Preparation method of N-cyano alkyl substituted lactam

Abstract

The invention provides a preparation method of N-cyano alkyl substituted lactam, which comprises the following steps: dissolving lactam in an organic amine medium with a specific alkaline dissociation constant and melting-boiling point to form a solution, adding alpha, beta-unsaturated nitrile into the organic amine medium solution of lactam, and recovering the organic amine medium after the reaction is finished to obtain the N-cyano alkyl substituted lactam. The alkaline dissociation constant of the organic amine medium at normal temperature is 3.0-4.2, and the melting point of the organic amine medium is less than or equal to 0 DEG C and the boiling point of the organic amine medium is greater than or equal to 45 DEG C under the conditions of 0 DEG C and 101.3 kPa. Based on this, the method can not only avoid generation of impurity salts due to additional addition of alkaline substances, but also can effectively inhibit alpha, beta, beta, beta, beta, beta, beta, beta, beta-beta, beta-beta, beta-beta, beta-beta, beta-beta, beta-beta, beta-beta, beta and the conversion rate of lactam and the yield of the product are improved due to the occurrence of the self-polymerization reaction of beta, beta-unsaturated nitrile.

Description

Technical Field

[0001] The invention relates to the technical field of synthesis of lactam derivatives, and specifically provides a method for preparing N-cyanoalkyl substituted lactam. Background Art

[0002] The addition reaction of lactam with α, β-unsaturated nitrile is often used to prepare N-cyanoalkyl substituted lactam. N-cyanoalkyl substituted lactam can be hydrogenated to obtain N-aminoalkyl substituted lactam, which can be further dehydrated to obtain diazabicyclic compounds and their derivatives with the following structure: ; However, the addition reaction of lactam with α, β-unsaturated nitrile usually encounters problems such as low conversion rate, low yield and more by-products caused by the self-polymerization of α, β-unsaturated nitrile reaction. Chinese invention patent CN1268627C discloses a method for preparing 1,8-diazabicyclo[5.4.0]undec-7-ene, wherein in the addition reaction of caprolactam and acrylonitrile, the conversion rate calculated by caprolactam is 96-99%, and the yield of the intermediate product N-cyanoethyl caprolactam (calculated by caprolactam) is only 89-93%. Since acrylonitrile is easily polymerized above 50°C to produce by-products, Chinese invention patent CN117327014A proposes a method of using Lewis acid catalyst to activate the carbon-carbon double bond of acrylonitrile, thereby reducing the reaction temperature and reducing the side reaction of acrylonitrile self-polymerization. However, commonly used and easily available Lewis acids, such as aluminum chloride and zinc chloride, usually have low solubility in organic solvents, and the alkaline catalyst added during the reaction will react with the Lewis acid and even form insoluble substances, making it difficult to give full play to the expected catalytic effect of the Lewis acid, so the technical solution has certain problems in terms of feasibility. In addition, adding an inhibitor to the reaction system can inhibit the side reaction of acrylonitrile self-polymerization. Commonly used inhibitors can be selected from 4-methoxyphenol, hydroquinone, etc., but these inhibitors will form organic-inorganic salts when encountering alkaline catalysts such as sodium hydroxide in the reaction. If a large amount of inhibitors are used, coking and other phenomena often occur in the reactor in the subsequent reaction process, requiring frequent cleaning, reducing production efficiency, and having an adverse effect on product separation and purification.

[0003] Therefore, the art needs a new method for preparing N-cyanoalkyl substituted lactam to solve the above technical problems. Summary of the invention

[0004] In view of the deficiencies in the prior art, the present invention discloses a method for preparing N-cyanoalkyl substituted lactam to solve the above problems existing in the prior art, that is, to solve the problems in the prior art that the addition reaction of lactam with α, β-unsaturated nitrile has low conversion rate and low yield, and more by-products are caused by the self-polymerization of the α, β-unsaturated nitrile reaction.

[0005] In order to achieve the above technical objectives, the present invention provides a method for preparing N-cyanoalkyl substituted lactam: an α, β-unsaturated nitrile and a lactam are subjected to an addition reaction to obtain a product, N-cyanoalkyl substituted lactam, an organic amine medium is added to the addition reaction, and the alkaline dissociation constant of the organic amine medium at room temperature is 3.0-4.2.

[0006] In the above technical scheme, the present invention is based on a large number of experimental studies, and it is found that organic amine has certain alkalinity, which can play a catalytic role in this reaction, promote the reaction of lactam and α, beta-unsaturated nitrile, improve conversion rate and yield, and secondly, under the conditions of the present invention, the self-polymerization of α, beta-unsaturated nitrile that may occur is a free radical mechanism, which can be more significantly occurred in hydrocarbon solvents such as benzene, toluene, dimethylbenzene used in the prior art, and the organic amine limited by the present invention contains a hydrogen atom directly connected to the nitrogen atom in its molecule, and it has a certain active hydrogen atom in addition to the unpaired electron on the nitrogen atom, which can suppress the generation of free radicals and combine to generate oligomeric by-products, and has no influence on the reaction of lactam and unsaturated nitrile belonging to the electrophilic-nucleophilic mechanism. Therefore, in the addition reaction of the prior art route, an organic amine medium with a specific alkaline dissociation constant is added, which improves the conversion rate and yield of the product, and suppresses the generation of the self-polymerization side reaction of α, beta-unsaturated nitrile simultaneously.

[0007] The examples of the present invention further illustrate the optimization process of the alkaline dissociation constant of organic amines, which is preferably 3.2-3.6.

[0008] In order to improve the selectivity, stability and solvent performance of the reaction, further, the organic amine medium has a melting point of ≤0°C and a boiling point of ≥45°C under the conditions of 0°C and 101.3 kPa.

[0009] Furthermore, the organic amine medium is at least one of a primary amine and a secondary amine. The organic amine mediator includes compounds having the following general formula: NHQR; wherein Q is selected from any one of a hydrogen atom and an alkyl group having 1 to 3 carbon atoms, and R is selected from any one of an alkyl group having 2 to 6 carbon atoms or an oxygen-containing alkyl group, Preferably, Q is selected from any one of a hydrogen atom, a methyl group, an ethyl group, and a n-propyl group, and R is selected from any one of an ethyl group, an n-propyl group, an n-butyl group, an isobutyl group, a tert-butyl group, a cyclohexyl group, and a 2-hydroxypropyl group. The embodiment of the present invention further illustrates the optimization process of the organic amine medium. Optionally, the organic amine medium is any one of n-propylamine, n-butylamine, isobutylamine, tert-butylamine, ethylenediamine, cyclohexylamine or n-hexylamine, and any one of n-butylamine or isobutylamine is further preferred.

[0010] Furthermore, the lactam is a compound having the following general formula: ; Wherein, n is 1-9, and the embodiment of the present invention further illustrates the optimization process of lactam. Optionally, n is 2-8, and more preferably 3-7.

[0011] Furthermore, the α,β-unsaturated nitrile is a compound having the following general formula: ; Among them, U, T, and V are selected from any one of a hydrogen atom and a methyl group.

[0012] Specifically, the preparation method of the N-cyanoalkyl substituted lactam comprises the following specific steps: Step (1): dissolving lactam in an organic amine medium to form a solution; Step (2): adding the α,β-unsaturated nitrile to the organic amine medium solution of the lactam and stirring; Step (3): After no obvious heat release occurs, the reaction is completed, and the organic amine medium is recovered and further separated to obtain the N-cyanoalkyl substituted lactam.

[0013] Furthermore, the embodiment of the present invention further illustrates the optimization process of the stirring temperature of step (2), wherein the stirring temperature of step (2) is 0-40°C, preferably 0-30°C, and more preferably 0-10°C.

[0014] Furthermore, the embodiment of the present invention further illustrates the optimization process of the molar ratio of lactam to α, β-unsaturated nitrile in step (2), wherein the molar ratio of lactam to α, β-unsaturated nitrile in step (2) is 1:(1-2), preferably 1:(1.05-1.5), more preferably 1:(1.1-1.4), and more preferably 1:(1.2-1.3).

[0015] Furthermore, the α,β-unsaturated nitrile in step (2) can be added dropwise or all at once.

[0016] Furthermore, the ratio of lactam to organic amine medium in the two feeding methods is different. Optionally, when the α, β-unsaturated nitrile is added dropwise, the mass ratio of lactam to organic amine medium is 1: (1-10), preferably 1: (1-5), and more preferably 1: (1-2); or when the α, β-unsaturated nitrile is added all at once, the mass ratio of lactam to organic amine medium is 1: (5-20), preferably 1: (8-15), and more preferably 1: (9-12). In the two feeding methods, the temperature rise of the reaction system is controlled at ≤ 2°C, preferably ≤ 1°C, and more preferably ≤ 0.5°C.

[0017] Furthermore, the organic amine medium can be recycled and reused after the reaction is completed, and the recycling method can be selected from any one of distillation, vacuum distillation, and crystallization.

[0018] Compared with the prior art, the invention has the following beneficial effects: the invention provides a method for preparing N-cyanoalkyl substituted lactam, wherein an organic amine medium having a specific alkaline dissociation constant and a melting point is added to α, β-unsaturated nitrile and lactam to carry out an addition reaction to obtain the product N-cyanoalkyl substituted lactam; the preparation method improves the conversion rate of lactam raw materials and the selectivity of N-cyanoalkyl substituted lactam products, inhibits the self-polymerization side reaction of α, β-unsaturated nitrile, improves the utilization rate of raw materials, and improves the convenience of post-treatment of the reaction system. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The preferred embodiments of the present invention are described below in conjunction with the accompanying drawings to further understand the technical solution of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention. In the accompanying drawings: Figure 1 This is a gas chromatogram of the product N-cyanoethyl caprolactam of Example 1.3 of the present invention; Figure 2 This is a liquid chromatography-mass spectrometry spectrum of N-cyanoethyl caprolactam, the product of Example 1.3 of the present invention; Figure 3 This is a liquid chromatography-mass spectrometry spectrum of N-cyanoethyl caprolactam, the product of Comparative Example 1 of the present invention. DETAILED DESCRIPTION

[0020] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0021] In order to facilitate the understanding of the present invention, the present invention will be described more comprehensively below, and preferred embodiments of the present invention are given. However, it should be understood that these embodiments are only used for more detailed description and should not be understood as limiting the present invention in any form, that is, not limiting the scope of protection of the present invention.

[0022] Gas chromatography detection conditions Injection volume 0.4 μL, injector temperature 240°C, column flow 2.3 mL / min, purge flow 3 mL / min, split ratio 50, column oven temperature program 150°C (5 min) - gradient temperature increase (15 min) ~ 300°C (5 min), sampling rate 40 ms, sampling time 25 min, tail gas flow 24 mL / min, flame ionization detector used, hydrogen flow 32 mL / min, air flow 200 mL / min.

[0023] Liquid chromatography-mass spectrometry chromatographic detection conditions The chromatographic column was hypersil GOLD, 100×2.1, the mobile phase was pure acetonitrile, 0.3 mL / min, the column temperature was 40°C, the injection volume was 5 μL, the mass spectrometry ionization mode was ESI, the mass spectrometry was an Orbitrap mass analyzer, the mass voltage was 3.8 kV, the ion source temperature was 350°C, and the scanning range was 150-2000.

[0024] Example 1 (Changing the type of lactam) Add a certain amount of lactam into a 500 mL reactor, add 200 g of n-butylamine (melting point -49 °C, boiling point 78 °C, pK b =3.36), under the condition of controlling the stirring rate at 300rpm, 58.3g (1.1mol) of acrylonitrile was added dropwise into the reactor at a rate of 1g / min, and a jacket circulation cooling system with active cooling function was used to automatically control the temperature of the material in the reactor with 5℃ as the target value to remove the reaction heat. After the addition was completed, stirring was continued for 10min, and samples were taken for gas chromatography analysis.

[0025] The effects of different lactams on product conversion and yield are shown in Table 1: Table 1

[0026] As shown in Table 1, different lactams have higher conversion rates and product yields. When the lactam is caprolactam, the conversion rate and yield are the highest. The gas chromatogram and liquid chromatography-mass spectrometry spectra are as follows: Figure 1 and Figure 2 As shown, Figure 1The peak with a retention time of 2.324 min is the chromatographic peak of residual unreacted caprolactam; the peak with a retention time of 6.427 min is the chromatographic peak of N-cyanoethyl caprolactam generated by the reaction of caprolactam and acrylonitrile.

[0027] Example 2 (Changing the Type of Unsaturated Nitrile) Add 113 g of caprolactam (1 mol) and 200 g of n-butylamine (melting point -49 °C, boiling point 78 °C, pK b =3.36), under the condition of controlling the stirring rate at 300rpm, a certain mass of unsaturated nitrile was added dropwise into the reactor at a rate of 1g / min, and a jacket circulation cooling system with active cooling function was used to automatically control the temperature of the material in the reactor with 5°C as the target value to remove the reaction heat. After the addition was completed, stirring was continued for 10min, and samples were taken for gas chromatography analysis.

[0028] The effects of different unsaturated nitriles on product conversion and yield are shown in Table 2: Table 2

[0029] As shown in Table 2, different types of unsaturated nitrile have higher conversion rate and product yield. When the unsaturated nitrile is 2-methyl-2-butenenitrile, the conversion rate is 99.3% and the product yield is 99.1%.

[0030] Example 3 (Changing the reaction temperature) Add 113 g of caprolactam (1 mol) and 200 g of n-butylamine (melting point -49 °C, boiling point 78 °C, pK b =3.36), under the condition of controlling the stirring rate at 300rpm, 58.3g (1.1mol) of acrylonitrile was added dropwise into the reactor at a rate of 1g / min, and a jacket circulation cooling system with active cooling function was used to automatically control the temperature of the material in the reactor as a specific target value to remove the reaction heat. After the addition was completed, stirring was continued for 10min, and samples were taken for gas chromatography analysis.

[0031] The effects of different reaction temperatures on product conversion and yield are shown in Table 3: Table 3

[0032] As shown in Table 3, when the reaction temperature is in the range of 0-40°C, it has a higher conversion rate and product yield. When the reaction temperature is 0-10°C, the conversion rate and product yield are optimal; when the reaction temperature exceeds 40°C (Example 3.5, Example 3.6), the conversion rate and product yield are reduced.

[0033] Example 4 (Changing the Type of Organic Amine Medium) 113 g of caprolactam (1 mol) and 200 g of a specific type of organic amine were added to a reactor with a volume of 500 mL. Under the condition of controlling the stirring rate at 300 rpm, 58.3 g of acrylonitrile (1.1 mol) was added dropwise to the reactor at a rate of 1 g / min. A jacket circulation cooling system with an active cooling function was used to automatically control the temperature of the material in the reactor at 10°C to remove the reaction heat. After the addition was completed, stirring was continued for 10 minutes, and samples were taken for gas chromatography analysis.

[0034] The effects of different organic amine media on product conversion and yield are shown in Table 4: Table 4

[0035] As shown in Table 4, when the organic amine medium is n-propylamine, isobutylamine, tert-butylamine, cyclohexylamine, n-hexylamine and ethylenediamine, high conversion rate and high product yield are achieved.

[0036] Example 5 (Changing the amount of acrylonitrile) Add 113 g of caprolactam (1 mol) and 200 g of n-butylamine (melting point -49 °C, boiling point 78 °C, pK b =3.36), under the condition of controlling the stirring rate at 300rpm, a specific mass of acrylonitrile was added to the reactor at a rate of 1g / min, and the temperature of the material in the reactor was automatically controlled at 5°C using a jacket circulation cooling system with an active cooling function to remove the reaction heat. After the addition was completed, stirring was continued for 10min, and samples were taken for gas chromatography analysis.

[0037] The effects of different acrylonitrile dosages on product conversion and yield are shown in Table 5: Table 5

[0038] As shown in Table 5, when the molar ratio of caprolactam to acrylonitrile is in the range of 1:1-1.5, there is no significant difference in conversion rate and product yield, and both are relatively high. When the ratio of unsaturated nitrile is 1:1.01 (Example 5.5), the reaction effect (conversion rate, yield) is deteriorated.

[0039] Example 6 (Acrylonitrile Dropwise Addition) Add 113 g of caprolactam (1 mol) and a certain amount of n-butylamine (melting point -49 °C, boiling point 78 °C, pK b=3.36), 58.3 g of acrylonitrile (1.1 mol) was added dropwise under the condition of controlling the stirring rate at 300 rpm. During this period, a jacket circulation cooling system with active cooling function was used to automatically control the temperature of the material in the kettle at 5°C to remove the reaction heat. After the addition was completed, stirring was continued for 10 minutes, and samples were taken for gas chromatography analysis.

[0040] When acrylonitrile was added dropwise, the effects of different amounts of n-butylamine on product conversion and yield were shown in Table 6: Table 6

[0041] As shown in the results of Table 6, when the acrylonitrile is added dropwise and the mass ratio of caprolactam to n-butylamine is 1:(1-2), the product has a higher conversion rate and product yield.

[0042] Example 7 (Acrylonitrile is added all at once) Add 22.6 g of caprolactam (0.2 mol) and a certain amount of n-butylamine (melting point -49 °C, boiling point 78 °C, pK b =3.36), under the condition of controlling the stirring rate at 300rpm, 15.9g acrylonitrile (0.3mol) was added all at once. During this period, a jacket circulation cooling system with active cooling function was used to automatically control the temperature of the material in the kettle at 5℃ to remove the reaction heat. After the addition was completed, stirring was continued for 10min, and samples were taken for gas chromatography analysis.

[0043] When acrylonitrile is added all at once, the effects of different amounts of n-butylamine on product conversion and yield are shown in Table 7: Table 7

[0044] As shown in the results of Table 7, when the acrylonitrile is added all at once and the mass ratio of caprolactam to n-butylamine is 1:8-13, the product has a higher conversion rate and product yield.

[0045] Example 8 (Precision of Temperature Control) Add 113 g of caprolactam (1 mol) and 200 g of n-butylamine (melting point -49 °C, boiling point 78 °C, pK b=3.36), under the condition of controlling the stirring rate at 300rpm, 58.3g of acrylonitrile (1.1mol) was added dropwise to the reactor at a rate of 1g / min or in a one-time addition manner, and a jacket circulation cooling system with active cooling function or a common circulating water cooling system was used to automatically control the temperature of the material in the reactor at 5°C to remove the reaction heat. After the addition was completed, stirring was continued for 10min, and samples were taken for gas chromatography analysis.

[0046] The results of different temperature control methods and temperature rise ranges and the corresponding conversion yields are shown in Table 8: Table 8

[0047] As shown in the results of Table 8, when the temperature rises within 2°C, the conversion rate and yield of the product are both high, and when the temperature rises above 2°C, the conversion rate and yield of the product are significantly reduced.

[0048] Example 9 (Separation of organic amine medium) Example 9 is used as an example to illustrate the separation of the organic amine medium. The product system obtained in Example 1.3 is distilled, and after discarding the front fraction (mainly a small amount of unreacted acrylonitrile, etc.), the fraction with a boiling point of 78°C (n-butylamine) is collected. The residue at the bottom of the kettle is N-cyanoethyl caprolactam. Due to the high reaction conversion rate, the amount of unreacted caprolactam residue in the residue at the bottom of the kettle is small, and it can be directly used in the subsequent production process. Example 9 is only used as an exemplary description, and the separation operation of the organic amine medium is not restrictive. The recovery method can be selected from any one of distillation, vacuum distillation, and crystallization, as long as the separation purpose is achieved.

[0049] Comparative Example 1 (Using Non-Organic Amine Solvent) Add 113g of caprolactam (1mol), 200g of toluene, 1.6g of sodium hydroxide, and 1g of hydroquinone to a reactor with a volume of 500mL. Under the condition of controlling the stirring rate at 300rpm, add 58.3g of acrylonitrile (1.1mol) to the reactor at a rate of 1g / min. Use a jacket circulation cooling system with active cooling function to automatically control the temperature of the material in the reactor at 5℃ to remove the reaction heat. After the addition is completed, continue to stir for 10 minutes, take a sample for gas chromatography analysis, and the conversion rate is 98.2% and the yield is 97.8%. Use liquid chromatography-mass spectrometry for analysis, such as Figure 3 As shown, a by-product with an obvious mass-to-charge ratio gap of 53 can be observed, because the relative molecular mass of acrylonitrile is 53, so the by-product is the self-polymerization product of acrylonitrile. In all the aforementioned embodiments, liquid chromatography-mass spectrometry analysis is performed, and no by-product signal with a gap of 53 can be observed. Therefore, adding an organic amine medium can suppress the self-polymerization side reaction of α, β-unsaturated nitrile.

[0050] So far, the technical solutions of the present invention have been described in conjunction with the preferred embodiments shown in the accompanying drawings. However, it is easy for those skilled in the art to understand that the protection scope of the present invention is obviously not limited to these specific embodiments. Without departing from the principle of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will fall within the protection scope of the present invention.

Claims

1. A method for preparing an N-cyanoalkyl substituted lactam, characterized in that: The α,β-unsaturated nitrile and lactam are subjected to addition reaction to obtain the product N-cyanoalkyl substituted lactam. An organic amine medium is added in the addition reaction. The alkaline dissociation constant of the organic amine medium at room temperature is 3.0-4.

2.

2. The method for preparing an N-cyanoalkyl substituted lactam according to claim 1, characterized in that: The melting point of the organic amine medium under the conditions of 0°C and 101.3 kPa is ≤0°C, and the boiling point is ≥45°C.

3. The method for preparing N-cyanoalkyl substituted lactam according to claim 1, characterized in that: The organic amine medium is at least one of a primary amine and a secondary amine.

4. The method for preparing N-cyanoalkyl substituted lactam according to claim 1, characterized in that: The organic amine mediator includes compounds having the following general formula: NHQR; Wherein, Q is selected from any one of a hydrogen atom and an alkyl group having 1 to 3 carbon atoms, and R is selected from any one of an alkyl group having 2 to 6 carbon atoms or an oxygen-containing alkyl group.

5. The method for preparing N-cyanoalkyl substituted lactam according to claim 1, characterized in that: The lactam is a compound having the following general formula: ； Where n is 1-9; And / or, the α,β-unsaturated nitrile is a compound having the following general formula: ； Among them, U, T, and V are selected from any one of a hydrogen atom and a methyl group.

6. The method for preparing N-cyanoalkyl substituted lactam according to claim 1, characterized in that: The preparation method of the N-cyanoalkyl substituted lactam comprises the following specific steps: Step (1): dissolving lactam in an organic amine medium to form a solution; Step (2): adding the α,β-unsaturated nitrile to the organic amine medium solution of the lactam and stirring; Step (3): After no obvious heat release occurs, the reaction is completed, and the organic amine medium is recovered and further separated to obtain the N-cyanoalkyl substituted lactam.

7. The method for preparing N-cyanoalkyl substituted lactam according to claim 6, characterized in that: In the step (2), the stirring temperature is 0-40°C.

8. The method for preparing N-cyanoalkyl substituted lactam according to claim 6, characterized in that: In the step (2), the molar ratio of lactam to α, β-unsaturated nitrile is 1:(1-2).

9. The method for preparing N-cyanoalkyl substituted lactam according to claim 6, characterized in that: In the step (2), the α,β-unsaturated nitrile is added dropwise or all at once.

10. The method for preparing N-cyanoalkyl substituted lactam according to claim 9, characterized in that: The α,β-unsaturated nitrile is added dropwise, and the mass ratio of lactam to organic amine medium is 1:(1-10), or the α,β-unsaturated nitrile is added all at once, and the mass ratio of lactam to organic amine medium is 1:(5-20). In both addition methods, the temperature rise of the reaction system is controlled at ≤2°C.

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