Selectivity in Halogenation

Up to now, we have limited our discussions to the halogenation of methane. Beginning our study with such a simple compound allowed us to concentrate on the thermodynamics and kinetics of the reaction. Now we consider halogenation of the higher alkanes, meaning those of higher molecular weight. 

Halogenation is a substitution, where a halogen atom replaces a hydrogen. 

In methane, all four hydrogen atoms are identical, and it does not matter which hydrogen is replaced. In the higher alkanes, replacement of different hydrogen atoms leads to different products. In the chlorination of propane, for example, two monochlorinated (just one chlorine atom) products are possible. One has the chlorine atom on a primary carbon atom, and the other has the chlorine atom on the secondary carbon atom. 

Definitions of primary, secondary, and tertiary hydrogens. There are six primary hydrogens in propane and only two secondary hydrogens, yet the major product results from replacement of a secondary hydrogen. 

First propagation step Abstraction (removal) of a primary or secondary hydrogen 

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Selectivity in halogenation is found to decrease with rise in temperature. 

The factors governing selectivity in halogenation of alkanes follow ... 

Activation Energy and theTemperature Dependence of Rates 147 4-10 Transition States 148 4-11 Rates of Multistep Reactions 149 4-12 Temperature Dependence of Halogenation 150 4-13 Selectivity in Halogenation 151 4-14 The Hammond Postulate 157 4-15 Radical Inhibitors 161 4-16 Reactive Intermediates 162... 

Positional selectivity in halogen exchange is governed by factors similar to those in direct deprotonation, such as acidity of the corresponding C-H and the presence of directing groups. 

A synthesis of the natnral product meridianin D demonstrates selectivity in halogen-lithium exchange and substrate selectivity, using a halogenated boronic acid. The presence of the A-tosyl probably controls the halogen exchange selectivity. ... 

The synthesis of thieno[2,3- f]imidazole illustrates again the selectivity in halogen-metal exchange processes in imidazoles, hi this sequence a vinyl was used as A-protecting group, and it includes a nucleophilic displacement of bromine from the 4-position, activated by the 5-aldehyde. 

Free-radical halogenation of adamantane has been examined. By product analysis of halogenations in the presence and in the absence of oxygen it was possible to conclude that (a) the 1-adamantyl radical is more readily formed, (b) the 1-adamantyl radical has a longer lifetime, and (c) 1-adamantyl radical is less selective in halogen abstraction than the 2-adamantyl radical. This... 

Because the nature of the halogen atom can be varied, these salts show useful selectivity in their alkylation reaetions. We also prepared other halonium ions and studied their alkylating ability. 

Properties. As prepared, the polymer is not soluble in any known solvents below 200°C and has limited solubiUty in selected aromatics, halogenated aromatics, and heterocycHc Hquids above this temperature. The properties of Ryton staple fibers are in the range of most textile fibers and not in the range of the high tenacity or high modulus fibers such as the aramids. The density of the fiber is 1.37 g/cm which is about the same as polyester. However, its melting temperature of 285°C is intermediate between most common melt spun fibers (230—260°C) and Vectran thermotropic fiber (330°C). PPS fibers have a 7 of 83°C and a crystallinity of about 60%. 

Important differences are seen when the reactions of the other halogens are compared to bromination. In the case of chlorination, although the same chain mechanism is operative as for bromination, there is a key difference in the greatly diminished selectivity of the chlorination. For example, the pri sec selectivity in 2,3-dimethylbutane for chlorination is 1 3.6 in typical solvents. Because of the greater reactivity of the chlorine atom, abstractions of primary, secondary, and tertiary hydrogens are all exothermic. As a result of this exothermicity, the stability of the product radical has less influence on the activation energy. In terms of Hammond s postulate (Section 4.4.2), the transition state would be expected to be more reactant-like. As an example of the low selectivity, ethylbenzene is chlorinated at both the methyl and the methylene positions, despite the much greater stability of the benzyl radical ... 

The success of the halo ketone route depends on the stereo- and regio-selectivity in the halo ketone synthesis, as well as on the stereochemistry of reduction of the bromo ketone. Lithium aluminum hydride or sodium borohydride are commonly used to reduce halo ketones to the /mm-halohydrins. However, carefully controlled reaction conditions or alternate reducing reagents, e.g., lithium borohydride, are often required to avoid reductive elimination of the halogen. 

The comparative ease with which a benzylic hydrogen is abstracted leads to high selectivity in free-radical halogenations of alkylbenzenes. Thus, chlorination of toluene... 

Additional control of the nucleophilic substitution pathways a and b should be possible by varying the properties of the heteroarylium moiety in 33 as well as the substituent R and, to a minor extent, by the nature of the C-bonded halogen. Tire cation of 7a appeared to be an especially useful model compound and was thus selected in order to systematically study these influences and to define a standard situation. Structure 7a is easily accessible in excellent yield, and its molecular size allowed high-level MO calculations. 

Similar selectivity in displacement reactions is shown by 3,6-dichloropyridazine (153) (available by halogenation of the product from maleic anhydride and hydrazine). Thus, reaction of the dihalide with the sodium salt from sulfanilamide (93) affords fiulfachloropyridazine (104). Reaction of this last with sodium methoxide under somewhat more drastic conditions results in displacement of the remaining chlorine to give sulfamethoxypyrida-zine (105). ... 

Bases function in a more complex way than simply by acting as a halogen acceptor, for they cannot always be used interchangeably, and the product may depend on the base used (58,68,69). Diamines, such as ethylene-, propylene-, or hexamethylene diamines may function differently than monoamines. Diamines were thought to function through chelate formation (32). Loven and Speckamp (40) concluded that selectivity in reduction of a... 

On Pd/C, carbon-carbon double bonds and halogens are usually reduced before the N-oxides. The final selectivity in the hydrogenation of N-oxides has been shown to depend on the pH, the catalyst system used, and the functional groups present and their position. PtSx was a superior catalyst with a higher assay and yield in the selective hydrogenation of 6-chloro-2(lH)-hydroxyqui-noxaline-4-oxides (43) (Scheme 4.139).534... 

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