Project Overview

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test 3 11/08 coverage 5 end 7? (opt act
resolution)-acetylene rx
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CHEM 333
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Chapter 7
synthesis
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7c
7a
7b
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Chapter 6 Summary
strong
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• CHAPTER 7
• Alkenes and Alkynes I Properties and Synthesis.
• Elimination Reactions of Alkyl Halides
• E/Z system
• Relative stability of alkenes
• Cycloalkenes
• Synthesis of alkenes - elimination
• Dehydrohalogenation of R-X
• Acid catalyzed dehydration of R-OH
• Carbocation stability rearrangement
• Acidity of terminal acetylenes
• Synthesis of acetylenes
• Replacement of the acetylene hydrogen
• Alkylation of alkynide anions
• Hydrogenation of alkenes and alkynes
• Catalyst for hydrogenation of alkenes and alkynes
• Organic synthesis - introduction

black repetition
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Introduction
Alkenes
Hydrocarbons containing CC Old name olefins
Alkynes Hydrocarbons containing CC Common name
acetylenes
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(E) - (Z) System for Designating Alkene
Diastereomers
Cis-Trans System Useful for 1,2-disubstituted
alkenes Examples
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Examples
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(E) - (Z) System Difficulties encountered for
trisubstituted and tetrasubstituted alkenes
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The Cahn-Ingold-Prelog (E) - (Z) Convention
Based on the atomic number of attached atoms
(like R/S) Higher atomic number, higher priority
(like R/S)
Determine higher priority at C1 and C2
Compare priorities on C1 and C2
(E) configuration highest priority groups (i.e.
Cl Br) on opposite side of the double bond
(Z) configuration highest priority groups on
same side of the olefin
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example
(Z)-3-bromo-4-tert-butyl-3-octene
(Z)-9,9,9-tribromo-5-ethenylnon-4-ene
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Relative Stabilities of Alkenes
Cis and trans alkenes do not have the same
stability
crowding
less stable
more stable
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3A. Heat of Reaction
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7 kJ/mol
5 kJ/mol
Enthalpy
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Overall Relative Stabilities of Alkenes
The more highly substituted an olefin is, the
greater the stability.
Relative stabilities of alkenes
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Cycloalkenes
Cycloalkenes with 7 carbon atoms or fewer - only
the cis form
trans cyclooctene has been isolated and is
chiral (enantiomers)
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Synthesis of Alkenes via Elimination Reactions
Dehydrohalogenation of Alkyl Halides
Dehydration of Alcohols
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How to Favor an E2 Mechanism
Use a 2o or 3o R-X (steric hindrance inhibits
SN2) For 1o R-X, use t-BuOK (steric bulk inhibits
SN2)
High concentration of a strong base (e.g.
alkoxide) (weak base allows SN1 or E1
to compete)
EtONa/EtOH t-BuOK/t-BuOH typically for E2 rxs
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Zaitsevs Rule
Some deHXs will only form a single product
trace of ether
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DeHX with more than one option
-Ha
-Hb
Zaitsevs Elimination Rule the more highly
substituted alkene product predominates
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Zaitsevs Rule In elimination reactions, the more
highly substituted alkene product predominates
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Small bases (e.g. EtO? or HO?) favor the more
substituted (more stable) alkene - Zaitsevs Rule
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Zaitsevs Rule - ?-eliminations
single product
mixtures
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Mechanism for an E2 Reaction
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?G1
?G2
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6C. Formation of the Less Substituted Alkene
(Bulky Base)
Zaitsevs rule elimination forming the most
stable alkene
Hofmanns Rule the major elimination product is
the less substituted, less stable alkene
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• Zaitsev Rule vs. Hofmann Rule

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• Zaitsev Rule vs. Hofmann Rule

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6D. The Stereochemistry of E2 Reactions
Transition state 5 atoms of an E2 reaction must
lie in the same plane - coplanar
Two conformations anti coplanar
syn coplanar
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anti coplanar
syn coplanar
preferred
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Orientation Requirement H and Br best anti
periplanar (trans-coplanar)
only H is anti periplanar to Br
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E2 Elimination where there are 2 axial ß-hydrogens
both Ha and Hb hydrogens are anti to Cl
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E2 where only an axial ß hydrogen is in less
stable conformer
less stable H anti to Cl
No Hs anti to Cl
100 Hofmann
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less stable hydrogen anti to Cl
E2 t.s. is anti coplanar
100 Hofmann
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Acid-Catalyzed Dehydration of Alcohols
heat strong acid - dehydrates (lose water)
alcohols - forms an alkene
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• The temperature and concentration of acid
  required depend on the structure of the alcohol

1O alcohols -most difficult
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2o alcohols dehydrate under milder conditions.
3o alcohols 20 aqueous sulfuric acid at 85C
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7A. E1 Mechanism for Dehydration of 2o 3o
alcohols
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7B. Carbocation Stability the Transition State
Recall
most stable
least stable
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7C. E2 Mechanism for Dehydration of 1o Alcohols
1o alcohol
protonated alcohol
alkene
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Carbocation Stability Molecular Rearrangements
Rearrangements during Dehydration of 2o Alcohols
2o carbocation
3o carbocation
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common carbocation rearrangements 1,2-migration
of an alkyl group
hydride 1,2-migration
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The Acidity of Terminal Alkynes
acetylenic hydrogen
pKa 44
pKa 25
pKa 50
relative basicity of the conjugate base
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Synthesis of Alkynes by Elimination Reactions
Dehydrohalogenation of Vicinal Dihalides

2 eq. or xs
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Examples
amount of base to complete conversion
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Deprotonation and Alkylation of Terminal Alkynes
acetylide anion
Acetylide anions - useful for synthesis of other
alkynes
? SN2 reaction, only good for methyl 1o
substrate 2o and 3o substrate undergo E2
elimination
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Example
SN2
E2
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Hydrogenation of Alkenes
Hydrogenation is a syn addition reaction
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Syn and Anti Additions
syn addition places components of the reagent on
the same side (or face) of the reactant
heterolytic
homolytic
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An anti addition adding reagent components on
opposite faces of the reactant
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Hydrogenation of Alkynes converted to alkanes
syn addition but .
2X!
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15A. Synthesis of cis-Alkenes by Syn Addition of
H2
via Ni2B (P-2) catalyst
using Lindlars catalyst Pd/CaCO3, quinoline
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15B. Synthesis of trans-Alkenes by Anti Addition
Alkynes can be converted to trans-alkenes by
dissolving metal reduction
anti addition
Also used H2NR or HNR2
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Mechanism
vinyl radical
radical anion
trans alkene
vinyl anion
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Why Organic Synthesis?
Supply compounds not readily available
naturally occurring /or biologically active
compounds Also provide novel materials
nanochemicals (switches, wires, etc.) polymers,
composites, drugs, etc.
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retrosynthetic analysis goal-generate as many
synthetic routes as possible
Target compound
Pseudoterosin A, E.J. Corey, et. al., JACS,
1989, 111, 5472
Ch. 7 - 54
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Identifying Precursors
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Retrosynthetic Analysis
SN2 on 1o alkyl halide good
disconnection 1
disconnection 2
reject SN2 on 2o alkyl halide ? E2 (strong base -
2o R-X)
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Synthesis
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Summary of Methods for the Preparation of Alkenes
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Summary of Methods for the Preparation of Alkynes
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Review Problems
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Chapters 6 7
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Cl? from top
SN1 (racemization) E1
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• Example

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