A method for synthesizing dithiocarbamate derivatives
By synthesizing dithiocarbamate derivatives with compounds of formula I, carbon disulfide and methanol or trifluoroethanol at room temperature, the problems of high costs and harsh conditions in the prior art are solved, and an efficient and environmentally friendly synthesis method is achieved.
Patent Information
- Application Number
- CN202411228278.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-03
- Publication Date
- 2025-09-02
- Estimated Expiration
- 2044-09-03
AI Technical Summary
The existing methods for synthesizing dithiocarbamate compounds require the use of expensive and highly toxic reaction substrates, and the reaction conditions are harsh and there is a lack of environmentally friendly simple synthesis methods.
The dithiocarbamate derivative was synthesized by room temperature stirring using the compound represented by formula I, carbon disulfide, methanol or trifluoroethanol as solvents, and the use of oxidants and metal catalysts were avoided, and the use of oxidants and metal catalysts were separated and purified by silica gel column chromatography.
It has achieved efficient synthesis of dithiocarbamate derivatives under mild conditions, with good yields and green environmental protection, reducing reaction costs and impact on the environment.
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Figure CN119101013B_ABST
Abstract
Description
Technical Field
[0001] The present 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's primarily used in the rubber, leather, and textile industries, particularly in the production of man-made fibers such as viscose. It's also used in the pharmaceutical, pesticide, and organic synthesis industries. It can be used as an intermediate in the production of certain pharmaceuticals and in the synthesis of certain organic compounds, contributing to the development of the pharmaceutical, chemical, and manufacturing industries.
[0003] Tetrahydropyrrole and other secondary amine compounds, due to their rich chemical structures and diverse biological activities, hold broad application prospects in drug development and other fields. Certain secondary amine compounds possess neuromodulatory properties and can be used to treat depression, anxiety, and epilepsy. Furthermore, secondary amine compounds like tetrahydropyrrole are widely used in other fields, such as as monomers or additives in polymer materials to improve their properties.
[0004] Dithiocarbamate compounds are widely used in agriculture, biochemistry, medicinal chemistry, materials science, and organic synthesis. Some compounds containing dithiocarbamate structural units have been shown to exhibit biological activity, such as herbicides and fungicides in agriculture, and antitumor, anticancer, and antibacterial properties in medicine (e.g., epalrestat and brassinolide). Furthermore, dithiocarbamates can serve as protecting groups and linkers in peptide synthesis and as building blocks in the synthesis of organic compounds.
[0005] In addition, Kaliyamoorthy Alagiri's group has demonstrated a method for synthesizing 2-((4-methylphenyl)sulfonylamino)-1-phenylethylpyrrolidine-1-dithiocarboxylate compounds using conventional heating conditions, aziridine and sodium diethylaminodithiocarboxylate as reaction substrates, and CH3CN as solvent.
[0006]
[0007] He Muxue's research group has demonstrated that under electrical conditions, using tetrabutylammonium tetrafluoroborate as the electrolyte and acetonitrile as the solvent, they achieved a three-component dehydrogenative coupling reaction of methyl benzoate compounds, secondary amine compounds, and CS2.
[0008]
[0009] However, conventional methods for synthesizing these compounds require expensive and toxic substrates, photocatalysts, electrocatalysts, acids, bases, and strong oxidants, and they also require long reaction times and demanding conditions. Based on current research, a new, efficient, simple, and environmentally friendly method for synthesizing thioamino compounds is needed. Summary of the Invention
[0010] To address the above issues, the present invention provides a method for synthesizing dithiocarbamate derivatives. This method utilizes room temperature stirring, using a compound represented by Formula I, carbon disulfide, and a compound represented by Formula II as reaction substrates, and an inexpensive and low-toxic reagent such as methanol as a solvent. This method utilizes mild, green conditions to synthesize thioalkyl compounds, filling a gap in synthetic methods 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 any one of 4-CH3-phenyl, 4-F-phenyl, phenyl and hydrogen;
[0016]
[0017] 2) reacting the compound obtained in step 1) at a temperature of 20-30° 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) comprises 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 0.2 mmol:3 mL:0.4 mmol:0.4 mmol.
[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 synthesis of dithiocarbamate derivatives by the present invention does not require oxidants and other metal catalysts, 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 for use 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] Figure 9 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 5.
[0046] Figure 10 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 5.
[0047] Figure 11 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 6.
[0048] Figure 12 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 6.
[0049] Figure 13 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 7.
[0050] Figure 14 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 7.
[0051] Figure 15 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 8.
[0052] Figure 16 This is the carbon spectrum of the dithiocarbamate derivative prepared in Example 8.
[0053] Figure 17 This is the hydrogen spectrum of the dithiocarbamate derivative prepared in Example 9.
[0054] Figure 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 any one of 4-CH3-phenyl, 4-F-phenyl, phenyl and hydrogen;
[0059]
[0060]
[0061] 2) reacting the compound obtained in step 1) at a temperature of 20-30° 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 particularly limit the method of silica gel column chromatography separation and purification, 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 with reference to the 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 (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), tetrahydropyrrole (0.4 mmol), and finally a magnet were added to a test tube. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 4a was isolated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4a in a 90% yield. The reaction equation is as follows:
[0076]
[0077] 1 H NMR (400MHz, CDCl3, ppm): δ7.72 (d, J = 8.4Hz, 2H), 7.31-7.26 (m, 5H), 7.23-7.21 (m, 2H), 5.27-5.1 8(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 (100MHz, CDCl3, 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 (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), tetrahydropyrrole (0.4 mmol), and finally a magnet were added to a test tube. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 4b was isolated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4b in an 84% yield. The reaction equation is as follows:
[0081]
[0082] 1 H NMR (400MHz, CDCl3, 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 (100MHz, CDCl3, 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] To a test tube, 1c (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), tetrahydropyrrole (0.4 mmol), and finally a magnet were added. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 4c was isolated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4c in an 82% yield. The reaction equation is as follows:
[0086]
[0087] 1H NMR (400MHz, CDCl3, 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 (100MHz, CDCl3, ppm): δ192.3, 143.3, 142.8, 137.9, 130.1 (d, J = 8.2Hz, 1C), 128.1 (d, J = 197.7Hz, 1 C),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] To a test tube, 1d (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), 3b (0.4 mmol), and finally a magnet were added. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 4d was isolated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4d in an 86% yield. The reaction equation is as follows:
[0091]
[0092] 1 H NMR (400MHz, CDCl3, 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 (100MHz, CDCl3, 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] To a test tube, 1d (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), 3c (0.4 mmol), and finally a magnet were added. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 4e was isolated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4e in an 80% yield. The reaction equation is as follows:
[0096]
[0097] 1 H NMR (400MHz, CDCl3, 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 (100MHz, CDCl3, 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] To a test tube, 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. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 4f was isolated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4f in a 79% yield. The reaction equation is as follows:
[0101]
[0102] 1 H NMR (400MHz, CDCl3, 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, CDCl3, ppm): δ 13 C NMR (101MHz, CDCl3) 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] To a test tube, 1d (0.2 mmol), methanol (2 mL), trifluoroethanol (1 mL), carbon disulfide (0.4 mmol), 3e (0.4 mmol), and finally a magnet were added. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, the compound was separated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4 g in an 86% yield. The reaction equation is as follows:
[0106]
[0107] 1 H NMR (400MHz, CDCl3, 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 (100MHz, CDCl3, 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] To a test tube, 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. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 4h was isolated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4h in an 87% yield. The reaction equation is as follows:
[0111]
[0112] 1H NMR (400MHz, CDCl3, 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), 5.07-5.04(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 (100MHz, CDCl3, 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] To a test tube, 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. The reaction was allowed to react at room temperature for 5 h, and the progress of the reaction was monitored by thin-layer chromatography until the reaction was complete. Finally, compound 4i was isolated and purified by 200-300 mesh silica gel column chromatography to obtain compound 4i in an 84% yield. The reaction equation is as follows:
[0116]
[0117] 1 H NMR (400MHz, CDCl3, 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), 5.03-5.0 0(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 (100MHz, CDCl3, 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 involves separately adding aziridine (1 equiv), sodium diethylaminodithiocarbamate (1.05 equiv), and CH3CN (3 mL), heating to 80°C, and reacting for 12 hours. Finally, the product is separated and purified by 200-300 mesh silica gel column chromatography, yielding a 99% yield of a mixed regioisomer compound.
[0120]
[0121] In contrast to this method, the carbon disulfide, tetrahydropyrrole, and other heavy amine compounds in the present invention are all commercially available products and can be purchased directly without pretreatment, reducing reaction costs and achieving higher atom economy. Furthermore, the present invention offers mild reaction conditions, eliminating the stringent temperature requirements of the reaction and achieving environmental friendliness.
[0122] Although the above embodiment provides a detailed description of the present invention, 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 scope of protection of the present invention.
Claims
1. A method for synthesizing dithiocarbamate derivatives, characterized in that: For the following steps: 1) mixing a compound represented by formula I, an alcohol reagent, carbon disulfide and a compound represented by formula II to obtain a mixture; The compound represented by formula I is any one of the following compounds: The compound represented by formula II is any one of the following compounds: 2) reacting the mixture obtained in step 1) at a temperature of 20-30° C. for 5 h to obtain a dithiocarbamate derivative; The structural formula of the dithiocarbamate derivative is shown in Formula III: The alcohol reagent in step 1) is methanol and trifluoroethanol; The volume ratio of methanol to trifluoroethanol is 2:1; 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 0.2 mmol:3 mL:0.4 mmol:0.4 mmol; 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; the mobile phase used in the silica gel column chromatography separation and purification is petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate is 4:1.