Method for preparing N-(2-substituted ethyl) amides and N-vinyl amides

Abstract

The invention relates to the technical field of amide compounds, and discloses a method for preparing N-(2-substituted ethyl) amide and N-vinyl amide, and a method for preparing N-(2-substituted ethyl) amide, the method comprises the following steps: under alkaline conditions, amide is contacted with 1, 2-disubstituted ethane to carry out substitution reaction, the amide has a structure shown in a formula (1), the 1, 2-disubstituted ethane has a structure shown in a formula (2), and the 1, 2-disubstituted ethane has a structure shown in a formula (3). The 1, 2-disubstituted ethane has a structure as shown in a formula (2), and in the formula (1), R1 and R2 are respectively and independently H or C1-C5 alkyl; in formula (2), R3 and R4 are each independently Cl, Br, I, a hydrocarbyl acyloxy group or a hydrocarbyl sulfonyloxy group. According to the method for synthesizing the required raw materials, only one-step reaction is needed, the synthesis route is simplified, the amide raw material and the 1, 2-disubstituted ethane raw material are cheap, and the raw material cost can be remarkably reduced. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the technical field of amide compounds, and particularly relates to a method for preparing N-(2-substituted ethyl) amide and N-vinyl amide. Background Art

[0002] Vinylic alkyl amides are a new type of functional monomers, which have advantages such as high polymerization activity and good water solubility. The enterprises that master the synthesis process of N-vinyl alkyl amides worldwide include BASF in Germany, Mitsubishi Chemical in Japan, and Showa Denko in Japan. The above processes all need to undergo a high-temperature cracking process, and the cracking temperature is above 300 °C, resulting in a reduction in the yield and purity of N-vinyl alkyl amides.

[0003] In response to the problem of the high cracking temperature, Zhejiang Xinyong Biochemical Co., Ltd. has disclosed a method for synthesizing N-vinyl formamide. It uses formamide and ethylene oxide to react to prepare N-(2-hydroxyethyl) formamide. N-(2-hydroxyethyl) formamide is esterified with an acid anhydride to obtain N-(2-acetoxyethyl) formamide. N-(2-acetoxyethyl) formamide can be eliminated at 70 °C to obtain N-vinyl formamide. This method can significantly reduce the elimination temperature, but the reaction raw material ethylene oxide has a low boiling point and is prone to ring-opening polymerization.

[0004]

[0005] The Changchun Institute of Applied Chemistry has disclosed a method for preparing N-vinyl alkyl amides from formamide, acetaldehyde and an acid anhydride. Formamide first reacts with acetaldehyde to obtain N-(α-hydroxyethyl) formamide. N-(α-hydroxyethyl) formamide reacts with an acid anhydride to form N-(α-acyloxyethyl) formamide. N-(α-acyloxyethyl) formamide is pyrolytically eliminated to obtain N-vinyl formamide. This method can also reduce the cracking temperature, but the raw material acetaldehyde has a low boiling point and poor stability, making it difficult to store. At the same time, the reaction intermediate has poor stability.

[0006]

[0007] Although the above N-vinyl alkyl amide synthesis methods can reduce the cracking reaction and improve the product yield and purity, the reaction raw materials and intermediates have poor stability, resulting in low safety and relatively harsh process conditions for the above methods. In addition, the use of acid anhydride esterification is accompanied by the generation of a large amount of by-product acid, which is highly corrosive to the equipment and has a high waste liquid treatment cost. Summary of the Invention

[0008] The object of the present invention is to overcome the problem of poor stability of reaction raw materials and intermediates in the prior art, and to provide a method for preparing N-(2-substituted ethyl)amide and N-vinylamide. The present invention uses amide and 1,2-disubstituted ethane as raw materials for substitution reaction. The raw materials have strong stability and low price, and at the same time have the advantages of fewer reaction steps, mild reaction conditions and less corrosion to equipment.

[0009] To achieve the above object, the first aspect of the present invention provides a method for preparing N-(2-substituted ethyl)amide, the method comprising: under basic conditions, contacting amide with 1,2-disubstituted ethane for a substitution reaction, wherein the amide has the structure shown in formula (1), and the 1,2-disubstituted ethane has the structure shown in formula (2),

[0010]

[0011] wherein, in formula (1), R 1 and R 2 are each independently H or an alkyl group of C 1 -C 5 ; in formula (2), R 3 and R 4 are each independently Cl, Br, I, hydrocarbyl acyloxy or hydrocarbyl sulfonyloxy.

[0012] The second aspect of the present invention provides a method for preparing N-vinylamide, the method comprising: under basic conditions, carrying out an elimination reaction on the N-(2-substituted ethyl)amide prepared by the method described above.

[0013] Through the above technical solutions, at least the following beneficial effects are obtained:

[0014] (1) Compared with the prior art for preparing N-vinylamide by high-temperature pyrolysis, the method provided by the present invention can prepare the raw material for the reaction of preparing N-vinylamide - N-(2-substituted ethyl)amide of the present invention at a lower reaction temperature, and the N-vinylamide can be prepared from the raw material through a one-step elimination reaction. The synthesis method of the present invention does not involve high-temperature and high-pressure processes, has low requirements for the material of the reaction instrument, and has low process cost, and has good economy.

[0015] (2) Compared with the synthesis routes of the raw materials required for the preparation of N-vinylamide by the existing acid anhydride esterification reaction, the method for synthesizing the raw materials required in the present invention only requires one-step reaction, simplifies the synthesis route, and the amide raw materials and 1,2-disubstituted ethane raw materials in the present invention are inexpensive, which can significantly reduce the raw material cost. At the same time, the amide raw materials and 1,2-disubstituted ethane raw materials in the present invention have high boiling points, strong stability and no corrosion, have low requirements for storage conditions and storage equipment, and have no safety risks. Moreover, the stability of N-(2-substituted ethyl)amide in the present invention is significantly better than that of N-(α-acyl-oxyethyl)amide. Detailed implementation mode

[0016] The endpoints and any values within the ranges disclosed herein are not limited to the exact ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of each range, between the endpoint values of each range, between the endpoint value of each range and a single point value, and between single point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein.

[0017] The first aspect of the present invention provides a method for preparing N-(2-substituted ethyl)amide, the method comprising: under alkaline conditions, contacting an amide with 1,2-disubstituted ethane for a substitution reaction, wherein the amide has the structure shown in formula (1), and the 1,2-disubstituted ethane has the structure shown in formula (2),

[0018]

[0019] wherein, in formula (1), R 1 and R 2 are each independently H or an alkyl group of C 1 -C 5 ; in formula (2), R 3 and R 4 are each independently Cl, Br, I, a hydrocarbon acyl-oxy group or a hydrocarbon sulfonyl-oxy group.

[0020] In the present invention, the alkyl group of C 1 -C 5 can be a straight-chain alkyl group, a branched-chain alkyl group or a cycloalkyl group, wherein, R 1 and R 2 are each independently H, methyl, ethyl, propyl, butyl, pentyl.

[0021] According to the present invention, preferably, the hydrocarbon acyl-oxy group is an acyl-oxy group of a C 1 -C 8 hydrocarbon group, and more preferably an acyl-oxy group of a C 1 -C 5 alkyl group.

[0022] According to the present invention, preferably, the hydrocarbylsulfonyloxy group is C 1 -C 15 the hydrocarbylsulfonyloxy group of a hydrocarbyl group, more preferably C 1 -C 5 the hydrocarbylsulfonyloxy group of an alkyl group, C 6 -C 10 the hydrocarbylsulfonyloxy group of an aryl group.

[0023] According to the present invention, preferably, relative to 1 mol of the amide, the amount of the 1,2-disubstituted ethane used is 1 - 5 mol (for example, 1 mol, 1.5 mol, 2 mol, 2.5 mol, 3 mol, 3.5 mol, 4 mol, 4.5 mol, 5 mol, and the ranges composed of any two of the above), more preferably 2 - 3 mol.

[0024] According to the present invention, preferably, the substitution reaction conditions include: the reaction temperature is 0 - 80 °C, more preferably 25 - 60 °C; the reaction time is 6 - 12 h, more preferably 8 - 10 h.

[0025] According to the present invention, preferably, the substitution reaction is carried out under the condition of a protective gas. More preferably, the protective gas is an inert gas. Further preferably, the protective gas includes nitrogen and / or an inert gas (helium, argon, krypton, etc.). Even more preferably, the protective gas is nitrogen.

[0026] According to the present invention, preferably, the amide includes at least one of formamide, acetamide, propionamide, butyramide, valeramide, N-methylformamide, N-ethylformamide, N-propylformamide, N-butylformamide, N-pentylformamide, N-methylacetamide, N-ethylacetamide, N-propylacetamide, N-butylacetamide, N-pentylacetamide, N-methylpropionamide, N-ethylpropionamide, N-propylpropionamide, N-butylpropionamide, N-pentylpropionamide, N-methylbutyramide, N-ethylbutyramide, N-propylbutyramide, N-butylbutyramide, N-pentylbutyramide, N-methylvaleramide, N-ethylvaleramide, N-propylvaleramide, N-butylvaleramide, and N-pentylvaleramide.

[0027] According to the present invention, preferably, the 1,2-disubstituted ethane includes at least one of 1,2-dichloroethane, 1,2-dibromoethane, 1,2-diiodoethane, ethylene glycol diformate, ethylene glycol diacetate, ethylene glycol dipropionate, ethylene glycol dibutyrate, ethylene glycol divalerate, ethylene glycol dimethanesulfonate, ethylene glycol bis(trifluoromethanesulfonate), and ethylene glycol bis(p-toluenesulfonate).

[0028] According to the present invention, preferably, the basic substance is an inorganic base and / or an organic base; more preferably, the inorganic base is at least one of hydroxides of alkali metals, salts of alkali metals, and hydrides of alkali metals; the organic base is an alkoxide of alkali metal, an alkyl alkali metal, an alkylamino alkali metal, or an alkylsilylamino alkali metal. Further preferably, the organic base is an alkoxide of alkali metal C 1 -C 5 alcoholate, C 1 -C 5 alkyl alkali metal, C 1 -C 5 alkylamino alkali metal, C 1 -C 5 alkylsilylamino alkali metal.

[0029] According to the present invention, preferably, the basic substance is at least one of potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium hydride, potassium hydride, sodium methoxide, potassium methoxide, lithium methoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, lithium diisopropylamide, sodium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, and n-butyllithium.

[0030] According to the present invention, preferably, with respect to 1 mol of the amide, the amount of the basic substance used is 1 - 2 mol (for example, 1 mol, 1.1 mol, 1.2 mol, 1.3 mol, 1.4 mol, 1.5 mol, 1.6 mol, 1.7 mol, 1.8 mol, 1.9 mol, 2 mol, and the ranges formed by any two of the above), and more preferably 1.1 - 1.3 mol.

[0031] According to the present invention, preferably, the substitution reaction is carried out in the presence of a solvent, and the solvent is at least one of N,N-dimethylformamide, toluene, and xylene; more preferably N,N-dimethylformamide.

[0032] According to the present invention, preferably, with respect to 1 mol of the amide, the amount of the solvent used is 1000 - 3000 mL, and more preferably 1800 - 2000 mL.

[0033] According to the present invention, preferably, the method further includes quenching the reaction with a quenching agent after the substitution reaction is completed, and then extracting with an extracting agent. More preferably, the quenching agent is a saturated ammonium chloride solution, and the extracting agent is ethyl acetate.

[0034] According to the present invention, preferably, the method further includes removing the extracting agent from the extraction phase to obtain N-(2-substituted ethyl)amide. More preferably, the way to remove the extracting agent from the extraction phase is vacuum distillation.

[0035] According to the present invention, preferably, the method further includes subjecting the N-(2-substituted ethyl) amide after removing the extractant in the extraction phase to column chromatography separation. More preferably, the mobile phase used in the column chromatography separation is n-hexane and ethyl acetate. Further preferably, the volume ratio of n-hexane to ethyl acetate is 1:0.5 - 2. The stationary phase used in the column chromatography separation can be a silica gel stationary phase, a polymer stationary phase, etc. commonly used in the art.

[0036] The synthetic route for preparing N-(2-substituted ethyl) amide of the present invention is as follows:

[0037]

[0038] According to a particularly preferred embodiment of the present invention, the method for preparing N-(2-substituted ethyl) amide includes: adding 115 - 120 mmol of potassium tert-butoxide to a reactor, purging with nitrogen to remove oxygen, then adding 180 - 200 mL of N,N-dimethylformamide, 290 - 300 mmol of 1,2-dichloroethane, and 98 - 100 mmol of N-methylacetamide. After the feeding is completed, the temperature is raised to 55 - 60 °C for reaction at the reaction temperature for 9.5 - 10 h; after the reaction is completed, saturated ammonium chloride solution is added to quench the reaction, ethyl acetate (190 - 200 mL) is added for extraction, and then the solvent is removed by distillation under reduced pressure. N-(2-substituted ethyl) amide is obtained through column chromatography separation (the volume ratio of n-hexane to ethyl acetate is 1:1 - 1.1).

[0039] The second aspect of the present invention provides a method for preparing N-vinyl amide, which includes: under alkaline conditions, subjecting the N-(2-substituted ethyl) amide prepared by the above-mentioned method to an elimination reaction.

[0040] According to the present invention, preferably, the conditions for the elimination reaction include: the reaction temperature is 100 - 160 °C, and the reaction time is 1 - 8 h; more preferably, the conditions for the elimination reaction include: the reaction temperature is 120 - 140 °C, and the reaction time is 4 - 6 h.

[0041] According to the present invention, preferably, the alkaline conditions are provided by an alkaline substance, and the alkaline substance is a sterically hindered strong base, more preferably an alkali metal alkoxide, and further preferably an alkali metal C 3 -C 8 alkoxide, and even more preferably potassium tert-butoxide and / or sodium tert-butoxide.

[0042] According to the present invention, preferably, relative to 1 mol of N-(2-substituted ethyl) amide, the amount of the basic substance used is 1-2 mol (for example, 1 mol, 1.1 mol, 1.2 mol, 1.3 mol, 1.4 mol, 1.5 mol, 1.6 mol, 1.7 mol, 1.8 mol, 1.9 mol, 2 mol, and the ranges composed of any two of the above), more preferably 1.1-1.5 mol.

[0043] According to the present invention, preferably, the preparation process of N-vinyl amide is carried out in the presence of a solvent, and the solvent is at least one of N,N-dimethylformamide, toluene, and xylene; more preferably N,N-dimethylformamide. Further preferably, relative to 1 mol of N-(2-substituted ethyl) amide, the amount of the solvent used is 1000-4000 mL, and even more preferably 2000-3000 mL.

[0044] According to the present invention, preferably, the elimination reaction is carried out under the condition of a protective gas. More preferably, the protective gas is an inert gas. Further preferably, the protective gas includes nitrogen and / or inert gases (helium, argon, krypton, etc.). Even more preferably, the protective gas is nitrogen.

[0045] The synthetic route for preparing N-vinyl amide of the present invention is as follows:

[0046]

[0047] According to a particularly preferred embodiment of the present invention, the method for preparing N-vinyl amide includes: putting N-(2-substituted ethyl) amide into a reactor, purging with nitrogen to remove oxygen, then adding potassium tert-butoxide, heating to 135-140 °C to the elimination reaction temperature and reacting for 5.5-6 h; after the reaction is completed, performing vacuum distillation to obtain N-vinyl amide; wherein, relative to 1 mol of N-(2-substituted ethyl) amide, the amount of potassium tert-butoxide used is 1.4-1.45 mol.

[0048] The present invention also relates to a method for preparing a polymer, which includes: preparing N-vinyl amide according to the method as described above; then mixing the obtained N-vinyl amide as monomer D’ with monomer A’, monomer B’, monomer C’ and an initiator and carrying out a polymerization reaction under solution polymerization reaction conditions. The polymer prepared by this method has both the ability to thicken in the aqueous phase and the performance of emulsifying viscous oil with low dynamic viscosity, can achieve viscosity reduction of viscous oil, and is applicable to the exploitation of water flooding reservoirs. Among them, monomer A′, monomer B′, monomer C′, the initiator, the polymerization reaction, etc. are detailed in CN202311522670.5, CN202311522771.2, CN202311519415.5, which are hereby incorporated herein by reference in their entirety.

[0049] The present invention will be described in detail below through examples. In the following examples,

[0050] The following substitution reaction and elimination reaction are both carried out under normal pressure.

[0051] The stationary phase used for the following column chromatography separation is a silica gel stationary phase.

[0052] The following raw materials are all commercially available products.

[0053] Yield of N-(2-substituted ethyl)amide = Actual yield of target product / Theoretical yield of target product × 100%.

[0054] The detection method for the purity of N-(2-substituted ethyl)amide is to use the internal standard method of 1H NMR for detection.

[0055] Yield of N-vinylamide = Actual yield of target product / Theoretical yield of target product × 100%.

[0056] The detection method for the purity of N-vinylamide is to use the internal standard method of 1H NMR for detection.

[0057] Examples 1 - 6

[0058] (1) Take a basic substance, after purging with nitrogen to remove oxygen, add N,N-dimethylformamide (200 mL), the structural amide shown in formula (1), and the 1,2-disubstituted ethane shown in formula (2). After adding the materials, raise the temperature to the substitution reaction temperature and react for a period of time; after the reaction is completed, add saturated ammonium chloride solution to quench the reaction, add ethyl acetate (200 mL) for extraction, and then distill off the solvent under reduced pressure. After column chromatography separation (the volume ratio of n-hexane:ethyl acetate is 1:1), N-(2-substituted ethyl)amide is obtained. The types and dosages of the basic substance, the structural amide shown in formula (1), and the 1,2-disubstituted ethane shown in formula (2), the reaction temperature and reaction time are shown in Table 1. The yields and purities of the obtained products are shown in Table 1.

[0059] (2) Take the N-(2-substituted ethyl)amide (100 mmol) prepared in step (1), after purging with nitrogen to remove oxygen, add N,N-dimethylformamide (300 mL) and a basic substance, raise the temperature to the elimination reaction temperature and react for a certain time; after the reaction is completed, distill off the solvent under reduced pressure to obtain N-vinylamide. The types and dosages of the basic substance, the temperature and time of the elimination reaction are shown in Table 1. The yields and purities of the obtained product N-vinylamide are shown in Table 1.

[0060] Table 1

[0061]

[0062]

[0063] Example 7

[0064] It was carried out according to the method of Example 1, except that in step (1), sodium hydroxide was replaced with an equimolar amount of n-butyllithium. The yield of N-(2-bromoethyl)acetamide obtained in step (1) was 69.5%, and the purity was 75.8%.

[0065] Example 8

[0066] It was carried out according to the method of Example 2, except that in step (1), N,N-dimethylformamide was replaced with an equal volume of toluene. The yield of N-(2-bromoethyl)acetamide obtained was 42.6%, and the purity was 49.6%.

[0067] Comparative Example 1

[0068] It was carried out according to the method of Example 2, except that in step (1), no basic substance was added. The yield of N-(2-bromoethyl)acetamide obtained was 11.2%, and the purity was 45.9%.

[0069] Comparative Example 2

[0070] It was carried out according to the method of Example 2, except that in step (2), no basic substance was added. The yield of N-vinylacetamide obtained was 2.9%, and the purity was 23.5%.

[0071] Nuclear magnetic characterization of the product N-(2-bromoethyl)acetamide obtained in step (1) of Example 1: 1 H NMR(500MHz,DMSO-d 6 )δ7.28(t,J=4.3Hz,1H,NH),3.73–3.68(m,2H,N-CH 2 ),3.58(td,J=5.9,0.6Hz,2H,CH 2 Br),1.94(s,3H,CH 3 ).

[0072] Nuclear magnetic characterization of the product N-vinylacetamide obtained in step (2) of Example 1: 1 H NMR(500MHz,DMSO-d 6 )δ7.91(d,J=9.1Hz,1H,NH),7.23(q,J=9.1Hz,1H,N-CH=CH 2 ),5.06(dd,J=9.2,2.5Hz,1H,N-CH=CH 2 ),4.96(dd,J=9.2,2.5Hz,1H,N-CH=CH 2 ),2.05(s,3H,CH3 ).

[0073] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited thereto. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, including any other suitable combination of each technical feature. These simple modifications and combinations should also be regarded as the content disclosed by the present invention and fall within the protection scope of the present invention.

Claims

1. A method for preparing N-(2-substituted ethyl)amide, characterized in that: The method comprises: under alkaline conditions, contacting an amide with 1,2-disubstituted ethane to carry out a substitution reaction, wherein the amide has a structure shown in formula (1), and the 1,2-disubstituted ethane has a structure shown in formula (2). Among them, in formula (1), R 1 and R 2 Each independently is H or a C1-C5 alkyl group; in formula (2), R 3 and R 4 Each is independently Cl, Br, I, a hydrocarbyl acyloxy group or a hydrocarbyl sulfonyloxy group.

2. The method according to claim 1, wherein: Relative to 1 mol of amide, the amount of the 1,2-disubstituted ethane used is 1-5 mol, preferably 2-3 mol.

3. The method according to claim 1, wherein: The substitution reaction conditions include: reaction temperature of 0-80°C, preferably 25-60°C; reaction time of 6-12h, preferably 8-10h.

4. The method according to claim 1, wherein: The substitution reaction is carried out under the condition of protective gas, preferably, the protective gas is nitrogen.

5. The method according to claim 1, wherein: The amide includes at least one of formamide, acetamide, propionamide, butyramide, valeramide, N-methylformamide, N-ethylformamide, N-propylformamide, N-butylformamide, N-pentylformamide, N-methylacetamide, N-ethylacetamide, N-propylacetamide, N-butylacetamide, N-pentylacetamide, N-methylpropionamide, N-ethylpropionamide, N-propylpropionamide, N-butylpropionamide, N-pentylpropionamide, N-methylbutanamide, N-ethylbutanamide, N-propylbutanamide, N-butylbutanamide, N-pentylbutanamide, N-methylvaleramide, N-ethylvaleramide, N-propylvaleramide, N-butylvaleramide and N-pentylvaleramide.

6. The method according to claim 1, wherein: The 1,2-disubstituted ethane includes at least one of 1,2-dichloroethane, 1,2-dibromoethane, 1,2-diiodoethane, ethylene glycol diformate, ethylene glycol diacetate, ethylene glycol dipropionate, ethylene glycol dibutyrate, ethylene glycol divalerate, ethylene glycol dimethanesulfonate, ethylene glycol ditrifluoromethanesulfonate and ethylene glycol dip-toluenesulfonate.

7. The method according to claim 1, wherein: The alkaline substance is an inorganic base and / or an organic base; preferably at least one of potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium hydride, potassium hydride, sodium methoxide, potassium methoxide, lithium methoxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, lithium diisopropylamide, sodium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide and n-butyllithium.

8. The method according to claim 1, wherein: The amount of the alkaline substance used is 1-2 mol, preferably 1.1-1.3 mol, relative to 1 mol of amide.

9. A method for preparing N-vinyl amide, characterized in that: The method comprises: under alkaline conditions, subjecting the N-(2-substituted ethyl)amide prepared by the method described in any one of claims 1 to 8 to an elimination reaction.

10. The preparation method according to claim 9, wherein: The conditions of the elimination reaction include: a reaction temperature of 100-160°C and a reaction time of 1-8h; preferably, the conditions of the elimination reaction include: a reaction temperature of 120-140°C and a reaction time of 4-6h; And / or, the alkaline condition is provided by an alkaline substance, the alkaline substance is a strong base with large steric hindrance, preferably an alkali metal alkoxide, more preferably potassium tert-butoxide and / or sodium tert-butoxide; Preferably, relative to 1 mol of N-(2-substituted ethyl)amide, the amount of the alkaline substance used is 1-2 mol, preferably 1.1-1.5 mol; And / or, the elimination reaction is carried out under the condition of protective gas, preferably, the protective gas is nitrogen.

Images