RETROSYNTHETIC

APPROCH
TO
ORGANIC SYNTHESIS
FUNCTIONAL GROUP
INTERCONVERSION

Dr. Shaikh S. Nizami

Department of Chemistry
University of Karachi
 FUNCTIONAL
GROUPS
INTERCONVERSIONS
 CONTENTS
 Definition of Functional Group
Interconversion (FGIs)
 Importance of FGIs
 Functional group containing
heteroatoms
 Unsaturated hydrocarbons
 Removal of Functional Groups
Definition of Functional
Group Interconversion
The process of writing
one functional group
for another to help
synthetic planning is
known as FGI
Definition of Functional
Group Interconversion
 FGI can be done by
 Substitution

 Addition

 Elimination

 Oxidation

 Reduction
 Why FGI is needed?
A TM containing more than
one functional group, one
functional group may interfere
with desired reaction on
second functional group during
a synthesis.
 Why FGI is needed?
 This problem can be solved
into ways
 a) Use of protecting group

 b) Change in synthetic strategy

(using FGI)
 Importance of FGIs
 It helps in identifying suitable
disconnection.
 Consider the synthesis of
ketone containing a double
bond.
 Alkenes may be prepared by
the dehydration of alcohol.
 Importance of FGIs
O

Ph Ph
TM
First step in the retrosynthetic
analysis of TM could be functional
group interconversion to an alcohol
But which alcohol ?
 Importance of FGIs
FGI O OH

i Ph Ph
O

Ph Ph
TM FGI O

ii Ph Ph
OH
 RETROSYNTESIS
O
FGI O OH
Ph Ph
i Ph Ph
TM
Matched Latent Polarity
O O
(Consonant)
_
Ph Ph
+
O
OH
+ H Ph
Ph
 RETROSYNTESIS

O O
FGI
Ph Ph Ph Ph
ii
OH
Mismatched Latent Polarity
(Dissonant)
 Functional group
containing heteroatoms
 For convenience these
functional groups will be
initially divided into three
major classes depending
upon their oxidation level
a) Carboxylic acid and their
derivatives
 Compounds in this class are the highest
oxidation level of organic compounds
 It includes
 Carboxylic acid (RCO2H)
 Esters/lactone (RCOO2R)
 Amide/lactam (RCONHR)
 They may be interconverted by a series
of simple reactions
 Transformations of
carboxylic acid derivatives
O O O H2O
R C N
R O R' R OH

H2O H2O SOCl2 H2O

H+/ or PCl5
R’OH
O O O
RO - NH3
R OR' R Cl R NH2
b) Aldehydes, ketones and
their derivatives
 Functional groups in this class
are at lower oxidation level
than class (a)
 It includes the features C=X in
which the carbon atom is
bonded directly to either
hydrogen or carbon.
b) Aldehydes, ketones and
their derivatives
 The group includes
 Aldehydes (RHC=O)

 Ketones (RR’C=O)

 Imines (RR’C=NR”)

 Hydrazones (RR’C=NNHR”)

 Oximes (RR’C=NOH)
 Transformations of
aldehydes
R'O OR' O
2R’OH/H + HS(CH2)3SH/H+
R H S S
R H
aldehyde H H

H2O R’NH2

R' R’=alkyl, aryl,(imine)

N R’=NMe2 (hydrazones)
R’=OH (oxime)
R H
 c) Alcohols and their
derivatives
 Apart from Alcohols (ROH)
themselves, this class includes
 Amines (RNH2)

 Thiols (RSH)

 Disulphides (RSSR)

 Ethers (ROR)

 Alkyl halides (RX)

 Interconversions of
alcohols and halides

SOCl2 or
HBr PCl5
R Br R OH R Cl
HO- HO-
 Use of a sulphonic ester
as a leaving group
R’SO2Cl
R OH R OSO2R'

Nu-

R Nu + R’SO3-
 Interconversions between
the three oxidation levels
a,b & c above
 To move between groups
classified in the previous section,
it is necessary to perform a
reduction or oxidation at some
stage.
 Oxidation

 Many methods have been

developed for the oxidation of
organic compounds.
 It is possible to transform a
low oxidation level FG into any
group of higher level.
 Oxidation
Primary alcohol
O O
CrO3 /H+
R OH PCC
or PDC
R H R OH
Secondary alcohol
OH O
PCC or PDC
R R R R
PCC= pyridinium chlorochromate
PDC= pyridinium dichromate
 Reduction
O LiAlH4
Esters R OH
R OR' +
R’OH
O
Amides LiAlH4
R NH2 R NH2

Nitriles 1 eq.
DIBAL-H O
LiAlH4
R NH2 R CN
Low temp. R H
 Unsaturated
Hydrocarbons
OH
HO OH

H2,Pd/C
BH3,NaOH/
H2O2 OsO4

RCO3H O3
H O H
HBr
Br CHO
CHO
 Removal of Functional Group
Alcohol to corresponding hydrocarbon
Alcohol
Dehydration

Alkene

Hydrogenation

Alkane
Removal of Functional Group
Aldehydes/ ketones to hydrocarbons

Clemmensen
O Zn,HCl H H

R R'(H)
R R'(H) NH2NH2,KOH
Wolf-Kishner