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A kind of synthetic method of fluoroacetonitrile

A synthesis method, the technology of fluoroacetonitrile, applied in the field of synthesis of fluoroacetonitrile, can solve the problems of long reaction steps, environmental pollution, large production loss, etc., and achieve the effects of mild reaction conditions, shortened process route, and low production cost

Active Publication Date: 2016-05-18
杭州拜善晟生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The traditional synthesis method of fluoroacetonitrile is to obtain p-toluenesulfonyl-protected hydroxyacetonitrile through the reaction of hydroxyacetonitrile and p-toluenesulfonyl chloride, and then react with potassium fluoride to obtain the target product. The reaction steps of this route are relatively long, and the production loss of each step will be Large and polluting, its waste discharge will cause environmental pollution
The second method is to use the flowing afterglow (flowing afterglow) device, chloroacetonitrile and gaseous fluoride ion generation S N 2 reaction, the route yield is low, not practical; the third method, using fluoroacetamide, dehydration under the condition of phosphorus pentoxide, needs to prepare fluoroacetamide in advance. In addition, hydroxyacetonitrile is a highly regulated substance Drugs, the use of which as raw materials has certain restrictions on industrial production

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] 1. At room temperature, add 1.2Kg of bromoacetonitrile and 500g of anhydrous potassium fluoride into a 3L reaction flask, add 600ml of glycerin, turn on the electric stirrer, and start heating, the temperature rises to 74°C, and react for 5.5h.

[0021] 2. After the above reaction is completed, cool to 58°C, install a distillation device, heat up to 100°C, and distill, and cool the contact bottle with dry ice until no liquid flows out; the yield of the product in this step is 95.2%, and the purity reaches 95.8%.

[0022] 3. The above product was placed in a 500ml single-necked bottle, distilled at 110°C under normal pressure, and the fraction at 78-80°C was collected, and the contact bottle was cooled with acetone to obtain fluoroacetonitrile with a purity of 99.5%.

Embodiment 2

[0024] 1. At room temperature, add 1Kg of bromoacetonitrile and 480g of anhydrous sodium fluoride to a 3-liter reaction flask, add 600ml of dimethyl fumarate, turn on the electric stirrer, and start heating, and the temperature rises to 83 °C, react for 3.5h.

[0025] 2. After the above reaction is completed, cool to 50°C, install a distillation device, heat up to 120°C, and distill, and cool the contact bottle with dry ice until no liquid flows out. This step product yield is 96%, and purity has reached 96.3%.

[0026] 3. The above product was placed in a 500ml single-necked bottle, distilled at 110°C under normal pressure, and the fraction at 78-80°C was collected. The liquid contact bottle was cooled with an acetone bath to obtain fluoroacetonitrile with a purity of 99.8%.

Embodiment 3

[0028] 1. At room temperature, add 1.3Kg of chloroacetonitrile and 580g of anhydrous lithium fluoride into a 3-liter reaction flask, add 600ml of ethylene glycol, turn on the electric stirrer, and start heating, and the temperature rises to 100°C. Reaction 6h.

[0029] 2. After the above reaction is completed, cool to 52°C, install a distillation device, heat up to 110°C, and distill, and cool the contact bottle with dry ice until no liquid flows out. The product yield of this step is 95.4%, and the purity has reached 96.1%.

[0030] 3. The above product was placed in a 500ml single-necked bottle, distilled at 120°C under normal pressure, and the fraction at 78-80°C was collected, and the contact bottle was cooled with an acetone bath to obtain fluoroacetonitrile with a purity of 99.8%.

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Abstract

The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing fluoroacetonitrile. The method comprises the following steps: performing substitution reaction on an acetonitrile derivative and inorganic fluoride salt in a polar solvent, and distilling and purifying for multiple times, thereby obtaining a high-purity product fluoroacetonitrile, wherein the formula of the substation reaction is YF+XCH2CN->FCH2CN+YX. According to the method, the acetonitrile derivative and the inorganic fluoride salt are adopted to react to obtain a target product at one time, virulent raw materials are avoided, the process route is shortened, and the yield is high; as the polar organic solvent which is low in price, easy to obtain and environment-friendly is adopted, environment pollution is avoided; the method is conductive to achieving industrialization production of fluoroacetonitrile, is gentle in reaction condition, low in production cost, high in yield and environment-friendly.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a synthesis method of fluoroacetonitrile. Background technique [0002] Fluoroacetonitrile is a pharmaceutical intermediate, widely used in the synthesis of pesticides and pharmaceutical products, and has huge potential market value. For example: the reaction of fluoroacetonitrile and tert-butyl acetic acid produces tert-butyl-3-amino-4-fluoro-crotonate, which undergoes Borch reduction under acidic conditions to generate 3-amino-4-fluorobutyric acid, 3 -Amino-4-fluorobutyric acid can be used to treat diseases caused by nervous system excitation and inhibition disorders; its benzindole derivatives can be used as 5HT3 receptor antagonists; fluoroacetonitrile is used to synthesize fluorocytosine and its derivatives, which are widely used It is used in anticancer compositions; in addition, fluoroacetonitrile is also an important intermediate for the synthesis of α-fluori...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C253/30C07C255/10
Inventor 王喆明杨叶伟江世坤
Owner 杭州拜善晟生物科技有限公司