A favorable method for synthesizing N-heterocyclic carbene catalysts.

Abstract

The present invention relates to the synthesis of triazolium N-heterocyclic carbene (NHC) catalyst salts in various salt forms prepared from 2-methylaniline, 2-methylphenylhydrazine hydrochloride or 2-methylphenylhydrazine. The molecules thus prepared are useful for catalysis of carbene reactions and are advantageous due to the absence of chlorinated or fluorinated intermediates and the absence of chlorine or fluorine in the final structure.

Description

Technical Field

[0001] Technical Field The present invention relates to the synthesis of salts of triazolium N - heterocyclic catalysts in various salt forms prepared from 2 - methylaniline, 2 - methylphenylhydrazine hydrochloride or 2 - methylphenylhydrazine. The molecules prepared in this way are useful in the catalytic reactions of carbene reactions, and they are advantageous in that they have no chlorinated or fluorinated intermediates and no chlorine or fluorine in the final structure, resulting in improved biodegradability and reduced toxicity.

Background Art

[0002] Background Art N - heterocyclic carbene (NHC) catalysts have been shown to be useful in various chemical reactions. Producing general - purpose chemicals from renewable feedstocks is an ongoing priority in the field of sustainable green chemistry. Catalytic chemical processes that operate using catalysts that are biodegradable, low in toxicity, and economical to synthesize on a commercial scale are highly desirable for sustainability.

[0003] The usefulness of such catalysts is exemplified by their use in the synthesis of 5 - methyl - 2 - furoic acid derivatives prepared from 5 - (chloromethyl) - 2 - furfuraldehyde. This usefulness is discussed in detail in U.S. Patent No. 8,710,250 and U.S. Patent No. 9,108,940, which are incorporated herein by reference.

[0004] NHC catalysts function by circulating between the carbene and the reagent targeted during the reaction. This recycling allows for the synthesis of large amounts of products in high yields with small amounts of catalyst. The catalyst binds to the substrate, converts electrophilic carbon to nucleophilic carbon for the reaction, and is then released to function again.

[0005] The economic value of an NHC catalyst is related to the ratio of catalyst to reagents required for the reaction, and the overall yield, including side reactions or by-product reactions. Embodiments of the present invention provide methods for the synthesis and use of NHC, which have been found to enable remarkably high yields in reactions such as those described in U.S. Patent Nos. 8,710,250 and 9,108,940. The described synthesis procedure produces an NHC catalyst from readily available compounds that do not contain chlorine or fluorine, thus making the catalyst and synthesis process environmentally friendly. [Overview of the project] [Problems that the invention aims to solve]

[0006] Summary of the Invention In one exemplary embodiment, the present invention provides a method for preparing an NHC catalyst of formula 1 (Figure 1) through a series of steps starting from 2-methylaniline. This method involves (a) contacting 2-methylaniline with aqueous hydrochloric acid to form a chloride amine, while maintaining a local temperature of 0-5°C (e.g., 250cc volume) including the site of contact with the chemicals; (b) contacting the chloride amine with a diazotizing reagent in solution to form a diazonium chloride salt, while maintaining a local temperature of 0-5°C (e.g., 250cc volume) including the site of contact with the chemicals; (c) adding a reducing agent to convert the diazonium chloride salt to 2-methylphenylhydrazine hydrochloride, while maintaining a local temperature of 0-5°C (e.g., 250cc volume) including the site of contact with the chemicals; (d) filtering to recover the 2-methylphenylhydrazine hydrochloride salt as a solid; and (e) contacting the recovered 2-methylphenylhydrazine hydrochloride salt with an aqueous base to form free 2-methylphenylhydrazine. (f) Extracting 2-methylphenylhydrazine from an aqueous base solution with an organic solvent to provide a solution of 2-methylphenylhydrazine in an organic solvent; (g) Drying the solution of 2-methylphenylhydrazine by adding a drying agent; (h) Removing the drying agent by filtration; (i) Contacting the dried 2-methylphenylhydrazine solution with the reaction product of 2-pyrrolidine and dimethyl sulfate to produce the iminohydrazone of formula 2 (Figure 2) in an organic solvent; (j) Removing excess solvent by distillation of the iminohydrazone of formula 2 solution; (k) Recovering the iminohydrazone of formula 2 as a salt; (l) Contacting the iminohydrazone salt of formula 2 with an organic solvent and trimethyl orthoformate to produce a methyl sulfate salt of the N-heterocyclic carbene catalyst of formula 1; (m) Recovering the N-heterocyclic carbene catalyst of formula 1 as a salt. [Means for solving the problem]

[0007] In one exemplary embodiment, the present invention provides a method for preparing the NHC catalyst of Formula 1 through a series of steps starting from 2-methylphenylhydrazine hydrochloride. This method comprises: (a) contacting a 2-methylphenylhydrazine hydrochloride salt with an aqueous base to form free 2-methylphenylhydrazine; (b) extracting 2-methylphenylhydrazine from the aqueous base solution with an organic solvent to provide a solution of 2-methylphenylhydrazine in the organic solvent; (c) drying the solution of 2-methylphenylhydrazine by adding a desiccant; (d) removing the desiccant by filtration; and (e) transferring the dried 2-methylphenylhydrazine solution to 2-pyrrolidine (f) Contacting the reaction product of n and dimethyl sulfate to produce the iminohydrazone of formula 2 in an organic solvent; (g) Distilling the solution of the iminohydrazone of formula 2 to remove excess solvent; (h) Recovering the iminohydrazone of formula 2 as a salt; (i) Contacting the iminohydrazone salt of formula 2 with an organic solvent and trimethyl orthoformate to produce a methyl sulfate salt of the N-heterocyclic carbene catalyst of formula 1; (i) Recovering the N-heterocyclic carbene catalyst of formula 1 as a salt.

[0008] In one exemplary embodiment, the present invention provides a method for preparing an NHC catalyst of formula 1 through a series of steps starting from 2-methylphenylhydrazine. This method comprises: (a) contacting a solution of 2-methylphenylhydrazine with the reaction product of 2-pyrrolidine and dimethyl sulfate to produce an iminohydrazone of formula 2 in an organic solvent; (b) distilling the solution of iminohydrazone of formula 2 to remove excess solvent; (c) recovering the iminohydrazone of formula 2 as a salt; (d) contacting the iminohydrazone salt of formula 2 with an organic solvent and trimethyl orthoformate to produce a methylsulfate salt of the N-heterocyclic carbene catalyst of formula 1; and (e) recovering the N-heterocyclic carbene catalyst of formula 1 as a salt. [Brief explanation of the drawing]

[0009] Brief explanation of the drawing [Figure 1]The molecule of Equation 1 is shown. [Figure 2] The molecule shown in Equation 2 is the iminohydrazone precursor of the molecule in Equation 1. [Figure 3] This shows the reaction between 2-methylaniline and hydrochloric acid to produce 2-methylaniline hydrochloride. [Figure 4] This shows the reaction of 2-methylaniline hydrochloride with sodium nitrite and hydrochloric acid to produce a diazonium salt. [Figure 5] This shows the reaction of a diazonium salt with stannous chloride and hydrochloric acid to produce 2-methylphenylhydrazine hydrochloride. [Figure 6] This shows the reaction between 2-methylphenylhydrazine hydrochloride and sodium hydroxide for the production of 2-methylphenylhydrazine. [Figure 7] This shows the reaction between 2-pyrrolidine and dimethyl sulfate for producing an intermediate precursor of iminohydrazone. [Figure 8] This shows the reaction between an intermediate precursor for the production of iminohydrazone and 2-methylphenylhydrazine. [Figure 9] The reaction of iminohydrazone with trimethyl orthoformate to produce the desired NHC of formula 1 is shown. [Figure 10] The numerator of Equation 3 is shown. [Modes for carrying out the invention]

[0010] Detailed explanation The detailed description below is intended to describe exemplary embodiments of the present invention and is not intended to represent the only form in which the invention can be constructed or utilized. This specification reveals exemplary functions and a set of steps for constructing and operating the present invention. Since the method consists of many steps, it should be understood that identical or equivalent functions and sets can be achieved by different embodiments, and these are intended to be included within the scope of the invention. For example, the present invention involves recovering intermediate chemicals for use in further steps. This allows for the use of apparatus of different sizes and capacities in subsequent steps and for evaluating the purity and quality of the intermediately collected chemicals. As a further example, the relative weight of components can be varied to take purity levels into consideration.

[0011] Based on the capacity to store intermediate chemicals, the steps of this method can be grouped into stages. In the first stage, 2-methylphenylhydrazine hydrochloride is produced from the reactions shown in Figures 3-5. In the second stage, 2-methylphenylhydrazine is produced from the reactions shown in Figure 6. In the third stage, an iminohydrazone precursor is produced from the reactions shown in Figures 7-8. In the fourth stage, an NHC catalyst is produced (Figure 9). Each stage includes operations that may occur in individual reactors and associated equipment.

[0012] The method for producing NHC of Formula 1 can proceed from three different starting chemicals, depending on commercial viability and their availability. The three possible starting chemicals are 2-methylaniline (requiring all four steps), 2-methylphenylhydrazine hydrochloride (requiring steps 2-4), and 2-methylphenylhydrazine (requiring steps 3-4). 2-methylphenylhydrazine hydrochloride can be produced from 2-methylaniline, and subsequently 2-methylphenylhydrazine can be produced from 2-methylphenylhydrazine hydrochloride.

[0013] Methods involving a series of sequential chemical reactions benefit from optimized yields at each step. For preferred yield, highest quality, and maximum flexibility, this method is preferably carried out starting from 2-methylaniline. The series of reactions from 2-methylaniline to 2-methylphenylhydrazine (Figures 3-6, first and second steps) are related to the synthesis of phenylhydrazine from aniline, first reported in early 1875 by Emil Fischer, “Ueber aromtatische Hydrazinverbindigen”, Berichte der deutscen chemischen Gesellschaft, 8, 589-594, which is incorporated herein by reference. Variations in such processes are commercially used to produce related compounds. The steps of this invention differ significantly from those in the reference due to differences in chemical structure, the need for high yield, and the desire for a more environmentally friendly process. The current reaction method, starting with 2-methylaniline, is highly exothermic. The heat generated can destroy intermediates in the reaction sequence, potentially leading to reduced yield, contamination, and increased costs. It is preferable that the chemicals in the first and second steps be produced using current technologies, considering both quality and cost.

[0014] Explanation of the first stage In the first stage (Figures 3-5), as the amount of the desired chemical increases, it may be useful to strictly control heat transfer from the reaction vessel so that the temperature remains within the range of approximately 0-5°C. If the temperature exceeds this range, the yield and purity of the product will decrease dramatically. If the temperature is below this range, the reaction will slow down, making it difficult to maintain the reaction rate. To maintain the reaction rate, 2-methylaniline can be added in approximately 45-50 minutes in the reaction in Figure 3, and the reaction can be completed in 1 hour from the start of addition. In the reaction in Figure 4, the addition of NaNO2 can be done in approximately 45-50 minutes, and the reaction can be completed in 2 hours from the start of addition. The reduction reaction using SnCl2 can be completed in 2 hours, and the reaction can be completed in 3 hours from the start of addition. Cooling systems that cannot maintain these rates and times may reduce the yield. In addition, heat generated locally at the chemical addition site can cause degradation even if the bulk temperature is within the range. To avoid these problems related to reaction kinetics, it is preferable that stirring and heat transfer, especially in large vessels, have internal cooling, such that local reaction mixing is near a cooling surface that can remove heat at a rate matching the desired addition rate. Since the reaction takes place in a hydrochloric acid medium and involves highly reactive intermediates that can react with most metals, the structural materials must be carefully selected. Metal cooling coils or titanium or Hastelloy metal coils thinly coated with polymer materials can be used.

[0015] The product from the first stage (Figure 5) is recovered by filtration. It can then be vacuum-dried for use in further stages. Vacuum drying may involve a vacuum pump or air scrubbing to remove hydrochloric acid fumes reaching the atmosphere. The filtrate contains a high concentration of Sn(Cl)4. To recover Sn, the filtrate can be neutralized with an aqueous sodium hydroxide solution to a pH of approximately 7.5, at which point Sn(OH)4 precipitates, and the residual water has a Sn content well below 10 mg / L (ppm). This Sn(OH)4 can then be dried to obtain SnO2, which can be used as a raw material for producing tin metal. This reprocessing is environmentally friendly and cost-effective. An alternative reducing agent that can be used in the first stage is sodium bisulfite. This reducing agent is used in the production of phenylhydrazine from aniline. However, it requires a long heating step not necessary with SnCl2 and is not currently economically recyclable.

[0016] In a typical first-stage reaction of a size suitable for production up to 0.2 gram-moles (24.4 grams), a 1-liter reaction flask equipped with a magnetic stirrer is used. At the 1-liter level, when internally cooled with a -10°C fluid, an internal coil of 304 stainless steel closely contained within a linear low-density polyethylene tube can be used to maintain the desired addition rate and reaction temperature range. The flask is also cooled with the same fluid. Most of the reaction is carried out at 0°C, and the reaction is maintained in the range of 0 to 5°C, preferably not exceeding 5°C until after the reaction is complete. Add 128 mL of concentrated HCl and 72 mL of water to the flask. All subsequent additions are made below the liquid level in the reactor near the stirrer. When the temperature reaches about 0°C, 21.4 grams of 2-methylaniline pre-cooled to 0 to 5°C can be slowly added over about 50 minutes while maintaining the range of 0 to 5°C. An additional 10 minutes (elapsed time 1 hour) is allowed for the formation of the amine chloride. Next, a pre-cooled solution (0 to 5°C) of 13.8 grams of sodium nitrite, NaNO2, in 32 mL of water is added over about 50 minutes while maintaining the range of 0 to 5°C. The reaction is complete in the next 70 minutes, which is 2 hours from the start of the addition of NaNO2. A pre-cooled solution (0 to 5°C) of 76 grams of SnCl2 in 60 mL of 31 wt% HCl and 140 mL of water (total approximately 200 mL) is slowly added over the next 2 hours while maintaining the range of 0 to 5°C. The reaction can be complete in the next 1 hour. Filter the precipitate and wash the filter cake with approximately 50 mL of a solution of 15 mL of 31 wt% HCl and 35 mL of water. Dry the cake in a vacuum at about 40°C. Collect the filtrate and store it for the reprocessing of SnCl4.

[0017] Description of the second stage In the second stage, 2-methylphenylhydrazine hydrochloride is converted to 2-methylhydrazine by treatment with 10 - 20% aqueous sodium hydroxide. This is conveniently extracted from the aqueous phase with a water-immiscible solvent, which is used in a further stage. The 2-methylphenylhydrazine in the solvent is dried by the addition of a drying medium such as zeolite or anhydrous sodium sulfate. For example, if the selected solvent is toluene, the amount of water in the solvent is 0.5 - 0.6 grams per liter and can be removed quickly and easily. The treatment in the second stage also serves as a purification means for 2-methylphenylhydrazine. Water-soluble compounds and base-reactive compounds are removed as they remain in the aqueous phase.

[0018] The second stage can be carried out on many scales depending on the amount of 2-methylphenylhydrazine hydrochloride to be treated. The reaction used is based on each 100 grams of crude 2-methylphenylhydrazine hydrochloride. Therefore, the size of the container depends on the size of the crude raw material to be treated. A volume of about 500 mL per 100 grams can be appropriate. About 250 mL of a 25% solution of sodium hydroxide, NaOH, is placed in a 500 mL flask equipped with a stirring and heating device. 100 grams of hydrazine hydrochloride is added to the NaOH solution with stirring. The temperature is set to about 45°C. While continuing to stir, about 250 mL of toluene at room temperature is added. This cools the system below 45°C. All stirring is stopped and the layers are separated. The layers can be separated by gravity separation. About 5 grams of anhydrous Na2SO4 can be added to the toluene solution. The solution is mixed for about 30 minutes and then stopped to precipitate the Na2SO4 hydrate. The solution is filtered to recover the filtrate, and the filter cake can be washed with toluene. The product is a solution of 2-methylphenylhydrazine in toluene. As an example, a yield of 90 - 95% can be achieved.

[0019] Description of the third stage The third step of the reaction begins with the reaction of 2-pyrrolidine with dimethyl sulfate (Figure 7) to produce an intermediate. This reaction can be carried out in the same solvent used in the second step, for example, toluene, so that 2-methylphenylhydrazine can be added simply as a solution in the same solvent. Another chemical can be used instead of dimethyl sulfate. Trimethyloxonium tetrafluoroborate is an example of such another chemical. The typical triazolium NHC in Figure 10 was synthesized using tetrafluoroborate, which remains as an NHC anion. This reagent is not only difficult to use due to its toxicity, but also adds excess fluorine when attempting to dispose of or recover the catalyst after use. Since NHC catalysts undergo some decomposition during use, the final environmental kinetics of the NHC must be considered in commercial processes using these compounds.

[0020] The product of the third step is an iminohydrazone precursor of NHC, as shown in Figure 8, after the reaction of 2-methylphenylhydrazine with the intermediate formed in the reaction shown in Figure 7. The resulting methanol can be removed from the reaction mixture by vacuum distillation. When toluene is used as the solvent, the methanol-toluene azeotrope can be removed in the early fraction, followed by the removal of toluene. Once the remaining toluene concentration becomes very low and the product begins to crystallize, the product can be washed with ethyl acetate or a similar solvent to complete the crystallization. The solvent is preferably one that does not azeotrope with toluene. This allows the product to be easily recovered by filtration from the solvent and then distillation of both solvents. The iminohydrazone precursor can then be vacuum dried and stored for use in the fourth step.

[0021] A typical small-scale reaction in the third stage is carried out in a 2-liter or 3-liter vessel. This vessel is equipped with a distillation column to reflux the solvent during the reaction and to allow vacuum distillation of the solvent, such as toluene, after the reaction is complete. The vessel is equipped with a stirring and heating device. 1 liter (approximately 867 grams) of toluene is added to the reaction flask. Next, 35 grams of 2-pyrrolidone, C4H7NO is added. Next, 52 grams of dimethyl sulfate is added. The flask is heated at 80°C for 4 hours with stirring. Heating is stopped and the vessel and its contents are allowed to cool to room temperature. Next, 50 grams of 2-methylphenylhydrazine dissolved in toluene is added. The vessel is heated at 80°C for 5 hours. Heating is stopped and the vessel is allowed to cool to room temperature. Vacuum is applied at a pressure of approximately 20-30 Torr while maintaining the temperature at approximately 20°C. The solvent is removed by separation, and the first fraction containing methanol and some toluene, and then the toluene fraction, are recovered. The temperature can be slightly increased as needed until only about 200-250 mL of solvent remains. Stop the distillation and add about 400 mL of ethyl acetate. The precursor product is solid and can be recovered by filtration. The filtrate is stored for recovery. This product can be vacuum-dried and used in the fourth step.

[0022] Explanation of Stage 4 In the fourth step, the iminohydrazone precursor from the third step is reacted with trimethyl orthoformate in a suitable solvent to form the desired NHC catalyst (Figure 9). Solvents such as toluene can be used in all steps requiring a solvent, thereby reducing solvent storage and enabling the recovery and reuse of the same solvent within the facility for the entire process. After the reaction is complete, excess trimethyl orthoformate and solvent can be recovered by vacuum distillation, and the product can be washed with a suitable solvent in which the product does not dissolve. The product can be filtered, recovered, and dried under vacuum. The filtrate can be reprocessed for reuse of the solvent and residual trimethyl orthoformate. The product of this step is the final NHC of Equation 1.

[0023] A typical reaction of the fourth stage can be carried out in a 20-22 liter reactor. The reactor is equipped with a reflux column and connected to a receiver via a condenser for use in vacuum distillation. The reactor is fitted with a stirrer and means of supplying controlled heat. Approximately 10-11 kg of toluene is added to the reactor. Next, 693 grams of the iminohydrazone precursor from the third stage are added. Then, 1.3 kg of trimethyl orthoformate (TMOF) is added. Heat is applied to maintain a temperature of approximately 100°C and ensure good reflux of the TMOF and toluene. The reaction is continued for 12-18 hours. Once the reaction is complete, the system can be switched to distillation, and approximately 2 / 3 of the volume in the reactor can be removed. This is approximately 7 liters. Under vacuum, the temperature can be lowered to match the active distillation rate without flooding the distillation column. Once the solvent has been removed and a volume of 3-4 liters remains, approximately the same amount of ethyl acetate can be added to completely crystallize the product. The formed solid can be filtered and washed with an additional amount of ethyl acetate (approximately 1 liter). The solid product can be dried under vacuum without heat to remove any residual solvent. The filtrate can be stored for reprocessing to recover ethyl acetate and toluene. A yield of 70% can be achieved.

[0024] industrial use The NHC catalyst of Formula 1 can be used in chemical reactions in the same way as any other NHC catalyst. In methods for producing methyl-2-methyl-5-floate as described in U.S. Patents 8,710,250 and 9,108,940, it may be more effective than the NHC shown in Figure 10. The weight ratio of the NHC used in this invention is the same or slightly lower, but the yield of the reaction using the NHC of Formula 1 is higher and the generation of byproducts is lower. The NHC catalyst of Formula 1 can also be used at lower weight ratios than the other five NHCs tested in the same floate ester reaction. [Examples]

[0025] Example 1. Preparation of 2-methylphenylhydrazine hydrochloride from 0.05 gram-moles of 2-methylaniline. The reaction size was adjusted to a 250 mL reaction flask fitted with a magnetic stirrer. The flask was cooled in a bath at -10°C to -15°C. The reaction was carried out in the range of 0 to 5°C, never exceeding 5°C. 32 mL of concentrated (31 wt%) HCl and 18 mL of water were added to the flask. All subsequent additions were made below the liquid surface in the reactor near the stirrer. When the temperature reached approximately 2 to 3°C, 5.35 grams of 2-methylaniline, pre-cooled to 0 to 5°C, was slowly added over approximately 50 minutes while maintaining the 0 to 5°C range. A further 10 minutes (1 hour elapsed time) was allowed for the formation of the chloride amine. Next, a pre-cooled solution of 3.5 grams of sodium nitrite, NaNO2 (0 to 5°C), in 8 mL of water was added over approximately 50 minutes while maintaining the 0 to 5°C range. The reaction was completed in the next 70 minutes, which was 2 hours from the start of NaNO2 addition. A pre-cooled solution of 19 grams of SnCl2 in 15 mL of 31 wt% HCl and 35 mL of water (total approximately 50 mL) was slowly added over the next 2 hours while maintaining the temperature in the range of 0–5°C. The reaction was then completed over 1 hour. The precipitate was filtered, and the filtered cake was washed with 15 mL of a solution of 4.5 mL of 31 wt% HCl and 10.5 mL of water. The cake was vacuum-dried at approximately 40°C. 7.01 grams of the final product were obtained, and the yield was 88%.

[0026] Example 2. Preparation of 2-methylphenylhydrazine hydrochloride from 0.1 gram-moles of 2-methylaniline The reaction size was adjusted to a 500 mL reaction flask fitted with a magnetic stirrer. The flask was cooled in a bath at -10°C to -15°C. The reaction was carried out in the range of 0 to 5°C, never exceeding 5°C. 64 mL of concentrated (31 wt%) HCl and 36 mL of water were added to the flask. All subsequent additions were made below the liquid surface in the reactor near the stirrer. When the temperature reached approximately 2°C, 10.7 grams of 2-methylaniline, pre-cooled to 0 to 5°C, was slowly added over approximately 50 minutes while maintaining the 0 to 5°C range. A further 10 minutes (1 hour elapsed time) was allowed for the formation of the chloride amine. Next, a pre-cooled solution of 6.9 grams of sodium nitrite, NaNO2 (0 to 5°C), in 16 mL of water was added over approximately 50 minutes while maintaining the 0 to 5°C range. The reaction was completed in the next 70 minutes, which was 2 hours from the start of NaNO2 addition. A pre-cooled solution of 38 grams of SnCl2 in 30 mL of 31 wt% HCl and 70 mL of water (total approximately 100 mL) was slowly added over the next 2 hours while maintaining the temperature in the range of 0–5°C. The reaction was then completed over 1 hour. The precipitate was filtered, and the filtered cake was washed with 30 mL of a solution of 9 mL of 31 wt% HCl and 21 mL of water. The cake was vacuum-dried at approximately 40°C. 10.3 grams of the final product were obtained, and the yield was 65%.

[0027] The decrease in yield in Example 2 indicates that internal cooling is desirable when the reaction volume increases. The change in surface-to-volume ratio between the 250 mL flask and the 500 mL flask indicates that locally controlling heat transfer throughout the reactor is preferable for high yields.

[0028] Example 3. Production of 2-methylphenylhydrazine from 2-methylphenylhydrazine hydrochloride Approximately 160 mL of a 25% sodium hydroxide (NaOH) solution was placed in a 500 mL flask equipped with a stirring and heating device. Next, 63 grams of 2-methylphenylhydrazine hydrochloride were added to the NaOH solution with stirring. The temperature was set to approximately 45°C. After 30 minutes, heating was stopped, and 150 mL of room temperature toluene was added with stirring. Stirring was stopped, and the layers were separated. The layers were separated by gravity. Next, 4 grams of anhydrous Na₂SO₄ were added to the toluene solution. The solution was stirred for 30 minutes to precipitate Na₂SO₄ hydrate. The solution was filtered, the filtrate was collected, and the filter cake was washed with approximately 15 mL of toluene. The product was a solution of 2-methylphenylhydrazine in toluene. When this 2-methylphenylhydrazine solution was measured by GC / MS, it contained 42-44 grams of 2-methylphenylhydrazine. The yield was 86-90%.

[0029] Example 4. Production of an iminohydrazone precursor catalyst from 2-methylphenylhydrazine A 3-liter reaction vessel equipped with distillation columns for reflux and for subsequent distillation after the reaction was complete was used. The vessel had a stirring and heating device. Approximately 700 grams (800 mL) of toluene was added to the reaction flask. Next, 21 grams of 2-pyrrolidone, C4H7NO was added. Then, 31 grams of dimethyl sulfate was added. The flask was heated at 80°C for 4 hours with stirring. Heating was stopped, and the vessel and its contents were cooled to room temperature. Next, 30 grams of 2-methylphenylhydrazine dissolved in 150 grams of toluene was added. The vessel was heated at 80°C for 5 hours with stirring. Heating was stopped, and the vessel was cooled to room temperature. Vacuum was applied at a pressure of 20-30 Torr while maintaining the temperature at approximately 20°C. The solvent was removed until a volume of approximately 200 mL remained in the flask. Distillation was stopped, and 300 mL of ethyl acetate was added. The precursor product was solid and was recovered by filtration. The filtration cake was washed with approximately 40 mL of additional ethyl acetate. The filtrate was saved for recovery. The product was vacuum-dried to a certain weight. The weight of the solid after drying was 43 grams.

[0030] Example 5. Production of NHC catalyst from iminohydrazone precursor A distillation column was attached to a 1-liter reactor and connected to a receiver via a condenser for use in vacuum distillation. The reactor was equipped with a stirrer and a means of supplying controlled heat. 600 grams (approximately 700 mL) of toluene was added to the reactor. Next, 43 grams of the iminohydrazone precursor from the third step were added. Then, 80 grams of trimethyl orthoformate (TMOF) were added. Heat was applied to maintain a temperature of approximately 100°C, and the TMOF and toluene were refluxed well. The reaction was continued for 18 hours. At this point, the system was switched to distillation, and a total of 450 mL of toluene and excess TMOF were removed. After distillation was complete and the system was cooled to ambient temperature, 250 mL of ethyl acetate was added. The formed solid was filtered and washed with an additional 50 mL of ethyl acetate on filter paper. The solid product was dried under vacuum. The filtrate was saved for reprocessing to recover ethyl acetate and toluene. The weight of the obtained product was 37.5 grams.

[0031] Example 6. Use of an NHC catalyst for the production of methyl-5-methyl-2-floate A 22L three-necked reaction vessel was used. A heating mantle and jacket were attached to it. The central neck had a stirrer with blades wide enough to sweep the bottom of the vessel. A thermocouple was attached to one neck, which was connected to the heating mantle's thermal control electronics. A distillation column was attached to the other neck. At the joint at the top of the reflux condenser was a thermocouple for measuring the vapor temperature leading to the condenser. The condenser led to a receiver, which was connected to a vacuum distillation source. 12.54 kg of a solution of 1.18 kg of 5-chloromethyl-2-furfuraldehyde (CMF) in toluene was added to the reaction vessel. Stirring was started, and 1,040 g of anhydrous sodium carbonate, Na2CO3, was added. Next, 400 g of methanol was added. Then, 11.7 g of the NHC catalyst of formula 1 was added. The temperature of the mixture was raised to 80-81°C, and the reaction was continued for 4 hours. At the end of this time, toluene and excess methanol were removed by fractional vacuum distillation using a vacuum pressure of 20–30 Torr. This was started at 20°C and the distillation of the methyl-5-methyl-2-floate fraction was completed at 120–130°C. Methyl-5-methyl-2-floate was recovered in the final fraction. The final fraction was redistilled to produce methyl-5-methyl-2-floate, which was found to be 99% pure as measured by GC / MS analysis. At the completion of the reaction, 1,070 grams of floate were produced, and 1,010 grams were recovered. This was a yield of 93%, which was higher than the normal range for other NHC catalysts.

[0032] The present invention has been described in relation to various exemplary embodiments. It will be understood that the above description is merely illustrative of the application of the principles of the present invention, and that its scope is determined by the claims as seen in the specification. Other variations and modifications of the present invention will be apparent to those skilled in the art.

Claims

1. A method for synthesizing the N-heterocyclic carbene catalyst salt of formula 1, comprising: (a) contacting 2-methylaniline with aqueous hydrochloric acid to form a chloride amine; (b) contacting the chloride amine with a diazotizing reagent in solution to form a diazonium chloride salt; (c) adding a reducing agent to convert the diazonium chloride salt to 2-methylphenylhydrazine hydrochloride; (d) filtering to recover the 2-methylphenylhydrazine hydrochloride as a solid; (e) contacting the recovered 2-methylphenylhydrazine hydrochloride salt with an aqueous base to form free 2-methylphenylhydrazine; (f) extracting the 2-methylphenylhydrazine from the aqueous base solution with an organic solvent to obtain the 2-methylphenylhydrazine in the organic solvent. A method comprising: (g) providing a solution of 2-methylphenylhydrazine; (h) drying the solution of 2-methylphenylhydrazine by adding a drying agent; (i) contacting the dried 2-methylphenylhydrazine solution with the reaction product of 2-pyrrolidine and dimethyl sulfate to produce the iminohydrazone of formula 2 in an organic solvent; (j) distilling the solution of the iminohydrazone of formula 2 to remove excess solvent; (k) recovering the iminohydrazone of formula 2 as a solid salt; (l) contacting the iminohydrazone salt of formula 2 with an organic solvent and trimethyl orthoformate to produce a methyl sulfate salt of the N-heterocyclic carbene catalyst of formula 1; and (m) recovering the N-heterocyclic carbene catalyst of formula 1 as a salt. 【Chemistry 1】 【Chemistry 2】

2. The method according to claim 1, wherein the diazotizing reagent is sodium nitrite (NaNO2).

3. The method according to claim 1, wherein the reducing agent is stannous chloride.

4. The method according to claim 1, wherein the temperature in steps (a), (b), and (c) is locally maintained at 0°C to 5°C throughout the entire reactor, where locally means in units of 250 cc of volume.

5. The method according to claim 1, wherein the temperature of step (i) is 60°C to 80°C.

6. The method according to claim 1, wherein the temperature of step (l) is 80°C to 100°C.

7. The method according to claim 1, wherein the solvent in step (f), (i), and (l) is an aromatic hydrocarbon.

8. The method according to claim 1, wherein the solvent in step (f), (i), or (l) is selected from the group consisting of toluene, a mixture of xylene, m-xylene, o-xylene, and p-xylene.

9. The method according to claim 1, wherein the synthesis begins with step (e) using 2-methylphenylhydrazine hydrochloride.

10. The synthesis begins with step (i) using 2-methylphenylhydrazine. The method according to claim 1.

11. The method according to claim 1, wherein the filtrate after step (d) is neutralized with a hydroxide base to produce stannic hydroxide, which is then filtered and dried to produce stannic oxide (SnO2) for reprocessing into tin, and the tin salt is recovered by subsequently producing stannous chloride.

Images