Improved Process For The Synthesis Of1,4,7,10-Tetraazacyclododecane And Its Derivatives

Due to the unique spatial structure and excellent coordination ability of macrocyclic polyamines, it can coordinate with mrtal ions, orgnic cations, organic anions, neutral molecules, so it is excellent coordination abilityligands. Therefore it can form a variety of coordination complex, and have extensive use of these complexes in the emerging field of molecular recognition, artificial enzyme, and medical diagnosis, etc.This paper firstly introduces the use of1,4,7,10-Tetraazacyclododecane(cyclen) and its derivatives, and then describes the preparation methods of cyclen, such as Stetter method, Richman-Atkins method, Weisman method, Glyoxal condensation reaction, diethyl oxalate condensation reaction and amide acetal method. Focus on the modifying and optimizing the procedures of1,4,7,10-Tetraazacyclododecane,1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid,1,4,7,10-Tetrabenzyl-1,4,7,10-tetraazacyclododecane.This thesis is following the technical guideline for synthesizing process of chemical substances, comprehensive consideration of the literature synthesis routes. From the aspect of the economic benefits, environmental benefits and the feasibility of the operation, eventually selected the most suitable synthetic route for industrial production. Base on the proposed synthetic route, this thesis will focus on the following two aspects:1. A series of single factor experiments. While other conditions remain unchanged, examine certain factors (such as raw material selection, molar ratio of reaction materials, solvent selection, feeding sequence, the feed ratio, catalyst, reaction temperature, reaction time, the number of washing in post-processing, crystallization temperature, recycling of the unreactioned raw materials, purification of the products, solvent recovery ease of the operation, security, etc.)to the product quality and yield of the reaction. And thus help us find out the best reaction conditions and a suitable post-processing method.2. A series of destructive tests, such as the tolerance range of raw materials or a few intermediates or impurities, the scope of the feed ration, reaction time, temperature changes drying time, ect., have implemented to analysise their influence on the quality and yield of the product.In conclusion, this thesis has optimized the reaction conditions and post-processing, simplified the reaction operation, reduced the production cost, improved the yield and quality of the products, finded out a adaptived industrial synthetic process.