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Synlett 2007(8): 1257-1258  
DOI: 10.1055/s-2007-977444
LETTER
© Georg Thieme Verlag Stuttgart · New York

Preparation of Amidines by Amidoxime Reduction with Potassium Formate

Kristina Nadrah, Marija Sollner Dolenc*
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia
Fax: +386(1)4258031; e-Mail: marija.sollner@ffa.uni-lj.si;
Further Information

Publication History

Received 16 January 2007
Publication Date:
18 April 2007 (online)

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Abstract

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

Key words

palladium - reductions - amidines - green chemistry

18

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.

19

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.

20

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.