A Simple Homemade Reaction Station for use in Parallel Solution-Phase Synthesis. Optimization of a Regioselective One-Step Deprotective o-formylation Reaction Mediated by the Vilsmeier-Haack Reagent POCl3⋅DMF

Abstract

We report herein the fabrication of a simple and price-affordable portable reaction station for use in parallel solution-phase synthesis. This homemade device uses currently available laboratory components and equipment. Specifically designed to fit standard magnetic hotplates/stirrers, it can simultaneously hold up to 24 heated and magnetically stirred glass reactors of both 10 and 50 mL capacities. Glass reactors are connected by flexible 16-gauge metal needles to a central gas manifold equipped with an inlet/outlet for vacuum and inert gases. Reaction temperatures can be optimally varied from -78 ( composite function)C to 150 degrees C. Using a statistical screening DOE method, this parallel array reactor station has been successfully operated to optimize the one-step deprotective O-formylation of a sterically hindered bis-O-tert-butyldiphenylsilyl (O-TBDPS) aromatic diol. The latter transformation was mediated by the Vilsmeier-Haack reagent POCl3.DMF using a range of Lewis acid and metal salt promoters, including their binary combinations.

Transition Metal Ions as Efficient Catalysts for Facile Ortho-Formylation of Phenols under Vilsmeier–Haack Conditions

“…Herewith now we report the selective formylation of phenols promoted by metal ions under V-H conditions. Nevertheless, in one of the earlier reports metal ions in conjunction with DMF/POCl 3 have been used for one step deprotective O-formylation of bis-O-tertiary butyl diphenyl silyl (O-TBDPS) aromatic diol [28].…”

Synthetic Utility of the Vilsmeier–Haack Reagent in Organic Synthesis

“…76 In 2006, Kotlyar et al reported the Vilsmeier-Haackmediated O-formylation of the sterically hindered bis-Otert-butyldiphenylsilyl (O-TBDPS) aromatic diol 155 using a range of Lewis acids and metal salt promoters to give product 156 (Scheme 46). 77 The reaction proceeded efficiently and product 156 was obtained in 79% yield.…”

CuCN-Mediated O-Alkylation of N,N,-Dimethylformamide with Alkyl Halides

“…[2] A more compelling alternative method for the synthesis of formate ester derivatives is via an O-alkylation of amides with alkyl halides. [3] Reports that exploit dimethylformamide (DMF) as a formate anion equivalent in the synthesis of formate ester have also been revealed.…”