Preparation of Amidines by Amidoxime Reduction with Potassium Formate

Abstract

Amidines can be prepared by reducing acylated amid­oxime with potassium formate. The method has proved to be very simple and effective.

palladium - reductions - amidines - green chemistry

References and Notes

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<A NAME="RG00707ST-18">18</A>

Typical Procedure for Reduction of Amidoxime: The parent amidoxime (1 mmol) was dissolved in a mixture of glacial AcOH (1 mL) and potassium formate solution in MeOH (10 mmol), followed by the addition of 10% Pd/C. The mixture was stirred at r.t. until the reaction was complete based on TLC. Isolation and purification were performed as described in ref. 19 to yield pure amidine hydrochloride.

<A NAME="RG00707ST-19">19</A>

Typical Procedure for Reduction of Amidoxime via the Acylated Intermediate: Potassium formate was prepared in situ from HCOOH (10 mmol) and K₂CO₃ (5 mmol) in MeOH (1.5 mL). The parent amidoxime (1 mmol) was dissolved in AcOH (1 mL) and Ac₂O (1.1 mmol) was added at r.t. After 5 min, potassium formate solution in MeOH was added, followed by 10% Pd/C. The mixture was stirred at r.t. until reaction was complete based on TLC. The solids were filtered, washed with MeOH or EtOH, and the filtrate was evaporated. The residue was dissolved in anhyd EtOH and 5 M HCl in anhyd EtOH (12 equiv) was then added. The solids were filtered, washed with anhyd EtOH and the filtrate was evaporated to yield pure amidine hydrochloride.

<A NAME="RG00707ST-20">20</A>

Representative Spectroscopic Data for Compound 2: ¹H NMR (300 MHz, DMSO-d ₆): δ = 3.92 (s, 3 H, Me), 7.78 (t, J = 7.8 Hz, 1 H, ArH), 8.11 (d, J = 7.8 Hz, 1 H, ArH), 8.28 (d, J = 7.8 Hz, 1 H, ArH), 8.38 (s, 1 H, ArH), 9.37 (s, 2 H, NH₂), 9.58 (s, 2 H, NH₂ ⁺). ¹³C NMR (300 MHz, DMSO-d ₆): δ = 166.1, 134.8, 133.7, 131.1, 130.5, 129.6, 53.5. HRMS: m/z [M⁺] calcd for C₉H₁₀N₂O₂: 178.0742; found: 178.0750.