Method for synthesizing dithiocarbamate derivative

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing a dithiocarbamate derivative. Comprising the following steps: mixing a compound shown as a formula I, an alcohol reagent, carbon disulfide and a compound shown as a formula II to obtain a mixture; and reacting the obtained mixture at the temperature of 20-30 DEG C for 5 hours to obtain the dithiocarbamate derivative. The method for synthesizing the dithiocarbamate derivative does not need an oxidant and a metal catalyst, can react at room temperature, and is green, environment-friendly, high in reaction tolerance and good in yield.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing dithiocarbamate derivatives. Background Art

[0002] Carbon disulfide is a colorless liquid with a strong odor. It is mainly used in the rubber industry and leather and textile industry, especially in the production of artificial fibers such as viscose fibers. In addition, carbon disulfide can also be used in the pharmaceutical, pesticide and organic synthesis industries. Carbon disulfide can be used to produce intermediates for some drugs and can also be used to synthesize some organic compounds, which is conducive to promoting the development of pharmaceutical, chemical and manufacturing industries.

[0003] Tetrahydropyrrole and other secondary amine compounds have broad application prospects in drug development and other fields due to their rich chemical structures and diverse biological activities. Some of these secondary amine compounds have neuromodulatory functions and can be used to treat depression, anxiety, epilepsy, etc. In addition, tetrahydropyrrole and other secondary amine compounds are also widely used in other fields. For example, they can be used as monomers or additives in polymer materials to improve the performance of materials.

[0004] Dithiocarbamate compounds are widely used in agriculture, biochemistry, medicinal chemistry, materials and organic synthesis. Some compounds containing dithiocarbamate structural units have been proven to have biological activity, such as herbicides and fungicides in agriculture, and anti-tumor, anti-cancer and antibacterial effects in the medical field (such as epalrestat, brassinolide, etc.). In addition, dithiocarbamates can also be used as protective groups and linkers in peptide synthesis, and as building blocks for the synthesis of organic compounds.

[0005] In addition, Kaliyamoorthy Alagiri's group has demonstrated that under conventional heating conditions, using aziridine and sodium diethylaminodithiocarbamate as reaction substrates, using CH 3 A method for synthesizing 2-((4-methylphenyl)sulfonylamino)-1-phenethylpyrrolidine-1-carbodithioate compound as a solvent.

[0006]

[0007] He Muxue's research group has confirmed that under the condition of electricity, using tetrabutylammonium tetrafluoroborate as electrolyte and acetonitrile as solvent, methyl benzoate compounds, secondary amine compounds and CS 2 Three-component dehydrogenative coupling reaction.

[0008]

[0009] However, in the process of synthesizing such compounds, conventional synthesis methods require the use of expensive and highly toxic reaction substrates, photocatalysts, electrocatalysis, acids, bases and strong oxidants, etc., and the reaction time is long and the conditions are harsh. Based on the current research situation, an effective, simple and environmentally friendly new method is needed to synthesize thioamino compounds. Summary of the invention

[0010] In order to solve the above problems, the present invention provides a method for synthesizing dithiocarbamate derivatives. The method adopts a room temperature stirring method, uses a compound shown in Formula I, carbon disulfide and a compound shown in Formula II as reaction substrates, and methanol and other cheap and low-toxic reagents as solvents to synthesize dithiocarbamate derivatives. The thioalkyl compounds are synthesized under mild and green conditions, which fills the gap in the synthesis method in this field.

[0011] In order to achieve the above object, the present invention provides the following technical solutions:

[0012] The present invention provides a method for synthesizing dithiocarbamate derivatives, comprising the following steps:

[0013] 1) mixing a compound represented by formula I, an alcohol reagent, carbon disulfide and a compound represented by formula II to obtain a mixture;

[0014]

[0015] Wherein R is selected from 4-CH 3 -phenyl, 4-F-phenyl, phenyl and hydrogen;

[0016]

[0017] 2) reacting the compound obtained in step 1) at a temperature of 20 to 30° C. for 5 h to obtain a dithiocarbamate derivative;

[0018] The structural formula of the dithiocarbamate derivative is shown in Formula III:

[0019]

[0020]

[0021] Preferably, the alcohol reagent in step 1) includes methanol and trifluoroethanol;

[0022] The volume ratio of the methanol to trifluoroethanol is 2:1.

[0023] Preferably, in step 1), the molar ratio of the compound represented by formula I, the volume of the alcohol reagent, the molar ratio of carbon disulfide and the compound represented by formula II is 0.2mmol:3mL:0.4mmol:0.4mmol.

[0024] Preferably, the compound represented by formula I in step 1) is any one of the following compounds:

[0025]

[0026] Preferably, the compound represented by formula II in step 1) is any one of the following compounds:

[0027]

[0028] Preferably, after the reaction in step 2), a reactant is obtained, and the reactant is separated and purified by silica gel column chromatography to obtain a dithiocarbamate derivative.

[0029] Preferably, the mobile phase used in the silica gel column chromatography separation and purification is petroleum ether and ethyl acetate.

[0030] Preferably, the volume ratio of petroleum ether to ethyl acetate is 4:1.

[0031] Beneficial effects:

[0032] 1. The present invention does not require oxidants or other metal catalysts to synthesize dithiocarbamate derivatives, and is green and environmentally friendly.

[0033] 2. The reaction can be carried out at room temperature, the conditions are mild, and the yield is good.

[0034] 3. High reaction tolerance, various types of substituents can react well.

[0035] 4. Methanol and trifluoroethanol are used as solvents in the reaction, which is green and environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required to be used in the embodiments are briefly introduced below.

[0037] Figure 1 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 1.

[0038] Figure 2 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 1.

[0039] Figure 3 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 2.

[0040] Figure 4 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 2.

[0041] Figure 5 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 3.

[0042] Figure 6 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 3.

[0043] Figure 7 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 4.

[0044] Figure 8 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 4.

[0045] Fig. 9 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 5.

[0046] Fig.10 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 5.

[0047] Fig.11 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 6.

[0048] Fig.12 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 6.

[0049] Fig.13 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 7.

[0050] Fig.14 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 7.

[0051] Fig.15 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 8.

[0052] Fig.16 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 8.

[0053] Fig.17 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 9.

[0054] Fig.18 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 9. DETAILED DESCRIPTION

[0055] The present invention provides a method for synthesizing dithiocarbamate derivatives, comprising the following steps:

[0056] 1) mixing a compound represented by formula I, an alcohol reagent, carbon disulfide and a compound represented by formula II to obtain a mixture;

[0057]

[0058] Wherein R is selected from 4-CH 3 -phenyl, 4-F-phenyl, phenyl and hydrogen;

[0059]

[0060]

[0061] 2) reacting the compound obtained in step 1) at a temperature of 20 to 30° C. for 5 h to obtain a dithiocarbamate derivative;

[0062] The structural formula of the dithiocarbamate derivative is shown in Formula III:

[0063]

[0064] In the present invention, the alcohol reagent preferably includes methanol and trifluoroethanol. In the present invention, the volume ratio of methanol and trifluoroethanol is preferably 2:1. In the present invention, the molar ratio of the compound represented by formula I, the volume of the alcohol reagent, the molar ratio of carbon disulfide and the compound represented by formula II is preferably 0.2mmol:3mL:0.4mmol:0.4mmol. In the present invention, the compound represented by formula I is preferably any one of the following compounds:

[0065]

[0066] In the present invention, the compound represented by formula II is preferably any one of the following compounds:

[0067]

[0068] In the present invention, a crude product is obtained after the reaction is completed, and the crude product is preferably separated and purified by silica gel column chromatography to obtain a dithiocarbamate derivative. In the present invention, the mobile phase used for the silica gel column chromatography separation and purification is preferably petroleum ether and ethyl acetate. In the present invention, the volume ratio of petroleum ether to ethyl acetate is preferably 4:1. The present invention does not specifically limit the method for separation and purification by silica gel column chromatography, and conventional methods can be used.

[0069] The reaction equation for preparing dithiocarbamate derivatives of the present invention is as follows:

[0070]

[0071] Wherein, 1 is a compound represented by formula I, 2 is carbon disulfide, 3 is a compound represented by formula II, and 4 is a dithiocarbamate derivative.

[0072] In order to further illustrate the present invention, the present invention is described in detail below in conjunction with embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0073] Example 1

[0074] The preparation method of this embodiment comprises the following steps:

[0075] 1a (0.2mmol), methanol (2mL), trifluoroethanol (1mL), carbon disulfide (0.4mmol), tetrahydropyrrole (0.4mmol) and finally a magnet were added to the test tube in sequence. The reaction was allowed to react for 5h at room temperature and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 4a was separated and purified by 200-300 mesh silica gel column chromatography with a yield of 90%. The reaction equation is as follows:

[0076]

[0077] 1 H NMR (400 MHz, CDCl 3 ,ppm): δ7.72(d,J=8.4Hz,2H),7.31-7.26(m,5H),7.23-7.21(m,2H),5.27-5.18(m,2H), 3.92-3.83(m,2H),3.77-3.70(m,1H),3.57-3.47(m,3H),2.42(s,3H),2.07-1.91(m,4H); 13 C NMR (100 MHz, CDCl 3 , ppm): δ190.7,143.3,137.5,137.2,129.6,129.0,128.2,127.2,55.3,53.6,50.7,47.9,26.0,24.2,21.6.

[0078] Example 2

[0079] The preparation method of this embodiment comprises the following steps:

[0080] 1b (0.2mmol), methanol (2mL), trifluoroethanol (1mL), carbon disulfide (0.4mmol), tetrahydropyrrole (0.4mmol) and finally a magnet were added to the test tube in sequence. The reaction was allowed to react for 5h at room temperature and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 4b was obtained by separation and purification by 200-300 mesh silica gel column chromatography with a yield of 84%. The reaction equation is as follows:

[0081]

[0082] 1 H NMR (400 MHz, CDCl 3 ,ppm): δ7.65(d,J=8.0Hz,2H),7.21-7.19(d,J=8.4Hz,2H),7.03(s,4H),5.14-5.07(m,2H),3.86 -3.77(m,2H),3.70-3.65(m,1H),3.49-3.39(m,3H),2.35(s,3H),2.25(s,3H),2.00-1.85(m,4H); 13 C NMR (100 MHz, CDCl 3 , ppm): δ190.9,143.2,138.2,137.3,134.3,129.7,129.6,128.1,127.2,55.2,53.3,50.7,48.0,26.0,24.2,21.6,21.2.

[0083] Example 3

[0084] The preparation method of this embodiment comprises the following steps:

[0085] 1c (0.2mmol), methanol (2mL), trifluoroethanol (1mL), carbon disulfide (0.4mmol), tetrahydropyrrole (0.4mmol) and finally a magnet were added to the test tube in sequence. The reaction was allowed to react for 5h at room temperature and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 4c was separated and purified by 200-300 mesh silica gel column chromatography with a yield of 82%. The reaction equation is as follows:

[0086]

[0087] 1 H NMR (400 MHz, CDCl 3,ppm): δ7.59(d,J=7.6Hz,2H),7.23-7.09(m,4H),7.00(d,J=10Hz,1H),6.92-6.88(m,1H),6.59(d,J= 5.2Hz,1H),4.62-4.59(m,1H),3.96-3.83(m,3H),3.54-3.38(m,3H),2.37(s,3H),2.10-1.99(m,4H); 13 C NMR (100 MHz, CDCl 3 ,ppm): δ192.3,143.3,142.8,137.9,130.1(d,J=8.2Hz,1C),128.1(d,J=197.7Hz,1C),122.3 ,114.7(d,J=21.2Hz,1C),113.8(d,J=22.2Hz,1C),58.7,55.7,50.9,41.3,26.0,24.3,21.5.

[0088] Example 4

[0089] The preparation method of this embodiment comprises the following steps:

[0090] 1d (0.2mmol), methanol (2mL), trifluoroethanol (1mL), carbon disulfide (0.4mmol), 3b (0.4mmol) and finally a magnet were added to the test tube in sequence. The reaction was allowed to react for 5h at room temperature and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 4d was obtained by separation and purification by 200-300 mesh silica gel column chromatography with a yield of 86%. The reaction equation is as follows:

[0091]

[0092] 1 H NMR (400 MHz, CDCl 3 ,ppm): δ7.75(d,J=8.0Hz,2H),7.30(d,J=8.0Hz,2H),5.27-5.25(m,1H),4.29 -3.92(m,4H),3.73(s,4H),3.50-3.46(m,2H),3.32-3.27(m,2H),2.42(s,3H); 13 C NMR (100 MHz, CDCl 3 ,ppm): δ196.4,143.5,137.2,129.7,127.1,66.2,42.5,36.0,21.5.

[0093] Example 5

[0094] The preparation method of this embodiment comprises the following steps:

[0095] 1d (0.2mmol), methanol (2mL), trifluoroethanol (1mL), carbon disulfide (0.4mmol), 3c (0.4mmol), and finally a magnet were added to the test tube in sequence. The reaction was allowed to react for 5h at room temperature, and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 4e was obtained by separation and purification by 200-300 mesh silica gel column chromatography with a yield of 80%. The reaction equation is as follows:

[0096]

[0097] 1 H NMR (400 MHz, CDCl 3 ,ppm): δ7.75(d,J=8.0Hz,2H),7.29(d,J=8.4Hz,2H),5.32(s,1H),4.24(s,2H),3 .83(s,2H),3.47-3.44(m,2H),3.31-3.27(m,2H),2.42(s,3H),1.71-1.65(m,6H); 13 C NMR (100 MHz, CDCl 3 ,ppm): δ194.4,143.4,137.2,129.7,127.1,42.8,36.0,24.2,21.5.

[0098] Example 6

[0099] The preparation method of this embodiment comprises the following steps:

[0100] 1d (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), 3d (0.4 mmol), and finally a magnet were added to the test tube in sequence. The reaction was allowed to react for 5 h at room temperature, and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, compound 4f was separated and purified by 200-300 mesh silica gel column chromatography, and the yield was 79%. The reaction equation is as follows:

[0101]

[0102] 1 H NMR (400 MHz, CDCl 3,ppm): δ7.75(d,J=8.4Hz,2H),7.29(d,J=8.0Hz,2H),5.35-5.33(m,1H),3.88-3.84(m,2H) ,3.59-3.55(m,2H),3.31-3.26(m,2H),2.41(s,3H),1.75-1.67(m,4H),0.95-0.90(m,6H); 13 C NMR (100 MHz, CDCl 3 ,ppm):δ 13 C NMR (101 MHz, CDCl 3 )δ195.1,143.3,137.2,129.7,127.1,57.2,54.5,42.8,36.0,21.5,20.7,19.6,11.2.

[0103] Example 7

[0104] The preparation method of this embodiment comprises the following steps:

[0105] 1d (0.2mmol), methanol (2mL), trifluoroethanol (1mL), carbon disulfide (0.4mmol), 3e (0.4mmol) and finally a magnet were added to the test tube in sequence. The reaction was allowed to react for 5h at room temperature and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, the compound 4g was obtained by separation and purification by 200-300 mesh silica gel column chromatography with a yield of 86%. The reaction equation is as follows:

[0106]

[0107] 1 H NMR (400 MHz, CDCl 3 ,ppm): δ7.75(d,J=8.4Hz,2H),7.30(d,J=8.0Hz,2H),5.13-5.10(m,1H),3.52(s,3H),3.46-3.43(m,2H),3.32-3.28(m,5H),2.42(s,3H); 13 C NMR (100 MHz, CDCl 3 ,ppm): δ196.2,143.4,137.2,129.7,127.1,45.6,42.7,41.6,36.4,21.5.

[0108] Example 8

[0109] The preparation method of this embodiment comprises the following steps:

[0110] 1a (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), 3c (0.4 mmol), and finally a magnet were added to the test tube. The reaction was allowed to proceed for 5 h at room temperature, and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, the compound 4h was separated and purified by 200-300 mesh silica gel column chromatography, and the yield was 87%. The reaction equation is as follows:

[0111]

[0112] 1 H NMR (400 MHz, CDCl 3 ,ppm): δ7.71(d,J=8.4Hz,2H),7.32-7.27(m,5H),7.23-7.20(m,2H),5.25-5.21(m,1H),5.07-5.0 4(m,1H),4.30-4.18(m,2H),3.80-3.73(m,3H),3.53-3.47(m,1H),2.43(s,3H),1.69-1.62(m,6H); 13 C NMR (100 MHz, CDCl 3 , ppm): δ193.3,143.3,137.3,137.2,129.6,129.0,128.4,128.3,127.2,54.3,47.8,24.2,21.6.

[0113] Example 9

[0114] The preparation method of this embodiment comprises the following steps:

[0115] 1a (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), 3f (0.4 mmol), and finally a magnet were added to the test tube. The reaction was allowed to proceed for 5 h at room temperature, and the reaction progress was monitored by thin layer chromatography until the reaction was complete. Finally, the compound 4i was separated and purified by 200-300 mesh silica gel column chromatography, and the yield was 84%. The reaction equation is as follows:

[0116]

[0117] 1 H NMR (400 MHz, CDCl 3,ppm): δ7.64(d,J=8.4Hz,2H),7.22-7.19(m,5H),7.15-7.13(m,2H),5.16-5.12(m,1H),5.03-5.00(m,1H), 3.93-3.88(m,2H),3.71-3.65(m,1H),3.6-3.55(m,2H),3.46-3.40(m,1H),2.35(s,3H),1.20-1.12(m,6H); 13 C NMR (100 MHz, CDCl 3 , ppm): δ193.5,143.3,137.3,137.4,129.6,129.0,128.4,128.3,127.2,54.3,49.9,47.9,46.9,21.6,12.6,11.5.

[0118] Comparative Example 1

[0119] The existing method for preparing dithiocarbamate compounds is to add aziridine (1 equiv), sodium diethylaminodithiocarbamate (1.05 equiv), CH 3 CN (3 mL) was heated to 80°C and reacted for 12 h. Finally, the product was separated and purified by 200-300 mesh silica gel column chromatography to obtain a mixed compound of regioisomers with a yield of 99%.

[0120]

[0121] Compared with this method, the carbon disulfide, tetrahydropyrrole and other heavy amine compounds in the scheme of the present invention are all commercially available products, which can be directly purchased without pretreatment, thus reducing the reaction cost and having higher atom economy. Secondly, the reaction conditions of the present invention are mild, which solves the harsh temperature requirements in the reaction and is green and environmentally friendly.

[0122] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for synthesizing dithiocarbamate derivatives, characterized in that: The following steps are involved: 1) mixing a compound represented by formula I, an alcohol reagent, carbon disulfide and a compound represented by formula II to obtain a mixture; Wherein, R is selected from any one of 4-CH3-phenyl, 4-F-phenyl, phenyl and hydrogen; 2) reacting the mixture obtained in step 1) at a temperature of 20 to 30° C. for 5 hours to obtain a dithiocarbamate derivative; The structural formula of the dithiocarbamate derivative is shown in Formula III:

2. The method according to claim 1, characterized in that The alcohol reagent in step 1) includes methanol and trifluoroethanol; The volume ratio of the methanol to trifluoroethanol is 2:

1.

3. The method according to claim 1, characterized in that In the step 1), the molar ratio of the compound represented by formula I, the volume of the alcohol reagent, the molar ratio of carbon disulfide and the compound represented by formula II is 0.2mmol:3mL:0.4mmol:0.4mmol.

4. The method according to claim 1, characterized in that: The compound represented by formula I in step 1) is any one of the following compounds:

5. The method according to claim 1, characterized in that The compound represented by formula II in step 1) is any one of the following compounds:

6. The method according to claim 1, characterized in that After the reaction in step 2), a reactant is obtained, and the reactant is separated and purified by silica gel column chromatography to obtain a dithiocarbamate derivative.

7. The method according to claim 6, characterized in that The mobile phases used in the silica gel column chromatography separation and purification are petroleum ether and ethyl acetate.

8. The method according to claim 7, characterized in that The volume ratio of petroleum ether to ethyl acetate is 4:1.

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