Research On The Synthesis Of N-Heterocycle And S-Heterocycle Involving Amidines

Amidines are an important synthon for the construction of many pharmaceutically molecules,natural products and agrochemicals.N-Heterocyclic and S-heterocyclic are widely employed in the fields of synthetically organic chemistry,medicine,materials.Therefore,the development of efficient,highly selective C-N/S-N bonds formation based on amidines as nitrogen source has become an important research field in organic chemistry and synthetic chemistry.The formation of C-N bond based on amidines is one of the important methods for synthesizing N-heterocyclic compounds,such as pyrimidines,quinazolines and benzimidazoles.Compare with the formation reaction of the C-N bond,the formation reaction of the S-N bond is relatively less.The emergence of constructing S-N bond base on amidines opens the door for future investigations of this versatile heterocycles scaffold,such as thiadiazole and isothiazole.In this dissertation,we have investigated synthesis of thiadiazole,isothiazole,isoquinolinone and isoquinoline derivatives from amidines.The main contents are as follows:1.We have developed straightforward and efficient access to 3,5-diarylsubstituted-1,2,4-thiadiazoles from amidines,elemental sulfur,and methylarenes or benzaldehydes under transition-metal-free conditions.The methyl group attached to quinolines and aldehydes successfully served as the carbon source,and elemental sulfur acted as the sulfur source to selectively assemble the five-membered 1,2,4-thiadiazole moiety.Functional groups such as halogen and trifluoromethyl were well tolerated under the optimized reaction conditions.This three-component approach affords a facile route for the rapid synthesis of unsymmetrical 3,5-diaryl substituted 1,2,4-thiadiazoles.2.We have developed a novel approach for the synthesis of 3-arylamino-1,2-benzisothiazoles via S-N bond formation from amidines and elemental sulfur under transition-metal-free conditions.The new strategy required only cheap reagents,such as K3PO4 and air,and shows good to excellent yields to target isothiazoles,broad substrate scope and excellent functional groups tolerance.The resulting sulfur-containing compounds could be transformed to useful organic synthons.3.We have demonstrated an efficient and convenient nickel-catalyzed annulation of substituted 2-halobenzamides with alkynes to give the corresponding isoquinolinone in excellent results.This redox neutral isoquinolone synthesis operates under mild conditions,is not sensitive to air or water and does not require an external oxidant and base,and shows broad substrate scope,excellent functional groups tolerance and good to excellent yields.This interesting reactivity should find a broader use in the preparation and functionalization of biologically active compounds having the isoquinolinone core.4.We have reported a novel nickel(?)-catalyzed 1-aminoisoquinoline synthesis by debenzylation and annulation of N-benzyl-2-halobenzamides and alkyne.Owing to the importance of the products,simplicity in the experimental procedure,high regioselectivity and high yield,this efficient strategy would be of synthetic utility.Exploiting the same strategy,we have successfully developed a novel approach for the synthesis of benzo[4,5]imidazo[2,1-a]isoquinolines via double C-N bond formation.