‫به نام خدا‬
Advanced Organic
Chemistry
‫روشهای‬
‫سنتز مواد آلی‬
Dr Morteza Mehrdad
University of Guilan, Department of Chemistry,
Rasht, Iran
m-mehrdad@guilan.ac.ir
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References:
1. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry:
Reactions and Synthesis (Part B), 5th ed., Springer, 2007.
2. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry:
Structure and Mechanisms (Part A), 5th ed., Springer, 2007.
3. House, H. O. Modern Synthetic Reactions, 2nd Edition, W. A.
Benjamin, Menlo Park, 1972.
4. Smith, M. B. Organic Synthesis, 2nd edition McGraw-Hill, NY, 2000.
5. Warren, S. Organic Synthesis: The Disconnection Approach, John
Wiley & Sons, New York, 1991.
6. Nicolaou, K. C. and Sorensen, E. J. Classics in Total Synthesis:
Targets, Strategies and Methods, VCH Publishers, New York, 1996.
7. Fuhrhop, J. H.; Li, G. Organic Synthsis, John Wiley & Sons, New
York, 2003.
8. Pine, S. H.; Hendrickson, J. B.; Cram, D. J.; Hammond, G. S. Organic
Chemistry, McGraw-Hill Inc., Tokyo, 1980.
Synthesis
(from the Greek word synthesis [ Suntithenai ] = [Sun(together) + tithenai(to put)]=
the process of putting together)
synthetic organic chemistry
Synthetic chemistry
synthetic inorganic chemistry
is the science of
constructing
molecules from
atoms and/or
(usually) simpler
molecules.
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organic synthesis
synthetic organic chemistry
science of synthetic chemistry
chemical synthesis
total synthesis
is the process by which a particular molecule is
synthesized in the laboratory.
is the chemical synthesis of a molecule, usually a natural
product, from relatively simple starting materials
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ORGANIC SYNTHESIS
Target Oriented
(Total Synthesis)
Natural
Products
Methods Oriented
Designed
Molecules
Materials Science
Interesting
Molecules
Biologically
Interesting
Molecules
Reagents
Catalysts
Theoretically
Interesting
Molecules
Synthetic
Strategies
Synthetic
Tactics
Medically
Interesting
Molecules
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Organic synthesis
1. Design of a synthesis
2. Constraction reactions
3. Functional group interconversions
4. Stereochemistry
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1. Design of synthesis
a. Initial consideration in synthesis design
• Carbon skeleton
• Functional group
(Synthon)
b. The retro-synthetic approach
(target molecule)
(Disconnetion)
c. Starting materials
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d.
Yield and reaction specificity
overall yield is the mathematical product of the yields of all the
individual steps
Overall yield = 100 x (1 x 0.87 x 0.67 x 0.55) = %32
1. minimum number of steps
2. a good precedent of high yields
3. competing reactions are minimal
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2. Constraction reactions
a. Half-reactions and recognition patterns
b. Annelation reactions
c. Fragmentation reactions
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Nucleophilic Half-Reactions
(Products)
(Starting Materials)
Organometallic
Aldol or Claisen
(enolate reactions)
Friedel- Crafts
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Electrophilic Half-Reactions
(Products)
(Starting Materials)
Alkylation
Carbonyl addition
Conjugated addition
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Construction chart of the
Major half-reactions.
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2
2
4
2
2
3
3
3
2
2
3
3
3
3
2
5
3
4
2
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span = A relation between the functional groups which are
usually the key to bond-forming processes
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Recognition patterns between
span and constructions
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2. Constraction reactions
a. Half-reactions and recognition patterns
b. Annelation reactions
c. Fragmentation reactions
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2. Constraction reactions
a. Half-reactions and recognition patterns
b. Annelation reactions
c. Fragmentation reactions
Reactions which make carbon-carbon bonds are construction reactions.
those that cleave carbon-carbon bonds are called fragmentation reactions:
Ozonolysis is an important fragmentation used as a source of carbonyl
groups.
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The other important fragmentation is the decarboxylation of -keto acids
and -diacids
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3. Functional group interconversions
a. Altering functional groups
b. Removing functional groups
c. Selectivity
d. Protecting groups
Hydroxy and
carbonyl group
interconversions
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Some interaction versions of the carboxylic acid family and other
terminal groups.
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3. Functional group interconversions
a. Altering functional groups
b. Removing functional groups
c. Selectivity
d. Protecting groups
Common methods for Removing functional groups.
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3. Functional group interconversions
a. Altering functional groups
b. Removing functional groups
c. Selectivity
d. Protecting groups
1. Hydride reductions:
Sodium borohydride generally reduces only ketones, aldehydes, and acyl halides;
lithium aluminum hydride reduces those compounds as well as compounds of the
carboxylic acid family.
2. Catalytic hydrogenation
3. Saturated carbons
4. Cyclic reactions
5. Carbonyl groups
6. Carbon-carbon double bonds
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3. Functional group interconversions
a. Altering functional groups
b. Removing functional groups
c. Selectivity
d. Protecting groups
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4. Stereochemistry
A target molecule with n chiral centers has 2n possible stereoisomers.
Many modern syntheses begin with one stereoisomer of a naturally
occurring material such as a terpene, a carbohydrate, or an amino
acid.
In such sequences it is very important to utilize reactions of known
stereospecificity.
The major reactions which offer stereochemical control:
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Bulky
reagent
More stable
Eq isomer
Less stable
Ax isomer
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enolization
more stable isomer
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