Synthesis of Drug -2
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Transcript of Synthesis of Drug -2
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ALDEHYDES AND KETONES
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Aldehyde
Ketone
O
C
R HR = H, alkyl, aryl
O
C
R R'
R and R' = alkyl or arylR and R' cannot be hydrogen!
STRUCTURE
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NOMENCLATURE
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Choose the longest continuous carbon chain thatcontains the carbonyl carbon
Number from the end of the chain closest to thecarbonyl carbon
Ketone ending is -one
IUPAC Nomenclature of Ketones
Do the ketonessection of Organic Nomenclatureprogram!
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CH 3
C
CH 2
CH 2CH 3
O
2-Pentanone
EXAMPLES
O
C
CH2 CH
CH3 CH2
CH2
CH3
CH3
4-Ethyl-3-hexanone
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O
CH
CH3
CH3
3-Isopropylcyclopentanone
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Common, or Trivial, Names
Name each group attached to the carbonyl
group as an alkyl group
Combine into a name, according to the pattern:
alkyl alkyl ketone
NOTE: This is not all one word!
KETONES
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CH 3
C
CH 2
CH 2CH 3
O
Methyl propyl ketone
Example of Common Names
O
CCH2 CH2
CH3 CH3
Diethyl ketone
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O
C
CH3 CH3
acetone
dimethyl ketone
A common laboratory
solvent and cleaning
agent
SPECIAL CASES
C
O
benzophenone
diphenyl ketone
C
O
CH3
acetophenone
methyl phenyl ketoneKNOW
THESE
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Choose the longest continuous carbon chain thatcontains the carbonyl carbon
Number from the end of the chain closest to the
carbonyl carbon (carbon #1!)
Aldehyde ending is -al
IUPAC Nomenclature of Aldehydes
Do the aldehydessection ofOrganic Nomenclatureprogram.
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EXAMPLES
CH3
CH2
CH2
CH2
CO
H
pentanal
CH3
CH
CH
CO
HCH3
Cl
2-chloro-3-methylbutanal
1
2
3
4
always carbon 1aldehyde group is
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O
C
H H
O
CCH
3H
O
C
CH2
HCH3
O
C
C HCH2
CH3
O
C
C HCH2
CH2
CH3
O
C
CH2
HCH2
CH2
CH2
CH3
Formaldehyde Acetaldehyde Propionaldehyde
Butyraldehyde Valeraldehyde
Caproaldehyde
1 2 3
4 5
6
Common Names of the Aldehydes
RECOGNIZE
THESE
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O
C
H H
O
C
H CH3
C
O
H
SPECIAL CASES
formaldehyde
acetaldehyde
benzaldehyde
KNOW
THESE
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C
C C C C C C H
O
Forming Common Names of Aldehydes
CHO
Cl
-chlorocaproaldehyde( -chlorohexanal )
CHO
Cl
-chlorocaproaldehyde( -chlorohexanal )
USE OF GREEK LETTERS
.
is always the end of the chain, no matter how long
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Molecular Geometry
Carbonyl group = Planar Triangle
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Common Aldehydes
Carbonyl group = Planar Triangle
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Common Ketones
Carbonyl group = Planar Triangle
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Polar Property
Carbonyl group = Planar Triangle
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Boiling Points
Carbonyl group = Planar Triangle
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Solubility in Water
Carbonyl group = Planar Triangle
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Physical Properties
Carbonyl group = Planar Triangle
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Preparing Aldehyde
1. Oxidation of primary alcohol and oxidative
cleavage of alkenes
o Primary alcohol can be oxidized to givealdehydes. The reaction is often carried out
using piridinium chlorochromate (PCC) in
dichloromethane solvent at room temperature
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2. Alkenes with at least one vinylic hydrogenundergo oxodative cleavage when treated
with ozone to yield aldehydes.
If the ozonolysis reaction is carried out on acyclic alkene, a dicarbonyl compound
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3. Carboxylic acid derivatives can be partiallyreduced to yield aldehydes
DIBAH : diisobutylaluminium hydride
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Preparing Ketones
1. Secondary alcohol are oxidized by a
variety of reagent to give ketones
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2. Ozonolysis of alkenes yield ketones if oneof the unsaturated carbon atom is
disubtitused
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3. Aryl ketones are prepared by FriedelCrafts
acylation of an aromatic ring with an acid
chloride in the presence of AlCl3 catalyst
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REACTIVITY OF THE C=O GROUP
NUCLEOPHILIC ADDITION
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O
C
.. :+-
O
C
.. :-+
THE CARBONYL GROUP
electrophilicat carbon
nucleophilicat oxygen
Nu:nucleophilesattack here
H+ or E+electrophilesadd here
GENERALIZED CHEMISTRY
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CYANOHYDRINS
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+ CN
_
R C R
O
R C R
O
CN
R C R
O
CN
+ R C R
O
CN
H
: : : :
: : :
..
..
_
_..
OH2
A cyanohydrin
Addition of CyanideBuffered to pH 6-8
In acid solution there would be little CN-,
and HCN (g) would be a problem (poison).
a cyanohydrin
:C N:
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N
N
N
N
CH3
CH3
CH2CH
2COOH
CH2CH
2COOH
CH3
CH3
Fe
C
N..
CYANIDE ION BONDS TO HEMOGLOBIN
Cyanide bonds(irreversibly) to the
site (Fe II) where
oxygen usually bonds.
CYANIDE ISIS A POISON
You die of
suffocation -
lack of oxygen.
HCN is a gas that you can easily breathe into your lungs.
..
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ORGANOMETALLICS
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+
(R-MgBr)
M_ +
H2O
H+
R M
O
C
R R
R C R
O
R
R C R
O
R
H
+ M (OH)x
: : : :
:
..
..
(R-Li)
Addition of Organometallic Reagents
ether
These reagents cannot
exist in acid solution
workup
step
alcohol
:R -
Synthesis of Alcohols
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Summary of Reactions of
Organometallics with
Carbonyl Compounds
Organometallics with ketones yield
tertiaryalcohols
Organometallics with aldehydes yield
secondaryalcohols
Organometallics with formaldehyde yieldprimaryalcohols.
Organometallics with carbon dioxide yield
carboxylic acids.
etc.
All review
to you
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OH
OHO
CCl
Cl
Cl H
OH
OH
C
O
HCl
Cl
Cl
SOME STABLE HYDRATES
chloral chloral hydrate
cyclopropanone cyclopropanonehydrate
120o expected60o required
109o expected60o required
sp2 sp3
+
these also indicate that hydrates are possible
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Oxidation of Aldehydes
and Ketones
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Aldehydes are readily oxidized to yield
carboxylic acid
Ketones are generally inert toward
oxidation
The difference is a consequence of structure: Aldehydes have a CHO proton that can
be abstracted during oxidation, but ketones
do not
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Many oxidizing agents, including KMnO4
and hot HNO3 convert aldehydes intocarboxylic acids
CrO3 in aqueous acid is a more common
choice in the laboratory.
The oxidation occurs rapidly at room
temperature and results in good yields
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In the such cases, the laboratory oxidation
of an aldehyde can be carried out using a
solution of silver oxide, Ag2O, in aqueous
ammonia, that so-called Tollens reagent
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Aldehyde oxidation occur through
intermediate 1,1-diols, or hydrates which
are formed by reversible nucleophilic
addition of water to carbonyl groups
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Ketones are inert to the most oxidizing
agents but undergo a slow cleavage reaction
when treated with hot alkaline KMnO4.
The CC bond next to the carbonyl group
is broken, and carboxylic acid are produced