Nucleophilic Substitution @ Saturated Carbon: SN1 & SN2

Question 1

Sn1

Answer 1

unimolecular/ first order nucleophilic substitution
1 molecule involved in RDS
nucleophile has no bearing on rate
acid protonates carbonyl or makes something into good LG
reactive intermediate
rate = k1 [RL] (RL = generalised substrate structure = R (C framework) + L = leaving group)
sp3–>sp2 planar carbocation–>sp3
tertiary reactants

Question 2

Sn2

Answer 2

bimolecular/ second order nucleophilic substitution
2 molecules involved in RDA
transition state (incoming nucleophile and leaving group both attached) indicated by BRACKETS
rate = k2 [RL] [Nu:]
direct sp3–>sp3
primary reactants

Question 3

substrate structure: steric hinderance

Answer 3

ease of nucleophile approach:
big groups harder to approach so more difficult to form t.s.
so Sn2 less likely as more substituents are attached to C centre being attacked
to do w/ HOMO-LUMO interaction

transition state formation
5-coordinate, trigonal bipyramidal
some bond angles decrease from 109.5 to 90
and some increase to 120
more numerous substituents = higher energy (harder to form) t.s. as greater steric clashes when reduced bond angle present

Sn1 more substituents = stabilisation of carbocation (nothing to do w/ steric hinderance)

Question 4

hyperconjugation & Sn1 carbocation stability

Answer 4

hyperconjugateion = σ conjugation
sp2 carbocation:
120 degrees minimises BP repulsion (VSEPR = valence e- pair repulsion theory)
e- placed in bonds with most s character (lower in energy) 33% rather than 25%

increasing number of substituents on C increases rate of Sn1

addition of methyl groups stabilised carbocation: small stabilisation from partial bonding electron pairs on R groups lowers MO energy of empty p orbital

Question 5

substrate structure: factors affecting Sn2 transition state stability

Answer 5

adjacent double bonds:
stabilised by adjacent πc=c & π*c=c
same for benzyl group but more stabilisation
can invoke both e- withdrawal and donation as stabilising factor

carbonyl groups:
stabilised by adjacent π*c=o withdrawal (can’t be donation as v. ∂- O)
ALSO new LUMO lower in energy from C-Br Lumo combination with C=O Lumo

Question 6

hybridisation state:

Answer 6

why no Sn1/2 at sp2 centres
via Sn1, stabilised carbocation has to form
- e.g. benzene ring + (benzene carbocation - no stabilisation from double bonds as all orthogonal to +ve charge)

via Sn2,

• nucleophile approach repelled by electron density in double bonds
• approach of nucleophile into σ* clocked by rest of aromatic ring
• with aromatic rings inversion of centre attacked is impossible (would have to break all bonds)

Question 7

π bond and lone pair donation & Sn1 carbocation stability

Answer 7

π bond donation, through conjugation:
double bonds
aromatic rings (more double bonds so more resonance forms so more stabilisation)
- positive charge stabilised by delocalisation

L.P. donation: STRONGEST OF ALL STABILISING EFFECTS, assists LG departure

Question 8

regioselectivity

Answer 8

choice of positions on substrate where it can react

favoured reactions have more reactive starting materials or lower energy transition state

Question 9

stereochemical outcome of single enantiomer of SM + Sn1

Answer 9

racemic mixture
reaction proceeds via planar carbocation
incoming Nu can attack from above or below
==> 1:1 mix of enantiomers (racemic mixture/ RACEMATE)

Question 10

stereochemical outcome of single enantiomer of SM + Sn2

Answer 10

single enantiomer
reaction proceeds is CONCERTED
proceeds via transition state
Sn2 gives STEREOCHEMISTRY INVERSION at attacked C atom (racemisation doesn’t occur)

Question 11

Sn1 + nucleophile effects

Answer 11

none
RDS = LG loss
good and bad nucleophiles all give products
nucleophile need not be deprotonated to make it more reactive (e.g. H2o –> OH-) as its already attacking a highly reactive carbocation

Question 12

Sn2 + nucleophile effects

Answer 12

nucleophile Very important, plays part in RDS
carbonyl chemistry: pKa of HNu = good guide to nucleophilicity (rate of reaction)
substitution at saturated carbon MORE COMPLICATED…

when atom forming bond is SAME over nucleophile range,
nucleophilicity PARALLELs basicity

when atom forming bond is DIFFERENT over nucleophile range:
PhS- better nucleophile than PhO- yet has lower pKaH (S l.p. HOMO higher in energy so closer to R-LG σ* Lumo so better interaction)
Often substrate C-LG bond is ONLY SLIGHTLY POLARISED (electrostatics are less the driving force of the reaction and HOMO-LUMO interactions dominate)
so SOFT NUCLEOPHILES OFTEN REACT BEST

/LOWER DOWN PERIODIC TABLE = larger atom = more electron shells = higher energy lone pair (HOMO) = closer energy HOMO and LUMO (electrophile σ*) = better interaction = more favourable Sn2 process

Question 13

LGA & saturated carbons

Answer 13

same as previously discussed

important for Sn1&2 as in both involved in RDS

Question 14

why are ethers generally unreactive in nucleophilic substitution

outcome of this…

if ether reacted…

Answer 14

C-O bond v. strong
very little bond angle strain
alkoxide anion similar in LGA to OH- ion (pKa alcohols = 15-18, water = 15.7) - alkoxides are usually shit LGs

so often used as solvent

if ether is reacted must usually be

• protonated first
• reacted under vigorous conditions (strong acids & high T)

Question 15

epoxides and substitution

Answer 15

Cs and O in epoxides are sp3 hybridised thus desired bond angle = 109.5
3 membered rings so angle = 60 = 45.5 degrees less than desired
release of ring strain makes epoxides v. good electrophiles in Sn2 reactions