Chapter 7
Organohalides
• Alkyl halide: a compound containing a
halogen atom covalently bonded to an sp3
hybridized carbon atom
– given the symbol RX
• If the halogen is bonded to an sp2 hybridized
carbon, the compound is called a vinylic halide
• If the halogen is bonded to a benzene ring, it is
called an aryl halide, given the symbol Ar-X
X
R
C
C
R
R
A haloalkene
(a vinylic halide)
X
A haloarene
(an aryl halide)
Naming Alkyl Halides
Step 1: Find the longest chain, and name it as the
parent.
Step 2: Number the carbons of the parent chain
beginning at the end nearer the first substituent,
regardless of whether it is alkyl or halo.
Step 3: Write the name
– halogen substituents are indicated by the prefixes fluoro-,
chloro-, bromo-, and iodo- and listed in alphabetical
order with other substituents
Preparing Alkyl Halides
1. Addition reactions of HX and X2 with alkenes
2. The reaction of an alkane with Cl2
3. The most general method for preparing alkyl
halides is to make them from alcohol
•
Primary and secondary alcohols are best converted
into alkyl halides by treatment with thiony chloride
or phosphorus tribromide
Thionyl chloride
Phosphorus tribromide
Reactions of Alkyl Halides:
Grignard Reagents
•
•
Grignard Reagents: alkyl halides react with
magnesium metal in ether solvent
Organometallic compounds
•
•
A Grignard Reagents is formally the magnesium
salt, R3C-+MgX, of a carbon acid, R3C-H, and is a
carbon anion, or carbanion
Carbon anions are very strong bases
Nucleophilic Substitution Reactions
•
Alkyl halides react with nucleophiles/bases (such as
hydroxide ion); either they undergo
– Substitution of the X group by the neucleophile
– Elimination of HX to yield an alkene
Walden’s cycle of reactions interconverting (+)- and (-)-malic acids.
(1896)
•
•
•
•
Nucleophilic substitution reaction: a reaction in
which one nucleophile is substituted for another
Nucleophile: an atom or group of atom that can
donate a pair of electrons to another atom or group of
atom to form a new covalent bond; a Lewis base
a nucleophile (Nu: or Nu:-) reacts with substrate R-X
and substitutes for a leaving group X:- to yield the
product R-Nu
Two major pathways:
–
–
SN1 reaction
SN2 reaction
• If the nucleophile is negatively charged, the atom
donating the pair of electrons in the substitution
reaction becomes neutral in the product
• If the nucleophile is uncharged, the atom donating
the pair of electrons in the substitution reaction
becomes positively charged in the product
The SN2 Reaction
An SN2 reaction takes place in a single step without
intermediates when the entering nucleophile
attacks the substrate from a direction 180o away
from the leaving group
S = substitution
N = nucleophilic
2 = bimolecular
Bond breaking and bond forming occur simultaneously
Rate of SN2 Reactions
An SN2 reaction takes place in a single step when
substrate and nucleophile collide and react
–
–
If we double the concentration of OH-, the frequency of
collision between the two reactants double and the
reaction rate also double
If we double the concentration of CH3Br, the reaction
rate doubles
SN2 reactions are said to be Bimolecular reaction
because the rate of the reaction depends on the
concentrates of two substances– alkyl halide and
nucleophile
Stereochemistry of SN2 Reactions
As the incoming nucleophile attacks the substrate and
begins pushing out the leaving group on the opposite
side, the configuration of the molecule inverts (S→R)
Steric effects in SN2 Reactions
•
•
•
Methyl halides (CH3-X) are the most reactive substrates,
followed by primary alkyl halides (RCH2-X)
Alkyl branching next to the leaving group slows the
reaction greatly for secondary halides (R2CH-X)
Branching effectively halts the reaction for tertiary halide
(R3C-X)
Vinylic (R2C=CRX) and aryl (Ar-X) halides are
completely unreactive toward SN2 displacement
This lack of reactivity is due to steric hindrance
The leaving groups in SN2 Reactions
•
•
•
The best leaving groups are those that give the most
stable anions (anions of strong acids)
A halide ion (I-, Br-, Cl-) is the most common
leaving groups
F-, OH-, OR-, and NH2- are rarely found as leaving
groups
The SN1 Reaction
•
•
Most nucleophilic substitutions take place by the
SN2 pathway
The SN1 reaction takes place only
–
–
•
•
•
on tertiary substrates
under neutral or acidic conditions in a hydroxylic
solvent (water or alcohol)
Loss of the leaving group before the incoming
nucleophile approaches
Loss of the leaving group gives a carbocation
intermediate
The reactivity order is 3o>2o>1o>methyl
? R-OH + HBr → R-Br + H2O
Rates of SN1 Reactions
•
The rate of an SN1 reaction depends only on the
concentration of the substrate
Stereochemistry of SN1 Reactions
•
For an SN1 reaction at a stereocenter, the product is
a racemic mixture
The leaving groups in SN1 Reactions
•
The SN1 reactivity order of leaving groups is:
Eliminations: The E2 Reaction
1. The nucleophile/base can substitute for the leaving
group in an SN1 or SN2 reaction
2. The nucleophile/base can also cause elimination of
HX, leading to formation of an alkene
•
Zaitsev’s rule: in the elimination of HX from an
alkyl halide, the more highly substituted alkene
product predominates
• Three different mechanisms
The mechanism of the E2 reaction
Eliminations: The E1 and E1cB Reactions
• E1 mechanism: breaking of the R-X bond
is complete before reaction with base to
break the C-H bond begins.
• Only R-X is involved in the rate-limiting
step
The mechanism of the E1 reaction
•
The E1 and SN1 reactions normally occur in
competition whenever an alkyl halide is treated in a
hydroxylic (protic) solvent with a nonbasic
nucleophile
•
The E1cB reaction
– Take place through a carbanion intermediate
– Have a poor leaving group, such as –OH
– Predominates in biological pathways
A Summary of Reactivity:
SN1, SN2, E1, E1cB, and E2
•
•
Primary alkyl halide (RCH2X) reacts by an
–
SN2 if a good nucleophile is used
–
–
E2 if a strong base is used (OH , OR )
E1cB if the leaving group is two carbons away from a
carbonyl group (HO-C-C-C=O)
-
-
Secondary alkyl halide (R2CHX) reacts by
– SN2 if a weakly basic nucleophile is used
– E2 if a strong base is used
•
Tertiary alkyl halide (R3CX) reacts by an
–
–
E2 if a strong base is used
Mixture of SN1 and E1 pathways under neutral or acidic
condition