Orientation of halogenation

Relative orientation of halogen to substituent. b Relative orientation of the two methoxycarbonyl groups. 

Halogen bonding also manifests itself in the relative orientations of halogen derivatives in the crystalline state [149]. Indeed, the modes of interaction in many nonhydrogen-bonded noncovalent systems, ranging from gas phase complexes to molecular crystals, can be satisfactorily rationalized in terms of molecular surface electrostatic potentials [44,55,150]. In several instances, we have used this approach to explain anomalously high measured solid densities [151,152]. 

Table 6 The orientation of halogen dimers predicted from the radial density topology of the monomer...

Enolization is the rate-determining step in the halogenation of normal ketones. Where alternate directions for enolization exist, the preferred direction (and hence the position of kinetic bromination) depends on the substituents and stereochemistry. Furthermore, the orientation of the bromine introduced depends on stereochemical and stereoelectronic factors. 

A very similar situation is encountered in the electrophilic addition of unsymmetrical adducts (e.g. HBr) to vinyl halides (e.g. CH2=CHBr), where the inductive effect of halogen controls the rate, but relative mesomeric stabilisation of the carbocationic intermediate controls the orientation, of addition (p. 185). 

Addition is initiated by the positively polarised end (the less electronegative halogen atom) of the unsymmetrical molecule, and a cyclic halonium ion intermediate probably results. Addition of I—Cl is particularly stereoselective (ANTI) because of the ease of formation (and relative stability compared with carbocations) of cyclic iodonium ions. With an unsymmetrical alkene, e.g. 2-methylpropene (32), the more heavily alkyl-substituted carbon will be the more carbocationic (i.e. the less bonded to Br in 33), and will therefore be attacked preferentially by the residual nucleophile, Cle. The overall orientation of addition will thus be Markownikov to yield (34) ... 

The reason for the different behavior of dienes like 41 and monoenes 37 or 42 is not yet established. It is hard to believe that simple steric factors should make up for the different orientation of the olefin that approaches a metal carbene intermediate. More likely is stereochemical control by an ylide-type interaction between the halogen atom of the (sterically more flexible) monoenes 37 or 42 and the electrophilic metal carbene. 

N. Vass, "The Nature of the Alternating Effect in Carbon Chains. Pt. XXIII. Anomalous Orientation by Halogens, and Its Bearing on the Problem of the Ortho-Para-Ratio in Aromatic Substitution," JCS 131 (1928) 417425. 

The orientation of the addition of HC1 to a variety of halogen-substituted 1,3-butadienes has been extensively studied under preparative conditions39-43. The results are given in Table 3. No significant polymerization was observed and the products were in all cases those resulting from a 1 1 addition process. The regiochemistry control by the position of the chlorine atom was quite versatile. A Cl at C(l) favored formation of the 4,3-adduct whereas with Cl on C(2) the 1,4-adduct predominated. The competition between substitution by chlorine and methyl attenuated but did not markedly modify this orientation. However, all these reactions were quite slow and took from 5 to 10 h, even in the presence of a catalyst (mostly cuprous chloride). Therefore, product... 

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