Background and overview[1][2]
Benzoyl isocyanate is an organic intermediate that can be used to prepare urea compounds and can be obtained by the reaction of benzamide and triphosgene.
Preparation[1-2]
The synthesis methods of arylformyl isocyanate in the prior art mainly include 1. Synthesis using arylformyl chloride and isocyanate. This method has high synthesis cost. 2. Use aryl formamide and oxalyl chloride to synthesize. This method is widely used in production. However, the atom economy of this method is not high, resulting in high production costs. 3. It is synthesized from aryl formamide and phosgene as raw materials. The production cost of this process is low, but the disadvantage is that the phosgene used is a highly toxic gas. It was once used in the manufacture of poison gas bombs. Its production and use are strictly restricted internationally, especially after the 9.11 incident in the United States. The restrictions became even stricter.
In our country, phosgene is a particularly highly toxic substance produced and used at designated locations and is not allowed to be transported. In addition, this reaction requires equipment with high air tightness, multiple safety precautions, and high investment. Therefore, it is almost impossible for ordinary enterprises to use phosgene to produce arylformyl isocyanate.
Method 1, CN201810469886.2 overcomes the shortcomings of using oxalyl chloride or phosgene in the existing technology, and provides a safe and reliable synthesis method of arylformyl isocyanate with high yield, low cost and less waste. Examples are as follows:
In a four-necked flask equipped with a mechanical stirrer, thermometer, constant pressure dropping funnel, and reflux condenser, add 2.97g bis(trichloromethyl) carbonate and 20ml ethyl acetate at -5~5°C. Mix and stir. Dissolve 7.27g of benzamide in 30ml of ethyl acetate solution through a constant pressure dropping funnel, and slowly drop it into the above solution. The dropping process is at a low temperature of -5~5°C. After adding, stir for 30 minutes, slowly raise the temperature to the high temperature stage of 75~80℃, and add dropwise a solution of 2.97g bis(trichloromethyl)carbonate dissolved in 20ml ethyl acetate at this reaction temperature, for 3~3.5 hours After the addition, continue the reaction at this temperature for 2 hours. After the reaction, the ethyl acetate is recovered, and then distilled under reduced pressure to obtain 7.93g of benzoyl isocyanate with a yield of 89.89%. The purity of the product is 98.34% as measured by GC. Nuclear magnetic resonance spectrum (BRUKE): 1H NMR (300MHz, CDCl3): δ (ppm) 7.99-8.05 (t, 2H), 7.71-7.78 (m, 1H),7.59-7.64(t,2H).
Method 2,
Under cooling in an ice-water bath, a mixed solution of benzoyl urea (0.73g, 6.0mmol) in 1,2-dichloroethane (7mL) was slowly added dropwise to oxalyl chloride (0.94g, 7.5mmol) and dried. In a solution of 1,2-dichloroethane (7mL), control the dropping speed (2 drops/second). After the addition is completed, stir at room temperature for 1 hour, raise the temperature to 50°C and keep stirring for 17 hours, leave it to room temperature, and evaporate the solvent. An oily substance was obtained, and then fractionated under reduced pressure to obtain 0.70g of colorless liquid benzoyl isocyanate, with a yield of 79.3%.
Main reference materials
[1] CN201810469886.2 A synthesis method of arylformyl isocyanate
[2] CN201610030488.1 Arylurea-coupled quinazoline compounds and preparation methods, pharmaceutical compositions and pharmaceutical uses
