Research On Reaction Of Guanidine Transformation Through Arylsulfonyl-Activated Thioureas

Guanidine is an important nitrogen-containing organic compound, which widely existed in natural products such as protein, nucleic acid and folic acid, micro quantity in plenty of plants, animals and human such as radish, sugar beet, rice husk, mushroom and bean etc. Guanidine is a kind of strong organic base which shows biological activity, and the neutral guanidine can transform to a stable protonated guanidine ion with a positive charge in the pH of the physiological medium. Guanidine functional group can easily form hydrogen bonds, and has high stability and strong physiological activity. For the amidogen in guanidine can neutralize the acid to form dissoluble salt, the drug which contains guanidinium group not only can be easily transported in vivo, but also has good selectivity in absorbing and osmosis, and it plays important role in many kinds of medicines such as antihypertensive, antiviral and hypoglycemic drugs. Because of strong basicity, high stability, fine biological activity of guanidine compounds, it becomes wider and wider in the application fields, and provoke the chemists and pharmacists great interests in the synthesis and application of guanidine.Iodine is a kind of purplish black with metallic luster crystal. It is widely used in many kinds of organic reactions as a catalyst because of its inexpensive, secure and low toxicity. It has advantages of high yield, short reaction time and high selectivity in iodine catalyzed organic reactions, which is an environmental friendly reagent, and has become an active field in organic chemistry.This thesis divided into three parts. The first part of the thesis summarized the application and synthesis of guanidine. Guanidine plays a very important role in the applications of antibacterial agents, drugs, natural products, molecular recognition and catalysis in organic reactions. The extensive applications and remarkable efficacy of the guanidine urged the development of the high efficiency and environmental protection in synthesis of guanidine. This thesis summarized various routes of the preparations of the guanidine and its derivatives such as thiourea, isothiourea, carbodiimides and pyrazole-1-carboximidamides. Particularly, the catalysts of Mukaiyama reagent, EDCI, and HgCl2 in thiourea were emphasized.The second part was the core of the thesis, which explored the iodine-mediated guanidines formation Pbf activated thioureas. This part summarized the application of iodine in organic reactions as a catalyst, including iodine cyclization reaction, the introduction of protecting group reaction, deprotection group reaction and alcohol, aldehyde oxidation to esters, nitriles amines. Pbf-Cl(2,2,4,6,7-pentamethyldi-hydrobenzofuran-5-sulfonyl chloride) was synthesized through two-step reactions with 1,3,5-trimethylphenol as the starting material. Then the ammonia and the triphosgene were used to prepare Pbf-NCS, which was important to synthesis of various thioureas. Pbf-NCS could react with varies of primary amines and secondary amines to obtain Pbf activated thioureas. The thioureas which were made of Pbf-NCS and primary amine can form guanidine through carbodiimide intermediate in the presence of iodine. Aromatic amines with strong electron-withdrawing substituted group such as nitro group can not react with Pbf thioureas. We obtained N-Pbf-N′,N′′-disubstituted guanidine or N-Pbf-N′,N′′,N′′′-trisubstituted guanidine in the presence of iodine. The structures of the products were identified by elemental analysis, 1H NMR, 13C NMR and MS analysis, which were conformed the expected structures. We also compared the desulfurization ability of the iodine in the guanidinylation process to the Mukaiyama reagent and EDCI. We concluded that usually iodine can replace the Mukaiyama reagent or EDCI as an alternative low cost and low toxicity reagent in guanidinylation reaction with Pbf-activated thiourea.In the third part of the thesis, electron-drawing group activated thioureas guanidinylation was discussed, and there was no effect under gentle conditions in the presence of iodine. Pbf, Boc, PhCO, Cbz and Ph group are weaker in electron-withdrawing ability than Pbf group.The fourth part was the reaction of Pbf-activated thiourea and aziridine in the presence of iodine. Aziridine was synthesized through four-step reactions with 1,3,5-trimethylbenzene as the starting material. We did some elementary research on the reaction of Pbf-activated thiourea and aziridine.