Preparation method of tert-butyl isothiocyanate
By reacting tert-butylamine with carbon disulfide to generate tert-butyl thiocarbamate thioester, and then removing the H2S unit with a desulfurization reagent, the problems of low purity and difficult wastewater treatment in the existing technology are solved, and high-purity, high-yield tert-butyl isothiocyanate preparation is achieved.
Patent Information
- Application Number
- CN202511803486.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-03
- Publication Date
- 2026-03-06
AI Technical Summary
Existing methods for synthesizing tert-butyl isothiocyanate suffer from problems such as the use of high-temperature catalysts leading to byproduct formation, difficulty in improving purity, and challenges in wastewater treatment.
tert-butylamine reacts with carbon disulfide to produce tert-butylthiocarbamate thioester, and then H2S units are removed under the action of a desulfurizing agent to produce tert-butyl isothiocyanate. The reaction is carried out using conventional reagents and at low temperature to avoid high-temperature catalysis.
It increased product purity to 99%, reduced wastewater generation, enhanced the safety of the reaction and operation, and lowered costs.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, and more specifically, relates to a method for preparing tert-butyl isothiocyanate. Background Technology
[0002] In the pesticide field, thiamethoxam plays a crucial role in controlling crop pests and diseases as an important insecticide. tert-butyl isothiocyanate, as a key intermediate for thiamethoxam, makes the optimization of its synthetic process particularly important. Furthermore, in the pharmaceutical field, the unique chemical properties of tert-butyl isothiocyanate offer possibilities for the development of novel drugs. Researchers can modify its structure to develop drug molecules with higher activity and selectivity. In materials science, it may also serve as a functional monomer, participating in the synthesis of novel materials and bringing new opportunities for improving material performance.
[0003] Currently, the main reported method for preparing tert-butyl isothiocyanate is the tert-butane-thiocyanate method, which is also a common and traditional route for synthesizing tert-butyl isothiocyanate. In this method, tert-butane and a metal thiocyanate are first added to the reaction system to generate tert-butyl thiocyanate. Tert-butyl thiocyanate then needs to be isomerized by heating or using a catalyst to convert it into tert-butyl isothiocyanate.
[0004] In this synthetic method, the nucleophilic substitution reaction requires a highly polar solvent, such as a metal thiocyanate like zinc thiocyanate. These reagents may be expensive, and the treatment of metal salts generates wastewater, posing a significant environmental burden. Furthermore, the isomerization of tert-butyl thiocyanate to isothiocyanate requires a high temperature of 120-150°C and a catalytic amount of Lewis acid (such as AlCl3). At high temperatures, intramolecular rearrangement easily occurs to form tert-butyl cyanosulfide (a stable byproduct, accounting for 5%-8%), making it difficult to achieve a purity of the target product exceeding 95%. Summary of the Invention
[0005] In view of this, the purpose of this invention is to provide a method for preparing tert-butyl isothiocyanate with good product purity, high yield, and using conventional reagents in the route, which greatly improves the safety of the reaction and operation.
[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: The method for preparing tert-butyl isothiocyanate according to embodiments of the present invention includes: Step S1 involves reacting tert-butylamine with carbon disulfide to generate tert-butylthiocarbamate thioester. Step S2 involves reacting the tert-butyl thiocarbamate with a desulfurizing agent to generate tert-butyl isothiocyanate.
[0007] According to some embodiments of the present invention, in step S1, the reaction is carried out in a first solvent under the action of an inorganic base, wherein the first solvent is selected from one or more of ethyl acetate, dichloromethane, tetrahydrofuran, acetonitrile, etc.
[0008] Furthermore, the inorganic base is selected from one or more of sodium carbonate, potassium carbonate, and cesium carbonate.
[0009] Furthermore, the molar ratio of carbon disulfide: tert-butylamine: inorganic base is 1:(1.0~1.5):(1.0~1.5).
[0010] Furthermore, in step S1, the reaction temperature is 5~10℃; the reaction time is 2~8 h.
[0011] Further, after the reaction is complete, the reaction solution is filtered, the filter cake is washed, and the washing liquid and filtrate are combined and concentrated under reduced pressure to obtain tert-butylthiocarbamate thioester.
[0012] According to some embodiments of the present invention, in step S2, the desulfurization reagent is one or more of n-butylphosphine or its solution, cyanuric chloride, and ethyl chloroformate.
[0013] Further, the desulfurization reagent is an ethyl acetate solution of n-butylphosphine anhydride, and step S2 includes: The tert-butyl thiocarbamate thioester was added to dichloromethane, and the reaction system was cooled to 0-5°C. Then, the desulfurization reagent was added dropwise to the reaction system. After the addition was complete, the temperature was raised to 25-30°C to carry out the removal reaction, generating the tert-butyl isothiocyanate.
[0014] Furthermore, the molar ratio of the tert-butylthiocarbamate thioester to the n-butylphosphine anhydride is 1:(1.05-1.1).
[0015] Further, in step S2, after the reaction is completed, the reaction solution is added dropwise to an ammonium chloride aqueous solution for quenching and separation. After washing the organic phase, it is dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain crude tert-butyl isothiocyanate. The crude tert-butyl isothiocyanate is purified by reduced pressure distillation to obtain purified tert-butyl isothiocyanate.
[0016] The above-described technical solution of the present invention has at least one of the following beneficial effects: According to the preparation method of the present invention, the chemicals used in the route are all conventional reagents, which greatly improves the safety of the reaction and operation; Furthermore, the preparation method according to the embodiments of the present invention does not require high-temperature catalysis and does not produce unnecessary byproducts, thereby obtaining a product with a purity of up to 99%; Furthermore, the preparation method according to the embodiments of the present invention does not generate a large amount of wastewater containing metal salts, making it environmentally friendly and safe. Detailed Implementation
[0017] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention are within the scope of protection of the present invention.
[0018] The preparation method of tert-butyl isothiocyanate according to embodiments of the present invention is described in detail below.
[0019] The method for preparing tert-butyl isothiocyanate according to embodiments of the present invention includes: Step S1 involves reacting tert-butylamine with carbon disulfide to generate tert-butylthiocarbamate thioester. Step S2 involves reacting the tert-butyl thiocarbamate with a desulfurizing agent to generate tert-butyl isothiocyanate.
[0020] In other words, according to the preparation method of this invention, tert-butylamine and carbon disulfide are used as starting materials. A nucleophilic reaction is first carried out to generate the intermediate tert-butylthiocarbamate thioester. Subsequently, under the action of a desulfurizing agent, the H2S unit is removed to obtain the target product, tert-butyl isothiocyanate. The preparation method of this application eliminates the need for a high-temperature isomerization process using a catalyst, avoids the generation of unnecessary byproducts, helps improve product purity, and uses conventional reagents in the synthetic route, greatly improving the safety of the reaction and operation.
[0021] The nucleophilic substitution reaction (i.e., step S1) and the removal reaction (i.e., step S2) will be described in detail below.
[0022] (1) Nucleophilic substitution reaction That is, step S1: react tert-butylamine with carbon disulfide to generate tert-butylthiocarbamate thioester.
[0023] According to some embodiments of the present invention, the nucleophilic substitution reaction is carried out in a first solvent in the presence of an inorganic base, wherein the first solvent is selected from one or more of ethyl acetate, dichloromethane, tetrahydrofuran, acetonitrile, etc. The presence of an inorganic base is beneficial and promotes the reaction while preventing the generation of unwanted byproducts.
[0024] Furthermore, the inorganic base is selected from one or more of sodium carbonate, potassium carbonate, and cesium carbonate. Potassium carbonate is preferred.
[0025] Specifically, the reaction formula of tert-butylamine with carbon disulfide is shown in the following formula (1):
[0026] For example, carbon disulfide, potassium carbonate, and dichloromethane (i.e., the first solvent) can be added to a reaction flask, and a dichloromethane solution of tert-butylamine can be added dropwise to carry out the nucleophilic substitution reaction.
[0027] In some embodiments of the present invention, the molar ratio of carbon disulfide:tert-butylamine:inorganic base is 1:(1.0~1.5):(1.0~1.5). Through a series of optimization experiments, a slight excess of tert-butylamine and inorganic base will increase the product yield. Preferably, the ratio is 1:1.05:1.05.
[0028] Furthermore, in step S1, the reaction temperature is 5~10℃; the reaction time is 2~8 h.
[0029] Further, after the reaction is complete, the reaction solution is filtered, the filter cake is washed, and the washing liquid and filtrate are combined and concentrated under reduced pressure to obtain tert-butylthiocarbamate thioester.
[0030] Therefore, the separation of intermediate products from residual reactants is simple and easy to operate, does not generate a large amount of wastewater, is environmentally friendly, and is suitable for large-scale industrial production.
[0031] (2) Removal reaction That is, step S2: react tert-butyl thiocarbamate with a desulfurizing agent to generate tert-butyl isothiocyanate.
[0032] In other words, after obtaining the intermediate tert-butyl thiocarbamate, a desulfurizing agent is used to remove one H2S unit from the thiol group to obtain tert-butyl isothiocyanate.
[0033] In some embodiments of the present invention, one or more of the following can be selected as desulfurization agents: n-butylphosphine anhydride or its solution (e.g., 50% ethyl acetate solution), cyanuric chloride, and ethyl chloroformate. These desulfurization agents are low in toxicity, non-corrosive, pose little safety threat to operators, are easy to operate, and have high industrial compliance.
[0034] Preferably, the desulfurization reagent is n-butylphosphine (50% ethyl acetate solution), which has low hazard, excellent activity, and is easy to handle.
[0035] In some embodiments of the present invention, the removal reaction process specifically includes: The tert-butyl thiocarbamate thioester was added to dichloromethane, and the reaction system was cooled to 0-5°C. Then, the desulfurization reagent was added dropwise to the reaction system. After the addition was complete, the temperature was raised to 25-30°C to carry out the removal reaction, generating the tert-butyl isothiocyanate.
[0036] In other words, the reaction is carried out in a dichloromethane system at a temperature of 25-30°C (around room temperature) and for a reaction time of, for example, 2-6 hours, preferably 3 hours.
[0037] Specifically, its reaction formula is shown in equation (2) below:
[0038] In some embodiments of the present invention, the molar ratio of tert-butylthiocarbamate thioester to n-butylphosphine anhydride may be, for example, 1:(1.05-1.1). A slight excess of the dehydrating agent n-butylphosphine anhydride (50% ethyl acetate solution) helps to promote the reaction, increase the yield, and the unreacted dehydrating agent n-butylphosphine anhydride (50% ethyl acetate solution) is easier to remove than tert-butylthiocarbamate thioester.
[0039] According to some embodiments of the present invention, after the removal reaction is completed, the reaction solution is added dropwise to an aqueous solution of ammonium chloride for quenching and separation. After washing the organic phase, it is dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain crude tert-butyl isothiocyanate. The crude tert-butyl isothiocyanate is purified by vacuum distillation to obtain purified tert-butyl isothiocyanate.
[0040] Therefore, according to the preparation method of this application, the post-processing is simple and easy to operate, impurities are easy to separate, and the purity of the obtained product can be as high as 99%.
[0041] According to the preparation method of the present invention, compared with the prior art synthesis methods, the reaction temperature is lower, the conversion rate is higher, and the obtained intermediate has better purity and higher yield. In addition, the reagents used in this method have a high safety factor.
[0042] The preparation method of the present invention will be further described in detail below through specific embodiments.
[0043] Example 1: (1) Nucleophilic substitution reaction Carbon disulfide (35 g, 0.479 mol, 1.0 eq) and potassium carbonate powder (48.33 g, 0.503 mol, 1.05 eq) were added to 10 times their weight of dichloromethane (350 g, 10 w / w). The mixture was cooled to 5-10 °C in an ice-water bath, and tert-butylamine (35.36 g, 0.503 mol, 1.05 eq) was added dropwise. The dropwise addition process was slightly exothermic. After the addition was completed, the mixture was kept at this temperature for 2 hours, and a large amount of solid precipitated out.
[0044] After the reaction of tert-butylamine was monitored by TLC (DCM:MeOH=1:1) until complete, the reaction solution was filtered, and the filter cake was washed with a small amount of dichloromethane (15 g). The washing solution and the filtrate were combined and concentrated under reduced pressure to obtain tert-butylthiocarbamate thioester (65.0 g), with a yield of 91.0%.
[0045] (2) Removal reaction Step 1: Add tert-butylthiocarbamate thioester (65.0 g, 0.436 mol, 1.0 eq) to dichloromethane (70 g, 2 w / w), cool to 5 °C in an ice-water bath, and add n-butylphosphine anhydride (50% ethyl acetate solution) (92.6 g, 0.480 mol, 1.1 eq) dropwise, controlling the temperature at 5-10 °C, and maintain the temperature for 3 h after the addition is complete.
[0046] After the reaction was completed, the reaction solution was added dropwise to 70 mL of 3 mol / L ammonium chloride aqueous solution for quenching and separation. The organic phase was then washed once with water and once with saturated brine. The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain crude tert-butyl isothiocyanate. The crude tert-butyl isothiocyanate was purified by vacuum distillation to remove the solvent at 40 °C. Using an oil pump (200~400 Pa), an oil temperature of 40 °C, and a distillation temperature of 35 °C, the product was distilled off to obtain purified tert-butyl isothiocyanate (43.8 g), with a yield of 87.1% and a gas phase purity of 99.1%.
[0047] The obtained product was subjected to nuclear magnetic resonance (NMR) experiments to confirm its structure. The data are as follows: 1 H NMR (Model: AVANCE III HD 400M, CDCl3, 400MHz): δ 1.41 (s, 9H); 13 C NMR (Model: AVANCE III HD 400M, CDCl3, 151MHz): δ 115.0, 58.3, 30.7.
[0048] The test results are consistent with the structure of tert-butyl isothiocyanate.
[0049] Example 2:
[0050] (1) Nucleophilic substitution reaction Carbon disulfide (1.0 kg, 13.16 mol, 1.0 eq) and potassium carbonate powder (1.9 kg, 13.82 mol, 1.05 eq) were added to 10 times their weight of dichloromethane (10 kg, 10 w / w). The mixture was cooled to 5-10 °C in an ice-water bath, and tert-butylamine (1.01 kg, 13.82 mol, 1.05 eq) was added dropwise. The dropwise addition process was slightly exothermic. After the addition was completed, the mixture was kept at this temperature for 2 hours, and a large amount of solid precipitated out.
[0051] After the reaction of tert-butylamine was completed by TLC (DCM:MeOH=1:1), the reaction solution was filtered, and the filter cake was washed with a small amount of dichloromethane (0.3 kg). The washing solution and the filtrate were combined and concentrated under reduced pressure to obtain tert-butylthiocarbamate thioester (1.863 kg), with a yield of 95.0%.
[0052] (2) Removal reaction 1.863 kg, 12.5 mol, 1.0 eq of tert-butylthiocarbamate thioester was added to dichloromethane (3.73 kg, 2 w / w), and the mixture was cooled to 5 °C in an ice-water bath. Then, 4.72 kg, 13.12 mol, 1.05 eq of n-butylphosphine anhydride (50% ethyl acetate solution) was added dropwise, and the temperature was controlled at 5-10 °C. The reaction was maintained at this temperature for 3 h after the addition was complete.
[0053] After the reaction was completed, the reaction solution was added dropwise to 2 kg of 3 mol / L ammonium chloride aqueous solution for quenching and separation. The organic phase was washed once with water and once with saturated brine. The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain crude tert-butyl isothiocyanate. The crude tert-butyl isothiocyanate was purified by vacuum distillation to remove the solvent at 40 °C. The product was distilled off using an oil pump (200~400 Pa), an oil temperature of 40 °C, and a fractionation temperature of 35 °C to obtain purified tert-butyl isothiocyanate (1.30 kg), with a yield of 90.2% and a gas phase purity of 99.4%.
[0054] The obtained product was subjected to nuclear magnetic resonance (NMR) experiments to confirm its structure. The data are as follows: 1 H NMR (Model: AVANCE III HD 400M, CDCl3, 400MHz): δ 1.45 (s, 9H); 13 C NMR (Model: AVANCE III HD 400M, CDCl3, 151MHz): δ 115.3, 58.0, 30.2.
[0055] The test results are consistent with the structure of tert-butyl isothiocyanate.
[0056] In summary, the method for preparing a tert-butyl isothiocyanate of the present invention has the advantages of being simple to operate, having high safety, high product purity, low cost, and high yield.
[0057] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A method for preparing tert-butyl isothiocyanate, characterized by, The application relates to a preparation method of tert-butyl isothiocyanate. Step S1: tert-butylamine is reacted with carbon disulfide to generate tert-butyl thiocarbamic sulfide; Step S2: the tert-butyl thiocarbamic sulfide is removed by a desulfurization reagent to generate tert-butyl isothiocyanate.
2. The production method according to claim 1, characterized by, In the step S1, the reaction is carried out in a first solvent under the action of an inorganic base, wherein the first solvent is selected from one or more of ethyl acetate, dichloromethane, tetrahydrofuran, acetonitrile and the like.
3. The production method according to claim 2, characterized by, The inorganic base is selected from one or more of sodium carbonate, potassium carbonate and cesium carbonate.
4. The production method according to claim 2, characterized by, The molar ratio of carbon disulfide: tert-butylamine: inorganic base is 1: (1.0-1.5): (1.0-1.5).
5. The production method according to claim 2, characterized by, In the step S1, the reaction temperature is 5-10 DEG C, and the reaction time is 2-8 h.
6. The preparation method according to claim 2, characterized in that, After the reaction is completed, the reaction liquid is filtered, the filter cake is washed, the washing liquid and the filtrate are combined, and the combined solution is concentrated under reduced pressure to obtain the tert-butyl thiocarbamic sulfide.
7. The preparation method according to claim 1, characterized in that, In the step S2, the desulfurization reagent is one or more of n-butyl phosphoric anhydride or a solution thereof, trichloroisocyanuric acid and ethyl chloroformate.
8. The production method according to claim 7, characterized by, When the desulfurization reagent is an ethyl acetate solution of n-butyl phosphoric anhydride, the step S2 comprises: The tert-butyl thiocarbamic sulfide is added into dichloromethane, the reaction system is cooled to 0-5 DEG C, then the desulfurization reagent is added dropwise into the reaction system, after the dropwise addition is completed, the temperature is increased to 25-30 DEG C to carry out the removal reaction, and the tert-butyl isothiocyanate is generated.
9. The production method according to claim 8, characterized by, The molar ratio of the tert-butyl thiocarbamic sulfide and n-butyl phosphoric anhydride is 1: (1.05-1.1).
10. The preparation method according to claim 8, characterized in that, After the reaction is completed, the reaction liquid is added dropwise into an aqueous ammonium chloride solution to quench, the organic phase is washed, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain a crude tert-butyl isothiocyanate; the crude tert-butyl isothiocyanate is purified by reduced pressure distillation to obtain purified tert-butyl isothiocyanate.