Transcript Slajd 1 - Instytut Chemii Organicznej PAN

The Pyrrole - reactivity
H
N
Jan Lewtak
Pyrrole - numbering
3 
4
5
N
H
1
2 
Plan of the lecture. Review of the reactions with pyrrole
 Electrophilic attack at carbon
 Condensation
 Oxidising
 Reducing
 Cycloaddition
 Toxicity
Protonation
H H
+
N
H
H
H
+ H+
+ H+
+
N
H
N
H
N
H H
Stability:
Most stable
medium
least stable
No mesomeric
stabilisation
Nitration & Sulfonation
NO2
AcONO2
AcOH, -10°C
N
H
N
H
NO2
N
H
4:1
N
H
1) PySO3, 100°C
2) H+
N
H
SO3H
Halogenation
X
X
N
H
SO2Cl2 (1equiv)
Cl 0°C
1) or 2) or 3)
X
N
H
X = Cl(1), Br(2), I(3)
1) SO2Cl2(4equiv)
2) Br2, 0°C
3) KI, AcOH
N
H
X
Bromination
1) bromohydantoin,
AIBN
2) (Boc)2O, NEt3
N
H
Br
N
Boc
NBS, THF, -78°C
Br
N
Boc
Br
Br
N
Boc
Br
Br
NBS, THF, -78°C
N
Sii-Pr3
N
Sii-Pr3
1equiv NBS
N
Sii-Pr3
2equiv NBS
Acylation
Cl3CCOCl
N
H
CCl3
N
H
O
Vilsmeier formylation
DMF, POCl3
H
N
H
N
H
Modified Vilsmeier
method:
O
DMF, oxalyl chloride
N
H
Friedel - Crafts acylation
N
H
O
PhCOOH, TFAA
MeCOCl, AlCl3
N
Tos
N
Tos
Ph
N
Tos
O
CN
Acylation
R
N
H
O
O
RCOCl, AlCl3
R
R
O
N
H
R
O
N
H
Basic conditions
1.BuLi 2. PhCONR2 3.OHN
PG
Ph
N
H
O
Alkylation
CH3I or
Br
poly-alkylated derivatives,
oligomers
N
H
PhSOCH=CHCOMe
N
H
N
H
N
H
N2
EtO2C
O
98%
CO2Et
CO2Et
N
H
CO2Et
71%
Condensation
HCHO, Na2CO3
N
H
84%
HO
N
H
OH
N
N
p-Me2NC6H4CHO
N
H
HCl, EtOH
90%
N
H
N
H
coloured
Condensation of pyrrole with itself
H
HClconc
+
N
H
N
H
polymer
H
H
H
H+
N
H
N
H
N
H
HN
pyrrole
HN
HN
H
N
H
HN
H
Oxidising of C-substituents
Et
Me
Et
Me
CAN, THF, AcOH
EtO2C
Me
N
H
O
EtO2C
N
H
H
CAN, 8equiv
N
H
MeCN/H2O OHC
N
H
CHO
25%
N
PG
CHO
20%
CAN, 8equiv
N
PG
CO2Et
EtO2C
OHC
MeCN/H2O
CO2Et
EtO2C
CAN, 8equiv
N
H
MeCN/H2O
OHC
N
H
CHO
15%
Mr Voloshchuk
conditions
Oxidation of the heterocyclic ring
O
N
CO2But
O2
O
O
OH
CO2But
N
45%
lactam
CO2Me
O
O
O
N
N
35%
10%
cleavage product
CO2But
epoxide
Reactions of C-metallated pyrroles
n-BuLi
N
N
EtI
N
85%
Li
MgBr2
Et
N
MgBr
N
Br
PdCl2
Br
Br
N
Boc
1) BuLi, THF
2) CO2
HO2C
CO2H
N
Boc
N
N
Reactions of C-metallated pyrroles
SnMe3
N
CO2But
Br
N
CO2But
Br
30%
N
N
t
CO2But CO2Bu
N
CO2But
tripyrrole
N
H
N
H
O
Pd-C
Pd-C
POCl3
N
H
N
N
H
N
H
bipyrrole
N
H
N
H
N
H
N
Reducing in acidic conditions
Zn, AcOH
H2, Pt, AcOH
N
H
63%
N
H
N
H
25%
Decarboxylation, bromination and formylation of
carboxylic derivatives
Me
Me
Me
Me
NH2C2H4OH
N
H
CO2H
75%
Br2, Py
N
H
CO2Et
N
H
Br
50%
N
H
CO2Et
CHO
MeOCHCl2
EtO2C
N
H
AlCl3, DCM
80%
EtO2C
N
H
Cycloaddition
CO2Et
TMS
N
CO2Et
O
CO2Et
17%
OH
Br
N
Ts
Br
Br
Br
Br
N
CO2Et
Br
N
H
And now… important type of reactivity in laboratory
work. „In vivo” reactivity.
Produkt toksyczny przy wdychaniu.
Działa szkodliwie przez drogi
oddechowe.
Ryzyko poważnego uszkodzenia oczu.
W przypadku wysłuchania wykładu nt. pirolu natychmiast skontaktować się
z Ośrodkiem Zatruć i zapewnić warunki do odpoczynku w pozycji umożliwiającej
swobodne oddychanie.
Thank You for Your Attention