Microwave-Assisted Parallel Synthesis of Fused Heterocycles in a Novel Parallel Multimode Reactor

Abstract

New rotor types using disposable glass vials for small-scale parallel synthesis in multimode microwave reactors are introduced. One rotor comprises 16 groups of four vials, whereas the second uses four silicon carbide plates with a 6 x 4 matrix to process the vials. Both rotors achieve utmost temperature homogeneity upon microwave irradiation and can be used for microwave-mediated reactions at temperatures of up to 200 degrees C and pressures of 20 bar. The generation of three different heterocycle libraries furnishing thiophenes, oxindoles, and benzimidazoles using the new rotor types is described.

The Gewald reaction in dye chemistry

“…Microwave ovens provide a clean, economic, and attractive means of heating that is superior to conventional oil baths. Numerous reports highlighting the microwave‐assisted Gewald reaction have been published . Microwave irradiation in combination with heterogeneous catalysts has also been used for the efficient synthesis of 2‐aminothiophenes .…”

Microwaves in Heterocyclic Chemistry

“…Banik and co-workers demonstrated that a solvent-free mixture of 2,5-dimethoxytetrahydrofuran and an amine with iodine (5 mol%) in an automated microwave oven afforded in short reaction time (∼5 min) N-substituted pyrroles in good yields (75-98%) [5]. A microwave process is highly beneficial in a small-scale parallel synthesis of 2-aminothiophenes by the Gewald reaction [6]. The 24 members of the 2-aminobenzo[b]thiophene library have been synthesized (10 min, 120 • C, in ethanol solution) in 22-78% yields and excellent purities.…”

“…This approach involved trifluoroacetic acid (TFA) as catalyst [11]. (NH 4 ) 6 Mo 7 O 24 ·4H 2 O has also been used as catalyst [12]. Hydrazinolysis of substituted imidazo[1,2-a]pyrimidines into 4(5)-substituted 2-amino-1H-imidazoles has been performed under microwave irradiation at 120 • C [Eq.…”

Tools for Monitoring Reactions Performed Using Microwave Heating

“…Although not applied to reaction monitoring per se, IR thermography has been used to probe the homogeneity of heating in silicon carbide well plates under microwave irradiation [23,24]. Silicon carbide is highly microwave absorbing, chemically inert, and has a very high thermal conductivity and melting point [25].…”