synthesis of Morphine

1. HO
OH
Cl
O
pyridine
benzoyl chloride
HO
O
O
-HCl
NaNO2/AcOH
HO
O
O
N
H
benzoylation
nitrosation
H2/Pt
reductive
hydrogenation
HO
O
O
H2N FeCl3
oxidation O
O
O
O
SO2/CH3OH
O
O
O
O
S
O
O
unstable cyclic suilfate
HO
O
O
HO
dimethylsulfate/
CH3OH
methylation
addition of sulphur dioxide
decomposition
H3CO
O
O
H3CO KOH/HCl
hydrolysis
H3CO
OH
H3CO
H
OH
-C
6H5COOH
-H
2O
i) NaNO2/AcOH
ii) H2/Pt
iii) FeCl3
H3CO
O
H3CO
O
H2C
COOC2H5
CN
H3CO
OH
H3CO
O
NC
C2H5OOC
1,4-Micheal addition
H3CO
O
H3CO
O
NC
C2H5OOC H
keto-enol
tautomerism
K2[Fe(CN)6]
oxidation
H
H3CO
O
H3CO
O
NC
C2H5OOC
OH H
H3CO
O
H3CO
O
NC
HOOC
- C
2H5OH - CO
2
H3CO
O
H3CO
O
NC Diels-Alder
reaction
1,3-butadiene
H3CO
O
H3CO
O
NC
H3CO
O
H3CO
O
rewrite
C
N
H3CO
O
H3CO
O
C
N
Cu-Cr alloy
cyclisation
130 0
C
rearrangement
H3CO
H3CO
O
C
O
N
H2/Pt
H3CO
H3CO
O
C O
NH
Wolf-Kishner
reduction
H3CO
H3CO
C O
NH
reductive
hydrogenation
decarboxylatiom
hydrolysis
KOH/CH3OH
CH3I
H3CO
H3CO
C O
N
CH3
N-methylation
LiAlH4
reduction
H3CO
H3CO
CH2
N
CH3
H2O/H
H3CO
H3CO
CH2
N
CH3
HO
NH2
-NH
2
/KOH/
HO-CH2
-CH
2
-OH
HO
HO
CH2
N
CH3
HO
oppenaur
oxidation
HO
HO
CH2
N
CH3
O
2,4-DNPH
HO
HO
CH2
N
CH3
N
H
N
O2N
NO2
- H
2O
Br2/AcOH
HO
HO
CH2
N
CH3
N
H
N
O2N
NO2
Br
H2O/H
HO
CH2
N
CH3
O
O
- 2,4-DNPH
LiAlH4
reduction
HO
CH2
N
CH3
O
HO
Morphine
step 2
step 1
step 3 step 4 step 5
step 6 step 7 step 8
step 9, 10, 11
step 12
step 13
step 14 step 15
step 16
step 17
step 18
step 19 step 20
step 21
step 27
step 26
step 25
step 24
step 23
step 22
step 28
step 29 step 30
selective
hydrolysis
hydrolysis
addition
bromination
hydrolysis
cyanoethylacetate
hydrazine hydrate
HO
Dr. D. PARTHIBAN,
Assistant Professor,
Department of Chemistry.
R.V. Govt Arts College,
chengalpattu
SYNTHESIS OF MORPHINE