Alcohol-Initiated Dinitrile Cyclization in Basic Media: A Route Toward Pyrazino[1,2-a]indole-3-Amines

Abstract

A selective route to the formation of 1-alkoxypyrazino[1,2-a]indole-3-amines through alcohol-initiated dinitrile cyclization, starting from N-(cyanomethyl)indole-2-carbonitriles under basic conditions, was discovered. The resulting compounds were shown to be unstable in solution, and a three-component reaction of the dinitrile, alcohol, and aromatic aldehyde was used to overcome the problem.

Key words

pyrazinoindoles - cyclization - dinitriles - domino reaction - multicomponent reaction - transition-metal free

• References and Notes

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• 42 X-ray diffraction data for 4d were collected on a Bruker APEX DUO diffractometer [λ(MoKα) = 0.71073 Å, ω-scans, 2θ < 56°]. Yellow crystals of C₂₀H₁₇N₃O₂ at 120(2) K are monoclinic, space group P2₁/c, a = 17.855(3), b = 5.7930(8), c = 15.267(2) Å, β = 96.335(3)°, V = 1569.5(4) Å3, Z = 4 (Z′ = 1), d_calc = 1.402 g cm^–3. Intensities of 3789 independent reflections (R_int = 0.0876) out of 17025 collected were used in structure solution and refinement. The structure was solved by direct methods and refined by the full-matrix least-squares technique against F² in anisotropic approximation. The hydrogen atom connected to the oxygen atom was found from difference Fourier synthesis and refined isotropically. Other hydrogen atoms were placed in calculated positions and refined in the riding model with U_iso(H) equal to 1.5 U_eq(Cm) and 1.2 U_eq(Ci) of the connected methyl and other carbon atoms. The refinement converged to R₁ = 0.0499 [calculated for 2473 observed reflections with I > 2σ(I), wR₂ = 0.1015, and GOF = 0.999]. All calculations were performed with the SHELX software package (see Ref. 43). Atomic coordinates, bond lengths and angles, and thermal parameters have been deposited at the Cambridge Crystallographic Data Center with the accession number CCDC 1580729, and can be obtained free of charge via www.ccdc.cam.ac.uk/getstructures.
• 43 Sheldrick GM. Acta Crystallogr., Sect. C 2015; 71: 3