Mild Access to N‐Formylation of Primary Amines using Ethers as C1 Synthons under Metal‐Free Conditions

Abstract

A new synthetic protocol has been developed for the synthesis of N‐formamide derivatives using ethers as a C1 synthon under metal‐free reaction conditions. The reaction is proposed to proceed through C−H functionalization, C−O cleavage, and C−N bond formation. This protocol is applicable to a variety of primary amines resulting in N‐formamides in moderate to good yields. 1,4‐dioxane was chosen as best C1 synthon after screening with various ethers. Mechanistic studies disclosed that the reaction proceeds through a radical pathway. While using α‐amino ketones a α‐alkylation product was formed rather than formylation. By replacing dioxane with Tetramethylethylenediamine (TMEDA) under standard conditions also gave the N‐formamide derivatives in moderate yields.magnified image

Radical Rearrangement of Aryl/Alkylidene Malononitriles via Aza Michael Addition/Decynoformylation/Addition Sequence: An Access to α-Aminonitriles and α-Aminoamides

“…Based on the previously reported reactions, a plausible reaction mechanism was proposed for synthesis of α-aminonitriles ( 3 ) (Scheme ). First, the reaction was initiated with 1,4-addition of aniline on arylidene malononitrile to form intermediate I .…”

Silver-Catalyzed, N-Formylation of Amines Using Glycol Ethers

“…Solvent proved to be crucial for formylation activity (Table , entries 10–17). In contrast to the TBHP-promoted reaction, which performed passably well (47% vs 60%) using THF in place of 1,4-dioxane, no formylation activity was observed in the silver-catalyzed reaction using this solvent (entry 10), hinting at a distinct reaction mechanism. No formylation activity was also observed using 1,3-dioxane and dioxolane.…”

An Environmentally Benign, Catalyst‐Free N−C Bond Cleavage/Formation of Primary, Secondary, and Tertiary Unactivated Amides

“…N ‐(2,4‐Dimethylphenyl)formamide [18d] ( 3 h ): Using the experimental procedure EP‐1 , the product was obtained as off‐white solid in 91 % yield. A mixture of rotamers is observed; 1 H NMR (400 MHz, CDCl 3 ) δ 8.45 (d, J =11.2 Hz, 0.62H), 8.39 (s, 0.37H), 8.17 (br, s, 0.58H), 7.66 (d, J =8.6 Hz, 0.36H), 7.35 (br, s, 0.28H), 7.00 (t, J =7.2 Hz, 2.69H), 2.29 (d, J =10.3 Hz, 3H), 2.24 (d, J =15.6 Hz, 3H).…”