Sn1 and Sn2 reactions Flashcards
features of Sn1 reactions
Unimolecular - one molecule involved in RDS
sp2 planar reactive carbocation intermediate formed
features of Sn2 reactions
bimolecular - 2 molecules involved in RDS
concerted attack/leaving, transition state sp2 C
p-orbital used to share electrons between Nu and LG
ROR eqn Sn1
rate = k1[RL]
ROR eqn Sn2
rate = k2[RL][Nu]
depends on both bc two molecules involved in RDS
reaction energy profile Sn1 vs Sn2 reactions
Sn1 has a dip of lower energy at the carbocation intermediate, two higher energy transition states w partial bonds
Sn2 highest energy point is the transition state
four main variables to consider for sub at saturated C
substrate structure (think of this as equivalent to C=O reactivity)
Nu strength
LG ability
Solvent
two main considerations with substrate structure
steric hindrance (ie. ease of Nu approach)
factors influencing carbocation (Sn1) / transition state (Sn2) STABILITY
identify the HOMO and LUMO in Sn1 and Sn2 reactions
HOMO = Nu LP
LUMO = C-X sigma*
general rule for how substrate affects Sn1 / Sn2 pathway
Sn2 reactions become less likely the more substituents there are on the C centre being attacked
due to steric hindrance
Sn1 more likely the more substituents attached because of stabilisation of carbocation rather than steric hindrance
two factors which affect carbocation stability in Sn1 reactions
hyperconjugation (sigma conj)
pi-bond and lone pair donation
what is hyperconugation?
donation of adjacent sigma-bond electrons (often from alkyl groups) into the empty p-orbital of the carbocation (recall carbocation is sp2 hybridised!)
common misconceptions about hyperconjugation
- that stabilisation of carbocation is due to attached EDG
- that stabilisation occurs via the sigma bond directly attached to the C being attacked
BOTH INCORRECT
relative effect of pi-bond / lone pair donation compared to hyperconjugation
both are stronger effects
stabilise the carbocation more than hyperconjugation
how does pi-bond donation work?
pi-bonds can donate through conjugation - +ve carbocation charge stabilised by delocalisation (draw resonance forms)
how does lone pair donation work?
assists in the departure of the leaving group (pushes it off in one step)
think about it like LG leaves, resulting in +ve charge which is moved by LP
generally, look for it when there are two atoms possessing a lone pair of e- attached to the same C
what is the oxonium ion?
+ve on O (due to its LPs donating?)
acts like an activated carbonyl group,
how are the partial bonds in the Sn2 transition state formed? refer to FMO
two partial bonds are formed from mixing the filled and vacant HOMO and LUMO orbitals together
(hence stabilising delocalisation is possible from either filled OR vacant orbitals)
what types of substituents stabilise the Sn2 transition state?
both EDG and EWG!
in particular, adjacent double bonds (pi and pi) and adjacent C=O (pi)
why are C=O groups better at stabilising the Sn2 transition state than C=C?
the pi* of C=O combines with nearby sigma* of C-LG to form a new lower energy molecular LUMO, thus making it a more reactive starting material
define regioselectivity
the preference of the reaction (bond breaking/forming) happening at one place over any other
influenced by factors like steric hindrance and stabilisation
name a substrate type that is bad for both Sn1 and Sn2
neopentyl
poorly stabilised carbocation, AND tertiary group sterically hinders
stereochemical outcome of Sn1 reactions
racemic mixture
planar carbocation - incoming Nu may attack from either top or bottom face, resulting in 1:1 enantiomers mix
stereochemical outcome of Sn2 reactions
single enantiomer produced due to back-face attack, resulting in an inversion of stereochemistry
are Sn1 or Sn2 reactions favoured at sp2 C centres?
NEITHER.
Sn1 or Sn2 Nu sub CANNOT occur at sp2 C’s (this year anyway)
explain why Sn1 cannot happen at a sp2 C
LG leaves, resulting empty sp2 HAO is perpendicular to the p-orbitals in which the double bond electrons are
cannot be used to stabilise +ve charge
three reasons why Sn2 cannot happen at a sp2 C aromatic rings
- Nu- approach repelled by e-density of double bonds
- back-face attack into sigma* blocked by ring
- ring makes inversion impossible
importance of the nucleophile in Sn1 reactions
Nu NOT important in Sn1 - bc the RDS is the loss of leaving group, Nu attacks a highly reactive carbocation
importance of the nucleophile in Sn2 reactions
Nu VERY important in Sn2, bc involved in the RDS
predicting rate of reaction of a Nu at C=O vs substitution at saturated C (Sn2)
for C=O, easy to predict - Nucleophilicity parallels basicity hence pKa (higher pKa better Nu)
but NOT the case for Sn2
approach to consider nucleophilicity for Sn2 reactions
involved in RDS hence important - but more complicated than for attack at C=O.
to compare: split into 1. atom forming the bond is the same and 2. atom forming bond is NOT the same
nucleophilicity for Sn2 reactions - atom forming the bond is the SAME
eg. for comparing oxyanion Nu (O forms bond)
nucleophilicity parallels basicity – hence higher pKa = better nucleophile
(lower pKa = more acidic = more stable oxyanion)
nucleophilicity for Sn2 reactions - atom forming the bond is NOT the same
Sn2 reactions are HOMO-LUMO dominated (vs C=O large dipole hence electrostatics driven) so SOFT nucleophiles will often react best
lower on table –> larger atom –> higher HOMO –> closer HOMO-LUMO –> better interaction
eg. PhS- (pKa 6.4) > PhO- (10)
I- > Br- > Cl- > F-
two factors to consider for halide leaving groups
C-X bond strength
halide ion stability (pKa values)
trend in C-X bond strength going down G17
decreasing bond strength
F>Cl>Br>I
trend in acidity / pKa / anion stability going down G17
increasing acidity and decreasing pKa DOWN the group F–>I
hence greater anion stability and increasing leaving group ability
leaving group ability going down G17
increasing leaving group ability - I- is the best LG, F- is not particularly good
why is OH- not usually a leaving group in Nu sub @ saturated C for alcohols? (3 reasons)
- pKa of H2O is 15.7 - not a good leaving group
- Nu will often be basic enough to just remove the proton instead, forming NuH
- even if removed, hydroxide is basic enough to remove the proton from the alcohol anyway, preventing further reaction
two ways OH can be made into a better leaving group
- protonation
- sulfonate ester formation
both of which lower the pK of the leaving group
how does protonation of the -OH group impact its leaving ability?
protonate to OH2+, which is now a good leaving group pKa= -1.7 (for H3O+)
so the RDS in the mechanism becomes the loss of water, not the loss of hydroxide
reaction takes place in the presence of STRONG / CONC ACID
what reagents are used to convert an OH group to a sultanate ester?
using para-Toluenesulfonates (tosylates, OTs)
and pyridine
write TsCl, Py above arrow
OH becomes OTs group
why are tosylates better leaving groups than hydroxide?
lower pKa.
15.7 for H2O vs -1.3 for TsOH
two steps in mechanism for making a sultanate ester from alcohol
- Nucleophilic attack of the alcohol’s O lone pair onto the sulfonyl chloride (attacks at S, -Cl leaves)
- proton removal by pyridine (lone pair on N removes H) giving pyridinium hydrochloride salt (Py-HCl) as byproduct
why do the two steps in the mechanism for the conversion of an alcohol to sultanate ester not occur in reverse order? ie. protonation of alc by pyridine first, then attack of oxyanion?
because pyridine is only weakly basic and not strong enough to take the proton off the alcohol
pyridine pKa = 5, actually much more acidic than alcohol pKa=16
in what cases is the tosylate the best option to use?
in any reaction where acidic conditions cannot be used (ie OH cannot be protonated)
for example, C-C bond formation using an organometallic reagent as nucleophile
what is an epoxide?
a cyclic ether with a three-membered ring
very reactive due to substantial ring strain
why are ethers generally unreactive in Nu substitution?
very little bond angle strain
strong C-O bond
pKa of alkoxide anion similar to that of hydroxide ion (pKa alcohols usually 15-18) hence not a good leaving group
(more reactive if protonated, as for alcohols)
what makes epoxides good electrophiles in Sn2 reactions?
severe bond angle strain:
three membered rings - all sp3 hybridised so desired bond angle is 109.5˚ so the angle is dramatically constrained to 60˚
poorer overlap = weaker C-O bond
how are amino alcohols formed from reaction of epoxides?
epoxide will react with uncharged amine nucleophiles to give amino aochols
(N lone pair attacks into a C = Sn2 and release of ring strain, then ±H+)
pg. 129
relative stereochemistry of produce formed when epoxide ring is fused to another ring
the group added ends up on the OPPOSITE side of the OH group
because Sn2 attacks from one face of the ring, pushing the O- to the other face
optimum solvent for Sn1 reactions
polar protic solvents
optimum solvent for Sn2 reactions
polar aprotic solvents
why are polar protic solvents best for Sn1 reactions?
ions formed (carbocation intermediate and its counterion) during Sn1 reaction process
polar protic solvents will solvate both the intermediate ions, ie. stop it from regenerating/reversing
∂- part stabilises carbonation, ∂+ part stabilises LG and prevents reforming SM
examples of polar protic solvents
H2O
ROH
CH3COOH
why are polar aprotic solvents best for Sn2 reactions?
the Nu is often an anion, which is added to the reaction with its cation counterion
polar aprotic solvents solvate CATIONS well but not anions, hence making the anions more reactive nucleophiles by “taking away” their cations
effective because no ions are formed in Sn2 (vs carbocation int in Sn1)
examples of polar aprotic solvents
Acetone (propanone)
dimethylsulfoxide DMSO (acetone w S=O instead of C=O)
N,N-dimethylformamide DMF
no protons to pair w anions, hence only solvates cations with the ∂- of C=O or S=O
what do dielectric constants show?
a measurement of polarity
higher dielectric constant = more polar
order common polar protic solvents by polarity
most to least:
H2O, methanol, ethanol, acetic acid
spotting retrosynthesis of epoxides
a structure w a Nu attached to one C and an OH attached to he next
may have arisen from Nu attack into epoxide
