ORGANOHALIDES + Nucleophilic Reactions (SN1
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Transcript ORGANOHALIDES + Nucleophilic Reactions (SN1
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