CN110563599A - method for preparing 3-methoxy-N-phenylpropionamide - Google Patents
method for preparing 3-methoxy-N-phenylpropionamide Download PDFInfo
- Publication number
- CN110563599A CN110563599A CN201910820497.4A CN201910820497A CN110563599A CN 110563599 A CN110563599 A CN 110563599A CN 201910820497 A CN201910820497 A CN 201910820497A CN 110563599 A CN110563599 A CN 110563599A
- Authority
- CN
- China
- Prior art keywords
- phenylpropionamide
- reaction
- methoxy
- methylthio
- target product
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of fine chemical engineering, and discloses a method for preparing 3-methoxy-N-phenylpropionamide. The method comprises the following specific steps: 3-methylthio-N-phenylpropionamide is used as a raw material, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) and potassium carbonate are used as additives, and the reaction is carried out in methanol at 110 ℃ for 24 hours to obtain a target product, namely 3-methoxy-N-phenylpropionamide. The method is simple and convenient to operate, 3-methylthio-N-phenylpropionamide is used as a reaction raw material, a target product is efficiently synthesized in one step, toxic reagents of acryloyl chloride and transition metal salt are avoided, and the method has potential application value.
Description
Technical Field
the invention belongs to the field of fine chemical engineering, and relates to a method for preparing 3-methoxy-N-phenylpropionamide.
background
3-methoxy-N-phenylpropionamide is an important organic compound, the parent skeleton of the compound is widely existed in various natural products with pharmaceutical activity, and the compound is also an important organic synthesis intermediate. Therefore, how to directly and efficiently synthesize 3-methoxy-N-phenylpropionamide has attracted a high attention from chemists.
Only one example of a method for synthesizing 3-methoxy-N-phenylpropionamide has been reported (Chemical Communications,2013,49,517), which synthesizes 3-methoxy-N-phenylpropionamide using N-phenylacrylamide and methanol as raw materials, copper chloride as a catalyst and cesium carbonate as a base additive, and dichloromethane as a reaction solvent, but the synthesis method still has the following disadvantages: firstly, synthesizing a raw material N-phenyl acrylamide, wherein toxic and volatile acryloyl chloride is needed; secondly, the process requires the use of toxic transition metal catalysts. Therefore, it is necessary to search for a method for synthesizing 3-methoxy-N-phenylpropionamide with high efficiency and green color.
Disclosure of Invention
the invention aims to overcome the defects of the prior art and provide a high-efficiency and green synthesis method of 3-methoxy-N-phenylpropionamide.
The invention relates to a method for synthesizing 3-methoxy-N-phenylpropionamide, which comprises the following steps: sequentially adding 3-methylthio-N-phenylpropionamide, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt [ Selectfluor ] and potassium carbonate into a sealed tube containing a reaction solvent methanol, violently stirring for 24 hours at 110 ℃, and after the reaction is finished, sequentially concentrating a reaction solution and carrying out column chromatography separation to obtain a target product, namely the 3-methoxy-N-phenylpropionamide.
The reaction solvent of the system of the invention is methanol.
The concentration of the reaction system in the present invention was 0.6 mol/liter.
In the invention, the molar ratio of the 3-methylthio-N-phenylpropionamide, the 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt and the potassium carbonate is 1: 1: 3.
The reaction temperature in the present invention is 110 ℃.
The reaction time in the present invention is 24 hours.
the following two possible reaction mechanisms are involved in the invention: firstly, 3-methylthio-N-phenyl propionamide generates corresponding N-phenyl acrylamide under the action of Selectfluor, and secondly, the N-phenyl acrylamide and methanol obtain a target product, namely 3-methoxy-N-phenyl propionamide under the action of potassium carbonate; secondly, the 3-methylthio-N-phenylpropionamide is subjected to Selectfluor reaction to produce the corresponding 3-methylsulfinyl-N-phenylpropionamide, and the 3-methylsulfinyl-N-phenylpropionamide is subjected to alcohol substitution reaction under the action of methanol and potassium carbonate to produce the 3-methoxy-N-phenylpropionamide.
Detailed Description
The following examples will help illustrate the invention, but do not limit its scope.
Specific example 1:
The synthesis method comprises the following steps: methanol (10mL), 3-methylthio-N-phenylpropionamide (6mmol,1.17g), 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt [ Selectfluor ] (6mmol,2.12g) and potassium carbonate (18mmol,2.48g) were added in this order to a 100mL sealed tube, the reaction temperature was controlled at 110 ℃ and the reaction was stirred vigorously for 24 hours. After the reaction is finished, the reaction solution is concentrated and separated by column chromatography in turn, and the target product 3-methoxy-N-phenylpropionamide (0.97g, 90%) can be obtained.
The reaction involves the following equation:
Specific example 2:
The synthesis method comprises the following steps: methanol (10mL), 3-methylthio-N-phenylpropionamide (6mmol,1.17g), 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt [ Selectfluor ] (6mmol,2.12g) and potassium carbonate (12mmol,1.65g) were added in this order to a 100mL sealed tube, the reaction temperature was controlled at 110 ℃ and the reaction was stirred vigorously for 24 hours. After the reaction is finished, the reaction solution is concentrated and separated by column chromatography in turn, and the target product 3-methoxy-N-phenylpropionamide (0.59g, 55%) can be obtained.
The reaction involves the following equation:
Specific example 3:
Comparative experiment: methanol (10mL), 3-methylthio-N-phenylpropionamide (6mmol,1.17g) and potassium carbonate (18mmol,2.48g) were added sequentially in a 100mL sealed tube, the reaction temperature was controlled at 110 ℃ and the reaction was stirred vigorously for 24 hours. After the reaction is finished, reaction liquid is concentrated and separated by column chromatography in sequence, and the target product 3-methoxy-N-phenylpropionamide cannot be separated.
The reaction involves the following equation:
The nuclear magnetic data and the mass spectrum data of the target product 3-methoxy-N-phenylpropionamide are as follows:
1H NMR(300MHz,CDCl3)δ8.28(brs,1H),7.44(d,J＝7.6Hz,2H),7.28–7.11(m,2H),7.01(t,J＝7.4Hz,1H),3.64(t,J＝6.0Hz,2H),3.35(s,3H),2.55(t,J＝5.7Hz,2H).
13C NMR(101MHz,CDCl3)δ169.87,138.07,128.96,124.13,119.92,68.63,58.95,38.00.
LCMS(ESI,m/z):180.05[M+H]+.
The foregoing describes alternative embodiments of the invention to teach those skilled in the art how to make and reproduce the invention. Some conventional technical aspects have been simplified and omitted for the purpose of teaching the inventive arrangements. Those skilled in the art will appreciate variations from this aspect that fall within the scope of the invention.
Claims (5)
1. A process for the preparation of 3-methoxy-N-phenylpropionamide characterized by: sequentially adding 3-methylthio-N-phenylpropionamide, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt and potassium carbonate into a sealed tube containing a reaction solvent methanol, violently stirring, and after the reaction is finished, sequentially concentrating a reaction solution and carrying out column chromatography separation to obtain a target product, namely the 3-methoxy-N-phenylpropionamide, wherein the molar ratio of the 3-methylthio-N-phenylpropionamide, the 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt to the potassium carbonate is 1: 1: 3.
2. the method as claimed in claim 1, further comprising reduced pressure distillation after the reaction, column chromatography separation and collection of the target product.
3. the method of claim 1, wherein: the reaction temperature was 110 ℃.
4. The method of claim 1, wherein: the reaction time was 24 hours.
5. The method of claim 1, wherein: the concentration of the reaction system was 0.6 mol/liter.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910820497.4A CN110563599B (en) | 2019-09-02 | 2019-09-02 | Method for preparing 3-methoxy-N-phenylpropionamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910820497.4A CN110563599B (en) | 2019-09-02 | 2019-09-02 | Method for preparing 3-methoxy-N-phenylpropionamide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110563599A true CN110563599A (en) | 2019-12-13 |
| CN110563599B CN110563599B (en) | 2022-03-22 |
Family
ID=68777378
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910820497.4A Active CN110563599B (en) | 2019-09-02 | 2019-09-02 | Method for preparing 3-methoxy-N-phenylpropionamide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110563599B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113135865A (en) * | 2021-04-01 | 2021-07-20 | 常州大学 | Method for preparing N-phenyl- (3-benzotriazole) propionamide |
| CN113816882A (en) * | 2021-11-09 | 2021-12-21 | 常州大学 | Method for preparing 2-alkyl thiobenzonitrile |
| CN115260050A (en) * | 2022-08-04 | 2022-11-01 | 常州大学 | Method for preparing 3-bromo-N-arylpropionamide by participation of NBS |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104789040A (en) * | 2014-01-21 | 2015-07-22 | 株式会社理光 | Image forming apparatus and image forming method |
| CN108675938A (en) * | 2018-06-29 | 2018-10-19 | 常州大学 | A kind of new method preparing N- n-butyl acryloyloxy ethyl amides |
| CN109232476A (en) * | 2018-11-06 | 2019-01-18 | 常州大学 | A kind of new method preparing N- phenyl -3- morpholine propionamide |
-
2019
- 2019-09-02 CN CN201910820497.4A patent/CN110563599B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104789040A (en) * | 2014-01-21 | 2015-07-22 | 株式会社理光 | Image forming apparatus and image forming method |
| CN108675938A (en) * | 2018-06-29 | 2018-10-19 | 常州大学 | A kind of new method preparing N- n-butyl acryloyloxy ethyl amides |
| CN109232476A (en) * | 2018-11-06 | 2019-01-18 | 常州大学 | A kind of new method preparing N- phenyl -3- morpholine propionamide |
Non-Patent Citations (1)
| Title |
|---|
| KE YANG等: "Metal-Free C–S Bond Cleavage to Access N-Substituted Acrylamide and β-Aminopropanamide", 《EUROPEAN JOURNAL OF ORGANIC CHEMISTRY》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113135865A (en) * | 2021-04-01 | 2021-07-20 | 常州大学 | Method for preparing N-phenyl- (3-benzotriazole) propionamide |
| CN113816882A (en) * | 2021-11-09 | 2021-12-21 | 常州大学 | Method for preparing 2-alkyl thiobenzonitrile |
| CN113816882B (en) * | 2021-11-09 | 2022-07-19 | 常州大学 | Method for preparing 2-alkyl thiobenzonitrile |
| CN115260050A (en) * | 2022-08-04 | 2022-11-01 | 常州大学 | Method for preparing 3-bromo-N-arylpropionamide by participation of NBS |
| CN115260050B (en) * | 2022-08-04 | 2023-08-22 | 常州大学 | Method for preparing 3-bromo-N-aryl propionamide by using NBS |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110563599B (en) | 2022-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110563599B (en) | Method for preparing 3-methoxy-N-phenylpropionamide | |
| CN111777536A (en) | Method for preparing asymmetric disulfide | |
| CN111560624B (en) | Method for continuously preparing isobenzofuran compounds by using microchannel reaction device | |
| CN109232476B (en) | Method for preparing N-phenyl-3-morpholine propionamide | |
| CN111205279A (en) | Polysubstituted benzodihydrofuran heterocyclic compound and preparation method and application thereof | |
| CN110590734B (en) | Method for synthesizing 2-methyl-4H-benzo [ d ] [1,3] oxathiacyclohexadiene-4-one | |
| CN110407742B (en) | Method for preparing 3-bromo-4-methylsulfonylpyridine | |
| CN111848464B (en) | Method for preparing 2- (methylsulfinyl) benzoic acid | |
| Molander et al. | Novel processes for stereoselective organic synthesis | |
| CN110452138B (en) | Method for preparing N-phenyl-3-methylsulfonyl propionamide | |
| CN109438414B (en) | Method for preparing benzo 1, 3-oxathiane-4-ketone | |
| CN111253331B (en) | Method for synthesizing spiroisoxazoline by using dihydrochalcone as raw material | |
| CN108947995B (en) | Preparation method of polysubstituted oxadiazine derivative | |
| CN110317170B (en) | Green synthesis method of 3-phenanthridinyl propyl formate compound | |
| CN108912001B (en) | Catalytic synthesis method of 1, 3-dicarbonyl compound | |
| CN110078608B (en) | Method for synthesizing 2-benzyl-2-ethyl pentanal through beta-position derivatization reaction of aliphatic aldehyde | |
| CN111732552A (en) | Method for synthesizing 1, 3-oxazole-2-thioketone by palladium catalysis | |
| CN111153826B (en) | Synthesis method of 3-ethoxy-N-p-tolylpropionamide | |
| CN110156683B (en) | Synthesis method of quinoline oxide | |
| CN110655485A (en) | Preparation method of N-substituted indolone | |
| CN117263872B (en) | Synthesis method of 2-acetylpyrazine | |
| CN111943925B (en) | Synthesis method of chromanone compounds | |
| CN113135865B (en) | Method for preparing N-phenyl-3- (benzotriazole-1-yl) propionamide | |
| CN116768723A (en) | Tevaleraldehyde remote polyarylation method | |
| CN108675960B (en) | Catalytic synthesis method of 6-difluorophenanthridine compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |