Synlett, Table of Contents Synlett 2018; 29(12): 1649-1653DOI: 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 Affiliations Recommend Article Abstract Buy Article All articles of this category 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 Key wordsvinylogous Blaise reaction - pyridinones - pyridine ring synthesis - zinc catalysis - bromoalkenoates Full Text References References 1 Murugan R. Scriven EF. V. In Pyridines: From Lab to Production . Scriven EF. V. Academic Press; Oxford: 2013. Chap. 1 2 Anderson T. Justus Liebigs Ann. Chem. 1846; 60: 86 3 Pozharskiĭ AF. Soldatenkov AT. Katritzky AR. Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry, Biochemistry and Applications . Wiley; Chichester: 2011. 2nd ed 4 Hamama WS. Waly M. El-Hawary I. Zoorob HH. Synth. Commun. 2014; 44: 1730 5a Mitscher LA. Chem. Rev. 2005; 105: 559 5b Li Q. Mitscher LA. Shen LL. Med. Res. Rev. 2000; 20: 231 6a Wall ME. Wani MC. Cook CE. Palmer KH. McPhail AT. Sim GA. J. Am. Chem. Soc. 1966; 88: 3888 6b Ljungman M. Hanawalt PC. Carcinogenesis 1996; 17: 31 6c Efferth T. Fu Y.-J. Zu Y.-G. Schwarz G. Konkimalla VS. B. Wink M. Curr. Med. Chem. 2007; 14: 2024 7a Aly R. Katz HI. Kempers SE. Lookingbill DP. Lowe N. 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Brković DV. Marinković AD. Hem. Ind. 2014; 68: 1 13 Keller PA. Abdel-Hamid MK. Abdel-Megeed AM. Pyridines: From Lab to Production . Scriven EF. V. Academic Press; Oxford: ; Chap. 2; 15 14 Kröhnke F. Zecher W. Curtze J. Drechsler D. Pfleghar K. Schnalke KE. Weis W. Angew. Chem. Int. Ed. Engl. 1962; 1: 626 15a Guareschi I. Mem. Reale Accad. Sci. Torino II 1896; 46: 7,11,25 15b Guareschi I. Atti Accad. Sci. Torino 1900; 36: 443 15c Baron H. Remfry FG. P. Thorpe JF. J. Chem. Soc. Trans 1904; 85: 1726 ; 16 Hantzsch A. Justus Liebigs Ann. Chem. 1882; 215: 1 17 Chichibabin AE. Russ. J. Phys. Chem. 1905; 37: 1229 18 Petrenko-Kritschenko P. J. Prakt. Chem. 1912; 85: 1 19a Blaise EE. C. R. Hebd. Seances Acad. Sci. 1901; 132: 478 19b Blaise EE. C. R. Hebd. Seances Acad. Sci. 1901; 132: 987 19c Blaise EE. Bull. Soc. Chim. Fr. 1906; 35: 589 19d For reviews, see: Rao HS. P. Rafi S. Padmavathy K. Tetrahedron 2008; 64: 8037 19e Kim JH. Ko YO. Bouffard J. Lee S.-g. Chem. Soc. Rev. 2015; 44: 2489 20 Rao HS. P. Muthanna N. Eur. J. Org. Chem. 2015; 1525 21 Rao HS. P. Muthanna N. Synlett. 2016; 27: 2014 22 Rao HS. P. Rafi S. Padmavathy K. Lett. Org. Chem. 2008; 5: 527 23 Detailed information on the optimization of the reaction conditions is given in Table 1 of the Supplementary Information. 24 Kröhnke F. Zecher W. Angew. Chem. 1962; 74: 811 25 Smith CL. Hirschhäuser C. Malcolm GK. Nasrallah DJ. Gallagher T. Synlett. 2014; 25: 1904 26a Arendt J. Rajaratnam SM. Br. J. Psychiatry 2008; 193: 267 26b Zlotos DP. Arch. Pharm. (Weinheim) 2005; 338: 229 27a Rice LE. Boston MC. Finklea HO. Suder BJ. Frazier JO. Hudlicky T. J. Org. Chem. 1984; 49: 1845 27b Fürstner A. Synthesis 1989; 571 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. Supplementary Material Supplementary Material Supporting Information
