Alkyl Halides Help

Nomenclature

Alkyl halides have the general formula RX, where R is an alkyl or substituted alkyl group and X is any halogen atom (F, Cl, Br, or I). These compounds are named as the parent hydrocarbon, using fluoro-, chloro-, bromo-, or iodo- as the substituent names. For example,

is named 3-bromo-2-chlorohexane.

Classification is based on the structural features: RCH₂Br is 1°, R₂CHBr is 2°, and R₃CBr is 3°.

Synthesis of Alkyl Halides

Alkyl halides are usually prepared from alcohols or from alkenes, although they can be prepared directly from alkanes.

1. Halogenation of alkanes with Cl2 or Br2. These reactions are usually initiated by light (hv) and involve radical intermediates. Several steps are involved, and summarized as follows:

Initiation (produces 2 halogen radicals):

Propagation (produces product and continues the chain):

Termination (reactions that destroy radicals):

2.   From alcohols (ROH) with HX, PX₃, or SOCl₂. These reactions are similar to the nucleophilic substitution reactions discussed later in this chapter.

3. Addition of HX to alkenes. These reactions, which tend to follow Markovnikov's rule5

4. By reaction of alkenes with X₂ (X = Br, Cl) to give 1,2-dihalides. These electrophilic addition reactions are discussed more fully in Chapter 5.

Chemical Reactions of Alkyl Halides

Alkyl halides react with nucleophiles and with strong bases. Reactions with nucleophiles result in substitution, while elimination reactions result from reactions with bases.

Nucleophilic Substitution. Substitution reactions are reactions in which one group (a halogen, for example) is replaced by another group. Alkyl halides are electrophiles, so they react with nucleophiles to give substitution products. The halide ion that is displaced by the incoming nucleophile is called the leaving group.

Nucleophile + Substrate → Product + Leaving Group

Sulfonates are excellent leaving groups—much better than the halides. One of the best leaving groups (better than Br^–) is CF₃SO₃^–, called triflate.

S_n1 and S_n2 Mechanisms

The two major mechanisms of nucleophilic substitution are S_n1 and S_n2. The "S" means substitution, the "n" refers to the fact that a nucleophile is involved, and the "1" and "2" indicate the order of the reaction. S_n1 is a first-order reaction mechanism, meaning that only a single molecule is involved in the transition state for the rate-determining step. S_n2 is a second-order reaction in which 2 molecules (alkyl halide and nucleophile) come together in the transition state for the slow (rate determining) step.

The mechanism of the S_n1 reaction is shown below. Upon heating the alkyl halide, the C–X bond breaks, creating a carbocation and the halide ion leaves. The carbocation then reacts with a nucleophile to produce the substitution product.

Since the carbocation is so reactive, the strength of the nucleophile has no effect on the rate of S_n1 substitution. Also since a cation must be formed, this reaction is limited to 3° and 2° halides. The success of S_n1 reactions is sensitive to the nature of the leaving group: only the better leaving groups will permit this reaction to proceed.

The mechanism of the S_n2 reaction is quite different. In this mechanism, the nucleophile attacks the alkyl halide at the same time that the bond to the leaving group is breaking. There is a requirement that the nucleophile must attack the carbon that bears the halogen directly behind the C–X bond, also known as "backside attack." As the new bond forms and the C–X bond breaks, the carbon undergoes "inversion," as shown in the example on the next page, in which the nucleophile is iodide and the leaving group is bromide.

Notice that the starting material has the R configuration, but the product has the S configuration. This inversion of stereochemistry is a hallmark of the S_n2 reaction. In contrast, racemization occurs in S_n1 reactions since the sterochemistry of the starting material is destroyed as the planar cation intermediate is formed.

In S_n2 subsitution, the strength of the nucleophile as well as the nature of the leaving group and the substrate are all important. Only the more powerful nucleophiles will successfully react with alkyl halides. The alkyl halide substrate must not be sterically crowded, or the nucleophile will not be able to approach closely enough to displace the leaving group. As a result, S_n2 reactions are most favorable with methyl halides (such as CH₃I) and 1° halides (like CH₃CH₂Br), and never occur at 3° centers.

Elimination Reactions. Elimination reactions, which produce alkenes, can occur in competition with substitution reactions. As in substitution reactions, there are 2 common mechanisms for elimination reactions, the E1 and E2 mechanisms. In a β-elimination (dehydrohalogenation) reaction, a halogen and a hydrogen atom are removed from adjacent carbon atoms to form a double bond between the two C's. The reagent commonly used to remove HX is the strong base KOH in ethanol.

The E1 Mechanism. Like the S_n1 mechanism, the E1 mechanism is a 2-step process that proceeds via a cation intermediate.

The E2 Mechanism. The E2 reaction is a single-step, bimolecular reaction in which no intermediate is formed. This reaction proceeds via a transition state that has an antiperiplanar arrangement of the leaving group and the proton that is being removed. In this arrangement, the hydrogen and the leaving group lie in the same plane, pointing in opposite directions. As a result, the reaction is stereospecific—only one of the possible cis/trans stereoisomers is formed.

Substitution versus Elimination. S_n2 reactions are preferred when the halide is a good leaving group (I^–, Br^–) and when the substrate is unhindered (methyl, 1°, or 2°) and the nucleophile is a weak base (such as Cl^–, Br^–, or I^–). E2 is preferred when a strong base is used (KOH, NaOCH₃). S_n1 and E1 can also compete, with the major products usually resulting from substitution.

Practice problems for these concepts can be found at:  Alkyl Halides Practice Problems