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Solvent-free Synthesis of 2-Aminothiazole |96-50-4| and Its Derivatives

2017-03-13 来源:亚科官网
13 March 2017
  Thiazole ring is an important structural unit, the amino thiazole compounds play an important role in the anti-bacterial, anti-inflammatory, anti-allergy, and lowering blood pressure drugs and so on. 2-aminothiazole and its derivatives have been widely used in many fields such as industrial production and drug research and development because of the biological activity of broad-spectrum antimicrobial sterilization, which has important value [1]. In the synthesis of 2-aminothiazole and its derivatives, the solvent-free method has received more attentions in recent years. This paper will introduce a solvent-free and catalyst-free synthesis method.
  The present method for synthesizing 2-aminothiazole derivatives from ketones (aldehydes) and (substituted) thiourea are as follows: (a) classical method: Direct reaction of iodine, thiourea and ketone; (b) Hantzsch's: Halogenated ketone (aldehydes) and substituted thiourea react in different solvents; (c) solid phase synthesis [2]. The reaction time of classical method is long, it generally takes more than ten hours, Hantzsch's method is high cost, and easy to cause pollution, the post-processing is also more complex; solid phase synthesis method is relatively new, but the scope of application need to be further expanded. In order to achieve the goal of green chemistry and increase the yield, the researchers [3] synthesized 2-substituted thiazole derivatives through the Hantzsch's reaction with a halogenated ketone or thiourea or substituted thiourea in a solvent-free, catalyst-free condition, which greatly reduce the amount of thiourea or substituted thiourea.
无溶剂法绿色合成2-氨基噻唑及其衍生物
  The specific steps are as follows: put halogenate ketone, thiourea or substituted thiourea in a dry round bottom flask, install reflux condenser tube, place it in 100°C oil bath for heating reaction, tracking the reaction until the raw materials are disappeared. The mixture was cooled to room temperature, transferred to 10 mL cold water with a small amount of ethanol, neutralized with a small amount of NH4HCO3 aqueous solution, and the solid was precipitated, filtered, washed with an aqueous 40% ethanol solution and dried. The crude product was washed and recrystallized with 70% ethanol solution.
  The researchers also explored and analysed the conditions that affect the reaction, the results are as follows:
  Reaction temperature: The ratio of α-bromoacetophenone and thiourea or thiourea is 1:1.5, and the reaction can proceed smoothly at 100°C. And then the reaction temperature is increased, the yield of the product is not improved; if the reaction temperature is lower than 100℃, the reaction time is prolonged and the yield is reduced.
  Ingredient ratio: When the reaction temperature is 100℃, when n(α-bromoacetophenone): n(thiourea or substituted thiourea) is 1:2.0, 1:1.5 and 1:1.0, the yield of 2-amino-4-phenylthiazole were 91%, 90% and 94%, respectively. Increasing the amount of thiourea or substituted thiourea, the yield of 2-amino-4-phenylthiazole decreased slightly.
  Substrate’s structure: On the basis of the selected heating temperature and the ratio of raw materials, in the absence of solvent and catalyst conditions, with halogenate ketone, thiourea or thiosemicarb as raw material, when bromoaryl ethyl ketone containing the electron-withdrawing group is the starting material, the yield of 2-aminothiazole is higher than that of the electron-containing group.
  The use of organic solvents in the synthesis of organic compounds is more common, but the process is complex, and the cost is high, and seriously pollute the environment. The solvent-free and catalyst-free method is an effective method for synthesizing 2-aminothiazole derivatives, which has the characteristics of mild reaction conditions, fast reaction speed, high product yield and simple operation.
References
[1] Hu Aixi, He Limin, Xia Lin, et al. Synthesis of 2-Aminothiazole Compounds. Chinese Journal of Medicinal Chemistry, 2006, 16, 229.
[2] Cheng Chongyun, Jiang Fengchao. Synthesis of 2-Aminothiazole Derivatives by Microwave Irradiation in Solvent-free Conditions. Organic Chemistry, 2005 (7): 826-829.
[3] Wang Shuxiang, Wu Qianqian, Duan Jie, etc. Solvent-free synthesis of 2-aminothiazole and 2-methyl thiazole derivatives. Journal of Hebei University. 2010, 30, 53-57.
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Edited by the Editorial Office of Suzhou Yacoo Science Co., Ltd.