Oxidative Annulations Involving DMSO and Formamide: K₂S₂O₈ Mediated Syntheses of Quinolines and Pyrimidines

Abstract

An efficient strategy toward 4-arylquinolines and 4-arylpyrimidines from readily available precursors is described. Oxidative annulation promoted by K2S2O8 involving anilines, aryl ketones, and DMSO as a methine (CH−) equivalent leads to 4-arylquinolines via a cascade that entails generation of a sulfenium ion, subsequent C–N and C–C bond formations, and cyclization. The application of this strategy to the activation of acetophenone–formamide conjugates toward the synthesis of 4-arylpyrimidines is also described.

Dimethyl Sulfoxide: Yesterday's Solvent, Today's Reagent

“…In 2017, Singh et al. synthesized 4‐arylquinolines 54 by an oxidative annulation reaction of anilines 40 , aryl methyl ketones 39 and DMSO 1 as a methine (=CH) source in the presence of FeCl 3 as catalyst and K 2 S 2 O 8 as oxidant at 120 °C (Scheme ) . 4‐Arylquinoline derivatives 54 were obtained using substituted anilines 40 , acetophenones 39 and DMSO 1 in moderate to good yields (43–80%) (Scheme ).…”

Reaction Medium as the Installing Reservoir for Key Functionalities in the Molecules

“…Singh and Jadhav (2017) have synthesized 4‐arylquinolines from anilines and ketones by K 2 S 2 O 8 mediated activation of DMSO as a one carbon synthone (Scheme ) . Present protocol involves the generation of a sulfenium ion, subsequent C−N and C−C bond formations, and cyclisation for the synthesis of 4‐aylquinolines by iron catalyst.…”

Dimethyl Sulfoxide Serves as a Dual Synthon: Construction of 5‐Methyl Pyrimidine Derivatives via Four Component Oxidative Annulation

“…Keywords: Activation of dimethyl sulfoxide; potassium persulfate mediated; Dual synthon; Multicomponent annulation reaction; 5-methyl pyrimidine derivatives Dimethyl sulfoxide (DMSO) has been extensively utilized as a cheap and versatile solvent in organic synthesis. [1] Besides being an effective polar aprotic medium, activation of DMSO has become a constantly fascinating research area [2] because it can serve as a multipurpose fragment donor such as oxygen source, [3] sulfur source [4] and carbon source [5,[7][8][9][10] for incorporation into target molecules. In particular, by the capture of sulfenium ion [5f,6] generated in situ from the activation of DMSO, examples for the rapid assembly of heterocyclic compounds have been realized.…”

“…In particular, by the capture of sulfenium ion [5f,6] generated in situ from the activation of DMSO, examples for the rapid assembly of heterocyclic compounds have been realized. [7][8][9][10] However, in these annulation reactions, the sulfenium ion was generally intercepted by various elaborately designed substrates to proceed in an intramolecular manner, [7] illustrations for intermolecular multicomponent annulation reactions by employing DMSO as an essential building block remain rare. In 2016, our group developed an appealing I 2 /Cu(NO 3 ) 2 · 3H 2 Omediated reaction for the preparation of substituted pyridines by trapping the in situ-generated sulfenium ion (Scheme 1,a).…”

“…3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 lines via a cascade that entails generation of a sulfenium ion, subsequent CÀN and CÀC bond formations, and cyclization (Scheme 1,c). [10] Despite these advancements, there is still a demand for the development of new multicomponent annulation reactions related to sulfenium ion generated from DMSO that allow efficient construction of other heterocycles. Herein, we report an unusual K 2 S 2 O 8 mediated four component reaction for the construction of 5-methyl pyrimidine derivatives (Scheme 1,d).…”