[14148-42-6]  · C9H9N3  · 8-Hydrazinoquinoline  · (MW 159.21)

(Fischer indole synthesis: pyrido[3,2-g]indoles)

Alternate Name: 8-HQ.

Physical Data: pale yellow solid; mp 63.5-64 °C.

Solubility: sol ether, dichloromethane, ethanol.

Preparative Methods: the original preparation of the reagent involved the diazotization of commercially available 8-aminoquinoline followed by reduction with tin(II) chloride.1 An improved one-step method has been developed which starts with the less expensive 8-hydroxyquinoline.2 Sulfur dioxide (10 g) is dissolved in hydrazine hydrate (80 mL), 8-hydroxyquinoline (10.16 g) is added and the mixture is refluxed for 7 d. Every 48 h, EtOH (10 mL) is added to dissolve any starting material which may have sublimed into the condenser. The mixture is cooled, 2 M NaOH (100 mL) is added, and the resulting emulsion is extracted with CHCl3 (4 × 75 mL). The combined organic layers are washed with brine (20 mL), dried over MgSO4, and concentrated. The residue crystallizes upon standing and may be recrystallized from CH2Cl2 and pentane to afford 8.7 g (78%) of 8-HQ as pale yellow needles (eq 1).

Handling, Storage, and Precautions: the reagent is sensitive to air and light and is best kept under an inert atmosphere at 0 °C in the dark. Slow decomposition occurs with time and the material turns brown. In the early stages it can be repurified by recrystallization. Use in a fume hood.

Pyrido[3,2-g]indole Synthesis.

8-Hydrazinoquinoline provides a very useful method for the direct introduction of the pyrido[3,2-g]indole subunit. Other isomers of 8-HQ behave in an analogous fashion.3 Treatment of 5,6,7,8-tetrahydro-8-quinolone with 8-HQ in EtOH results in precipitation of the hydrazone in essentially pure from. This material may then be heated with Polyphosphoric Acid (PPA), basified, and extracted with CH2Cl2 to provide a dihydrodipyridocarbazole (eq 2).2

The reaction also works with appropriate diketones to introduce two pyridoindole subunits. If the reactants are only combined in equimolar amounts, an intermediate monoketone derivative may be obtained (eq 3).2

Related Reagents.

Acetone Hydrazone; Hydrazine; Phenylhydrazine; Polyphosphoric Acid.

1. Hünig, S.; Werner, H. LA 1959, 628, 46.
2. Hegde, V.; Hung, C.-Y.; Madhukar, P.; Cunningham, R.; Höpfner, T.; Thummel, R. P. JACS 1993, 115, 872.
3. (a) Buu-Hoï, N. P.; Périn, F.; Jacquignon, P. JCS 1960, 4500. (b) Buu-Hoï, N. P.; Périn, F.; Jacquignon, P. JCS 1962, 146.

Randolph P. Thummel

University of Houston, TX, USA

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