Mild and Efficient Coupling of Diazo Compounds with Azaaromatic Systems under Solvent-Free Conditions

Abstract

Diazoesters and diazoketones undergo smooth coupling with activated quinolines and isoquinolines under extremely mild conditions to afford diazo-(2-ethoxy-2-oxoethyl)-1,2-dihydro­quinolines and -isoquinolines, respectively, in good to high yields with high selectivity.

Key words

azaaromatic compounds - solvent-free reactions - diazo compounds

References and Notes

• 1 Balasubramanian M. Keay JG. Pyridines and Their Benzo Derivatives: Application, In Comprehensive Heterocyclic Chemistry II   Vol. 5:  Katrizky AP. Rees VW. Scriven EF. Pergamon; Oxford: 1996.  p.245-300  
• 2a For a review, see: Stout DM. Meyers AI. Chem. Rev.  1982,  82:  223 
• 2b Comins DL. Sajan PJ. Pyridines and Their Benzo Derivatives: Reactivity at the Ring, In Comprehensive Heterocyclic Chemistry II   Vol. 5:  Katrizky AP. Rees VW. Scriven EF. Pergamon; Oxford: 1996.  p.37 
• 2c Comins DL. Zhang Y. Joseph SP. Org. Lett.  1999,  1:  657 
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• 2e Magnus P. Rodro Aguez-Lopez J. Mulholland K. Matthews I. J. Am. Chem. Soc.  1992,  114:  382 
• 2f Brana MF. Moran M. Perez de Vega MJ. Pita-Romero I. J. Org. Chem.  1996,  61:  1369 
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• 4 Yadav JS. Reddy BVS. Gupta MK. Prabhakar A. Jagadeesh B. Chem. Commun.  2004,  2124 
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6

General Procedure: Diazoketones (1.2 mmol) and N-acylquinolinium ion (1 mmol), generated in situ from quinoline (1 mmol) and ethyl chloroformate (1.2 mmol), were mixed and the resulting mixture was stirred at r.t. for the appropriate time (Table [1] ). After complete conversion as indicated by TLC, the reaction mixture was diluted with H₂O (10 mL) and extracted with CH₂Cl₂ (2 × 15 mL). The combined extracts were dried over anhyd Na₂SO₄, and concentrated in vacuo. The resulting product was purified by column chromatography on silica gel (Merck, 100-200 mesh; EtOAc-hexane, 2:8) to afford the pure products.
Spectroscopic data for selected compounds are as follows:
Ethyl 1-(1-Diazo-2-ethoxy-2-oxoethyl)-3-methyl-1,2-dihydro-2-isoquinolinecarboxylate (3f): yellow viscous liquid. IR (KBr): 2925, 2853, 2070, 1716, 1642, 1456, 1374, 1307, 1242, 1176, 1117, 1065, 1007, 878, 813, 759 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 6.16-7.27 (m, 3 H), 7.04 (d, J = 6.9 Hz, 1 H), 6.50 (s, 1 H), 5.95 (s, 1 H), 4.20 (q, J = 6.9 Hz, 4 H), 2.29 (s, 3 H), 1.33 (t, J = 6.9 Hz, 3 H), 1.28 (t, J = 6.9 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.2 (2 × C), 21.7, 29.6, 51.6, 60.8, 62.2, 114.9, 124.3, 125.5, 127.1, 128.3, 129.4, 130.9, 135.8, 153.3, 165.2. EIMS-MS: m/z = 352 [M + Na]⁺, 324.1, 302.1, 278. HRMS (ESI): m/z calcd for C₁₇H₁₉N₃O₄Na: 352.1273; found: 352.1290.
Ethyl 5-Bromo-1-(1-diazo-2-ethoxy-2-oxoethyl)-1,2-dihydro-2-isoquinolinecarboxylate (3g): yellow viscous liquid. IR (KBr): 2982, 2933, 2094, 1724, 1695, 1631, 1556, 1446, 1398, 1372, 1331, 1273, 1194, 1099, 1016, 934, 900, 868, 767, 706, 660, 588 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 7.41 (d, J = 7.8 Hz, 1 H), 6.94-7.19 (m, 3 H), 6.28 (s, 1 H), 6.05 (d, J = 8.5 Hz, 1 H), 4.23 (q, J = 7.0 Hz, 2 H), 4.14 (q, J = 7.0 Hz, 2 H), 1.29 (t, J = 7.0 Hz, 3 H), 1.19 (t, J = 7.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.2 (2 × C), 29.6, 51.1, 60.8, 62.9, 106.5, 120.1, 125.4, 126.6, 128.2, 129.6, 130.6, 132.5, 152.5, 164.5. EIMS-MS: m/z (%) = 418 (70), 416 (100) [M + Na]⁺. HRMS (ESI): m/z calcd for C₁₆H₁₆N₃O₄NaBr: 416.0221; found: 416.0239.


Ethyl 5-Bromo-1-(1-diazo-2-oxo-2-phenylethyl)-1,2-dihydro-2-isoquinolinecarboxylate (3l): yellow viscous liquid. IR (KBr): 2924, 2854, 2074, 1723, 1625, 1446, 1399, 1372, 1334, 1276, 1192, 1105, 1016, 954, 900, 768, 705, 645 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.24-7.54 (m, 8 H), 7.06 (t, J = 7.5 Hz, 1 H), 6.71 (s, 1 H), 6.12 (d, J = 8.3 Hz, 1 H), 4.31 (q, J = 6.7 Hz, 2 H), 1.34 (t, J = 6.7 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.3, 29.6, 50.9, 63.1, 106.3, 120.3, 125.7, 127.2 (2 × C), 128.1, 128.5 (2 × C), 128.6, 129.5, 129.7, 130.5, 131.8, 132.6, 152.9, 186.3. EIMS-MS: m/z (%) = 450 (70), 448 (100) [M + Na]⁺. HRMS (ESI): m/z calcd for C₂₀H₁₆N₃O₃NaBr: 448.0272; found: 448.0284.