8.6. Assessing SN1, SN2, E1, E2: Which will happen?

More detailed analysis

The most important factors to consider are the structure of the electrophilic 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 nucleophiles 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).

General guidelines

  • Leaving group (usually a halogen) is required – if none is present, none of these reactions occurs!
  • 1o favors SN2 or E2, never SN1 or E1 (unless resonance can happen). 3o easily does E2, never SN2.
  • sp2 C-X compounds (e.g., aryl halides) do not undergo nucleophilic substitution, and eliminations are difficult.
  • Strong base/nucleophile => SN2 or E2
  • Weak base/nucleophile => SN1 or E1
  • Polar aprotic solvent helps SN2; polar protic helps SN1/E1.
  • Heat favors elimination (E1/E2), cold favors substitution (SN1/SN2)

The following tables summarize the expected outcomes of alkyl halide reactions with two common classes of oxygen nucleophiles: Strong (hydroxide, ¯OH or alkoxides, ¯OR’) and weak (water, H2O or alcohols, R’OH). It is assumed that the alkyl halides have one or more beta-hydrogens, making elimination possible; and that polar solvents are used.

Primary alkyl halide R-X Cold Hot
Strong (reaction with ¯OH or ¯OR’) SN2
 E2, some SN2
Weak (reaction with H2O or R’OH) V. slow SN2 or no reaction
 Slow E2 or SN2
Secondary alkyl halide R-X Cold Hot
Strong (reaction with ¯OH or ¯OR’) SN2, possibly some E2
 E2
Weak (reaction with H2O or R’OH) Slow SN1 Slow SN1 or E1
Tertiary alkyl halide R-X Cold Hot
Strong (reaction with ¯OH or ¯OR’) E2, possibly some SN1
 E2
Weak (reaction with H2O or R’OH) SN1, possibly E1 E1

Note that some anionic nucleophiles are less basic than ¯OH/OR’, such as acetate CH3COO¯ (weakly basic) or iodide (non-basic).  These will tend to give more substitution and much less elimination.

Ammonia (NH3) and amines (usually RNH2 or R2NH), are common uncharged nitrogen nucleophiles.  These are more powerful nucleophiles than water or alcohols, but they are also basic, leading to more elimination in cases where this is possible.