New examples of specific-base catalysis in mononuclear rearrangements of heterocycles found via a designed modification of the side-chain structure

Francesca D’Anna,Susanna Guernelli,Gabriella Macaluso,Vincenzo Frenna,Domenico Spinelli,Salvatore Marullo,Girolamo Cirrincione

doi:10.3998/ark.5550190.0010.811

Francesca D’Anna, Susanna Guernelli + Show 5 more

Open Access

https://doi.org/10.3998/ark.5550190.0010.811

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Abstract

To select suitable candidates for the occurrence of specific-base-catalysis in MRH of (Z)-hydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole we have designed a modification of the side-chain structure by linking a strong electron-withdrawing system to the hydrazono group. Thus we have synthesized the (Z)-semicarbazone (3d), the (Z)-phenylsemicarbazone (3e), and the (Z)-acetylhydrazone (3f) of the above oxadiazole and examined their kinetic behavior in dioxane/water in a large range of proton concentrations (pS + 4.0−14.5). In all the pS + range examined only a base-catalyzed process has been evidenced (no uncatalysed path occurs). The behavior at the largest pS + values (the reactivity tends to a limiting rate constant) and that at variable concentrations of buffer have furnished clear evidence for the occurrence of a specificbase-catalysed process, thus reaching the target proposed and confirming the prevision.

Highlights

The study of the synthesis and of the reactivity of heterocyclic compounds is one of the main subjects of organic chemists, sometimes for pure scientific interest and for the large use of heterocyclic derivatives as synthones or as masked functionalities[1] as well as in practical applications.[2]
The title rearrangement has been studied in the temperature range 288.1–313.1 K in the pS+ range 3.9–14.8.7a-g The apparent-rate-constants [(kA,R)3d–f] at some pS+ values (5.0, 7.0, 9.0, 11.0, and 13.0) and at 293.1 K together with the thermodynamic parameters calculated at 293.1 K are collected in Table 1
At first sight two other comments can be made: a) the occurrence of the uncatalyzed pathway could not be evidenced for 3d–f according with the very low nucleophilic character for the semicarbazonic or the acetylhydrazonic Nα nitrogen;7a,g,j b) the trend observed for the apparent-rate-constants at high pS+ values suggests the formation of an Arrhenius complex for the base-catalyzed pathway and the occurrence of a specific-base-catalysis.[9]

Summary

Introduction

The study of the synthesis and of the reactivity of heterocyclic compounds is one of the main subjects of organic chemists, sometimes for pure scientific interest and for the large use of heterocyclic derivatives as synthones or as masked functionalities[1] as well as in practical applications (from medicinal chemistry to materials industry).[2].

Results

Conclusion