Cracking method of phenethyl sulfide compound

Abstract

The invention provides a cracking method of a phenethyl sulfide compound, and relates to the technical field of organic chemistry. The cracking method provided by the invention comprises the following steps: in an oxygen-containing environment, a solvent environment and the participation of organic alkali, enabling a phenethyl sulfide compound to react at 20-40 DEG C for 2-5 hours, then breaking a carbon-sulfur bond, and preparing a cracking product. According to the method, transition metal does not need to be used as a catalyst, meanwhile, cracking deprotection can be conducted on the phenethyl sulfide compound at the mild reaction temperature, the method is environmentally friendly, and the operation process is simple and safe.

Description

Technical Field

[0001] The present invention relates to the technical field of organic chemistry, and in particular to a cracking method for phenethyl sulfide compounds. Background Art

[0002] Thiophenol compounds are important aromatic raw materials and are widely used in the synthesis of organic compounds such as medicines, materials, and dyes. However, since the thiol group is sensitive to oxidants and bases, protection and deprotection of thiophenols are essential during organic synthesis. Since arylalkyl sulfides have high chemical stability under various reaction conditions, they have become the more commonly used thiophenol protecting groups. To date, many reagents or reagent combinations that can be used for the deprotection of arylalkyl sulfides have been developed, such as proton acids, Lewis acids, nucleophiles, oxidants, reducing agents, and transition metal catalysts. Although the above reagents have made some progress in the deprotection of arylalkyl sulfides, there are still many defects, such as harsh reaction conditions and the need to use expensive transition metal catalysts. Therefore, there is an urgent need to provide a solution to improve the above problems. Summary of the Invention

[0003] The present invention aims to provide a method for cracking phenethyl sulfide compounds, which does not require the use of transition metals as catalysts and can crack and deprotect phenethyl sulfide compounds at a relatively mild reaction temperature. The method is environmentally friendly and has a simple and safe operation process.

[0004] The present invention provides a cracking method for phenethyl sulfide compounds, comprising: reacting the phenethyl sulfide compounds at 20° C.-40° C. for 2 h-5 h in an oxygen-containing environment, a solvent environment, and the presence of an organic base, breaking the carbon-sulfur bond and obtaining a cracking product.

[0005] Optionally, the phenethyl sulfide compound includes one of a phenethyl fatty sulfide compound, a phenethyl thiocarboxylate compound, and a benzopentathiophene compound.

[0006] Optionally, the phenethyl sulfide compound includes one of a phenethyl fatty sulfide compound and a benzopentathiophene compound.

[0007] Optionally, the phenethyl fatty sulfide compound further includes a phenethyl thiocarboxylate compound.

[0008] Optionally, the structural formula of the phenylethyl fatty sulfide compound is as shown in Formula I:

[0009]

[0010] Among them, R 1 With R 2 are independently hydrogen, C1 to C40 Fatty groups, C4 to C 40 aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group.

[0011] Optionally, the structural formula of the thiocarboxylic acid phenethyl ester compound is as shown in Formula II:

[0012]

[0013] Among them, R 3 and R 4 are independently hydrogen, C1 to C 40 Fatty groups, C4 to C 40 aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group.

[0014] Optionally, the structural formula of the benzopentathiophene compound is as shown in Formula III:

[0015]

[0016] Among them, R 5 、R 6 and R 7 are independently hydrogen, C1 to C 40 Fatty groups, C4 to C 40 aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group.

[0017] Optionally, the C1 to C 40 The aliphatic group includes one of methyl, ethyl, propyl, isopropyl, butyl and benzyl.

[0018] Optionally, the C4 to C 40 The aromatic group includes one of a pyridine derivative, a phenyl group, a substituted phenyl group, a 1-naphthyl group, and a 2-naphthyl group.

[0019] Optionally, the halogen includes one of fluorine, chlorine, bromine and iodine.

[0020] Optionally, the pyrolysis products of the phenylethyl fatty sulfide compound include styrene compounds and thiophenol compounds.

[0021] Optionally, when the thiocarboxylic acid phenethyl ester compound is cracked, the cracking products include styrene compounds and thiocarboxylic acid compounds.

[0022] Optionally, the pyrolysis products of the benzopentathiophene compound include benzenethiol compounds.

[0023] Optionally, the reaction formula for cracking the phenylethyl fatty sulfide compound is:

[0024]

[0025] Optionally, the reaction formula for cracking the thiocarboxylic acid phenethyl ester compound is:

[0026]

[0027] Optionally, the reaction formula for cracking the benzopentathiophene compound is:

[0028]

[0029] Optionally, the solvent environment includes one of dimethyl sulfoxide and N,N-dimethylformamide.

[0030] Optionally, the organic base includes one of t-BuONa and t-BuOK.

[0031] Optionally, the oxygen concentration in the oxygen-containing environment is 10%-100%.

[0032] Optionally, the molar ratio of the organic base to the phenylethylamine compound is (2-6):1.

[0033] Alternatively, the phenethyl sulfide compound is reacted at 20° C.-40° C. for 2 h-5 h, then quenched, extracted, and separated by column chromatography to obtain a cleavage product. DETAILED DESCRIPTION

[0034] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. Unless otherwise defined, the technical terms or scientific terms used herein should be the common meanings understood by people with ordinary skills in the field to which the present invention belongs.

[0035] The present invention provides a method for cracking phenethyl sulfide compounds, comprising reacting the phenethyl sulfide compound at 20°C-40°C for 2-5 hours in an oxygen-containing environment and a solvent environment with an organic base, followed by cleavage of the carbon-sulfur bond to produce a cracking product. The method does not require the use of a transition metal catalyst and can be used to crack and deprotect the phenethyl sulfide compound at a relatively mild reaction temperature. It is environmentally friendly and has a simple and safe operation process.

[0036] Specifically, phenethyl sulfide compounds include phenethyl fatty sulfide compounds and benzopentathiophene compounds. Furthermore, phenethyl fatty sulfide compounds also include phenethyl thiocarboxylate compounds. In fact, the cleavage method provided by the present invention has good applicability to different types of reaction substrates and different types of functional groups, and can rapidly cleave carbon-sulfur bonds in a relatively mild system without the need for a transition metal catalyst.

[0037] In some embodiments, the cleavage reaction is performed in a solvent environment comprising dimethyl sulfoxide (DMSO) or N,N-dimethylformamide (N,N-DMF), an organic base comprising t-BuONa or t-BuOK, and an oxygen concentration ranging from 10% to 100%. In practice, the organic base / solvent / oxygen environment system allows for efficient cleavage of phenylethyl sulfide compounds containing C-S bonds.

[0038] Specifically, the cleavage reaction can be carried out in an air atmosphere, and the efficiency of the cleavage reaction is higher in an air atmosphere than in an oxygen atmosphere or an inert atmosphere. In addition, the molar ratio of the organic base to the phenylethylamine compound in the solvent environment is (2-6):1.

[0039] In some embodiments, the phenethyl sulfide compound is reacted at 20°C-40°C for 2-5 hours, then quenched, extracted, and separated by column chromatography to obtain a cleavage product. In practice, a relatively large amount of water can be added to the reaction system during quenching. Furthermore, after quenching, multiple extractions can be performed with ethyl acetate. The combined extracts are then washed with sodium chloride solution, dehydrated, concentrated under reduced pressure, and purified by silica gel column chromatography.

[0040] Furthermore, the structural formula of the phenylethyl fatty sulfide compound is shown in Formula I:

[0041]

[0042] Among them, R 1 With R 2 are independently hydrogen, C1 to C 40 Fatty groups, C4 to C 40aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group.

[0043] Furthermore, the structural formula of the thiocarboxylic acid phenylethyl ester compound is shown in Formula II:

[0044]

[0045] Among them, R 3 and R 4 are independently hydrogen, C1 to C 40 Fatty groups, C4 to C 40 aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group.

[0046] Furthermore, the structural formula of the benzopentathiophene compound is shown in Formula III:

[0047]

[0048] Among them, R 5 、R 6 and R 7 are independently hydrogen, C1 to C 40 Fatty groups, C4 to C 40 aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group.

[0049] In fact, C1 to C 40 The aliphatic group includes one of methyl, ethyl, propyl, isopropyl, butyl, benzyl, C4 to C 40 The aromatic group includes one of a pyridine derivative, a phenyl group, a substituted phenyl group, a 1-naphthyl group, and a 2-naphthyl group, and the halogen includes one of a fluorine group, a chlorine group, a bromine group, and an iodine group.

[0050] Specifically, the cracking products of the phenylethyl fatty sulfide compound include styrene compounds and thiophenol compounds, and the reaction formula during the cracking is:

[0051]

[0052] Specifically, the pyrolysis products of the thiocarboxylic acid phenylethyl ester compound include styrene compounds and thiocarboxylic acid compounds, and the reaction formula during pyrolysis is:

[0053]

[0054] Specifically, the pyrolysis products of the benzopentathiophene compounds include benzenethiol compounds, and the reaction formula during the pyrolysis is:

[0055]

[0056] Example 1

[0057] This embodiment 1 provides a method for cracking phenethyl sulfide compounds, comprising the following steps:

[0058] S1. Add 0.8 mmol (76.9 mg) of sodium tert-butoxide, 0.2 mmol of phenylethyl aryl sulfide, and 2 mL of DMSO into a 25 mL reaction tube and stir at 30°C in a dry air atmosphere for 4 h to fully break the carbon-sulfur bond.

[0059] S2. After adding 10 mL of deionized water to the reaction system of step S1 for quenching, 1 mol / L hydrochloric acid was added to adjust the pH of the reaction system to 1, and extraction was performed with 5 mL of ethyl acetate and repeated three times. The extracts were combined to obtain an organic phase, and the organic phase was washed with 30 mL of saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. After purification by silica gel column chromatography, the cleavage products styrene and thiophenol were obtained.

[0060] Wherein, the reaction formula in Example 1 is:

[0061]

[0062] Example 2 to Example 11

[0063] Examples 2 to 11 provide a method for cracking a phenethyl sulfide compound, respectively. The difference from Example 1 is that the type of the phenethyl sulfide compound and the reaction time are shown in Table 1 below.

[0064] Table 1 Phenethyl sulfide compounds, reaction time, cleavage products and yields

[0065]

[0066]

[0067]

[0068] The nuclear magnetic resonance characterization of the cracking product styrene in Examples 1 to 10 is as follows: 1H NMR(400MHz, CDCl3)δ:7.39(d,J=8.0Hz,2H),7.30(t,J=8.0Hz,2H),7.22(t,J=8.0Hz ,2H),6.70(dd,J=12.0,20.0Hz,1H),5.73(d,J=16.0Hz,1H),5.22(d,J=16.0Hz,1H). 13 C NMR (101MHz, CDCl3) δ: 137.7, 137.0, 128.6, 127.9, 126.3, 113.9.

[0069] The nuclear magnetic resonance characterization of the pyrolysis product thiophenol in Example 1 is as follows: 1 H NMR (300MHz, CDCl3): δ: 7.34-7.30 (m, 4H), 7.20 (t, J = 6.9Hz, 1H), 3.49 (s, 1H) ppm. 13 C NMR (75MHz, CDCl3): δ130.8,129.4,129.1,115.6ppm.

[0070] The nuclear magnetic resonance characterization of the cleavage product p-hydroxythiophenol in Example 2 is as follows: 1 H NMR (300MHz, CDCl3): δ: 7.25 (d, J = 8.7Hz, 2H), 6.76 (d, J = 8.4Hz, 2H), 4.75 (s, 1H), 3.37 (s, 1H); 13 C NMR (75MHz, CDCl3): δ154.2, 132.5, 139.9, 116.1.

[0071] The nuclear magnetic resonance characterization of the cleavage product 2-mercaptobenzothiazole in Example 3 is as follows: 1 H NMR (300MHz, CDCl3): δ: 11.59 (s, 1H), 7.42 (d, J = 8.0Hz, 1H), 7.33-7.21 (m, 3H); 13 C NMR (75MHz, CDCl3): δ190.8,140.1,129.9,127.1,124.6,121.3,112.1.

[0072] The nuclear magnetic resonance characterization of the cleavage product p-chlorobenzenethiophenol in Example 4 was as follows: 1 H NMR (300MHz, CDCl3): δ: 7.21 (s, 4H), 3.46 (s, 1H) ppm. 13 C NMR (75MHz, CDCl3): δ131.6, 130.7, 129.2, 129.1ppm.

[0073] The nuclear magnetic resonance characterization of the pyrolysis product p-toluene thiophenol in Example 5 was as follows: 1 H NMR (300MHz, CDCl3): δ: 7.21 (d, J = 8.1Hz, 2H), 7.07 (d, J = 8.1Hz, 2H), 3.41 (s, 1H), 2.32 (s, 3H) ppm. 13 C NMR (75MHz, CDCl3): δ: 135.5, 129.8, 129.8, 126.5, 20.8ppm.

[0074] The nuclear magnetic resonance characterization of the cleavage product p-methoxythiophenol in Example 6 was as follows: 1 H NMR (300MHz, CDCl3): δ: 7.22 (d, J = 8.7Hz, 2H), 6.76 (d, J = 8.7Hz, 2H), 3.73 (s, 3H), 3.32 (s, 1H) ppm. 13 C NMR (75MHz, CDCl3): δ: 138.1, 132.3, 116.2, 114.6, 55.2ppm.

[0075] The nuclear magnetic resonance characterization of the cleavage product 2,6-dimethylthiophenol in Example 7 was as follows: 1 H NMR (300MHz, CDCl3): δ: 7.10-7.00 (m, 1H), 3.28 (s, 1H), 2.40 (s, 6H) ppm. 13 C NMR (75MHz, CDCl3): 136.1, 131.2, 128.1, 125.1, 22.2ppm.

[0076] The nuclear magnetic resonance characterization of the cleavage product p-mercaptobenzoic acid in Example 8 was as follows: 1 H NMR (300MHz, DMSO-d6): δ13.11(br-s,1H),7.92(d,J=8.7Hz,2H),7.62(d,J=8.7Hz,2H),3.38(s,1H)ppm. 13 C NMR (75MHz, DMSO-d6): δ167.1,141.3,130.8,130.2,126.6ppm.

[0077] The nuclear magnetic resonance characterization of the cleavage product p-bromobenzenethiophenol in Example 9 was as follows: 1 H NMR (300MHz, CDCl3): δ: 7.36 (d, J = 8.5Hz, 2H), 7.15 (d, J = 8.7Hz, 2H), 3.43 (s, 1H); 13C NMR (75MHz, CDCl3): 132.0, 130.8, 129.8, 119.3.

[0078] The nuclear magnetic resonance characterization of the pyrolysis product thiobenzoic acid in Example 10 is as follows: 1 H NMR (300MHz, CDCl3): δ: 7.93 (d, J = 7.8Hz, 2H), 7.63 (t, J = 7.4Hz, 1H), 7.48 (t, J = 7.4Hz, 2H), 4.52 (s, 1H); 13 C NMR (101MHz, CDCl3) δ190.2,136.5,133.9,128.7,127.8.

[0079] The cleavage product (E)-2-(1-cyclohexylprop-1-en-2-yl)benzenethiol in Example 11 was characterized by nuclear magnetic resonance as follows: 1 H NMR (300MHz, CDCl3): δ: 1.05-1.35 (m, 6H), 1.60-1.74 (m, 4H), 1.86 (d, J=1.2Hz, 0.56×3H), 1.87 (d, J=1.2Hz, 0.44×3H), S15 2.22-2.31(m,0.44×1H),2.59-2.69(m,0.56×1H),5.65(dd,J=1.2Hz,8.8Hz,0.56 ×1H),5.75(dd,J=1.2Hz,8.8Hz,0.44×1H),7.14-7.18(m,1H),7.23-7.28(m,3H). 13 C NMR (101MHz, CDCl3) δ18.1,24.2,25.6,25.7,25.8,25.9,32.6,32.8,38.4,38.8,125.9,126.0,12 6.2,126.4,127.7,128.6,128.7,129.5,129.8,130.5,133.1,133.4,135.1,135.6,142.0,142.8.

[0080] While the embodiments of the present invention have been described in detail above, it will be apparent to those skilled in the art that various modifications and variations of these embodiments are possible. However, it should be understood that such modifications and variations are within the scope and spirit of the present invention as set forth in the claims. Furthermore, the invention described herein is susceptible to other embodiments and may be practiced or implemented in a variety of ways.

Claims

1. A method for cracking phenethyl sulfide compounds, characterized in that: include: In an oxygen-containing environment, a solvent environment and the participation of an organic base, a phenethyl sulfide compound is reacted at 20°C-40°C for 2h-5h, and then the carbon-sulfur bond is broken to obtain a cracking product.

2. The cracking method according to claim 1, characterized in that The phenethyl sulfide compound includes one of a phenethyl fatty sulfide compound and a benzopentathiophene compound; preferably, the phenethyl fatty sulfide compound also includes a phenethyl thiocarboxylate compound.

3. The cracking method according to claim 2, wherein: The structural formula of the phenylethyl fatty sulfide compound is shown in Formula I: Among them, R 1 With R 2 are independently hydrogen, C1 to C 40 Fatty groups, C4 to C 40 aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group; Preferably, the structural formula of the thiocarboxylic acid phenethyl ester compound is as shown in Formula II: Among them, R 3 and R 4 are independently hydrogen, C1 to C 40 Fatty groups, C4 to C 40 aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group; And / or, the structural formula of the benzopentathiophene compound is as shown in Formula III: Among them, R 5 、R 6 and R 7 are independently hydrogen, C1 to C 40 Fatty groups, C4 to C 40 aromatic group, alkoxy group, trifluoromethoxy group, trifluoromethyl group, nitro group, cyano group, alkyl group, hydroxyl group, carboxyl group, aldehyde group, carbonyl group, ester group, amino group, sulfonyl group, amide group or halogen group.

4. The cracking method according to claim 3, wherein: C1 to C 40 The aliphatic group includes one of methyl, ethyl, propyl, isopropyl, butyl and benzyl; and / or, the C4 to C 40 The aromatic group includes one of a pyridine derivative, a phenyl group, a substituted phenyl group, a 1-naphthyl group, and a 2-naphthyl group; and / or the halogen includes one of a fluorine group, a chlorine group, a bromine group, and an iodine group.

5. The cracking method according to claim 2, wherein: The pyrolysis products of the phenylethyl fatty sulfide compounds when they are pyrolyzed include styrene compounds and thiophenol compounds. Preferably, the pyrolysis products of the phenylethyl thiocarboxylate compounds when they are pyrolyzed include styrene compounds and thiocarboxylic acid compounds; the pyrolysis products of the benzopentathiophene compounds when they are pyrolyzed include benzenethiol compounds.

6. The cracking method according to claim 2, wherein: The reaction formula when the phenylethyl fatty sulfide compound is cracked is: Preferably, the reaction formula for cracking the thiocarboxylic acid phenethyl ester compound is: The reaction formula for cracking the benzopentathiophene compound is:

7. The cracking method according to claim 1, characterized in that The solvent environment includes one of dimethyl sulfoxide and N,N-dimethylformamide; and / or the organic base includes one of t-BuONa and t-BuOK; and / or the oxygen concentration in the oxygen-containing environment is 10%-100%; and / or the molar ratio of the organic base to the phenylethylamine compound is (2-6):

1.

8. The cracking method according to claim 1, characterized in that The phenethyl sulfide compound is reacted at 20° C.-40° C. for 2 h-5 h, then quenched, extracted, and separated by column chromatography to obtain a cleavage product.

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