A method for synthesizing methyl amino-methyl-phenylcarbamate compounds from p-toluidine

Abstract

This invention discloses a method for synthesizing methyl amino-methyl-phenylcarbamate compounds from p-toluidine. The method uses p-toluidine as a raw material, employs anhydrous zinc acetate catalyst and the green solvent dimethyl carbonate, to first prepare methyl p-toluylcarbamate, followed by one-step direct amination to prepare methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate. This invention has advantages such as readily available raw materials, an environmentally friendly reaction process, high atom utilization, and a first-step reaction yield of up to 96% and a second-step reaction yield of up to 35.7%.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis, specifically a method for synthesizing methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate from p-toluidine. Background Technology

[0002] Methylaniline is a collective term for amine compounds in which the ortho, para, or meta hydrogen atoms on the benzene ring of the aniline molecule are replaced by methyl groups. It has three isomers: o-methylaniline, m-methylaniline, and p-methylaniline. p-Toluidine is an important chemical raw material, used as a dye intermediate, and also as an intermediate in pharmaceuticals such as pyrimethamine and pesticides such as glyphosate. It can undergo various chemical reactions. Methyl p-toluenecarbamate is an important intermediate used in organic synthesis for the non-phosgene method to prepare monoisocyanates, synthesize non-toxic polyurethanes, and produce N-substituted pyrroles and N-substituted carbamates. It is often used as an excellent directing and leaving group. In the pharmaceutical field, it can be used as a sedative, insecticide, and fungicide. Methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate are also important organic intermediates, mainly used in the methoxycarbonylation to prepare methyl toluenedicarbamate, which can serve as a precursor for toluenediisocyanate.

[0003] Traditional methods for synthesizing carbamates often use highly toxic phosgene or isocyanate derivatives as raw materials. Phosgene is a highly toxic gas, posing significant safety hazards to operators and causing serious environmental pollution and safety problems. In recent years, dimethyl carbonate, as a widely used basic organic synthesis raw material, has shown good reactivity and can serve as an ideal substitute for phosgene and dimethyl sulfate. Wang Yanji et al. (CN03156418) used zinc acetate as a catalyst to react 2,4-diaminotoluene and dimethyl carbonate to produce methyl 2,4-toluenedicarbamate, in which the intermediate methyl 3-amino-4-methylphenylcarbamate is generated. Li Qun et al. (Fine Petrochemicals, 2013, 30(05):59-62.) used toluene as a solvent, added 2,4-diaminotoluene and methyl chloroformate as raw materials, and zinc chloride as a catalyst to react and produce methyl 3-amino-4-methylphenylcarbamate. However, the yield was low, and the byproduct HCl needed to be neutralized with triethylamine. Furthermore, the 2,4-diaminotoluene used as the raw material was mostly prepared by the reduction of dinitrotoluene, which is a controlled substance and has certain hazards. Currently, there is a lack of research in the academic community on the preparation of methyl 2-amino-4-methylphenylcarbamate. Therefore, it is very important to explore a reaction route with high yield, environmental friendliness, and high atom utilization. Summary of the Invention

[0004] The purpose of this invention is to address the problems of low atom utilization, poor yield, and environmental pollution in current methods for synthesizing methyl 3-amino-4-methylphenylcarbamate, and to provide a method for synthesizing amino-methyl-phenylcarbamate compounds from p-toluidine. This method uses p-toluidine as a raw material, employs anhydrous zinc acetate catalyst and the green solvent dimethyl carbonate, to first prepare p-toluylcarbamate, followed by one-step direct amination to prepare methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate. This invention has advantages such as readily available raw materials, high atom utilization, and an environmentally friendly reaction process.

[0005] The technical solution of this invention is:

[0006] A method for synthesizing methyl amino-methyl-phenylcarbamate compounds from p-toluidine, the method comprising the following steps:

[0007] The first step is to prepare methyl p-toluenecarbamate from p-toluidine.

[0008] p-Toluidine, the first catalyst, and dimethyl carbonate were added to a high-pressure reactor. After sealing, the reactor was stirred and reacted at 110–180°C in an oxygen-free atmosphere for 2–10 hours to obtain the product p-toluylcarbamate.

[0009] The molar ratio is as follows: dimethyl carbonate: p-toluidine = 5-30; the first catalyst is an organic salt catalyst, p-toluidine: first catalyst (based on metal atoms) = 10-200;

[0010] The first catalyst is anhydrous zinc acetate, zinc acetate dihydrate, or manganese acetate.

[0011] The preferred material ratio is dimethyl carbonate: p-toluidine = 10-25; p-toluidine: first catalyst (based on metal atoms) = 15-150; the preferred reaction temperature is 130-160℃; and the preferred reaction time is 2-8h.

[0012] The second step involves preparing methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate from methyl p-tolylcarbamate.

[0013] Methyl p-toluylcarbamate, a second catalyst, hydroxylamine-O-sulfonic acid, and an acidic medium were added to a reactor. The reaction was carried out at atmospheric pressure and at 40–90 °C with constant temperature stirring for 0.25–3 h. The organic phase in the reaction solution was then separated to obtain the products methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate.

[0014] The molar ratio of the materials is as follows: methyl p-toluene: hydroxylamine-O-sulfonic acid = 0.1-5, and the molar ratio of the second catalyst (calculated as iron or vanadium atoms) is methyl p-toluene = 0.01-0.6.

[0015] Add 0.001~0.010 mol of methyl p-toluenecarbamate to every 15 mL of acidic medium;

[0016] The second catalyst is ferrous sulfate, ferrous chloride, ferric chloride, or ammonium metavanadate; the acidic medium consists of lower fatty acids and water, or lower fatty acids, water, and inorganic acids; the volume percentage of lower fatty acids is 17%–83%, the volume percentage of water is 17%–83%, and the volume percentage of inorganic acids is 0%–15%.

[0017] The lower fatty acids are formic acid, acetic acid, or propionic acid; the inorganic acids are hydrochloric acid, sulfuric acid, or phosphoric acid.

[0018] The preferred reaction temperature is 50–80°C, and the preferred reaction time is 0.5–1.5 h. The preferred acidic medium composition is acetic acid:water = 5:15–16:4. The preferred molar ratio of catalyst to methyl p-toluenecarbamate is 0.02–0.5, and the preferred molar ratio of methyl p-toluenecarbamate to hydroxylamine-O-sulfonic acid is 0.25–4.2.

[0019] The essential features of this invention are:

[0020] Methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate are important raw materials for the synthesis of methyl toluenedicarbamate, the latter being a significant source for the synthesis of toluene diisocyanate. Methyl 3-amino-4-methylphenylcarbamate was initially discovered only as an intermediate in the synthesis of methyl 2,4-methyl toluenedicarbamate, but since the starting material was 2,4-diaminotoluene, its production was mostly achieved through the reduction of 2,4-dinitrotoluene, which carries certain risks. To date, no complete synthetic route exists for methyl 2-amino-4-methylphenylcarbamate.

[0021] This invention uses p-toluidine as a raw material to synthesize methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate in two steps. p-Toluidine itself can be prepared by one-step amination of toluene, avoiding the potential hazards associated with nitrotoluene. The product of the first-step methoxycarbonylation reaction—methyl p-toluylcarbamate—can not only participate in the second-step reaction but can also serve as a raw material for the synthesis of monoisocyanates, exhibiting high atom utilization, sustainability, and environmental friendliness. Furthermore, the second-step reaction utilizes hydroxylamine-O-sulfonic acid for one-step amination, resulting in mild reaction conditions, short reaction time, simple equipment, and convenient operation.

[0022] The beneficial effects of this invention are as follows:

[0023] (1) This method is the first to design a relatively systematic synthetic route for methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate. It has high atom utilization, mild reaction conditions, and the yield of the first step reaction can reach 96% and the yield of the second step reaction can reach 35.7%.

[0024] (2) This method is the first to realize the reaction from monoaminotoluene to diaminotoluene-like compounds, and a one-step amination reaction is realized on monoaminocarbamate compounds, making them suitable as raw materials for the synthesis of diaminocarbamates, with good research and application prospects.

[0025] (3) The catalyst is readily available and inexpensive, and has good catalytic performance.

[0026] (4) Use dimethyl carbonate as both reactant and solvent for methoxycarbonylation reaction instead of toluene and methyl chloroformate.

[0027] (5) A new route for the direct synthesis of methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate from methyl aniline has been opened up, breaking the previous production approach from dinitrotoluene to toluene diisocyanate, making the whole process route conform to the characteristics of inherent safety and green environmental protection. Detailed Implementation

[0028] (I) For the first step reaction, the reaction formula is:

[0029]

[0030] Example 1: 0.03 mol of p-toluidine, 50 mL (0.5944 mol), and 0.0005 mol of anhydrous zinc acetate catalyst were added to a high-pressure reactor. The reactor was sealed, and N2 was introduced to replace the air in the reactor to ensure an oxygen-free atmosphere. The reaction was mechanically stirred at 140 °C for 4 hours, then stopped. After the reaction solution cooled to room temperature, the supernatant was centrifuged to allow the catalyst to settle at the bottom. The supernatant was filtered and analyzed by high-performance liquid chromatography (HPLC). The remaining supernatant was subjected to vacuum distillation at 50 °C. The resulting solid was dried overnight in a vacuum oven at 80 °C and used as the raw material for the second step of the reaction. The reaction results showed that the conversion rate of p-toluidine was 98.1%, and the yield of methyl p-toluene carbamate was 96.2%.

[0031] The characterization method was as follows: high performance liquid chromatography, using a UV detector, with methanol-water solution as the mobile phase at a ratio of 7:3, a flow rate of 0.6 mL / min, a column temperature of 30 ℃, a detection wavelength of 232 nm, and external standard method for quantification.

[0032] Example 2: The other steps are the same as in Example 1, except that zinc acetate dihydrate is added as the catalyst. The conversion rate of p-toluidine is 0%, and the yield of p-toluylcarbamate is 87.5%.

[0033] Example 3: The other steps are the same as in Example 1, except that manganese acetate is added as the catalyst. The conversion rate of p-toluidine is 12.1%, and the yield of p-toluylcarbamate is 3.6%.

[0034] Example 4: The other steps are the same as in Example 1, except that 0.0002 mol of anhydrous zinc acetate catalyst is added. The conversion rate of p-toluidine is 97.36%, and the yield of p-toluene carbamate is 90.24%.

[0035] Example 5: The other steps are the same as in Example 1, except that 0.001 mol of anhydrous zinc acetate catalyst is added. The conversion rate of p-toluidine is 97.05%, and the yield of p-toluene carbamate is 88.98%.

[0036] Example 6: The other steps are the same as in Example 1, except that 0.002 mol of anhydrous zinc acetate catalyst is added. The conversion rate of p-toluidine is 95.63%, and the yield of p-toluene carbamate is 82.53%.

[0037] Example 7: The other steps were the same as in Example 1, except that 25 mL (0.2967 mol) of dimethyl carbonate was added. The conversion rate of p-toluidine was 69.39%, and the yield of p-toluene carbamate was 58.26%.

[0038] Example 8: The other steps were the same as in Example 1, except that 37 mL (0.4444 mol) of dimethyl carbonate was added. The conversion rate of p-toluidine was 80.38%, and the yield of p-toluene carbamate was 71.86%.

[0039] Example 9: The other steps were the same as in Example 1, except that 63 mL (0.7444 mol) of dimethyl carbonate was added. The conversion rate of p-toluidine was 95.12%, and the yield of p-toluene carbamate was 89.82%.

[0040] Example 10: Other steps were the same as in Example 1, except that the reaction time was 2 hours. The conversion rate of p-toluidine was 97.46%, and the yield of p-toluylcarbamate was 87.06%.

[0041] Example 11: Other steps were the same as in Example 1, except that the reaction time was 6 hours. The conversion rate of p-toluidine was 95.82%, and the yield of p-toluylcarbamate was 85.31%.

[0042] Example 12: Other steps were the same as in Example 1, except that the reaction time was 8 hours. The conversion rate of p-toluidine was 80.28%, and the yield of p-toluylcarbamate was 76.1%.

[0043] Example 13: Other steps were the same as in Example 1, except that the reaction temperature was 130°C. The conversion rate of p-toluidine was 82.4%, and the yield of p-toluylcarbamate was 81.57%.

[0044] Example 14: The other steps were the same as in Example 1, except that the reaction temperature was 150°C. The conversion rate of p-toluidine was 92.53%, and the yield of p-toluylcarbamate was 87.23%.

[0045] Example 15: The other steps were the same as in Example 1, except that the reaction temperature was 160°C. The conversion rate of p-toluidine was 90.67%, and the yield of p-toluylcarbamate was 85.44%.

[0046] As can be seen from the above examples, the catalytic system is simple to operate, has a high yield of methyl p-toluenecarbamate, the catalyst is readily available, and exhibits good activity and selectivity, and is easily separated from the reaction system. Analysis of the data in the examples shows that the most active catalyst is anhydrous zinc acetate, which exhibits high conversion and yield under the experimental conditions of 140°C, p-toluidine (0.03 mmol), dimethyl carbonate (50 mL, 0.5944 mol), and anhydrous zinc acetate (0.0005 mol).

[0047] (II) For the second step reaction

[0048]

[0049] Example 16: 0.002 mol of vacuum-dried methyl p-toluenecarbamate (from Example 1), 0.0036 mol of hydroxylamine-O-sulfonic acid, and 0.0003 mol of ferrous sulfate were placed in a 100 mL three-necked flask. 15 mL of acidic medium (acetic acid:water volume ratio 15:5) was added. The mixture was heated to 60 °C, refluxed, and stirred at constant temperature under atmospheric pressure for 1 h. After the reaction, the reaction solution was cooled to room temperature, and a 30% sodium hydroxide solution was gradually added dropwise until the pH of the reaction solution was neutral. The organic phase was extracted and analyzed by high-performance liquid chromatography (HPLC). The results showed that the conversion rate of methyl p-toluenecarbamate was 71.39%, the yield of methyl 2-amino-4-methylphenylcarbamate was 26.08%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 9.67%.

[0050] The characterization method is the same as in Example 1.

[0051] Example 17: The other steps are the same as in Example 16, except that 0.001 mol of methyl p-toluenecarbamate is added. The conversion rate of methyl p-toluenecarbamate is 72.84%, the yield of methyl 2-amino-4-methylphenylcarbamate is 25.96%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 7.43%.

[0052] Example 18: The other steps are the same as in Example 16, except that 0.005 mol of methyl p-toluenecarbamate is added. The conversion rate of methyl p-toluenecarbamate is 63.64%, the yield of methyl 2-amino-4-methylphenylcarbamate is 21.54%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 6.47%.

[0053] Example 19: The other steps are the same as in Example 16, except that 0.010 mol of methyl p-toluenecarbamate is added. The conversion rate of methyl p-toluenecarbamate is 58.35%, the yield of methyl 2-amino-4-methylphenylcarbamate is 17.43%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 5.12%.

[0054] Example 20: The other steps are the same as in Example 16, except that ferrous chloride is added as the catalyst. The conversion rate of methyl p-toluenecarbamate is 8.67%, the yield of methyl 2-amino-4-methylphenylcarbamate is 3.3%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 1.75%.

[0055] Example 21: The other steps are the same as in Example 16, except that ferric chloride is added as the catalyst. The conversion rate of methyl p-toluenecarbamate is 5.63%, the yield of methyl 2-amino-4-methylphenylcarbamate is 2.27%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 1.28%.

[0056] Example 22: The other steps are the same as in Example 16, except that ammonium metavanadate is added as the catalyst. The conversion rate of methyl p-toluenecarbamate is 15.28%, the yield of methyl 2-amino-4-methylphenylcarbamate is 8.72%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 3.58%.

[0057] Example 23: The other steps are the same as in Example 16, except that 0.0002 mol of ferrous sulfate catalyst is added. The conversion rate of methyl p-toluenecarbamate is 65.14%, the yield of methyl 2-amino-4-methylphenylcarbamate is 22.17%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 8.52%.

[0058] Example 24: The other steps are the same as in Example 16, except that 0.0004 mol of ferrous sulfate catalyst is added. The conversion rate of methyl p-toluenecarbamate is 63.96%, the yield of methyl 2-amino-4-methylphenylcarbamate is 21.1%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 7.91%.

[0059] Example 25: The other steps are the same as in Example 16, except that 0.0005 mol of ferrous sulfate catalyst is added. The conversion rate of methyl p-toluenecarbamate is 55.53%, the yield of methyl 2-amino-4-methylphenylcarbamate is 20.7%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 7.87%.

[0060] Example 26: Other steps were the same as in Example 16, except that 0.0024 mol of hydroxylamine-O-sulfonic acid was added. The conversion rate of methyl p-toluenecarbamate was 45.49%, the yield of methyl 2-amino-4-methylphenylcarbamate was 21.1%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 7.91%.

[0061] Example 27: Other steps were the same as in Example 16, except that 0.003 mol of hydroxylamine-O-sulfonic acid was added. The conversion rate of methyl p-toluenecarbamate was 71.69%, the yield of methyl 2-amino-4-methylphenylcarbamate was 23.95%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 9.37%.

[0062] Example 28: The other steps are the same as in Example 16, except that 0.004 mol of hydroxylamine-O-sulfonic acid was added. The conversion rate of methyl p-toluenecarbamate was 74.98%, the yield of methyl 2-amino-4-methylphenylcarbamate was 21.99%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 7.65%.

[0063] Example 29: Other steps are the same as in Example 16, except that the ratio of the added acidic medium is formic acid:water = 15:5. The conversion rate of methyl p-toluenecarbamate is 28.55%, the yield of methyl 2-amino-4-methylphenylcarbamate is 8.68%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 4.44%.

[0064] Example 30: Other steps are the same as in Example 16, except that the ratio of the added acidic medium is propionic acid:water = 15:5. The conversion rate of methyl p-toluenecarbamate is 23.72%, the yield of methyl 2-amino-4-methylphenylcarbamate is 12.25%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 4.18%.

[0065] Example 31: Other steps are the same as in Example 16, except that the ratio of the added acidic medium is hydrochloric acid:acetic acid:water = 3:12:5. The conversion rate of methyl p-toluenecarbamate is 32.94%, the yield of methyl 2-amino-4-methylphenylcarbamate is 1.55%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 0.75%.

[0066] Example 32: Other steps are the same as in Example 16, except that the ratio of the added acidic medium is sulfuric acid:acetic acid:water = 3:12:5. The conversion rate of methyl p-toluenecarbamate is 66.87%, the yield of methyl 2-amino-4-methylphenylcarbamate is 0.85%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 0.32%.

[0067] Example 33: Other steps are the same as in Example 16, except that the ratio of the added acidic medium is phosphoric acid:acetic acid:water = 3:12:5. The conversion rate of methyl p-toluenecarbamate is 40.42%, the yield of methyl 2-amino-4-methylphenylcarbamate is 21.05%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 10.72%.

[0068] Example 34: Other steps are the same as in Example 16, except that the ratio of the added acidic medium is acetic acid:water = 5:15. The conversion rate of methyl p-toluenecarbamate is 30.28%, the yield of methyl 2-amino-4-methylphenylcarbamate is 14.32%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 7.18%.

[0069] Example 35: Other steps are the same as in Example 16, except that the ratio of the added acidic medium is acetic acid:water = 10:10. The conversion rate of methyl p-toluenecarbamate is 52.65%, the yield of methyl 2-amino-4-methylphenylcarbamate is 18.62%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 8.61%.

[0070] Example 36: Other steps are the same as in Example 16, except that the ratio of the added acidic medium is acetic acid:water = 16:4. The conversion rate of methyl p-toluenecarbamate is 52.65%, the yield of methyl 2-amino-4-methylphenylcarbamate is 22.94%, and the yield of methyl 3-amino-4-methylphenylcarbamate is 7.81%.

[0071] Example 37: Other steps were the same as in Example 16, except that the reaction time was 0.5 h. The conversion rate of methyl p-toluenecarbamate was 81.67%, the yield of methyl 2-amino-4-methylphenylcarbamate was 15.99%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 6.37%.

[0072] Example 38: The other steps were the same as in Example 16, except that the reaction time was 0.75 h. The conversion rate of methyl p-toluenecarbamate was 78.59%, the yield of methyl 2-amino-4-methylphenylcarbamate was 16.34%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 8.32%.

[0073] Example 39: Other steps were the same as in Example 16, except that the reaction time was 1.5 h. The conversion rate of methyl p-toluenecarbamate was 78.59%, the yield of methyl 2-amino-4-methylphenylcarbamate was 14.38%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 7.18%.

[0074] Example 40: The other steps were the same as in Example 16, except that the reaction temperature was 50°C. The conversion rate of methyl p-toluenecarbamate was 77.55%, the yield of methyl 2-amino-4-methylphenylcarbamate was 8.55%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 3.69%.

[0075] Example 41: The other steps were the same as in Example 16, except that the reaction temperature was 70°C. The conversion rate of methyl p-toluenecarbamate was 73.56%, the yield of methyl 2-amino-4-methylphenylcarbamate was 14.56%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 5.26%.

[0076] Example 42: The other steps were the same as in Example 16, except that the reaction temperature was 80°C. The conversion rate of methyl p-toluenecarbamate was 70.82%, the yield of methyl 2-amino-4-methylphenylcarbamate was 8.51%, and the yield of methyl 3-amino-4-methylphenylcarbamate was 3.26%.

[0077] As can be seen from the above examples, the catalytic system is simple to operate, the catalyst is readily available and exhibits good catalytic activity, and it is easily separated from the reaction system. Analysis of the data in the examples shows that the ferrous sulfate catalyst exhibits the best activity. Under the experimental conditions of 60°C and a volume ratio of methyl p-toluenecarbamate (0.002 mmol), hydroxylamine-O-sulfonic acid (0.0036 mol), ferrous sulfate (0.0003 mol), acetic acid, and water of 15:5, the conversion rate and yield of the reaction are relatively high.

[0078] Matters not covered in this invention are common knowledge.

Claims

1. A method for synthesizing methyl amino-methyl-phenylcarbamate compounds from p-toluidine, characterized in that the method comprises the following steps: The first step is to prepare methyl p-toluenecarbamate from p-toluidine. p-Toluidine, the first catalyst, and dimethyl carbonate were added to a high-pressure reactor. After sealing, the reactor was stirred and reacted at 110–180°C in an oxygen-free atmosphere for 2–10 hours to obtain the product p-toluylcarbamate. in, The molar ratio is: dimethyl carbonate : p-toluidine = 5-30; the first catalyst is an organic salt catalyst, p-toluidine : first catalyst = 10-200; the number of moles of the first catalyst is calculated in terms of metal atoms; The first catalyst is anhydrous zinc acetate, zinc acetate dihydrate, or manganese acetate. The second step involves preparing methyl 2-amino-4-methylanilinecarbamate and methyl 3-amino-4-methylanilinecarbamate from methyl p-tolylcarbamate. Methyl p-toluylcarbamate, a second catalyst, hydroxylamine-O-sulfonic acid, and an acidic medium were added to a reactor. The reaction was carried out at atmospheric pressure and at 40–90 °C with constant temperature stirring for 0.25–3 h. The organic phase in the reaction solution was then separated to obtain the products methyl 2-amino-4-methylphenylcarbamate and methyl 3-amino-4-methylphenylcarbamate. The molar ratio of the materials is as follows: methyl p-toluene: hydroxylamine-O-sulfonic acid = 0.1-5, and the molar ratio of the second catalyst is methyl p-toluene = 0.01-0.6; the number of moles of the second catalyst is calculated in terms of iron atoms or vanadium atoms. Add 0.001~0.010 mol of methyl p-toluenecarbamate to every 15 mL of acidic medium; The second catalyst is ferrous sulfate, ferrous chloride, ferric chloride or ammonium metavanadate; The acidic medium consists of lower fatty acids and water, or lower fatty acids, water, and inorganic acids; the volume percentage of lower fatty acids is 17%–83%, the volume percentage of water is 17%–83%, and the volume percentage of inorganic acids is 0%–15%. The lower fatty acids mentioned are formic acid, acetic acid, or propionic acid.

2. The method for synthesizing amino-methyl-phenylcarbamate compounds from p-toluidine as described in claim 1, characterized in that in the first step, the material ratio is dimethyl carbonate: p-toluidine = 10-25; p-toluidine: first catalyst = 15-150, wherein the molar number of the first catalyst is calculated in terms of metal atoms; the reaction temperature is 130-160℃; and the reaction time is 2-8h.

3. The method for synthesizing amino-methyl-phenylcarbamate compounds from p-toluidine according to claim 1, characterized in that, in the second step, the reaction temperature is 50-80°C, the reaction time is 0.5-1.5 h; the acidic medium composition is acetic acid:water = 5:15-16:4; the molar ratio of catalyst to p-toluylcarbamate is 0.02-0.5; and the ratio of p-toluylcarbamate to hydroxylamine-O-sulfonic acid is 0.25-4.

2.

4. The method for synthesizing methyl amino-methyl-phenylcarbamate compounds from p-toluidine as described in claim 1, characterized in that: The inorganic acid is hydrochloric acid, sulfuric acid, or phosphoric acid.

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