A Photochemical Protocol for the Synthesis of Weinreb and Morpholine Amides from Carboxylic Acids

Abstract

In recent years, the development of light‐mediated methods for synthetic applications has attracted high interest, because such methods constitute alternative approaches for the production of valuable chemical products. We study herein a photochemical protocol for the synthesis of Weinreb amides and morpholine amides from carboxylic acids. Various carboxylic acids were directly coupled to N,O‐dimethylhydroxylamine, upon irradiation with either LED 370 nm or sunlight in the presence of 4‐dimethylaminopyridine and bromotrichloromethane, providing Weinreb amides in moderate to high yields. Similarly, morpholine amides were obtained in satisfactory to high yields under sunlight or LED 370 nm irradiation. Thus, the versatile building blocks Weinreb amides and morpholine amides may be efficiently synthesized directly from carboxylic acids by light‐mediated approaches, without the need of coupling reagents or pre‐activation of carboxylic acids.

One-Pot Oxidative Amidation of Aldehydes via the Generation of Nitrile Imine Intermediates

“…This afforded morpholino­( p -tolyl)­methanone ( 2p ) (32.4 mg, 32%) as an orange solid. Spectroscopic data were consistent with the literature …”

“…Spectroscopic data were consistent with the literature. 34 R f = 0.18 (petroleum ether/ethyl acetate, 7:3); 1 H NMR (500 MHz, CDCl 3 ) δ 7.31 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 7.8 Hz, 2H), 3.69 (s, 8H), 2.38 (s, 3H); 13 C{ 1 H} NMR (126 MHz, CDCl 3 ) δ 170.8, 140.2, 132.5, 129.3 (2 × CH), 127.4 (2 × CH), 67.1, 59.7, 38.3, 31.4, 29.8; LCMS (ESI) m / z : [M + H] + Calcd for C 12 H 16 NO 2 206.1; Found 206.2 at 6.48 min.…”

“…Morpholino(p-tolyl)methanone (2p). 34 The reaction was performed according to the general procedure using 4-methylbenzaldehyde (65.0 μL, 0.550 mmol) and morpholine (219 μL, 2.50 mmol). The crude residue was purified by flash column chromatography (15% ethyl acetate in petroleum ether) followed by further purification by filtration through a short pad of silica, eluting with 15% ethyl acetate in hexane.…”

“…Spectroscopic data were consistent with the literature. 34 N-Benzyl-2-methylbenzamide (2q). 35 The reaction was performed according to the general procedure using 2-methylbenzaldehyde (65.0 μL, 0.550 mmol) and benzylamine (273 μL, 2.50 mmol).…”