Synlett 2023; 34(05): 429-432
DOI: 10.1055/a-1946-6522
cluster
Special Edition Thieme Chemistry Journals Awardees 2022

A Facile and Mild Alkylation Protocol of NH-Diphenyl Sulfondiimines

Zeyu Xu
,
Shuaisong Su
,
Xue Li
,
Tiezheng Jia
This work is supported by Natural Science Foundation of Guangdong Province (2022A1515011770), Guangdong-Joint Foundation of Shenzhen (2021B1515120046), Shenzhen Nobel Prize Scientists Laboratory Project (C17783101), and Guangdong Provincial Key Laboratory of Catalysis (2020B121201002).


Abstract

As a promising pharmacophore, sulfondiimines have drawn increasing attention in recent years, but their uptake in medicinal chemistry is jeopardized by the scarcity of related transformations. Herein, we report a facile and mild N-alkylation protocol of NH-diphenyl sulfondiimines with alkyl halides to prepare a myriad of N-alkylated diphenyl sulfondiimines. Owing to air atmosphere, room temperature, as well as mild reaction conditions, this protocol has exhibited great potential in organic synthesis and medicinal chemistry by the late-stage functionalization of natural products.

Supporting Information



Publication History

Received: 20 June 2022

Accepted after revision: 18 September 2022

Accepted Manuscript online:
18 September 2022

Article published online:
14 October 2022

© 2022. Thieme. All rights reserved

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  • 12 General Procedure for Alkylation To an oven-dried microwave vial equipped with a stir bar were added 1a (185.2 mg, 0.5 mmol) and Cs2CO3 (243.8 mg, 0.75 mmol). Acetone (0.5 mL) and benzyl bromide (2a, 79.0 μL, 0.75 mmol) were added via syringe, and the vial was sealed with a septum. The reaction was stirred for 6 h at room temperature under an air atmosphere. Upon completion of the reaction, the solvent was concentrated under reduced pressure, and the residue was purified by flash chromatography on silica gel (eluted with EtOAc–hexane = 1:4) to give the pure product 3aa. R f = 0.3 (EtOAc–hexane = 1:4); mp 128.3–128.9 °C. 1H NMR (600 MHz, CDCl3): δ = 7.98–7.95 (m, 4 H), 7.72 (d, J = 8.0 Hz, 2 H), 7.51–7.47 (m, 2 H), 7.43–7.38 (m, 4 H), 7.29–7.26 (m, 4 H), 7.23–7.19 (m, 1 H), 7.03 (d, J = 8.0 Hz, 2 H), 3.95 (s, 2 H), 2.28 (s, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 142.1, 140.9, 140.5, 138.4, 132.9, 129.3, 129.0, 128.5, 128.1, 127.4, 126.9, 126.6, 47.0, 21.4 ppm. IR (thin film): 1495, 1403, 1292, 1149, 1071, 1038, 1061, 848, 749, 720 cm–1. HRMS: m/z calcd for C26H25O2N2S2 +: 461.1352; found: 461.1347 [M + H]+.