Chapter 4: Alcohols and Alkyl Halides

S_N2 mechanism

S_N2 indicates a substitution, nucleophilic, bimolecular reaction, described by the kinetic expression : rate = k [Nu][R-LG]

This pathway is a concerted mechanism (single step) as shown by the following reaction coordinate diagrams, where there is simultaneous attack of the nucleophile and displacement of the leaving group.
 

	Single step reactions have no intermediates and only a single transition state (TS).  In an SN2 there is simultaneous formation of the carbon-nucleophile bond and breaking of the carbon-leaving group bond, hence the reaction proceeds via a TS in which the central C is partially bonded to five groups.  The reaction profiles shown here are simplified and do not include the equilibria for protonation of the -OH.
General case		SN2 reaction

The following issues are relevant to the S_N2 reactions of alcohols:

The effect of the alkyl group: R-
Reactivity order :  CH₃-  >  CH₃CH₂-  >  (CH₃)₂CH-  >  (CH₃)₃C-

For alcohols reacting with HX, methyl and 1^o systems are more likely to react via an S_N2 reaction since the carbocations are too high energy for the S_N1 pathway to occur.

The effect of the leaving group: -LG
Once again the leaving group is a water molecule formed by protonation of the -OH group. -OH on its own is a poor leaving group.

The effect of the nucleophile: Nu
Since the nucleophile is involved in the rate determining step, the nature of the nucleophile is very important in an S_N2 reaction. More reactive nucleophiles will favour an S_N2 reaction.

Stereochemistry
When the nucleophile attacks in an S_N2  it is on the opposite side to the position of the leaving group. As a result, the reaction will proceed with an inversion of configuration, however, this is only observable if the substitution center is a chirality center (chapter 7). 

SN2 MECHANISM FOR REACTION OF ALCOHOLS WITH HBr
Step 1: An acid/base reaction. Protonation of the alcoholic oxygen to make a better leaving group. This step is very fast and reversible.  The lone pairs on the oxygen make it a Lewis base.
Step 2: Simultaneous formation of C-Br bond and cleavage of the C-O bond allows the loss of the good leaving group, a neutral water molecule, to give a the alkyl bromide. This is the rate determining step.

© Dr. Ian Hunt, Department of Chemistry