Synthesis 2021; 53(10): 1760-1770
DOI: 10.1055/s-0040-1706639
paper

N-Chlorinative Ring Contraction of 1,4-Dimethoxyphthalazines via a Bicyclization/Ring-Opening Mechanism

Jeong Kyun Im
,
Ilju Jeong
,
ByeongDo Yang
,
Hyeon Moon
,
Jun-Ho Choi
,
Won-jin Chung
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science & ICT (NRF-2020R1F1A1076028) and by ‘GIST Research Institute (GRI)’ grant funded by the GIST in 2020.


Abstract

An unprecedented N-chlorinative ring contraction of 1,2-diazines was discovered and investigated with an electrophilic chlorinating reagent, trichloroisocyanuric acid (TCICA). Through optimization and mechanistic analysis, the assisting role of n-Bu4NCl as an exogenous nucleophile was identified, and the optimized reaction conditions were applied to a range of 1,4-dimethoxyphthalazine derivatives. Also, an improvement of overall efficiency was demonstrated by the use of a labile O-silyl group. A bicyclization/ring-opening mechanism, inspired by the Favorskii rearrangement, was proposed and supported by the DFT calculations. Furthermore, the efforts on scope expansion as well as the evaluation of other electrophilic promoters revealed that the newly developed ring contraction reactivity is a unique characteristic of 1,4-dimethoxyphthalazine scaffold and TCICA.

Supporting Information



Publication History

Received: 26 October 2020

Accepted after revision: 14 November 2020

Publication Date:
21 December 2020 (online)

© 2020. Thieme. All rights reserved

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