A Novel Three-Component Reaction: Synthesis of Some Complex Annelated Quinolines from Simple Acetanilides and via Intramolecular 1,3-Dipolar Cycloaddition of Azide to Nitrile

Biswajita Baruah; Mohit L. Deb; Pulak J. Bhuyan

doi:10.1055/s-2007-982568

LETTER

A Novel Three-Component Reaction: Synthesis of Some Complex Annelated Quinolines from Simple Acetanilides and via Intramolecular 1,3-Dipolar Cycloaddition of Azide to Nitrile

Biswajita Baruah, Mohit L. Deb, Pulak J. Bhuyan*
Medicinal Chemistry Division, Regional Research Laboratory, Jorhat 785006, Assam, India
Fax: +91(376)2370011; e-Mail: pulak_jyoti@yahoo.com;

Abstract

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Abstract

Synthesis of a novel class of tetrazolo[4′,5′:1,6]pyrido[2,3-d]quinolines from simple acetanilides and via intramolecular 1,3-dipolar cycloaddition of azides to nitriles using a three-component one-pot protocol is reported.

Key words

quinolines - acetanilides - multicomponent reaction - cyano-stabilised carbanion - intramolecular 1,3-dipolar cycloaddition reactions

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References

References and Notes

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Three-Component Reaction
To a mixture of 2-chloro-3-formylquinoline (2a, 192 mg, 1 mmol), ethyl cyanoacetate (3a, 140 mg, 1.24 mmol) and NaN₃ (4, 80 mg, 1.24 mmol) in DMF (10 mL) were added two drops of water. A catalytic amount (1-2 drops) of Et₃N was then added to the reaction mixture and it was allowed to stir for 4 h at 50-60 °C. After completion of the reaction, the mixture was cooled to r.t. and poured into H₂O under continuous stirring. A brown solid precipitated that was shown to be almost totally pure 5a. However, it was further purified by preparative TLC using EtOAc-hexane (3:7); mp 205 °C, yield 234 mg (80%). ¹H NMR (CDCl₃): δ = 1.43 (t, 3 H), 4.32 (q, 2 H), 7.26 (s, 1 H), 7.60-8.05 (m, 4 H), 8.63 (s, 1 H). ¹³C NMR (CDCl₃): δ = 14.50 (CH₃), 61.20 (CH₂C=O), 112.55 (C-5), 123.75 (C-4), 124.00 (C-2), 126.20 (C-7), 127.45 (C-3), 127.70 (C-6), 131.00 (C-6a), 136.20 (C-11b), 138.36 (C-8), 145.12 (C-8a), 146.67 (C-5a), 151.25 (C-1a), 171.75 (C=O). MS: m/z = 316 [M + Na]⁺. IR (CHCl₃): 2923.70, 2852.60, 1742.80 cm^-1. Anal. Calcd for C₁₅N₅O₂H₁₁: C, 61.43; H, 3.75; N, 23.89. Found: C, 61.43; H, 3.82; N, 23.95.

2-Chloro-3-formyl quinoline (2a, 384 mg, 2 mmol) was mixed with ethyl cyanoacetate (3a, 260 mg, 2.17 mml) in toluene (10 mL). One drop of piperidine was added and the reaction mixture was allowed to stir at r.t. for 1 h. The solvent was evaporated and the yellow solid obtained was purified by recrystallisation from EtOH.
Compound [Aa] (R¹ = H, R² = CO₂Et): mp 110 °C, yield 516 mg (98%). ¹H NMR (CDCl₃): δ = 1.43 (t, 3 H), 4.43 (q, 2 H), 7.46-815 (m, 4 H), 8.74 (s, 1 H), 9.05 (s, 1 H). IR (CHCl₃): 2226.70, 1730.90 cm^-1.

The condensed product [Aa] (286 mg, 1 mmol) was mixed with NaN₃ (4, 80 mg, 1.24 mmol) in DMF (10 mL) and 2 drops of H₂O were added. The reaction mixture was allowed to stir for 4 h at 50-60 °C. After completion of the reaction the mixture was cooled to r.t. and poured into H₂O under continuous stirring. A brown coloured solid which appeared was filtered and purified by preparative TLC using EtOAc-hexane (3:7) to furnish 5a (176 mg, 60%).