Green Chemistry Research And Application Of Direct Amidation Mediated By Boric Acid

Amidation is one of the most important chemical transformations and is frequently used in pharmaceutical industry.A great number of currently employed amidation methods have several disadvantages including high cost,environment hazard,poor atom-and step economy,waste disposal issues and lack of functional selectivity.Boric acid catalyzed direct amidation between carboxylic acids and amines provides a solution to the aforementioned problems.Boric acid direct catalyzed amidation,nevertheless,has its own shortcomings in that unsatisfied catalytic ability and limited scope are often accounted.The objective of this present research is focused on the improvements of the catalytic ability of boric acid in this direct amidation reaction.The objective of this present research is focused on the improvements of the catalytic ability of boric acid in this direct amidation reaction.Firstly,we have found that some Lewis bases such as N,N,N’,N’tetramethylpropane-1,3-diamine stipulated the catalytic ability of boric acid in this amidation reaction.The Lewis base aided boric acid catalyzed reaction worked well with both aliphatic and aromatic amines bearing a hydroxyl group with high chemical specificity.No formation of ester was observed.Second,the catalytic ability of boric acid was enhanced remarkably by silica gel supported.For the direct amidation of aromatic acids,such as benzoic acid,harsh reaction conditions,such as high amount of boric acid and high temperature are often required to drive the amidation to completion.With silica gel support,the same amidation undergoes smoothly without harsh conditions.With aromatic amines,only low amount of silica gel supported boric acid is needed.In conclusion,Lewis base assisted or silica gel supported boric acid catalyzed direct amidation provides an enhancement of the utility of the already valuable direct amidation between carboxylic acids and amines.By virtue of the advantages offered by the Lewis base assistance and the silica gel support,organic molecular architects could synthesize with ease a great number of pharmaceutically useful drug intermediates.