Haloalkanes
Structure of Haloalkanes
• Haloalkane (alkyl halide): A compound
containing a halogen atom covalently bonded to
an sp3 hybridized carbon.
• often represented as RX
Nomenclature of Haloalkanes
• Locate the parent alkane.
• Locate each halogen on the parent chain.
• Number the parent chain to give the substituent
encountered first the lower number.
• Show halogen substituents by the prefixes
fluoro-, chloro-, bromo-, and iodo- and list them
in alphabetical order with other substituents.
Common names of haloalkanes
• Several polyhaloalkanes are common solvents
and are generally referred to by their common or
trivial names.
• Simple haloalkanes can also be named as alkyl
halides.
• The focus is the halogen atom (fluoride, chloride,
bromide or iodide) and becomes the second half of
the name.
• The carbon branch attached to the halogen is named
as usual and becomes the first half of the name.
CH3
F
CH
3
methyl fluoride
IUPAC: fluoromethane
H3C
H2
C
H3C
C
I
CH3
Br
ethyl bromide
IUPAC: bromoethane
t-butyl iodide
IUPAC: 2-iodo-2-methyl
propane
Some Applications of Haloalkanes
• Refrigerants
• Freons are chlorofluorocarbons (CFCs)
• Release of CFC gases into the atmosphere contributes
to ozone destruction.
• Montreal Protocol is an international treaty (1989) to
phase-out use of CFCs.
• Much lower ozone-depleting alternatives are the
hydrofluorocarbons (HFCs) and the
hydrochlorofluorocarbons (HCFCs).
• Solvents
• Methylene chloride, chloroform, trichlor, carbon
tetrachloride (among others) are used to dissolve grease
(in machine shops and dry cleaners!).
• Propellents
• HFC-134a (1,1,1,2-tetrafluoroethane) is used as a
propellent in “canned air”.
• Anesthetics
• Many hydrochlorofluorocarbons are using in anesthesia.
• The earliest anesthetics were ethers; thus, many modern
anesthetics are halogenated ethers.
CF3
F
Cl
CHF2
F3C
O
isoflurane
F3C
O
desflurane
CHF2
F3C
CHF2
O
sevoflurane
Reactions of Haloalkanes
• Nucleophilic substitution (SN1 or SN2)
• b-elimination (E1 or E2)
Nucleophilic Substitution
• Substitution takes place on an sp3 hybridized
(tetrahedral) carbon.
• Nucleophile attacks carbon making a new bond.
• Functional group that is being replaced is called
the leaving group.
Examples of Nucleophiles and their Products
Nucleophilic Substitution Mechanisms
SN2 Mechanism
• Chemists propose two limiting mechanisms for
nucleophilic substitutions.
• A fundamental difference between them is the timing
of bond breaking and bond forming steps.
• At one extreme, the bond making and bond
breaking take place simultaneously
• Such a reaction is designated SN2.
• S = substitution
• N = nucleophilic
• 2 = bimolecular (two species are involved in the ratedetermining step)
• rate = k[haloalkane][nucleophile]
• Both reactants are involved in the creation of the
transition state of the rate-determining step.
• The nucleophile attacks the reactive center from the
side opposite the leaving group. The key step is
reaction of a nucleophile and an electrophile to
form a new covalent bond.
• The product of an SN2 reaction at a stereocenter
maintains a specific chirality.
http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2_alternate.html
The Energy Diagram for the SN2 Reaction
• Note the transition state has a carbon with 5 bonds
(high energy, indeed!).
• No intermediate is formed.
SN1 Mechanism
• In the other limiting mechanism, bond breaking
between carbon and the leaving group is entirely
completed before bond forming with the
nucleophile begins.
• This mechanism is designated SN1 where
• S = substitution
• N = nucleophilic
• 1 = unimolecular (only one species is involved in the
rate-determining step)
• rate = k[haloalkane]
• SN1 is illustrated by the solvolysis of tert-butyl
bromide.
• Step 1: Break a bond to form a stable ion or
molecule. Ionization of the C-X bond gives a
carbocation.
• Step 2: Reaction of a nucleophile and an electrophile
to form a new covalent bond.
• Step 3: Take a proton away (deprotonation). Proton
transfer to methanol completes the reaction.
The Energy Diagram for the SN1 Reaction
• Note the formation of two transition states.
• Note especially the formation of a carbocation
intermediate.
• The formation of the carbocation in an SN1 reaction is
the key distinction between it and an SN2 reaction.
• For an SN1 reaction at a stereocenter, the
product is a racemic mixture.
• The carbocation is planar so that the
nucleophile can attack either side of the
intermediate.
Determination of Reaction Path in SN Reactions
• Whether an alkyl halide substrate reacts with a
nucleophile according to an SN1 or SN2
mechanism depends on several factors.
1. Structure of the nucleophile
2. Structure of the haloalkane
3. Structure of the leaving group
4. Polarity of the solvent
1. The Nucleophile
• Nucleophilicity: a kinetic property measured by the
rate at which a Nu: attacks a reference compound
under a standard set of experimental conditions.
• For example, nucleophilicity could be measured by
examining the rate at which a set of Lewis bases displaces
bromide ion from bromoethane in ethanol at 25 °C.
• Those Lewis bases that yield faster reaction rates are
better nucleophiles.
• OH- will react with CH3CH2Br faster than NH3. Therefore,
OH- is better nucleophile than NH3.
• Judging good nucleophiles from poor
• A species with a negative charge is a stronger nucleophile
than a neutral molecule.
• RS- is better than RSH.
• Nucleophilicity usually increases going down a column on
the periodic table because of increasing size and
polarizability.
• RO- < RS- < RSe- < RTe-
• Nucleophilicity vs. basicity. Strong bases are strong
nucleophiles, but not all strong nucleophiles are basic.
• I- is an excellent nucleophile, but a very weak base.
• A bulkier nucleophile is a weaker nucleophile.
• (C2H5)3N is a weaker nucleophile than NH3.
• Good vs. poor nucleophiles (An SN2 reaction needs a
good nucleophile; whereas an SN1 reaction does not.)
• Common nucleophiles and their nucleophilicity
2. The Haloalkane Substrate
• SN1 reactions
• Governed by electronic factors, namely the relative
stabilities of carbocation intermediates.
• Relative rates: 3° > 2° > 1° > methyl
• Tertiary and secondary alkyl halides get substituted
via this mechanism
• SN2 reactions
• Governed by steric factors, namely the relative ease
of approach of the nucleophile to the site of reaction.
• Relative rates: methyl > 1° > 2° > 3°
• Methyl, primary and sometimes secondary alkyl
halides get substituted via this mechanism.
• Steric factors
• Compare access to the reaction center in
bromoethane and 2-bromo-2-methylpropane (tertbutyl chloride).
• Effect of electronic and steric factors in competition
between SN1 and SN2 reactions of haloalkanes.
3. The Leaving Group
• The best leaving groups are very weak bases,
e. g., the halogens I–, Br–, and Cl– are
excellent leaving groups
• OH–, RO–, and NH2– are such poor leaving
groups that they are rarely if ever displaced in
nucleophilic substitution reactions.
• Hydroxide ion, OH–, is a poor leaving group.
• However, the –OH group of an alcohol can be
transformed into an excellent leaving group, H2O,
if the –OH group is first protonated by an acid to
form —OH2+.
4. The Solvent
• Protic solvent: a solvent that contains an
–OH group and is a hydrogen bond donor.
• Polar aprotic solvent: A solvent that does not
contain an –OH group and is not a hydrogen bond
donor.
• Polar aprotic solvents favor SN2 reactions.
• Formation of carbocations is more difficult in polar aprotic
solvents.
Summary of SN1 and SN2 Reactions of
Haloalkanes
• Example: Predict the product of each
reaction, its mechanism, and the
stereochemistry of the product.
b-Elimination
 b-Elimination: Removal of atoms or groups of
atoms from adjacent carbons to form a carboncarbon double bond.
• We study a type of b-elimination called
dehydrohalogenation (the elimination of HX).
• The label “b” implies that a functional group and a
hydrogen atom on the second carbon away from the
functional group are being eliminated.
• Zaitsev’s rule: The major product of a belimination is the more stable (the more highly
substituted) alkene. When cis-trans isomerism is
possible, the trans isomer is favored.
• There are two limiting mechanisms for
b-elimination reactions.
• E1 mechanism: at one extreme, breaking of the
C-X bond is completed before reaction with base
breaks the C-H bond.
• Only R-X is involved in the rate-determining step.
• Formation of carbocation makes the reaction rate
unimolecular.
• E2 mechanism: at the other extreme, breaking of
the C-X and C-H bonds is concerted.
• Both R-X and base are involved in the rate-determining
step.
• Since both substances are involved in the creation of
the transition state, the reaction is bimolecular.
Elimination Reaction Mechanisms
E1 Mechanism
• Step 1: Break a bond to give a stable molecule or
ion. Rate-determining ionization of C-X gives a
carbocation intermediate and halide ion.
• Step 2: Take a proton away. Proton transfer from
the carbocation to a base (in this case, the solvent)
gives the alkene.
E2 Mechanism
• A one-step mechanism; all bond-breaking and bondforming steps are concerted. Simultaneously (1) take a
proton away and (2) break a bond to form a stable ion or
molecule.
Summary of Elimination Reactions
Substitution versus Elimination
• Because many nucleophiles are also strong bases
(OH– and RO–), SN and E reactions often compete.
• The ratio of SN/E products depends on the relative rates
of the two reactions.
SN1 versus E1
• Reactions of 2° and 3° haloalkanes in polar
protic solvents give mixtures of substitution and
elimination products. Product ratios are difficult
to predict.
SN2 versus E2
• It is a little bit easier to predict the ratio of SN2 to
E2 products.
• Stronger bases (such as NH2-), lead to E2.
• Bulky bases (such as (CH3)3CO-), lead to E2
• More branching near the a and b carbons leads to E2.
• Yuck! We used a instead of a and b instead of b in previous overheads.
Summary of SN versus E for Haloalkanes
• For Methyl and Primary Haloalkanes
• For Secondary and Tertiary Haloalkanes
Substitution – Elimination matrix
SN2
SN1
E2
E1
3º << 2º < 1º
3º > 2º >> 1º
3º < 2º < 1º
3º > 2º >> 1º
Strong
nucleophile
Weak nucleophile
Strong or bulky
base required
Weak base
Polar aprotic
solvent
Polar protic
solvent
Solvent polarity
not important
Good ionizing
solvent
Rate =
k[halide][Nuc]
Rate = k[halide]
Rate =
k[halide][base]
Rate = k[halide]
1 step, concerted
2 steps, C+
1 step, concerted, 2 steps, C+,
inversion of
racemization
configuration
Substitution – Elimination flowchart
Summary of SN versus E for Haloalkanes
• Examples: Predict the major product and the
mechanism for each reaction.