Facile Microwave-Assisted Synthesis of Cyclic Amidinium Salts Adila Aidouni, Soufiane Bendahou, Albert Demonceau, and Lionel Delaude* Center for Education and Research on Macromolecules (CERM), Institut de chimie (B6a), UniVersite ´ de Lie `ge, Sart-Tilman par 4000 Lie `ge, Belgium ReceiVed June 19, 2008 The cyclization of N,N′-dialkyl or diaryl ethane-1,2-diamines or propane-1,3-diamines with inorganic ammonium salts and orthoesters proceeds briskly under microwave irradiation to afford the corresponding imidazolinium or tetrahydropyrimidinium salts. The transformation is highly versatile and tolerates a wide range of substituents and counterions. It could be scaled from 1 to 50 mmol without any difficulty. Because the workup is equally rapid and straightforward, this experimental procedure provides fast and convenient access to an important class of heterocyclic compounds that have found numerous applications as N-heterocyclic carbene precursors, organocatalysts, and ionic liquids. Introduction Cyclic amidinium salts (1) are the most common synthetic precursors for the preparation of N-heterocyclic carbenes (NHCs, 2). Since the first representative of these divalent carbon species was isolated and characterized by Arduengo and co-workers in 1991, 1 stable carbenes have been exten- sively studied. 2 Over the past 17 years, they have already afforded a whole new generation of nucleophilic reagents, 3 organocatalysts, 4 and organometallic catalysts, 5 including chiral ones, 6 that have revolutionized key areas of organic synthesis and polymer chemistry. Most NHCs investigated so far are five- or six-membered rings derived from imidazole 1,7 or pyrimidine, 8 respectively. Because of their high sensitivity toward oxygen and moisture, they are often generated in situ by deprotonation of the corresponding cyclic amidinium salts with a strong base, such as sodium hydride or potassium tert-butoxide (eq 1). Thus, imidazolinium or tetrahydropyrimidinium salts bearing a hydrogen substituent at the C2 position serve de facto as stable NHC ligand precursors in many catalytic systems. 7-9 Cyclic amidinium salts have also found applications on their own as organocatalysts 10 and ionic liquids (ILs). 11,12 Both research areas are currently attracting much interest because of their importance for “greening” chemical pro- cesses. So far, applications in these fields have relied mainly on aromatic imidazolium salts. However, their saturated imidazolinium counterparts have also attracted a great deal of attention lately. In particular, imidazolinium salts incor- porating a phenyl ring at the C2 position were found to be suitable catalysts for the aza Diels-Alder reaction. 13 They were also successfully employed as ionic liquid solvents for reactions involving medium and strong bases, such as quinuclidine and Grignard reagents. 14 The preparation of cyclic amidinium salts with a saturated backbone is usually achieved via condensation of a N,N′- disubstituted R,ω-alkanediamine and an inorganic ammonium salt with a triethyl orthoester in the presence of a catalytic amount of formic acid (eq 2). 15 Alternatively, a suitable R,ω- alkanediammonium salt may be used as a single starting material for the heterocyclic cation and its counterion (eq 3). In all cases, the orthoester serves both as a solvent and a reagent. Numerous variations on this experimental proce- dure have been reported in the literature. 16 They all require prolonged heating under reflux conditions to reach satisfac- tory conversions. Thus, reaction times ranging between a few hours and a few days are commonly encountered, unless ethanol is distilled off the reaction mixture to drive the cyclization more rapidly to completion. 17 Microwave-assisted organic synthesis (MAOS) has re- ceived increasing attention in recent years as a valuable technique for acceleration of chemical reactions. 18,19 The development of safe and reliable mono- or multimodal microwave reactors specifically designed for chemical ap- plications has significantly invigorated time-honored labora- tory practices. 20 Reduction in reaction time, increase in yield, and suppression of side-product formation are often claimed when switching from conductive to microwave heating. 21 Condensation reactions leading to heterocyclic products are particularly prone to microwave irradiation enhancements. 22 Dramatic accelerations have been reported for the synthesis * To whom correspondence should be addressed. E-mail: l.delaude@ ulg.ac.be. J. Comb. Chem. 2008, 10, 886–892 886 10.1021/cc800101k CCC: $40.75  2008 American Chemical Society Published on Web 10/10/2008