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Synlett 2018; 29(12): 1649-1653
DOI: 10.1055/s-0037-1610171
letter
© Georg Thieme Verlag Stuttgart · New York

Vinylogous Blaise Reaction: Conceptually New Synthesis of Pyridin-2-ones

H. Surya Prakash Rao*
Department of Chemistry, Pondicherry University, Pondicherry-605 014, India
,
Nandurka Muthanna
Department of Chemistry, Pondicherry University, Pondicherry-605 014, India
,
Ashiq Hussain Padder
Department of Chemistry, Pondicherry University, Pondicherry-605 014, India
› Author AffiliationsH.S.P.R. thanks the University Grants Commission (UGC), the Major Research Project (MRP) Special Assistance Program (SAP), and the ­Department of Science and Technology Fund for Improvement of S&T Infrastructure in Universities and Higher Educational Institutions (DST-FIST) programs. N.M. thanks the UGC for a fellowship. A.H.P. thanks Pondicherry University for a fellowship. The authors thank the Central Instrumentation Facility (CIF) and Department of Chemistry for the instrumentation facilities.
Further Information

Publication History

Received: 12 April 2018

Accepted after revision: 13 May 2018

Publication Date:
19 June 2018 (online)

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Abstract

A conceptually new synthesis of pyridine rings by a [C4 + CN] assembly has been developed by applying a vinylogous version of the classic Blaise reaction. The zinc-mediated reaction of (het)aryl or alkyl nitriles with ethyl-4-bromocrotonate provided a variety of C(6)-substituted pyridin-2-ones in a single-step.

Key words

vinylogous Blaise reaction - pyridinones - pyridine ring ­synthesis - zinc catalysis - bromoalkenoates

Supporting Information

    Detailed experimental procedures and spectra of the pyridin-2-ones 13a-m made in this study are given in the supplementary material available online at https://doi.org/10.1055/s-0037-1610171.
  • Supporting Information
 

  • References

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  • 28 Pyridin-2-ones 13a–m; General Procedure A solution of TMSCl (3 mol%) in anhyd 1,4-dioxane (1 mL) was added to a suspension of Zn dust (2 equiv) in anhyd 1,4-dioxane (3 mL), and the resulting suspension was refluxed with vigorous stirring for 25 min. The appropriate nitrile (2 mmol) in dry 1,4-dioxane (1 mL) and ethyl (E)-4-bromobut-2-enoate (12; 2 equiv) in dry 1,4-dioxane (1 mL) were simultaneously added dropwise to the refluxing suspension during 10 min by using two syringes. The resulting light-green mixture was refluxed until all the starting material was consumed and the color changed to brown (TLC; 3–6 h). The mixture was cooled to r.t. then centrifuged (700 rpm). The upper solution was decanted and the remaining solid was washed with 1,4-dioxane (4 × 1 mL). The 1,4-dioxane solutions were combined and concentrated to about 1 mL under reduced pressure in a rotatory evaporator. The residue was treated with 50% aq K2CO3 until the pH reached 13 (~5 mL). The resulting mixture was stirred for 30 min at r.t. (30 °C) then diluted with CH2Cl2 (10 mL) and H2O (10 mL). The organic layer was separated, washed sequentially with H2O (2 × 10 mL) and brine (10 mL), dried (Na2SO4), and evaporated under reduced pressure to give a crude product that was purified by column chromatography [silica gel (100–200 mesh); 15–60% EtOAc–hexane]. 6-Phenylpyridin-2(1H)-one (13a) By following the general procedure, the reaction of PhCN (5a; 201 mg, 1.94 mmol) with crotonate 12 (374 mg, 1.94 mmol) in the presence of Zn (252 mg, 3.88 mmol) and TMSCl (7 mg, 3 mol %) in 1,4-dioxane (6 mL) for 4 h, followed by hydrolysis with 50% aq K2CO3 (5 mL) gave a light-yellow solid; yield: 205 mg (62%); mp 194–195 °C; Rf = 0.5 (hexanes–EtOAc, 2:1). IR (KBr): 2904, 1643, 1612, 1550, 1493, 990, 921, 795, 761 cm–1. 1H NMR (400 MHz, CDCl3): δ = 12.49 (br s, 1 H), 7.72 (d, J = 6.9 Hz, 2 H), 7.59–7.40 (m, 4 H), 6.55–6.47 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 165.4, 147.1, 141.5, 133.6, 130.1, 129.2, 126.8, 118.7, 105.0. HRMS (ESI): m/z [M + H] calcd for C11H9NO: 172.0762; found: 172.0750.