution can be achieved.

[0028] Step 2: High-pressure hydrogenation reduction of Raney cobalt Dialkylmalondinitrile intermediates were dissolved in ethanol, and Raney cobalt hydrogenation catalyst was added. After hydrogen purging in a high-pressure reactor, cyano reduction was carried out at a controlled temperature of 50°C and a hydrogen pressure of 1.5 MPa. After the reaction was completed by GC online monitoring, Raney cobalt was recovered by filtration, and ethanol was removed under reduced pressure. The concentrated residue was added to water, and the pH was adjusted to ≥13 with 25% NaOH aqueous solution. High-purity dialkylmalondiamine was obtained by steam distillation.

[0029] Example 1 (Dimethylmalononitrile) Malononitrile and potassium carbonate were added to 600 ml of acetonitrile. The mixture was heated to a certain temperature, and dimethyl sulfate was added dropwise with stirring. The reaction was maintained at this temperature for 5-6 hours. After the reaction was complete, the temperature was lowered, the mixture was filtered, and the supernatant was concentrated to recover the acetonitrile. The residue was added to 300 ml of dichloromethane and 100 ml of water, and allowed to stand to separate into layers. The organic layer was dried over sodium sulfate and concentrated to a light yellow oily target product, with a yield of 93%.

[0030] Example 2 (Diethylmalononitrile) The conditions and processing were the same as in Example 1, except that dimethyl sulfate was replaced with diethyl sulfate in Example 1, with a yield of 91%.

[0031] Example 3 (Dicyclohexylmalononitrile) Malononitrile was added to 600 ml of acetonitrile, and a 30% methanol solution of sodium methoxide was added dropwise while stirring. The system was kept under slight reflux. After the addition was complete, the reaction continued for 1.0 h. Bromocyclohexane was then added dropwise, and the reaction was refluxed for eight hours after the addition was complete. The mixture was cooled to room temperature, and the precipitated salt was filtered out. The filtrate was concentrated, and 500 ml of dichloromethane and 200 ml of water were added. The mixture was allowed to stand and separate into layers. The organic layer was dried over sodium sulfate and concentrated to a light yellow oily target product, with a yield of 91%.

[0032] Example 4 (Methylcyclohexylmalononitrile) Malononitrile and potassium carbonate were added to 600 ml of acetonitrile. The mixture was heated to a certain temperature, and dimethyl sulfate was added dropwise with stirring. The reaction was maintained at this temperature for 2 hours. A 30% methanol solution of sodium methoxide was added in one go, followed by the dropwise addition of bromocyclohexane. After the addition was complete, the mixture was refluxed for 6 hours. After the reaction was completed, the temperature was lowered to a certain level, and the mixture was filtered. The supernatant was concentrated to recover the acetonitrile. The residue was added to 300 ml of dichloromethane and 100 ml of water, and allowed to stand to separate into layers. The organic layer was dried over sodium sulfate and concentrated to a light yellow oily target product, with a yield of 86%.

[0033] Example 5 (2,2-Butylmalononitrile) Malononitrile was added to 600 ml of acetonitrile, and a 30% methanol solution of sodium methoxide was added dropwise while stirring. The system was kept under slight reflux, and the reaction was continued for 1.0 h after the addition was complete. Then, 1,4-dibromobutane was added dropwise, and the reaction was refluxed for eight hours after the addition was complete. The mixture was cooled to room temperature, and the precipitated salt was filtered out. The filtrate was concentrated, and 400 ml of dichloromethane and 150 ml of water were added. The mixture was allowed to stand and separate into layers. The organic layer was dried over sodium sulfate and concentrated to a light yellow oily target product, with a yield of 80%.

[0034] Example 6 (Hydrogenation Reduction): The substituted dinitrile product obtained above was dissolved in 8 times its mass of an alcohol solvent (preferably ethanol), and 15% by mass of Raney cobalt catalyst was added (this catalyst can be prepared by conventional methods or purchased commercially). After vacuum displacement, the temperature was raised to 50°C. The reaction was carried out at -60℃ with hydrogen gas introduced to a pressure of 1.5 MPa. This pressure was maintained throughout the reaction, and samples were taken for GC monitoring to track the reaction progress. After the reaction, the catalyst was separated by filtration, and the solvent was distilled off under reduced pressure. The concentrate was added to 5 times its mass of water, and the pH was adjusted to ≥13 with a 25% sodium hydroxide aqueous solution. Subsequent steam distillation yielded the product. The results are summarized in the table below:

[0035] Working principle: The core of this invention is a two-stage reaction logic: Alkylation stage: A strong base abstracts an active hydrogen from the middle carbon of malononitrile to generate a carbanion, which attacks the alkylating agent to undergo nucleophilic substitution, completing dialkylation step by step, precisely controlling the disubstituted sites, and avoiding the generation of monosubstituted and polyalkyl impurities; the asymmetric substitution products are synthesized through staged feeding. Hydrogenation reduction stage: Raney cobalt selectively reduces cyano groups (-CN) to primary amines (-CH2NH2) under medium temperature and medium pressure hydrogen atmosphere without dealkylation or carbon chain breaking side reactions; after hydrogenation, a strong base is used to adjust the pH to a high level to neutralize the acidic salts bound to the amino group, and steam distillation is used to achieve rapid separation from inorganic salts and high-boiling-point impurities by utilizing the volatility of amines. In the derivatized hydrolysis hydrogenation route, the cyano group is first hydrolyzed to an amide, and Raney cobalt simultaneously reduces the amide carbonyl group and the cyano group, ultimately generating the target diamine product, thus expanding the process adaptability to different raw material pretreatment scenarios. The above describes and illustrates the basic principles, main features, and advantages of this invention. Those skilled in the art should understand that this invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made without departing from the spirit and scope of this invention, and all such changes and modifications fall within the scope of the invention as claimed.

Claims

1. A novel method for preparing dialkylpropylenediamine, characterized in that: The following steps are included: S1: Alkylation process: Using malononitrile as the starting material, a dialkylation reaction is carried out with an alkylating agent in an alkaline system and in the presence of an organic solvent to obtain a dialkylmalononitrile intermediate; S2: Hydrogenation reduction process: The dialkyl malononitrile intermediate obtained in S1 is dissolved in an alcohol solvent, and the cyano group is reduced under hydrogen pressure and temperature conditions using Raney cobalt as a catalyst. S3: Purification: After the reaction, the catalyst is separated and the solvent is removed. The product is then purified by alkaline steam distillation to obtain the target dialkylpropanediamine. S4: In the dialkylpropylenediamine molecule, the two substituents R1 and R2 on the 2-carbon position are independently selected from C1~C6 straight-chain alkyl and C5~C6 cycloalkyl.

2. The method for preparing a novel dialkylpropylenediamine according to claim 1, characterized in that: The alkali used in the alkylation step S1 is selected from at least one of potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, and sodium hydride, and the reaction solvent is acetonitrile.

3. The method for preparing a novel dialkylpropylenediamine according to claim 1, characterized in that: The alkylating agent in the S1 step alkylation process is selected from one of dialkyl sulfate, dialkyl carbonate, and alkyl halide. When preparing asymmetric substitution products, two different alkylating agents are added dropwise in two stages.

4. The method for preparing a novel dialkylpropylenediamine according to claim 1, characterized in that: Process control conditions for the alkylation process in step S1: Symmetrical alkyl substitution: Heat the system to 45°C, add the alkylating agent dropwise, and maintain the temperature for 5-6 hours; Cycloalkyl / asymmetric alkyl substitution: First add alkali and reflux for 1 hour to remove hydrogen, then add alkyl halide dropwise, and reflux the reaction for 6-8 hours in total; After the reaction, the inorganic salts of the system were removed by filtration, the acetonitrile was recovered by concentration, the organic phase was extracted with dichloromethane, and the intermediate was obtained by drying and concentration with sodium sulfate.

5. The method for preparing a novel dialkylpropylenediamine according to claim 1, characterized in that: In the S2 step of hydrogenation reduction, ethanol is selected as the alcohol solvent, and the amount of solvent added is 8 times the mass of the dialkylmalononitrile intermediate. The amount of Raney cobalt catalyst added is 15% of the mass of the intermediate. The hydrogenation temperature is 50°C, the hydrogen pressure is 1.5 MPa, and the reaction endpoint is monitored by gas chromatography.

6. The method for preparing a novel dialkylpropylenediamine according to claim 1, characterized in that: In the purification step following hydrogenation reduction in step S3, the Raney cobalt catalyst is recovered by filtration, ethanol is removed by vacuum distillation, the concentrated material is mixed with 5 times its mass of pure water, and the pH of the system is adjusted to ≥13 by 25wt% sodium hydroxide aqueous solution. The dialkylpropylenediamine product is then collected by steam distillation.

7. The method for preparing a novel dialkylpropylenediamine according to claim 1, characterized in that: The dialkylmalononitrile intermediate obtained in step S1 is first hydrolyzed to prepare dialkylmalonamide, and then the amide is reduced by hydrogenation using Raney cobalt catalysis to obtain dialkylmalonamide.

8. The method for preparing a novel dialkylpropylenediamine according to claim 1, characterized in that: The Raney cobalt catalyst is either Raney cobalt or a cobalt-aluminum alloy dissolved in an alkaline solution.

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