Halogenation regioselective

The regioselectivity of the second step is consistent with MarkownikofF s rule because a halogen atom can stabilize a carbocation by resonance. 

Preparation of the substituted piperazine required for sul-falene (114) starts with bromination of 2-aminopiperazine to give the dihalide (150). Displacement of halogen by sodium methoxide proceeds regioselectively at the more reactive 3 position to give 151. Hydrogenolysis over palladium on charcoal gives the desired intermediate (152). 

Both electrophilic and nucleophilic reactions can generate halogenopur-ines with differences in regioselectivity dependent on substituents and on the nature of the substrate (anion, neutral molecule, or cation). In the neutral molecule nucleophilic displacements occur in the order 2 > 4 > 6 in the anion the imidazole ring may be sufficiently 7r-excessive for attack to occur at C-2, and the nucleophilic substitution order becomes 4 > 6 > 2. Strong electron donors are usually necessary to promote 2-halogenation by electrophilic halogen sources. 

Alkoxybenzenes were highly regioselectively halogenated by use of copper(II) halides supported on alumina to give 4-halo-alkoxybenzenes in high yield. Bromination of alkoxybenzenes with alumina-supported copper(II) bromide occurred at lower temperature than chlorination with alumina-supported copper(II) chloride (ref. 14). 

Regioselectivity in the halogenation of unsymmetrical ketones can be attained by treatment of the appropriate enol borinate of the ketone with NBS or NCS. The desired halo ketone is formed in high yield. Another method for achieving the... 

The regioselective halogenation of pyridinium-A -(2 -pyridyl)aniinide 7 with N-halosuccinimides, combined with a reduction of the N-N bond, provides a convenient preparation of 5-halo- and 3,5-dihalo-2-aminopyridines 8 <95T(51)8649>. 

When used with A-chloro-, A-bromo-, and A-iodosuccinimide, iron(III) chloride catalyzes the introduction of halogens into arenes. The reaction works well even with deactivated aromatic rings but in some cases the regioselective course is difficult to control (Scheme 39) [49]. 

There are also procedures in which the enolate is generated quantitatively and allowed to react with a halogenating agent. Regioselectivity can then be controlled by the direction of enolate formation. Among the sources of halogen that have been used under these conditions are bromine,125 (V-chlorosuccinimide,126 trifluoromethanesul-fonyl chloride,127 and hexachloroethane.128... 

---