A method for preparing a raft reagent by reducing and decomposing sodium trifluoromethylsulfinate

Abstract

The application discloses a method for preparing a RAFT reagent by reducing and decomposing sodium trifluoromethylsulfinic acid. The method uses sodium trifluoromethylsulfinic acid and bromide and thiourea as raw materials, uses triphenyl phosphine and diphenyl chlorophosphine as a reducing agent, uses sodium carbonate as an alkali, and uses acetonitrile as a solvent. Sodium trifluoromethylsulfinic acid is reacted with bromide and thiourea by reducing and decomposing to obtain a trithiocarbonate compound, and the trithiocarbonate compound is a commonly used RAFT reagent. The raw material used in the method is cheap and easy to obtain, the reactants are all non-irritating and low-toxicity and safe reagents, the reaction condition is mild, the substrate range is wide, and the method is suitable for large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and relates to a method for synthesizing a RAFT reagent trithiocarbonate compound from sodium trifluoromethyl sulfinate, bromide, and thiourea. Background Technology

[0002] Sodium trifluoromethyl sulfinate (CF3SO2Na) is a colorless, odorless, and non-toxic sulfur-containing compound frequently used in organic chemical synthesis. It can introduce trifluoromethyl thio groups (CF3S) into the product. - Sodium trifluoromethyl sulfinate (CSF2) is highly compatible with the synthesis of organic compounds containing sulfur carbonyl groups, either through conversion of the thiocarbonyl fluoride skeleton. Its advantages as a sulfur source lie in the directional introduction of sulfur atoms, mild reaction characteristics, and safe and simple operation. Compared with traditional sulfur sources such as thiols (RSH) and carbon disulfide (CS2), sodium trifluoromethyl sulfinate has the following advantages: Compared with thiols, thiols have strong reducing properties and are easily oxidized, requiring strict anhydrous and oxygen-free protection during the reaction; otherwise, byproducts similar to disulfides (RSSR) are easily generated. Furthermore, the pungent odor of thiols places high demands on the operating environment, making them unsuitable for large-scale production. Sodium trifluoromethyl sulfinate (CF3SO2Na), as a stable inorganic salt, is not easily oxidized, does not require anhydrous or oxygen-free operation (some reactions can even be carried out in air or aqueous phase), and does not generate byproducts such as disulfides (RSSR). Its reaction selectivity is significantly improved compared to thiols, and it has no special odor, making it more environmentally friendly than thiols. In today's increasingly green and safe synthesis environment, it is more suitable for large-scale production. In contrast, carbon disulfide is a low-boiling-point, volatile liquid (boiling point 46.3℃), prone to volatilization during the reaction, requiring excessive feed, and unsuitable for industrial transportation and storage. Furthermore, the nucleophilic addition reaction of carbon disulfide easily leads to polymerization or by-addition reactions, generating byproducts such as polysulfides. Carbon disulfide also has high toxicity and flammability, and due to its low boiling point and volatility, it requires safety isolation and explosion-proof devices during use. These drawbacks limit its large-scale application. Sodium trifluoromethyl sulfinate (CF3SO2Na) is a solid reagent, non-volatile, non-flammable, and can be precisely added without excess. Its reaction is a site-directed reaction, with only the trifluoromethyl thioyl group (CF3S) reacting. - The skeletal groups of thiocarbonyl fluoride (CSF2) are transferred, resulting in no polymerization side reactions, high product purity, and few side reactions.

[0003] RAFT stands for Reversible Addition-Fragmentation Chain Transfer Polymerization, which is one of the core methods of living, controlled radical polymerization (CRP). Its core components consist of four units: polymer monomer, initiator, chain transfer agent (RAFT reagent), and solvent, with the chain transfer agent (RAFT reagent) being the core regulatory unit. In this polymerization reaction, the monomer undergoes chain initiation under the action of an initiator, generating primary growth radicals. These growing radicals attack the thiocarbonyl (C=S) group (electrophilic center) in the chain transfer agent, generating a stable thiocarbonyl radical intermediate (dormant species). This step is a reversible, fast reaction that rapidly consumes the active growing radicals. Subsequently, the stable thiocarbonyl radical intermediate (dormant species) undergoes selective fragmentation, breaking the SR bond and generating new stable thiocarbonyl radical intermediates (dormant species) and radicals. This step is a reversible, slow reaction that determines the polymerization rate. This cycle of chain transfer ensures that the concentration of active radicals in the system remains at approximately the same level, fundamentally inhibiting irreversible termination and achieving active and controllable polymerization. The core characteristics of this polymerization are a linear relationship between polymer molecular weight and monomer conversion rate, a narrow molecular weight distribution, and the ability to precisely synthesize polymers with complex structures such as block, graft, and star structures.

[0004] Trithiocarbonate compounds, due to the synergistic effect of their intramolecular thiocarbonyl groups (C=S) and thioether bonds (CS), can significantly alter the physicochemical properties of the parent molecule. Because the C=S double bonds in their molecules can undergo reversible addition-fragmentation chain transfer reactions with active polymer free radicals, they can achieve active and controllable free radical polymerization by stabilizing the free radical concentration in the system. This gives them the ability to act as core reagents for regulating RAFT (reversible addition-fragmentation chain transfer) polymerization, and thus they can be used as chain transfer agents (RAFT reagents).

[0005] Reference 1 (Zafer Uyar, Ulku Arslan, Mustafa Degirmenci. A photofunctional trithiocarbonate RAFT agent enabling ultrafast and fast synthesis of well-defined telechelic polymeric photoinitiators[J] Polymer. 325, 128293;2025) utilized a pre-prepared trithiocarbonate compound PI-CTA-PI to perform RAFT polymerization on different monomers under light irradiation, obtaining complex polymers with different structures and fixed end groups. The reaction formula is as follows:

[0006] .

[0007] Document 2 (Mariia L, Levit E, Sivtsov. RAFT-polymerization of N-vinylsuccinimide mediated by S,S´-dibenzyl trithiocarbonate: Synthesis of homopolymers, block-copolymers and amphiphilic derivatives as drug deliverysystems[J]. Reactive and Functional Polymers, 217, 106497; (2025) A novel polymer for biomedical applications was developed. Using dibenzyl trithiocarbonate (DBTTC) as a chain transfer agent (RAFT reagent), N-vinylsuccinimide (VSI) was radically polymerized. The trithiocarbonate groups shifted from the central position to different asymmetric positions depending on the synthesis conditions and chain length. The polymer product, PVSI-DBTTC, was copolymerized with O-cholesterol acrylate (ChA) to synthesize a triblock copolymer RAFT reagent. Subsequently, the VSI units were hydrolyzed to N-vinylsuccinic acid (VSAA) units, yielding the amphiphilic triblock copolymer PVSAA-b-PChA-b-PVSAA. This copolymer can self-assemble into micelles in aqueous solution. These micelles exhibit extremely low cytotoxicity and very low macrophage uptake in cells, while retaining the potent anticancer activity of drugs such as irinotecan, making it an excellent choice for preserving the active release of anticancer drugs. The reaction formula is as follows:

[0008]

[0009] .

[0010] Over the past few decades, numerous methods for synthesizing trithiocarbonates have been developed. Currently, thiols, carbon disulfide, and phosgene are primarily used in these reactions, with reactions mainly involving halogenated hydrocarbons and halogenated aromatic hydrocarbons. However, these sulfur-based raw materials have limitations; they are often odorous or highly toxic, and the reactions inevitably produce sulfur-containing byproducts that are difficult to separate, hindering large-scale synthetic applications. Compared to these reactions, the reduction and decomposition of sodium trifluoromethyl sulfinate in organic reactions to prepare trithiocarbonates is more challenging and significant. Using sodium trifluoromethyl sulfinate ensures a safe and low-toxicity reaction, and the other sulfur source in the reactants, thiourea, is a low-toxicity, odorless solid. This method offers low raw material costs and avoids the production of large amounts of sulfur-containing byproducts. Compared to commercially available products, this method reduces the cost of synthesizing trithiocarbonates by more than half, enabling large-scale industrial production.

[0011] Reference 3 (HC Godt, RE Wang. The Synthesis of Organic Trithiocarbonates[J] Org Chem, 26(10): 4047-4051; 1961) is one of the earliest documents on the synthesis of trithiocarbonates. This method uses thiols to react with carbonyl chloride (phosgene) to prepare trithiocarbonates under the condition of sodium hydroxide as a base. However, this method uses raw materials with strong pungent odors such as thiols, and carbonyl chloride is a highly toxic gas. In addition, the substrate must contain aromatic groups, which limits the application scope of this reaction and makes it difficult to use effectively. It is impossible to synthesize trithiocarbonate compounds on a large scale. The reaction formula is as follows:

[0012] .

[0013] Reference 4 (Iacopo Degani, Rita Fochi, Antonella Gatti, et al. Phase-Transfer Synthesis of Symmetrical and Unsymmetrical Dialkyl Trithiocarbonates[J]. Synthesis, 894-899; 1986) reported a method for producing sodium trithiocarbonate by first reacting sodium sulfide with carbon disulfide, and then reacting the obtained sodium trithiocarbonate with thiols to synthesize trithiocarbonates. However, this method requires the prior synthesis of sodium trithiocarbonate before reacting with thiols, which necessitates pre-synthesis and involves cumbersome reaction steps. Moreover, the sodium sulfide used is relatively expensive compared to other sulfides such as sodium trifluoromethyl sulfinate and thiourea, resulting in high costs and limiting its practical value, making large-scale synthesis impossible. The reaction formula is as follows:

[0014] .

[0015] Reference 5 (Barahman Movassagh, Mohammad Soleiman-Beigi, Mohammad Nazari. AFacile KF / Al2O3-Mediated, One-Pot Synthesis of Symmetrical Trithiocarbonates from Alkyl Halides and Carbon Disulfide [J]. Chem Lett, 39(22): 22-23; 2008) reported a method for synthesizing trithiocarbonates from thiols and carbon disulfide mediated by potassium fluoride and alumina. However, this method contains a large amount of excess carbon disulfide, a toxic and volatile reagent, and thiols with a pungent odor, making the reaction highly dangerous and difficult to carry out on a large scale. The reaction formula is as follows:

[0016] .

[0017] Reference 6 (Aoyagi N, Ochiai B, Endo, T. Mild and efficient one-step synthesis of trithiocarbonates using minimum amount of CS2. Synlett, 4, 636-638; 2006) reports a one-pot synthesis method for trithiocarbonate structures using benzyl chloride and carbon disulfide in cesium carbonate catalysis with acetonitrile as solvent. Subsequently, different chloride structures were used to generate the corresponding trithiocarbonates. However, this method uses highly toxic and volatile carbon disulfide as a raw material, and inevitably produces sulfur-containing byproducts during the reaction, making large-scale synthesis difficult. The reaction formula is as follows:

[0018] .

[0019] In summary, current methods for synthesizing trithiocarbonate compounds generally suffer from drawbacks such as poor substrate universality, relatively high cost, the need for pre-prepared raw materials, and the use of raw materials with irritating odors or high volatility and toxicity. Therefore, finding a greener, safer method that can directly synthesize these compounds in large quantities has significant practical value and importance. Summary of the Invention

[0020] This invention discloses a method for preparing RAFT reagents by the reductive decomposition of sodium trifluoromethyl sulfinate. The purpose of this invention is to provide a method for preparing trithiocarbonate compounds through the reductive decomposition of sodium trifluoromethyl sulfinate and the synthesis of bromides and thioureas, characterized by a reasonable process, safe and low-toxicity reactants, and low raw material costs. This method uses sodium trifluoromethyl sulfinate as a raw material, which, after reductive decomposition, is reacted with bromides and thioureas to synthesize trithiocarbonate compounds.

[0021] The technical solution to achieve the objective of this invention is:

[0022] A method for synthesizing trithiocarbonate compound (A) from sodium trifluoromethyl sulfinate (B), bromide (C), and thiourea (D) is as follows: Using sodium trifluoromethyl sulfinate (B), bromide (C), and thiourea (D) as raw materials, triphenylphosphine and diphenylphosphine chloride as reducing agents, sodium carbonate as a base, and acetonitrile as a solvent, the bromide and thiourea are first refluxed in acetonitrile at 85°C for 2 hours under the action of sodium carbonate in a reactor. Then, in another reactor, triphenylphosphine, diphenylphosphine chloride, and sodium trifluoromethyl sulfinate are mixed in acetonitrile, causing the sodium trifluoromethyl sulfinate to decompose. Simultaneously, nitrogen gas is introduced so that the decomposed gas enters the reactor after the bromide and thiourea reaction. The reaction is carried out under nitrogen protection at room temperature for 2-4 hours. After the reaction, the reaction solution is separated and purified to obtain trithiocarbonate compound (A). The reaction formula is as follows:

[0023] ,

[0024] The bromide is selected from benzyl bromide, 1-(bromomethyl)-2-methylbenzene, 1-(bromomethyl)-4-methylbenzene, 1-bromo-2-methylbenzene, 1-bromo-4-methylbenzene, 2-bromoethylbenzene, and bromocyclohexane.

[0025] Furthermore, the molar ratio of sodium trifluoromethyl sulfinate to bromide and thiourea is 1~3:1:1~2, preferably 2:1:1.2.

[0026] Furthermore, the molar ratio of triphenylphosphine, diphenylphosphine chloride and sodium trifluoromethyl sulfinate is 1~2:0~2:1, preferably 1:1:1.

[0027] Furthermore, the molar ratio of sodium carbonate to bromide is 1 to 3:1, preferably 1.5:1.

[0028] Furthermore, the solvent used is acetonitrile.

[0029] Furthermore, the reaction sequence is as follows: first, bromide is reacted with thiourea, and then sodium trifluoromethyl sulfinate is added to reduce and decompose the gas.

[0030] Further, the specific method for separation and purification is as follows: the reaction solution is diluted with ethyl acetate, filtered through a sintered glass funnel, and the solvent is removed by vacuum distillation. The crude product is separated by column chromatography to obtain trithiocarbonate compounds. The eluent is a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:3.

[0031] Compared with the prior art, the present invention has the following advantages:

[0032] (1) The present invention obtains the corresponding trithiocarbonate products by reducing and decomposing sodium trifluoromethyl sulfinate and reacting it with bromide and thiourea. The substrate range of the obtained products is relatively wide, and no sulfur-containing by-products are generated during the reaction process. The products are easy to separate and purify to obtain products with high purity. Therefore, a high conversion rate can be maintained under the condition of a certain scale of reaction.

[0033] (2) The raw materials required for this invention, sodium trifluoromethyl sulfinate, bromide, and thiourea reagent, are economical and easy to store. The reducing agent and alkali used in the reaction process are also very inexpensive. The synthesized trithiocarbonate compounds can save more than half the cost compared with the same products on the market, providing feasible conditions for large-scale industrial production.

[0034] (3) The sulfur sources used in this invention, sodium trifluoromethyl sulfinate and thiourea, are green, safe and have low toxicity, and have no obvious odor. Compared with sulfur sources such as thiols and carbon disulfide, which have malodorous or highly toxic odors, the sulfur sources used in this invention are mild and safe, and therefore have the feasibility of industrial synthesis.

[0035] (4) The reaction steps of the present invention are simple, and the reaction process does not require the step-by-step preparation of intermediate products to generate the final product. Moreover, the reaction conditions are mild and easy to achieve, which can greatly save manpower and material resources and facilitate the synthesis of trithiocarbonate compounds. Attached Figure Description

[0036] Figure 1 It is dibenzyl trithiocarbonate. 1 H NMR spectrum;

[0037] Figure 2 It is dibenzyl trithiocarbonate. 13 C NMR spectrum;

[0038] Figure 3 It is bis(2-methylbenzyl)trithiocarbonate 1 H NMR spectrum;

[0039] Figure 4 It is bis(2-methylbenzyl)trithiocarbonate 13 C NMR spectrum;

[0040] Figure 5 It is bis(4-methylbenzyl)trithiocarbonate 1 H NMR spectrum;

[0041] Figure 6 It is bis(4-methylbenzyl)trithiocarbonate 13 C NMR spectrum;

[0042] Figure 7 It is bis(2-tolyl)trithiocarbonate 1 H NMR spectrum;

[0043] Figure 8 It is bis(2-tolyl)trithiocarbonate 13 C NMR spectrum;

[0044] Figure 9 It is bis(4-tolyl)trithiocarbonate 1 H NMR spectrum;

[0045] Figure 10 It is bis(4-tolyl)trithiocarbonate 13 C NMR spectrum;

[0046] Figure 11It is diphenylethyl trithiocarbonate 1 H NMR spectrum;

[0047] Figure 12 It is diphenylethyl trithiocarbonate 13 C NMR spectrum;

[0048] Figure 13 It is dicyclohexyl trithiocarbonate. 1 H NMR spectrum;

[0049] Figure 14 It is dicyclohexyl trithiocarbonate. 13 C NMR spectrum. Detailed Implementation

[0050] To better understand the present invention, the technical solution of the present invention will be specifically described below through specific embodiments.

[0051] Example 1

[0052] First, 17.105 g (100 mmol) benzyl bromide, 9.120 g (120 mmol) thiourea, 15.900 mg (150 mmol) sodium carbonate, and 500 ml acetonitrile were added to a reactor, and the mixture was refluxed at 85°C for 2 hours. Then, in another reactor, 34.210 g (200 mmol) sodium trifluoromethyl sulfinate, 70.455 g (200 mmol) triphenylphosphine, 44.120 g (200 mmol) diphenylphosphine chloride, and 500 ml acetonitrile were added to reduce and decompose the sodium trifluoromethyl sulfinate. Simultaneously, nitrogen gas was introduced so that the decomposed gas entered the reactor containing the bromide and thiourea after the reaction. The reaction was carried out in the reactor at room temperature for 2 hours under nitrogen protection. After the reaction was complete, the reaction solution was diluted with 1000 mL of ethyl acetate, filtered using a sintered glass funnel, and then the solvent was removed by vacuum distillation. The crude product was separated by column chromatography (using a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:3) to obtain 19.425 g of dibenzyl trithiocarbonate, with a yield of 67%.

[0053] Dibenzyl trithiocarbonate 1 See H NMR spectrum Figure 1 , 13 See the C NMR spectrum. Figure 2 .

[0054] 1H NMR (500 MHz, Chloroform-d) δ 7.37 (d, J = 8.4 Hz, 4H), 7.34 (d, J= 7.5 Hz, 4H), 7.32-7.28 (m, 2H), 4.65 (s, 4H).

[0055] 13 C NMR (126 MHz, CDCl3) δ 222.81, 135.03, 129.38, 128.82, 127.90,41.65.

[0056] Example 2

[0057] First, 18.505 g (100 mmol) of 1-(bromomethyl)-4-methylbenzene, 9.120 g (120 mmol) of thiourea, 15.900 mg (150 mmol) of sodium carbonate, and 500 ml of acetonitrile were added to a reactor, and the mixture was refluxed at 85°C for 2 hours. Then, in another reactor, 34.210 g (200 mmol) of sodium trifluoromethyl sulfinate, 70.455 g (200 mmol) of triphenylphosphine, 44.120 g (200 mmol) of diphenylphosphine chloride, and 500 ml of acetonitrile were added to reduce and decompose the sodium trifluoromethyl sulfinate. Simultaneously, nitrogen gas was introduced so that the decomposed gas entered the reactor containing the bromide and thiourea after the reaction. The reaction was carried out in the reactor at room temperature for 2.5 hours under nitrogen protection. After the reaction was complete, the reaction solution was diluted with 1000 mL of ethyl acetate, filtered using a sintered glass funnel, and then the solvent was removed by vacuum distillation. The crude product was separated by column chromatography (using a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:3) to obtain 22.580 g of bis(4-methylbenzyl)trithiocarbonate, with a yield of 71%.

[0058] bis(4-methylbenzyl)trithiocarbonate 1 See H NMR spectrum Figure 5 , 13 See the C NMR spectrum. Figure 6 .

[0059] 1 H NMR (500 MHz, Chloroform-d) δ 7.32 (d, J = 7.9 Hz, 4H), 7.22 (d, J= 7.8 Hz, 4H), 4.67 (s, 4H), 2.43 (s, 6H).

[0060] 13C NMR (126 MHz, CDCl3) δ 222.89, 137.50, 131.76, 129.41, 129.20,41.38, 21.19.

[0061] Example 3

[0062] First, 17.105 g (100 mmol) of 1-bromo-4-methylbenzene, 9.120 g (120 mmol) of thiourea, 15.900 mg (150 mmol) of sodium carbonate, and 500 ml of acetonitrile were added to a reactor, and the mixture was refluxed at 85°C for 2.5 hours. Then, in another reactor, 34.210 g (200 mmol) of sodium trifluoromethyl sulfinate, 70.455 g (200 mmol) of triphenylphosphine, 44.120 g (200 mmol) of diphenylphosphine chloride, and 500 ml of acetonitrile were added to reduce and decompose the sodium trifluoromethyl sulfinate. Simultaneously, nitrogen gas was introduced so that the decomposed gas entered the reactor containing the bromide and thiourea after the reaction. The reaction was carried out in the reactor under nitrogen protection at room temperature for 2 hours. After the reaction was complete, the reaction solution was diluted with 1000 mL of ethyl acetate, filtered using a sintered glass funnel, and then the solvent was removed by vacuum distillation. The crude product was separated by column chromatography (using a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:3) to obtain 18.560 g of bis(4-tolyl)trithiocarbonate, with a yield of 64%.

[0063] bis(4-tolyl)trithiocarbonate 1 See H NMR spectrum Figure 9 , 13 See the C NMR spectrum. Figure 10 .

[0064] 1 H NMR (500 MHz, Chloroform-d) δ 7.46 (d, J = 8.1 Hz, 4H), 7.32 (d, J= 7.7 Hz, 4H), 2.45 (s, 6H).

[0065] 13 C NMR (126 MHz, CDCl3) δ 226.21, 141.16, 135.41, 130.37, 127.25,21.54.

[0066] Example 4

[0067] First, 18.505 g (100 mmol) of 2-bromoethylbenzene, 9.120 g (120 mmol) of thiourea, 15.900 mg (150 mmol) of sodium carbonate, and 500 ml of acetonitrile were added to a reactor, and the mixture was refluxed at 85°C for 2 hours. Then, in another reactor, 34.210 g (200 mmol) of sodium trifluoromethyl sulfinate, 70.455 g (200 mmol) of triphenylphosphine, 44.120 g (200 mmol) of diphenylphosphine chloride, and 500 ml of acetonitrile were added to reduce and decompose the sodium trifluoromethyl sulfinate. Simultaneously, nitrogen gas was introduced so that the decomposed gas entered the reactor containing the bromide and thiourea after the reaction. The reaction was carried out in the reactor at room temperature for 4 hours under nitrogen protection. After the reaction was complete, the reaction solution was diluted with 1000 mL of ethyl acetate, filtered using a sintered glass funnel, and then the solvent was removed by vacuum distillation. The crude product was separated by column chromatography (using a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:3) to obtain 13.995 g of diphenylethyl trithiocarbonate, with a yield of 44%.

[0068] diphenylethyl trithiocarbonate 1 See H NMR spectrum Figure 11 , 13 See the C NMR spectrum. Figure 12 .

[0069] 1 H NMR (500 MHz, Chloroform-d) δ 7.39-7.32 (m, 4H), 7.28 (d, J = 7.4Hz, 6H), 3.68-3.61 (m, 4H), 3.07-3.00 (m, 4H).

[0070] 13 C NMR (126 MHz, CDCl3) δ 223.54, 139.42, 128.48, 128.44, 126.56,37.75, 34.30.

[0071] Example 5

[0072] First, 16.300 g (100 mmol) of bromocyclohexane, 9.120 g (120 mmol) of thiourea, 15.900 mg (150 mmol) of sodium carbonate, and 500 ml of acetonitrile were added to a reactor, and the mixture was refluxed at 85°C for 2 hours. Then, in another reactor, 34.210 g (200 mmol) of sodium trifluoromethyl sulfinate, 70.455 g (200 mmol) of triphenylphosphine, 44.120 g (200 mmol) of diphenylphosphine chloride, and 500 ml of acetonitrile were added to reduce and decompose the sodium trifluoromethyl sulfinate. Simultaneously, nitrogen gas was introduced so that the decomposed gas entered the reactor containing the bromide and thiourea after the reaction. The reaction was carried out in the reactor at room temperature for 4 hours under nitrogen protection. After the reaction was complete, the reaction solution was diluted with 1000 mL of ethyl acetate, filtered using a sintered glass funnel, and then the solvent was removed by vacuum distillation. The crude product was separated by column chromatography (using a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:3) to obtain 15.340 g of dicyclohexyl trithiocarbonate, with a yield of 56%.

[0073] Dicyclohexyl trithiocarbonate 1 See H NMR spectrum Figure 13 , 13 See the C NMR spectrum. Figure 14 .

[0074] 1 H NMR (500 MHz, Chloroform-d) δ 7.78 – 7.66 (m, 4H), 7.49 (dd, J =5.1, 2.2 Hz, 6H), 5.68 (s, 1H).

[0075] 13 C NMR (126 MHz, Chloroform-d) δ 130.04, 129.83, 129.58, 129.26,120.10 (q, J = 327.6 Hz), 72.09.

[0076] Comparative Example 1

[0077] This comparative example is basically the same as Example 1, except that the reducing agents triphenylphosphine and diphenylphosphine chloride are replaced with only diphenylphosphine chloride. The reaction produces almost no product and cannot be separated.

[0078] Comparative Example 2

[0079] This comparative example is basically the same as Example 1, except that the reducing agents triphenylphosphine and diphenylphosphine chloride are not used, and no product is produced in the reaction, making separation impossible.

[0080] Comparative Example 3

[0081] This comparative example is basically the same as Example 1, except that sodium carbonate is replaced with sodium hydroxide. The reaction produces almost no product and cannot be separated.

[0082] Comparative Example 4

[0083] This comparative example is basically the same as Example 1, except that the reaction temperature of bromide and thiourea is room temperature, yielding 3.190 g of dibenzyl trithiocarbonate with a yield of 11%.

[0084] Comparative Example 5

[0085] This comparative example is basically the same as Example 1, except that the reaction temperature is 85°C throughout the process, yielding 13.625 g of dibenzyl trithiocarbonate with a yield of 47%.

[0086] Comparative Example 6

[0087] This comparative example is basically the same as Example 1, except that the solvent acetonitrile was replaced with toluene, yielding 13.695 g of dibenzyl trithiocarbonate, with a yield of 41%.

[0088] Comparative Example 7

[0089] This comparative example is basically the same as Example 1, except that the solvent acetonitrile was replaced with dichloromethane to obtain 9.570 g of dibenzyl trithiocarbonate, with a yield of 33%.

[0090] Comparative Example 8

[0091] This comparative example is basically the same as Example 1, except that nitrogen is not introduced so that the gas in the sodium trifluoromethyl sulfinate reactor enters the reactor of bromide and thiourea, and the reaction produces no products and cannot be separated.

[0092] Comparative Example 9

[0093] This comparative example is basically the same as Example 1, except that sodium trifluoromethyl sulfinate, triphenylphosphine, and diphenylphosphine chloride are directly added to the reactor of bromide and thiourea for reaction, and the product contains a large amount of phosphorus-containing byproducts that cannot be separated.

[0094] The above embodiments do not limit the present invention in any way. All technical solutions obtained by equivalent substitution or equivalent transformation fall within the protection scope of the present invention.

Claims

1. A method for preparing RAFT reagent by the reduction decomposition of sodium trifluoromethyl sulfinate, characterized in that, Specifically, the reaction involves using sodium trifluoromethyl sulfinate, bromide, and thiourea as raw materials, triphenylphosphine and diphenylphosphine chloride as reducing agents, sodium carbonate as a base, and acetonitrile as a solvent. First, in a reactor, bromide and thiourea are refluxed in acetonitrile at 85°C for 2 hours under the influence of sodium carbonate. Then, in another reactor, triphenylphosphine, diphenylphosphine chloride, and sodium trifluoromethyl sulfinate are mixed in acetonitrile, causing the sodium trifluoromethyl sulfinate to decompose. Simultaneously, nitrogen gas is introduced, allowing the decomposed gas to enter the reactor containing the bromide and thiourea after their reaction. The reaction is carried out under nitrogen protection at room temperature for 2-4 hours. After the reaction, the reaction solution is separated and purified to obtain trithiocarbonate compounds. The reaction formula is as follows: The bromide is selected from benzyl bromide, 1-(bromomethyl)-2-methylbenzene, 1-(bromomethyl)-4-methylbenzene, 1-bromo-2-methylbenzene, 1-bromo-4-methylbenzene, 2-bromoethylbenzene, and bromocyclohexane.

2. The method according to claim 1, characterized in that, The molar ratio of sodium trifluoromethyl sulfinate to bromide and thiourea is 1~3:1:1~2.

3. The method according to claim 2, characterized in that, The molar ratio of sodium trifluoromethyl sulfinate to bromide and thiourea is 2:1:1.

2.

4. The method according to claim 1, characterized in that, The molar ratio of triphenylphosphine, diphenylphosphine chloride and sodium trifluoromethyl sulfinate is 1~2:0~2:

1.

5. The method according to claim 4, characterized in that, The molar ratio of triphenylphosphine, diphenylphosphine chloride and sodium trifluoromethyl sulfinate is 1:1:

1.

6. The method according to claim 1, characterized in that, The molar ratio of sodium carbonate to bromide is 1~3:

1.

7. The method according to claim 6, characterized in that, The molar ratio of sodium carbonate to bromide is 1.5:

1.

8. The method according to claim 1, characterized in that, The solvent used is acetonitrile.

9. The method according to claim 1, characterized in that, The reaction sequence is as follows: first, bromide is refluxed with thiourea at 85°C, and then sodium trifluoromethyl sulfinate is added to reduce and decompose the gas.

10. The method according to claim 1, characterized in that, The specific method for separation and purification is as follows: the reaction solution is diluted with ethyl acetate, filtered through a sand core funnel, and the solvent is removed by vacuum distillation. The crude product is separated by column chromatography to obtain trithiocarbonate compounds. The eluent is a mixture of petroleum ether and ethyl acetate in a volume ratio of 100:3.

Images