Study On The Oxidation Of C-H Bonds In The Side Chain Of Pyridine To Ketones

The ketones containing pyridine structure are important intermediates for the synthesis of fine chemicals,such as pharmaceuticals,natural products,agricultural chemicals,dyes et al.The oxidation of C-H bonds in the side chain of pyridine is one of the most direct and efficient synthetic methods for the preparation of these ketones.The oxidation of the C-H bonds in the side chain of pyridine remains a challenge owing to the electronegative nitrogen in the pyridine ring,so there are few studies on the oxidation of C-H bonds in the side chain of pyridine to ketones.This article had mainly studied the oxidation of C-H bonds in the side chain of pyridine to ketones with benzylpyridine compounds,6,7-dihydro-5H-cyclopenta[b]pyridine compounds and 2-ethylpyridine as substrates.The main contents are as follows:Choosing benzylpyridine compounds as substrates,the oxidation of C-H bonds in the side chain of pyridine to ketones had been studied based on synergistic H₄NI-AcOH catalyst and molecular oxygen,and the ketones were obtained in 61-97%yield.This protocol showed excellent chemoselectivity,and benzyl methyl,benzyl ethyl and methylthio were left untouched.This oxidation reaction was promoted by the pyridinium salts formed by AcOH and benzylpyridine compounds.The synergistic effect between H₄NI and AcOH was demonstrated by control experiments.H₄NI was oxidized to I₂ which catalyzed this oxidation reaction.AcOH not only take part in the process of the oxidation of H₄NI to I₂ but also improve the selectivity of this oxidation reaction.The 18O-labeled experiment demonstrated that the carbonyl oxygen atom of the ketones products originated from dioxygen.The EPR experiments demonstrated that this oxidation reaction proceeded through a free radical mechanism.Choosing benzylpyridine compounds,6,7-dihydro-5H-cyclopenta[b]pyridine compounds and 2-ethylpyridine as substrates,the oxidation of C-H bonds in the side chain of pyridine to ketones had been studied using Mn（OTf）2 as catalyst,and the ketones were obtained in 31-88%yield.Compared with the methods reported in previous literatures,this protocol replaced CrO3 with tert-butyl hydroperoxide（65%in water）which is environmentally friendly.This protocol replaced H₂SO4-HOAC which would be corrosive to the equipment and lead to the pollution of the environment with H₂O.Single crystal X-ray diffraction experiment proved the structure of 6,7-dihydro-5H-cyclopenta[b]pyridin-5-one.The complexs from Mn（NO₃）₂ and 1,10-phenanthroline were pyrolysed in nitrogen atmosphere forming MnO_x-N@C.The oxidation of C-H bonds in the side chain of pyridine to ketones had been studied using MnO_x-N@C as catalyst with benzylpyridine compounds and 6,7-dihydro-5H-cyclopenta[b]pyridine compounds as substrates,and the ketones were obtained in 38-95%yield.MnO_x-N@C（600 ℃）had the highest catalytic activity.The MnO_x-N@C（600 ℃）was initially characterized by transmission electron microscopy（TEM）and X-ray photoelectron spectroscopy（XPS）.The MnO_x-N@C（600 ℃）was successfully recycled up to six times without any significant loss of activity,and this result showed that MnO_x-N@C（600 ℃）had good stability.