阅读说明：本技术 一种异氰酸甲酯的制备方法 (Preparation method of methyl isocyanate ) 是由 刘兴超 朱占元 杨国军 孔凯丽 刘文杰 于 2020-04-25 设计创作，主要内容包括：本发明公开一种异氰酸甲酯的制备方法,包括以下步骤：氮气保护下,将甲胺盐酸盐和三光气溶于有机溶剂中,搅拌降温,滴加有机碱溶液,滴毕,保温反应,反应毕,常压蒸馏,控制顶温温度,收集馏分,得到异氰酸甲酯。本方法避免传统工艺中光气的使用,采用三光气与甲胺反应,安全性较高,有利于操作者防护,操作便利,此方法不局限于实验室,不需要耐压耐高温的特种设备,产能可达百公斤级,适用于精细化工企业如医药企业。(The invention discloses a preparation method of methyl isocyanate, which comprises the following steps: under the protection of nitrogen, dissolving methylamine hydrochloride and triphosgene in an organic solvent, stirring and cooling, dropwise adding an organic alkali solution, keeping the temperature for reaction after dropwise adding, distilling at normal pressure after reaction, controlling the top temperature, and collecting fractions to obtain methyl isocyanate. The method avoids using phosgene in the traditional process, adopts triphosgene to react with methylamine, has higher safety, is beneficial to the protection of operators, is convenient to operate, is not limited in a laboratory, does not need special pressure-resistant and high-temperature-resistant equipment, has the capacity of reaching the hundred kilogram level, and is suitable for fine chemical enterprises such as pharmaceutical enterprises.)

1. A preparation method of methyl isocyanate is characterized by comprising the following steps:

under the protection of nitrogen, dissolving methylamine hydrochloride and triphosgene in an organic solvent, stirring and cooling, dropwise adding an organic alkali solution, keeping the temperature for reaction after dropwise adding, distilling at normal pressure after reaction, controlling the top temperature, and collecting fractions to obtain methyl isocyanate.

2. The process for producing methyl isocyanate according to claim 1, wherein: the molar ratio of the methylamine hydrochloride to the triphosgene is 1-5: 1, and the molar ratio of the methylamine hydrochloride to the organic base is 1-5: 1.

3. The process for producing methyl isocyanate according to any one of claims 1 or 2, characterized in that: the organic solvent is halogenated aromatic hydrocarbon with high boiling point.

4. The process for producing methyl isocyanate according to claim 3, wherein: the organic solvent is one or a mixture of more than two of chlorobenzene, bromobenzene, dichlorobenzene or dibromobenzene.

5. The process for producing methyl isocyanate according to claim 1, wherein: the dropping temperature is-5 ℃, the heat preservation reaction temperature is-5-20 ℃, and the top temperature is 40-50 ℃.

6. The process for producing methyl isocyanate according to any one of claims 1 or 2, characterized in that: the organic base is one or a mixture of more than two of triethylamine, pyridine, diisopropylethylamine or DBU.

7. The process for producing methyl isocyanate according to claim 1, wherein: the heat preservation reaction time is 1-10 h.

Technical Field

The invention belongs to the technical field of organic synthesis, relates to synthesis of an organic intermediate, and particularly relates to a preparation method of methyl isocyanate.

Background

Methyl isocyanate is one of important varieties in monoalkyl isocyanates and has wide application. Methyl isocyanate is often used in the polymer industry, plastic industry, pesticide industry, pharmaceutical industry, and other fields. In the polymer and plastics industries, methyl isocyanate is a monomer for the synthesis of polyisocyanates, polycyanoesters, polyureas, polymeric binders; in the agrochemical industry, methyl isocyanate is an important intermediate in the manufacture of insecticides such as carbaryl, pyrantel and herbicides such as prosulfocarb, molinate and the like; in the pharmaceutical industry, methyl isocyanate is an important intermediate for the preparation of anti-glioma temozolomide.

There are various synthetic routes for methyl isocyanate. The currently common industrial method is a methylamino formyl chloride method, methylamine and phosgene are firstly reacted to obtain an intermediate methyl amino formyl chloride, then a molecule of hydrogen chloride is removed to obtain methyl isocyanate, and the method needs special pressure-resistant and high-temperature-resistant equipment. In addition, there are various laboratory scale synthesis methods such as hoffman degradation method, but no industrialization has been achieved. Therefore, it is particularly necessary to find a process for preparing methyl isocyanate which allows for scale-up production.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a preparation method of methyl isocyanate. The method avoids using highly toxic substances such as phosgene and the like, is simple and convenient to operate, easy to control and high in product purity, and is suitable for preparing methyl isocyanate in a scale of hundreds of kilograms.

The invention is realized by the following technical scheme:

a preparation method of methyl isocyanate comprises the following steps:

under the protection of nitrogen, dissolving methylamine hydrochloride and triphosgene in an organic solvent, stirring and cooling, dropwise adding an organic alkali solution, keeping the temperature for reaction after dropwise adding, distilling at normal pressure after reaction, controlling the top temperature, and collecting fractions to obtain methyl isocyanate.

The reaction equation is:

。

the invention further improves the scheme as follows:

the molar ratio of the methylamine hydrochloride to the triphosgene is 1-5: 1, and the molar ratio of the methylamine hydrochloride to the organic base is 1-5: 1.

The organic solvent is halogenated aromatic hydrocarbon with high boiling point.

The organic solvent is one or a mixture of more than two of chlorobenzene, bromobenzene, dichlorobenzene or dibromobenzene.

The dropping temperature is-5 ℃, the heat preservation reaction temperature is-5-20 ℃, and the top temperature is 40-50 ℃.

The organic base is one or a mixture of more than two of triethylamine, pyridine, diisopropylethylamine or DBU.

The heat preservation reaction time is 1-10 h.

The invention has the beneficial effects that:

1) the use of phosgene in the traditional process is avoided, the process adopts the reaction of triphosgene and methylamine hydrochloride, the safety is higher, the protection of operators is facilitated, and the operation is convenient.

2) The process is not limited to a laboratory, special pressure-resistant and high-temperature-resistant equipment is not needed, the capacity can reach hundreds of kilograms, and the process is suitable for fine chemical engineering enterprises such as pharmaceutical enterprises.

Detailed Description

Example 1

Under the protection of nitrogen, triphosgene (440.7g,1.49mol) and methylamine hydrochloride (200g, 2.97mol) are dissolved in 500mL of chlorobenzene, stirred, cooled, the internal temperature is reduced to-2 ℃, a chlorobenzene (100mL) solution of pyridine (117.9g,1.49mol) is slowly dripped, the temperature is controlled not to exceed 5 ℃ in the dripping process, and the temperature is kept at 5 ℃ for 4 hours after dripping. After the reaction is finished, distilling at normal pressure, controlling the top temperature to be 42-46 ℃, and collecting fractions to obtain 120g of methyl isocyanate with the yield of 71%.

Example 2

Under the protection of nitrogen, triphosgene (440.7g,1.49mol) and methylamine hydrochloride (200g, 2.97mol) are dissolved in 500mL bromobenzene, stirred, cooled, the internal temperature is reduced to-2 ℃, and a chlorobenzene (100mL) solution of pyridine (117.9g,1.49mol) is slowly dripped, the temperature is controlled not to exceed 5 ℃ in the dripping process, and the temperature is kept at 10 ℃ for 4 hours after dripping. After the reaction is finished, distilling at normal pressure, controlling the top temperature to be 42-46 ℃, and collecting fractions to obtain 105g of methyl isocyanate with the yield of 62%.

Example 3

Under the protection of nitrogen, triphosgene (881.3g,2.97mol) and methylamine hydrochloride (200g, 2.97mol) are dissolved in 1000mL of chlorobenzene, stirred, cooled, the internal temperature is reduced to-2 ℃, a chlorobenzene (200mL) solution of pyridine (234.9g,2.97mol) is slowly dripped, the temperature is controlled not to exceed 5 ℃ in the dripping process, and the heat preservation reaction is carried out for 4 hours at 10 ℃. After the reaction is finished, distilling at normal pressure, controlling the top temperature to be 42-46 ℃, and collecting fractions to obtain 130g of methyl isocyanate with the yield of 77%.

Example 4

Under the protection of nitrogen, triphosgene (440.7g,1.49mol) and methylamine hydrochloride (200g, 2.97mol) are dissolved in 500mL of chlorobenzene, stirred, cooled, the internal temperature is reduced to 0 ℃, and a chlorobenzene (100mL) solution of pyridine (117.9g,1.49mol) is slowly dripped, wherein the temperature is controlled not to exceed 5 ℃ in the dripping process, and the heat preservation reaction is carried out for 6 hours at 10 ℃. After the reaction is finished, distilling at normal pressure, controlling the top temperature to be 42-46 ℃, and collecting fractions to obtain 123g of methyl isocyanate with the yield of 73%.

Example 5

Under the protection of nitrogen, triphosgene (440.7g,1.49mol) and methylamine hydrochloride (200g, 2.97mol) are dissolved in 500mL of chlorobenzene, stirred, cooled, the internal temperature is reduced to-2 ℃, a chlorobenzene (100mL) solution of diisopropylethylamine (192.6g,1.49mol) is slowly dripped, the temperature is controlled not to exceed 5 ℃ in the dripping process, and the temperature is kept at 20 ℃ for 4 hours after dripping. After the reaction is finished, distilling at normal pressure, controlling the top temperature to be 42-46 ℃, and collecting fractions to obtain 110g of methyl isocyanate with the yield of 65%.

Example 6

Under the protection of nitrogen, triphosgene (219.7kg) and methylamine hydrochloride (100kg) are dissolved in 250L chlorobenzene, stirred and cooled, the internal temperature is reduced to-2 ℃, a chlorobenzene (50L) solution of pyridine (58.6kg) is slowly dripped, the temperature is controlled not to exceed 5 ℃ in the dripping process, and the temperature is kept at 5 ℃ for 6 hours after dripping is finished. After the reaction is finished, distilling at normal pressure, controlling the top temperature to be 42-46 ℃, and collecting fractions to obtain 62kg of methyl isocyanate with the yield of 73.3%.