Hydrazone iodination

Source: Wikipedia, the free encyclopedia.

Hydrazone iodination is an

DBU.[1][2] First published by Derek Barton
in 1962 the reaction is sometimes referred to as the Barton reaction (although there are many different Barton reactions) or, more descriptively, as the Barton vinyl iodine procedure.

The reaction has earlier roots with the 1911 discovery by Wieland and Roseeu that the reaction of hydrazones with iodine alone (without base) results in the azine dimer (structure 2 in scheme 1).

Iodination of hydrazones
Iodination of hydrazones

In the original Barton publication[3] the reaction was optimized by using a strong guanidine base, the inverse addition of the hydrazone to an iodine solution, and by exclusion of water.

Barton vinyl iodide synthesis
Barton vinyl iodide synthesis

When iodine as an

selenyl bromides, the corresponding vinyl selenides are obtained:[4]

Vinyl selenide synthesis
Vinyl selenide synthesis

Reaction mechanism

The reaction mechanism proposed in the original Barton publication is outlined as follows:

Hydrazone iodization reaction mechanism
Hydrazone iodization reaction mechanism

The hydrazone is

oxidized by iodine into a diazo intermediate. In the next step, iodine reacts as an electrophile; displacement of nitrogen then generates an iodocarbonium ion. When the reaction site is not sterically hindered, a second iodide can recombine to form the geminal di-iodide; otherwise an elimination reaction leads to the vinyliodide. When water is present, the reaction product can revert to the ketone
.

This reaction is related to the Shapiro reaction.

Scope

An example of this procedure is the reaction of 2,2,6-trimethylcyclohexanone to the hydrazone by reaction with hydrazine and triethylamine in ethanol at reflux followed by reaction of the hydrazone with iodine in the presence of 2-tert-butyl-1,1,3,3-tetramethylguanidine (cheaper than DBU) in diethyl ether at room temperature.[5] Another example can be found in the Danishefsky Taxol total synthesis.

In one study

free radical 7. Loss of nitrogen results in radical species 8. The radical position gets transferred to the alkene in 9 which later recombines with iodide to 10. Note that in absence of the alkene 8 would accept an iodide radical and the geminal di-iodide then loses HI to form the vinyl iodide. The actual process taking place is path A with elimination of HI to the diazo compound 4 followed by a diazoalkane 1,3-dipolar cycloaddition
to the pyrazoline 5 in 85% yield.

Hydrazone iodination mechanism internal trapping

References

  1. ^ Studies on the oxidation of hydrazones with iodine and with phenylselenenyl bromide in the presence of strong organic bases; an improved procedure for the synthesis of vinyl iodides and phenyl-vinyl selenides Barton, D. H. R.; Bashiardes, G.; Fourrey, J.-L. Tetrahedron 1988, 44, 147 Abstract
  2. ^ An improved preparation of vinyl iodides Derek H. R. Barton, George Bashiardes and Jean-Louis Fourrey Tetrahedron Letters Volume 24, Issue 15 , 1983, Pages 1605-1608 Abstract
  3. ^ A new synthesis of phenylvinylselenides Derek H. R. Barton, George Bashiardes and Jean-Louis Fourrey Tetrahedron Letters Volume 25, Issue 12 , 1984, Pages 1287-1290 Abstract
  4. ^ Preparation and reactions of 2-tert-butyl-1,1,3,3-tetramethylguanidine: 2,2,6-trimethylcyclohexen-1-yl iodide Derek H. R. Barton, Mi Chen, Joseph Cs. Jászberényi, and Dennis K. Taylor Organic Syntheses, Coll. Vol. 9, p.147 (1998); Vol. 74, p.101 (1997) Article Archived 2005-11-17 at the Wayback Machine
  5. Chemical Communications, 2006, 1831 - 1832 Abstract

See also