CN113548977A - Process for producing N-methyl-beta-alanine derivative - Google Patents
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Abstract
The invention provides a preparation method of an N-methyl-beta-alanine derivative, which comprises the following steps: acylating a compound RCOOH and oxalyl chloride to prepare a first reaction liquid; adding methylamine into the first reaction liquid to carry out a first substitution reaction to prepare a second reaction liquid; adding sodium hydride into the second intermediate reaction liquid, stirring, adding chloropropionic acid or bromopropionic acid, and performing a second substitution reaction to prepare an N-methyl-beta-alanine derivative; the N-methyl-beta-alanine derivative has the following structural general formula:
Description
Technical Field
The invention relates to the field of fine chemical engineering, in particular to a preparation method of an N-methyl-beta-alanine derivative.
Background
The surfactant is an organic compound which can obviously reduce the surface tension of the liquid under a lower concentration, and has multiple performances of solubilization, wetting, foaming, defoaming, emulsification, dispersion and the like based on the characteristic, so the surfactant becomes a fine chemical product with wide application, and can be applied to various fields of daily chemical industry, textile printing and dyeing, rubber plastics, food, medicine, papermaking printing, leather, coating, metal processing, petroleum and the like. Among them, for personal care products such as toilet soap, bath lotion, facial cleanser and the like, safety and skin mildness are mainly considered at present, and besides the surfactant is required to have functions of cleaning, foaming, moistening and the like, the surfactant is also required to not damage epidermal cells, not act on skin protein and keep skin grease and skin per se in a normal state. Among many surfactants, N-methyl- β -alanine derivatives are preferred because of their high affinity for skin, low irritation, high safety, and good moisturizing effect.
The conventional method for preparing N-methyl- β -alanine derivatives and the corresponding problems are as follows: (1) the preparation method is characterized in that acrylic ester derivatives or acrylic acid cyanogen and methylamine are subjected to Michael addition reaction and then are subjected to substitution reaction with acyl chloride, the acrylic ester derivatives and acrylic acid cyanogen in the raw materials adopted by the preparation method are easy to polymerize, the cost of the acyl chloride is high, and acid is generated in the substitution reaction process, so that the requirement on equipment is high, a large amount of alkali is required to be added to neutralize the acid, and finally, high-concentration inorganic salt is produced, and the comprehensive cost is high; (2) the N-methyl-N-benzylamine is taken as a raw material, hydrogenation reduction is needed for deprotection, the hydrogenation reaction is unsafe, and the large benzyl groups are removed in the deprotection process, so that the atom economy is not met; (3) the reaction process of using chloropropionic acid or bromopropionic acid as a raw material and methylamine generates more byproducts, the yield is low, and partial byproducts even have potential safety hazards.
Disclosure of Invention
Based on the above, the invention provides a preparation method of the N-methyl-beta-alanine derivative, the preparation method carries out the preparation of the N-methyl-beta-alanine derivative through a one-pot reaction, the byproducts are less, and the raw material cost is low.
The invention is realized by the following technical scheme.
A method for preparing N-methyl-beta-alanine derivatives, comprising the following steps:
acylating a compound RCOOH and oxalyl chloride to prepare a first reaction liquid;
adding methylamine into the first reaction liquid to carry out a first substitution reaction to prepare a second reaction liquid;
adding sodium hydride into the second intermediate reaction liquid, stirring, adding chloropropionic acid or bromopropionic acid, and carrying out a second substitution reaction to prepare the N-methyl-beta-alanine derivative;
the N-methyl-beta-alanine derivative has the following structural general formula:
wherein R is a straight chain alkyl group having 10 to 20C atoms or a branched chain alkyl group having 10 to 20C atoms.
In one embodiment, the solvent used in the acylation reaction is dichloromethane or N, N-dimethylformamide.
In one embodiment, the solvent used in the first substitution reaction is dichloromethane or N, N-dimethylformamide.
In one embodiment, the methylamine is an aqueous methylamine solution.
In one embodiment, R is a straight chain alkyl group having 11 to 15C atoms or a branched chain alkyl group having 11 to 15C atoms.
In one embodiment, R is a straight chain alkyl group having 11C atoms, a branched alkyl group having 11C atoms, a straight chain alkyl group having 13C atoms, a branched alkyl group having 13C atoms, a straight chain alkyl group having 15C atoms, or a branched alkyl group having 15C atoms.
In one embodiment, the temperature of the acylation reaction is between-5 ℃ and 5 ℃; the time of acylation reaction is 3.5 h-4.5 h.
In one embodiment, the temperature of the first substitution reaction is from-20 ℃ to 25 ℃; the time of the first substitution reaction is 4-12 h.
In one embodiment, the stirring time is 20min to 40 min.
In one embodiment, the temperature of the second substitution reaction is 0 ℃ to 25 ℃; the time of the second substitution reaction is 4-12 h.
Compared with the prior art, the preparation method of the N-methyl-beta-alanine derivative has the following beneficial effects:
the preparation method of the N-methyl-beta-alanine derivative takes organic carboxylic acid, oxalyl chloride, methylamine and chloropropionic acid or bromopropionic acid as raw materials, adopts a one-pot method to prepare the N-methyl-beta-alanine derivative, and generates few byproducts in the reaction process and accords with atom economy.
Furthermore, the preparation method disclosed by the invention has the advantages of cheap and easily-obtained raw materials and low comprehensive cost, and is beneficial to industrialization.
Detailed Description
In order that the invention may be more fully understood, reference will now be made to the accompanying examples. The preferred embodiments of the present invention are given in the examples. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The words "preferably," "more preferably," in the present disclosure refer to embodiments of the disclosure that may, in some instances, provide certain benefits. However, other embodiments may be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, nor is it intended to exclude other embodiments from the scope of the invention.
When a range of values is disclosed herein, the range is considered to be continuous and includes both the minimum and maximum values of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values of the range is included. Further, when multiple range-describing features or characteristics are provided, the ranges may be combined. In other words, unless otherwise indicated, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein.
The invention provides a preparation method of an N-methyl-beta-alanine derivative, which comprises the following steps:
acylating a compound RCOOH and oxalyl chloride to prepare a first reaction liquid;
adding methylamine into the first reaction liquid to carry out a first substitution reaction to prepare a second reaction liquid;
adding sodium hydride into the second intermediate reaction liquid, stirring, adding chloropropionic acid or bromopropionic acid, and carrying out a second substitution reaction to prepare the N-methyl-beta-alanine derivative;
the N-methyl-beta-alanine derivative has the following structural general formula:
wherein R is a straight chain alkyl group having 10 to 20C atoms or a branched chain alkyl group having 10 to 20C atoms.
It is understood that, in the above-mentioned method for producing an N-methyl- β -alanine derivative, the first reaction solution is directly subjected to the next reaction without being subjected to post-treatments such as separation and purification, i.e., the production method of the present invention employs a one-pot method.
Oxalyl chloride is an important carboxylic acid derivative, and has important application in organic synthesis, drug synthesis and the like.
In one embodiment, the solvent used in the acylation reaction is dichloromethane or N, N-dimethylformamide. Preferably, the solvent used in the acylation reaction is dichloromethane. The yield was highest when dichloromethane was chosen.
Methylene chloride is an organic substance of the formulaIs CH2Cl2It is colorless transparent liquid, and has irritant odor similar to ether compounds. The gas is slightly soluble in water, is soluble in ethanol and ether, is a non-flammable low-boiling point solvent under the conventional use condition, can generate a weakly-flammable mixed gas when the steam in high-temperature air has high concentration, and is often used for replacing flammable petroleum ether, ether and the like.
In a specific example, R is a straight chain alkyl group having 11 to 15C atoms or a branched chain alkyl group having 11 to 15C atoms. Further, R is a linear alkyl group having 11C atoms, a branched alkyl group having 11C atoms, a linear alkyl group having 13C atoms, a branched alkyl group having 13C atoms, a linear alkyl group having 15C atoms, or a branched alkyl group having 15C atoms.
In one specific example, the temperature of the acylation reaction is between-5 ℃ and 5 ℃. As will be appreciated, in the present application, the temperature of the acylation reaction includes, but is not limited to, -5 ℃, -4 ℃, -3 ℃, -2 ℃, -1 ℃, 0 ℃, 1 ℃, 2 ℃, 3 ℃, 4 ℃, 5 ℃. Preferably, the temperature of the acylation reaction is 0 ℃.
In a specific example, the time of the acylation reaction is 3.5h to 4.5 h. It is understood that in the present application, the time of the acylation reaction includes, but is not limited to, 3.5h, 3.6h, 3.7h, 3.8h, 3.9h, 4.0h, 4.1h, 4.2h, 4.3h, 4.4h and 4.5 h. Preferably, the time of the acylation reaction is 4 h.
Acylation, otherwise known as acylation, is the reaction in organic chemistry in which hydrogen or another group is replaced by an acyl group. The compound which provides the acyl group is called an acylating agent. Specifically, in the present application, the acylation reaction is represented by the following general formula:
in a specific example, the acylation reaction is followed by the following steps: and concentrating the reaction solution, carrying out the next reaction on the concentrated reaction solution, recovering the obtained solvent, carrying out alkali washing, and removing acid in the solvent, so that the solvent can be reused to participate in the reaction.
In one embodiment, the solvent used in the first substitution reaction is dichloromethane or N, N-dimethylformamide. Preferably, the solvent used in the first substitution reaction is dichloromethane. The yield was highest when dichloromethane was chosen.
Specifically, the solvent used in the first substitution reaction is dried dichloromethane.
It is to be understood that the dried solvent refers to a solvent after removing water, and in the present invention, the solvent used in the first substitution reaction may be obtained by drying a solvent recovered by concentrating the reaction solution after the completion of the acylation reaction, in view of cost.
In one particular example, methylamine is an aqueous methylamine solution.
The methylamine water solution is colorless and transparent monomethylamine water solution, has ammonia smell, is easily soluble in water, is soluble in ethanol and diethyl ether, and has weak alkalinity. Can be used for rubber vulcanization accelerator, dye, medicine, pesticide, etc. The methylamine solution needs to be sealed and stored in a cool and ventilated place to avoid the sunlight irradiation, avoid the use of a device which is easy to generate static electricity and prevent violent impact and vibration.
More specifically, the concentration of the methylamine water solution is 30-50%. Preferably, the concentration of the aqueous methylamine solution is 40%.
In one specific example, the temperature of the first substitution reaction is from-20 ℃ to 25 ℃; the time of the first substitution reaction is 4-12 h.
Preferably, the temperature of the first substitution reaction is-20 ℃ to 0 ℃; the time of the first substitution reaction is 4-12 h.
It is understood that, in the present application, the temperature of the first substitution reaction includes, but is not limited to, -20 ℃, -15 ℃, -10 ℃, -9 ℃, -8 ℃, -7 ℃, -6 ℃, -5 ℃, -4 ℃, -3 ℃, -2 ℃, -1 ℃, 0 ℃.
It is understood that the time of the first substitution reaction is 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h in the present application.
Specifically, in the present application, the general formula of the first substitution reaction is as follows:
RCOCl+CH3NH2→RCONHCH3+HCl
in a specific example, the stirring time is 20min to 40 min.
It is understood that in the present application, the stirring time includes, but is not limited to, 20min, 21min, 22min, 23min, 24min, 25min, 26min, 27min, 28min, 29min, 30min, 31min, 32min, 33min, 34min, 35min, 36min, 37min, 38min, 39min and 40 min. Preferably, the stirring time is 30 min.
In one specific example, the temperature of the second substitution reaction is from 0 ℃ to 25 ℃.
It is understood that, in the present application, the temperature of the second substitution reaction includes, but is not limited to, 0 ℃, 5 ℃, 10 ℃, 11 ℃, 12 ℃, 13 ℃, 14 ℃, 15 ℃, 16 ℃, 17 ℃, 18 ℃, 19 ℃, 20 ℃, 21 ℃, 22 ℃, 23 ℃, 24 ℃ and 25 ℃.
In a specific example, the time for the second substitution reaction is 4 to 12 hours.
It is understood that, in the present application, the time of the second substitution reaction includes, but is not limited to, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12 h. Preferably, the time for the second substitution reaction is 6 h.
Specifically, in the present application, the general formula of the second substitution reaction is as follows:
in a specific example, the second substitution reaction further comprises the following steps: and (5) distilling under reduced pressure.
The vacuum distillation is used for separating and purifying compounds, and is especially suitable for separating and purifying high boiling point substances and compounds which are not heated to decompose, oxidize or polymerize when the boiling point is not reached in the atmospheric distillation. In the present application, the organic solvent is removed by distillation under reduced pressure.
In a more specific example, a method for preparing an N-methyl- β -alanine derivative, comprising the steps of:
s1: dissolving a compound RCOOH with a dichloromethane solvent, wherein R is a linear alkyl group having 10 to 20C atoms or a branched alkyl group having 10 to 20C atoms; after the dissolution is finished, slowly dripping oxalyl chloride into the solution for acylation reaction, wherein the temperature of the acylation reaction is-5 ℃ to 5 ℃, and the time of the acylation reaction is 3.5 hours to 4.5 hours;
s2: concentrating the solution after the acylation reaction, mixing the solution with dried dichloromethane, slowly dripping methylamine water solution into the solution to carry out a first substitution reaction, wherein the temperature of the first substitution reaction is-20-0 ℃, and the time is 4-12 h;
s3: after the first substitution reaction is finished, adding sodium hydride into the system in batches, stirring vigorously for 20-40 minutes, then slowly dropwise adding chloropropionic acid or bromopropionic acid into the solution to perform a second substitution reaction, wherein the temperature of the second substitution reaction is 0-25 ℃, the time of the second substitution reaction is 4-12 hours, and removing the organic solvent by reduced pressure distillation to obtain an oily product.
The washing and protecting product refers to a cleaning product, a skin-care product, a hair-care product or other cleaning and protecting products. Cleaning products including facial cleanser products, facial soap products, facial cleanser products, make-up removal products, blackhead removal products, exfoliating products, and cleaning products for particular parts of the teeth and body are within the scope of cleaning products. Skin care products include many types, such as lotions, creams, sunscreens, essential oils, barrier creams, masks, eye creams, hand creams, lip balms, body lotions, and also skin care ointments, which are all within the scope of skin care products. Hair care products are products for caring hair, such as shampoo, hair conditioner, hair mask, hair wax, hair spray, styling water, gel, hair dye, and the like. In addition, slimming creams, firming creams, sweat-removing sprays, etc. are also within the product category of the washing and caring product.
It is to be understood that in the present application, the personal care products include, but are not limited to, personal care products.
The method for producing the N-methyl- β -alanine derivative of the present invention will be described in further detail with reference to the following examples. The starting materials used in the following examples are all commercially available products unless otherwise specified.
Example 1
This example provides a method for preparing an N-methyl- β -alanine derivative, which comprises the following steps:
s1: dissolving C in dichloromethane11H23COOH, after the dissolution is finished, slowly dripping oxalyl chloride into the solution for acylation reaction at the temperature of 0 ℃ for 4 hours to obtain a first intermediate product C11H23COCl；
S2: concentrating and separating the solution after the acylation reaction is finished; then washing with alkali solution to recover dichloromethane;
s3: the first intermediate product C is11H23COCl is dissolved in dried dichloromethane, then methylamine solution is slowly dropped into the solution for carrying out the first substitution reaction, the temperature condition of the reaction is 0 ℃, and a second intermediate product C is prepared11H23CONHCH3；
S4: after the first substitution reaction is finished, sodium hydride is added into the reaction system in batches, the mixture is stirred vigorously for 30 minutes, chloropropionic acid is slowly added into the solution dropwise, the mixture is stirred and reacted for 6 hours at the temperature of 0 ℃, and the organic solvent is removed by reduced pressure distillation, so that a white solid product is obtained, wherein the total yield is 93%.
The structural formula of the final product is shown as follows:
the product characterization is as follows:
1H NMR(400MHz,CDCl3):δ3.64(t,J＝6.8Hz,2H),3.06(s,3H),2.65-2.50(m,2H),2.30(t,J＝7.6Hz,2H),1.65-1.56(m,2H),1.29-1.25(m,16H),0.88(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ175.3,174.4,44.6,36.5,33.6,33.3,32.9,31.9,29.6-29.3(5C),25.0,22.6,14.1。
example 2
This example provides a method for preparing an N-methyl- β -alanine derivative, which comprises the following steps:
s1: dissolving C in dichloromethane13H27COOH, after the dissolution is finished, slowly dripping oxalyl chloride into the solution for acylation reaction at the temperature of 0 ℃ for 4 hours to obtain a first intermediate product C13H27COCl；
S2: concentrating and separating the solution after the acylation reaction is finished; then washing with alkali solution to recover dichloromethane;
s3: the first intermediate product C is13H27COCl is dissolved in dried dichloromethane, then methylamine solution is slowly dropped into the solution for carrying out the first substitution reaction, the temperature condition of the reaction is 0 ℃, and a second intermediate product C is prepared13H27CONHCH3；
S4: after the first substitution reaction is finished, adding sodium hydride into the reaction system in batches, stirring vigorously for 30 minutes, then slowly dropwise adding chloropropionic acid into the solution, stirring and reacting at room temperature for 6 hours, and distilling under reduced pressure to remove the organic solvent to obtain a white solid product with the total yield of 89%.
The structural formula of the final product is shown as follows:
the product characterization is as follows:
1H NMR(400MHz,CDCl3):δ3.65(t,J＝6.8Hz,2H),3.05(s,3H),2.67-2.48(m,2H),2.30(t,J＝7.2Hz,2H),1.65-1.55(m,2H),1.31-1.22(m,20H),0.89(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ175.5,174.5,45.8,36.6,33.6,33.3,32.9,31.9,29.6-29.3(7C),25.2,22.5,14.1。
example 3
This example provides a method for preparing an N-methyl- β -alanine derivative, which comprises the following steps:
s1: dissolving C in dichloromethane15H31COOH, after the dissolution is finished, slowly dripping oxalyl chloride into the solution for acylation reaction at the temperature of 0 ℃ for 4 hours to obtain a first intermediate product C15H31COCl；
S2: concentrating and separating the solution after the acylation reaction is finished; then washing with alkali solution to recover dichloromethane;
s3: the first intermediate product C is15H31COCl is dissolved in dried dichloromethane, then methylamine solution is slowly dropped into the solution for carrying out the first substitution reaction, the temperature condition of the reaction is 0 ℃, and a second intermediate product C is prepared15H31CONHCH3；
S4: after the first substitution reaction is finished, adding sodium hydride into the reaction system in batches, stirring vigorously for 30 minutes, then slowly dropwise adding chloropropionic acid into the solution, stirring and reacting at room temperature for 6 hours, and distilling under reduced pressure to remove the organic solvent to obtain a white solid product with the total yield of 90%.
The structural formula of the final product is shown as follows:
the product characterization is as follows:
1H NMR(400MHz,CDCl3):δ3.66(t,J＝6.8Hz,2H),3.04(s,3H),2.64-2.46(m,2H),2.31(t,J＝7.2Hz,2H),1.65-1.53(m,2H),1.30-1.20(m,24H),0.89(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ175.3,174.1,45.7,36.6,33.5,33.3,32.9,31.9,29.9-29.0(9C),25.1,22.5,14.1。
example 4
This example provides a method for preparing an N-methyl- β -alanine derivative, which comprises the following steps:
s1: dissolving C in tetrahydrofuran solvent15H31COOH, after the dissolution is finished, slowly dripping oxalyl chloride into the solution for acylation reaction at the temperature of 0 ℃ for 4 hours to obtain a first intermediate product C15H31COCl；
S2: concentrating and separating the solution after the acylation reaction is finished; then washing with alkali solution to recover dichloromethane;
s3: the first intermediate product C is15H31COCl is dissolved in dried tetrahydrofuran, then methylamine solution is slowly dropped into the solution for carrying out the first substitution reaction, the temperature condition of the reaction is room temperature, and a second intermediate product C is prepared15H31CONHCH3；
S4: after the first substitution reaction is finished, sodium hydride is added into the reaction system in batches, the mixture is stirred vigorously for 10 minutes, chloropropionic acid is slowly added into the solution dropwise, the mixture is stirred and reacted for 6 hours at room temperature, and the organic solvent is removed by reduced pressure distillation, so that a white solid product is obtained, wherein the total yield is 65%.
The structural formula of the final product is shown as follows:
the product characterization is as follows:
1H NMR(400MHz,CDCl3):δ3.66(t,J＝6.8Hz,2H),3.04(s,3H),2.64-2.46(m,2H),2.31(t,J＝7.2Hz,2H),1.65-1.53(m,2H),1.30-1.20(m,24H),0.89(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ175.3,174.1,45.7,36.6,33.5,33.3,32.9,31.9,29.9-29.0(9C),25.1,22.5,14.1。
example 5
This example provides a method for preparing an N-methyl- β -alanine derivative, which comprises the following steps:
s1: dissolving C in dichloromethane15H31COOH, after the dissolution is finished, slowly dripping oxalyl chloride into the solution for acylation reaction at the temperature of 0 ℃ for 4 hours to obtain the productFirst intermediate product C15H31COCl；
S2: concentrating and separating the solution after the acylation reaction is finished; then washing with alkali solution to recover dichloromethane;
s3: the first intermediate product C is15H31COCl is dissolved in dried dichloromethane, then methylamine solution is slowly dropped into the solution for carrying out the first substitution reaction, the temperature condition of the reaction is 0 ℃, and a second intermediate product C is prepared15H31CONHCH3；
S4: after the first substitution reaction is finished, sodium hydride is added into the reaction system in batches, the mixture is stirred vigorously for 30 minutes, chloropropionic acid is slowly added into the solution dropwise, the mixture is stirred and reacted for 6 hours at the temperature of 50 ℃, and the organic solvent is removed by reduced pressure distillation, so that a white solid product is obtained, wherein the total yield is 49%.
The structural formula of the final product is shown as follows:
the product characterization is as follows:
1H NMR(400MHz,CDCl3):δ3.66(t,J＝6.8Hz,2H),3.04(s,3H),2.64-2.46(m,2H),2.31(t,J＝7.2Hz,2H),1.65-1.53(m,2H),1.30-1.20(m,24H),0.89(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ175.3,174.1,45.7,36.6,33.5,33.3,32.9,31.9,29.9-29.0(9C),25.1,22.5,14.1。
example 6
This example provides a method for preparing an N-methyl- β -alanine derivative, which comprises the following steps:
s1: dissolving C in dichloromethane13H27COOH, after the dissolution is finished, slowly dripping oxalyl chloride into the solution for acylation reaction at the temperature of 0 ℃ for 4 hours to obtain a first intermediate product C13H27COCl；
S2: concentrating the solution after the acylation reaction is finished;
s3: the first intermediate product C is13H27COCl is dissolved in undried dichloromethane, then methylamine solution is slowly dropped into the solution for carrying out the first substitution reaction, the temperature condition of the reaction is room temperature, and a second intermediate product C is prepared13H27CONHCH3；
S4: after the first substitution reaction is finished, adding sodium hydride into the reaction system in batches, stirring vigorously for 30 minutes, then slowly dropwise adding chloropropionic acid into the solution, stirring and reacting at room temperature for 6 hours, and distilling under reduced pressure to remove the organic solvent to obtain a solid product with the total yield of 19%.
The structural formula of the final product is shown as follows:
the product characterization is as follows:
1H NMR(400MHz,CDCl3):δ3.66(t,J＝6.8Hz,2H),3.04(s,3H),2.64-2.46(m,2H),2.31(t,J＝7.2Hz,2H),1.65-1.53(m,2H),1.30-1.20(m,24H),0.89(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ175.3,174.1,45.7,36.6,33.5,33.3,32.9,31.9,29.9-29.0(9C),25.1,22.5,14.1。
comparative example 1
The present comparative example provides a method for preparing an N-methyl- β -alanine derivative, as follows:
s1: dissolving C in dichloromethane13H27COOH, after the dissolution is finished, slowly dripping oxalyl chloride into the solution for acylation reaction at the temperature of 0 ℃ for 4 hours to obtain a first intermediate product C13H27COCl；
S2: concentrating and separating the solution after the acylation reaction is finished; then washing with alkali solution to recover dichloromethane;
s3: the first intermediate product C is13H27COCl is dissolved in dried dichloromethane and then slowly dissolvedDropping methylamine solution into the solution to carry out the first substitution reaction at the temperature of 0 ℃ to obtain a second intermediate product C13H27CONHCH3；
S4: after the first substitution reaction is finished, slowly dropwise adding chloropropionic acid into the solution, stirring and reacting for 6 hours at room temperature, and distilling under reduced pressure to remove the organic solvent to obtain an oily product, wherein the total yield is 0%.
The results of the effect verification experiments of examples 1 to 6 and comparative example 1 are summarized in table 1.
TABLE 1
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, so as to understand the technical solutions of the present invention specifically and in detail, but not to be understood as the limitation of the protection scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. It should be understood that the technical solutions provided by the present invention, which are obtained by logical analysis, reasoning or limited experiments, are within the scope of the appended claims. Therefore, the protection scope of the patent of the invention is subject to the content of the appended claims, and the description can be used for explaining the content of the claims.
Claims (10)
1. A method for preparing N-methyl-beta-alanine derivatives, which is characterized by comprising the following steps:
acylating a compound RCOOH and oxalyl chloride to prepare a first reaction liquid;
adding methylamine into the first reaction liquid to carry out a first substitution reaction to prepare a second reaction liquid;
adding sodium hydride into the second intermediate reaction liquid, stirring, adding chloropropionic acid or bromopropionic acid, and carrying out a second substitution reaction to prepare the N-methyl-beta-alanine derivative;
the N-methyl-beta-alanine derivative has the following structural general formula:
wherein R is a straight chain alkyl group having 10 to 20C atoms or a branched chain alkyl group having 10 to 20C atoms.
2. The process for producing an N-methyl- β -alanine derivative according to claim 1, wherein the solvent used in the acylation reaction is dichloromethane or N, N-dimethylformamide.
3. The process for producing an N-methyl- β -alanine derivative according to claim 1, wherein the solvent used in the first substitution reaction is dichloromethane or N, N-dimethylformamide.
4. The process for the preparation of an N-methyl- β -alanine derivative according to claim 1, wherein the methylamine is an aqueous methylamine solution.
5. The method for producing an N-methyl- β -alanine derivative according to claim 1, wherein R is a straight-chain alkyl group having 11 to 15C atoms or a branched-chain alkyl group having 11 to 15C atoms.
6. The method for producing an N-methyl- β -alanine derivative according to claim 5, wherein R is a straight-chain alkyl group having 11C atoms, a branched-chain alkyl group having 11C atoms, a straight-chain alkyl group having 13C atoms, a branched-chain alkyl group having 13C atoms, a straight-chain alkyl group having 15C atoms, or a branched-chain alkyl group having 15C atoms.
7. The method for producing an N-methyl- β -alanine derivative according to claim 1, wherein the temperature of the acylation reaction is-5 ℃ to 5 ℃; the time of acylation reaction is 3.5 h-4.5 h.
8. The method for producing an N-methyl- β -alanine derivative according to claim 1, wherein the temperature of the first substitution reaction is-20 ℃ to 25 ℃; the time of the first substitution reaction is 4-12 h.
9. The method for producing an N-methyl- β -alanine derivative according to any one of claims 1 to 8, wherein the stirring time is 20 to 40 min.
10. The method for producing an N-methyl- β -alanine derivative according to any one of claims 1 to 8, wherein the temperature of the second substitution reaction is 0 ℃ to 25 ℃; the time of the second substitution reaction is 4-12 h.
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