SN1 Reaction

SN2 Reaction

Stereochemistry

Substitution occurs with a mixture of retention and inversion at astereocenter
Br312HOH 2O

312retention

21423423Rate = k [R–Br]+ H 3O Br

1

123[14Br][23(doubling theconcentration ofwater has noeffect on the rate)

4

H 2O ]

Fastest for tertiary, slowest for primary

Tertiary

2350°C

1BrSecondary

23

13

150°C

134–H

Step 3:deprotonation

HHO2134Path AOH 21H

Stepwise - leaving groupleaves (slow) forming acarbocation, which is thenattacked by a nucleophile(fast)

H 2O 2(R)

1.2 × 10 6

11.6+ H 3O Br

11+ H 3O Br

2(likely occuring through SN 2 mechanism)
From "March's Advanced Organic Chemistry", 5th Ed. p. 431

Mechanism

H1OHH 2O
22Rate+ H 3O Br

OH50°C

123H 2OBrPrimary

HOH 2O

H2Br

31BondsBroken
C2 –Br

C2 –CNOne stereoisomer

The rate of the reaction is sensitive to the concentration of thesubstrate AND the nucleophile
Br423CNC NNa

4132Rate = k [R–Br] [+ NaBr

11OH 2Path B3OH 224(S)–H

Step 3:
deprotonation
134H2OH(S)Path B gives retention (S)"Big Barrier"

12[34Br

123(doubling theconcentration of
CN doubles the rate)4[ :CN ]]

Unimolecular
Bimolecular(substrate only) (substrate and nucleophile)
Carbocation
stability

Steric hindrance
1° > 2° >>3°(fastest)

Nucleophile

Weak (generallyneutral)

Strong (generallybearing a negativecharge)

Solvent

Polar protic(e.g. alcohols)

Polar aprotic(e.g. DMSO, acetone)

Stereochemistry

Mix of retention
and inversion

InversionComparing SN1 vs. SN2 reactions

Slowest for tertiary, fastest for primary (methyl even faster)
BrTertiary

4Na

2344323Methyl

21H 3CNCC N

41Br

SecondaryPrimary

SN23° > 2° >>1°(fastest)

Rate

Na

41BrBr

NaNa

321C N

42323C NRate< 0.001CNC N

111H
324(S)

BrThe key skill to start with is identifying the leaving group
Look for halogens (Cl, Br, I) or tosylates/mesylates (OTs, OMs)
Alternatively, look for alcohols (OH) if acid is present
Once you've identified the leaving group, instpect the carbon it isattached to. How many carbons is that carbon connected to? That
will tell you if the carbon is primary, secondary, or tertiary. If there are
no attached carbons, that's the special case of "methyl" (SN 2 for sure!)

CN~20

If the carbon is tertiary, it's likely SN1. You can rule out SN 2 due to sterichindrance.
If the carbon is primary, it's likely SN 2. You can rule out SN1 due to the fact thatprimary carbocations are unstable [one exception: resonance stabilizedcarbocations].

CN~1000

Next, examine the nucleophile. A negatively charged nucleophile
generally indicates an SN 2 reaction. A neutral nucleophile (such asH 2O or ROH) generally indicates an SN1 reaction.

1H 3C

1N C

HRate LawCN]

Finally, check the solvent. A polar aprotic solvent (such as DMSO,acetone, acetonitrile, or DMF) generally indicates SN 2, whereas apolar protic solvent such as H 2O or ROH generally indicates SN1
conditions.

In the "backside attack", the nucleophile attacks the substrate from the backside
in a single step, resulting in inversion of configuration.

BrSN1

Alkyl halide(electrophile)

Rate Law

One step (backside attack)(S) alkyl halide

Carbocation

4(R)Path A gives inversion (R)Br+ NaMechanism

Step 1: Loss ofleaving group (slow)

Step 2: Attack of nucleophileon carbocation (fast)
Can occur from either side of
the flat carbocation(Path A or Path B)

32

SubstrateSubstrateBr41

RateRateRate

3

BondsFormed

CNC NNaOne stereoisomer

inversion

HO142inversion!
This substitution reaction results in an inversion of configuration at C-2

The rate of the reaction is ONLY sensitive to the concentration ofthe substrate (and not the nucleophile)
H 2O

Br+ H 3O BrRate Law
Br

Stereochemistry
Substitution occurs with inversion of configuration at chiral centersOH
3

SN1 vs. SN2 SummaryδN C–Hδ+ δ–
Brpartial bonds!

Transition stateHN C2134(R)If you found this useful, click hereto check out more great organicchemistry “cheat sheets” !

• Explains bimolecular rate law (depends on conc. of nucleophile and substrate)• Explains inversion of stereochemistry• Explains sensitivity to steric hindrance (bulky groups slow down backside attack)This is called the SN2 mechanism(Substitution, Nucleophilic, bimolecular)This sheet Copyright 2015 MasterOrganicChemistry.com
Questions, comments? james@masterorganicchemistry.com