Synthesis of amides from imines using Et 3 SiH/Zn system Mohammad Ghaffarzadeh,* Somaye Heidarifard, Fereshteh Faraji and Somaye Shahrivari Joghan A simple and efficient approach for the synthesis of amides by the reaction of imines and acyl chlorides in the presence of Et 3 SiH/Zn system in THF at ambient temperature is reported. Mild reaction conditions, good yields of products, short reaction time and operational simplicity are the advantages of this procedure. Copyright © 2012 John Wiley & Sons, Ltd. Keywords: amide; imine; triethylsilane; reduction; fentanyl Introduction Amides are a very important class of organic compounds, with a wide range of applications. The amide bond appears as an impor- tant structural component in peptides, polymers, and many natural products and pharmaceuticals. [1–4] Various amides are biologically active and show antifungal, antihistamine, anthelmintic and anti- bacterial properties. [5–8] Because of their obvious importance, several methods have been described for the synthesis of amides. [9–17] However, the majority of amide bond syntheses involve the use of stoichiometric amounts of coupling reagents, making them generally expensive and wasteful procedures. [18] Many of these methods have some disadvantages, such as the use of toxic metals, strong Lewis acids, expensive reagents, low yield and drastic reaction conditions. These difficulties have encouraged efforts towards the identification and development of more atom-efficient, catalytic methods for amide bond formation, as evidenced by the increasing number of publications in this area in recent years. [9,19–23] The hydrosilylation of imines, in which the Si-H bond is added across the C=N bond, is an attractive alternative approach for the hydrogenation of imines as it is experimentally simple, does not require high pressure or temperature, and makes use of readily available silanes. Many transition metal complexes with metals, including Ru, [24] Rh, [25] Ti, [26] Ir, [27] Cu, [28] and Zn, [29] have been used as catalysts for imine hydrosilylation. Although, hydrosilylation of imines to amines in the presence of transition metal-based catalysts has been reported as a synthetic strategy over the years, [24–29] the synthesis of amides via transi- tion-metal catalyzed hydrosilylation of imines has not yet been reported. Therefore, we sought to develop a new, simple and straightforward method for amide formation from imines using an Et 3 SiH/Zn system. The use of zinc is of great interest, owing to its abundance and biological relevance. Experimental The chemicals used in this work were obtained from Fluka and Merck and were used without purification. Zinc dust has been activated sufficiently by ethylene dibromide (EDB) in THF. [30] Melting points were measured on a Buchi B-545 apparatus. 1 H NMR spectra were recorded on a Bruker-DRX 500 Avance spectrometer at 500.13 MHz. IR spectra were recorded using a Shimadzu FT-IR-8300 spectrophotometer. Mass spectra were recorded on a JEOL MAT312 mass spectrometer operating at an ionization potential of 70 eV. Elemental analyses were performed using a Heracus CHN-O-Rapid analyzer. General Procedure for the Preparation of Amide 3 A mixture of imine (1 mmol), acyl chloride (2 mmol), Et 3 SiH (4 mmol) and zinc dust with chemically activated surface (1.2mmol) in THF (5ml) was stirred at room temperature for 30 min. After completion of the reaction, progress of reaction was m\onitored using TLC (eluent:EtOAc/petroleum ether, 1:3), the re- action mixture was filtered, and 20 ml H 2 O was added to the filtrate, which was extracted with CH 2 Cl 2 (3  5 ml). The organic layer was dried over anhydrous MgSO 4 and concentrated by rotary evapora- tion. The residue was purified by flash column chromatography (EtOAc/petroleum ether) to afford the pure product. The amide products 3a, 3c, 3g and 3k are known compounds and were characterized by 1 H NMR spectroscopic data and their melting points, which agreed with reported values. [31,32] N-Benzyl-N-phenylpropionamide (3b) Cream oil; [32] IR (KBr): 3032, 2872, 1639, 1586, 806. 1 H NMR (500 MHz, CDCl 3 ): d 7.29 (m, 8H, H-Ar), 7.01 (d, J = 6.9 Hz, 2H, H-Ar), 4.92 (s, 2H, NCH 2 ), 2.12 (q, J = 7.3 Hz, 2H, CH 2 ), 1.11 (t, J = 7.3 Hz, 3H, Me). 13 C NMR (125 MHz, CDCl 3 ): d 10.1 (Me), 28.2 (CH 2 -CO), 53.4 (CH 2 N), 127.7 (CH), 128.3 (CH), 128.7 (CH), 128.8 (CH), 129.2 (CH), 129.9 (CH), 138.1 (C ipso ) and 142.9 (C-N), 174.4 (CO). MS (E.I.) (70 eV): m/z (%) 239 (M + , 30), 182 (50), 104 (12), 91 (45), 77 (12), * Correspondence to: Mohammad Ghaffarzadeh, Chemistry and Chemical Engineering Research center of Iran (CCERCI), PO Box 14335–186 Tehran, Iran. E-mail: mghaffarzadeh@ccerci.ac.ir Chemistry and Chemical Engineering Research center of Iran (CCERCI), PO Box 14335-186, Tehran, Iran Appl. Organometal. Chem. 2012, 26, 103–107 Copyright © 2012 John Wiley & Sons, Ltd. Full Paper Received: 1 September 2011 Revised: 2 December 2011 Accepted: 2 December 2011 Published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/aoc.1870 103