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. 2024 May 22:12:1378746.
doi: 10.3389/fchem.2024.1378746. eCollection 2024.

Evaluation of functional group compatibility and development of reaction-accelerating additives in ammonium salt-accelerated hydrazinolysis of amides

Jeesoo Choi  1 , Anna Nawachi  1 , Natsuki Saito  1 , Yuta Kondo  1 , Hiroyuki Morimoto  2 , Takashi Ohshima  1
Affiliations

Evaluation of functional group compatibility and development of reaction-accelerating additives in ammonium salt-accelerated hydrazinolysis of amides

Jeesoo Choi et al. Front Chem. .

Abstract

Functional group compatibility in an amide bond cleavage reaction with hydrazine was evaluated for 26 functional groups in the functional group evaluation (FGE) kit. Accurate and rapid evaluation of the compatibility of functional groups, such as nitrogen-containing heterocycles important in drug discovery research, will enhance the application of this reaction in drug discovery research. These data will be used for predictive studies of organic synthesis methods based on machine learning. In addition, these studies led to discoveries such as the unexpected positive additive effects of carboxylic acids, indicating that the FGE kit can propel serendipitous discoveries.

Keywords: amide bond cleavage; carboxylic acid; functional group compatibility; functional group evaluation kit; zinc trifluoromethanesulfonate.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

SCHEME 1
SCHEME 1
Ammonium salts promoted cleavage of amide bond with hydrazine and further transformation to esters.
FIGURE 1
FIGURE 1
Reaction with additive A0. aDetermined by 19F NMR analysis of the crude mixture using 4-(trifluoromethoxy)anisole (0.1 mmol) as an internal standard. bThe amount of additives were calculated by 1H NMR analysis of the crude mixture using 4-(trifluoromethoxy)anisole (0.1 mmol) as an internal standard.
FIGURE 2
FIGURE 2
The symbols in FGE kit.
SCHEME 2
SCHEME 2
Formation of byproducts derived from additives A4, A5, A15, A16, A18 and A21.
SCHEME 3
SCHEME 3
Formation of byproducts derived from additives A10, A11, and A13.
FIGURE 3
FIGURE 3
Two-dimensional representations of the product yield (%) and remaining additives (%).
SCHEME 4
SCHEME 4
Formation of byproducts derived from additives A1, A17, A6 and A24.
See this image and copyright information in PMC

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