A preparation method of N-cyanoalkyl substituted lactam

Abstract

The invention provides a method for preparing an N-cyanoalkyl substituted lactam. The method comprises the following steps: dissolving a lactam in an organic amine medium having a specific alkaline dissociation constant and melting and boiling points to form a solution; adding an α,β-unsaturated nitrile to the organic amine medium solution of the lactam; recovering the organic amine medium after completion of the reaction; and further separating the organic amine medium to obtain a pure N-cyanoalkyl substituted lactam. The organic amine medium has an alkaline dissociation constant of 3.0-4.2 at room temperature, a melting point of ≤0°C under the conditions of 0°C and 101.3 kPa, and a boiling point of ≥45°C. Based on this, the method can avoid the generation of impurity salts due to the additional addition of alkaline substances, effectively inhibit the occurrence of self-polymerization reaction of the α,β-unsaturated nitrile, and improve the conversion rate of the lactam and the yield of the product.

Description

Technical Field

[0001] The present 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 lactams with α,β-unsaturated nitriles is often used to prepare N-cyanoalkyl-substituted lactams. N-cyanoalkyl-substituted lactams can be hydrogenated to obtain N-aminoalkyl-substituted lactams, which can then be dehydrated and ring-closed to obtain diazabicyclic compounds and their derivatives with the following structure:

[0003]

[0004] However, the addition reaction of lactams with α,β-unsaturated nitriles typically suffers from low conversion rates, low yields, and a large number of byproducts caused by the self-polymerization of the α,β-unsaturated nitriles. Chinese invention patent CN1268627C discloses a method for preparing 1,8-diazabicyclo[5.4.0]undec-7-ene. In the addition reaction of caprolactam and acrylonitrile, the conversion calculated based on caprolactam is 96-99%, while the yield of the intermediate product, N-cyanoethylcaprolactam (based on caprolactam), is only 89-93%. Because acrylonitrile readily polymerizes above 50°C, resulting in the formation of byproducts, Chinese invention patent CN117327014A proposes a method using a Lewis acid catalyst to activate the carbon-carbon double bonds of acrylonitrile, thereby lowering the reaction temperature and reducing the side effects of acrylonitrile self-polymerization. However, commonly available Lewis acids, such as aluminum chloride and zinc chloride, typically have low solubility in organic solvents. Furthermore, the base catalyst added during the reaction reacts with the Lewis acid, even forming insoluble compounds. This makes it difficult to fully utilize the intended catalytic effect of the Lewis acid, thus hindering the feasibility of this technical solution. Furthermore, adding a polymerization inhibitor to the reaction system can suppress the side reaction of acrylonitrile self-polymerization. Commonly used polymerization inhibitors include 4-methoxyphenol and hydroquinone. However, these polymerization inhibitors form organic-inorganic salts when exposed to base catalysts such as sodium hydroxide in the reaction. Using large amounts of these inhibitors can often lead to coking in the reactor during subsequent reaction processes, requiring frequent cleaning, reducing production efficiency, and adversely affecting product separation and purification.

[0005] Therefore, the art needs a new method for preparing N-cyanoalkyl substituted lactam to solve the above technical problems. Summary of the Invention

[0006] In view of the deficiencies in the prior art, the present invention discloses a method for preparing an N-cyanoalkyl substituted lactam to solve the above-mentioned problems existing in the prior art, namely, solving the problems in the prior art of low conversion rate and yield of the addition reaction of lactam with α,β-unsaturated nitrile and a large number of by-products caused by the self-polymerization of the α,β-unsaturated nitrile.

[0007] To achieve the above technical objectives, the present invention provides a method for preparing an N-cyanoalkyl substituted lactam: an α,β-unsaturated nitrile and a lactam are subjected to an addition reaction to obtain the product N-cyanoalkyl substituted lactam, an organic amine medium is added to the addition reaction, and the organic amine medium has an alkaline dissociation constant of 3.0-4.2 at room temperature.

[0008] In the technique scheme, the present invention is on the basis of a large amount of experimental studies, find that organic amine has certain alkalescence, can play the effect of catalysis in this reaction, promote lactam and α, the reaction of beta-unsaturated nitrile, improve transformation efficiency and yield, secondly, under conditions of the present invention, α, the possible self polymerization of beta-unsaturated nitrile is a free radical mechanism, can comparatively significantly occur in hydrocarbon solvents such as the benzene that prior art uses, toluene, dimethylbenzene, and the organic amine that the present invention limits is owing to containing the hydrogen atom that directly links to each other with the nitrogen-atoms, it is except having the unpaired electron on the nitrogen-atoms, also has the hydrogen atom with certain activity, can suppress the generation of free radical and combine to generate oligomeric by-products, and do not affect the lactam that belongs to electrophilic-nucleophilic mechanism and the reaction of unsaturated nitrile.Therefore in prior art route addition reaction, add the organic amine medium with specific alkaline dissociation constant, improve transformation efficiency and yield of product, suppress α simultaneously, the generation of the self polymerization side reaction of beta-unsaturated nitrile.

[0009] 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.

[0010] In order to improve the selectivity, stability and solvent performance of the reaction, the organic amine medium further has a melting point of ≤0°C and a boiling point of ≥45°C under the conditions of 0°C and 101.3kPa.

[0011] Furthermore, the organic amine medium is at least one of a primary amine and a secondary amine.

[0012] The organic amine mediator includes a compound having the following general formula:

[0013] NHQR

[0014] 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.

[0015] Preferably, Q is selected from any one of hydrogen atom, methyl, ethyl, and n-propyl, and R is selected from any one of ethyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclohexyl, and 2-hydroxypropyl.

[0016] 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 further preferably any one of n-butylamine or isobutylamine.

[0017] Furthermore, the lactam is a compound having the following general formula:

[0018]

[0019] Wherein, n is 1-9. The embodiment of the present invention further illustrates the optimization process of lactam. Optionally, n is 2-8, and more preferably 3-7.

[0020] Furthermore, the α,β-unsaturated nitrile is a compound having the following general formula:

[0021]

[0022] Among them, U, T, and V are selected from any one of a hydrogen atom and a methyl group.

[0023] Specifically, the preparation method of the N-cyanoalkyl substituted lactam comprises the following specific steps:

[0024] Step (1): dissolving the lactam in an organic amine medium to form a solution;

[0025] Step (2): adding the α,β-unsaturated nitrile to the organic amine medium solution of the lactam and stirring;

[0026] Step (3): After no obvious heat is released, the reaction is completed, and the organic amine medium is recovered and further separated to obtain the N-cyanoalkyl substituted lactam.

[0027] 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.

[0028] 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 further preferably 1:(1.2-1.3).

[0029] Furthermore, the α,β-unsaturated nitrile in step (2) can be added dropwise or all at once.

[0030] Furthermore, the ratio of lactam to organic amine medium in the two addition 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 addition methods, the temperature rise of the reaction system is controlled at ≤2°C, preferably ≤1°C, and more preferably ≤0.5°C.

[0031] 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.

[0032] Compared with the prior art, the present invention has the following beneficial effects: the present invention provides a method for preparing N-cyanoalkyl substituted lactam, wherein an organic amine medium having a specific alkaline dissociation constant and melting and boiling points is added to an α,β-unsaturated nitrile and a lactam to carry out an addition reaction to obtain the N-cyanoalkyl substituted lactam product; the preparation method improves the conversion rate of the lactam raw material and the selectivity of the N-cyanoalkyl substituted lactam product, inhibits the self-polymerization side reaction of the α,β-unsaturated nitrile, improves the utilization rate of the raw materials, and improves the convenience of post-processing of the reaction system. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The following describes preferred embodiments of the present invention in conjunction with the accompanying drawings to further understand the technical solutions 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:

[0034] Figure 1 This is a gas chromatogram of N-cyanoethyl caprolactam, the product of Example 1.3 of the present invention;

[0035] Figure 2 This is a liquid chromatography-mass spectrometry spectrum of N-cyanoethyl caprolactam, the product of Example 1.3 of the present invention;

[0036] 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

[0037] The following will be combined with 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, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts shall fall within the scope of protection of the present invention.

[0038] To facilitate understanding of the present invention, the present invention will be described in more detail below, with preferred embodiments of the present invention provided. However, it should be understood that these embodiments are provided for further explanation only and are not intended to limit the present invention in any manner, i.e., they do not limit the scope of protection of the present invention.

[0039] Gas chromatography detection conditions

[0040] The injection volume was 0.4 μL, the injector temperature was 240°C, the column flow rate was 2.3 mL / min, the purge flow rate was 3 mL / min, the split ratio was 50, the column oven temperature program was 150°C (5 min) - gradient temperature increase (15 min) ~ 300°C (5 min), the sampling rate was 40 ms, the sampling time was 25 min, the tail gas flow rate was 24 mL / min, a flame ionization detector was used, the hydrogen flow rate was 32 mL / min, and the air flow rate was 200 mL / min.

[0041] Liquid chromatography-mass spectrometry chromatographic detection conditions

[0042] 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 spectrometer 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.

[0043] Example 1 (Changing the type of lactam)

[0044] A certain amount of lactam was added to a 500 mL reactor, and 200 g of n-butylamine (melting point -49 ° C, boiling point 78 ° C, pK b =3.36), and under the condition of controlling the stirring rate at 300 rpm, 58.3 g (1.1 mol) of acrylonitrile was added dropwise to the reactor at a rate of 1 g / min. A jacketed circulation cooling system with an active cooling function was used to automatically control the temperature of the material in the reactor with a target temperature of 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.

[0045] The effects of different lactams on product conversion and yield are shown in Table 1:

[0046]

[0047] 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 1 The 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.

[0048] Example 2 (Changing the Type of Unsaturated Nitrile)

[0049] Add 113g of caprolactam (1 mol) and 200g of n-butylamine (melting point -49°C, boiling point 78°C, pK b =3.36), a certain mass of unsaturated nitrile was added dropwise to the reactor at a rate of 1 g / min under the condition of controlling the stirring rate at 300 rpm. A jacketed circulation cooling system with an active cooling function was used to automatically control the temperature of the material in the reactor with a target temperature of 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.

[0050] The effects of different unsaturated nitriles on product conversion and yield are shown in Table 2:

[0051]

[0052] As shown in Table 2, different types of unsaturated nitriles have high conversion rates and product yields. When the unsaturated nitrile is 2-methyl-2-butenenitrile, the conversion rate is 99.3% and the product yield is 99.1%.

[0053] Example 3 (Changing the reaction temperature)

[0054] Add 113g of caprolactam (1 mol) and 200g of n-butylamine (melting point -49°C, boiling point 78°C, pK b =3.36), and under the condition of controlling the stirring rate at 300 rpm, 58.3 g (1.1 mol) of acrylonitrile was added dropwise to the reactor at a rate of 1 g / min. A jacketed circulation cooling system with an active cooling function was used to automatically control the temperature of the material in the reactor to a specific target value to remove the reaction heat. After the addition was completed, stirring was continued for 10 minutes, and samples were taken for gas chromatography analysis.

[0055] The effects of different reaction temperatures on product conversion and yield are shown in Table 3:

[0056]

[0057] As shown in Table 3, the reaction temperature is within the range of 0-40°C, and the conversion rate and product yield are relatively high. When the reaction temperature is between 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 decrease.

[0058] Example 4 (Changing the Type of Organic Amine Medium)

[0059] 113 g of caprolactam (1 mol) and 200 g of a specific type of organic amine were added to a 500 mL reactor. 58.3 g of acrylonitrile (1.1 mol) was added dropwise to the reactor at a rate of 1 g / min while controlling the stirring rate at 300 rpm. A jacketed circulating cooling system with an active cooling function was used to automatically control the temperature of the reactor material 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.

[0060] The effects of different organic amine media on product conversion and yield are shown in Table 4:

[0061]

[0062] 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.

[0063] Example 5 (Changing the amount of acrylonitrile)

[0064] Add 113g of caprolactam (1 mol) and 200g of n-butylamine (melting point -49°C, boiling point 78°C, pK b =3.36), a specific mass of acrylonitrile was added dropwise to the reactor at a rate of 1 g / min while controlling the stirring rate at 300 rpm. A jacketed circulating cooling system with an active cooling function 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 10 minutes, and samples were taken for gas chromatography analysis.

[0065] The effects of different acrylonitrile dosages on product conversion and yield are shown in Table 5:

[0066]

[0067] As shown in Table 5, when the molar ratio of caprolactam to acrylonitrile is within the range of 1:1-1.5, the conversion rate and product yield are both high and similar. When the unsaturated nitrile ratio is 1:1.01 (Example 5.5), the reaction performance (conversion rate and yield) deteriorates.

[0068] Example 6 (Acrylonitrile Dropwise Addition)

[0069] 113 g of caprolactam (1 mol) was added to a 500 mL reactor, and a certain amount of n-butylamine (melting point -49 ° C, boiling point 78 ° C, pK b =3.36), and under the condition of controlling the stirring rate at 300 rpm, 58.3 g of acrylonitrile (1.1 mol) was added dropwise. During this period, a jacketed circulating cooling system with an 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.

[0070] When acrylonitrile was added dropwise, the effects of different n-butylamine dosages on product conversion and yield were shown in Table 6:

[0071]

[0072] As shown in 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.

[0073] Example 7 (Acrylonitrile is added all at once)

[0074] 22.6 g of caprolactam (0.2 mol) was added to a 500 mL reactor, and a certain amount of n-butylamine (melting point -49 ° C, boiling point 78 ° C, pK b =3.36), and under the condition of controlling the stirring rate at 300 rpm, 15.9 g of acrylonitrile (0.3 mol) was added all at once. During this period, a jacketed circulation cooling system with an 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 then samples were taken for gas chromatography analysis.

[0075] When all acrylonitrile was added at once, the effects of different n-butylamine dosages on product conversion and yield are shown in Table 7:

[0076]

[0077] As shown in 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.

[0078] Example 8 (Precision of Temperature Control)

[0079] Add 113g of caprolactam (1 mol) and 200g of n-butylamine (melting point -49°C, boiling point 78°C, pK b =3.36), and 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 or in a one-time addition manner. A jacketed circulating 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 10 minutes, and samples were taken for gas chromatography analysis.

[0080] The results of different temperature control methods and temperature increase ranges as well as the corresponding conversion rates and yields are shown in Table 8:

[0081]

[0082] As shown in Table 8, when the temperature rises within 2°C, the conversion rate and yield of the product are high. When the temperature rises above 2°C, the conversion rate and yield of the product decrease significantly.

[0083] Example 9 (Separation of organic amine medium)

[0084] Example 9 illustrates the separation of an organic amine medium. The product system obtained in Example 1.3 was distilled, and after discarding the front fraction (primarily consisting of a small amount of unreacted acrylonitrile, etc.), the fraction with a boiling point of 78°C (n-butylamine) was collected. The residue at the bottom of the still is N-cyanoethyl caprolactam. Due to the high reaction conversion rate, the amount of unreacted caprolactam in the residue is low, allowing it to be directly used in subsequent production processes. Example 9 is provided for illustrative purposes only. The separation of the organic amine medium is not restrictive, and recovery methods can be selected from any of distillation, vacuum distillation, and crystallization, as long as the separation objective is achieved.

[0085] Comparative Example 1 (Using Non-Organic Amine Solvent)

[0086] 113g of caprolactam (1mol), 200g of toluene, 1.6g of sodium hydroxide, and 1g of hydroquinone were added to a 500mL reactor. 58.3g of acrylonitrile (1.1mol) was added dropwise to the reactor at a rate of 1g / min while stirring at 300rpm. A jacketed circulation cooling system with active cooling function was used to automatically control the temperature of the reactor material at 5°C to remove the reaction heat. After the addition was completed, stirring was continued for 10 minutes. Samples were taken for gas chromatography analysis, and the conversion rate was 98.2% and the yield was 97.8%. Liquid chromatography-mass spectrometry was used for analysis, as shown in FIG. Figure 3 As shown in FIG. 3 , 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, the by product is the autopolymerization product of acrylonitrile. In all the aforementioned embodiments, liquid chromatography-mass spectrometry analysis was performed and the by product signal with an interval of 53 could not be observed. Therefore, adding the organic amine medium can suppress the autopolymerization side reaction of α,β-unsaturated nitrile.

[0087] Thus far, the technical solutions of the present invention have been described in conjunction with the preferred embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art may make equivalent changes or substitutions to the relevant technical features, and the technical solutions after such changes or substitutions will fall within the scope of protection of the present invention.

Claims

1. A method for preparing an N-cyanoalkyl substituted lactam, characterized in that: An α,β-unsaturated nitrile and a lactam are subjected to an addition reaction to obtain a product, an N-cyanoalkyl substituted lactam, wherein an organic amine medium is added to the addition reaction, wherein the organic amine medium has an alkaline dissociation constant of 3.0-4.2 at room temperature, and the organic amine medium is selected from a compound 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; The lactam is a compound having the following general formula: ； Where n is 1-9; 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.

2. The method for preparing an N-cyanoalkyl substituted lactam according to claim 1, wherein 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.

3. The method for preparing N-cyanoalkyl substituted lactam according to claim 1, wherein The preparation method of the N-cyanoalkyl substituted lactam comprises the following specific steps: Step (1): dissolving the 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 is released, the reaction is completed, and the organic amine medium is recovered and further separated to obtain the N-cyanoalkyl substituted lactam.

4. The method for preparing N-cyanoalkyl substituted lactam according to claim 3, wherein In the step (2), the stirring temperature is 0-40°C.

5. The method for preparing N-cyanoalkyl substituted lactam according to claim 3, wherein In the step (2), the molar ratio of lactam to α,β-unsaturated nitrile is 1:(1-2).

6. The method for preparing N-cyanoalkyl substituted lactam according to claim 3, wherein: In the step (2), the α,β-unsaturated nitrile is added dropwise or all at once.

7. The method for preparing N-cyanoalkyl substituted lactam according to claim 6, wherein: The α,β-unsaturated nitrile is added dropwise, with a mass ratio of lactam to organic amine medium of 1:(1-10), or the α,β-unsaturated nitrile is added all at once, with a mass ratio of lactam to organic amine medium of 1:(5-20). In both addition methods, the temperature rise of the reaction system is controlled to be ≤2°C.

Images