Catalytic and Mechanistic Approach to the Metal-Free N-Alkylation of 2-Aminopyridines with Diketones

Abstract

N-alkylation of amines is an important catalytic reaction in synthetic chemistry. Herein, we report a simple strategy for the N-alkylation of 2-aminopyridines with 1,2-diketones using BF3·OEt2 as a catalyst. The reaction proceeds under aerobic conditions, leading to the formation of a diverse range of substituted secondary amines in good to excellent yields. A close inspection of the mechanistic pathway using various spectroscopic techniques and the computational study revealed that the reaction proceeds through the formation of an iminium–keto intermediate with the liberation of CO2.

One‐pot Expedient Green Synthesis of N‐benzhydrylpyridine‐2‐amines Using Gooseberry Amla Fruit Extract (GAFE): A Naturally Occurring Organocatalyst

“…Reactions performed using 0.002 mmol of compound 1 a and 2 a' with DMF (2.00 ml) as solvent followed by different acid catalysts (3 ml). have reported the synthesis of such heterocycles [49] using H 3 PO 4 , HCl, CH 3 COOH and BF 3 .OEt 2 . However, they have reported the use of BF 3 .OEt 2 with 30 mol % which gave the product with a yield of 77 %.…”

“…Since, it has the composition of various acids as shown in Figure 1, the mol % was not calculated. Nad et al have reported the synthesis of such heterocycles [49] using H 3 PO 4 , HCl, CH 3 COOH and BF 3 .OEt 2 . However, they have reported the use of BF 3 .OEt 2 with 30 mol % which gave the product with a yield of 77 %.…”

“…Chemistry Pinaki Nad and co-workers, [49] proposed a straightforward method for N-alkylating 2-aminopyridines using 1,2-diketones while utilising hydrochloric acid (150 °C, 24 h, xylene, yield 44 %), and BF 3 OEt 2 (150 °C, 24 h, xylene, yield 77 %) as an acid catalyst for the synthesis of N-benzhydrylpyridine-2-amines. In the present study, title compounds 3 aa'-jj' were synthesized from various substituted 2-aminopyridines 1 a-e and different substituted 1,2-diphenylethane-1,2-diones 2 a'-b' at 150°C by refluxing in an oil bath for 48 h to obtain substantial yield of more than 95 % which is significantly higher than the earlier reported publication.…”

“…Plausible mechanism for the synthesis of title compounds 3 aa'-jj'. [49] C 6 À H proton of pyridine moiety, and proton attached to the αbranched carbon of secondary amine is resonated as singlet in the range of 4.67-5.97 ppm and the rest of the protons are resonated at their respective aromatic regions. In the 13 C NMR spectral analysis, the carbon attached to secondary amine and two phenyl rings, is resonated at 57.59-65.40 ppm and C 2 carbon of pyridine ring, is resonated in the region 150.18-157.02 ppm respectively.…”