The Study Of A Methodology For The Indoles Synthesis Mediated By NaH

The indole skeleton is a ubiquitous element in many pharmacologically active nature compounds,thus the research topic of developing the methods for the indoles synthesis that feature mildness and efficiency with broad substrates scope are always valued by the synthetic scientists around the world.Many methods such as the Fisher indole synthesis published as early as 1883 for synthesizing indoles have been reported.After that,many other renowned name reactions for the indoles synthesis have also been published.With the application of transition-metal in the synthetic field,such metals such as palladium,gold,etc.were also used in the indoles synthesis.In this aspect,a variety of strategies have been taken for the indoles synthesis depending on the substrates.For example,o-alkynlaniline derivatives was transferred to indoles by hydroamination reaction.In addition,other methods such as base,ammonium-fluoride-mediated reaction from o-alkynlaniline derivatives to indoles are also presented as some examples.In this thesis we reported a novel methodology for the synthesis of indoles from o-alkynlaniline derivatives mediated by cheap NaH at room temperature.This isserendipity during our aiming at installing a Bn group onto the N atom of the o-alkynlaniline derivatives.We firstly explored the possible group on the terminal alkyne and the protecting group on the N atom.To our surprise,only the TMS at the terminal alkyne other than aryl or alkyl group and the Ac-protected N atom could promote this reaction to work.Secondly,after carefully screening the reaction conditions,we finally conformed two equivalents of NaH,DMF as the reaction medium at room temperature is the optimal reaction condition.Thirdly,a series of o-alkylaniline derivatives were synthesized and then characterized by 1H NMR,13C NMR,IR spectrum and HRMS.As for the solid unknown substrates,we also tested their melting point.Next,we explored the substrate scope of this method.The results demonstrated that the substitute group such as Cl,F,CF3,CH3 and acetyl at the p-site of the o-alkylaniline are well tolerated and modest yields are obtained for most of these substrates.And the unknown prodocts were charactered by 1H NMR,13C NMR,IR spectrum and HRMS.We also found that in the presence of 1-bromomethyl-4-methylbenzene,a N-Bn protected indole was obtained,while in the absence of it,a NH-indole was also obtained.