Acetylation Of Pyridines And One-pot Synthesis Of2,4,5-trisubstituted Oxazoles

1. Acetylation of pyridines by alanine/S2O82/Ag+Initially acetyaltion of4-acetylpyridine has been investigated by using sodium pyruvate as acetylation reagent and S2O/2/Ag+. Then we explored the possibility of replacing sodium pyruvate with alanine. The experimental results showed alanine could replace pyruvate for acetylation of pyridines, which mainly took place at2-position of pyridines. The yields of acetylation products increased with adding of NaHCO3, increasing the usage of persulfate and alanine, and elongating the reaction time. The optimal conditions are:(NH4)S2O8(6.0eq), alanine(3.0eq), NaHCO3(2.0eq), AgNO3(0.1eq), CH2C12/H2O(1/1, v/v), room temperature. Under these conditions, the yields for the acetylation of4-acetylpyridine and N-(t-butyl)isonicotinamide are31%and37%, respectively.2. One-pot synthesis of2,4,5-trisubstituted oxazoles from N-acyl amino acids.By a combination of cyclodehydration of N-acyl amino acids with N,N’-diisopropyl-carbodiimide (DIC) and noN-classical Wittig olefination of the resultant5(4H)-oxazolones with Ph3P=CHCN and Ph3P=CHCOOEt,5-oxazoleacetonitriles and5-oxazoleacetates were synthesized in one-pot in41-85%and57-70%yields, respectively. The optimal conditions are: DIC (1.1eq), CH2Cl2as solvent to form5(4H)-oxazolones, to remove CH2Cl2, add ylide(1.2eq), and reflux for3h by using toluene as solvent. In addition, the formation of phosphorus ylide can also be combined into one-pot by adding phosphonium salt(1.2eq) and DABCO (1.8eq) to replace the ylide, and thus the corresponding oxazoles can be obtained in14-69%yields.N-Acyl amino acids and reagents used are stable and easy to get and a wider range of substrates can be chosen, so this one-pot protocol provides a simple way for the synthesis of2,4,5-trisubstituted oxazoles.