- predict the products and specify the reagents for SN1, SN2, E1 and E2 reactions with stereochemistry
- propose mechanisms for SN1, SN2, E1 and E2 reactions
- draw, interpret, and apply Reaction Energy Diagrams for SN1, SN2, E1 and E2 reactions
Summary of Reaction Patterns
Having discussed the many factors that influence nucleophilic substitution and elimination reactions of alkyl halides, we must now consider the practical problem of predicting the most likely outcome when a given alkyl halide is reacted with a given nucleophile. As we noted earlier, several variables must be considered, the most important being the structure of the alkyl group and the nature of the nucleophilic reactant.In general, in order for an SN1 or E1 reaction to occur, the relevant carbocation intermediate must be relatively stable. Strong nucleophile favor substitution, and strong bases, especially strong hindered bases (such as tert-butoxide) favor elimination.
The nature of the halogen substituent on the alkyl halide is usually not very significant if it is Cl, Br or I. In cases where both SN2 and E2 reactions compete, chlorides generally give more elimination than do iodides, since the greater electronegativity of chlorine increases the acidity of beta-hydrogens. Indeed, although alkyl fluorides are relatively unreactive, when reactions with basic nucleophiles are forced, elimination occurs (note the high electronegativity of fluorine).
The following table summarizes the expected outcome of alkyl halide reactions with nucleophiles. It is assumed that the alkyl halides have one or more beta-hydrogens, making elimination possible; and that low dielectric solvents (e.g. acetone, ethanol, tetrahydrofuran & ethyl acetate) are used. When a high dielectric solvent would significantly influence the reaction this is noted in red. Note that halogens bonded to sp2 or sp hybridized carbon atoms do not normally undergo substitution or elimination reactions with nucleophilic reagents.
Experimental observations are reported for the following reactions. These reactions include a range of alkyl halide structures in a variety of reaction conditions to illustrate the reaction patterns summarized above. In describing these, it is useful to designate the halogen-bearing carbon as alpha and the carbon atom(s) adjacent to it as beta, as noted in the first four equations shown below. Replacement or substitution of the halogen on the α-carbon (colored maroon) by a nucleophilic reagent is a commonly observed reaction, as shown in equations 1, 2, 5, 6 & 7 below. Also, since the electrophilic character introduced by the halogen extends to the β-carbons, and since nucleophiles are also bases, the possibility of base induced H-X elimination must also be considered, as illustrated by equation 3. Finally, there are some combinations of alkyl halides and nucleophiles that fail to show any reaction over a 24 hour period, such as the example in equation 4. For consistency, alkyl bromides have been used in these examples. Similar reactions occur when alkyl chlorides or iodides are used, but the speed of the reactions and the exact distribution of products will change.
In order to understand why some combinations of alkyl halides and nucleophiles give a substitution reaction, whereas other combinations give elimination, and still others give no observable reaction, we must investigate systematically the way in which changes in reaction variables perturb the course of the reaction. The following general equation summarizes the factors that will be important in such an investigation.
Friendly Reminder: One conclusion, relating the structure of the R-group to possible products, should be immediately obvious. If R- has no beta-hydrogens an elimination reaction is not possible, unless a structural rearrangement occurs first. The first four halides shown on the left below do not give elimination reactions on treatment with base, because they have no β-hydrogens. The two halides on the right do not normally undergo such reactions because the potential elimination products have highly strained double or triple bonds. It is also worth noting that sp2 hybridized C–X compounds, such as the three on the right, do not normally undergo nucleophilic substitution reactions, unless other functional groups perturb the double bond(s).
1. Identify the dominant reaction mechanism (SN1, SN2, E1, or E2) and predict the major product for the following reactions.