A method for preparing bis(4-methylthiophenyl)dideuteriomethane

Abstract

The present application relates to the fine chemical technology field, specifically to a kind of preparation of bis (4-tolyl sulfenyl) di-deuteromethane method.The domestic research and synthesis of bis (4-tolyl sulfenyl) di-deuteromethane are less reported, only a few foreign literatures provide corresponding preparation method.Aiming at the above problems, the present application provides a kind of preparation of bis (4-tolyl sulfenyl) di-deuteromethane method, the present application is reacted by 4-methyl phenyl sulfenol and 1-(chloro di-deuteromethyl)-1,4-diazabicyclo [2.2.2] octane-1-ammonium chloride in the acetonitrile solution containing HI, bis (4-tolyl sulfenyl) di-deuteromethane is successfully prepared, the synthetic route of the present application is simple and efficient, raw material is easy to obtain, and has good commercial value.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of fine chemical industry, and particularly relates to a method for preparing bis(4-methylthiophenyl) dideuteromethane. BACKGROUND

[0002] Bis(4-methylthiophenyl) dideuteromethane is an important class of dithioacetal compounds, which can react with various electrophilic reagents such as halogenated alkanes, epoxides, ketones and aldehydes as important organic intermediates. In addition, the compound can also be used as a ligand of metal catalyst for different organic catalytic reactions.

[0003] At present, there are few reports on the synthesis method of deuterated dithioacetal derivatives. Only one foreign literature (Qian Chen, Guodian Yu, Xiaofeng Wang, et al. Cs2CO3-promoted methylene insertion into disulfide bonds using acetone as a methylene source. [J]. Organic & Biomolecular Chemistry, 2018, 16, 4086. DOI: 10.1039 / c8ob00877a.) successfully synthesized bis(phenylthio) methane with single deuterium. The method in the foreign literature is to use diphenyl disulfide and deuterium water as raw materials, and cesium carbonate and 8-crown-6 ether-6 are used as reaction additives at the same time, and bis(4-methylthio) monodeuteromethane is successfully prepared. SUMMARY

[0004] The existing problems in the prior art are that a new method for preparing bis(4-methylthiophenyl) dideuteromethane is sought. In view of the above problems, the present application provides a method for preparing bis(4-methylthiophenyl) dideuteromethane, which comprises the following preparation steps:

[0005] (1) 4-methylthiophenol reacts with 1-(chlorodideuteromethyl)-1,4-diazabicyclo[2.2.2]octane-1- ammonium chloride in acetonitrile containing HI to generate bis(4-methylthiophenyl) dideuteromethane, and the chemical structural formula of 1-(chlorodideuteromethyl)-1,4-diazabicyclo[2.2.2]octane-1- ammonium chloride is as follows:

[0006]

[0007] The chemical structural formula of bis(4-methylthiophenyl) dideuteromethane is as follows:

[0008]

[0009] Me in the above chemical structural formula represents a methyl substituent.

[0010] Preferably, the reaction temperature is greater than 60℃ and less than 120℃.

[0011] Preferably, the reaction temperature is 120℃.

[0012] Preferably, the reaction temperature is 100℃.

[0013] Preferably, the amount ratio of 4-methylphenyl sulfide to 1-(chloro-dideuteromethyl)-1,4-diazabicyclo[2.2.2]octane-1-ium chloride, acetonitrile, HI is 0.2mmol:0.1-0.6mmol:1-3mL:0.2-0.4mmol.

[0014] Preferably, the amount ratio of 4-methylphenyl sulfide to 1-(chloro-dideuteromethyl)-1,4-diazabicyclo[2.2.2]octane-1-ium chloride, acetonitrile, HI is 0.2mmol:0.2mmol:2mL:0.2mmol.

[0015] Preferably, the amount ratio of 4-methylphenyl sulfide to 1-(chloro-dideuteromethyl)-1,4-diazabicyclo[2.2.2]octane-1-ium chloride, acetonitrile, HI is 0.2mmol:0.2mmol:2mL:0.3mmol.

[0016] Preferably, the amount ratio of 4-methylphenyl sulfide to 1-(chloro-dideuteromethyl)-1,4-diazabicyclo[2.2.2]octane-1-ium chloride, acetonitrile, HI is 0.2mmol:0.2mmol:2mL:0.4mmol.

[0017] Preferably, the reaction time is 1-24h.

[0018] Preferably, the reaction time is 6-12h.

[0019] Preferably, the reaction time is 6h.

[0020] The present application has the following beneficial effects:

[0021] The present application provides a new method for synthesizing bis(4-methylthio) dideuteromethane, which successfully prepares bis(4-methylthio) dideuteromethane by reacting 4-methylphenyl sulfide with 1-(chloro-dideuteromethyl)-1,4-diazabicyclo[2.2.2]octane-1-ium chloride in acetonitrile solution. The synthesis route of the present application is simple and efficient, the raw materials are easy to obtain, and has good commercial value. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 The hydrogen spectrum of bis(4-methylthio) dideuteromethane obtained in Example 1.

[0023] Figure 2 The hydrogen spectrum of bis(4-methylthiophenyl)methane obtained in the comparative example. DETAILED DESCRIPTION

[0024] The application will be described in detail below with reference to the following examples. It should be understood that the following examples are merely illustrative of the embodiments of the application and are not intended to limit the scope of the application.

[0025] 1-(chlorodideuteromethyl)-1,4-diazabicyclo[2.2.2]octane-1- ammonium chloride (DABCO·CD2Cl2) in the following examples of the application was prepared according to the method reported in the literature (Guangke He, Yuan Li, Zilun Yu, Zhaoqiang Chen, et al. Selectfluor TM -catalyzed oxidative cyclization ofynamides enables facilesynthesis of oxazolidine-2,4-diones.[J].Organic Chemistry Frontiers,2019,6,3644.DOI:10.1039 / c9qo00845d.) according to the following steps:

[0026] 1g 1,4-diazabicyclo[2.2.2]octane (DABCO) was stirred with 2mL deuterated dichloromethane (CD2Cl2) at room temperature for 12h, and after filtration, the white solid product DABCO·CD2Cl2 was obtained.

[0027] Example 1

[0028] In a 25mL sealed tube, 4-methylthiophenol (0.2mmol, 24.84mg), DABCO·CD2Cl2(0.4mmol, 79.8mg), acetonitrile (2.0mL), HI (0.2mmol, 24μL) were added in turn, and after uniform mixing, constant temperature stirring was carried out at 100℃ for 12h. After the reaction was completed, the obtained reaction liquid was concentrated and separated by column chromatography to obtain bis(4-methylthiophenyl) di-deuteromethane with a yield of 80%.

[0029] The chemical reaction formula of the above reaction process is as follows:

[0030]

[0031] The hydrogen spectrum of bis(4-methylthiophenyl) di-deuteromethane is shown in the accompanying drawings. Figure 1 The hydrogen spectrum data is as follows:

[0032] 1 HNMR (300 MHz, CDC13): δ 7.35-7.32 (m, 4H), 7.14-7.11 (m, 4H), 2.34 (s, 6H).

[0033] Example 2 is the same as Example 1 except that in Example 2, the amount of DABCO-CD2Cl2used is 0.1 mmol and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 66%.

[0034] Example 3 is the same as Example 1 except that in Example 3, the amount of DABCO-CD2Cl2used is 0.2 mmol and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 95%.

[0035] Example 4 is the same as Example 1 except that in Example 4, the amount of DABCO-CD2Cl2used is 0.6 mmol and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 70%.

[0036] Example 5 is the same as Example 3 except that in Example 5, the amount of HI used is 0.1 mmol and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 0%.

[0037] Example 6 is the same as Example 3 except that in Example 6, the amount of HI used is 0.3 mmol and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 84%.

[0038] Example 7 is the same as Example 3 except that in Example 7, the amount of HI used is 0.4 mmol and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 70%.

[0039] Example 8 is the same as Example 3 except that in Example 8, the reaction time is 1 h and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 60%.

[0040] Example 9 is the same as Example 3 except that in Example 9, the reaction time is 6 h and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 99%.

[0041] Example 10 is the same as Example 3 except that in Example 10, the reaction time is 24 h and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 95%.

[0042] Example 11 is the same as Example 9 except that in Example 11, the reaction solvent is ethyl acetate and the yield of bis(4-methylthiophenyl)dideuteriomethane obtained is 0%.

[0043] Example 12 is the same as Example 9 except that in Example 12 the reaction solvent is tetrahydrofuran and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 0%.

[0044] Example 13 is the same as Example 9 except that in Example 13 the reaction solvent is toluene and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 0%.

[0045] Example 14 is the same as Example 9 except that in Example 14 the reaction solvent is N,N-dimethylformamide and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 0%.

[0046] Example 15 is the same as Example 9 except that in Example 15 the reaction solvent is dimethylsulfoxide and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 0%.

[0047] Example 16 is the same as Example 9 except that in Example 16 the reaction solvent is methanol and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 0%.

[0048] Example 17 is the same as Example 9 except that in Example 17 the amount of acetonitrile is 1 mL and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 64%.

[0049] Example 18 is the same as Example 9 except that in Example 18 the amount of acetonitrile is 3 mL and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 99%.

[0050] Example 19 is the same as Example 9 except that in Example 19 the reaction temperature is 25°C and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 0%.

[0051] Example 20 is the same as Example 9 except that in Example 20 the reaction temperature is 60°C and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 0%.

[0052] Example 21 is the same as Example 9 except that in Example 21 the reaction temperature is 120°C and the yield of bis(4-methylphenylsulfanyl)dideuteromethane is 74%.

[0053] Comparative Example 1 is the same as Example 1 except that in Comparative Example 1 DABCO-CD2Cl2 is replaced with DABCO-CH2Cl2 which is prepared as follows:

[0054] 1 g 1,4-diazabicyclo[2.2.2]octane (DABCO) was stirred with 2 mL dichloromethane (CH2Cl2) at room temperature for 12 h, and the solid product DABCO-CH2Cl2was obtained after filtration.

[0055] The product obtained in Comparative Example 1 was bis(4-methylthiophenyl)methane. The hydrogen spectrum of the bis(4-methylthiophenyl)methane is shown in the description accompanying the drawings. Figure 2

[0056] The above ideal embodiments according to the present application are used as the inspiration, and through the above description, relevant staff can make various changes and modifications without deviating from the technical idea of the present application. The technical scope of the present application is not limited to the content in the description, and the technical scope must be determined according to the scope of claims.​

Claims

1. A method for preparing bis(4-toluenethio)dideuterium methane, characterized in that, The preparation steps include the following: (1) 4-Methylthiophenol reacts with 1-(dideuterylchloromethyl)-1,4-diazabicyclo[2.2.2]octane-1-ammonium chloride in an organic solvent containing HI to generate bis(4-tolylthio)dideuterium methane, the chemical structural formula of which is as follows: ， The chemical structural formula of the bis(4-toluenethio)dideuterium methane is as follows: ， In the above chemical structural formula, Me represents a methyl substituent; The organic solvent used in the above reaction process is acetonitrile; The above reaction temperature is greater than 60℃ and lower than 120℃; In the above reaction process, the ratio of 4-methylthiophenol to 1-(dichlorodeuterylmethyl)-1,4-diazabicyclo[2.2.2]octane-1-ammonium chloride, organic solvent, and HI is 0.2 mmol: 0.1-0.6 mmol: 1-3 mL: 0.2-0.4 mmol.

2. The method for preparing bis(4-toluenethio)dideuterium methane according to claim 1, characterized in that, The reaction temperature is 120°C.

3. The method for preparing bis(4-toluenethio)dideuterium methane according to claim 1, characterized in that, The reaction temperature is 100℃.

4. The method for preparing bis(4-toluenethio)dideuterium methane according to claim 1, characterized in that, The ratio of 4-methylthiophenol to 1-(dichlorodeuterylmethyl)-1,4-diazabicyclo[2.2.2]octane-1-ammonium chloride, organic solvent, and HI was 0.2 mmol:0.2 mmol:2 mL:0.2 mmol.

5. The method for preparing bis(4-toluenethio)dideuterium methane according to claim 1, characterized in that, The ratio of 4-methylthiophenol to 1-(dichlorodeuterylmethyl)-1,4-diazabicyclo[2.2.2]octane-1-ammonium chloride, organic solvent, and HI was 0.2 mmol:0.2 mmol:2 mL:0.3 mmol.

6. The method for preparing bis(4-toluenethio)dideuterium methane according to claim 1, characterized in that, The ratio of 4-methylthiophenol to 1-(dichlorodeuterylmethyl)-1,4-diazabicyclo[2.2.2]octane-1-ammonium chloride, organic solvent, and HI was 0.2 mmol:0.2 mmol:2 mL:0.4 mmol.

7. The method for preparing bis(4-toluenethio)dideuterium methane according to claim 1, characterized in that, The reaction time is 6-12 hours.

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