NUCLEOPHILLIC SUBSTITUTIONS WITH EXAMPLES

SUBSTITUTION by making a new bond AT THE SAME TIME as breaking the old bond

• substitution requires a bond to be broken AND a new bond to be formed

• the LOWEST energy way of doing this (unless precluded by steric or other effects, see later) is to MAKE THE NEW BOND (getting some energy "back") at the same time as BREAKING THE OLD BOND, this is SN2

Example

This is fundamentally just a Lewis acid/base reaction of the kind we saw when we were learning about Lewis acid/base reactions, the Lewis base has the high energy chemically reactive electrons, which are used to make a new bond to the Lewis acid, and a stronger bond is formed (C-O in the example above) and a weaker bond is broken (C-Br above)

• HO– is the Lewis Base and Nucleophile

• the halide is the Lewis acid/electrophile

• the Br– anion is the Leaving Group

The halide AND the nucleophile (2 molecules) are involved in the rate determining step and so the reaction rate depends upon the concentration of them both, the reactions is kinetically SECOND (2nd) order

Examples of SN2 Reactions; Give the major organic product in the following reactions

• we understand these SN2 reactions a simple Lewis acid/base processes

• identify the Lewis base/NUCLEOPHILE as the reactant with the high energy electrons

• the Lewis acid/nucleophile must react with the Lewis acid/ELECTROPHILE

Factors Controlling SN2 Reactivity: Leaving Group Ability

Good leaving groups are:

• stable/less reactive as an anion

• which means generally weak bases (have weak X-H bonds)

• polarize the C–LG bond (and are polarizable to make strong partial bonds in transition state)

Recall

Similarly

• INCREASING leaving group ability going down the periodic

• anion stability increases I– > Br– > Cl–

• the bond strength increases C-I < C-Br < C-Cl, i.e. the iodide anion is stable because when it reacts it makes WEAK BONDS

2.2  Factors Controlling SN2 Reactivity: Solvent Effects

Polar APROTIC  (NON-hydrogen-bonding) Solvents: There are Several, you need to know these

• Polar protic solvents have WEAKER intermolecular ion-dipole forces with dissolved ions

• The ion-dipole interactions certainly solvent and stabilize ions, but the H-bonding effect particularly on anions is MISSING

• There is a usually a SMALLER energy difference between reactants and the transition state when SN2 reactions are performed in polar APROTIC solvents, SN2 reactions in polar APROTIC solvents are usually faster than in polar protic solvents 

• you NEED TO KNOW the polar APROTIC solvents, this is not easy because they are different structures, learn them by working with them

Factors Controlling SN2 Reactivity: Nucleophilicity

Summary: Nucleophilicity order is sometimes difficult to remember, but favored by.....

1. anion over neutral

2. less electronegative over more electronegative

3. small atomic size over large atomic size in aprotic solvents

4. large atomic size over small atomic size in protic solvents

• These factors are all quite predictable except GOING DOWN THE PERIODIC TABLE (again!)

Factors Controlling SN2 Reactivity:  Steric Effects

First Order Nucleophilic Substitution (SN1) Reaction

• here the solvent "helps" to break the C–Br bond, the reaction is a solvolysis reaction (lysis - bond breaking)

We need a new substitution MECHANISM to account for this: The SN1 Mechanism

• the SN1 reaction requires a polar protic solvent to stabilize the ionic (cation and halide) intermediates

• usually requires heat (energy) to break the C–X bond unimolecularly

• ONLY the halide (not the nucleophile) involved in the R.D.S., thus SN1 (1 means only 1 reactant in the R.D.S.)

• requires a stable intermediate cation, NO SN1 for methyl or primary halides

3.1  Stereochemistry of SN1 Reactions: Racemization (?)

Example

Distinguishing SN1 and SN2 Reactions

• NOTE: the factors above favor the reactions by making them go faster, e.g. SN2 is FASTER at a primary carbon, SN1 is faster at a tertiary carbon, SN1 is faster in polar protic solvents etc.

• However, weak nucleophiles do not favor SN1 because they make Sn1 reactions faster, they don't, but they do make competing SN2 reactions SLOWER

• SN2 reactions are not precluded by polar protic solvents, they are just faster in aprotic solvents

Examples:  assign the mechanism of the following reactions to SN1 or SN2

Example Problems: Give the major organic product of reactions

• polar aprotic solvent, strong nucleophile, SN2, Br- better leaving group

• 1 equivalent means exactly the same number of nucleophiles as organic reactants, which in this context means that there is only enough nucleophile to substitute one of the halide leaving groups

• polar protic solvent and heat, no strong nucleophile and allylic halide, must be SN1. 

• polar aprotic solvent, strong nucleophile, SN2, allylic position more reactive

• 1 EQUIVALENT will ONLY REACT at the carbon where SN2 will be fastest