Synthesis process of methyl cyanocarbamate

Abstract

The invention discloses methyl cyanamide synthesis technique, belongs to the field of pharmaceutical synthesis technology, synthesis technique, comprises the following steps:By grafted carrier, toluene, methacryloylpropyl dimethyl benzyl ammonium chloride and azobisisobutyronitrile mixing, under nitrogen protection condition, 80 DEG C of stirring reactions 7 8h, after reaction terminates, through filtration, vacuum drying, obtain supported catalyst;Cyanamide is diluted with water, methyl chloroformate is subsequently added, and it is regulated that reaction system pH value is 9 11, adds supported phase-transfer catalyst, and setting temperature is 45 50 DEG C, stirring reaction, obtains methyl cyanamide.The process flow of the present invention is simple, by the control of reaction conditions and the operation such as adding supported phase-transfer catalyst in technique, improve reaction efficiency, reduce the generation of by-products, improve product purity.

Description

Technical Field

[0001] The invention belongs to the technical field of drug synthesis, and particularly relates to a synthesis process of methyl cyanamide. Background Art

[0002] Methyl cyanocarbamate is an important intermediate in the synthesis of the pesticide fungicide carbendazim. After methyl chloroformate is prepared, cyanamide (H2N-CN) generated by the hydrolysis of lime nitrogen (Ca=N-CN) is used to carry out a cyanamination reaction to produce methyl cyanocarbamate. Methyl cyanocarbamate can condense with o-phenylenediamine [C6H4(NH2)2] in an acidic aqueous solution to obtain carbendazim.

[0003] The existing technology uses the lime nitrogen method to produce cyanamide. Since lime nitrogen decomposes into alkaline in water, by-products are easily generated during the production of cyanamide, resulting in low purity of cyanamide, affecting the purity of methyl cyanamide formate and further affecting the purity and conversion rate of carbendazim. The reaction time is long, the yield is low, and there is severe corrosion to the equipment. Summary of the Invention

[0004] The present invention aims to provide a process for synthesizing methyl cyanamide to solve the problem of low purity in the process for synthesizing methyl cyanamide.

[0005] The purpose of the present invention can be achieved through the following technical solutions:

[0006] The synthesis process of methyl cyanamide comprises the following steps:

[0007] The grafted carrier, toluene, methacryloylpropyl dimethylbenzyl ammonium chloride and azobisisobutyronitrile were mixed, stirred and reacted at 80°C for 7-8 hours under nitrogen protection. After the reaction, the mixture was filtered and vacuum dried to obtain a supported catalyst.

[0008] Cyanamide is diluted with water, and then methyl chloroformate is added. The pH of the reaction system is adjusted to 9-11. A supported phase transfer catalyst is added, and the temperature is set to 45-50°C. The reaction is stirred to obtain methyl cyanamide. Using commercially available cyanamide as the raw material reduces the introduction of impurities when lime nitrogen is used as the raw material. Diluting cyanamide before use in production can prevent precipitation of materials during the reaction, which can affect the reaction process.

[0009] Furthermore, the dilute cyanamide is diluted with water to a mass fraction of 6-7%. The dilution degree of cyanamide will affect the progress of the reaction, and maintaining it in the range of 6-7% allows it to participate in the reaction better.

[0010] Furthermore, the usage ratio of the graftable carrier, toluene, methacryloylpropyldimethylbenzyl ammonium chloride and azobisisobutyronitrile is 7-8 g:100 mL:2-3 g:0.1 g.

[0011] Furthermore, the molar ratio of cyanamide to methyl chloroformate is 1:1.01, and the amount of the supported phase transfer catalyst added is 4-5% of the mass of the cyanamide. Reusing the catalyst has little impact on the reaction yield and product purity, and using a supported catalyst can save costs.

[0012] Furthermore, sodium hydroxide is selected as a pH regulator for adjusting the pH value of the reaction system. Selecting sodium hydroxide as a pH regulator does not introduce new impurities and simplifies post-processing.

[0013] Furthermore, the graftable carrier is prepared by the following steps:

[0014] Mix the carrier with a 90% ethanol aqueous solution, add γ-methacryloxypropyltrimethoxysilane, set the temperature to 50°C, and react for 24 hours. After the reaction, filter, wash with alcohol, and vacuum dry to obtain a graftable carrier. The ratio of carrier, ethanol aqueous solution, and γ-methacryloxypropyltrimethoxysilane is 10g:100mL:10g.

[0015] Furthermore, the carrier is one of mesoporous molecular sieve and nano-silica.

[0016] Beneficial effects of the present invention:

[0017] The process flow of the present invention is simple, and the reaction efficiency is improved by controlling the reaction conditions and adding a supported phase transfer catalyst in the process. The added supported phase transfer catalyst can, on the one hand, enable more complete contact between cyanamide and methyl chloroformate, and on the other hand, the quaternary amino group on the supported phase transfer catalyst dissociates into hydroxide ions, which are alkaline, and can better maintain the pH value of the system, keep the system stable, reduce the generation of by-products, improve the reaction efficiency, and improve the purity of the product. DETAILED DESCRIPTION

[0018] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts shall fall within the scope of protection of the present invention.

[0019] Example 1

[0020] This embodiment provides a process for synthesizing methyl cyanamide, comprising the following steps:

[0021] Mix the mesoporous molecular sieve with a 90% ethanol aqueous solution, add γ-methacryloxypropyltrimethoxysilane, set the temperature to 50°C, and react for 24 hours. After the reaction, filter, wash with alcohol, and vacuum dry to obtain a graftable carrier. The ratio of carrier, ethanol aqueous solution, and γ-methacryloxypropyltrimethoxysilane is 10g:100mL:10g.

[0022] A graftable carrier, toluene, methacryloylpropyl dimethylbenzyl ammonium chloride and azobisisobutyronitrile were mixed and stirred at 80°C for 7 hours under nitrogen protection. After the reaction, the catalyst was filtered and vacuum dried to obtain a supported catalyst. The amount ratio of the graftable carrier, toluene, methacryloylpropyl dimethylbenzyl ammonium chloride and azobisisobutyronitrile was 7g:100mL:2g:0.1g.

[0023] Cyanamide was diluted with water to a 6% mass fraction of cyanamide. Methyl chloroformate was then added. The pH of the reaction system was adjusted to 11 with sodium hydroxide. A supported phase transfer catalyst was added. The temperature was set to 45°C, and the reaction was stirred. The reaction was filtered and concentrated to obtain methyl cyanamide. The molar ratio of cyanamide to methyl chloroformate was 1:1.01. The amount of supported phase transfer catalyst added was 4% of the mass of cyanamide. The product had a purity of 99.7% and a yield of 86.5%.

[0024] Example 2

[0025] This embodiment provides a process for synthesizing methyl cyanamide, comprising the following steps:

[0026] Mix the mesoporous molecular sieve with a 90% ethanol aqueous solution, add γ-methacryloxypropyltrimethoxysilane, set the temperature to 50°C, and react for 24 hours. After the reaction, filter, wash with alcohol, and vacuum dry to obtain a graftable carrier. The ratio of carrier, ethanol aqueous solution, and γ-methacryloxypropyltrimethoxysilane is 10g:100mL:10g.

[0027] A graftable carrier, toluene, methacryloylpropyl dimethylbenzyl ammonium chloride and azobisisobutyronitrile were mixed and stirred at 80°C for 8 hours under nitrogen protection. After the reaction, the catalyst was filtered and vacuum dried to obtain a supported catalyst. The amount ratio of the graftable carrier, toluene, methacryloylpropyl dimethylbenzyl ammonium chloride and azobisisobutyronitrile was 7g:100mL:3g:0.1g.

[0028] Cyanamide was diluted with water to a 7% mass fraction of cyanamide. Methyl chloroformate was then added. The pH of the reaction system was adjusted to 10 with sodium hydroxide. A supported phase transfer catalyst was added. The reaction was set to 50°C with stirring, followed by filtration and concentration to obtain methyl cyanamide. The molar ratio of cyanamide to methyl chloroformate was 1:1.01. The amount of supported phase transfer catalyst added was 5% of the mass of cyanamide. The product had a purity of 99.6% and a yield of 85.8%.

[0029] Example 3

[0030] This embodiment provides a process for synthesizing methyl cyanamide, comprising the following steps:

[0031] Mix the mesoporous molecular sieve with a 90% ethanol aqueous solution, add γ-methacryloxypropyltrimethoxysilane, set the temperature to 50°C, and react for 24 hours. After the reaction, filter, wash with alcohol, and vacuum dry to obtain a graftable carrier. The ratio of carrier, ethanol aqueous solution, and γ-methacryloxypropyltrimethoxysilane is 10g:100mL:10g.

[0032] A graftable carrier, toluene, methacryloylpropyl dimethylbenzyl ammonium chloride and azobisisobutyronitrile were mixed and stirred at 80°C for 8 hours under nitrogen protection. After the reaction, the catalyst was filtered and vacuum dried to obtain a supported catalyst. The amount ratio of the graftable carrier, toluene, methacryloylpropyl dimethylbenzyl ammonium chloride and azobisisobutyronitrile was 8g:100mL:3g:0.1g.

[0033] Cyanamide was diluted with water to a 7% mass fraction of cyanamide. Methyl chloroformate was then added. The pH of the reaction system was adjusted to 9 with sodium hydroxide. A supported phase transfer catalyst was added. The temperature was set to 50°C, and the reaction was stirred. The reaction was filtered and concentrated to obtain methyl cyanamide. The molar ratio of cyanamide to methyl chloroformate was 1:1.01. The amount of supported phase transfer catalyst added was 5% of the mass of cyanamide. The product had a purity of 99.6% and a yield of 86.9%.

[0034] Example 4

[0035] Compared with Example 3, this example replaced the supported phase transfer catalyst with a supported phase transfer catalyst that had been reused 10 times, and the remaining raw materials and preparation process remained the same as Example 3. The product had a purity of 99.5% and a yield of 86.1%.

[0036] Comparative Example 1

[0037] Compared with Example 3, this comparative example did not add a supported phase transfer catalyst, and the remaining raw materials and preparation process remained the same as Example 3. The product had a purity of 93.4% and a yield of 81.5%.

[0038] The experimental results show that the addition of a supported phase transfer catalyst to the process of preparing methyl cyanamide can reduce the generation of by-products, improve reaction efficiency, and increase the purity of the product to over 99%.

[0039] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus.

[0040] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A process for synthesizing methyl cyanocarbamate, characterized in that: The steps include: The carrier and a 90% by volume ethanol aqueous solution were mixed, γ-methacryloyloxypropyltrimethoxysilane was added, the temperature was set at 50°C, the reaction was carried out for 24 hours, and after the reaction was completed, the mixture was filtered, washed with alcohol, and vacuum dried to obtain a graftable carrier; the amount ratio of the carrier, the ethanol aqueous solution, and γ-methacryloyloxypropyltrimethoxysilane was 10g:100mL:10g; the amount ratio of the graftable carrier, toluene, methacryloylpropyldimethylbenzyl ammonium chloride, and azobisisobutyronitrile was 7-8g:100mL:2-3g:0.1g; the graftable carrier, toluene, methacryloylpropyldimethylbenzyl ammonium chloride, and azobisisobutyronitrile were mixed, stirred at 80°C under nitrogen protection for 7-8 hours, and after the reaction was completed, the mixture was filtered and vacuum dried to obtain a supported catalyst; Cyanamide is diluted with water, and then methyl chloroformate is added. The pH value of the reaction system is adjusted to 9-11. A supported phase transfer catalyst is added, and the temperature is set to 45-50° C. The reaction is stirred to obtain methyl cyanamide. Cyanamide is diluted with water to a mass fraction of 6-7%.

2. The process for synthesizing methyl cyanamide according to claim 1, wherein The molar ratio of cyanamide to methyl chloroformate is 1:1.01; and the added amount of the supported phase transfer catalyst is 4-5% of the mass of the cyanamide.

3. The process for synthesizing methyl cyanamide according to claim 1, wherein Sodium hydroxide is selected as the pH regulator for adjusting the pH value of the reaction system.

4. The process for synthesizing methyl cyanamide according to claim 1, wherein: The carrier is one of mesoporous molecular sieve and nano silicon dioxide.