Hydrazone iodination 3452748 152088632 2007-08-18T19:02:56Z ~K 95839 minor fixes '''Hydrazone iodination''' is an [[organic reaction]] in which a [[hydrazone]] is converted in a [[vinyl halide|vinyl iodide]] by reaction of [[iodine]] and a non-nucleophilic base such as [[DBU (chemistry)|DBU]]<ref>''A new reaction of hydrazones'' [[Derek Harold Richard Barton|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]</ref><ref>''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'' [[Derek Harold Richard Barton|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]</ref> . First published by [[Derek Harold Richard Barton|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''). [[Image:HydrazoneIodination.png|500px|center|Iodination of hydrazones]] In the original Barton publication<ref>''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]</ref> 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. [[Image:BartonVinylIodideSynthesis.png|300px|center|Barton Vinyl Iodide Synthesis]] When iodine as an [[electrophile]] is replaced by [[aromatic]] [[selenyl bromide]]s, the corresponding vinyl selenides are obtained:<ref>''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]</ref> [[Image:VinylSelenideSynthesis.png|400px|center|Vinyl Selenide Synthesis]] ==Reaction mechanism== The [[reaction mechanism]] proposed in the original Barton publication is outlines as follows: [[Image:HydrazoneIodizationReactionMechanism.png|600px|center|Hydrazone Iodization Reaction Mechanism]] The hydrazone gets [[organic oxidation|oxidized]] by iodine to a [[diazo]] intermediate. In the next step iodine reacts as a [[nucleophile]] and displacement of nitrogen generates an [[carbocation|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 [[cyclohexanone|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 [[guanidine|2-tert-butyl-1,1,3,3-tetramethylguanidine]] (cheaper than DBU) in [[diethyl ether]] at [[room temperature]]<ref>''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]</ref> . Another example can be found in the [[Danishefsky Taxol total synthesis]]. In one study<ref>''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] </ref> 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.<ref>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.</ref> The actual process taking place is path A with [[elimination reaction|elimination]] of HI to the [[diazo]] compound '''4''' followed by a [[diazoalkane 1,3-dipolar cycloaddition]] to the pyrazoline '''5''' in 85% yield. [[Image:HydrazoneIodinationMechanism.png|600px|center|Hydrazone Iodination Mechanism internal trapping]] == References == {{reflist}} == See also == *[[Shapiro reaction]] [[Category:Substitution reactions]]