Wender indole synthesis

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The Wender indole synthesis is a name reaction in organic chemistry . It is a synthetic method for indole derivatives, which was described in 1981 by Paul Anthony Wender (* 1947).

Overview reaction

In the Wender indole synthesis, the N -acylorthohaloaniline first reacts with butyllithium and then reacts in an S N 2 reaction with an α-haloketone to form the N -acylindole derivative. X and Y are the halogens chlorine, bromine or iodine.

Reaction mechanism

In the proposed reaction mechanism, the strong base butyllithium is first used to produce a C, N -dianion 2 from the N -acylorthohaloaniline 1 . 2 then reacts in an S N 2 reaction with an α-haloketone to form intermediate 3 . The anion 3 then reacts intramolecularly to form the alkoxide 4 . Intermediate product 5 is formed from 4 by proton transfer , which yields the N -acylindole derivative 6 with elimination of water . X and Y are the halogens chlorine, bromine or iodine.

modification

The Wender indole synthesis was extended to synthesize N -dimethylurea protected indoles . To do this, N- phenyl- N, N -dimethylurea first reacts with a strong base to form the dianion, which, when cooled, reacts with diethyl pyruvate to form isatin.

application

The Wender indole synthesis is used in many areas of the synthesis of indole derivatives.

Individual evidence

  1. a b c Zerong Wang: Comprehensive Organic Name Reactions and Reagents . John Wiley & Sons, Inc., Hoboken, NJ, USA 2010, ISBN 978-0-470-63885-9 , pp. 2980-2982 , doi : 10.1002 / 9780470638859 ( wiley.com ).
  2. a b c Paul A. Wender, Alan W. White: Methodology for indole synthesis . In: Tetrahedron Letters . tape 22 , no. 16 , 1981, pp. 1475–1478 , doi : 10.1016 / S0040-4039 (01) 90354-5 ( elsevier.com [accessed May 15, 2019]).
  3. M. Sainsbury: Heterocyclic chemistry . Ed .: Royal Society of Chemistry. Royal Society of Chemistry, Cambridge 2001, ISBN 978-1-84755-106-1 , pp. 68 .
  4. Keith Smith, Gamal A. El-Hiti, Amba P. Shukla: Variation in site of lithiation with ring substituent of N′-aryl-N, N-dimethylureas: application in synthesis . In: Journal of the Chemical Society, Perkin Transactions 1 . No. 16 , 1999, p. 2305–2313 , doi : 10.1039 / a903464a ( rsc.org [accessed May 15, 2019]).