Synthesis And Structure Characteristics Of 8-hydroxyquinoline Derivatives

At present the synthesis of bio-active quinoline derivatives is one of the hot areas of chemistry and medicine.In recent years,many quinoline derivatives have been synthesized,which were more and more used as new organic ligands and drug intermediates due to their special molecular structures.Quinoline derivatives play so important role in various fields that more and more scientists pay attention to their study.For example,8-hydroxyquinoline can be used to synthesize some biological active and pharmacological active compounds with sterilization,antibacterial,antihypertensive,anti-inflammatory analgesic,allergy,antidepressant,antitumor,and etc.In the field of medicine,quinoline derivatives were originally used as antimalarial drugs,made brilliant achievements.It is a major breakthrough in the history of antimalarial drugs.The antimalarial mechanism is changing the parasite growth environment to inhibit the activity of lysosomal enzymes;interaction with DNA double helix chain or inhibiting DNA and RNA polymerase to inhibit parasite value-added,have side effects on the malaria parasite.In this dissertation,we synthesized series quinoline derivatives taking 8-hydroxyquinoline(8-OHQ)as starting materials,studied their various chemical and physical properties.Because of no relational literature reported,we proposed two synthetic routes.1)8-hydroxyquinoline as raw material,reacted with ethyl bromoactate under basic condition to get intermediates ethyl ester,then reacted stepwise with epichlorohydrin and ammonia,underwent ammonia ester exchange to obtain target products finally.2)8-hydroxyquinoline as raw material,reacted with ethyl bromoactate under basic condition to get intermediates ethyl ester,then reacted with 1,3-diamino-2-propanol to get immediate,which underwent ammonia ester exchange with various acids to obtain eight similar target products.These 8-hydroxyquinoline derivatives were structurely characterized by NMR and Mass spectroscopy.The result revealed that the yield in step 3 of route 1 was less than 10%,the product was unstable,and metamorphosed easily.Correspondingly,there were three steps in route 2,and the yield of each step was high.The overall yield was about20%.Eventually we synthesized 8-hydroxyquinoline derivatives by route 2.To optimize the route,a series of experiments were examined,feeding ratio,reaction temperature,reaction time of substitution reaction,ammonia ester exchange reaction and condensation reaction have been tested,a suitable condition was found to synthesize 8-hydroxyquinoline derivatives.