阅读说明：本技术 一种制备异硫氰酸酯的新方法 (Novel method for preparing isothiocyanate ) 是由 朱守记 于 2020-06-19 设计创作，主要内容包括：本发明涉及一种制备异硫氰酸酯的新方法,包括以下步骤：将有机伯胺和苯异硫氰酸酯加入到高沸点溶剂中,在氮气保护的条件下进行搅拌,反应温度保持100℃～150℃或加热回流、常压条件下反应1-9h,反应完成后,待反应液冷却,通过真空旋转蒸发除去溶剂,浓缩物经硅胶柱色谱提纯得异硫氰酸酯。本发明优点在于：1)本发明所使用的原料有机伯胺和苯异硫氰酸酯均是常见的化工原料,特别是苯异硫氰酸酯价廉易得；2)本发明反应条件较为温和,安全性高,温度一般在100℃～150℃,常压下反应；3)本发明工艺过程及后处理简单,易于操作,成本低,产品纯度高,工业化应用前景好。(The invention relates to a novel method for preparing isothiocyanate, which comprises the following steps: adding organic primary amine and benzene isothiocyanate into a high-boiling-point solvent, stirring under the protection of nitrogen, keeping the reaction temperature at 100-150 ℃ or heating, refluxing and reacting for 1-9h under normal pressure, cooling the reaction liquid after the reaction is finished, removing the solvent through vacuum rotary evaporation, and purifying the concentrate through silica gel column chromatography to obtain the isothiocyanate. The invention has the advantages that: 1) the raw materials organic primary amine and the raw materials benzeneisothiocyanate used in the invention are common chemical raw materials, and particularly the benzeneisothiocyanate is cheap and easy to obtain; 2) the reaction condition is mild, the safety is high, the temperature is generally 100-150 ℃, and the reaction is carried out under normal pressure; 3) the invention has simple process and post-treatment, easy operation, low cost, high product purity and good industrial application prospect.)

1. A preparation method of isothiocyanate shown in formula (I) is characterized by comprising the following steps: adding organic primary amine and benzene isothiocyanate into a high-boiling-point solvent, stirring under the protection of nitrogen, keeping the reaction temperature at 100-150 ℃, reacting for 1-9 hours under normal pressure, cooling the reaction liquid after the reaction is finished, removing the solvent through vacuum rotary evaporation, and purifying the concentrate through silica gel column chromatography to obtain the isothiocyanate;

RN＝C＝S(Ⅰ)；

in the general formula (I), R is one of the following,

2. the process for producing an isothiocyanate according to claim 1, wherein: the high boiling point solvent is at least one of toluene, p-xylene and o-xylene.

3. The process for producing an isothiocyanate according to claim 1, wherein: the reaction temperature is maintained at 100-150 ℃ and is changed into heating reflux.

Technical Field

The invention relates to a preparation method of isothiocyanate, in particular to a method for generating corresponding isothiocyanate by organic primary amine and benzene isothiocyanate through substitution reaction under the condition of high temperature.

Background

Isothiocyanate is an extremely important organic synthesis intermediate, can be used for synthesizing sulfur-containing, nitrogen-containing and other heterocyclic compounds with good biological activity, and is widely applied to the fields of pesticides, medicines and the like. At present, a large number of isothiocyanate compounds are found to have strong biological activities of bacteriostasis, tumor resistance and the like. For example, benzyl isothiocyanate, phenethyl isothiocyanate, have good bacteriostatic activity against Bacillus cereus (gram-positive bacteria), while 3-butenyl isothiocyanate, 4-pentenyl isothiocyanate, have potent bacteriostatic activity against Aeromonas hydrophila (Jang M, et al, Journal of food science,2010,75, M412-M416). 4-Methylsulfonylbutyhiocyanate can prevent the activation of proto-cancer cells and induce the production of detoxification enzymes (such as quinone reductase and glutathione S-transferase), and is effective in preventing the formation of mammary tumors in rats (Grubb C D et al, Plant Science (Shannon),2002,162, 0-152.).

Currently, many methods for preparing isothiocyanates exist. The organic primary amine compound is a common chemical raw material and is easy to obtain. Therefore, the method for preparing the isothiocyanate by taking the organic primary amine as the raw material has better industrial application prospect, and mainly relates to three different methods. The first method is to directly synthesize isothiocyanate (Lizhen et al, organic chemistry 2015,035, 1999-2003) by using organic primary amine and thiophosgene as raw materials, but the thiophosgene used as the raw material in the method is volatile and has high toxicity, and the product has potential safety hazard in the transportation and storage processes. The second method is that Organic primary amine and carbon disulfide form an intermediate dithioamino salt under the action of alkali, and further react with a desulfurization reagent to prepare isothiocyanate (Rince W, et al, Journal of Organic Chemistry,2007,72,3969-3971.), however, the method has harsh reaction conditions and complicated post-treatment, and the carbon disulfide is volatile and easy to explode. The third method is that organic primary amine reacts with phenylthiocarbamate to generate intermediate thiocarbamate, and the intermediate thiocarbamate is cracked into isothiocyanate (Synthesis,2013,44,1667-1674) under the condition of alkalinity or high temperature. Although phenyl thiocarbonate is less toxic than thiophosgene, it is expensive and not easy to develop.

In view of good biological activity of isothiocyanate and downstream products thereof and the defects of the existing preparation method of the compounds, the invention provides a method for preparing isothiocyanate by taking organic primary amine and benzene isothiocyanate as raw materials so as to lay a good foundation for developing isothiocyanate and downstream high-added-value products thereof with potential application value in the fields of medicines or pesticides and the like.

Disclosure of Invention

The present invention has been made to solve the above-mentioned problems occurring in the prior art, and an object of the present invention is to provide a novel method for producing an isothiocyanate ester.

In order to solve the technical problems, the technical scheme provided by the invention is as follows: a method for preparing isothiocyanate shown in a formula (I) comprises the following steps: adding organic primary amine and benzene isothiocyanate into a high-boiling-point solvent, stirring under the protection of nitrogen, keeping the reaction temperature at 100-150 ℃ or heating, refluxing and reacting for 1-9h under normal pressure, after the reaction is finished, cooling the reaction liquid, removing the solvent through vacuum rotary evaporation, and purifying the concentrate through silica gel column chromatography to obtain the isothiocyanate (RN ═ C ═ S);

RN＝C＝S(Ⅰ)；

reaction formula is

In the formula (I), R is one of the following:

CH₃CH₂CH₂CH₂-, formula (I) is an isothiocyanate, formula (II) is an organic primary amine.

As a preferable mode, the high boiling point solvent used is at least one of toluene, p-xylene and o-xylene.

The invention has the advantages that: 1) the raw materials organic primary amine and the raw materials benzeneisothiocyanate used in the invention are common chemical raw materials, and particularly the benzeneisothiocyanate is cheap and easy to obtain; 2) the reaction condition is mild, the safety is high, the temperature is generally 100-150 ℃, and the reaction is carried out under normal pressure; 3) the invention has simple process and post-treatment, easy operation, low cost, high product purity and good industrial application prospect.

Drawings

FIG. 1 is an infrared (FT-IR) analysis spectrum of 3-p-menthene-1-isothiocyanate as a substance of the present invention.

FIG. 2 shows the substance 3-p-menthene-1-isothio of the present inventionOf cyanate esters¹H nuclear magnetic resonance (¹H NMR) analytical profile.

FIG. 3 shows the preparation of 3-p-menthene-1-isothiocyanate of the present invention¹³C nuclear magnetic resonance (¹³C NMR) analysis pattern.

FIG. 4 is a mass spectrum (GC-MS) analysis spectrum of 3-p-menthene-1-isothiocyanate as a substance of the present invention.

In FIG. 1, the horizontal axis represents the wave number (cm)^-1) The ordinate represents transmittance (%).

Detailed Description