Hetarynic Synthesis and Chemical Transformations of Dihydrodiquinolinopyrazines

Irina-Claudia Grig-Alexa; Ethel Garnier; Adriana-Luminita Finaru; Lucia Ivan; Christian Jarry; Jean-Michel Léger; Paul Caubère; Gérald Guillaumet

doi:10.1055/s-2004-830876

LETTER

Hetarynic Synthesis and Chemical Transformations of Dihydrodiquinolinopyrazines

Irina-Claudia Grig-Alexa^a,b, Ethel Garnier^a, Adriana-Luminita Finaru^a,b, Lucia Ivan^b,c, Christian Jarry^d, Jean-Michel Léger^d, Paul Caubère^a, Gérald Guillaumet*^a
^a Institut de Chimie Organique et Analytique, UMR CNRS 6005, Université d’Orléans, BP 6759, 45067 Orléans Cedex 2, France
e-Mail: gerald.guillaumet@univ-orleans.fr;
^b Laboratorul de Sinteza Organica si Analiza Structurala, Universitatea Bacau, 157, Calea Marasesti, 600115 Bacau, Romania
^c Laboratorul de Sinteza Organica, Facultatea de Chimie, Universitatea Bucuresti, Bd. Elisabeta, Bucuresti, Romania
^d Pharmacochimie, EA 2962, Université Victor Segalen Bordeaux II, 146, rue Léo Saignat, 33076 Bordeaux Cedex, France

Abstract

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Abstract

New dihydrodiquinolinopyrazines (DHDQP) were easily obtained by hetarynic dimerization of 2-alkylamino-3-bromoquinolines in the presence of complex base NaNH₂-t-BuONa. Functionalization and derivatization of these new heterocycles are described.

Key words

dihydrodiquinolinopyrazines - formylation - nucleophilic nitration

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References

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Under optimal conditions 1 equiv of bromo derivative necessitates 2 equiv of complex base (in other words 4 equiv NaNH₂ and 2 equiv of t-BuONa) and one supplementary equiv of NaNH₂ for the formation of the sodium salt of the bromoamine. Thus, the basic reagent must be prepared by addition of 2 equiv of t-BuOH to 7 equiv of NaNH₂.

Compound 6b: IR (KBr): 1345, 1452 cm^-1. MS: m/z = 397 [M + 1]. ¹H NMR (250 MHz, CDCl₃): δ = 1.06 (6 H, q, J = 7.3 Hz, 2 CH₃), 1.54-1.58 (4 H, m, 2 CH₂), 1.70-1.82 (4 H, m, 2 CH₂), 4.12-4.15 (4 H, t, 2 CH₂N, J = 6.8 Hz), 6.79 (2 H, s), 7.15 (2 H, ddd, J = 7.3 Hz, J = 6.9 Hz, J = 1.2 Hz), 7.29 (2 H, ddd, J = 1.5 Hz, J = 6.9 Hz, J = 7.3 Hz), 7.40 (2 H, dd, J = 7.3 Hz, J = 1.5 Hz), 7.53 (2 H, dd, J = 7.3 Hz, J = 1.2 Hz). ¹³C NMR (62.5 MHz, CDCl₃): δ = 13.8 (2 CH₃), 20.6 (2 CH₂), 31.5 (2 CH₂), 41.3 (2 CH₂N), 119.1 (2 C), 119.5 (2 CH), 122.4 (2 CH), 126.0 (2 CH), 127.9 (2 CH), 129.7 (2 CH), 130.2 (2 C), 140.6 (2 C), 144.4 (2 C). Compound 7b: IR (KBr): 1347, 1455 cm^-1. MS: m/z = 397 [M + 1]. ¹H NMR (250 MHz, CDCl₃): δ = 1.06 (6 H, q, J = 7.2 Hz, 2 CH₃), 1.47-1.62 (4 H, m, 2 CH₂), 1.74-1.86 (4 H, m, 2 CH₂), 3.61 (2 H, t, J = 7.6 Hz, CH₂N), 4.49 (2 H, t, J = 7.6 Hz, CH₂N), 6.66 (2 H, s), 7.16 (2 H, ddd, J = 7.1 Hz, J = 6.8 Hz, J = 1.1 Hz), 7.32 (2 H, ddd, J = 1.2 Hz, J = 6.8 Hz, J = 7.5 Hz), 7.58 (2 H, dd, J = 7.1 Hz, J = 1.2 Hz), 7.65 (2 H, dd, J = 7.5 Hz, J = 1.1 Hz). ¹³C NMR (62.5 MHz, CDCl₃): δ = 13.8 (2 CH₃), 20.6 (2 CH₂), 32.9 (CH₂), 33.5 (CH₂), 41.3 (CH₂N), 42.9 (CH₂N), 116.6 (2 C), 120.3 (2 CH), 121.4 (2 CH), 123.3 (2 CH), 125.0 (2 CH), 127.8 (2 CH), 128.4 (2 C), 137.6 (2 C), 145.5 (2 C).

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Compound 8: IR (KBr): 1433, 1676 cm^-1. MS: m/z = 425 [M + 1]. ¹H NMR (250 MHz, CDCl₃): δ = 0.74 (t, 3 H, CH₃, J = 7.2 Hz), 1.03 (t, 3 H, CH₃, J = 7.2 Hz), 1.20-1.29 (m, 2 H, CH₂), 1.51-1.59 (m, 2 H, CH₂), 1.65-1.82 (m, 4 H, 2 CH₂), 4.24 (t, 2 H, CH₂N, J = 7.5 Hz), 4.31 (t, 2 H, CH₂N, J = 6.9 Hz), 7.14 (s, 1 H), 7.28-7.48 (m, 4 H), 7.56-7.64 (m, 2 H), 7.71 (d, 1 H, J = 8.1 Hz), 8.60 (dd, 1 H, J = 1.5 Hz, J = 8.1 Hz), 10.31 (s, 1 H, CHO). ¹³C NMR (62.5 MHz, CDCl₃): δ = 13.7, 14.0 (2 CH₃), 19.8, 20.3 (2 CH₂), 27.4, 30.4 (2 CH₂), 41.9, 56.7 (2 CH₂N), 114.2 (CH), 119.5, 123.2 (2 C), 123.6, 125.3, 125.6 (3 CH), 126.2, 126.8 (2 CH), 127.0 (C), 127.2, 127.4, 127.6 (3 CH) 129.5, 136.5, 142.3, 142.9, 146.4, 147.4 (6 C), 189.7 (CHO).

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Compound 15: IR (KBr): 1470, 1523 cm^-1. MS: m/z = 442 [M + 1]. ¹H NMR (250 MHz, CDCl₃): δ = 1.04 (t, 6 H, 2 CH₃, J = 6.8 Hz), 1.50-1.59 (m, 4 H, 2 CH₂), 1.69-1.78 (m, 4 H, 2 CH₂), 4.08-4.14 (m, 4 H, 2 CH₂N), 6.70 (s, 1 H), 6.87 (s, 1 H), 7.21-7.24 (m, 1 H), 7.31 (dd, 1 H, J = 1.2 Hz, J = 6.8 Hz), 7.37 (d, 1 H, J = 8.8 Hz), 7.42 (dd, 1 H, J = 1.2 Hz, J = 6.8 Hz), 7.55 (d, 1 H, J = 8.3 Hz), 7.88 (dd, 1 H, J = 2.2 Hz, J = 8.8 Hz), 8.34 (d, 1 H, J = 2.2 Hz). ¹³C NMR (62.5 MHz, CDCl₃): δ = 14.0, 14.1 (2 CH₃), 20.3, 20.4 (2 CH₂), 27.2, 27.3 (2 CH₂), 42.3, 42.5 (2 CH₂N), 110.2, 113.4, 118.3, 122.1, 124.9, 126.1, 126.8, 127.4 (9 CH), 128.1, 128.2, 131.9, 132.0, 141.9, 142.9, 144.0, 146.1, 146.5 (9 C).