pharmaceutical organic chemistry
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Pharmaceutical Organic Chemistry. 211 PHC – lec . 3 Dr. Ebtehal S AlAbdullah [email protected]. LECTURE CONTENTS:. Classes and Mechanisims of Organic Reactions Types of organic reaction ** Elimination ** Addition - PowerPoint PPT PresentationTRANSCRIPT
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Pharmaceutical OrganicPharmaceutical Organic
ChemistryChemistry
211 PHC –lec. 3211 PHC –lec. 3
Dr. Ebtehal S AlAbdullah Dr. Ebtehal S AlAbdullah
[email protected]@yahoo.com
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LECTURE CONTENTS:LECTURE CONTENTS:
Classes and Mechanisims of Organic Reactions
o Types of organic reaction ** Elimination ** Addition ** Rearrangement ** Free radical
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Elimination reactionElimination reaction
A reaction in which a molecule loses atom or group of atoms
from its structure.
Important method for preparation of alkenes
commonly for R-OH Dehydration (-H2O) of alcohols
and R-X Dehydrohalogenation (-HX) of alkyl halides
C C
X Y
C C + X Y
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There are three fundamental events in these
elimination reactions:
1. removal of a proton
2. formation of the CC p bond
3. breaking of the bond to the leaving group
ELIMINATION REACTIONELIMINATION REACTION
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Elimination reactions involving R-XElimination reactions involving R-X
2-bromopropane 2-bromopropane 2-bromopropane 2-bromopropane
The mechanismThe mechanism
KOH and NaOH as strong bases KOH and NaOH as strong bases
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ELIMINATION VS SUBSTITUTION R-X
Both reactions involve heating the R-X under reflux with KOH or NaOH
Nucleophilic substitution
The OH- present are good nucleophiles, and one possibility is a
replacement of the X by an -OH group to give an alcohol via a
nucleophilic substitution reaction.
2-bromopropane is converted into propan-2-ol.
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Elimination
R-X also undergo elimination reactions in the presence of sodium
or potassium hydroxide.
ELIMINATIONELIMINATION VERSUS VERSUS SUBSTITUTION SUBSTITUTION IN R-XIN R-X
Both reactions involve heating the R-X under reflux with KOH or NaOH
2-bromopropane has reacted to give an alkene - propene2-bromopropane has reacted to give an alkene - propene
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What decides whether you get substitution or elimination?
The reagents you are using are the same for both substitution or
elimination - the R-X and either NaOH or KOH.
In all cases, you will get a mixture of both reactions happening - some
substitution and some elimination.
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What you get most of depends on a number of factors.
1. The type of halogenoalkane This is the most important factor.
type of halogenoalkane substitution or elimination?
primary mainly substitution
secondary both substitution and elimination
tertiary mainly elimination
2. The solventWater encourages substitution. Ethanol encourages elimination.
3. The temperature Higher temperatures encourage elimination.
4. Concentration of the NaOH or KOH Higher concentrations favour elimination.
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Elimination reactions involving ROHElimination reactions involving ROH
Alcohols, like RX undergo elimination reactions to yield alkenes
because H2O is lost in the elimination, this reaction is called dehydration
C OHH3C
H3C
H3C
C CH2H3C
H3C
+ H2OH2SO4
60
HC OHH3C
H3C
CH
CH2H3C + H2OH2SO4
100
H2C OHH3C H2C CH2
+ H2OH2SO4
60primary
secandry
tertiary
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The mechanism - a simplified version
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Information Enrichment
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Drug Metabolism
• Drug metabolism can occur in every tissue (e.g. gut, lung and
kidney). However, the major drug metabolizing enzymes (DMEs)
are expressed at the highest levels in the liver, which thus
serves as the major organ of metabolic clearance
• Drug metabolism serves to control the exposure of a
potentially harmful substance. Usually via oxidation of a
lipophilic xenobiotic, DMEs increase the polarity and aqueous
solubility thus facilitating its elimination from the body
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Asian flush syndrome
Alcohol flush reaction (also known as Asian flush syndrome, Asian flush, Asian glow, among others) is a condition in which an individual's face or body experiences flushes or blotches as a result of an accumulation of acetaldehyde, a metabolic byproduct of the catabolic metabolism of alcohol. It is commonly thought that the
flush reaction is caused by an inability to metabolize alcohol.
CH3CH2OH + NAD+ ---> CH3CH=O + NADH + H+
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OH
cyclohexanol cyclohexene
Q: Show the mechanism of this reaction?
+ H2SO4
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Rearrangement Reactions
In this type of reactions, some atoms/groups shift
from one position to another within the substrate
molecule itself, give a product with a new
structure.
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Rearrangement reactionsRearrangement reactions
intramolecular atomic rearrangement, which involves
migration or shift of atoms
involves a nucleophilic attack at electron deficient atoms
e.g. C, O, N
Often a substituent moves from one atom to another atom in the same
molecule. In the example below the substituent R moves from carbon
atom 1 to carbon atom 2:
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Carbocation Rearrangement
1)
slow
++ Br
_
2)
+ +
3)
++ ROH + H
+
CH3 C CH CH3
CH3
CH3 Br
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3OR
a carbocation
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WWU -- Chemistry
A Closer Look...
+ +
+
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
CH3 C CH CH3
CH3
CH3
transition state
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WWU -- Chemistry
Carbocation Rearrangement
CH3 C CH CH3
CH3
CH3
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WWU -- Chemistry
Carbocation Rearrangement
CH3 C CH CH3
CH3
CH3
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WWU -- Chemistry
Carbocation Rearrangement
CH3 C CH CH3
CH3
CH3
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WWU -- Chemistry
Carbocation Rearrangement
CH3 C CH CH3
CH3
CH3
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WWU -- Chemistry
Carbocation Rearrangement
CH3 C CH CH3
CH3
CH3
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WWU -- Chemistry
Carbocation Rearrangement
CH3 C CH CH3
CH3
CH3
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Information Enrichment
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Gene rearrangement is a mechanism of genetic recombination in the early stages of immunoglobulin (Ig) and T cell receptors (TCR) production of the immune system. V(D)J recombination takes place in the
primary lymphoid tissue (the bone marrow for B cells, and Thymus for T cells) Types Kappa chain: V-J rearrangements
Lambda chain: V-J rearrangements
Hodgkin's disease which is a cancer originating from white blood cells called lymphocytes.
Hodgkin's lymphoma is characterized by the orderly spread of disease from one lymph node group to another and by the development of systemic symptoms with advanced disease.
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Free radical, radical, have no charge.
It result from homolytic cleavage.
It is unstable, highly reactive molecule.
Pairs of electrically neutral "free" radicals are formed
via homolytic bond breakage.
Free radical reactionFree radical reaction
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Free radical addition is an addition reaction
The addition may occur between a radical and a non-
radical, or between two radicals.
Radical chain mechanism are:
a) Initiation by a radical initiator: A radical is created from a non-
radical precursor.
b)Chain propagation
c)Chain termination: Two radicals react with each other to create a
non-radical species
MECHANISM OF THE REACTION
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Chlorination of Chlorination of MethaneMethane
CH4 + Cl2 CH3Cl + CH2Cl2 + CHCl3
+ CCl4 + HCl
It is a very complicated free radical reaction.
hv
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Home Work
Find 3 different disease caused by free radical
reactions inside the body
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Linkage with the life sciences
Information Enrichment
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Oxidation
Oxidation is the beginning of the deterioration process. Think of how a slice of apple turns brown when exposed to air. Oxidation leads to the formation
of free radicals which are unstable molecules in the body that have one unpaired electron. They can cause oxidation and damage to the cells. This is
how some diseases start. Free radical damage can occur because of too much exposure to radiation, to
smoke or because our cells have become overwhelmed by toxins in the environment. Even eating a diet high in saturated fats, over cooked meats
and processed foods over a long period of time can cause free radical damage.
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How Do Antioxidants Work?
Most people realize that we need antioxidants to prevent and fight disease but the role they play in maintaining your goal weight and even
losing fat is not so widely known. All antioxidants neutralize free radicals by either supplying the extra
electron or breaking down them down. Antioxidants help us stay vital into old age, detoxify our organs and
protect our cells from free radical damage. They support efficient metabolism helping us to lose fat more easily
and they support healthy brain chemistry.