Newsletter Issue 09 Mar-Apr 2009

Rapid and easy access to indoles via microwave-assisted Hemetsberger–Knittel synthesis

The synthesis of indole derivatives has been a major topic in organic and medicinal chemistry over the past several decades. One of the myths of the organic synthetic chemistry, Emil Fischer, devised a synthesis that has been one of the most used methods for the preparation of indoles. Many other methods are available, each with its successes and shortcomings, but still new methods are published each year. This paper by Laufer (Tuebingen, Germany) is one of those striking examples of how an old reaction is vastly improved by using microwave technology. The Hemetsberger–Knittel synthesis involves the condensation between an arylaldehyde and an azidoacetate to provide a-azidocinnamates which upon heating give indoles, but as usual the harsh conditions render the method less than ideal. After a short experimentation, conditions involing 200 W, 200 °C and 10 min of microwave irradiation time become the standard method to synthesize different indole-2-carboxylates from aldehydes.

Tetrahedron Lett., 2009, 50, pp 1708–1709. See: 10.1016/j.tetlet.2009.01.129

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