Selectivity of halogenation reaction of alkane

When alkanes larger than ethane are halogenated, isomeric products are formed. Thus chlorination of propane gives both 1-chloropropane and 2-chloropropane as mono-chlorinated products. Four constitutionally isomeric dichlorinated products are possible, and five constitutional isomers exist for the trichlorinated propanes. Can you write structural formulas for the four dichlorinated isomers?

The halogenation of propane discloses an interesting feature of these reactions. All the hydrogens in a complex alkane do not exhibit equal reactivity. For example, propane has eight hydrogens, six of them being structurally equivalent primary, and the other two being secondary. If all these hydrogen atoms were equally reactive, halogenation should give a 3:1 ratio of 1-halopropane to 2-halopropane mono-halogenated products, reflecting the primary/secondary numbers. This is not what we observe. Light-induced gas phase chlorination at 25 ºC gives 45% 1-chloropropane and 55% 2-chloropropane.

CH₃-CH₂-CH₃   +   Cl₂   →  45% CH₃-CH₂-CH₂Cl   +   55% CH₃-CHCl-CH₃

The results of bromination ( light-induced at 25 ºC ) are even more suprising, with 2-bromopropane accounting for 97% of the mono-bromo product.

CH₃-CH₂-CH₃   +   Br₂  →  3% CH₃-CH₂-CH₂Br   +   97% CH₃-CHBr-CH₃

These results suggest strongly that 2º-hydrogens are inherently more reactive than 1º-hydrogens, by a factor of about 3:1. Further experiments showed that 3º-hydrogens are even more reactive toward halogen atoms. Thus, light-induced chlorination of 2-methylpropane gave predominantly (65%) 2-chloro-2-methylpropane, the substitution product of the sole 3º-hydrogen, despite the presence of nine 1º-hydrogens in the molecule.

(CH₃)₃CH   +   Cl₂   →  65% (CH₃)₃CCl   +   35% (CH₃)₂CHCH₂Cl

.It should be clear from a review of the two steps that make up the free radical chain reaction for halogenation that the first step (hydrogen abstraction) is the product determining step. Once a carbon radical is formed, subsequent bonding to a halogen atom (in the second step) can only occur at the radical site. Consequently, an understanding of the preference for substitution at 2º and 3º-carbon atoms must come from an analysis of this first step.

First Step:       R₃CH   +   X·   →  R₃C·   +   H-X

Second Step:     R₃C·   +   X₂   →  R₃CX   +   X·

Since the H-X product is common to all possible reactions, differences in reactivity can only be attributed to differences in C-H bond dissociation energies. In our previous discussion of bond energy we assumed average values for all bonds of a given kind, but now we see that this is not strictly true. In the case of carbon-hydrogen bonds, there are significant differences, and the specific dissociation energies (energy required to break a bond homolytically) for various kinds of C-H bonds have been measured. These values are given in the following table.

The difference in C-H bond dissociation energy reported for primary (1º), secondary (2º) and tertiary (3º) sites agrees with the halogenation observations reported above, in that we would expect weaker bonds to be broken more easily than are strong bonds. By this reasoning we would expect benzylic and allylic sites to be exceptionally reactive in free radical halogenation, as experiments have shown. The methyl group of toluene, C₆H₅CH₃, is readily chlorinated or brominated in the presence of free radical initiators (usually peroxides), and ethylbenzene is similarly chlorinated at the benzylic location exclusively. The hydrogens bonded to the aromatic ring (referred to as phenyl hydrogens above) have relatively high bond dissociation energies and are not substituted.

C₆H₅CH₂CH₃ + Cl₂   →  C₆H₅CHClCH₃   +   HCl

Since carbon-carbon double bonds add chlorine and bromine rapidly in liquid phase solutions, free radical substitution reactions of alkenes by these halogens must be carried out in the gas phase, or by other halogenating reagents. One such reagent is N-bromosuccinimide (NBS), shown in the second equation below. By using NBS as a brominating agent, allylic brominations are readily achieved in the liquid phase.

The covalent bond homolyses that define the bond dissociation energies listed above may are described by the general equation:

R₃C-H   +   energy   →  R₃C·   +   H·

Since the hydrogen atom is common to all the cases cited here, we can attribute the differences in bond dissociation energies to differences in the stability of the alkyl radicals (R₃C·) as the carbon substitution changes. This leads us to the conclusion that:

Because alkyl radicals are important intermediates in many reactions, this stability relationship will prove to be very useful in future discussions. The enhanced stability of allyl and benzyl radicals may be attributed to resonance stabilization.
Formulas for the allyl and benzyl radicals are shown below. Draw structural formulas for the chief canonical forms contributing to the resonance hybrid in each case.

The poor stability of phenyl radicals, C₆H₅·, may in turn be attributed to the different hybridization state of the carbon bearing the unpaired electron (sp² vs. sp³).