Selective N-monomethylation Of Aromatic Amines & Synthesis Of Chiral Proline-Guanidine

In this thesis, the selective monomethylation of aromatic amines and synthesis of chiral proline-guanidine derivatives have been studied in detail.In partâ… , the selective monomethylation of aromatic amines were studied. Aromatic amines were acetylationed with acetic anhydride, the subsequent N-methylation reaction were carried out using CH3I and NaH in THF, and acid hydrolysis of the corresponding N-methyl acetanilides in ethylene glycol to generate the N-Methyl anilines. It gave specifical and high yields of the desired N-monomethylated aryl amines. The method was generally compatible with a wide range of functional groups, even those that may be sensitive to bases.In partâ…¡, new chiral proline-guanidine derivatives were synthesized. The reaction of N,N',N"-tri-Boc-guanidine with Cbz-proline afforded N,N'-di-Cbz- prolinoyl-N,N',N"-tri-Boc-guanidine. Subsequent deprotected the Boc group with TFA/CH₂Cl₂ to give N,N'-di-Cbz-prolinoyl-N,N'-di-Boc-guanidine intermediate. The chiral di-Boc-proline-guanidine was obtained with Pd/C-H₂ hydrogenation for deprotecting the Cbz group of the intermediate. The Boc groups on N,N'-di-Cbz-prolinoyl-N,N'-di-Boc-guanidine were rearranged from N on guanidine to N on pyrrolidine during the hydrogenation reaction, which was confirmed with Ms and NMR analysis. This New chiral proline-guanidine compounds may have potential to be used as organocatalyst in asymmetric synthesis and molecular recognition studies.