Research On The Synthesis Of Benzazepinone Conjugates Via Ugi Four-Component Reaction And Palladium-Catalyzed Hydroamidation

In recent years multi-component reactions (MCR) has been rapidly developed for their characteristics of facility, atom-economic and structural diversity of the products, and extensively used in the novel drug design and synthesis, combinational chemistry and synthesis of natural products. Ugi four-component reaction is one of the multi-component reactions, and through both Ugi and post-Ugi reaction, more complex and diverse molecules can be produced. In this thesis we will research a method for synthesis of the conjugates benzazepin-2-ones through Ugi-4CR and post intramolecular hydroamidation (IMHAD).In chapter one, the concept, mechanism for microwave-assisted reaction and its development has been briefly introduced and methods for synthesizing structure complex compounds via MCR, especially Ugi-4CR with post-Ugi reaction for those nucleophilic substitution, Suzuki reaction, Buckwald-Hartwig reaction, Heck reaction and ring-closing metalysis (RCM) have also discussed and then a research schedule of this thesis for synthesis of conjugates of benzazepinones 66 has been proposed.The second chapter is the key of this thesis, in this chapter, first, the IMHAD catalyzed by various of catalysts has been discussed, and then the results of the synthesis of the conjugates of benzepinones 66 via Ugi-4CR and the post reaction, SNAr and IMHAD, including the design of the schedule and detour and selection of the catalysis system have been discussed in detail. We first tried to synthesize the compound 65 from the compound 67 which was formed via Ugi-4CR and SNAr reaction from 2-aminophenol,2-bromobenzaldehyde, benzylisocyanide and 2-chloro-5-nitrobenzioc acid and then coupled with 1-alkyne, unfortunately the later reaction failed. Then we try to synthesize the compound 65 via Ugi-4CR and SNAr from 2-alkynylaldehyde, as a result, this is an effective route with total yield 57-81% for 2 steps. It was found that conditions, those suited for simple substrates, for intramolecular hydroamidation are not suited for the formation of 66 from complex substrate 65. However, for our detail research it was found that the intramolecular hydroamidation catalyzed by Pd(PhCN)2 can carry out in THF at 60℃with 61-74% yields. And a novel method for the synthesis of conjugates of benzazepin-2-ones has been established.In third chapter, the detail procedures and data of the IR,1HNMR 13C NMR, MS, HRMS and elemental analysis for all compounds and references are included.