CN113861086B - Synthesis method of sulfur-containing gamma, gamma-diarylamine butyrylamide compound - Google Patents

Synthesis method of sulfur-containing gamma, gamma-diarylamine butyrylamide compound Download PDF

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CN113861086B
CN113861086B CN202111205646.XA CN202111205646A CN113861086B CN 113861086 B CN113861086 B CN 113861086B CN 202111205646 A CN202111205646 A CN 202111205646A CN 113861086 B CN113861086 B CN 113861086B
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CN113861086A (en
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张兴国
杨松
张小红
康田梦
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Wenzhou University
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Abstract

The invention relates to a method for synthesizing a sulfur-containing gamma, gamma-diarylamine butyramide compound, which comprises the following steps:N- (2- (ethylthio) phenyl) butyl-3-enamide as reaction substrate, arylamine as nucleophilic reagent, palladium acetate as catalyst, ferric trichloride and ferrous acetate as oxidant, benzoic acid as additive, acetonitrile as solvent, reacting at 90 deg.C o C the reaction was stirred for 24 hours. And after the reaction is finished, filtering the reaction solution, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, carrying out column chromatography separation on the residue through a silica gel column, leaching the residue by using an eluent, collecting an effluent containing the target product, combining the effluent, and removing the solvent by vacuum concentration to obtain the target product. The invention has the advantages of simple and easily obtained raw materials, relatively mild reaction conditions, novel and simple preparation process, less pollution and low energy consumption.

Description

Synthesis method of sulfur-containing gamma, gamma-diarylamine butyrylamide compound
Technical Field
The invention relates to a method for synthesizing a sulfur-containing gamma, gamma-diarylamine butyramide compound.
Background
Olefins are the most abundant class of organic molecules available in large quantities from petrochemical feedstocks and renewable resources. The widespread existence of olefins and their unique reactivity make olefin functionalization a common reaction in organic synthesis, and transition metal-catalyzed olefin bifunctional has evolved as an important strategy to rapidly access building blocks found in a variety of valuable pharmaceutical and natural product building blocks. In recent years, a number of groups of topics completed a series of excellent works in this field, 2016,the Engle topic group reports palladium (II) catalyzed beta, gamma-bifunctional reactions of unactivated olefins: (J. Am. Chem. Soc. 2016, 13815122-15125); in 2018, the Engle topic group reported palladium (II) catalysisN,NBidentate oriented intermolecular aminohydroxylation of unactivated olefins (c)Org. Lett. 2018, 203853-3857); in 2019, the Zhao topic group reported that a three-component o-diarylation reaction of unactivated olefins was achieved by direct transmetallation of arylboronic acids (Chem. Sci. 2019, 10, 7952-7957). Probably because the sulfur atom easily poisons the palladium catalyst: (Org. Lett. 2012, 142164-2167), until now,N, Sbidentate directed olefin bifunctional reactions have been rarely reported.
Disclosure of Invention
Aiming at the defects existing at the present stage, the invention provides a method for preparing a new type of medicineN,SThe method for preparing the sulfur-containing gamma, gamma-diarylamine compound by using bidentate-oriented unactivated olefin and electron-rich aromatic hydrocarbon such as arylamine as reaction raw materials has the advantages of simple technical process, high yield, environmental protection and safety.
In order to achieve the purpose, the invention adopts the technical scheme that:
a synthetic method of a sulfur-containing gamma, gamma-diarylamine compound comprises the following steps: to be provided withN- (2- (ethylthio) phenyl) butyl-3-enamide as reaction substrate, arylamine as nucleophilic reagent, palladium acetate as catalyst, ferric trichloride and ferrous acetate as oxidant, benzoic acid as additive, acetonitrile, 1, 2-dichloroethane, hexafluoroisopropanol or methanol as solvent, and reaction at 90 deg.C o C, stirring and reacting for 24 hours, wherein the chemical reaction formula is as follows:
Figure 18682DEST_PATH_IMAGE001
and the-Ar is one of 4-N-methylphenyl, 4-N-ethylphenyl, 4-N-isopropylphenyl, 4-N-benzylphenyl, 4-N-phenylphenyl, 4-N, N-dimethylphenyl and 3-methyl-4-N-methylphenyl.
The invention adoptsBy a synthetic method usingN,SThe bidentate-oriented unactivated olefin and the electron-rich aromatic hydrocarbon such as arylamine react, a novel synthesis method of the sulfur-containing gamma, gamma-diarylamine compound is provided, the process is simple, no special instrument or mode is needed, the method is very suitable for the operation of people in the field, and the method has the advantages of simple operation, easy obtaining of products and the like.
As a further configuration of the invention, the molar percentage of catalyst to substrate is 20%.
According to the further arrangement of the invention, after the reaction is finished, the reaction solution is filtered, the filtrate is subjected to solvent removal by using a rotary evaporator to obtain a residue, the residue is subjected to column chromatography separation by using a silica gel column and is eluted by using an eluent, an effluent containing a target product is collected, the effluent is combined, and the solvent is removed by vacuum concentration to obtain the target product.
The method can directly synthesize the target product, does not need to separate intermediate products, can obtain the target product only by stirring and reacting under normal pressure, has the highest yield of 71 percent, greatly simplifies process engineering, reduces energy consumption and has excellent yield; in addition, the waste solution is less in the reaction process, and other polluted gases and liquid are not discharged, so that the method reduces the discharge of the waste solution, and has the advantages of protecting the environment and ensuring the health of operators; in addition, a series of sulfur-containing gamma, gamma-bisarylamine compounds can be prepared, and the method has better substrate universality. Thus, the invention fills the blank of the method for preparing the sulfur-containing gamma, gamma-diarylamine compound at the present stage and promotes the development of the polysubstituted gamma, gamma-diarylide derivative.
The mechanism of the invention is as follows: first, atN,SUnder the assistance of a bidentate guide group, carrying out N-H deprotonation, coordinating Pd (II) and a substrate to obtain alkene A, and attacking by a nucleophilic reagent to obtain a five-membered palladium ring intermediate B for nucleophilic palladium reaction to obtain a key pentacycloalkyl palladium (II) intermediate B. The palladium (II) intermediate B is then subjected to beta-H elimination to give the monoarylolefin C and to provide Pd (0), and the Pd (II) obtained is oxidized for the next catalytic cycle. Finally, the monoaryl alkene C coordinates with Pd (II) again, then nucleophilic reagent attacks and protonates to obtain gamma, gamma-biarylAn amine compound.
Figure 413891DEST_PATH_IMAGE002
Detailed Description
The invention discloses a method for synthesizing a sulfur-containing gamma, gamma-diarylamine compound, which comprises the following stepsN- (2- (ethylthio) phenyl) butyl-3-enamide as reaction substrate, arylamine as nucleophilic reagent, palladium acetate as catalyst, ferric trichloride and ferrous acetate as oxidant, benzoic acid as additive, acetonitrile, 1, 2-dichloroethane, hexafluoroisopropanol or methanol as solvent, and reaction on 90 deg.C o C, stirring and reacting for 24 hours, wherein the chemical reaction formula is as follows:
Figure 228263DEST_PATH_IMAGE003
and the-Ar is one of 4-N-methylphenyl, 4-N-ethylphenyl, 4-N-isopropylphenyl, 4-N-benzylphenyl, 4-N-phenylphenyl, 4-N, N-dimethylphenyl and 3-methyl-4-N-methylphenyl.
And after the reaction is finished, filtering the reaction solution, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, carrying out column chromatography separation on the residue through a silica gel column, leaching the residue by using an eluent, collecting an effluent containing the target product, combining the effluent, and removing the solvent by vacuum concentration to obtain the target product.
The first embodiment is as follows: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 62.06 mg (0.58 mmol) of N-methylaniline, 4.5 mg (0.02 mmol) of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidizing agent, 29.3 mg (0.24 mmol) of benzoic acid as additive in the 3 ml of solvent acetonitrile o C the reaction was stirred for 24 hours. And cooling after the reaction is finished, filtering the reaction solution to obtain a filtrate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, and leaching the residue by using a silica gel column and an eluent prepared from petroleum ether and ethyl acetate according to a volume ratio of 3The eluates were collected on a real gradient, checked by TLC, combined and the combined eluates were subjected to rotary evaporation to remove the solvent and dried in vacuo to give 57.2 mg of N- (2- (ethylthio) phenyl) -4, 4-bis (4- (methylamino) phenyl) butanamide in 66% yield as a yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 8.41 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.09 - 7.01 (m, 5H), 6.55 (d, J = 8.4 Hz, 4H), 3.80 (t, J = 7.2 Hz, 1H), 2.80 (s, 6H), 2.72 (q, J = 7.2 Hz, 2H), 2.43 - 2.36 (m, 4H), 1.19 (t, J = 7.2 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 171.4, 147.8, 139.9, 135.2, 133.9, 129.7, 128.7, 123.8, 122.5, 120.3, 112.7, 48.9, 36.7, 31.7, 31.0, 30.4, 14.9. HRMS (ESI) Calcd for C 26 H 31 N 3 OSNa + ([M + Na] + ) 456.2080, Found: 456.2075. 。
The second embodiment is as follows: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 70.18 mg (0.58 mmol) of N-ethylaniline, 4.5 mg (0.02 mmol) of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidizing agent, 29.3 mg (0.24 mmol) of benzoic acid as additive in the 3 ml of solvent acetonitrile o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is subjected to solvent removal by a rotary evaporator to obtain a residue, the residue is eluted by a silica gel column by using an eluent prepared by petroleum ether and ethyl acetate according to the volume ratio of 3. 1 H NMR (400 MHz, CDCl 3 ) δ 8.42 - 8.40 (m, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 7.2 Hz, 1H), 7.06 - 7.01 (m, 5H), 6.55 - 6.53 (m, 4H), 3.77 (t, J = 7.2 Hz, 1H), 3.11 (q, J = 7.2 Hz, 4H), 2.71 (q, J = 7.2 Hz, 2H), 2.41 - 2.37 (m, 4H), 1.24 - 1.67 (m, 9H). 13 C NMR (125 MHz, CDCl 3 ) δ 171.5, 146.9, 139.9, 135.3, 133.9, 129.7, 128.7, 123.8, 120.3, 113.0, 48.9, 38.8, 36.7, 31.7, 30.5, 15.1, 14.9. HRMS (ESI) Calcd for C 28 H 35 N 3 OSNa + ([M + Na] + ) 484.2393, Found: 484.2358.。
The third concrete embodiment: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 78.30 mg (0.58 mmol) of isopropylaniline, 4.5 mg (0.02 mmol) of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidizing agent, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of acetonitrile as solvent, 90 o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is subjected to solvent removal by using a rotary evaporator to obtain a residue, the residue is eluted by a silica gel column by using petroleum ether and ethyl acetate according to a volume ratio of 3 to 1, the effluent is collected according to a practical gradient, the effluent containing the target product is combined through TLC detection, the combined effluent is subjected to rotary evaporation by using the rotary evaporator to remove the solvent, and vacuum drying is carried out to obtain 58.6 mg of the N- (2- (ethylthio) phenyl) -4, 4-bis (4- (isopropylamino) phenyl) butanamide in a yellow oil state, wherein the yield is 60%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.42 - 8.40 (m, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.05 - 7.01 (m, 5H), 6.52 - 6.50 (m, 4H), 3.76 (t, J = 7.2 Hz, 1H), 3.60 - 3.54 (m, 2H), 2.72 (q, J = 7.2 Hz, 2H), 2.38 (m, 4H), 1.20 - 1.17 (m, 15H). 13 C NMR (125 MHz, CDCl 3 ) δ 171.5, 145.9, 139.9, 135.3, 133.6, 129.7, 128.7, 123.8, 122.5, 120.3, 113.5, 48.9, 44.5, 36.7, 31.8, 30.4, 29.8, 23.3, 14.9. HRMS (ESI) Calcd for C 30 H 39 N 3 OSNa + ([M + Na] + ) 512.2706, Found: 512.2706.。
The fourth concrete embodiment: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) But-3-enamide, 106.14 mg (0.58 mmol) of N-benzylaniline, 4.5 mg (0.02 mmol) of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidant, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of acetonitrile solvent in 90 mg of acetonitrile o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is subjected to solvent removal by using a rotary evaporator to obtain a residue, the residue is eluted by a silica gel column by using petroleum ether and ethyl acetate according to a volume ratio of 3 to 1, the effluent is collected according to a practical gradient, the effluent containing the target product is combined through TLC detection, the combined effluent is subjected to solvent removal by using the rotary evaporator in a rotating way, and vacuum drying is carried out to obtain 67.8 mg of 4, 4-bis (4- (benzylamino) phenyl) -N- (2- (ethylthio) phenyl) butanamide in a yellow oil form, wherein the yield is 58%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.42 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.38 - 7.28 (m, 11H), 7.08 - 7.03 (m, 5H), 6.58 (d, J = 8.4 Hz, 4H), 4.29 (s, 4H), 3.79 (t, J = 7.2 Hz, 1H), 2.71 (q, J = 7.2 Hz, 2H), 2.42 - 2.39 (m, 4H), 1.19 (t, J = 7.2 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 171.4, 146.6, 139.7, 135.2, 134.1, 129.7, 128.71, 128.68, 127.7, 127.3, 123.8, 122.5, 120.3, 115.5, 113.1, 49.0, 48.7, 36.6, 31.7, 30.4, 14.9. HRMS (ESI) Calcd for C 38 H 39 N 3 OSNa + ([M + Na] + ) 608.2706, Found: 608.2734.。
The fifth concrete embodiment: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 98.02 mg (0.58 mmol) of diphenylamine, 4.5 mg (0.02 mmol) of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidizing agent, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of acetonitrile as solvent, 90 o C the reaction was stirred for 24 hours. Cooling after the reaction, filtering the reaction solution to obtain a filtrate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, and passing the residue through a silica gel column, using petroleum ether and ethyl acetateEluting the eluent prepared according to the volume ratio of 3:1, collecting the effluent according to a practical gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent by rotating the combined effluent by using a rotary evaporator, and drying in vacuum to obtain 51.2 mg of the yellow oily N- (2- (ethylthio) phenyl) -4, 4-bis (4- (phenylamino) phenyl) butyramide with the yield of 46%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.62 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 7.6 Hz, 1H), 7.52 (t, J = 7.2 Hz, 1H), 7.46 - 7.42 (m, 3H), 7.42 (s, 1H), 7.38 - 7.36 (m, 4H), 7.24 - 7.21 (m, 9H), 7.10 (t, J = 7.2 Hz, 2H), 5.89 (s, 2H), 4.10 (t, J= 7.6 Hz, 1H), 2.93 (q, J = 7.2 Hz, 2H), 2.68 - 2.61 (m, 4H), 1.39 (t, J = 7.2 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 171.1, 143.6, 141.5, 139.7, 137.4, 135.2, 129.7, 129.4, 128.8, 124.0, 122.5, 120.9, 120.3, 118.4, 117.7, 49.3, 36.5, 31.5, 30.5, 14.9. HRMS (ESI) Calcd for C 36 H 35 N 3 OSNa + ([M + Na] + ) 580.2393, Found: 580.2386. 。
The sixth specific embodiment: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 70.18 mg (0.58 mmol) of N, N-dimethylaniline, 4.5 mg (0.02 mmol) of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidant, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of acetonitrile as solvent, in 90 ml of acetonitrile o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is subjected to solvent removal by a rotary evaporator to obtain a residue, the residue is eluted by a silica gel column by using an eluent prepared from petroleum ether and ethyl acetate according to the volume ratio of 3:1, the effluent is collected according to a practical gradient, the effluent containing the target product is combined through TLC detection, the combined effluent is subjected to solvent removal by rotation of the rotary evaporator, and vacuum drying is carried out to obtain 55.3 mg of white solid 4, 4-bis (4- (dimethylamino) phenyl) -N- (2- (ethylthio) phenyl) butanamide with the yield of 60%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.42 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.14 (d, J = 8.8 Hz, 4H), 7.03 (t, J = 7.6 Hz, 1H), 6.69 (d, J = 8.4 Hz, 4H), 3.83 (t, J = 7.6 Hz, 1H), 2.90 (s, 12H), 2.72 (q, J = 7.2 Hz, 2H), 2.48 - 2.37 (m, 4H), 1.19 (t, J = 7.2 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 171.4, 149.3, 139.9, 135.2, 133.3, 129.7, 128.5, 123.8, 122.5, 120.3, 113.1, 48.8, 40.9, 36.7, 31.6, 30.4, 14.9. HRMS (ESI) Calcd for C 28 H 35 N 3 OSNa + ([M + Na] + ) 484.2393, Found: 484.2375.。
The seventh specific embodiment: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 70.18 mg (0.58 mmol) of N, 2-dimethylaniline, 4.5 mg (0.02 mmol) of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidizing agent, 29.3 mg (0.24 mmol) of benzoic acid as additive in the solvent acetonitrile 3 ml o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is removed of the solvent by a rotary evaporator to obtain a residue, the residue is eluted by silica gel column through eluent prepared by petroleum ether and ethyl acetate according to the volume ratio of 3. 1 H NMR (400 MHz, CDCl 3 ) δ 8.45 - 8.42 (m, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.33 (t, J = 7.6 Hz, 1H), 7.09 - 7.02 (m, 3H), 6.97 (s, 2H), 6.56 (d, J= 8.0 Hz, 2H), 3.78 (t, J = 7.2 Hz, 1H), 2.87 (s, 6H), 2.73 (q, J = 7.2 Hz, 2H), 2.46 - 2.40 (m, 4H), 2.10 (s, 6H), 1.20 (t, J = 7.2 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 171.5, 145.6, 139.9, 135.2, 133.5, 129.7, 126.2, 123.8, 122.2, 120.2, 109.4, 49.0, 36.8, 31.7, 31.0, 30.4, 17.6, 14.9. HRMS (ESI) Calcd for C 28 H 35 N 3 OSNa + ([M + Na] + ) 484.2393, Found: 484.2385.。
The eighth embodiment: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 62.06 mg (0.58 mmol) of N-methylaniline, 0.02 mmol of palladium tetrakistriphenylphosphine as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidant, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of acetonitrile as solvent, in 90 ml of acetonitrile o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is removed of the solvent by using a rotary evaporator to obtain a residue, the residue is leached by a silica gel column by using an eluent prepared by petroleum ether and ethyl acetate according to the volume ratio of 3.
The specific embodiment is nine: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 62.06 mg (0.58 mmol) of N-methylaniline, 0.02 mmol of palladium chloride as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidant, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of acetonitrile as solvent, in 90 ml of acetonitrile o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is removed of the solvent by a rotary evaporator to obtain a residue, the residue is leached by a silica gel column by eluent prepared by petroleum ether and ethyl acetate according to the volume ratio of 3.
The specific embodiment ten: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) benzeneYl) but-3-enamide, 62.06 mg (0.58 mmol) of N-methylaniline, 0.02 mmol of bis (cyanophenyl) palladium dichloride as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidant, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of acetonitrile solvent in 90 mg of acetonitrile o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is removed of the solvent by using a rotary evaporator to obtain a residue, the residue is leached by a silica gel column by using an eluent prepared by petroleum ether and ethyl acetate according to the volume ratio of 3.
The first specific embodiment: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 62.06 mg (0.58 mmol) of N-methylaniline, 0.02 mmol of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidant, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of 1, 2-dichloroethane solvent, 90 o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is removed of the solvent by using a rotary evaporator to obtain a residue, the residue is leached by a silica gel column by using an eluent prepared by petroleum ether and ethyl acetate according to the volume ratio of 3.
The specific example twelve: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 62.06 mg (0.58 mmol) of N-methylaniline, 0.02 mmol of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidizing agent, 29.3 mg (0.24 mmol) of benzoic acid as additionAdding the mixture into 3 ml of hexafluoroisopropanol solvent and then adding the mixture into the mixture to obtain the finished product o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is removed of the solvent by using a rotary evaporator to obtain a residue, the residue is leached by a silica gel column by using an eluent prepared by petroleum ether and ethyl acetate according to the volume ratio of 3.
The specific example thirteen: 44.2 mg (0.2 mmol) of N- (2- (ethylthio) phenyl) but-3-enamide, 62.06 mg (0.58 mmol) of N-methylaniline, 0.02 mmol of palladium acetate as catalyst, 3.2 mg (0.02 mmol) of ferric chloride and 10.4 mg (0.06 mmol) of ferrous acetate as oxidant, 29.3 mg (0.24 mmol) of benzoic acid as additive in 3 ml of methanol as solvent, are dissolved in 90 o C the reaction was stirred for 24 hours. After the reaction is finished, cooling is carried out, the reaction liquid is filtered to obtain a filtrate, the filtrate is removed of the solvent by using a rotary evaporator to obtain a residue, the residue is leached by a silica gel column by using an eluent prepared by petroleum ether and ethyl acetate according to the volume ratio of 3.
The embodiment of the invention is as followsN,S-bidentate oriented non-activated alkene N- (2- (ethylthio) phenyl) but-3-enamide as a reaction substrate, arylamine as a nucleophile, palladium acetate as a catalyst, ferric chloride and ferrous acetate as oxidants, benzoic acid as an additive, one of acetonitrile, 1, 2-dichloroethane, hexafluoroisopropanol or methanol as a solvent, in 90 deg.f o C the reaction was stirred for 24 hours.
Wherein examples one to seven are variable with arylamine; examples eight to ten were run with catalyst palladium as the variable; examples eleven to thirteen variables based on solvent
According to the invention, the intermediate product does not need to be separated, the target product can be directly synthesized by simple raw materials, the process is simplified, the energy consumption is low, the waste solution discharge is reduced, the environmental pollution is reduced, and the yield reaches up to 71%; in the above embodiment, a series of gamma, gamma-bisarylamine butyramide derivatives can be prepared by reacting N- (2- (ethylthio) phenyl) but-3-enamide with arylamine with different substituents, and the method has certain substrate universality and operation simplicity. The present invention is not limited to the above embodiments, and those skilled in the art can implement the present invention in other embodiments according to the disclosure of the present invention, or make simple changes or modifications on the design structure and idea of the present invention, and fall into the protection scope of the present invention.

Claims (3)

1. A synthetic method of a sulfur-containing gamma, gamma-diarylamine butyrylamide compound comprises the following steps: to be provided withN- (2- (ethylthio) phenyl) butyl-3-enamide is used as a reaction substrate, arylamine is used as a nucleophilic reagent, and a catalyst is one of palladium acetate, palladium tetratriphenylphosphine, palladium chloride or bis (cyanophenyl) palladium dichloride; the oxidant is ferric trichloride and ferrous acetate; the additive is benzoic acid; the solvent is one of acetonitrile, 1, 2-dichloroethane, hexafluoroisopropanol or methanol at 90 deg.C o C, stirring and reacting for 24 hours, wherein the chemical reaction formula is as follows:
Figure DEST_PATH_IMAGE001
and the-Ar is one of 4-N-methylphenyl, 4-N-ethylphenyl, 4-N-isopropylphenyl, 4-N-benzylphenyl, 4-N-phenylphenyl, 4-N, N-dimethylphenyl and 3-methyl-4-N-methylphenyl.
2. The method for synthesizing the sulfur-containing gamma, gamma-bisarylamine butyramide compound according to claim 1, wherein: the molar percentage of catalyst to substrate was 20%.
3. The method for synthesizing the sulfur-containing gamma, gamma-bisarylamine butyramide compound according to claim 1, wherein: the method also comprises a post-processing method: and after the reaction is finished, filtering the reaction solution to obtain a filtrate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, performing column chromatography separation on the residue through a silica gel column, leaching the residue by using an eluent, collecting an effluent containing the target product, combining the effluent, and removing the solvent by vacuum concentration to obtain the target product.
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Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Jinwon Jeon 等.Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis .《Journal of the American Chemical Society》.2019,第141卷第10048-10159页. *
Joseph Derosa 等.Nickel-Catalyzed β,γ-Dicarbofunctionalization of Alkenyl Carbonyl Compounds via Conjunctive Cross-Coupling.《Journal of the American Chemical Society》.2017,第139卷第10657-10660页. *
Zhu-Zhu Zhang 等.Palladium-catalyzed g,g-Diarylation of alkenyl carbonyl compounds assisted by N,S-Bidentate auxiliary.《Tetrahedron》.2022,第129卷133138. *
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