aromatic compounds
TRANSCRIPT
RETROSYNTHETIC RETROSYNTHETIC APPROCHAPPROCH
TOTOORGANIC SYNTHESISORGANIC SYNTHESIS
Dr. Shaikh S. NizamiDr. Shaikh S. NizamiDepartment of ChemistryDepartment of ChemistryUniversity of KarachiUniversity of Karachi
RETROSYNTHESIS RETROSYNTHESIS
OFOF
AROMATIC AROMATIC
COMPOUNDSCOMPOUNDS
CONTENTSCONTENTS
1.Aromatic Eletrophilic Substitution Reactions
2.Aromatic Nucleophilic Substitution Reactions
Retrosynthesis of Aromatic Retrosynthesis of Aromatic Electrophilic Substitution Electrophilic Substitution
ReactionsReactions
TM
C X
SYNTHON REAGENT
R
_
+X
+
R
H
?R
X
Addition of cationic synthons to the aromatic ring
Reagents forReagents for Aromatic Aromatic Electrophilic SubstitutionElectrophilic Substitution
REAGENT REACTION
R+
RBr + AlCl3 Friedel-Crafts Alkylation
+ROH H+
+ H+Alkene
RCO+
+RCOCl AlCl3 Friedel-Crafts Acylation
SYNTHON
Reagents forReagents for Aromatic Aromatic Electrophilic SubstitutionElectrophilic Substitution
REAGENT REACTIONNO2
+
Cl2 FeCl3+
HNO3 H2SO4+ NitrationCl
+Chlorination
Br+ Br2 Fe+ Bromination
H2SO4 Sulphonation+SO2Cl
+SO2OH
ClSO2OH Chloro-Sulphonation
ArN2+
ArN2+Cl
-Diazocoupling
SYNTHON
Friedel-CraftsFriedel-Crafts AlkylationAlkylation
TM'BHT' butyled hydroxytoluenean antioxidant used in foodF.C. alkylation useful reactionfor tertiary halides
OH
Retrosynthesis of BHT & Retrosynthesis of BHT & SynthesisSynthesis
TM
C C
FriedelCrafts
_
OH
HH
+ +
Synthesis OH
+ H+
ort BuCl/AlCl3
TM
OH
Friedel-Crafts AcylationFriedel-Crafts Acylation
TM
C C
FriedelCrafts
_ + Cl
Rearrangement is possible in primary alkylhalide
Friedel-Crafts AcylationFriedel-Crafts Acylation
Cl
AlCl3
+
COCl
AlCl3
O
Zn,Hg
HCl(conc.)TM
One-carbon electrophile One-carbon electrophile for aromatic synthesisfor aromatic synthesis
TM
R
H
+ X+
REAGENT REACTION+CH2Cl CH2O/HCl/ZnCl2 Chloromethylation
+CHO CHCl3/
-OH Reimer-Tieman
Me2NCHO/POCl3VilsmeierHaak
-
R
X
SYNTHON
Retrosynthesis of Piperonol Retrosynthesis of Piperonol (perfumery compound) & (perfumery compound) &
SynthesisSynthesis
FGI
OO
CH2Cl
C-C
chloro-methylation
OO
H
Synthesis
OO
CH2O/ZnCl2HCl
OO
CH2Cl
Oxidation
hexamine
TM
TM
CHO
OO
AROMATIC SIDE CHAINS BY AROMATIC SIDE CHAINS BY Function Group Function Group InterconversionInterconversion
Y
R R
X
Y X Reagent
Reduction
-NO2
-NH2
H2, Pd, CSn,
conc.HCl-COR -CH(OH)R NaBH4
-COR -CH2R
Zn/Hg/conc.HCl
AROMATIC SIDE CHAINS BY AROMATIC SIDE CHAINS BY Functional Group Functional Group InterconversionInterconversion
Y
R R
X
OxidationY X Reagent
-CH2Cl -CHO hexamine-CH2R -CO2H KMnO4
-CH3
-COR-OCOR R’CO3H
Aromatic Side Chains by Aromatic Side Chains by Functional Group Functional Group InterconversionInterconversion
Y
R R
X
SubstitutionY X Reagent
-CH3
-CCl3 Cl2,PCl
5-CCl3
-CF3 SbF5-CN -COOH HO-, H2O
Nucleophilic Aromatic Nucleophilic Aromatic Substitution ReactionsSubstitution Reactions
Addition of an oxygen atomto an aromatic ring
Add anionic reagents RO- to an Aromatic compound with a leaving Group.
Nucleophilic Aromatic Nucleophilic Aromatic SubstitutionSubstitution
•Nucleophilic aromatic substitution works best when the leaving groups is N2 (diazonium salts)
•The synthetic sequence is nitration, reduction,diazotisationand substitution
Nucleophilic Aromatic Nucleophilic Aromatic SubstitutionSubstitution
RHNO3
H2SO4R
NO2 H2
Pd,C
R
NH2NaNO2
HCl, 5oCR
N2+
H2O
R
OH
Retrosynthesis of PhenolRetrosynthesis of Phenol
OH
BrMe
TM
subst.
via N2+
NH2
BrMe
C Br
bromination
NH2
Me
FGINO2
Me
C N
NitrationMe
SynthesisSynthesis
Me
HNO3
H2SO4
NO2
Me
Sn/H+
NH2
Me
HOAcNHAc
Me
Br2
NaOH
NH2
BrMe
NaNO2/HCl
H2OTM
Aromatic compounds made by Aromatic compounds made by nucleophilic displacement of nucleophilic displacement of
daizonium saltsdaizonium saltsArNH2
NaNO2
HClArN2
+ Z-
ArZ
Reagent_____ HO H2ORO ROHCN Cu(I)CNBr/Cl Cu(I)Br/Cu(I)ClI KIH H3PO2 or EtOH/H+
____Z_____
Retrosynthetic analysis & Retrosynthetic analysis & synthesissynthesis
Me
CNSubst.
Me
NH2
FGI
Me
NO2
Me
SYNTHESISSYNTHESIS
MeHNO3
H2SO4
Me
NO2
H2
Pd,c
Me
NH2
NaNO2,HClCu(I)CN
TM
NUCLEOPHILIC NUCLEOPHILIC SUBSTITUTION OF SUBSTITUTION OF
HALIDESHALIDESDirect displacement of halide from anaromatic ring is possible only if :
There are ortho and para nitro groupsOR
Similar electron-withdrawing groups
NUCLEOPHILIC NUCLEOPHILIC SUBSTITUTION OF SUBSTITUTION OF
HALIDESHALIDESCl
HNO3H2SO
4
Cl
NO2
NO2Nu-
Nu
NO2
NO2
Retrosynthetic analysisRetrosynthetic analysisTrifluralin B- a herbicideTrifluralin B- a herbicide
NC3H7
CF3
NO2O2N
Cl
CF3
NO2O2N
Cl
CF3
SYNTHESISSYNTHESIS
Cl
CF3
HNO3
H2SO
4
Cl
CF3
NO2O2N base
N-Pr2NH
TM