AN OVERVIEW

OF SN1 and SN2

REACTIONS
 SN2 REACTIONS
- a nucleophilic substitution reaction that takes
place in a single step by backside displacement
of the leaving group a group that is replaced in
a substitution reaction.
*This means that an entering nucleophile
attacks the substrate in 180o away from the
leaving group.)
- a reaction where the leaving group is displaced
at the same time the nucleophile approaches.
- In terms of reaction rate the exact speed at
which a reaction occurs (collision between the
substrate and the nucleophile):
*at a given concentration of the reactant, the
reaction takes place at a certain rate. Thus,
doubling the concentration of the the substrate
causes the frequency of collision between
substrate and the nucleophile to double, hence,
the rate of reaction is also doubled.
Thus, the origin of 2 in SN2:SN2 reactions are
said to be bimolecular because the rate of the
reaction depends on the concentrations of two
substances the substrate and the nucleophile.
Exercises:
a. What effects would the following changes have
on the SN2 reaction between CH3I and
NaCH3CO2?
1. the methyl iodide concentration is tripled?
2. Both the methyl iodide and sodium acetate
concentrations are doubled?
Mechanism of SN2 reaction
(show page 230 of the book Fundamentals of
Organic Chemistry, 7th ed by John McMurry).
Steric Effects on SN2 Reaction
The ease with which a nucleophile can approach a
substrate to carry out an SN2 reaction depends on
steric accessibility to the halide-bearing carbon.
*Bulky substrates, in which the halide-bearing
carbon atom is difficult to approach, react much
more slowly than those in which the carbon is
more accessible:
Trends of Reactivity of Alkyl halides
towards SN2 Reaction

Methyl halides are the most reactive substrates, followed by

primary alkyl halides. Alkyl branching next to the leaving group (Br)
in the above trend, slows the reaction greatly for secondary halides
and further branching effectively halts the reaction for tertiary
halides.
Note, Vinylic halide , (R2C=CRX) and Aryl halide,
(Ar X) are not included on the reactivity list because they are
completely unreactive toward SN2 displacements. This lack of
reactivity is due to steric hindrance. The incoming nucleophile
would have to burrow through part of the molecule to carry out
a displacement.
Exercises:
Which would you expect to be faster, the SN2 reaction of OH- ion
with 1-bromopentane or with 2-bromopentane?
Clue: The less hindered substrate will have a faster reaction
towards SN2 Reaction. 1-bromopentane is less hindered causing
it to react faster with OH- ion than 2-bromopentane.
2. Which of the following SN2 reactions would you expect to be
faster?
(a) Reaction of CN- (cyanide ion) with CH3CH(Br)CH3 or with
CH3CH2CH2Br?
(b) Reaction of I- ion with (CH3)2CHCH2Cl or with H2C=CHCl?
The Leaving Group in SN2 Reactions
- Because the leaving group is expelled with a
negative charge in most SN2 reaction, the BEST
leaving groups are those that give the most stable
anions (anions of strong acids)
Reactivity list of the Leaving Group

Note: The poorest leaving group is OH- ion while the best leaving
group is the I- ion.
Exercise:
Rank the following compounds in order of their
expected reactivity toward SN2 reaction:
CH3I, CH3F, CH3Br.
 SN1 Reaction
- A nucleophilic substitution reaction that takes
place in two steps through a carbocation
intermediate.
- In general, SN1 reactions take place only on
tertiary substrates and only under neutral or
acidic conditions in a hydroxylic solvent such as
water or alcohol.
- occurs by spontaneous loss of the leaving group
before the incoming nucleophile approaches
step 1.
Note:
Loss of the leaving group gives a carbocation
intermediate, which then reacts with the
nucleophile in a second step to yield the
substitution product step 2.
*This two-step mechanism explains why tertiary
alcohols react with HBr so much more rapidly
than primary or secondary ones do: SN1 reactions
can occur only when stable carbocation
intermediates are formed. The more stable the
carbocation intermediate, the faster the SN1
reaction. Thus, the reactivity order of alcohols
with HBr is the same as the stability order of
carbocations.
- In terms of reaction rate, SN1 reaction depends
only on the concentration of the substrate and is
independent of the nucleophile concentration.
Thus, the origin of the 1 in SN1: SN1 reactions are
unimolecular because the rate of the reaction
depends on the concentration of only one
substancethe substrate.
The observation that SN1 reactions are unimolecular
means that the substrate must undergo a
spontaneous reaction without involvement of the
nucleophile.
Exercises:
What effect would the following changes have on
the rate of the SN1 reaction of tert-butyl alcohol
with HBr?
(a) The HBr concentration is tripled.
(b) The HBr concentration is halved, and the tert-
butyl alcohol concentration is doubled.
Clue: Concentration of nucleophile has no effect on
reaction rate in SN1 reactions.
Answers:
a. Unchanged
b. Doubled
Reactivity order towards SN1 reactions

Reactivity order towards SN1 reaction is 3 > 2

> 1 and is backward from the normal SN2
reactions order.
Reactivity order of the leaving group
towards SN1 reactions
OH < Cl < Br < I H2O

Leaving Group Reactivity

Mechanism of the SN1 Reactions:

Show page 235 of the book Fundamentals of
Organic Chemistry, 7th ed. by John McMurry).
 Reactions of alcohols
Oxidation of Alcohols with milder (weak) oxidizing
agents.
Oxidation of Primary alcohols with PCC (Pyridinium
chlorochromate) or with periodinane in the
presence of CH2Cl2 (dichloromethane) yields an
ALDEHYDE.
Ex. What is the oxidation product of the reaction of
3,7-dimethyl-2,6-octadien-1-ol (commonly known
as geraniol) with PCC/periodinane in the
presence of CH2Cl2?
Note: Comparison on the oxidation products of
primary alcohols with H2CrO4 or NaCr2O7/H2SO4 or
CrO3/H2SO4 (classified as strong oxidizing agents)
against the oxidation products of primary alcohols
with milder oxidizing agents like PCC or
periodinane:
Primary alcohols (one C O bond) produce an
oxidation product with 3 C O bonds with strong
oxidizing agents while 2 C O bonds only with
milder oxidizing agents.
Addition of Alcohol with Hydrogen halide
(H-X)
Ex.
a. CH3OH + HBr CH3Br + H2O SN2
b. Cyclohexanol reacts with HBr yields
bromocyclohexane - SN2
c. Reaction between 2-methyl-2-butanol with HI
yields 2-iodo-2-methylbutane SN1
Addition of PCl3, PBr3, SOCl2 to alcohols
Ex:
1. Reaction of Cyclopentanol with thionylchloride
SOCl2 yields chlorocyclopentane (alkyl chloride)
- This reaction is an example of direct conversion
of alcohol to an alkyl chloride. Likewise, if you
want to produce alkyl bromide, use PBr3 instead
of PCl3 or SOCl2.
Conversion of Alcohols to ethers
- Alcohols are converted into ethers by formation of
the corresponding alkoxide ion followed by
reaction with an alkyl halide, a reaction known as
the Williamson ether synthesis.
Note: The alkoxide ion needed in the reaction can
be prepared either by reaction of an alcohol with
an alkali metal or by reaction with a strong base
such as sodium hydride, NaH.
Ex: Conversion of cyclopentanol to
methoxycyclopentane in the presence of NaH, and
further reacted with methyliodide an SN2
reaction
Reminder:
Unsymmetrical ethers are therefore best prepared by
reaction of the more hindered alkoxide partner with
the less hindered alkyl halide partner, rather than vice
versa.
Ex:
tert-Butyl methyl ether, for example, is best prepared by
reaction of tert-butoxide ion with iodomethane,
rather than by reaction of methoxide ion with 2-
chloro-2-methylpropane.
Exercises:
Problems 8.14 and 8.15 on page 275 of the book
Fundamentals of organic chemistry, 7th ed by
McMurry
Preparations of alcohols
1. Hydration of alkenes:
Alkene + water catalyzed by strong acid (H2SO4)
corresponding alcohol
Note: Be guided with Markovnikovs Rule to predict
the major and minor products.
Ex. Ethene + water yields ethanol
cyclohexene + water yields cyclohexanol
2. Reduction of Carbonyl Compounds
A carbonyl group + reducing agent [H] form an
alcohol
Ex. A. Reduction of an aldehyde to form a primary
alcohol
butanal + a reducing agent NaBH4 (sodium boro
hydride) in the presence of ethanol (ETOH) and
further reaction with an acid yields 1-butanol
B. Reduction of a Ketone to form a secondary alcohol
Dicyclohexyl ketone is reduced by NaBH4/ETOH in the
presence of H3O+ yields dicyclohexyl methanol
Note: only 1 H is added to the carbonyl group during
the reduction of either an aldehyde and ketone.
Reduction of Carboxyl group and esters
Reduction of carboxyl group and esters are not as
rapid as reduction of carbonyl group, that is why a
more powerful reducing agent such as lithium
aluminum hydride (LiAlH4) is abetter choice as a
reagent rather than NaBH4.
Note: There are 2 H atoms that are added to the
carbonyl group during the reduction of either the
carboxylic acid or ester.
Ex. What is produced when 9-octadecenoic acid
(oleic acid) is reduced by LiAlH4/ether in the
presence of an acid (H3O+)
Ans: 9-octadecen-1-ol
Reduction of Ester
What is the product of the reduction of methyl-2-
pentenoate
Ans: 2-penten-1-ol
Exercise:
1. What is the product of the reduction of 3-
hexanone?
2. What carbonyl compound(s) might you reduce to
obtain a. 4-methyl-2-hexanol? b. 4-methyl-2-
pentenal?
Grignard Reactions of Carbonyl
Compounds
Grignard reagents (RMgX) - prepared by reaction of
organohalides with magnesium (where R =1o, 2o
or 3o alkyl, aryl or vinylic while X = Cl, Br or I)
- react with carbonyl compounds to yield alcohols
in much the same way that hydride reducing
agents do.
- Just as carbonyl reduction involves addition of a
hydride ion to the CO bond, Grignard reaction
involves addition of a carbanion (R:- +MgX).
Show mechanism on page 266,
Note: methanal always yield a primary alcohol,
aldehydes with more than 2 C atoms always yield
secondary alcohols and ketones always yield tertiary
alcohol.
Examples:
a. Reaction of formaldehyde with Grignard reagent
(cyclohexylmagnesiumbromide) mixed with ether, in
the presence of acid, H3O+ yield cyclohexyl
methanol.
b. 3-methylbutanal reacts with
phenylmagnesiumbromide mixed with ether in the
presence of H3O+ yields ___________.
c. What is the reduction product of the reaction of
cyclohexanone with ethylmagnesiumbromidemixed
with ether in the presence of H3O+?
Answers:
b. 3-methyl-1-phenyl-1-butanol
c. 1-ethylcyclohexanol
Reinforcement Activity:
Show by reaction a possible way of synthesizing 2-
methyl-2-pentanol or 2-methylpentan-2-ol?
Possible Answers:
a. Reaction of 2-pentanone with
methylmagnesiumbromide
b. Reaction of acetone with propylmagnesiumbromide
c. Reaction of methylbutanoate with 2 moles of
methylmagnesiumbromide
Reactions of Phenols
a. Phenols can not be dehydrated by treatment with an
acid and cant be converted into halides by
treatment with HX (as compared with alcohol
though they have the same OH group).
b. Phenols can be converted to ether (Williamson ether
synthesis) by SN2 reaction with alkyl halide in the
presence of base and occurs easily compared to
alcohol because phenols are more acidic than
alcohols and phenols are readily formed into their
anions.
Ex. The reaction of o-nitrophenol with 1-bromobutane
in the presence of K2CO3 and acetone yields butyl o-
nitrophenyl ether
c. Electrpphilic Aromatic Substution Reaction of Phenols
- because OH is activating ortho and para directing
substituents in EAS reaction, they are reactive
substrates for electrophilic halogenation, nitration
and sulfonation reactions.
d. Phenols dont undergo oxidation reaction in the same
way that alcohols do because they do not have
hydrogen atoms attached o the carbon atom bearing
the hydroxyl (-OH) group. However, phenols are
oxidized by Na2Cr2O7 in the presence of an acid
producing 2,5-cyclohexadien-1,4-dione (commonly
known as quinone).
Note: present page 275 of McMurry book to discuss
the importance of quinones during enegy production
in aerobic organisms