Synthesis method of 2-(benzenesulfonamide)-3-oxo-3-phenyl propionate compound

Abstract

The invention provides a synthesis method of a 2-(benzenesulfonamide)-3-oxo-3-phenyl propionate compound, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: adding a benzoyl acetate compound, a sulfonamide compound and a photosensitizer into a solvent to prepare a reaction solution, reacting under blue light irradiation, and obtaining a target product after the reaction is finished. According to the invention, the problem of a large number of byproducts caused by various oxidants used in the traditional method is avoided; an organic photosensitizer 4CzIPN is used as a catalyst, so that the reaction time is greatly shortened, the reaction can be completed only in 10 minutes, the reaction efficiency is improved, and the product does not have metal residues; the reaction conditions of the reaction are mild, and the reaction can be carried out in a room-temperature air atmosphere.

Description

Technical Field

[0001] This invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionate ester compounds. Background Art

[0002] Nitrogen-containing compounds are of paramount importance due to their application in functionalizing various heteroaromatic rings, serving as the main structures for a wide range of biologically and pharmacologically active ingredients. Correspondingly, nitrogen-containing structures are a special type of subunit, widely used in natural products, agrochemicals, pharmaceuticals, and functional materials due to their fascinating physicochemical properties and bioactivity. Against this research background, the synthetic strategies for CN-C bonds have been a hot topic for chemists worldwide. With the continuous development of new reagents and methods, as well as new synthetic strategies and instrumental analysis, our understanding of these structures has deepened. Therefore, various strategies have been developed to obtain different nitrogen-containing scaffolds for practically efficient CN-C formation. Traditionally, CN-C bond formation reactions are established using common nitrogen-containing nucleophiles and electrophiles, such as amines, amides, and imines. However, sometimes the functional group compatibility of these related platforms is poor, requiring harsh reaction conditions. Given the importance of these compounds in scientific research, significant efforts have been made to develop alternative synthetic strategies for efficiently constructing CN-C bonds. Indeed, in accordance with the principles of sustainable and green chemistry, developing methods that can introduce nitrogen sources under mild and green conditions remains highly desirable.

[0003] Traditional carbon-nitrogen bond construction often requires transition metal catalysis or prefunctionalization of reactants. This not only leads to heavy metal contamination of the product but also generates a series of acidic byproducts, which is detrimental to environmental friendliness. For example, Barluenga et al. (J. Barluenga, MA. Fernandez, F. Aznar, C. Valdes, Chem. Commun. 2004, 1400.) used binap with prefunctionalized ethylene bromide to generate an amination product, producing byproducts such as hydrogen bromide. In alternative routes to the indole core, Willis et al. (MC. Willis, G. G. Brace, T. J. K. Findlay, I. P. Holmes, Adv. Synth. Catal. 2006, 348, 851.) used 2-(2-haloalkenyl)aryl halides as coupling moieties to primary amines to synthesize a series of indole derivatives, quantitatively generating two molecules of hydrogen chloride as a byproduct. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention proposes a method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionate esters. This method has high reaction efficiency and produces products without metal residues or byproducts.

[0005] To achieve the above objectives, the technical solution of the present invention is implemented as follows:

[0006] A method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionate compounds includes the following steps: adding benzoyl acetate compounds, sulfonamide compounds and photosensitizers into a solvent to prepare a reaction solution, carrying out the reaction under blue light irradiation, and obtaining the target product after the reaction is completed;

[0007] The structural formula of the benzoyl acetate compound is as follows: R 1 R is alkyl, halogen, nitro, and trifluoromethyl. 3 The alkyl substituent is 7 carbons or less and cyclohexyl; the preferred alkyl substituents are methyl, ethyl, isopropyl or butyl.

[0008] The structural formula of the sulfonamide compound is as follows: R 2 It can be alkyl, halogen, nitro, trifluoromethyl, trifluoromethoxy, celecoxib group and valdecoxib group.

[0009] The photosensitizer is 4CzIPN, with the following structural formula:

[0010] The solvent is dichloromethane, chloroform, acetonitrile, or ethyl acetate.

[0011] The molar ratio of the benzoyl acetate compound and the sulfonamide compound is 1:(2-4).

[0012] The amount of photosensitizer is 1-2 mol of the substance of the benzoyl acetate compound.

[0013] The ratio of the benzoyl acetate compound to the solvent is 0.1-0.2 mmol / mL.

[0014] The reaction was carried out at room temperature for 10 min to 4 h.

[0015] The structural formula of the 2-(benzenesulfonamide)-3-oxo-3-phenylpropionate compound is as follows: In the formula R 1 R is alkyl, halogen, nitro, and trifluoromethyl. 2 R is an alkyl, halogen, nitro, trifluoromethyl, trifluoromethoxy, celecoxib group, and valdecoxib group. 3 It consists of alkyl substituents with 7 or fewer carbon atoms and cyclohexyl groups.

[0016] Preferably, the blue light wavelength is 465nm.

[0017] The beneficial effects of this invention are:

[0018] (1) This method avoids the problem of a large number of byproducts caused by the use of various oxidants in traditional methods;

[0019] (2) This method uses organic photosensitizer 4CzIPN as a catalyst, which greatly shortens the reaction time to only 10 minutes, improves the reaction efficiency, and the product will not have metal residue.

[0020] (3) The reaction conditions are mild and the reaction can occur at room temperature in air. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 The 1H NMR spectrum of ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate;

[0023] Figure 2 The carbon NMR spectrum of ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate;

[0024] Figure 3 The 1H NMR spectrum of ethyl 2-((4-chlorophenyl)sulfonamido)-3-oxo-3-phenylpropionate;

[0025] Figure 4 The carbon NMR spectrum of ethyl 2-((4-chlorophenyl)sulfonamido)-3-oxo-3-phenylpropionate;

[0026] Figure 5 The 1H NMR spectrum of ethyl 2-((4-(tert-butyl)phenyl)sulfonamido)-3-oxo-3-phenylpropionate;

[0027] Figure 6 The carbon NMR spectrum of ethyl 2-((4-(tert-butyl)phenyl)sulfonamido)-3-oxo-3-phenylpropionate;

[0028] Figure 7 The 1H NMR spectrum of ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-(p-tolyl)propionate;

[0029] Figure 8The carbon NMR spectrum of ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-(p-tolyl)propionate;

[0030] Figure 9 The 1H NMR spectrum of ethyl 3-(4-fluorophenyl)-2-((4-methylphenyl)sulfonamido)-3-oxopropionic acid is shown.

[0031] Figure 10 The carbon NMR spectrum of ethyl 3-(4-fluorophenyl)-2-((4-methylphenyl)sulfonamido)-3-oxopropionic acid is shown.

[0032] Figure 11 The NMR fluorine spectrum of ethyl 3-(4-fluorophenyl)-2-((4-methylphenyl)sulfonamido)-3-oxopropionic acid;

[0033] Figure 12 The 1H NMR spectrum of methyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate;

[0034] Figure 13 The carbon NMR spectrum of methyl 2-((4-methylphenyl)sulfonamide)-3-oxo-3-phenylpropionate. DETAILED DESCRIPTION

[0035] 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.

[0036] Example 1

[0037] The structural formula of ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate in this embodiment is:

[0038]

[0039] In a test tube, 38.4 mg (0.2 mmol) of ethyl benzoyl, 149.3 mg (0.4 mmol) of 4-methyl-N-(phenyl-3-iodoenyl)benzenesulfonamide, 1.58 mg (1 mol%) of 4CzIPN, and 1.0 mL of dichloromethane were added. The mixture was magnetically stirred in air under 465 nm blue light irradiation and reacted at room temperature for 10 min. TLC analysis showed that the ethyl benzoyl reactant had reacted completely. The product, ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate, was purified by vacuum rotary evaporation and thin-layer chromatography. The product yielded 67.4 mg of ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate, with a yield of 93%. The product was further purified by...1 H NMR, 13 C NMR confirmed, such as Figure 1 and 2 shown. 1 HNMR(600MHz,Chloroform-d)δ8.02-7.96(m,2H),7.73(d,J=8.3Hz,2H),7.63(t,J=7.4Hz,1H),7.51-7.45(m,2H),7.2 4(d,J=8.1Hz,4H),5.95(d,J=8.9Hz,1H),5.58(d,J=8.9Hz,1H),3.99-3.95(m,2H),2.38(s,3H),1.05(t,J=7.1Hz,3H). 13 C NMR (151MHz, Chloroform-d) δ190.3,166.0,143.9,136.5,134.5,133.5,129.6,129.3,128.8,127.3,62.6,60.8,21.4,13.6.

[0040] Example 2

[0041] The structural formula of ethyl 2-((4-chlorophenyl)sulfonamido)-3-oxo-3-phenylpropionate in this embodiment is:

[0042]

[0043] The preparation method is as follows: In a test tube, add 38.4 mg (0.2 mmol) ethyl benzoyl, 157.4 mg (0.4 mmol) 4-methyl-N-(phenyl-3-iodoenyl)benzenesulfonamide, 1.58 mg (1 mol%) 4CzIPN, and 1.0 mL dichloromethane. Stir magnetically in air under 465 nm blue light irradiation and react at room temperature for 10 min. TLC analysis showed that the ethyl benzoyl reactant had reacted completely. The product, ethyl 2-((4-chlorophenyl)sulfonamido)-3-oxo-3-phenylpropionate, was purified by vacuum rotary evaporation and thin-layer chromatography. The mass of the product was 71.56 mg, with a yield of 80%. The product was further purified by... 1 H NMR, 13 C NMR confirmed, such as Figure 3 and 4 shown. 1H NMR(600MHz,Chloroform-d)δ8.03-7.98(m,2H),7.83-7.78(m,2H),7.69-7.64(m,1H),7.55-7.49(m,2H), 7.47-7.42(m,2H),6.08(d,J=8.8Hz,1H),5.63(d,J=8.8Hz,1H),4.08-3.97(m,2H),1.09(t,J=7.1Hz,3H). 13 C NMR (151MHz, Chloroform-d) δ189.8,165.7,139.6,138.1,134.7,133.3,129.3,128.9,128.7,128.0,62.8,60.7,13.7.

[0044] Example 3

[0045] The structural formula of ethyl 2-((4-(tert-butyl)phenyl)sulfonamido)-3-oxo-3-phenylpropionate in this embodiment is:

[0046]

[0047] The preparation method is as follows: In a test tube, add 38.4 mg (0.2 mmol) ethyl benzoyl, 157.4 mg (0.4 mmol) 4-tert-butyl-N-(phenyl-3-iodoenyl)benzenesulfonamide, 1.58 mg (1 mol%) 4CzIPN, and 1.0 mL dichloromethane. Stir magnetically in air under 465 nm blue light irradiation and react at room temperature for 10 min. TLC analysis showed that the ethyl benzoyl reactant had reacted completely. The product, ethyl 2-((4-(tert-butyl)phenyl)sulfonamide)-3-oxo-3-phenylpropionate, was purified by vacuum rotary evaporation and thin-layer chromatography. The mass of the product was 63.1 mg, with a yield of 78%. The product was further purified by... 1 HNMR, 13 CNMR confirmed, such as Figure 5 and 6 shown. 1 H NMR(600MHz,Chloroform-d)δ8.03-7.98(m,2H),7.81-7.76(m,2H),7.67-7.61(m,1H),7.52-7.45(m,4 H),5.99(d,J=9.0Hz,1H),5.62(d,J=9.0Hz,1H),4.02-3.89(m,2H),1.32(s,9H),1.05(t,J=7.1Hz,3H). 13C NMR (151MHz, Chloroform-d) δ190.1,165.9,156.9,136.3,134.5,133.4,129.3,128.8,127.2,126.0,62.6,60.8,35.1,31.0,13.7.

[0048] Example 4

[0049] The structural formula of ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-(p-tolyl)propionate in this embodiment is:

[0050]

[0051] The preparation method is as follows: In a test tube, add 41.2 mg (0.2 mmol) of ethyl 3-oxo-3-(p-tolyl)propionate, 157.4 mg (0.4 mmol) of 4-methyl-N-(phenyl-3-iodoenyl)benzenesulfonamide, 1.58 mg (1 mol%) of 4CzIPN, and 1.0 mL of dichloromethane. Stir magnetically in air under 465 nm blue light irradiation and react at room temperature for 10 min. TLC analysis showed that the ethyl benzoylpropionate reacted completely. The product, ethyl 2-((4-methylphenyl)sulfonamide)-3-oxo-3-(p-tolyl)propionate, was purified by vacuum rotary evaporation and thin-layer chromatography. The mass of the product was 61.0 mg, with a yield of 81%. The product was then subjected to further processing. 1 HNMR, 13 C NMR confirmed, such as Figure 7 and 8 shown. 1 HNMR(600MHz,Chloroform-d)δ7.91(d,J=8.0Hz,2H),7.75(d,J=8.1Hz,2H),7.31-7.24(m,4H) ,5.99(d,J=8.9Hz,1H),5.58(d,J=8.8Hz,1H),3.98(m,2H),2.44(s,3H),1.07(t,J=7.1Hz,3H). 13 C NMR (151MHz, Chloroform-d) δ189.4,166.1,145.8,143.8,136.6,130.9,129.6,129.51,129.50,127.2,62.5,60.7,21.8,21.4,13.6.

[0052] Example 5

[0053] The structural formula of ethyl 3-(4-fluorophenyl)-2-((4-methylphenyl)sulfonamido)-3-oxopropionic acid in this embodiment is:

[0054]

[0055] The preparation method is as follows: In a test tube, 42.0 mg (0.2 mmol) of ethyl 3-oxo-3-(p-fluorophenyl)propionate, 157.4 mg (0.4 mmol) of 4-methyl-N-(phenyl-3-iodoenyl)benzenesulfonamide, 1.58 mg (1 mol%) of 4CzIPN, and 1.0 mL of dichloromethane were added. The mixture was magnetically stirred in air under 465 nm blue light irradiation and reacted at room temperature for 10 min. TLC analysis showed that the ethyl benzoylpropionate had reacted completely. The product, ethyl 3-(4-fluorophenyl)-2-((4-methylphenyl)sulfonamide)-3-oxopropionate, was purified by vacuum rotary evaporation and thin-layer chromatography. The mass of the product was 68.4 mg, with a yield of 90%. The product was further purified by... 1 HNMR, 13 C NMR, 19 F NMR confirmed, such as Figure 9-11 shown. 1 H NMR(600MHz,Chloroform-d)δ8.10-8.04(m,2H),7.77-7.72(m,2H),7.28(d,J=8.2Hz,2H),7.18(t,J =8.5Hz,2H),5.95(d,J=9.0Hz,1H),5.56(d,J=9.0Hz,1H),4.06-3.93(m,2H),1.08(t,J=7.1Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ188.6,166.5(d,J=258.1Hz),165.9,144.0,136.4,132.2( d,J=9.6Hz),129.3,129.6,127.3,126.4,116.1(d,J=22.1Hz),62.7,60.8,21.5,13.69. 19 F NMR(565MHz,Chloroform-d)δ-101.80.

[0056] Example 6

[0057] The structural formula of methyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate in this embodiment is:

[0058]

[0059] The preparation method is as follows: In a test tube, add 35.6 mg (0.2 mmol) of methyl 3-oxo-3-phenylpropionate, 157.4 mg (0.4 mmol) of 4-methyl-N-(phenyl-3-iodoenyl)benzenesulfonamide, 1.58 mg (1 mol%) of 4CzIPN, and 1.0 mL of dichloromethane. Stir magnetically in air under 465 nm blue light irradiation and react at room temperature for 10 min. TLC analysis showed that the ethyl benzoylpropionate reacted completely. The product, methyl 2-((4-methylphenyl)sulfonamide)-3-oxo-3-phenylpropionate, was purified by vacuum rotary evaporation and thin-layer chromatography. The mass of the product was 65.2 mg, with a yield of 94%. The product was further purified by... 1 H NMR, 13 C NMR confirmed, such as Figure 12 and 13 shown. 1 H NMR(600MHz,Chloroform-d)δ8.03-7.98(m,2H),7.77-7.72(m,2H),7.68-7.62(m,1H),7.53-7.47(m ,2H),7.27(d,J=8.1Hz,2H),5.99(d,J=8.9Hz,1H),5.63(d,J=8.9Hz,1H),3.54(s,3H),2.40(s,3H). 13 C NMR (151MHz, Chloroform-d) δ189.9,166.4,143.9,136.4,134.6,133.3,129.6,129.3,128.8,127.3,60.6,53.2,21.5.

[0060] Comparative Example 1

[0061] The structural formula of ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate in this comparative example is:

[0062] The structural formula of the catalyst [Ir(dtbbpy)(ppy)2]PF6 is:

[0063]

[0064] In a test tube, 38.4 mg (0.2 mmol) of ethyl benzoyl, 149.3 mg (0.4 mmol) of 4-methyl-N-(phenyl-3-iodoenyl)benzenesulfonamide, 1.83 mg (1 mol%) of [Ir(dtbbpy)(ppy)2]PF6, and 1.0 mL of dichloromethane were added. The mixture was magnetically stirred in air under 465 nm blue light irradiation and reacted at room temperature for 10 min. TLC analysis showed that the ethyl benzoyl reactant had reacted completely. The product, ethyl 2-((4-methylphenyl)sulfonamido)-3-oxo-3-phenylpropionate, was purified by vacuum rotary evaporation and thin-layer chromatography. The mass of the product was 53.7 mg, with a yield of 74%.

[0065] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds, characterized in that: The following steps are involved: The benzoyl acetate compound, the sulfonamide compound and the photosensitizer are added into a solvent to prepare a reaction solution, and the reaction is carried out under the irradiation of blue light. After the reaction is completed, the target product is obtained.

2. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The structural formula of the benzoyl acetate compound is R 1 is alkyl, halogen, nitro or trifluoromethyl; R 3 It is an alkyl substituent having 7 or less carbon atoms or a cyclohexyl group.

3. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The structural formula of the sulfonamide compound is R 2 is alkyl, halogen, nitro, trifluoromethyl, trifluoromethoxy, celecoxib group or valdecoxib group.

4. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The photosensitizer is 4CzIPN, and the structural formula is 5. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The solvent is dichloromethane, chloroform, acetonitrile or ethyl acetate.

6. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The molar ratio of the benzoyl acetate compound to the sulfonamide compound is 1:(2-4).

7. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The amount of the photosensitizer is 1-2 mol% of the amount of the benzoyl acetate compound.

8. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The ratio of the benzoyl acetate compound to the solvent is 0.1-0.2 mmol / mL.

9. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The reaction is carried out at room temperature for 10 min-4 h.

10. The method for synthesizing 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compounds according to claim 1, characterized in that: The structural formula of the 2-(benzenesulfonamide)-3-oxo-3-phenylpropionic acid ester compound is Where R 1 is alkyl, halogen, nitro and trifluoromethyl; R 2 is alkyl, halogen, nitro, trifluoromethyl, trifluoromethoxy, celecoxib group and valdecoxib group; R 3 It is an alkyl substituent having 7 or less carbon atoms or a cyclohexyl group.

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