Scope and Utility of CsOH·H₂O in Amination Reactions via Direct Coupling of Aryl Halides and sec-Alicyclic Amines [1]

Abstract

Direct coupling of aryl halides with sec-alicyclic amines promoted by CsOH·H₂O in DMSO to the corresponding aryl substituted amines, with good to excellent yields, is reported herein. A variety of aryl halides and sec-alicyclic amines with a broad range of electronic diversity and functional groups was studied in this transformation, thus offering general applicability in organic synthesis.

CsOH·H₂O - base - aryl halides - sec-alicyclic amines - cross coupling

References

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11

General Procedure for the CsOH·H ₂ O-Promoted Amination of Aromatic Halides:
A mixture of aryl halide (1 mmol), the amine (1.2 mmol) and CsOH·H2O (2 mmol) in DMSO (3 mL) were taken in a sealed tube placed in preheated oil bath at 120 °C and then held at that temperature for 5-20 min. Then the reaction mixture was cooled to r.t., poured into water containing crushed ice, and stirred for 5 min. Sat. aq NH₄Cl solution was added to this mixture, and the organic portion was extracted with Et₂O (3 × 20 mL). The combined organic extracts were washed with a sat. NH₄Cl solution and brine, and dried over anhyd Na₂SO₄. After removal of the solvent the residue was purified by column chromatography on silica gel to furnish the product. All isolated compounds were fully characterized by comparing their spectroscopic data with authentic compounds.

Spectral data for selected compounds:
1-Methyl-4-(1-naphthyl) Piperazine (entry 8, Table 1): see ref. 13.
N -(4-Nitrophenyl) Piperidine (entry 2, Table 2): Yellow solid; mp 95 °C (lit. mp 104 °C); ¹H NMR (300 MHz, CDCl₃): d = 8.09 (d, 2 H, J = 9.3 Hz), 6.79 (d, 2 H, J = 9.9 Hz), 3.50 (m, 4 H), 1.75-1.65 (m, 6 H). MS (EI): m/z = 208.
N-(4-Methyl Phenyl) Morpholine (entry 4, Table 2): see ref. 14.

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