Fe-catalyzed esterification of amides via C–N bond activation |
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Authors: | Xiuling Chen Siying Hu Rongxing Chen Jian Wang Minghu Wu Haibin Guo Shaofa Sun |
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Affiliation: | Hubei University Of Science and Technology, China |
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Abstract: | An efficient Fe-catalyzed esterification of primary, secondary, and tertiary amides with various alcohols for the preparation of esters was performed. The esterification process was accomplished with FeCl3·6H2O, which is a stable, inexpensive, environmentally friendly catalyst with high functional group tolerance.An efficient Fe-catalyzed esterification of primary, secondary, and tertiary amides with various alcohols was performed. Esterification was accomplished with inexpensive, environmentally friendly FeCl3·6H2O, and with high functional group toleranceThe amide bond is not only employed as an important natural peptide skeleton in biological systems, but also as a versatile functional group in organic transformations.1,2 Among amide transformations,3,4 transamidation and esterification of amides have attracted widespread attention from organic chemists.5–11 In contrast to transamidation of amides, esterification of amides is relatively difficult because of the low nucleophilicity of alcohols compared with amines.12 To overcome this shortcoming, various processes for the esterification of amides have been developed, such as using an activating agent,6 employing twisted amides,7 and forming intramolecular assisted groups.8 For increasing the synthetic flexibility of esterification of amides, new catalytic systems Zn(OTf)2 and Sc(OTf)3 were developed by Mashima and Williams for the esterification of amides.9 Shimizu et al. reported CeO2 catalyzed esterification of amides.10 Off late, progress of the significant Ni-catalyzed esterification of amides has gained precedence.11 Although this approach produces satisfactory yield, the drawbacks such as the use of an expensive catalyst, generation of reagent waste, high temperature and the limited scope of the substrate still persists. Herein, under mild reaction conditions, we report a novel and efficient Fe-catalyzed esterification of amides for the synthesis of esters (eqn (1)). Compared to conventional methods, this esterification procedure is distinguished by using a stable, inexpensive, environment-friendly catalyst, i.e., FeCl3·6H2O with a low toxicity solvent. The catalytic system has wide functional group compatibility. The reactions of several primary, secondary, and tertiary amides with various alcohols have been well tolerated in this process. Moreover, esters were also as effective as esterification reagents for the esterification of amides by the acyl–acyl exchange process. In the course of our present study, a Co-catalyzed amide C–N cleavage to form esters was reported by Danoun et al.13 However, an additional additive (Bipy) and Mn (3 equiv.) were needed and the scope of the reaction was limited to only tertiary amides; primary or secondary amides were not compatible with this catalytic oxidation system.1We initially selected benzamide 1a and ethanol 2a as model substrates to screen the reaction conditions, and the results are summarized in | Open in a separate windowaReaction conditions: 1a (0.2 mmol), 2a (0.1 mL), catalyst (0.04 mmol, 20 mol%), H2SO4 (concentrated, 0.24 mmol), HNO3 (concentrated, 0.24 mmol), HCl (0.24 mmol, 36–38%), n-hexane (1.0 mL), 80 °C, 14 h.bGC yield using hexadecane as internal standard.cDMF was used as a solvent.d1,4-Dioxane was used as solvent.eToluene was used as solvent.fCH3CN was used as solvent.The substrate scope of esterification with alcohols was investigated under the optimized reaction conditions. As shown in |