The Pyrrole - reactivity
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The Pyrrole - reactivity
HN
Jan Lewtak
Pyrrole - numbering
NH1
2
34
5
Plan of the lecture. Review of the reactions with pyrrole
Electrophilic attack at carbon Condensation Oxidising Reducing Cycloaddition Toxicity
Protonation
Stability:
Most stable medium least stable
NH
NNH
+ H++ H+
H
H
H H
++N
H
HH
No mesomeric stabilisation
Nitration & Sulfonation
NH
NH
NH
NO2
NO2AcONO2AcOH, -10°C
4 : 1
NH
NH
SO3H1) PySO3, 100°C2) H+
Halogenation
NH
1) or 2) or 3)
NH
X
XX
XNH
ClSO2Cl2 (1equiv)0°C
X = Cl(1), Br(2), I(3)1) SO2Cl2(4equiv)2) Br2, 0°C3) KI, AcOH
Bromination
NH
N
Boc
Br
1) bromohydantoin, AIBN2) (Boc)2O, NEt3
N
N
Boc
NBS, THF, -78°C
N
Boc
Br Br
Sii-Pr3
NBS, THF, -78°C
N
Sii-Pr3
N
Sii-Pr3
Br Br Br
1equiv NBS 2equiv NBS
Acylation
NH
NH
CCl3
O
Cl3CCOCl
NH
Vilsmeier formylationDMF, POCl3
NH
H
O
N
Tos
PhCOOH, TFAA
N
Ph
OTos
MeCOCl, AlCl3
N
Tos
OFriedel - Crafts acylation
Modified Vilsmeier method:
NH
DMF, oxalyl chloride
NH
CN
Acylation
NH
R
O
NH
O
R
RCOCl, AlCl3
NH
R
O
O
R
Basic conditions
N
PG
1.BuLi 2. PhCONR2 3.OH-
NH
Ph
O
Alkylation
NH
CH3I orBr
poly-alkylated derivatives, oligomers
NH
PhSOCH=CHCOMe
NH
O
98%
NH
EtO2C CO2Et
N2
NH CO2Et
CO2Et
71%
Condensation
NH
HCHO, Na2CO3
NH OHHO
NH
NH
N
NH
N
p-Me2NC6H4CHO
HCl, EtOH
84%
90%
coloured
Condensation of pyrrole with itself
NH
NH
H
H+
N
H
HH
HClconc
NH HN
H+
NH HN
H
H
pyrroleNH HN
HN
polymer
Oxidising of C-substituents
NH
NH
CHOOHC
N N CHOOHC
NH
PG PG
EtO2C CO2Et
NH
CHOOHC
EtO2C CO2Et
CAN, 8equiv
CAN, 8equiv
CAN, 8equiv
MeCN/H2O
MeCN/H2O
MeCN/H2O
25%
20%
15%
NH
Me
EtMe
EtO2CCAN, THF, AcOH
NH
EtMe
EtO2CO
H
Mr Voloshchukconditions
Oxidation of the heterocyclic ring
N
O
CO2ButNO
O
CO2ButOH
CO2Me
N
O
N
O
O
CO2But
lactam cleavage product epoxide
45% 35% 10%
O2
Reactions of C-metallated pyrroles
N
n-BuLiN Li
85% MgBr2
N MgBrN Br
PdCl2N
N
EtI
N Et
N
Boc
Br Br
1) BuLi, THF2) CO2
N
Boc
HO2C CO2H
Reactions of C-metallated pyrroles
N
CO2But
SnMe3 N
CO2But
Br Br 30%N
CO2ButN
CO2But
N
CO2But
tripyrrole
NH
NH
OPOCl3
NH
N NH
NH
Pd-C
NH
NH
NH
N
Pd-C
bipyrrole
Reducing in acidic conditions
NH
NH
NH
Zn, AcOH
25%
H2, Pt, AcOH
63%
Decarboxylation, bromination and formylation of carboxylic derivatives
NH
CO2H
Me Me
NH
Me MeNH2C2H4OH
NH
CO2EtBr2, Py
NH
CO2Et
Br
75%
50%
NH
EtO2C
MeOCHCl2
AlCl3, DCM80%
NH
EtO2C
CHO
Cycloaddition
N
CO2EtOTMS
CO2Et
17%N
CO2Et
CO2EtOH
N
Ts
Br
Br
BrBr
NH
Br
Br
And now… important type of reactivity in laboratory work. „In vivo” reactivity.
W przypadku wysłuchania wykładu nt. pirolu natychmiast skontaktować się z Ośrodkiem Zatruć i zapewnić warunki do odpoczynku w pozycji umożliwiającej swobodne oddychanie.
Produkt toksyczny przy wdychaniu.Działa szkodliwie przez drogi oddechowe.Ryzyko poważnego uszkodzenia oczu.
Thank You for Your Attention
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