Polystyrene-carbamyl chloride

With imidazole being an essential pharmacophore, the solid-phase synthesis of non-annelated imidazoles has been reported in several publications ]50-52]. Houghten et al. devised a plethora of imidazole syntheses, but used exclusively the experimentally difficult HF cleavage ]53-55, and citations therein]. The preparation of 1,2,4-trisubstituted imidazoles via the solid-phase synthesis of N-alkyl-N-(]3-keto)amides using a carbazate linker has been demonstrated [67]. An approach for the preparation of 2-substituted azoles in a traceless fashion using a polystyrene-carbamyl chloride resin has been described by Deng and Hlasta [58]. 

Hlasta and Deng have developed a two-step solid-phase method for the decoration of azoles at C-2 [188]. First, imidazole was loaded onto a polystyrene-bound carbamyl chloride via a benzaldehyde bridge (Fig. 40). The 2-substi-tuted imidazole was efficiently cleaved in good yields in the presence of various nucleophiles (i.e., water, alcohols, and amines), trifluoroacetic acid, and boron trifluoride under microwave irradiation in a closed vessel at 120 °C for 5 min. 

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