Rapid Palladium-Catalyzed C3-Arylation of 2(1H)-Pyrazinones: Effect of Simultaneous Cooling on Microwave-Assisted Reactions on Solid Support

Abstract

An unprecedented microwave-assisted palladium-catalyzed reaction on polymer support with simultaneous cooling has been developed. It has also been illustrated that under simultaneous cooling, certain decomposition and side reactions during the reaction, because of heating, can be minimized.

Key words

2(1H)-pyrazinones - palladium catalysis - solid support - microwave - simultaneous cooling

References and Notes

• 1a Transition Metals for Organic Synthesis: Building Blocks and Fine Chemicals   2nd ed., Vol. 2:  Beller M. Bolm C. Wiley-VCH; Weinheim: 2004. 
• 1b Metal-Catalyzed Cross-Coupling Reactions   2nd ed., Vol. 1 and 2:  de Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004. 
• 1c Handbook of Organopalladium Chemistry for Organic Synthesis   Vol. 1:  Negishi E.-I. Beller M. Zapf A. Wiley; New York: 2002.  p.1209 
• 1d Ley SV. Thomas AW. Angew. Chem. Int. Ed.  2003,  42:  5400 
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• 2c Kappe CO. Dallinger D. Nat. Rev. Drug Discovery  2006,  5:  51 
• 3a Appukkuttan P. Hussain M. Gupta RK. Parmar VS. Van der Eycken E. Synlett  2006,  1491 
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• 4 Kaval N. Appukkuttan P. Van der Eycken E. The Chemistry of 2(1H)-pyrazinones in Solution and on Solid Support in Microwave-Assisted Synthesis of Heterocycles, In Topics in Heterocyclic Chemistry   Vol. 1:  Van der Eycken E. Kappe O. Springer; Heidelberg: 2006.  p.267 
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See power profile in Supporting Information.

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All microwave-irradiation experiments were carried out in a dedicated CEM-Discover-Coolmate monomode microwave apparatus (CEM Corporation P.O. Box 200 Matthews, NC 28106), operating at a frequency of 2.45 GHz with continuous irradiation power from 0-300 W. Reaction mixtures were efficiently stirred with a magnetic stirrer. The reactions were carried out in an open 10 mL double-walled glass vial which was cooled to 0-35 ˚C using a microwave transparent cooling liquid. The temperature of the cooling liquid was between 15 ˚C and 18 ˚C. Irradiation and cooling were started simultaneously, starting with the reaction mixture at r.t. The temperature was measured with a fiber-optic probe device inserted into the reaction vessel; a schematic representation of the setup can be found at
http://cemsynthesis.com

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Experimental details and characterization data (^¹H NMR, ^¹³C NMR, and HRMS) of all new compounds are available in the Supporting Information.