Halogen dance, bromine migration

Introduction of a 3-bromosubstituent onto thiophene is accompHshed by initial tribromination, followed by reduction of the a-bromines by treatment with zinc/acetic acid, thereby utilizing only one of three bromines introduced. The so-called halogen dance sequence of reactions, whereby bromothiophenes are treated with base, causing proton abstraction and rearrangement of bromine to the produce the most-stable anion, has also been used to introduce a bromine atom at position 3. The formation of 3-bromotbiopbene [872-31-1] from this sequence of reactions (17) is an efficient use of bromine. Vapor-phase techniques have also been proposed to achieve this halogen migration (18), but with less specificity. Table 3 summarizes properties of some brominated thiophenes. 

Indirect support for the above mechanisms is provided by the fact that treatment of di-, tri- and tetra-bromothiophenes with sodium alkoxide in DMSO results in partial debromination (72CC615). Replacement of DMSO by DMF results in bromine migration and polybromi-nation (Scheme 165). The same kind of halogen dance has also been observed on treatment of bromoiodothiophene with alkoxide (80JHC171). 

In order to test the viability of the halogen-dance reaction on a simple thiazole substrate, we studied the use of 2-bromothiazole in this reaction (60, Scheme 9). This compound was treated with LDA at -78 °C in ethereal solvents, however, under all conditions examined a dark intractable material was produced. We suspect that this is a result of lithiation at the 5-position to provide 61, followed by migration of the bromine to provide 2-lithio-5-bromothiazole (62). This species can then undergo an a-elimination and open to the unstable isocyanide (63), which decomposes to a complex mixture. Although 2-lithiothiazole is known be stable at -78 °C, we postulate that the electron withdrawing nature of the... 

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