Synthesis And Structural Characterization Of N,N’-disubstituted And N,N,N’-Trisubstituted Sulfonyl Formamidine Compounds

Amidine compounds have a unique structure and chemical properties and an important position in organic compounds containing nitrogen.Among them,N-sulfonyl amidine is the essential intermediate in many organic reactions,which can be used for the synthesis of heterocyclic compounds,chelating ligands of transition metals,etc.Besides,sulfonyl amidine is widely used in the design of biologically active drug molecules and the exploration of the lead compound.At present,the main synthesis methods of N-sulfonyl amidine include the multicomponent one-pot method,tertiary amine oxidation method,amide activation method,etc.However,in such reactions,usually special reagents need to be used,including transition metal catalysts and expensive and potentially explosive sulfonyl azide compounds.Moreover,most reactions are made at a high temperature.Therefore,it is important to develop and use easily available raw materials to efficiently synthesize N-sulfonyl amidine compounds.This master’s thesis proposes two methods of synthesizing sulfonyl formamidine under gentle conditions.The research contents and results are as follows.1.Synthesis of N,N’-disubstituted sulfonyl formamidine with the four-component one-pot method.With the raw materials of ethyl propiolate,primary amine,sodium azide,and sulfonyl chloride,the target compound sulfonyl amidine was synthesized at room temperature without catalyst or additive.The impact of solvent,feed ratio of reactants,temperature,alkali additives,and other factors on the reaction yield was discussed and the optimal reaction conditions were obtained.Acetonitrile was used as the solvent.The feed ratio of ethyl propiolate,primary amine,sodium azide,and sulfonyl chloride was 1:1:1.5:1.5.The temperature was the room temperature.Under the optimal conditions,the study on the suitability of substrate was made.The impact of different sulfonyl chloride and primary amine on the reaction was studied.The result showed that the method could only be applicable to aromatic sulfonyl chloride and products with a middle-tohigh yield were obtained.In the structural characterization with analysis methods such as nuclear magnetic resonance(NMR)and X-ray single crystal diffraction,it was found that N,N’-disubstituted sulfonyl amidine mainly constructed two kinds of isomers.Among them,the chain or low branched-chain primary amine mainly constructed the E-syn isomer.On the contrary,the tert-butylamine mainly constructed the E-trans isomer.2.The condensation reaction of N,N-dimethyl formamide(DMF)and sulfamide.Under the action of the activating agent of 4-nitrobenzene sulfonyl chloride,DMF and sulfamide directly reacted and produced the corresponding N,N,N’-trisubstituted sulfonyl amidine.Through the optimization of reaction conditions,we can know that the amount of 4-nitrobenzene sulfonyl chloride used is 1.5 equivalents.The reaction with DMF as the solvent was smoothly made under the conditions at room temperature and the target product with a high yield was obtained.Unfortunately,this method can be only used for the related reactions of DMF.It has no activity for other amides(N,N-formyldiethylamine,N,N-dimethylacetamide,etc.).