New Synthetic Methods For N-Aryl-N-Hydroxymethyl Amides And Methylenebisamides

Amides and their reactions are important in both organic chemistry and biochemistry because many bioactive compounds or their intermediates posses amide group. They are widely used in medicine, materials and biology.In this thesis, we investigated the condensation reaction between N-aryl amides and polyformaldehyde and the preparation of methylenebisamides using TCT- or DCMT-activated DMSO. This thesis includes the following three chapters.In chapter 1, the applications of amides are introduced in various fields and their recent research progress in organic synthesis is reviewed. The significant researchs include Ullmann-type coupling reaction, reduction, Weinreb amide reaction, amidocarbonylation, Gabriel synthesis, Hofmann rearrangement, Vilsmeier-Haack formylation, applications in synthesis of heterocyclic compounds, and palladium-catalyzed functionalization of C-H bonds of N-aryl amides.In chapter 2, the reactions of N-aryl amides with formaldehyde are described. So far, there has been no report on the condensation between N-aryl amides and formaldehyde. We believe this is due to the dual conjugation of the lone pair electrons on the nitrogen atom of the N-aryl amides with both the acyl groups and aryl groups. This makes the N-aryl amide nitrogen less nucleophilic. If a bulky group located close to the amide group on the aromatic ring can force the acyl group out of aromatic plane, only single conjugation of the nitrogen lone pair with acyl group is possible. This makes the N-aryl amide nitrogen more nucleophilic. We have prepared 14 amides with peri-CH and found they would be reactive enough to condense with formaldehyde under base promotation at room temperature. This experiment supports my idea and the X-ray data of the amide structures and infrared measurements provide additional evidence for the enhanced nucleophilicity of the amides with peri-CH.In chapter 3, two parts of contents are presented. Firstly, the applications of TCT, and its derivatives, and activated-DMSO in organic synthesis are introduced. Secondly, another part focuses on the synthesis of methylenebisamides using TCT or DCMT-activated DMSO. The aromatic amides can react with DMSO to give methylenebisamides under activation of TCT or DCMT. Especially, when DCMT is used as activated reagents, the aliphatic amides also efficiently react with DMSO to yield the corresponding methylenebisamides. We have succeeded in preparing 12 methylenebisamides using the method in good to fair yields. The procedure reported hererin is operationally simple, and requires inexpensive and commercial availble reagents. Plausible mechanism which involves two sulfonium salts intermediates of the reaction is proposed and supported by the experiments.