Transcript Organic Chemistry Introduction

Organic Chemistry I
Reactions of Alkenes and Alkynes
Unit 7
Dr. Ralph C. Gatrone
Department of Chemistry and Physics
Virginia State University
Fall, 2009
1
Chapter Objectives
• Present reactions of alkenes and alkynes
• Reactions related to those found in biology
• Must know reactions
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Preparation of Alkenes
• Precursors
• Alcohols (especially in biological chemistry)
• Alkyl Halides (industrial chemistry)
OH
strong acid
H
dehydration
X
strong base
H
dehydrohalogenation
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Biological Dehydration
• Rarely done on free alcohol
• Generally done on molecules containing carbonyl
and hydroxyl groups
H2O
-
HO
O2C
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CO2CO2-
aconitase
O2C
CO2CO2-
4
Reaction with X2
• Halogenation
• Reaction with Cl2 and Br2
Cl2
Cl
Cl
Br2
Br
Br
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Stereochemistry
• Reaction provides the trans product
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Explanation
• Not a carbocation intermediate as shown
• Bromonium ion intermediate forms
H
H
Br +
Br
H
H
Br
Br-
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Biological Halogenation
• Marine organisms
• Haloperoxidase
• H2O2 oxidizes Cl- or Br- to X+
Cl
Br
Cl
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Br
8
Reaction with X2 in H2O
• Cl2 in water yields HO-Cl (hypochlorous acid)
• Br2 in water yields HO-Br (hypobromous acid)
Br2/H2O
OH
Br
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Hydration of Alkenes
• Alkenes react with water to give alcohols
• Require high temperatures and pressures
H2O
CH3CH2OH
• Does not work well in the laboratory
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Biological Hydration of Alkenes
O
O
O-
-O
O
fumarate
fumarase
OH
-O
O
maleate
• Relatively rare reaction
• Cellular constraints are not present.
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Cellular Constraints
• Solvent is water
• Narrow pH range
• Fixed temperature
• Limited elemental choice
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Laboratory Hydration of Alkenes
Oxymercuration
Mercuric Acetate in THF
Markovnikov Product
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Laboratory Hydration of Alkenes
• Hydroboration
• Non-Markovnikov Product
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Mechanism of Hydroboration
• Borane is a Lewis acid
• Alkene is Lewis base
• Transition state involves
anionic development on B
• The components of BH3 add
across C=C
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Reduction and Oxidation
• Carbon always has 4 bonds
– Oxidation changes are more difficult to see
• Reduction:
– Increase in H content
– Decrease in O content
• Oxidation:
– Decrease in H content
– Increase in O content
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Reduction of Alkenes: Hydrogenation
•
•
•
•
Addition of H2
Requires Pt or Pd catalyst (or NR)
Heterogeneous Reaction
Process is not in solution
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Mechanism of Catalytic Hydrogenation
• Heterogeneous – reaction between phases
• Addition of H-H is syn
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Biological Reductions
• Rare Reaction
• Uses NADPH as reducing agent
NH2
N
O
O
N
H
HO
H
OH
O
P
O-
O
O
O
P O
N
N
OHO
O
N
-2
OPO2
NH2
Nicotinamide Adenine Dinucleotide Phosphate
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Oxidation of Alkenes: Epoxides
mcpba
O
CH2Cl2
H
O
OOH
peroxide
mcpba =
Cl
• Reaction with a peracid
• Epoxide or oxirane
• Cyclic ether
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Epoxide Preparation
• From Halohydrin
Br2/H2O
OH
base
O
Br
bromohydrin
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Biological Epoxidation
• Present in variety of processes
• Does not involve peracids
• Peroxides formed by reaction with O2
• Very selective reaction (see Figure 7.8)
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Hydroxylation of Alkenes
• Diol formation
H3O+
OH
O
OH
• Laboratory and Biological Reaction
• Biological process useful for detoxification
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Laboratory Hydroxylation
• Reaction with osmium tetroxide
• Stereochemistry of addition is syn (product is cis)
• Product is a 1,2-dialcohol or diol (also called a
glycol)
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Reaction with Carbenes
• H2C:
• The carbene functional group
• Carbenes are electrically neutral with six electrons in the outer
shell
• They add symmetrically to double bonds giving cyclopropanes
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Formation of Dichlorocarbene
• Base removes proton
•
•
from chloroform
Stabilized carbanion
remains
Unimolecular
Elimination of Clgives electron
deficient species,
dichlorocarbene
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Reaction of Dichlorocarbene
• Addition of dichlorocarbene is stereospecific cis
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Simmons-Smith Reaction
• Equivalent of addition of CH2:
• Reaction of diiodomethane with zinc-copper alloy
•
produces a carbenoid species
Forms cyclopropanes by cycloaddition
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Radical Reactions
• Mechanism of addition of HBr was hotly debated
• Non-Markovnikov product was observed
• Peroxides form readily in starting material
HBr
Br
HBr
Br
On occasion
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+
Br
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Radical Reactions - HBr
• If reaction is done with HBr/peroxides
• Get the non-Markovnikov product
HBr/peroxides
Br
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Radical Reactions: Polymer Formation
• Polymer – a very large molecule made of
repeating units of smaller molecules
(monomers)
• Biological Polymers
• Starch
• Cellulose
• Protein
• Nucleic Acid
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Polymers
• Alkene polymerization
• Initiator used generally is a radical
n
repeating
unit
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Mechanism
• Initiation
• Propagation
• Termination
• See page 241 in text for details
• High reactivity of radicals limits usefulness
• Not true in biological chemistry
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Biological Radical Reactions
• Enzyme permits a single substrate at a
time at the active site
• Greater control over reactivity
• Radical reactions are common
• Example given on page 244 for
biosynthesis of the PGAs
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Dienes
• Contain two double bonds
• Non-conjugated
• Conjugated
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Common Feature in Nature
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Conjugation
• Absorption of visible light produces color
• Conjugated hydrocarbon with many
double bonds are polyenes
• Lycopene - red color in tomatoes
• Carrotene – orange color
• Extended conjugation in ketones (enones)
found in hormones such as progesterone
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Conjugated Dienes
• Chemistry is slightly different
• More stable than non-conjugated dienes
• Heat of hydrogenation
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Greater Stability
• Why?
• Orbital Picture of alkene bonding
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Conjugated Diene
• Orbital picture of conjugated diene
• Electrons are delocalized (spread-out) over
the entire pi framework
• Impact upon the chemistry
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Reactions
• With HBr
Br
(71%)
HBr
H
Br
(29%)
H
• Why?
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Mechanism
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Allylic Cation
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Some Data
X
1,2 product
Nucleophile
Bromide
Chloride
H
H
HX
1,2 Product
71%
30%
X
1,4 product
1,4 Product
29%
70%
If HBr is added at 0 oC we see the above data.
If the reaction is done at 40 oC, we see 30% of the 1,2
product and 70% of the 1,4 product.
How do we explain these results?
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A
•
•
•
•
B+C
B forms faster than C
Energy of activation is lower for B than C
C is more stable than B
Constructing reaction energy diagram
energy
B
A
C
reaction progress
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Thermodynamic Control
• Transition state leading to more stable
species is higher in energy, therefore, it is
easier to get to the less stable product
• Reaction is reversable
• At high temperatures, sufficient E for both
reactions to occur
•A
B (fast) and A
C (slower)
• or B
A
C
• We see more stable product dominate.
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Kinetic Control
• At low temperatures
– Reaction is not reversable
– Equilibrium is not reached
– Insufficient energy for A to C
– Sufficient energy for A to B
– Less stable product dominates.
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Reactions of Alkynes
• Alkynes are rare in biological chemistry
• Chemistry is similar to alkenes
• Generally less reactive than alkenes
• Reactions can be stopped at alkene stage
using one equivalent of the reagent
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Reactions with HX
• Regiochemistry is Markovnikov
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Reactions with X2
• Initial addition gives trans intermediate
• Product with excess reagent is tetra-halide
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Reactions with H2
• Reduction using Pd or Pt does not stop
• Alkene is more reactive than alkyne
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Reactions with H2
• Lindler’s catalyst is poisoned
• Not as reactive
• Stops at cis-alkene
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Reduction using dissolving metals
•
•
•
•
Anhydrous ammonia (NH3) is a liquid below -33 ºC
Alkali metals dissolve in liquid ammonia
Provide a solution of e- in NH3
Alkynes are reduced to trans alkenes with sodium or
lithium in liquid ammonia
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Hydration of Alkynes
• Hydration (Hg+2) of terminal alkynes provides methyl
ketones
• Hydration (BH3) of terminal alkynes provides aldehydes
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Alkyne Acidity: Acetylide Anion
•
•
•
•
Terminal alkynes are weak Brønsted acids
pKa is approximately 25
alkenes and alkanes are much less acidic
Reaction of strong anhydrous bases with a
terminal acetylene produces an acetylide ion
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Alkylation of Acetylide Anions
• Acetylide ions are nucleophiles
• Acetylide ions are bases
• React with a primary alkyl halides
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