ORGANOHALIDES + Nucleophilic
Reactions (SN1/2, E1/E2/E1cB)
CH21 PS CLASS
Preparation of Organohalides
• From ALKENES C=C [just review old lessons]
• FOR TERTIARY ALCOHOLS, we can simply use
H-X (gas) X=Cl,Br in ether, 0°C
Preparation of Organohalides
• FOR TERTIARY ALCOHOLS, we can simply use
H-X (gas) X=Cl,Br in ether, 0°C
– Follows SN1 so a carbocation is formed,
– be careful with rearrangements!
Preparation of Organohalides
• FOR PRIMARY/SECONDARY ALCOHOLS: SOCl2
/ PBr3
Practice
Alkyl Fluorides
• Also from ALCOHOLS +
• HF / Pryidine
• (CH3CH2)2NSF3
Grignard Reagents
• Reaction of R-X with Mg over ether/THF to
form R-Mg-X organometallic compound.
Grignard Reagents: reduction of R-X
More samples:
Nucleophilic Reactions
• R-X, alkyl halides are ELECTROPHILES (positive
or electron-poor)
• They react with NUCLEOPHILES/BASES
(negative or electron-rich)
• Either substitution
– C-C-X becomes C-C-blah + X-
• or elimination reactions
– C-C-X becomes C=C + X-
SUBSTITUTION REACTIONS
•
•
•
•
S – substitution: R-X + Nu  R-Nu + XN – Nucleophilic
1 or 2  unimolecular or bimolecular rates
INVERSION (change of stereochemistry) CAN
HAPPEN!
Try this first…
SN2  BIMOLECULAR
• Bimolecular simply refers to the rate
depending on BOTH reactants because of the
nature of the mechanism
• Rate = k[RX][Nu]
• Rate depends on both because there is
ONE SINGLE COLLISION BETWEEN RX and Nu
to form a Nu-R-X transition state
SN2  BIMOLECULAR
SUBSTRATE
100% INVERSION OF
STEREOCHEMISTRY OCCURS!
LEAVING
GROUP
Factors that affect SN2 RXNS:
• STERIC EFFECTS TO INCOMING Nu:
– C=C-X (vinylic) and Ar-X (aryl) TOTALL UNREACTIVE
Factors that affect SN2 RXNS:
• THE NUCLEOPHILE
Factors that affect SN2 RXNS:
• THE LEAVING GROUP
should be stable on its own as a free anion
• Comparing halides, we go down the column
Factors that affect SN2 RXNS:
• Alcohols and fluorides usually do not undergo
SN2 because OH- and F- aren’t good leaving
groups
• This is why we use SOCl2 and PBr3 … THEY
CONVERT THE –OH INTO A BETTER LEAVING
GROUP
Factors that affect SN2 RXNS:
• Reaction SOLVENT can also affect the reaction.
• We prefer POLAR APROTIC SOLVENTS
– POLAR but no –OH or –NH in the molecule (no
H2O, NH3, etc…)
• Polar protic solvents form a CAGE around Nu
Practice
Practice
Practice
Practice
SN1  UNIMOLECULAR
• Unimolecular: rate depends only on the
substrate (mechanism), almost opposite of
SN2
• Rate = k[RX]
• Rate is only dependent on the slowest step
which is the spontaneous dissociation of your
leaving group. (molecules just don’t easily
dissociate!)
SN1  UNIMOLECULAR
SN1  UNIMOLECULAR
SN1  UNIMOLECULAR
STEREOCHEM IS LOST, A RACEMATE
FORM IS MADE, but usually not 50:50
SN1  UNIMOLECULAR
STEREOCHEM IS LOST, A RACEMATE
FORM IS MADE, but usually not 50:50
An ION PAIR BLOCKS THE OTHER SIDE!
Factors that affect SN1 RXNS:
• SUBSTRATE:
Factors that affect SN1 RXNS:
• LEAVING GROUP:
An –OH in acidic medium can
become –OH2+ and leave as H2O
which is very favorable
Factors that affect SN1 RXNS:
• NUCLEOPHILE: no effect, almost at all.
Factors that affect SN1 RXNS:
• SOLVENT: rates increase if you stabilize
carbocation transition state.
• POLAR PROTIC!
Factors that affect SN1 RXNS:
• SOLVENT: rates increase if you stabilize
carbocation transition state.
• POLAR PROTIC!
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE
Elimination Reactions
• More compliated (different mechanisms)
• The loss of H-X can lead to a MIXTURE of
alkene products (C-C-X  C=C + HX)
• But we can predict the most stable/major
poduct
• ZAITZEV’S RULE: base-induced eliminations
will form more stable alkene
E2 elimination
• Again, bimolecular so a single collision
between your Base B: and the alkyl halide.
E2 elimination
• Anti-periplanar is favored for transition state
E2 elimination
• Anti-periplanar is favored for transition state
Practice
Practice
Practice
Practice
E1 reaction
• Unimolecular, ALSO spontaneously forms
carbocation, but then followed by loss of H+
(taken by a base B: and not an attack by Nu:)
• COMPETES WITH SN1 reactions!
E1 reaction
E1 reactions
• No need for anti periplanar geometry
PRACTICE
PRACTICE
E1cB
• Unimolecular, but this time CARBANION
formed because a proton H+ is first removed
by a base.
• cB stands for “conjugate base” because you
deprotonate your carbon C-H into a C- and H+
• Usually favored for poor leaving groups (e.g. –
OH)
• Carbanion can be stabilized with C=O groups
nearby
E1cB
E1cB
PRESENCE OF C=O NEARBY CAN GIVE
RESONANCE STABILIZATION!
PREDICTING WHAT PREDOMINATES:
Slight Clarifications: BASE vs.
NUCLEOPHILE
BASE
• Affinity for a PROTON
• Strong base like R-O- or OH-
NUCLEOPHILE
• Usually a LEWIS BASE
• In this context, how
attracted to a CARBON
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE
PRACTICE