Novel Synthetic Route to Fluorinated β‐Carbolines by One‐Pot Reaction

Abstract

This paper describes a new strategy for the synthesis of 1‐trifluoromethyl‐ 9H‐pyrido[3,4‐b]indole 2 by one‐pot reaction of tryptophan methyl ester hydrochloride or tryptophan amide 1 and trifluoroacetic acid (TFA) in 60–78% yield via a possible intramolecular cyclization. The structures of 2a and 2e were confirmed by X‐ray crystallographic analysis.

Keywords:

• Fluorinated β‐carbolines
• 9H‐pyrido[3,4‐b]indoles
• trifluoroacetimidoyl chloride
• crystal structure
• one‐pot reaction

Acknowledgment

This work was supported by the National Natural Science Foundation of China (No. 20272075).

Notes

¹Crystal structure of 2a determination: Empirical formula: C₁₄H₉F₃N₂O₂: Formula weight: 294.23. T = 273 (2) K. Wavelength: 0.71073 Å. Crystal system: Monoclinic, P2 ₁/n. Unit cell dimensions: a = 10.9191 (7) Å, α = 90°; b = 7.8212 (6) Å, β = 99.013 (3) °; c = 15.1663 (10) Å, γ = 90°. V = 1279.22 (15) ų. Z = 4. ρ_Calcd = 1.528 g/m³. Absorption coefficient: 0.133 mm⁻¹. F (000): 600. Crystal size: 0.29 × 0.27 × 0.07 mm³. Theta range for data collection: 2.15° to 25.02°. Limiting indices: −12 < h < 12, −9 < k < 7, −12 < l < 18. Reflections collected: 6450. Independent Reflections: 2260[R (int) = 0.0350]. Completeness to θ = 25.02°, 99.9%. Absorption correction: None. Max. and min. transmission: 0.9908 and 0.9625. Refinement method: Full‐matrix least–squares on F ². Data/restraints/parameters: 2260/0/219. Goodness‐of‐fit on F ²: 1.438. Final R indices [I > 2σ (I)]: R ₁ = 0.1361, wR ₂ = 0.2070. R indices (all data): R ₁ = 0.1407, wR ₂ = 0.2089. Extinction coefficient: 0.0012 (12). Largest diff. peak and hole: 0.264 and −0.234 e Å⁻³. Crystal Structure of 2e Determination: Empirical formula: C₁₇H₁₅F₃N₂O₂: Formula weight: 336.31. T = 298 (2) K. Wavelength: 0.71073 Å. Crystal system: Monoclinic, P2 ₁/n. Unit cell dimensions: a = 8.1231 (4) Å, α = 90°; b = 17.1197 (8) Å, β = 93.615 (2) °; c = 11.6388 (6) Å, γ = 90°. V = 1615.33 (14) ų. Z = 4. ρ_Calcd = 1.383g/m³. Absorption coefficient: 0.115 mm⁻¹. F (000): 696. Crystal size: 0.49 × 0.37 × 0.19 min³. Theta range for data collection: 2.12° to 25.01°. Limiting indices: −7 < h < 9, −20 < k < 20, −13 < l < 13. Reflections collected: 8369. Independent Reflections: 2850 [R (int) = 0.0321]. Completeness to θ = 25.01°, 99.9%. Absorption correction: Semi‐empirical from equivalents. Max. and min. transmission: 0.9785 and 0.9459. Refinement method: Full‐matrix least–squares on F ². Data/restraints/parameters: 2850/0/227. Goodness‐of‐fit on F ²: 1.324. Final R indices [I > 26 (I)]: R ₁ = 0.1756, wR ₂ = 0.3339. R indices (all data): R ₁ = 0.1813, wR ₂ = 0.3369. Largest diff. peak and hole: 0.648 and −0.329 e Å⁻³.