PPT - Gmu

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Transcript PPT - Gmu

Electrophiles / Nucleophiles
Nucleophile
Electrophile
– A Lewis Base with a pair of unshared
electrons that seeks a positive part of an
atom.
- A Lewis Acid seeking an electron pair
Nucleophilic Substitution
Nucleophilic Substitution
Reaction initiated by a Nucleophile (Lewis Base) which
attacks an Electrophile, replacing a leaving group.


-
-
General Use
Substitution of Nucleophiles on primary and secondary
haloalkanes. The Halide serves as the leaving group.
SN1 Reactions
SN1 – Substitution, Nucleophilic, Unimolecular
a. Substitution – Nucleophile substitutes for leaving group
b. Unimolecular
 Rate of reaction is dependent on concentration of
only one of the reactants
 It is a first order reaction (sum of exponents in rate
equation = 1).
c. Multistep reaction, where overall rate of reaction is
determined by the slowest intermediate step.
SN2 Reactions
SN2 – Substitution, Nucleophilic, Multi-Molecular
a. Substitution in one step, where Nucleophile attacks
carbon bearing the leaving group, which departs from
back side of molecule.
b. A conversion of the molecular configuration occurs.
c. Multi-molecular - Reaction depends on the
concentration of each of the reactants; thus the
reaction is at least second order (sum of exponents in
rate equation is >= 2).
SN1 Reactions
Carbocations
a. Intermediate Organic molecules formed in an SN1
reaction contain a trivalent carbon atom that carries a
positive charge (electron deficient).
b.General structure is Trigonal Planar.
c. Relative stability related to number of Alkyl groups
attached to positively charge Carbon atom.
SN1 Reactions
d. Alkyl groups are electron releasing
The 2 electrons in filled sp3 orbitals of alkyl groups can
overlap with empty p-orbitals of positively charged
adjacent Carbon atoms that produces a stabilizing
affect on the Carbocation (Hyperconjugation).
 Electron density shifts toward the positive charge
 The C-H & C-C orbitals adjacent to the unfilled p
orbital of the Carbocation are filled.
 Sharing of the electron density Delocalizes the
positive charge, thus, stabilizing the system.
 Tertiary Carbocations have 3 C-H or C-C bonds that
can overlap the vacant p orbital producing more
hyperconjugation than would 2 C-H or C-C bonds.
 Thus, tertiary carbocations are more stable than
secondary carbocations, which are more stable than
primary carbocations.
SN1 Reactions
Stereochemistry
 The Trigonal Planar structure of a Carbocation permits
the Nucleophile to attack from either the front side or the
back side.
 A tertiary Carbocation substitution does not produce any
stereo implications.
 Some Carbocations, however, can produce different
products from two reaction possibilities.
 If one of the products is optically active and the other
optically inactive, the reaction is said to have proceeded
with Racemization.
SN1 Reactions
 Racemization occurs when the reaction causes a Chiral
molecule to be converted to an Achiral intermediate.
 Chiral Molecule – Molecule that is not superposable
on its mirror image.
Chiral molecules possess handedness; thus, are
capable of existing as enantiomers (stereoisomers
of each other)
 Achiral Molecule – Molecule that is superposable on
its mirror image.
Achiral molecules lack handedness, thus, are
incapable of existing as enatiomers
Electrophilic Aromatic Substitution
Benzene, an aromatic structure, is generally unreactive
(stable), but can be attacked by strong Electrophiles.
The stability of the aromatic ring ( bond structure) results in
substitution as opposed to addition of the Electrophile as
seen in the  bond structure of Alkenes and Alkynes.
Two Step Process:
1. Electrophile (E+) attacks  bond of ring and forms a
cationic (positively charged) intermediate - Carbocation.
a. The Carbocation (an Arrhenium Ion) is not aromatic.
b. The positive charge is delocalized.
c. The formation of the C-E bond results in an sp3
hybridized carbon in the ring, interrupting the cyclic
conjugation.
d. This arrangement is not thermodynamically stable.
2. A proton is lost from the ring regenerating the aromatic
ring, which is stable.
Electrophilic Aromatic Substitution
Electrophilic Substitution Directing Effects on Aromatic Ring
When substituted aromatic rings undergo attack by an Electrophile (positively
charged Lewis Acid), the group(s) already on the ring affect both the rate of
reaction and the Regioselectivity (orientation) of the site(s) of attack.
Thus, the original group on the ring determines where the attacking group will
substitute on ring, i.e., the ortho (1,6 positions), para (4 position) or meta
(3, 5 position) sites.
Deactivation:
If the substituted group withdraws (accepts) electrons from the ring:
 The electron density of the ring is decreased, deactivating the ring.
 Thus, the Energy of Transition is increased and
 The Free Energy of Activation is increased, resulting in
 The “High Energy Transition State” leading to the formation of the
delocalized “Arenium Ion” (positively charged Carbocation) to become
“Less Stable.”
 Therefore, the reaction rate is decreased relative to the rate on an
unsubstituted aromatic ring.
 The resulting Resonance” forms of the “Arenium Ion” favor the
substitution of the second group at the “Meta” position, i.e., position “3”
relative to the original group, ex. 3-nitrotrifluoromethylbenzene.
Electrophilic Substitution Directing Effects on Aromatic Ring
Activation:
If the substituted group Donates (releases) electrons to the ring:
 The electron density of the ring is increased, activating the ring.
 Thus, the Energy of Transition is decreased and
 The Free Energy of Activation is decreased, resulting in
 The “High Energy Transition State” leading to the formation of the
delocalized “Arenium Ion” (positively charged Carbocation) to become
“More Stable.”
 Therefore, the reaction rate is increased relative to the rate on an
unsubstitued aromatic ring.
 The resulting Resonance” forms of the “Arenium Ion” favor the
substitution of the second group at the “Ortho/Para” positions, i.e.,
positions “1, 4, 6” relative to the original group, ex. Orthobromotoluene.
Electrophilic Substitution Directing Effects on Aromatic Ring
C. Arrhenium Ion - The reaction rate-determining step in Electrophilic
Substitutions of substituted aromatic rings is the step that results in
the formation of a Carbocation (Arrhenium Ion or Sigma Complex)
If Q is an Activator - an electron-releasing (donating) group - relative to
hydrogen, the reaction occurs faster than substitution on an
unsubstituted ring. Resonance forms favor o,p-directing
If Q is a Deactivator- electron-withdrawing (accepting) group – the
reaction occurs slower than substitution on an unsubstituted aromatic
ring. Resonance forms favor m-directing.
Electrophilic Substitution Directing Effects on Aromatic Ring
D. Regioselectivity – Substitution Orientation
The Ortho/Para vs. Meta directing effect of the first substituted group
on the ring is accounted for by the interplay of two factors working
simultaneously, either of which can be dominate.
Induction Effect / Resonance Effect
1. Inductive Effect:
 An intrinsic electron-attracting or –releasing effect that results
from a nearby Dipole.
 Polarization is induced from electrostatic interaction of the 
bonds.
 Governed by relative Electronegativity of the involved atoms.
 If a substituted group is more electronegative than the carbon
in the ring, then the ring is at the positive end of the Dipole.
 Inductive effect tapers off rapidly with distance.
 The ring can be “Activated” or Deactivated” through the
Inductive Effect.
Electrophilic Substitution Directing Effects on Aromatic Ring
2. Induction – Activation by Electron Donation (Release)
Groups that donate (release) electrons to the ring by Induction are
Activating.
 The Methyl group (CH3) and other Alkyl groups donate electrons
(through Hyperconjugation effect) that delocalizes (stabilizes)
the positive charge on the intermediate Arenium ion ring making
it more receptive to the positive charge of the attacking
Electrophile.
 The resonance forms resulting from O,P attack benefit from this
stabilizing effect of the donated electrons forming a stable
intermediate Carbocation.
 In Meta attack, the resonance forms do not benefit from the
stabilized configuration.
 Thus, Ortho / Para products predominate.
Electrophilic Substitution Directing Effects on Aromatic Ring
Electrophilic Substitution Directing Effects on Aromatic Ring
3. Induction – Deactivation by Electron Withdrawal (Acceptance)
When substiuted on an aromatic ring, electronegative groups or
elements more electronegative than carbon form a Dipole with the
positive end of the Dipole attached directly to the ring.
An attack by a positively charged Electrophile attempts to put an
additional positive charge on the ring that destabilizes the
Intermediate Arenium ion (carbocation) resulting from the
Electrophilic attack. The Meta attack, however, is less affected by
this destabilization, thus, Meta substitution is more favored.
a. Electronegative groups or elements more electronegative
than carbon attached directly to the ring are electron
withdrawing.
-
-
- -  
C F
F 



-X

X (F, Cl, I)


R
-

F

- N- R
 
- O-R
Electrophilic Substitution Directing Effects on Aromatic Ring
3. Induction – Deactivation by Electron Withdrawal (Acceptance)
(Con’t)
b. Groups that form Dipoles
-
O
- C- G
G = H, R, OH, OR

O
- C-G

Electrophilic Substitution Directing Effects on Aromatic Ring
Electrophilic Substitution Directing Effects on Aromatic Ring
4. Resonance Effect
 Effect by which a substituent exerts either an electron-releasing or
–withdrawing effect through the  bond system of the aromatic
ring.
 Occurs through the  Bonds
 Occurs over Longer Range
 Particularly Strong In “Charged” Systems
 Presence of substituent may increase or decrease resonance
stabilization of the intermediate Arenium ion
Electrophilic Substitution Directing Effects on Aromatic Ring
4. Resonance (con’t)
a. Groups that donate (release) electrons by resonance are
Activating and they are O,P-directing
Benzene rings bearing, Methyl, Alkyl, Methoxy, Amino (NH2) and
Hydroxyl (OH) groups are strongly activated.
They bear one or more nonbonding electrons pairs, which can
participate in Resonance.
The Resonance form adds electron density to the delocalized ring
lending extra stability to the intermediate Arrhenium ion.
Note: These groups are electron withdrawing from an inductive
viewpoint (more electronegative than Carbon), but the Resonance
Effect dominates making them Otho/Para Directing.
Electrophilic Substitution Directing Effects on Aromatic Ring
Electrophilic Substitution Directing Effects on Aromatic Ring
2. Resonance (con’t)
b. Groups that withdraw electrons by Resonance are Deactivating.
 Groups bearing a polarized double or triple bond, whose
positive end is attached to the benzene ring.
 The Meta resonance forms of the substituted Benzene Ring do
not attempt to place additional positive charge next to the
Carbon atom attached to the Electron withdrawing group.
 The Meta forms are less destabilized and therefore favor Meta
substitution.
 Note: These groups are strongly deactivating from both the
Inductive Effect and the Resonance Effect and are Meta
directing.
Electrophilic Substitution Directing Effects on Aromatic Ring
Electrophilic Substitution Directing Effects on Aromatic Ring
Induction and Resonance Effects Oppose Each Other
The net effect on whether the first substituted group acts as an O,P
directing “Activator” (Electron Releaser) or a Meta-directing
“Deactivator’ (Electron Withdrawer) in the Electrophilic Substitution
Process depends on the relative dominance of:
Inductive Effect ( bond framework - Electronegativity)
vs.
Resonance Effect ( orbitals overlap aromatic  system).
Electrophilic Substitution Directing Effects on Aromatic Ring
Summary – Induction / Resonance:
Induction
 An intrinsic electron-attracting or –releasing effect that
results from a nearby Dipole.
 Groups that release (donate) electrons by induction
are activating and they are o,p-directing.
 Groups that withdraw (accept) electrons by induction
are deactivating and they are meta-directing
Resonance
 Occurs through the  Bonds
 Groups that release (donate) electrons by resonance
are activating and they are o,p-directing
 Groups that withdraw (accept) electrons by resonance
are deactivating and they are meta-directing
Electrophilic Substitution Directing Effects on Aromatic Ring
Effects of Deactivating (Electron Withdrawing) Groups on
the Orientation of Substituted Electrophiles
CF3 is strongly electron withdrawing (deactivating)
leaving the ring electron deficient with a developing
positive charge at the end of the dipole, i.e., on the
ring carbon atom adjacent to the Deactivating Group.
This deactivates (destabilizes) the ring to
Electrophilic substitution
As the positively charge Electrophile (E+) attacks
the Ortho/Para resonance structures it attempts
to add additional positive charge to the carbon
adjacent to the positively charged withdrawing
group, further destabilizing the ring; thus Ortho/
Para substitution are not favored.
In Meta attack the carbon atom bonded to the
deactivating CF3 group does not share as much
of the positive charge of the ring with the
Deactivating Group, i.e., the positive charge is
spread more evenly about the ring. Thus, the ring
is less deactivated than the Ortho/Para attack and
therefore is more susceptible to substitution at the
Meta position.
Electrophilic Substitution Directing Effects on Aromatic Ring
Effects of Activating (Electron Donating) Groups on the
Orientation of Substituted Electrophiles
The Amino group is a strong activating group.
Even though the amino group is more
Electronegative than the attached Carbon the
electron releasing resonance effect is much
more dominant that the Deactivating
electron Withdrawing effect.
In O or P attack the nonbonding pair of
electrons from the Nitrogen can form, through
resonance, an extra  bond to the Carbon atom
completing the outer octet of Electrons. This
stabilizes one of the Arenium ion (sigma
complex) resonance structures.
In Meta attack of a ring with a substituted
activating group, none of the resonance
structures are able to take advantage of the
resonance contribution from the non-bonding
pair of electrons. Therefore, the structure
remains less stable and less subject to
substitution at the Meta Position.
Electrophilic Substitution Directing Effects on Aromatic Ring
Ortho & Para Directors
Meta Directors
Activators (Donate, Release Electrons)
 Available pair of unbonded electrons to
donate to ring.
Methyl & Alkyl groups are activating
because of the stabilizing effect of sp2
hybridization (hyperconjugation) of an
unbonded electron in methyl radical.
Halogens have a net withdrawing effect
through induction, but there is sufficient
competition from resonance to make
them o,p directors.
 Protons on ring are more shielded
 Tendency for decreased Chemical Shift
Deactivators (Withdraw, Accept Electrons)
 No unbonded electron pairs
 Less Shielding of Protons on ring
 Tendency for increased Chemical Shift
Group
Name
Withdraw
Resonance
Donate
Induction
Donate
Resonance
Withdraw
Induction
Dominant Effect
Orientation
-NH2
Amino
X
X
Very Strongly Activating
Ortho, Para
-NHR
Alkylamino
X
X
Very Strongly Activating
Ortho, Para
-NR2
Dialkylamino
X
X
Very Strongly Activating
Ortho, Para
-OH
Hydroxy
X
X
Very Strongly Activating
Ortho, Para
Acylamino
X
X
Strongly Activating
Ortho, Para
Alkoxy
X
X
Strongly Activating
Ortho, Para
Acyloxy
X
X
Strongly Activating
Ortho, Para
-NHCR
-O-R
-R
-CH=CR2
-X
-CH2X
Alkyl
X
Weakly Activating
Ortho, Para
Aryl (aromatic)
X
Weakly Activating
Ortho, Para
Alkenyl
X
Weakly Activating
Ortho, Para
F, Cl, Br, I
X
X
Weakly Deactivating
Ortho, Para
Halomethyl
X
X
Weakly Deactivating
Ortho, Para
Formyl
X
X
Moderately Deactivating
Meta
Acyl
X
X
Moderately Deactivating
Meta
Carboxylic Acid
X
X
Moderately Deactivating
Meta
Ester
X
X
Moderately Deactivating
Meta
Acyl Chloride
X
X
Moderately Deactivating
Meta
-C≡N
Cyano
X
X
Moderately Deactivating
Meta
-SO3H
Sulfonic Acid
X
X
Moderately Deactivating
Meta
-CF3
Trifluoromethyl
X
Very Strongly Deactivating
Meta
-NO2
Nitro
X
Very Strongly Deactivating
Meta