Method for synthesizing dithioalkyl ketone compound by using diisopropylamine

Abstract

The invention discloses a method for synthesizing a dithio alkyl ketone compound by using diisopropylamine, which is characterized in that diisopropylamine is used as alkali, a cycloalkyl peroxy alcohol compound and a tetrasulfide compound are driven by illumination to generate a free radical coupling reaction, and the dithio alkyl ketone compound is successfully synthesized. The preparation method provided by the invention has the advantages of easily available raw materials and simple operation, has excellent functional group compatibility, can meet the synthesis requirements of target products with different structures, and has significant practical application value.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for synthesizing dithioalkyl ketone compounds using diisopropylamine. Background Technology

[0002] Disulfides, as key structural elements stabilizing the native conformation of proteins, possess unique chemical properties that have led to their widespread application in various fields such as natural product synthesis, drug development, food chemical modification, and material preparation. Among them, asymmetric disulfides, with their more unique structures and broader application prospects, have become a research hotspot in the field of organic synthesis.

[0003] In recent years, alkoxy-mediated carbon-carbon bond cleavage strategies have become a powerful tool for constructing carbon-carbon and carbon-heteroatom bonds due to their high reaction selectivity and good functional group compatibility. In this technical route, cycloalkyl peroxides have been proven to be a class of alkyl precursors with great application potential due to their readily available raw materials and controllable reactivity. Under transition metal catalysis or photocatalysis, these compounds can efficiently introduce ketone alkyl segments into the target molecule structure. In 2021, Guo Lina et al. reported a method using ferric trifluoromethanesulfonate (III) as a catalyst to achieve free radical coupling reactions between cycloalkyl peroxides and disulfide compounds, successfully preparing a series of thioalkyl ketones. However, this method and other existing technologies still have obvious limitations: on the one hand, existing technologies have not yet carried out reaction studies between cycloalkyl peroxides and tetrasulfides, which limits the substrate range and structural diversity of thioalkyl ketone synthesis; on the other hand, existing synthesis methods generally rely on transition metal catalysts, which not only leads to high reaction costs, but may also affect the application of products in fields with strict purity requirements such as biomedicine due to metal residue problems, which greatly restricts the industrial application prospects of this type of synthesis method.

[0004] Therefore, developing a method for synthesizing dithioalkyl ketones that does not require transition metal catalysts, has mild reaction conditions, a wide range of applicable substrates, and is easy to operate is of great practical significance and application value. Summary of the Invention

[0005] The purpose of this invention is to solve the technical problems existing in the current synthesis methods, such as the limited substrate range, high cost due to reliance on transition metal catalysts, and the risk of metal residue. The invention provides a method for synthesizing dithioalkyl ketones using diisopropylamine. This method does not require the addition of any photocatalyst. It can achieve the free radical coupling reaction of cycloalkyl peroxide compounds and tetrathioether compounds by relying solely on the synergistic effect of light and diisopropylamine to obtain a series of dithioalkyl ketone compounds.

[0006] The above-mentioned objective of the present invention is achieved through the following technical solution:

[0007] A method for synthesizing dithioalkyl ketone compounds using diisopropylamine includes the following steps:

[0008] A cycloalkyl peroxide compound, a tetrasulfide compound, diisopropylamine, and an organic solvent were mixed and subjected to a free radical coupling reaction under light irradiation to obtain the dithioalkyl ketone compound.

[0009] The structural formula of the cycloalkyl peroxy alcohol compound is: Among them, R 1 Selected from one or more of hydrogen, p-tert-butyl, p-chloro, p-trifluoromethyl, m-methoxy, o-methyl, m-dimethyl, 1-naphthyl, and 2-naphthyl; n is an integer from 0 to 7;

[0010] The structural formula of the tetrasulfide compound is as follows: Among them, R 2 It is tert-butyl, isopropyl, sec-butyl, 3-methylbut-2-yl, cyclopentyl, cyclohexyl or adamantyl.

[0011] This invention uses diisopropylamine as a base to drive a free radical coupling reaction between cycloalkyl peroxide compounds and tetrathioether compounds under light irradiation, successfully synthesizing dithioalkyl ketone compounds. This preparation method has the advantages of readily available raw materials and simple operation, and also has excellent functional group compatibility, which can meet the synthesis requirements of different structural target products, and has significant practical application value.

[0012] Further, the cycloalkyl peroxy alcohol compound is selected from one of (1-hydroperoxycyclopentyl)benzene, 1-(tert-butyl)-4-(1-hydroperoxycyclopentyl)benzene, 1-chloro-4-(1-hydroperoxycyclopentyl)benzene, 1-(1-hydroperoxycyclopentyl)-4-(trifluoromethyl)benzene, 1-(1-hydroperoxycyclopentyl)-3-methoxybenzene, 1-(1-hydroperoxycyclopentyl)-2-methylbenzene, 1-(1-hydroperoxycyclopentyl)-3,5-dimethylbenzene, 1-(1-hydroperoxycyclopentyl)naphthalene, 2-(1-hydroperoxycyclopentyl)naphthalene, (1-hydroperoxycyclohexyl)benzene, 1-hydroperoxy-1-phenylcycloheptane, 1-hydroperoxy-1-phenylcyclooctane, and 1-hydroperoxy-1-phenylcyclododecane.

[0013] Furthermore, the tetrasulfide compound is selected from one of tert-butyltetrasulfide, 1,4-di-sec-butyltetrasulfide, 1,4-bis(3-methylbutane-2-yl)tetrasulfide, cyclopentyltetrasulfide, cyclohexyltetrasulfide, and adamantanetetrasulfide.

[0014] Furthermore, the molecular formula of the diisopropylamine (iPr2NH) is [(CH3)2CH]2NH.

[0015] Furthermore, the molar ratio of the diisopropylamine, the cycloalkyl peroxide compound, and the tetrasulfide compound is (0.125-1):(1.5-2):(1-1.2).

[0016] Preferably, the molar ratio of the cycloalkyl peroxide compound to the tetrasulfide compound is 1.5:1.

[0017] Preferably, the molar ratio of diisopropylamine to tetrasulfide compound is 0.25:1.

[0018] Furthermore, the organic solvent is acetonitrile (MeCN), dichloromethane, or ethanol.

[0019] Furthermore, the illumination conditions are as follows: irradiation is performed using one or more LED lamps with a power of 20-40 W and a wavelength of 425 nm.

[0020] Furthermore, the irradiation distance is 15-30 cm.

[0021] Furthermore, the free radical coupling reaction is carried out in a nitrogen (N2) atmosphere.

[0022] Furthermore, the temperature of the free radical coupling reaction is 20-40 °C.

[0023] Furthermore, the free radical coupling reaction takes 6-12 h.

[0024] Furthermore, after the free radical coupling reaction is completed, one or more of the steps of filtration, concentration and purification are also included.

[0025] Compared with the prior art, the above-described technical solution of the present invention has the following advantages:

[0026] 1. This invention uses diisopropylamine as a base to drive a free radical coupling reaction between cycloalkyl peroxide compounds and tetrasulfide compounds under light conditions, successfully achieving the synthesis of dithioalkyl ketone compounds and providing a new method for the synthesis of such compounds.

[0027] 2. The preparation method provided by this invention uses readily available raw materials and has a convenient operation process. It does not require complex equipment or harsh reaction conditions. At the same time, the method exhibits excellent compatibility with various functional groups and can adapt to diverse substrate structures. It can meet the synthesis needs of target products with different structures, has outstanding practical application value, and has good prospects for industrial promotion. Detailed Implementation

[0028] Unless otherwise defined, 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 pertains. 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. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0029] This invention provides a method for synthesizing dithioalkyl ketone compounds using diisopropylamine, comprising the following steps:

[0030] A cycloalkyl peroxide compound, a tetrasulfide compound, diisopropylamine, and an organic solvent were mixed and subjected to a free radical coupling reaction under light irradiation to obtain the dithioalkyl ketone compound.

[0031] In one embodiment of the present invention, the reaction equation for synthesizing dithioalkyl ketones using diisopropylamine is as follows:

[0032] ;

[0033] Among them, R 1 Selected from one or more of hydrogen, p-tert-butyl, p-chloro, p-trifluoromethyl, m-methoxy, o-methyl, m-dimethyl, 1-naphthyl, and 2-naphthyl; n is an integer from 0 to 7; R 2 It is tert-butyl, isopropyl, sec-butyl, 3-methylbut-2-yl, cyclopentyl, cyclohexyl or adamantyl.

[0034] In one embodiment of the present invention, the method for synthesizing cycloalkyl peroxide compounds includes the following steps:

[0035] In a 500 mL three-necked flask, 1.07 g (44 mmol) of magnesium and 0.6 g of iodine were added sequentially as initiators. The flask was evacuated three times under nitrogen atmosphere to ensure a stable nitrogen atmosphere. Then, ultra-dry tetrahydrofuran (THF, 40 mL) was added, and the bromide was added at room temperature. (40 mmol) was slowly added dropwise to a three-necked flask. After the addition was complete, the reaction was maintained at room temperature for 30 min. After the reaction was complete, the system temperature was lowered to 0 °C, and a cycloalkyl ketone (20 mmol) was slowly added dropwise. After the addition was complete, the reaction was continued at 0 °C for 15 min, and then the temperature was raised to room temperature for 2 h. After the reaction was complete, the reaction mixture was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain cycloalkylaryl alcohols, which could be used directly in the next step without separation.

[0036] In a 500 mL round-bottom flask, 11.5 mL (200 mmol) of 30% hydrogen peroxide solution and 0.67 mL (10 mmol) of concentrated sulfuric acid solution were added sequentially. Then, a solution of dichloromethane (DCM, 5 mL) containing cycloalkyl alcohol (20 mmol) was slowly added dropwise to the round-bottom flask at 0 °C. After the addition was complete, the mixture was brought back to room temperature and stirred for 12 h. After the reaction was complete, the mixture was extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain cycloalkyl peroxide compounds in 50-75% yield.

[0037] Specifically, the reaction equation for the synthesis of cycloalkyl peroxy alcohols is as follows:

[0038] ;

[0039] Among them, R 1 It is selected from one or more of hydrogen, p-tert-butyl, p-chloro, p-trifluoromethyl, m-methoxy, o-methyl, m-dimethyl, 1-naphthyl and 2-naphthyl; n is an integer from 0 to 7.

[0040] In one embodiment of the present invention, the method for synthesizing tetrasulfide compounds includes the following steps:

[0041] Under a nitrogen atmosphere, anhydrous diethyl ether (10 mL) and 0.8 mL (10 mmol) of disulfide dichloride were added sequentially to a Shrek tube, which was then placed at a low temperature of -78 °C. Subsequently, alkyl thiols were slowly added dropwise. A mixture of 20 mmol triethylamine (Et3N) and 2.8 mL (20 mmol) anhydrous diethyl ether (Et2O, 20 mL) was prepared. After the reaction was completed, the reaction mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by silica gel column chromatography to obtain tetrasulfide compounds in 80-90% yield.

[0042] Specifically, the reaction equation for the synthesis of tetrasulfide compounds is as follows:

[0043] ;

[0044] Among them, R 2 It is tert-butyl, isopropyl, sec-butyl, 3-methylbut-2-yl, cyclopentyl, cyclohexyl or adamantyl.

[0045] The present invention will be further described below with reference to specific embodiments, so that those skilled in the art can better understand and implement the present invention, but the embodiments are not intended to limit the present invention.

[0046] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the materials and reagents used are commercially available.

[0047] Example 1

[0048] A method for synthesizing 5-(tert-butyldithio)-1-phenylpentan-1-one using diisopropylamine includes the following steps:

[0049] ;

[0050] In a glove box under a nitrogen atmosphere, (1-hydroperoxycyclopentyl)benzene (50 μL, 0.3 mmol), tert-butyltetrasulfide (46 μL, 0.2 mmol), diisopropylamine (7 μL, 0.05 mmol), and anhydrous acetonitrile (2 mL) were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs (30 W, 425 nm, 20 cm apart) at room temperature and stirred for 12 h. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-(tert-butyldithio)-1-phenylpentan-1-one, in 84% yield.

[0051] The product was dissolved in deuterated chloroform (CDCl3) (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKERAVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.99 - 7.90 (m, 2H), 7.59 - 7.52 (m, 1H), 7.49 - 7.41 (m, 2H), 2.99(t, J = 7.1 Hz, 2H), 2.75 (t, J = 7.2 Hz, 2H), 1.89 - 1.71 (m, 4H), 1.32 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 199.94, 136.94, 133.02, 128.61, 128.05, 47.78, 40.52, 38.08, 29.97, 28.94, 23.18.

[0052] Example 2

[0053] A method for synthesizing dithioalkyl ketone compounds using diisopropylamine is basically the same as that in Example 1, except that anhydrous acetonitrile is replaced with dichloromethane.

[0054] The yield of the obtained product was 57%.

[0055] Example 3

[0056] A method for synthesizing dithioalkyl ketone compounds using diisopropylamine is basically the same as that in Example 1, except that anhydrous acetonitrile is replaced with ethanol.

[0057] The yield of the obtained product was 73%.

[0058] Example 4

[0059] A method for synthesizing dithioalkyl ketone compounds using diisopropylamine is basically the same as that in Example 1, except that the reaction time is 6 h.

[0060] The yield of the product was 53%.

[0061] Example 5

[0062] A method for synthesizing dithioalkyl ketone compounds using diisopropylamine is basically the same as that in Example 1, except that the reaction time is 8 h.

[0063] The yield of the obtained product was 66%.

[0064] Example 6

[0065] A method for synthesizing 1-(4-(tert-butyl)phenyl)-5-(tert-butyldithio)pentan-1-one using diisopropylamine includes the following steps:

[0066] In a glove box under a nitrogen atmosphere, 0.3 mmol of 1-(tert-butyl)-4-(1-hydroperoxycyclopentyl)benzene, 0.2 mmol of tert-butyltetrasulfide, 0.05 mmol of diisopropylamine, and 2 mL of anhydrous acetonitrile were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs at a power of 30 W and a wavelength of 425 nm at a distance of 20 cm and stirred at room temperature for 12 h. The crude reaction mixture was diluted with 20 mL of ethyl acetate and washed with 30 mL of water. The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 1-(4-(tert-butyl)phenyl)-5-(tert-butyldithio)pentan-1-one, in 72% yield.

[0067] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.98 - 7.83(m, 2H), 7.52 - 7.41 (m, 2H), 2.97 (t, J = 7.1 Hz, 2H), 2.74 (t, J = 7.1 Hz,2H), 1.88 - 1.71 (m, 4H), 1.33 (d, J = 5.9 Hz, 18H); 13 C NMR (100 MHz, CDCl3)δ 199.57, 156.68, 134.39, 128.03, 125.53, 47.75, 40.55, 37.97, 35.10, 31.11,29.98, 28.99, 23.31.

[0068] Example 7

[0069] A method for synthesizing 5-(tert-butyldithio)-1-(4-chlorophenyl)pentane-1-one using diisopropylamine includes the following steps:

[0070] In a glove box under a nitrogen atmosphere, 0.3 mmol of 1-chloro-4-(1-hydroperoxycyclopentyl)benzene, 0.2 mmol of tert-butyltetrasulfide, 0.05 mmol of diisopropylamine, and 2 mL of anhydrous acetonitrile were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs at a power of 30 W and a wavelength of 425 nm at a distance of 20 cm and stirred at room temperature for 12 h. The crude reaction mixture was diluted with 20 mL of ethyl acetate and washed with 30 mL of water. The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-(tert-butyldithio)-1-(4-chlorophenyl)pentan-1-one, in 72% yield.

[0071] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.92 - 7.85(m, 2H), 7.45 - 7.38 (m, 2H), 2.95 (t, J = 7.0 Hz, 2H), 2.73 (t, J = 7.1 Hz,2H), 1.87 - 1.70 (m, 4H), 1.32 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 198.60, 139.42, 135.23, 129.47, 128.91, 47.79, 40.45, 38.06, 29.96, 28.84, 23.05.

[0072] Example 8

[0073] A method for synthesizing 5-(tert-butyldithio)-1-(3-methoxyphenyl)pent-1-one using diisopropylamine includes the following steps:

[0074] In a glove box under a nitrogen atmosphere, 0.3 mmol of 1-(1-hydroperoxycyclopentyl)-3-methoxybenzene, 0.2 mmol of tert-butyltetrasulfide, 0.05 mmol of diisopropylamine, and 2 mL of anhydrous acetonitrile were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs at a power of 30 W and a wavelength of 425 nm at a distance of 20 cm and stirred at room temperature for 12 h. The crude reaction mixture was diluted with 20 mL of ethyl acetate and washed with 30 mL of water. The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-(tert-butyldithio)-1-(3-methoxyphenyl)pent-1-one, in 68% yield.

[0075] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.56 - 7.46(m, 2H), 7.36 (t, J = 7.9 Hz, 1H), 7.10 (ddd, J = 8.2, 2.7, 1.0 Hz, 1H), 3.85(s, 3H), 2.98 (t, J = 7.1 Hz, 2H), 2.74 (t, J = 7.1 Hz, 2H), 1.88 - 1.71 (m,4H), 1.33 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 199.69, 159.84, 138.31, 129.58,120.68, 119.43, 112.30, 55.43, 47.76, 40.50, 38.18, 29.96, 28.91, 23.23.

[0076] Example 9

[0077] A method for synthesizing 5-(tert-butyldithio)-1-(3,5-dimethylphenyl)pentane-1-one using diisopropylamine includes the following steps:

[0078] In a glove box under a nitrogen atmosphere, 0.3 mmol of 1-(1-hydroperoxycyclopentyl)-3,5-dimethylbenzene, 0.2 mmol of tert-butyltetrasulfide, 0.05 mmol of diisopropylamine, and 2 mL of anhydrous acetonitrile were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs at a power of 30 W and a wavelength of 425 nm at a distance of 20 cm and stirred at room temperature for 12 h. The crude reaction mixture was diluted with 20 mL of ethyl acetate and washed with 30 mL of water. The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-(tert-butyldisulfide)-1-(3,5-dimethylphenyl)pentane-1-one, in 81% yield.

[0079] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J =1.8 Hz, 2H), 7.18 (s, 1H), 2.95 (t, J = 7.1 Hz, 2H), 2.74 (t, J = 7.1 Hz,2H), 2.36 (s, 6H), 1.86 - 1.70 (m, 4H), 1.32 (s, 9H); 13 C NMR (100 MHz, CDCl3)δ 200.31, 138.20, 137.12, 134.62, 125.86, 47.73, 40.56, 38.15, 29.98, 28.96,23.28, 21.26.

[0080] Example 10

[0081] A method for synthesizing 5-(tert-butyldithio)-1-(naphth-2-yl)pentan-1-one using diisopropylamine includes the following steps:

[0082] In a glove box under a nitrogen atmosphere, 0.3 mmol of 2-(1-hydroperoxycyclopentyl)naphthalene, 0.2 mmol of tert-butyltetrasulfide, 0.05 mmol of diisopropylamine, and 2 mL of anhydrous acetonitrile were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs at a power of 30 W and a wavelength of 425 nm at a distance of 20 cm and stirred at room temperature for 12 h. The crude reaction mixture was diluted with 20 mL of ethyl acetate and washed with 30 mL of water. The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-(tert-butyldithio)-1-(naphth-2-yl)pent-1-one, in 60% yield.

[0083] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 8.48 - 8.43(m, 1H), 8.02 (dd, J = 8.7, 1.8 Hz, 1H), 7.95 (d, J = 7.4 Hz, 1H), 7.90 -7.84 (m, 2H), 7.56 (dddd, J = 18.4, 8.2, 6.9, 1.4 Hz, 2H), 3.11 (t, J = 7.2Hz, 2H), 2.77 (t, J = 7.2 Hz, 2H), 1.93 - 1.85 (m, 2H), 1.84 - 1.75 (m, 2H), 1.33 (s, 9H); 13 C NMR (100MHz, CDCl3) δ 199.85, 135.56, 134.27, 132.55,129.66, 129.57, 128.46, 128.42, 127.79, 126.78, 123.90, 47.80, 40.56, 38.16, 29.99, 28.99, 23.35.

[0084] Example 11

[0085] A method for synthesizing 6-(tert-butyldithio)-1-phenylhexane-1-one using diisopropylamine includes the following steps:

[0086] In a glove box under a nitrogen atmosphere, (1-hydroperoxycyclohexyl)benzene (0.3 mmol), tert-butyltetrasulfide (0.2 mmol), diisopropylamine (0.05 mmol), and anhydrous acetonitrile (2 mL) were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs (30 W, 425 nm wavelength) at a distance of 20 cm and stirred at room temperature for 12 h. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product of 6-(tert-butyldithio)-1-phenylhexane-1-one in 67% yield.

[0087] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.99 - 7.91(m, 2H), 7.57 - 7.52 (m, 1H), 7.48 - 7.41 (m, 2H), 2.97 (t, J = 7.3 Hz, 2H), 2.71 (t, J = 7.3 Hz, 2H), 1.73 (dp, J = 17.2, 7.4 Hz, 4H), 1.52 - 1.43 (m,2H), 1.32 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 200.21, 137.01, 132.96, 128.59, 128.04, 47.72, 40.62, 38.37, 29.97, 29.15, 28.21, 23.84.

[0088] Example 12

[0089] A method for synthesizing 5-(sec-butyldithio)-1-phenylpentan-1-one using diisopropylamine includes the following steps:

[0090] In a glove box under a nitrogen atmosphere, (1-hydroperoxycyclopentyl)benzene (0.3 mmol), 1,4-disec-butyltetrathione (0.2 mmol), diisopropylamine (0.05 mmol), and anhydrous acetonitrile (2 mL) were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs (30 W, 425 nm, 20 cm) at room temperature and stirred for 12 h. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-(sec-butyldithio)-1-phenylpentan-1-one, in 66% yield.

[0091] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.98 - 7.93(m, 2H), 7.59 - 7.53 (m, 1H), 7.46 (ddd, J = 8.2, 6.6, 1.3 Hz, 2H), 3.00 (t,J = 7.0 Hz, 2H), 2.72 (t, J = 7.1 Hz, 2H), 1.89 - 1.75 (m, 4H), 1.74 - 1.60(m, 2H), 1.52 (tq, J = 14.3, 7.3 Hz, 1H), 1.29 (d, J = 6.8 Hz, 3H), 0.97 (t,J = 7.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 199.94, 136.95, 133.04, 128.62,128.06, 47.97, 39.56, 38.07, 28.90 (d, J = 8.8 Hz), 23.14, 20.17, 11.53.

[0092] Example 13

[0093] A method for synthesizing 5-((3-methylbut-2-yl)dithio)-1-phenylpentan-1-one using diisopropylamine includes the following steps:

[0094] In a glove box under a nitrogen atmosphere, (1-hydroperoxycyclopentyl)benzene (0.3 mmol), 1,4-bis(3-methylbutane-2-yl)tetrathane (0.2 mmol), diisopropylamine (0.05 mmol), and anhydrous acetonitrile (2 mL) were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs (30 W, 425 nm, 20 cm) at room temperature and stirred for 12 h. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-((3-methylbutane-2-yl)dithio)-1-phenylpentane-1-one, in 77% yield.

[0095] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.96 (dt, J= 7.1, 1.4 Hz, 2H), 7.60 - 7.52 (m, 1H), 7.50 - 7.42 (m, 2H), 3.00 (t, J =7.1 Hz, 2H), 2.72 (t, J = 7.0 Hz, 2H), 1.96 (pd, J = 6.8, 4.9 Hz, 1H), 1.90 -1.75 (m, 4H), 1.24 (d, J = 7.0 Hz, 3H), 1.01 - 0.91 (m, 6H); 13 C NMR (100 MHz, CDCl3) δ 199.90, 136.94, 133.02, 128.61, 128.04, 53.45, 39.22, 38.07, 31.99, 28.79, 23.15, 20.40, 18.06, 16.43.

[0096] Example 14

[0097] A method for synthesizing 5-(cyclopentyldithio)-1-phenylpentan-1-one using diisopropylamine includes the following steps:

[0098] In a glove box under a nitrogen atmosphere, (1-hydroperoxycyclopentyl)benzene (0.3 mmol), cyclopentyltetrasulfide (0.2 mmol), diisopropylamine (0.05 mmol), and anhydrous acetonitrile (2 mL) were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs (30 W, 425 nm, 20 cm apart) at room temperature and stirred for 12 h. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-(cyclopentyldithio)-1-phenylpentan-1-one, in 74% yield.

[0099] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.99 - 7.88(m, 2H), 7.59 - 7.51 (m, 1H), 7.45 (dd, J = 8.4, 6.9 Hz, 2H), 3.33 - 3.21 (m,1H), 3.00 (t, J = 7.0 Hz, 2H), 2.74 (t, J = 7.0 Hz, 2H), 1.95 (dddd, J =14.7, 9.7, 5.4, 2.3 Hz, 2H), 1.90 - 1.71 (m, 6H), 1.68 - 1.52 (m, 4H); 13 C NMR (100 MHz, CDCl3) δ 199.90, 136.93, 133.02, 128.61, 128.04, 50.22, 39.12, 38.07, 33.06, 28.91, 24.75, 24.71, 23.16.

[0100] Example 15

[0101] A method for synthesizing 5-(cyclohexyldithio)-1-phenylpentan-1-one using diisopropylamine includes the following steps:

[0102] In a glove box under a nitrogen atmosphere, (1-hydroperoxycyclopentyl)benzene (0.3 mmol), cyclohexyltetrasulfide (0.2 mmol), diisopropylamine (0.05 mmol), and anhydrous acetonitrile (2 mL) were placed into a dried 8 mL vial with a screw cap and a magnetic stir bar. The reaction mixture was placed under two LEDs (30 W, 425 nm wavelength) at a distance of 20 cm and stirred at room temperature for 12 h. The crude reaction mixture was diluted with ethyl acetate (20 mL) and washed with water (20 mL × 3). The organic layer was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by rapid chromatography using ethyl acetate and petroleum ether as eluents to give a yellow oily product, 5-(cyclohexyldithio)-1-phenylpentan-1-one, in 81% yield.

[0103] The product was dissolved in CDCl3 (approximately 0.4 mL), sealed in a tube, and analyzed at room temperature using a BRUKER AVANCEIII HD-400 liquid superconducting nuclear magnetic resonance spectrometer. The characterization data are as follows: 1H NMR (400 MHz, CDCl3) δ 7.95 (dt, J= 7.1, 1.4 Hz, 2H), 7.59 - 7.51 (m, 1H), 7.45 (dd, J = 8.3, 6.8 Hz, 2H), 2.99(t, J = 7.0 Hz, 2H), 2.71 (t, J = 7.1 Hz, 2H), 2.07 - 1.97 (m, 2H), 1.88 -1.73 (m, 6H), 1.64 - 1.57 (m, 1H), 1.49 - 1.10 (m, 6H); 13 C NMR (100 MHz, CDCl3) δ 199.92, 136.95, 133.03, 128.61, 128.05, 49.51, 39.82, 38.07, 32.88, 28.84, 26.10, 25.65, 23.16.

[0104] Comparative Example 1

[0105] A method for synthesizing dithioalkyl ketone compounds using triethylamine is basically the same as that in Example 1, except that diisopropylamine is replaced with triethylamine.

[0106] The yield of the product was 62%, but other byproducts were generated during the reaction.

[0107] Comparative Example 2

[0108] A method for synthesizing dithioalkyl ketone compounds using cesium carbonate is basically the same as in Example 1, except that diisopropylamine is replaced with cesium carbonate.

[0109] The yield of the obtained product was 15%.

[0110] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art should understand that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for synthesizing dithioalkyl ketone compounds using diisopropylamine, characterized in that, Includes the following steps: A cycloalkyl peroxide compound, a tetrasulfide compound, and diisopropylamine were mixed with an organic solvent and subjected to a free radical coupling reaction under light irradiation to obtain the dithioalkyl ketone compound. The structural formula of the cycloalkyl peroxy alcohol compound is: Among them, R 1 Selected from one or more of hydrogen, p-tert-butyl, p-chloro, p-trifluoromethyl, m-methoxy, o-methyl, m-dimethyl, 1-naphthyl, and 2-naphthyl; n is an integer from 0 to 7; The structural formula of the tetrasulfide compound is as follows: Among them, R 2 It is tert-butyl, isopropyl, sec-butyl, 3-methylbut-2-yl, cyclopentyl, cyclohexyl or adamantyl.

2. The method according to claim 1, characterized in that, The cycloalkyl peroxy alcohols are selected from one of (1-hydroperoxycyclopentyl)benzene, 1-(tert-butyl)-4-(1-hydroperoxycyclopentyl)benzene, 1-chloro-4-(1-hydroperoxycyclopentyl)benzene, 1-(1-hydroperoxycyclopentyl)-4-(trifluoromethyl)benzene, 1-(1-hydroperoxycyclopentyl)-3-methoxybenzene, 1-(1-hydroperoxycyclopentyl)-2-methylbenzene, 1-(1-hydroperoxycyclopentyl)-3,5-dimethylbenzene, 1-(1-hydroperoxycyclopentyl)naphthalene, 2-(1-hydroperoxycyclopentyl)naphthalene, (1-hydroperoxycyclohexyl)benzene, 1-hydroperoxy-1-phenylcycloheptane, 1-hydroperoxy-1-phenylcyclooctane, and 1-hydroperoxy-1-phenylcyclododecane.

3. The method according to claim 1, characterized in that, The tetrasulfide compound is selected from one of tert-butyltetrasulfide, 1,4-di-sec-butyltetrasulfide, 1,4-bis(3-methylbutane-2-yl)tetrasulfide, cyclopentyltetrasulfide, cyclohexyltetrasulfide, and adamantanetetrasulfide.

4. The method according to claim 1, characterized in that, The molar ratio of diisopropylamine, cycloalkyl peroxide compounds and tetrasulfide compounds is (0.125-1):(1.5-2):(1-1.2).

5. The method according to claim 1, characterized in that, The organic solvent is acetonitrile, dichloromethane, or ethanol.

6. The method according to claim 1, characterized in that, The illumination conditions are as follows: one or more LED lamps with a power of 20-40 W and a wavelength of 425 nm are used for illumination.

7. The method according to claim 1, characterized in that, The free radical coupling reaction was carried out in a nitrogen atmosphere.

8. The method according to claim 1, characterized in that, The temperature for the free radical coupling reaction is 20-40 °C.

9. The method according to claim 1, characterized in that, The free radical coupling reaction takes 6-12 hours.

10. The method according to claim 1, characterized in that, The free radical coupling reaction, once completed, may also include one or more of the steps of filtration, concentration, and purification.

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