Iron-Catalyzed Oxidative C-N Cross-Coupling Amidation Of Tertiaryamines And Functionalization Of Amides

The construction of C-N bonds is an important protocol in organic chemistry because C-N containing functional groups are widely found in bioactive natural products,synthetic drugs,organometallic complexes and functional materials,and they can also constitute the main skeleton of biological molecules such as peptides and proteins.Therefore,the simple and environmently approaches for the formation of C-N bond is more challenging and valuable work.In this paper,the oxidative C-N cross-coupling reaction of tertiary amines as well as the functionalization of amides were studied.(1)The oxidative C-N cross-coupling reaction of aromatic tertiary amines with the amides via iron-catalysis were studied.After examining the activities of various iron salts as catalyst under one atmosphere of oxygen as the oxidant,we found the cross-coupling reaction was carried out smoothly in the oxidation system of Fe(NO₃)₃·9H₂O/O₂ under mild conditions.Using the optimized reaction conditions,a different substituents N,N-dimethylaniline was coupled with a variety of amides/imides successfully,and also desired products were obtained in medium to high yield(51%?80%).Futhermore a possible mechanism of the reaction was proposed.(2)The methylene bisamides from amides were studied.Firstly,the reaction conditions were optimized by using benzamide and acetamide(formamide)as substrates.The results showed that iodine as the catalyst(20mol%),potassium persulfate as the oxidant(1equiv),N,N-dimethylacetamide as the methylene reagent and as the solvent,the reaction temperature was 80^oC.Only aromatic primary amides can react to generate the corresponding methylene bisamides,the yield of which is71%?90%.When other aliphatic,heterocyclic,and secondary amides were used as the substrates,no corresponding desired products can be obtained.(3)N-sulfonylamidines were synthesized from tertiary amides and sulfonamides.Firstly,with the p-toluenesulfonamide and N,N-dimethylacetamide(DMA)as substrates,the factors affecting the reaction yield such as halogenation reagent,solvent,temperature and reactant ratio were investigated.Using the optimal reaction conditions[n(sulfonamide):n(amide):n(POCl₃)=1:1.2:1.2,chlorobenzene as a solvent,the temperature is 80^oC],the substrate is extended,and the corresponding N-sulfonylamidine product has a maximum yield of 99%.