Theoretical Studies Of Multicomponent Condensation Synthesis Of Novel Barbiturate Derivatives

Density functional theory (DFT) calculations have been carried out to study the mechanisms of two muticomponent condensation reactions in the paper. The first is a research on the multicomponent reaction mechanism of prop-2-en-1-amine and alkyl propiolate with alloxan derivative. And the second is the theoretical investigation about mechanism of the synthesis of spiro-oxazinobarbiturate from azine, activated acetylene and 1,3-dimethylalloxan.The multicomponent reaction mechanisms of prop-2-en-l-amine and ethyl propiolate with alloxan were studied using density functional theory (DFT). The reaction mechanisms were found to consist of two stages. First, the prop-2-en-l-amine reacts with ethyl propiolate to form an electron-richβ-aminoacrylate through two competitive channels (channels a and b). Second, a nucleophilic addition ofβ-aminoacrylate to alloxan occurs via four possible channels (channels b1, b2, b3 and b4). The calculated results revealed that the most energetically favorable path is channel b4 and suggested that the water molecule plays as a proton transfer intermediate in the reaction. Our calculations demonstrated that the reaction occurs easily at room temperature, which agrees well with the experiment.The second topic is "A theoretical investigation of the synthesis of spiro-oxazinobarbiturate from azine, acetylene and 1,3-dimethylalloxan". The multicomponent reaction mechanisms of pyridine and methyl but-2-ynoate with 1,3-dimethylalloxan were studied using density functional theory at the B3LYP/6-31G(d,p) (gas-phase) and B3LYP/6-311++G(d,p) (liquid-phase) level of theory, respectively. The reaction mechanisms were found to consist of three steps. First, a nucleophilic addition of pyridine to methyl but-2-ynoate occurs, resulting in a zwitterionic intermediate M1. Second, M1 reacts with 1,3-dimethylallxan to yield the other intermediate M2. Last, the product of spiro-oxazinobarbiturate generates with a new bond form. The calculated results revealed that the suggested reaction channel is an energetically favorable path. The rate-limiting energy barrier for the reaction channel, in which the solvation effects were considered using PCM as implemented with the dry CH2Cl2, is 18.02 kcal/mol. Our calculations demonstrated that the reaction occurs easily at room temperature, which agrees well with the experiment.