Organic Chemistry Fifth Edition

1
Organic Chemistry II (Chem 234)Professor Duncan
J. Wardrop
Spring 2004
University of Illinois at Chicago
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16.9Preparation of EpoxidesA Review and a
Preview
3
Preparation of Epoxides
Epoxides are prepared by two major methods.Both
begin with alkenes.
1. reaction of alkenes with peroxy acids such as
meta-chloroperbenzoic acid(Section 6.18) 2.
conversion of alkenes to vicinalhalohydrins,
followed by treatmentwith base (Section 16.10)
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16.10Conversion of Vicinal Halohydrinsto
Epoxides
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Example
Note trans relationship
H
NaOH
O
H2O
H
(81)
q. Why not elimination to form olefins?
Intramolecular Williamson synthesis
a. pKa of OH group is much lower than C-H
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Epoxidation via Vicinal Halohydrins
Br
Br2
H2O
OH
antiaddition
inversion

• corresponds to overall syn addition ofoxygen to
  the double bond

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Epoxidation via Vicinal Halohydrins
Br
H3C
Br2
H
NaOH
H2O
H
O
CH3
OH
antiaddition
inversion

• corresponds to overall syn addition ofoxygen to
  the double bond

8
16.11Reactions of EpoxidesA Review and a
Preview
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Reactions of Epoxides

• All reactions involve nucleophilic attack at
  carbon and lead to opening of the ring.
• An example is the reaction of ethylene oxide
  with a Grignard reagent (discussed in Section
  15.4 as a method for the synthesis of alcohols).

10
Reaction of Grignard Reagentswith Epoxides
SN2

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Example
CH2
H2C


O
1. diethyl ether 2. H3O
(71)
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In general...
The reactions of epoxides involve attack by a
nucleophile and proceed with ring-opening to form
alcohols
d
NuH

d-
d
ethylene oxide
d-
13
In general...
For epoxides where the two carbons of thering
are differently substituted
Nuc -
Nuc-H/H
What factors control regioselectivity?
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Definintion

• Regioselective Term describing a reaction that
  can produce two (or more) constitutional isomers
  but gives one of them in greater amounts than the
  other. A reaction that is 100 regioselective is
  termed regiospecific.

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16.12Nucleophilic Ring-OpeningReactions of
Epoxides
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Example
NaOCH2CH3
CH3CH2OH
(50)
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Mechanism
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Example
KSCH2CH2CH2CH3
ethanol-water, 0C
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Stereochemistry
OCH2CH3
H
H
OH
(67)

• Inversion of configuration at carbon being
  attacked by nucleophile
• Suggests SN2-like transition state

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Stereochemistry
CH3
H3C
R
R
H
NH3
H
OH
O
H2N
H
R
H2O
S
H
H3C
CH3
(70)

• Inversion of configuration at carbon being
  attacked by nucleophile
• Suggests SN2-like transition state

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Stereochemistry
CH3
H3C
R
R
H
NH3
H
OH
O
H2N
H
R
H2O
S
H
H3C
CH3
(70)
H3C
H
?
?-
O
H3N
H
H3C
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Anionic nucleophile attacks less-crowded carbon
NaOCH3
CH3OH
(53)

• consistent with SN2-like transition state

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Anionic nucleophile attacks less-crowded carbon

1. diethyl ether 2. H3O
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Lithium aluminum hydride reduces epoxides
Hydride attacksless-crowdedcarbon
1. LiAlH4, diethyl ether 2. H2O
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16.13Acid-Catalyzed Ring-OpeningReactions of
Epoxides
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Example
CH3CH2OH
CH3CH2OCH2CH2OH
H2SO4, 25C
(87-92)

• CH3CH2OCH2CH2OCH2CH3 formed only on heating
  and/or longer reaction times

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Example
HBr
BrCH2CH2OH
10C
(87-92)

• BrCH2CH2Br formed only on heating and/or longer
  reaction times

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Mechanism

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Figure 16.6 Acid-Catalyzed Hydrolysis of
Ethylene Oxide
Step 1
H2C
CH2

O


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Figure 16.6 Acid-Catalyzed Hydrolysis of
Ethylene Oxide
Step 2
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Figure 16.6 Acid-Catalyzed Hydrolysis of
Ethylene Oxide
Step 3

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Acid-Catalyzed Ring Opening of Epoxides
Characteristics

• nucleophile attacks more substituted carbon of
  protonated epoxide
• inversion of configuration at site of
  nucleophilic attack

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Nucleophile attacks more-substituted carbon
CH3OH
H2SO4

• consistent with carbocation character at
  transition state

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Stereochemistry
H
OH
HBr
H
Br
(73)

• Inversion of configuration at carbon being
  attacked by nucleophile

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Stereochemistry
CH3
H3C
R
R
H
H
OH
O
CH3O
H
R
S
H
H3C
CH3
(57)

• Inversion of configuration at carbon being
  attacked by nucleophile

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Stereochemistry
CH3
H3C
R
R
H
H
OH
O
CH3O
H
R
S
H
H3C
CH3
H3C
H
?
?
?
H
O
CH3O
H
H
H3C
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anti-Hydroxylation of Alkenes
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Suggested Problems
Problems 16.23, 16.24, 16.26, 16.28, 16.29-16.33,
16.35 -------------------------------------------
---------- Office Hour Today, 315 p.m., SES
4446 ---------------------------------------------
--------
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Analytical Chemistry
Can be divided into two sections Separation of
mixtures and Identification of Components
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High Performance Liquid Chromatography
6 has highest affinity for column
1 has lowest affinity for column
Retention Time
Mobile Phase Solvent Under High
Pressure Stationary Phase Polymer Microspheres
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Gas Chromatography
Retention Time
Mobile Phase Gas (Helium or Hydrogen)
Stationary Phase Silicone Polymer (Grease)
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Structural Determination
INFORMATION REQUIRED TO DETERMINE MOLECULAR
STRUCTURE Molecular Formula and Mass (Mass
Spectrometry) Types of Functional Groups Present
in the Molecule (Infrared Spectroscopy) Number
of Protons and Types of Protons (1H Nuclear
Magnetic Resonance Spectroscopy) Number of
Carbons and Types of Carbon Atoms (13C Nuclear
Magnetic Resonance Spectroscopy)
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Mass Spectrometry Mass and Molecular Formula
The Mass of a Charged Particle Can Be Measured In
A Mass Spectrometer
Sample Molecule Held in Gas Phase
Radical Cations are High Energy Species and Are
Capable of Undergoing Fragmentation
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Mass Spectrometer - General Layout
Typical Mass Spectrum
Only charged particles are deflected by the Magnet
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Mass Spectrum of Toluene
BASE PEAK m/z 91 C7H7.
PARENT ION P m/z 92 C7H8.
PEAKS DUE TO PARENT ION FRAGMENTATION DAUGHTER
IONS
P1 m/z 93 12C613C1H8
i) The P1 Peak is Approximately 1 of the
Intensity of the Parent Ion. Why? ii) The Level
of Fragmentation is Quite Low. Why?
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Fragmentation of Toluene Parent Ion
C7H8. m/z 92
Benzyl cations are stabilized by resonance
Positive charge smeared across 7 carbon atoms
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Different Molecules Can Have the Same Molecular
Weight!
In most cases we dont know the formula of our
molecule ahead of time. SO How can we
distinguish between A and B?
A
B
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Accurate Mass Measurement is the Solution!
A
B
Mass Spectrometers are accurate enough to
distinguish between molecules which have the same
molecular formula
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Parent Ions Undergo Fragmentation
Parent Peaks (M.)
Daughter Peaks
Each Molecule Has a Unique Fragmentation Pattern
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Mass Spectrometer - Location of Fragmentation
Fragmentation Occurs Here
Typical Mass Spectrum
Only charged particles are deflected by the Magnet
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The Course of Fragmentation is Directed by
Daughter Ion Stability
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Fragmentation Patterns - Formation of Acylium
Cations
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Fragmentation Patterns - Formation of Acylium
Cations
Parent Peak m/z 142
Base Peak C4H9 m/z 57
C5H9O m/z 85
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The Course of Fragmentation is Directed by
Daughter Ion Stability (Alkenes)
m/z 72
Remember 3o gt 2o gtgt 1o cations
No Parent Peak at m/z 72! WHY?
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Fragmentation Patterns - Elimination of Water
No Parent Peak at m/z 74! WHY?a
See Page 273 for Review of E1 Elimination
Reactions
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Fragmentation Patterns - McLafferty Rearrangement
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McLafferty Rearrangement of Butyraldehyde
C3H4O, m/z 44
C4H8O, m/z 72
M1
You can recognize a McLafferty Rearrangement by
loss of 44 mass units (ethylene)