1,2-Dihydropyridazines as Versatile Synthetic Intermediates

Published as part of the Special Section 11^th EuCheMS Organic Division Young Investigator Workshop

Abstract

The reactivity of 1,2-dihydropyridazines under various conditions is described, leading to the formation of a variety of products, including 2-aminopyrroles, phenylenediamines, and several novel heterocyclic motifs.

Key words

dihydropyridazines - heterocycles - pyrroles - diazetidines - phenylenediamines

• References and Notes

• 1 Britten TK, Kemmitt PD, Halcovitch NR, Coote SC. Org. Lett. 2019; 21: 9232
• 2 Britten TK, Akien GR, Kemmitt PD, Halcovitch NR, Coote SC. Tetrahedron Lett. 2019; 60: 1498
• 3 Fisher TH, Crook JC, Chang S. Tetrahedron 1987; 43: 2443
• 4 Chen B, Scott ME, Adams B, Hrovat D, Borden WT, Lautens M. Org. Lett. 2014; 16: 3930
• 5a Altman LJ, Semmelhack MF, Hornby RB, Vederas JC. Chem. Commun. 1968; 686
• 5b Sheradsky T, Moshenberg R. J. Org. Chem. 1984; 49: 587
• 5c Sheradsky T, Moshenberg R. J. Org. Chem. 1985; 50: 5604
• 6 Methyl 2-[(Methoxycarbonyl)amino]-1H-pyrrole-1-carboxylate (2a); Typical ProcedureA solution of 1,2-dihydropyridazine 1a (520 mg, 2.62 mmol, 1.0 equiv) in o-xylene (5 mL) was refluxed for 5 h under argon. Purification by flash column chromatography [silica gel, hexane–EtOAc (100% hexane to 9:1)] gave a white solid; yield: 320 mg (1.61 mmol, 62%); mp 46–47 °C; R_f = 0.35 (hexane–EtOAc, 2:1). FTIR (ATR): 3349 (NH), 2950, 1724 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 9.05 (br s, 1 H, NH), 6.85 (dd, J = 3.6, 1.8 Hz, 1 H, Ar–H), 6.42–6.32 (br m, 1 H, Ar–H), 6.13 (t, J = 3.6 Hz, 1 H, Ar–H), 3.95 (s, 3 H, OMe), 3.77 (s, 3 H, OMe). ¹³C NMR (100 MHz, CDCl₃): δ = 153.1 (C=O), 152.4 (C=O), 130.5 (Ar–C), 114.0 (Ar–CH), 111.6 (Ar–CH), 98.4 (Ar–CH), 54.2 (OMe), 52.6 (OMe). HRMS (APCI): m/z [M + H]⁺calcd for C₈H₁₁N₂O₄: 199.0713; found: 199.0712. Note: To prevent degradation, the 2-aminopyrroles must be stored in the freezer under an inert atmosphere.
• 7 Arora PC, Mackay D. J. Chem. Soc. D 1969; 677