Studies On The Synthesis Of N,N’-Methylene Bisamides And Quinazolinones

Amides are one group of important organic compounds. Proteins are formed through the amide bonds between different amino acids. Amide compounds have been widely applied in industry and daily life. Hence, studies on the synthetic method of amides are of very important.In this paper, the synthesis of amides was reviewed. And the recent developed methods for the construction of N,N’-alkylidene bisamides and quinazolinones were mainly documented. Based on the works precedent, it was envisioned that we could try the synthesis of N,N’-methylene bisamides from benzamides/dimethyl sulfoxide and quinazolinones from primary alcohols and o-aminobenzamides.In this paper, the conditions of temperature and ratio of starting materials were screened. We found when 1.2 eq of I2 was used as a promoter, DMSO as solvent and one of the starting material, benzamides produced the desired product N,N’-methylene bisamides at 120 °C for 24 h. The yields were generally good(up to 91%). A wide of range of benzamides, which bore electro-withdrawing and electro-donating groups, could proceed the reaction smoothly.As electrochemistry is highly efficient and green in organic synthesis, in this paper, the reaction of alcohols and o-aminobenzamides was studied under the electrochemical conditions. After the optimization of reaction conditions, it was found that when LiClO4 was employed as electrolyte, the mixture of MeCN/H2O(ratio 48:2, v/v) as solvent, benzyl alcohols reacted with o-aminobenzamides to producce quinazolinones catalyzed by MnSO4. A wide range of alcohols could participate this reaction and gave good yields(up to 90%). Mechanistic studies had shown that MnSO4 was oxidized by anode oxidation and the produced higher valent Mn worked as an oxidant to convert benzyl alcohol to benzyl aldehyde. Cyclization occurred between benzyl aldehyde and o-aminobenzamides followed by the dehydrogenation to afford to desired product.