A process for the synthesis of 2-benzamido-2-phenyl-3-vinyl-1-indanone
By employing a series of precisely controlled reaction steps, 2-benzamido-2-phenyl-3-vinyl-1-indanone was synthesized using specific raw materials in a nitrogen atmosphere. This method solves the problems of single catalyst and low stereoselectivity in the synthesis of existing indanone compounds, achieving high yield and high stereoselectivity.
Patent Information
- Application Number
- CN202311718756.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-14
- Publication Date
- 2025-11-11
- Estimated Expiration
- 2043-12-14
AI Technical Summary
Existing methods for synthesizing indanone compounds suffer from problems such as reliance on a single catalyst, difficulty in introducing chiral centers, and low stereoselectivity.
Using N-(aryl(p-toluenesulfonyl)methyl)amide, thiazole carbene precursor, o-alkynylbenzaldehyde, acetonitrile, Pd(PPh3)4 and Cs2CO3 as raw materials, a series of reactions were carried out in a nitrogen atmosphere, including stirring, quenching, silica gel column chromatography separation and vacuum drying, to prepare 2-benzamido-2-phenyl-3-vinyl-1-indanone.
The efficient synthesis of 2-benzamido-2-phenyl-3-vinyl-1-indanone was achieved with a yield of 82%, high reaction efficiency, easy introduction of chiral carbon, and high stereoselectivity.
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Figure CN117720431B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of chemical synthesis technology of 2-benzamido-2-phenyl-3-vinyl-1-indanone, specifically to a method for synthesizing 2-benzamido-2-phenyl-3-vinyl-1-indanone. Background Technology
[0002] Indanones are important carbocyclic compounds that serve as useful skeletons in synthetic chemistry, biology, and materials science. These compounds are classified into several groups based on the position and number of carbonyl groups in their structure: 1-indanone, 1-indanone, 2-indanone, 1,2-indanedione, 1,3-indanedione, and ninhydrin. These compounds are synthetic precursors for many drugs and are widely used in drug development. The indanone skeleton is also a common synthetic precursor for many important aromatic and heterocyclic compounds. Because of the significant role of indanones in medicinal chemistry and organic synthesis, an increasing number of researchers are investigating their synthetic methods.
[0003] Methods for synthesizing 1-indanones and their derivatives include the Friedl-Crafts cyclization method, the Nazarov cyclization method, the polyphosphoric acid cyclization method, the transition metal-catalyzed ortho-bifunctionalized aromatic synthesis method, the CH bond-activated cyclization synthesis method, and the 2-alkynyl aldehyde / ketone-based synthesis method. Many synthetic methods for indanones have been reported. However, these methods have certain limitations, such as the use of a single catalyst, difficulty in introducing chiral centers, and low stereoselectivity. Therefore, we propose a method for synthesizing 2-benzamido-2-phenyl-3-vinyl-1-indanone to address the aforementioned problems. Summary of the Invention
[0004] The purpose of this invention is to provide a method for synthesizing 2-benzamido-2-phenyl-3-vinyl-1-indanone, in order to solve the problems currently found in the market as described in the background art.
[0005] To achieve the above objectives, the present invention provides the following technical solution: a method for synthesizing 2-benzamido-2-phenyl-3-vinyl-1-indanone, comprising the following steps:
[0006] S1: At room temperature, N-(aryl(p-toluenesulfonyl)methyl)amide (0.5 mmol), thiazolium carbene precursor (40.5 mg, 0.15 mmol, 30 mol%), and o-alkynylbenzaldehyde (0.75 mmol) were added to a dry double-necked round-bottom flask. Under a high-purity nitrogen atmosphere, dry acetonitrile (5 mL) was added using a syringe. The reaction mixture was stirred under nitrogen purging. Et3N (126.3 mg, 1.25 mmol, 2.5 equiv.) was added using a microsyringe.
[0007] S2: Continue stirring the reaction mixture under a nitrogen atmosphere to quench the reaction, remove the solvent, and separate the residue by silica gel column chromatography (PE:EA = 4:1 to 3:1) to obtain the o-amido ketone intermediate.
[0008] S3: The o-amidoketone intermediate was dried in a vacuum drying oven, and then acetonitrile (5 mL), Pd(PPh3)4 (115.6 mg, 0.1 mmol, 20 mol%) and Cs2CO3 (326 mg, 1 mmol, 2.0 equiv.) were added to the reaction flask under nitrogen protection, and the reaction was carried out again under nitrogen atmosphere at room temperature.
[0009] S4: Stop the reaction, remove the solvent, and separate the residue by silica gel column chromatography (PE:EA = 6:1 to 4:1) to give 2-benzamido-2-phenyl-3-vinyl-1-indanone.
[0010] Preferably, in step S1, the reaction mixture is continuously stirred for 5 minutes.
[0011] Preferably, in step S2, the reaction mixture is stirred for another 12 hours.
[0012] Preferably, in step S3, the o-amidoketone intermediate is dried in a vacuum drying oven for 24 hours.
[0013] Preferably, in step S3, the reactants are reacted in a nitrogen atmosphere at room temperature for 12 hours.
[0014] Compared with the prior art, the beneficial effects of the present invention are:
[0015] The synthesis method of this invention has high reaction efficiency, easily introduces chiral carbon, has high stereoselectivity, is novel in both method and product, and has a yield of 82%.
[0016] The above overview is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features of the invention will become readily apparent from the accompanying drawings and the following detailed description. Attached Figure Description
[0017] Figure 1 This is a schematic diagram illustrating the synthesis principle of 2-benzamido-2-phenyl-3-vinyl-1-indanone according to the present invention. Detailed Implementation
[0018] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0019] Please see Figure 1 A method for synthesizing 2-benzamido-2-phenyl-3-vinyl-1-indanone, comprising the following steps:
[0020] S1: At room temperature, N-(aryl(p-toluenesulfonyl)methyl)amide (0.5 mmol), thiazolium carbene precursor (40.5 mg, 0.15 mmol, 30 mol%), and o-alkynylbenzaldehyde (0.75 mmol) were added to a dry double-necked round-bottom flask. Under a high-purity nitrogen atmosphere, dry acetonitrile (5 mL) was added using a syringe. The reaction mixture was stirred continuously for 5 min under nitrogen purging. Et3N (126.3 mg, 1.25 mmol, 2.5 equiv.) was added using a microsyringe.
[0021] S2: The reaction mixture was stirred for 12 hours under a nitrogen atmosphere to quench the reaction. After removing the solvent, the residue was separated by silica gel column chromatography (PE:EA = 4:1 to 3:1) to obtain the o-amido ketone intermediate.
[0022] S3: The o-amidoketone intermediate was dried in a vacuum drying oven for 24 h. Then, under nitrogen protection, acetonitrile (5 mL), Pd(PPh3)4 (115.6 mg, 0.1 mmol, 20 mol%) and Cs2CO3 (326 mg, 1 mmol, 2.0 equiv.) were added to the reaction flask, and the reaction was carried out again under nitrogen atmosphere and at room temperature for 12 h.
[0023] S4: Stop the reaction, remove the solvent, and separate the residue by silica gel column chromatography (PE:EA = 6:1 to 4:1) to give 2-benzamido-2-phenyl-3-vinyl-1-indanone.
[0024] The synthesis method of this invention has high reaction efficiency, easily introduces chiral carbon, has high stereoselectivity, is novel in both method and product, and has a yield of 82%.
[0025] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Furthermore, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.
[0026] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.
Claims
1. A method for synthesizing 2-benzamido-2-phenyl-3-vinyl-1-indanone, characterized in that, Includes the following steps: S1: At room temperature, 0.5 mmol N-(aryl(p-toluenesulfonyl)methyl)amide, 40.5 mg, 0.15 mmol, 30 mol% thiazole carbene precursor, and 0.75 mmol o-alkynylbenzaldehyde were added to a dry two-necked round-bottom flask. Under a high-purity nitrogen atmosphere, 5 mL of dry acetonitrile was added using a syringe. The reaction mixture was stirred continuously for 5 min under nitrogen purging. 126.3 mg, 1.25 mmol, and 2.5 equiv were then added. Add it using a microsyringe; The structural formula of the thiazole carbene precursor is as follows: ； S2: The reaction mixture was stirred for 12 h under a nitrogen atmosphere to carry out the quenching reaction. After removing the solvent, the residue was separated by silica gel column chromatography with PE:EA = 4:1 to 3:1 to obtain the o-amido ketone intermediate. S3: The o-amidoketone intermediate was dried in a vacuum drying oven for 24 h, and then, under nitrogen protection, 5 mL of acetonitrile, 115.6 mg, 0.1 mmol, and 20 mol% were added. And 326 mg, 1 mmol, 2.0 equiv. Add it to the reaction flask and react again at room temperature under a nitrogen atmosphere for 12 h; S4: Stop the reaction, remove the solvent, and separate the residue by silica gel column chromatography with PE:EA = 6:1 to 4:1 to obtain 2-benzamido-2-phenyl-3-vinyl-1-indanone.