Synlett 2015; 26(02): 193-196
DOI: 10.1055/s-0034-1379550
letter
© Georg Thieme Verlag Stuttgart · New York

Regioselective Formation of 5-Methylene-6-methoxy-1,4,5,6-tetrahydropyridazines from the [4+2]-Cycloaddition Reaction of In Situ Generated 1,2-Diaza-1,3-dienes with Methoxyallene

Orazio A. Attanasi
Department of Biomolecular Sciences, Section of Organic Chemistry and Organic Natural Compounds, University of Urbino ‘Carlo Bo’, Via I Maggetti 24, 61029 Urbino (PU), Italy
,
Gianfranco Favi*
Department of Biomolecular Sciences, Section of Organic Chemistry and Organic Natural Compounds, University of Urbino ‘Carlo Bo’, Via I Maggetti 24, 61029 Urbino (PU), Italy
,
Fabio Mantellini
Department of Biomolecular Sciences, Section of Organic Chemistry and Organic Natural Compounds, University of Urbino ‘Carlo Bo’, Via I Maggetti 24, 61029 Urbino (PU), Italy
,
Serena Mantenuto
Department of Biomolecular Sciences, Section of Organic Chemistry and Organic Natural Compounds, University of Urbino ‘Carlo Bo’, Via I Maggetti 24, 61029 Urbino (PU), Italy
,
Giada Moscatelli
Department of Biomolecular Sciences, Section of Organic Chemistry and Organic Natural Compounds, University of Urbino ‘Carlo Bo’, Via I Maggetti 24, 61029 Urbino (PU), Italy
,
Simona Nicolini
Department of Biomolecular Sciences, Section of Organic Chemistry and Organic Natural Compounds, University of Urbino ‘Carlo Bo’, Via I Maggetti 24, 61029 Urbino (PU), Italy
› Author Affiliations
Further Information

Publication History

Received: 25 September 2014

Accepted after revision: 25 October 2014

Publication Date:
21 November 2014 (online)


Abstract

A regioselective inverse-electron-demand hetero-Diels–­Alder reaction of in situ generated 1,2-diaza-1,3-dienes with methoxyallene is reported. These Lewis and Brønsted acid free reactions benefit from operational simplicity and allow access to synthetically valuable 5-methylene-6-methoxy-1,4,5,6-tetrahydropyridazines in high yields.

 
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  • 18 Typical ProcedureTo a CH2Cl2 (3 mL) solution of N-acyl hydrazone 1a (0.150 g, 0.5 mmol) were added methoxyallene (2a, 0.258 g, 3.5 mmol) and Na2CO3 (0.265 g, 2.5 mmol) at 25 °C until complete disappearance of 1a (TLC monitoring, 30 h). After removal of the solvent, the residue was purified directly by flash column chromatography (silica gel, cyclohexane–EtOAc, 90:10) to give the corresponding 1,4,5,6-tetrahydropyridazine 3a as a pale yellow oil (0.134 g, 98%).
  • 19 Ethyl 6-Methoxy-5-methylene-3-phenyl-5,6-dihydropyridazine-1(4H)-carboxylate (3a) 1H NMR (400 MHz, CDCl3): δ = 1.40 (t, J = 7.2 Hz, 3 H), 3.30 (d, 2 J = 19.6 Hz, 1 H), 3.39 (s, 3 H), 3.52 (dt, 2 J = 19.6 Hz, 4 J = 2.8 Hz, 1 H), 4.30–4.41 (m, 2 H), 5.12 (d, 2 J = 2.8 Hz, 1 H), 5.26 (d, 2 J = 2.8 Hz, 1 H), 5.79 (s, 1 H), 7.35–7.41 (m, 3 H), 7.77–7.81 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 14.5 (q), 28.9 (t), 54.9 (q), 62.8 (t), 82.6 (d), 113.5 (t), 125.6 (d), 128.3 (d), 129.4 (d), 134.5 (s), 136.4 (s), 147.5 (s), 155.0 (s). IR (nujol): νmax = 1714. MS: m/z (%) = 274 (88), 257 (91), 249 (100), 235 (45). Anal. Calcd for C15H18N2O3 (274.32): C, 65.68; H, 6.61; N, 10.21. Found: C, 65.55; H, 6.58; N, 10.30.