The Reaction Of Fluoroalkanesulfonyl Fluoride And Aldoximes And The Synthesis Of 1-(Guanin-9-yl)Methoxy-2-(Guanin-7-yl)Methoxyethane

PART 1:Nitrile is a class of important chemical raw materials and synthetic intermediates. Nitriles can be used as perfumes, medicines, electro-optic materials,metal corrosion inhibitors and liquid crystal materials. In addition, some polyphosphazene polymers have found important applications in functional materials,aerospace, functional materials, petro-chemical and biomedical fields.Dehydration of aldoximes is the most popular method for the preparation of nitriles. Lots of dehydrating agents have been developed to mediate the dehydration of aldoximes. However, some of those reagents still suffered from the expensiveness,sensiblility to moisture and potential toxicity or exposiveness. Our group found that fluoroalkanesulfonyl fluoride can act as an excellent hydroxyl-activating reagent and can be used to promote the dehydration of aldoxime to form nitrile under alkaline condition. Mild reaction conditions and high yields are advantages of our method. The reaction can be run at room temperature and is completed in only five minutes. It will provide an alternative method for the preparation of nitriles in organic synthesis.The contents of this part includes the following two sections:1, The reported methods for the dehydration of aldoximes to nitriles were summaried.2, The reaction of fluoroalkanesulfonyl fluoride-mediated dehydration of aldoximes to nitriles was extensively investigated. The optimized reaction conditions are:reaction temperature is 25 ?, the solvent is dichloromethane, and n(aldoxime) : n(DBU) : n(Rf SO2F) = 1 : 1.5 : 2.0.PART 2:Acyclovir, named as 9-(2-hydroxyethoxymethyl)guanine, is a highly efficient broad-spectrum antiviral drugs. In this part, we explored the synthesis of1-(guanin-9-yl)methoxy-2-(guanin-7-yl)methoxyethane(3). 3 is one of the substances related to the antiviral drug acyclovir as recorded in European Pharmcopoeia(Edition8.0)(ACV impurity I). A two-step synthetic route was designed to synthesize 3. The condensation of 1,2-bis(acetyloxymethyloxy)ethane(1) with N2,9- diacetylguanine provided 2 followed by basic hydrolysis offering the target molecule 3. The structure of 3 was confirmed by 1H NMR, 13 C NMR, IR and ESI-MS spectra.This part consists of the following two sections:1. Summary of the synthetic methods for acyclovir.2. The synthesis of 1-(guanin-9-yl)methoxy-2-(guanin-7-yl)methoxyethane(3) was studied. The condensation of N2,9-diacetylguanine and1,2-bis(acetyloxymethyloxy)ethane(1) followed by hydrolysis smoothly furnishing the desired product 3.