21 July 2019
Free Radical Substitution
❑Reactivity in the Attacking Radical
❑The Effect of Solvent on Reactivity
❑Typical reactions with mechanisms
Reactivity in the Attacking Radical
Some radicals are much more selective than others.
The bromine atom is so selective that when only primary hydrogens are available, as in neopentane or tert-
butylbenzene, the reaction is slow or nonexistent; and isobutane can be selectively brominated to give tert-
butyl bromide in high yields.
Bromination reaction is slow
or nonexistent
neopentane
Bromination isobutane
reaction is slow
or nonexistent
tert-butylbenzene
N-Bromosuccinimide (NBS)
Toluene reacts with bromine atoms instantly (Radical reaction)
Ionic reaction
Bromination of other alkylbenzenes,for example, ethylbenzene and cumene, takes place exclusively
at the a position
Cumene
Ethylbenzene
Emphasizing the selectivity of Br.
The bond dissociation energy (C-H bond) is more important for radicals of low reactivity than for highly
reactive radicals.
Thus, bromine shows a greater tendency than chlorine to attack α to an electron-withdrawing group because
the energy of the C-H bond there is lower than in other places in the molecule.
Some radicals, for example, triphenylmethyl, are so unreactive that they abstract
hydrogens very poorly.
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Some free radicals (e.g., chloro) are electrophilic & some (e.g., tert-butyl) are nucleophilic.
But the predominant character of a free radical is neutral, whether it has slight electrophilic
or nucleophilic tendencies.
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The Effect of Solvent on Reactivity
The solvent usually has little effect on free-radical substitutions in contrast to ionic ones.
Indeed, reactions in solution are often quite similar in character to those in the gas phase,
where there is no solvent at all. However, in certain cases the solvent can make an appreciable
difference.
Chlorination of 2,3-dimethylbutane
Aromatic solvent
Aliphatic solvent 40% (More steric hindrance) 60% (Less steric hindrance)
Aromatic solvent 90% (More stable radical) 10% (Less stable radical)
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This type of effect is not found in cases where the differences in ability to abstract the atom
are caused by field effects of electron-withdrawing groups. In such cases, aromatic solvents
make little difference.
Much smaller, though real, differences in selectivity have been found when the solvent in
the chlorination of 2,3-dimethylbutane is changed from an alkane to CCl4. However, these
differences are not caused by formation of a complex between Cl atom & the solvent.
There are cases, however, where the rate of reaction for trapping a radical depends on the
polarity of the solvent, particularly in water.
N-Chlorosuccinimide
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REACTIONS
The reactions in this chapter are classified according to leaving group. The most
common leaving groups are hydrogen and nitrogen (from the diazonium ion); these
are considered first.
HYDROGEN AS LEAVING GROUP
Halogenation at an Alkyl Carbon
Polychloro substitution almost occur. When functional groups are present, favored positions
are those α to aromatic rings, while positions α to electron-withdrawing groups are least
likely to be substituted.
Tertiary carbons are most likely to be attacked and primary least. Positions α to an OR group
are very readily attacked.
For obtaining pure compounds, the chlorination reaction is essentially limited to substrates
with only one type of replaceable hydrogen (e.g., ethane, cyclohexane, neopentane).
The bromine atom is much more selective than the chlorine atom. As indicated it is often
possible to brominate tertiary and benzylic positions selectively.
High regioselectivity can also be obtained where the neighboring-group
mechanism can operate.
Some typical selectivity values of chlorination
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When it is another reagent, a similar cleavage occurs (catalyzed by light or, more commonly,
peroxides), followed by propagation steps that do not necessarily involve abstraction by
halogen.
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The order of reactivity of the halogens can be explained by energy considerations.
For the substrate methane, H values for the two principal propagation steps are
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