CH221 CLASS 18
CHAPTER 10: ALKYL HALIDES
Synopsis. This is an introductory class dealing with nomenclature, structure, radical halogenation, allyl and benzyl radicals, formation and uses of some organometallic compounds and oxidation/reduction.
Introduction
Halogenated organic compounds are widespread throughout nature and are very important in industry and in the laboratory as synthetic intermediates. Some examples of natural and commercially important organohalogen compounds are given below, but see also p. 335 in the textbook for other examples from nature.
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The major types of organohalogen compounds are illustrated below, where it can be seen that the classification depends on the type of carbon atom to which the halogen is attached. Furthermore, it will be shown that the group alkyl halides, which are especially emphasized in this course, can be subdivided into primary, secondary and tertiary halides.
Naming Alkyl Halides
To name alkyl halides, carry out the following steps.
Note that many halogen compounds are better known by their trivial names,
including methyl bromide (bromomethane), methylene chloride (dichloromethane), allyl chloride (1-chloro-2-propene) and benzyl bromide (bromophenylmethane).
Structure of Alkyl Halides: Polarity and Strength of the C-Hal (C-X) Bond
From Table 10.1 on p. 319 of the textbook, it is possible to make the following generalizations for the halomethanes, CH3-X.
CH3F CH3Cl CH3Br CH3I
C-X bond strength increases
C-X bond length increases
C-X bond polarity increases
Polarizability of X increases
The same generalizations are true for all alkyl halides. These factors make the halogen-containing carbon atom electrophilic in nature, which in turn is responsible for much of the important chemistry of alkyl halides (SN and E reactions – Chapter 11, see class 19).
Preparation of Alkyl Halides
We have seen already that alkyl halides can be prepared by the halogenation or hydrohalogenation of alkynes and alkenes (see classes 12, 13 and 15). We have also seen that light-initiated radical halogenation of alkanes and cycloalkanes yields alkyl halides (class 9). It is now time to time to consider the last method in a bit more detail, noting particularly the range of reactivities and the synthetic limitations of the method.
Radical Halogenation of Alkanes using Elemental Halogens: Chlorination
The one big limitation of this method (especially chlorination) is that it almost inevitably leads to a (often complex) mixture of products. Even chlorination of methane gives a mixture:
light
CH4 + Cl2 CH3Cl, CH2Cl2, CHCl3 and CCl4
The situation is even worse for the chlorination of alkanes that have more than one kinds of hydrogen:
In the first example, 30% of primary halide means that each one of the six primary hydrogens (CH3) is responsible for 30%/6 = 5% of product, whereas 70% of secondary alkyl halide means that each one of the four secondary hydrogens (CH2) is responsible for 70%/4 = 17.5% of the product. Hence, chlorination at secondary carbon occurs about 3.5 times the rate of chlorination at primary carbon.
Similarly, in the second example, chlorination occurs at the single tertiary carbon (CH) at about 5 times the rate of chlorination at the primary carbons.
The order of reactivity toward radical chlorination is
R-CH3 < R2CH2 < R3CH
1o 2o 3o
rel. rate 1 3.5 5
This order reflects the relative order of the C-H bond strengths: 3o < 2o < 1o. Since less energy is needed to break a tertiary C-H bond than either a 2o or a 1o C-H bond, the resulting tertiary radical is more stable than either a secondary or primary radical, as we have already noted (see class 10).
However, although the rates of chlorination at different carbon atoms are different, the difference is not great, so that in practice, some chlorination occurs at all sites.
Radical chlorination has poor selectivity
Bromination, on the other hand, is much more selective, mainly because of the lesser reactivity of the halogen species (in particular Br.):
Bromination at Allylic and Benzylic Carbon Atoms
Compounds with allylic and benzylic hydrogen atoms can be brominated readily using the mild brominating agent N-bromosuccinimide (NBS):
The reaction is thought to proceed via the following type of radical chain mechanism:
Bromination occurs preferentially at the allylic carbon because the allyl radical is more stable than any other possibility (vinylic and alkyl), a fact that is reflected by the relative bond energies:
Thus, it is possible to extend the previous radical stability sequence:
Vinyl < 1o alkyl (CH3) < 2o alkyl (CH2) < 3o alkyl (CH) < allyl (benzyl)
Resonance Stabilization of Allyl and Benzyl Radicals
The enhanced stability of allyl and benzyl radicals is best explained by the influence of resonance or delocalization.
One important synthetic consequence of the delocalized allyl radical is that more than one bromination product is often obtained:
Preparing Alkyl Halides from Alcohols
Just as alkyl halides are often key synthetic intermediates, so are alcohols and carbonyl compounds and hence a useful sequence is
Alkyl halides can be formed from alcohols by three basic methods, as summarized below.
E.g.
Reactions of Alkyl Halides: Formation of Grignard Reagents and Other Organometallic Compounds
Victor Grignard discovered that a dry alkyl halide will react with dry magnesium metal in a dry ether solvent to produce an organometallic compound with that behaves as if it has the structure R-Mg-X It is now called an alkylmagnesium halide or Grignard reagent:
In common with other organometallic compounds the metal-bound carbon atom is highly nucleophilic,
This carbon atom is also highly basic and hence Grignard reagents must be prepared in the absence of both water and acidic groups such as –COOH, -OH or –NH2 in the molecule.
Organometallic Coupling Reactions
Other organometallic compounds, like alkyllithiums, can be made in a similar manner to Grignard reagents, although many of these are even more sensitive to the presence of water.
These organolithium compounds can be used to make lithium diorganocopper compound (LiR2Cu), known as Gilman reagents,
Gilman reagents are useful coupling agents – they undergo alkylation reactions with alkyl halides:
These are versatile reactions, occurring at vinyl and aryl carbon atoms, as well as alkyl carbons,
A Note on Oxidation and Reduction in Organic Chemistry
Oxidations and reductions (redox reactions) have been met already at several points on this course (e.g. the perhydroxylation and hydrogenation of alkenes in class 14 and the hydrogenation of alkynes in class 15). At this point, it is worth noting qualitative ways (i.e. those that don’t involve the determination of oxidation numbers) of describing organic oxidation/reduction reactions.
OXIDATION – a reaction that results in loss of electron density at carbon, by either C-O, C-N or C-X (X = halogen) bond formation or by C-H bond breaking
REDUCTION – a reaction that results in gain of electron density at carbon, by either C-H bond formation or by C-O, C-N or C-X bond breaking
Examples
A list of common compounds (and corresponding functional groups) is given below, with alkanes being the most reduced and CO2, CCl4 being the most oxidized. Any conversion left right is an oxidation, whereas any conversion right left is a reduction.
CH3CH3alkanes / CH2=CH2
alkenes / CHCH
alkynes
CH3OH
alcohols / CH2=O
aldehydes and ketones / HCOOH
carboxylic acids / CO2
CH3Cl
Alkyl halides / CH2Cl2
dihalogen compounds / CHCl3
trihalogen compounds / CCl4
CH3NH2
amines / CH2=NH
imines / HCN
nitriles
LOWEST OXIDATION LEVEL / HIGHEST OXIDATION LEVELS