organic chemistry: nucleophilic aliphatic substitution reactions

hard nucleophiles and electrophiles

• high charge density (small and charged)

• low energy HOMO

• X^- is basic - likely to attack H⁺, C=O

soft nucleophiles and electrophiles

• low charge density (large and neutral)

• high energy HOMO

• X^- not basic - likely to attack sp³ hybridized carbon

S_N1 mechanism

• substitution nucleophilic unimolecular

• unimolecular - first order reaction, rate only dependent on concentration of alkyl halide

• nucleophile not involved in rate determining step - any nucleophile can be used but very basic ones may lead to elimination reaction

• 2 step mechanism - intermediate formed

• intermediate - local low point on reaction profile

• rate determining step - slowest step as most energy required, removing leaving group from carbocation, transition state formed at highest point of profile 

• racemic mixture of enantiomers produced as product

S_N1 mechanism: stable carbocation formation

• substrates that form stable carbocation essential

• tertiary carbocations most stable since 3 CH bonds present so more electron donating groups present to stabilise carbocation

• if double bonds present in carbocation stabilised by conjugation systems (resonance)

• benzene rings help to stabilise positive charge very effectively

• oxygen substituents good at stabilising since they have a lone pair which they can donate to the carbocation centre

S_N1 mechanism: leaving groups

• good leaving group needed - C-LG bond breaks spontaneously

• do not want leaving group which will be attracted to carbocation

• leaving group needs to be stable on its own

• better leaving group = no catalyst required

S_N1 mechanism: solvents

• polar protic solvents that can stabilize carbocation and leaving group best - can accept and donate H bonds to stabilise cationic and anionic species

• dielectric constant - gives idea of solvents ability to solvate anions/cations

• dipolar aprotic solvents - solvate cations but can’t stabilise anions so leaving group not stabilised

• aprotic solvents - interact with metal ion centres in other reagents

S_N2 mechanism

• substitution nucleophilic bimolecular

• bimolecular - second order, both nucleophile and alkyl halide involved in rate determining step

• 1 step mechanism - adding in nucleophile and pushing out leaving group in one step

• rate determining step - nucleophile attacking carbon centre, C-LG bond being broken

• nucleophile attacks sigma* orbital (LUMO) on back of carbon-LG bond 

• transition state has partial bonds between central C atom and LG and central C atom and nucleophile - p orbital shares 1 pair of electrons between old and new bonds

• since nucleophile attacks from back of carbon-LG bond there is an inversion of configuration in the product

S_N2 mechansim: leaving groups

• good leaving group needed - C-LG bond breaks spontaneously

• do not want leaving group which will be attracted to carbocation

• leaving group needs to be stable on its own

• better leaving group = no catalyst required

• correlations to pKa - more acidic = better leaving group as conjugate base (anion) more stable so ionises more easily

S_N2 mechanism: substrates

• unhindered substrates better - need to be able to get nucleophile coming in 

• primary carbocations best - nucleophile can easily push its way in past H atoms

• alkenes also good since the pi system of adjacent double bonds stabilises the transition state by conjugation

• nucleophilic attack fastest when pi* and sigma* orbitals combine to form new LUMO which is lower in energy and has largest coefficient - each grou

S_N2 mechanism: nucleophile

• good nucleophile essential since it is involved in the rate determining step

• basicity leads to nucleophilicity towards a proton - bases are better nucleophiles since they are unstable as anions so are more reactive

• good nucleophiles have high energy HOMO so can overlap well with low energy sigma* C-LG LUMO

• nucleophilic atoms better if have greater ionic radius - lone pair forming HOMO further from nucleus so less attracted to nuclear charge and higher in energy

• charged nucleophiles better than uncharged ones - more strongly attracted to carbocation

• primary nucleophiles best - less substituents which block it from reaching the stereogenic centre

S_N2 mechanism: solvent

• good solvents do not solvate the nucleophile - dipolar aprotic solvents best

• dipolar aprotic solvents solvate cations and leave anions alone - anion left nucleophilic