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The preparation process of cytosine

A preparation process, cytosine technology, applied in the field of cytosine preparation technology, can solve the problems of cytosine, such as expensive raw materials, long production cycle, environmental pollution, etc., to reduce labor operations and energy consumption, short production cycle, The effect of shortening the reaction time

Active Publication Date: 2016-08-17
ZHEJIANG XIANFENG TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existing synthetic methods of cytosine mainly include functional group conversion method and Pinner synthesis method; functional group conversion method is to synthesize cytosine with 2-mercapto-6-pyrimidinone as raw material, or use uracil or 2,4-dithiopyrimidine as Substrate, synthesize cytosine through processes such as hydrolysis; This synthesis method has the disadvantages of complicated operation, long production cycle, many by-products and serious environmental pollution; Pinner synthesis method is based on 3-alkoxyacrylonitrile or 3-alkoxyacrylonitrile , 3-alkoxypropionitrile is used as a raw material to synthesize cytosine, which is the main method for industrial production of cytosine at present. 3-alkoxyacrylonitrile or 3,3-alkoxypropionitrile is generally passed through the action of acetonitrile on sodium alkoxide It is synthesized by reacting with CO to generate 3-hydroxyacrylonitrile sodium salt, and then reacting with hydrochloric acid alcohol solution; however, its raw material price of cytosine produced by this method is relatively expensive, and the total yield is relatively low; therefore it is necessary to improve

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  • The preparation process of cytosine

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Effect test

Embodiment 1

[0014] Example 1: A preparation process of cytosine, the preparation process is as follows: put sodium methoxide (24.3g, 0.45mol) and 180mL methanol into the reaction kettle and stir evenly; put in 3-hydroxyacrylonitrile sodium salt (27.3g , 0.3mol) and urea (21.6g, 0.36mol); the temperature was raised to 60°C and the cyclization reaction was carried out for 10 hours to obtain a cyclization reaction solution; methanol was distilled off under normal pressure, and 170mL of water was slowly added to the residue; dropwise Add concentrated hydrochloric acid to adjust the pH value. When the pH is 7-7.5, cool to 10°C; after cooling, filter, wash with water, and dry to obtain 30.1 g of cytosine with a yield of 90.3% and an HPLC content of 99.4%.

Embodiment 2

[0015] Example 2: Sodium methoxide (17.8g, 0.33mol) and 180mL methanol were put into the reaction kettle and stirred evenly; 3-hydroxyacrylonitrile sodium salt (27.3g, 0.3mol) and urea monosodium salt (36.9g, 0.45mol); the temperature was raised to 40°C and the ring-closure reaction was carried out for 6 hours; the methanol was distilled off under normal pressure, and 180mL of water was slowly added to the residue; the pH value was adjusted by adding concentrated hydrochloric acid dropwise. Cool to 15°C; after cooling, filter, wash with water, and dry to obtain 30.5 g of cytosine with a yield of 91.5% and an HPLC content of 99.3%.

Embodiment 3

[0016] Example 3: Sodium methoxide (17.8g, 0.33mol) and 180mL methanol were put into the reaction kettle and stirred evenly; 3-hydroxyacrylonitrile sodium salt (27.3g, 0.3mol) and urea monopotassium salt (44.2g, 0.45mol); the temperature was raised to 40°C and the ring-closure reaction was carried out for 6 hours; the methanol was distilled off under normal pressure, and 180mL of water was slowly added to the residue; the pH value was adjusted by adding concentrated hydrochloric acid dropwise. Cool to 15°C; after cooling, filter, wash with water, and dry to obtain 30.5 g of cytosine with a yield of 91.5% and an HPLC content of 99.2%.

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Abstract

The invention discloses a technology for preparing cytosine. The technology comprises the following steps: selecting a 3-hydroxyl acrylonitrile sodium salt and urea or a urea alkali metal salt as raw materials; firstly, feeding a catalyst and an organic solvent to a reaction kettle in preparation; sequentially adding 3-hydroxyl acrylonitrile sodium salt and urea or urea alkali metal salt after evenly agitating; heating up to 40-90 DEG C and carrying out cyclization reaction for 6-10 hours, so as to obtain cyclization reaction liquid; evaporating out a solvent in the cyclization reaction liquid; adding water to the residue to dissolve; dropwise adding a hydrochloric acid to adjust the pH value; cooling when the pH achieves 7.0-7.5; filtering, washing and baking after cooling to 10-15 DEG C, so as to obtain the cytosine. The technology has the advantages of being simpler in processing step, short in production cycle, low in cost, and high in raw material conversion rate, the labor operation and energy consumption are greatly reduced, and the synthesized product is good in quality, high in yield, convenient in post-treatment, and applicable to industrial production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical intermediate synthesis, and in particular relates to a preparation process of cytosine. Background technique [0002] Cytosine is 4-amino-2-hydroxypyrimidine, which is one of the pyrimidine bases in nucleic acid, and is also an important intermediate in fine chemicals, pesticides and medicine; especially in the field of medicine, it is mainly used to synthesize anti-AIDS drugs and anti-hepatitis B drugs Mivudine, anticancer drugs gemcitabine, enoxitabine, and 5-fluorocytosine, etc. The existing synthetic methods of cytosine mainly include functional group conversion method and Pinner synthesis method; functional group conversion method is to synthesize cytosine with 2-mercapto-6-pyrimidinone as raw material, or use uracil or 2,4-dithiopyrimidine as Substrate, synthesize cytosine through processes such as hydrolysis; This synthesis method has the disadvantages of complicated operation, long...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/47
CPCC07D239/47
Inventor 何建兵肖木杰张文灿李明高飞飞
Owner ZHEJIANG XIANFENG TECH