Hydrazone iodination

Hydrazone iodination is an organic reaction in which a hydrazone is converted in a vinyl iodide by reaction of iodine and a non-nucleophilic base such as DBU . First published by D. H. R. Barton in 1962 the reaction is sometimes referred to as the Barton reaction (although one of many Barton reactions and not very descriptive) or the better phrased Barton vinyl iodine procedure.

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

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



When iodine as an electrophile is replaced by aromatic selenyl bromides, the corresponding vinyl selenides are obtained:



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



The hydrazone gets oxidized by iodine to a diazo intermediate. In the next step iodine reacts as a nucleophile and displacement of nitrogen generates an iodocarbonium ion. When the reaction site is not sterically hindered a second iodide can recombine to 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 . Another example can be found in the Danishefsky Taxol total synthesis.

In one study it is attempted to trap any reactive intermediate of this reaction with an internal alkene. When the hydrazone 1 in scheme 5 is reacted with iodine and triethylamine in toluene, the expected reaction product is not the di-iodide 10 through path B in a free radical mechanism. 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.