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 ["A new reaction of hydrazones" Barton, D. H. R. , R. E. O'Brien and S. Sternhell Journal of the Chemical Society,1962, 470 - 476 DOI: 10.1039/JR9620000470 [http://www.rsc.org/publishing/journals/article.asp?doi=JR9620000470 Abstract] ] ["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 [http://dx.doi.org/10.1016/S0040-4020(01)85102-4 Abstract] ] . 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 ["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 [http://dx.doi.org/10.1016/S0040-4039(00)81721-9 Abstract] ] 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: ["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 [http://dx.doi.org/10.1016/S0040-4039(01)80136-2 Abstract] ]

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.

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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 ["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) [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv9p0147 Article] ] . Another example can be found in the Danishefsky Taxol total synthesis.

In one study ["Observations on the reaction of hydrazones with iodine: interception of the diazo intermediates" Béatrice Quiclet-Sire and Samir Z. Zard Chemical Communications, 2006, 1831 - 1832 [http://dx.doi.org/10.1039/b602580c Abstract] ] 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. [Reaction sequence starting from 1: halogen addition reaction to di-iodide intermediate 2 followed by elimination reaction with loss of Hydrogen iodide to 3. In path B another equivalent of iodine reacts to the azo double bond followed by loss of HI and formation of 6. The nitrogen to iodine bond is weak and homolysis gives the nitrogen free radical 7. Loss of nitrogen results in radical species 8. The readical 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.

References

See also

*Shapiro reaction