The mechanism of the bischler‐napieralski reaction

Abstract

The Bischler‐Napieralski dihydroisoquinoline synthesis was proven to occur via imidoyl chlorides and the corresponding nitrilium salt. The two‐step process required much milder conditions (20°–50°) compared to drastic classical conditions of refluxing at 100°–200°. The Bischler‐Napieralski reaction is shown to share a common intermediate with two other well‐known reactions: the von Braun and the Ritter reactions.

Synthesis, DNA Binding and Antitumor Evaluation of Styelsamine and Cystodytin Analogues

“…[24] 110–111 °C); R f (3 EtOAc:1 Hex) 0.40; IR ν max (ATR) 3245, 3008, 2994, 1660, 1605, 1232 cm −1 ; 1 H NMR (CDCl 3 , 400 MHz) δ H 7.32–7.25 (3H, m, H-14, H-15 and H-16), 7.16 (2H, dd, J = 8.0, 2.0 Hz, H-13 and H-17), 6.71 (1H, d, J = 8.2 Hz, H-8), 6.59 (1H, d, J = 2.0 Hz, H-5), 6.54 (1H, dd, J = 8.2, 2.0 Hz, H-9), 5.36 (1H, br s, NH-1), 3.85 (3H, s, OMe), 3.81 (3H, s, OMe), 3.53 (2H, s, H 2 -11), 3.44 (2H, dt, J = 6.9, 6.9 Hz, H 2 -2), 2.67 (2H, t, J = 6.9 Hz, H 2 -3); 13 C NMR (CDCl 3 , 100 MHz) δ C 170.9 (C-10), 149.0 (C-6 or C-7), 147.6 (C-6 or C-7), 134.8 (C-12), 131.1 (C-4), 129.4 (C-13 and C-17), 129.0 (C-14 and C-16), 127.3 (C-15), 120.5 (C-9), 111.7 (C-5), 111.3 (C-8), 55.9 (OMe), 55.8 (OMe), 43.9 (C-11), 40.7 (C-2), 35.0 (C-3); (+)-ESIMS m/z 300 [M + H] + ; (+)-HRESIMS [M + H] + 300.1593 (calcd. for C 18 H 22 NO 3 , 300.1594).…”

Synthesis of Iminium Salts, Orthoesters and Related Compounds

“…the preparation of 13-keto orthoesters (374; equation 177) from fluorinated ketones,822 or the synthesis of trimethoxymethylalkyne from 1,4-dichloro-2,3-dibromo-2-butene. 823 (376) ( RO h C -0-C(ORh (377) N-N (Meohc-I(s>-'-C(OMeh (378) In the reaction of sodium methoxide with 3-trichloromethylpyridine the nicotinecarbaldehyde acetal (191) Pinner synthesis of orthoesters starting from alkoxymethyleneiminium salts (410; equation 192) (imino ester hydrohalides) is a standard procedure, which has been reviewed several times. 15 ,16,22,24,27 For some more recent results see ref.…”

Medicinal chemistry perspectives of 1,2,3,4-tetrahydroisoquinoline analogs – biological activities and SAR studies

“…Mechanistically, the reaction is said to proceed via intramolecular electrophilic aromatic substitution reaction. 15,16 The presence of an electron-donating group like hydroxy or methoxy favors the cyclization step.…”