Study On The Synthesis Of N-(Pyrrolidine) Benzamides With Biological Activities

Biological activities and synthetic methods of benzamides, N-ethyl-2-amino-methylpyrrolidine(EAMP) and guanidine are reviewed. Benzamides are wielded used as antipsychotics, dopamine adography, agricultural antimicrobial and antinflamatory antiallergic medicine. EAMP is an important medical intermediates and is wildly used as antipsychotics. There is a chiral carbon atom in the EAMP's molecule and it has been proved that the S-EAMP has higher biological activity than that of the D-EAMP. Guanidines are strong organic bases and they are protonation in a wild biological environment range. So guanidines are label to interacting with ligand , receptor , enzyme and substrate through hydro-bond and electrostatic interaction. For those reasons, guanidines play a big part in medicines. But guanidines have not been applied in the benzamide antipsychotics. In this article, guanidine is inducted to the benzene ring of the benzamide antipsychotics, then estimate the biological activities of the new compoundsFirst, 4-amino-2-methoxybenzoate is obtained from the reaction of p-aminosalicylic acid and dimethyl sulfate in the presence of potassium hydroxide in the absolute acetone. Then the 4-amino-2-methoxybenzoate reacts with KOH to form the 4-amino-2-methoxybenzoic acid . The 4-guanidine-2-methoxyl benzoic acid sulfite formed from the reaction 4-amino-2-methoxyl benzoic acid and aminoiminomethanesulfonic acid (AIMSOA). Next the guanidine's sulfite reacts with HCl to form the 4-guanidine-2-methoxyl benzoic acid hydrochloride. The S-EAMP is obtained by resolved with D-(-)- tartaric acid. Finally, the target products—N-[(1-ethyl-2-prolidine)methyl]-4-guanidine -2-methoxyl benzamides are prepared from the reaction of the 4-guanidine-2-methoxyl benzoyl chloride ,which formed from 4-guandine-2-methoxyl benzoic acid ,and racemic EAMP and S-EAMP. The structure of title compounds and intermediates were identified by elemental analysis, IR and 1H-NMR. The effects of the reaction conditions on the yield were investigated and reacting conditions optimized.The toxicology and pharmacology experiments is examining for the two newcompounds , which will indicate the effect of guanidines for the benzamide antipsychotics.