Unexpected ring-opening of 2,3-dihydropyridines

Michael-Hannes Hoffelner,Nadine Kretschmer,Marcel Kaiser,Adelheid Brantner,Robert Saf,Pascal Mäser,Robert Weis,Werner Seebacher,Rudolf Bauer,Ferdinand Belaj,Eva-Maria Pferschy-Wenzig,Muaaz Alajlani

doi:10.1007/s00706-021-02850-3

Abstract

The reaction of 2,3-dihydropyridines with sulfonyl halides surprisingly yielded open chain dienes with sulfonylimine structure. The products were specific out of several possible isomers and, therefore, a separation of isomers was not necessary. All new compounds were characterized using FT-IR spectroscopy, HRMS, and NMR spectroscopy. A bicyclic by-product from the reaction of a 2,3-dihydropyridine with mesyl chloride was isolated and its structure elucidated using a single X-ray crystal analysis. Some biological activities, like antimicrobial and cytotoxic properties were investigated.Graphic abstract

Highlights

Sulfonylimines have been described recently as important reagents and intermediates for the syntheses of heterocycles [1,2,3], heterocyclic arrangements [4], cycloadditions [5, 6] and asymmetric Friedel–Crafts reactions [7] as well as for Germany the synthesis of natural products [8, 9]
We already described some reactions of 2,3-dihydropyridines like benzylation in ring positions 1 and 3 [15,16,17] as well as the reaction with benzoyl halides to acyl derivatives [18] and investigated the antiprotozoal, antimicrobial, and anticancer potencies of these products [15,16,17,18]. It seems that the conjugated double bond system and a nitrogen in position 4 are important for those activities, since reduction of the double bonds to a piperidine-4-amine [16] or the hydrolysis to a keto group resulted in a complete loss of activity
Starting compounds were the bases 1a–1d of 6-unsubstituted tetrahydropyridin-4-ylidene ammonium salts (THPS) which were prepared from their 6-methylsulfanyl analogues via selective reduction with deactivated Raney nickel [19]

Summary

Introduction

Sulfonylimines have been described recently as important reagents and intermediates for the syntheses of heterocycles [1,2,3], heterocyclic arrangements [4], cycloadditions [5, 6] and asymmetric Friedel–Crafts reactions [7] as well as for Germany the synthesis of natural products [8, 9]. C15H20N2O2S) Reaction of 573 mg of 1a (3.76 mmol) in 33 cm3 of CH2Cl2 with 698 mg of benzenesulfonyl chloride (3.95 mmol) in the presence of 1.141 g of TEA (11.28 mmol) yielded after 4 d a residue which was purified by CC using (CH2Cl2:MeOH = 30:1) as eluent.

Results

Conclusion