Química Orgânica II - Site de utilizadores

Química Orgânica II
Ciências Farmacêuticas
Bioquímica
Química
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Química Orgânica II – S1
Sistemas conjugados
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Revisão de conceitos fundamentais
Ligação química deslocalizada
Síntese
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Química Orgânica II
Conjugated systems
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Polyenes
Lycopene
β-caroten
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enones
Extended conjugation in ketones
hormones
progesterone
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Levonorgestrel implants
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CYPROTERONE ACETATE
CH 3
O
C
O
O
C
CH 3
H
H
H
Antiandrogenic properties
O
Cl
CYPROTERONE ACETATE (ANDROCUR)
Steroid Aromatase
A
B
O
HO
Estrogens
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PROGESTERONE
CH3
C
O
it is also an important
intermediate in steroid
biogenesis in all tissues that
produce steroids (testes,
adrenal cortex)
H
H
Natural hormone secreted
by the corpus luteum and the
placenta ( a C-21 steroid)
H
O
PROGESTERONE
Intestinal absorption is quite erratic; must be micronized for
most effective absoption (Prometrium)
19-NOR STEROIDS
OH
OH
C
C
CH
H
H
H
H
H
H
O
O
NORETHINDRONE
NORETHINODREL
Chemical analogues of testosterone - some retain some
androgenic activity such as norethindrone
CH
Polyene antibiotics
Nystatin
amphotericin B
Polyene antibiotics bind to
sterols within the fungal
membrane, disrupting its
integrity. This makes the
membrane leaky, leading to
a loss of small molecules
from the fungal cell.
Nystatin
antifungal antibiotic obtained from
Streptomyces noursei
http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?id=618&type=display
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conducting polymers
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Names and definitions
IUPAC
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IUPAC
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IUPAC
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Conjugated and Nonconjugated
Dienes
If double bonds are separated by only one single
bond, they are conjugated and their orbitals
interact
The conjugated diene 1,3-butadiene has properties
that are very different from those of the
nonconjugated diene, 1,5-pentadiene
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Diens:
Compounds with two double bonds
Isolated: (two or more single bonds between them)
Conjugated: (one single bond between them)
Cumulated: (zero single bonds between them: allenes)
C C C
Conjugated double bonds are found to be the most stable.
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Hexadienes
1,4
2,3
2,4
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conjugation
Isolated double bondes:
Conjugated: (one single bond between them and alignment of p orbitals)
Aromatic: (extra stability)
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Conjugated Dienes
Synthesis and Stability
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Synthesis of Conjugated Dienes
Typically by elimination in allylic halide
Specific industrial processes for large scale
production of commodities by catalytic
dehydrogenation and dehydration
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Stability
Conjugated dienes are more
stable than nonconjugated
dienes based on heats of
hydrogenation
Hydrogenating 1,3-butadiene
releases 16 kJ/mol less heat
than 1,4-pentadiene
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14.2 Molecular Orbital Description
of 1,3-Butadiene
The single bond between the
conjugated double bonds is
shorter and stronger than sp3
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The bonding π-orbitals are made from
4 p orbitals that provide greater
delocalization and lower energy than
in isolated C=C
The 4 molecular orbitals include fewer
total nodes than in the isolated case
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Molecular orbitals of etene
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Molecular Orbitals of 1,3-Butadiene
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Molecular Orbital Description of
1,3-Butadiene
In addition, the single bond between the two
double bonds is strengthened by overlap of p
orbitals
In summary, we say electrons in 1,3-butadiene are
delocalized over the π bond system
Delocalization leads to stabilization
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Electrophilic Additions to Conjugated Dienes:
Allylic Carbocations
Review: addition of electrophile to C=C
Markovnikov regiochemistry via more stable
carbocation
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Carbocations from Conjugated
Dienes
Addition of H+ leads to delocalized
secondary allylic carbocation
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Products of Addition to Delocalized
Carbocation
Nucleophile can add to either cationic site
The transition states for the two possible products are
not equal in energy
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Practice Problem 14.1: Products?
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14.4 Kinetic vs. Thermodynamic
Control of Reactions
At completion, all reactions are at
equilibrium, and the relative concentrations
are controlled by the differences in free
energies of reactants and products
(Thermodynamic Control)
If a reaction is irreversible or if a reaction is
far from equilibrium, then the relative
concentrations of products depends on how
fast each forms, which is controlled by the
relative free energies of the transition
states leading to each (Kinetic Control)
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Kinetic and Thermodynamic Control
Example
Addition to a conjugated diene at or below room
temperature normally leads to a mixture of products
in which the 1,2 adduct predominates over the 1,4
adduct
At higher temperature, product ratio changes and 1,4
adduct predominates
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