Synthesis and Microbicidal Activity of Substituted 1,2,3-Triazoles having Amide and Hydroxy Functionality

Abstract

Pyrimidines and pyridines are choice for modern day medicinal chemistry. Pyrimidine synthons are synthesized form guanidine and different substituted malonates. One of such pyrimidine ring synthon is 2-amino-5-carboethoxy-4-hydroxy pyrimidine. The commercially deployed synthesis involved a mixture of KOH and guanidine carbonate and gradual temperature controlled addition of diethylethoxy methylene melonate giving a yellow precipitate. The precipitate is cooled to around 5 °C and recrystallized from ethanol-water mixture. Though purity is never an issue in this popular process, yields are very low (70-75 %). The GC analysis of reaction mixture indicated that almost starting material was left unreacted and the first yellow precipitate formation is the rate determining step. We report silica functionalized magnetic particles as material support for synthesis of 2-amino-5carboethoxy-4-hydroxy pyrimidine. The cyclization reaction yields are reported to be enhanced due to presence of "near-homogeneous" nanomaterial catalyst. The prominent catalyst of interest to us is Fe3O4@SiO2 of 40 nm size. The particles are produced by modified Stober process giving consistent yields and coating of SiO2. The structural characterization is performed with SEM, TEM, IR and the data are consistent across multiple batches. The use of 40 nm size Fe3O4@SiO2 enabled higher yields of cyclization step in synthesis of 2-amino-5-carboethoxy-4-hydroxy pyrimidine. The mechanism of catalysis is stabilization of hetero atoms on the acidic silica surface and hence formation of pyrimidine. The study with different sized nanoparticles has indicated 40 nm size seems to be optimum and ability of catalysis is reduced as the size of nanoparticles has increased. The reaction performed at different batch sizes has indicated that 5 % (w/v) catalyst is optimal in the reaction. This process modification has far reaching applications in medicinal chemistry and bulk drug synthesis.

Synthesis, antibacterial and antifungal activity of myricetin derivatives containing piperidine and amide fragments

“…At present, the chemical structure of SDHIs on the market all contain amide bonds, so they are also called amide pesticides. Many studies have shown that amides had broad-spectrum antibacterial, [29][30][31] antiviral, 32 insecticidal 33 and herbicidal 34,35 activities. They were widely used in agricultural production such as methuroxam and fludixamide (Fig.…”