Solid Phase Synthesis Of Heterocyclic Compounds Based On The Resin-bound Acylhydrazine Reagent

In this thesis, the preparation of polymer-supported acylhydrazine reagent and their applications in solid phase organic synthesis of heterocyclic compounds were discussed.First, resin-bound acylhydrazine is prepared from Merrifield resin. In this course, conversion of methyl ester resin into acylhydrazide resin was attempted under various reaction conditions. We found that resin-bound methyl benzoic ester can be converted completely when HMPA was used as solvent.Then, the well-prepared resin-bound acylhydrazine reagent was applied in solid phase organic synthesis of heterocyclic compounds. Our main work was as follow:a) resin-bound acylhydrazine reacted with CS₂ under basic conditions , these were cyclized giving the resin bound 1, 3, 4- oxadiazole-2-thiones. Then treating with electrophilic reagents, cleavaged by TFA, 1, 3, 4-oxadiazole-2-thiones derivatives was prepared.b) resin-bound acylhydrazine reacting with isothiocyanate gave resin-bound thiosemicarbazides, which can be cyclized in acidic or basic conditions, afforded resin-bound 2-arylamino-1, 3, 4-thiadiazole or 4H- 1,2,4- triazole -3 -thiones derivatives. After cleavaged with TFA, we got the desired compounds.c) Dinucleophilic site exists in acylhydrazine, which can undergo tandem reaction with kinds of dielectrophilic reagents. We applied resin-bound acylhydrazine into solid phase organic synthesis of adenosine acceptor inhibitors, and we got the fused 1,2,4-triazol[1,5c]pyrimidine derivatives in good yields and high purities.The method presented in thesis allows much simplier workup procedures . And the starting material was easy-available, reaction condition was mild. Efficient solid phase organic synthesis of 1, 3, 4-oxadiazole-2-thiones, 2-arylamino -1, 3, 4- thiadiazole, AH-1, 2, 4-triazole-3-thiol derivatives and adenosine acceptor inhibitors were developed.