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. 2019 Feb 26;9(1):2787.
doi: 10.1038/s41598-019-39240-z.

Metal- and solvent-free synthesis of amides using substitute formamides as an amino source under mild conditions

Feng Zhang  1 , Lesong Li  2 , Jingyu Zhang  2 , Hang Gong  3
Affiliations

Metal- and solvent-free synthesis of amides using substitute formamides as an amino source under mild conditions

Feng Zhang et al. Sci Rep. .

Abstract

This study described an efficient and practical approach for amide synthesis. The reaction was conducted under metal- and solvent-free conditions at a mild temperature (40 °C) in air, and readily available formamides were used as an amino source. This reaction can be easily upgraded to the gram level with an excellent yield.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Cross-coupling reaction of formamide with a carboxylic acid derivative.
Figure 2
Figure 2
Selected optimization resultsa. aUnless otherwise noted, all reactions were conducted on a 0.5 mmol scale; Yields were determined by 1H NMR spectroscopy using nitromethane as internal standard. bUsing DMF (5 equiv, 194 μL). cUnder the atmosphere of argon. dSolvent free, using DMF (5 equiv, 194 μL).
Figure 3
Figure 3
Scope of amide synthesisa. aUnless otherwise noted, all reactions were conducted on a 0.5 mmol scale, amide compounds (5 equiv), KOtBu (2.5 equiv, 140 mg) in a sealed tube under an atmosphere of air for 3 h. Isolated yield was showed out brackets, 1H NMR yield were showed in brackets. b10 equiv of amide 2 was used, temperature is 70 °C. c10 equiv of amide 2 was used, temperature 80 °C. d1.5 mL DMF was used, 4 equiv KOtBu was used, temperature is 80 °C. ePeroxide (0.1 mmol), KOtBu (5 equiv), HCONH2 (25 equiv), temperature is 80 °C.
Figure 4
Figure 4
Control experiments.
Figure 5
Figure 5
Proposed mechanism.
Figure 6
Figure 6
Gram-scale reaction and application of amides.
See this image and copyright information in PMC

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