Post on 21-Dec-2015
Bilrubin: (formerly referred to as haematoidin) is the yellow breakdown product of normal heme catabolism, caused by the body's clearance of aged
red blood cells which contain hemoglobin.
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood.
Synthesis of pyrrole, Knorr Synthesis
L. Knorr, Ber. 17, 1635 (1884); Ann. 236, 290 (1886); L. Knorr, H. Lange, Ber. 35, 2998 (1902).
The original Knorr synthesis employed two equivalents of ethyl acetoacetate, one of which was converted to ethyl 2-oximinoacetoacetate by dissolving it in glacial acetic acid, and slowly adding one equivalent of saturated aqueous sodium nitrite, under external cooling. Zinc dust was then stirred in, reducing the oxime group to the amine.
CH3 O
EtO2C
CH3 O
NEtO2C
OH
CH3 O
NH2EtO2CAcOH
CH3 O
NH2EtO2C CH3O
CO2Et
N
CH3
CH3
CO2Et
EtO2C
NaNO2 Zn
AcOH
+
Nitrosation of aliphatic carbon atoms
The nitrosation reaction consists in the replacement of a hydrogen atom by the nitroso group with the formation of a nitroso or oximo derivative. With a few exceptions, the replacement of hydrogen on an aliphatic carbon atom requires the presence of an electron-attracting groups adjacent to the carbon to be nitrosated. Acyl, aroyl, carbonyl, carboxy, carbalkoxyl, nitrogen, cyano, imino, and aryl groups may serve as activators. Monoketones are readily converted into alpha-oximino ketones, whereas monoesters containing no other activating groups do not undergo the reaction. Victor Meyer discovered the reaction in 1873–1874.
ON
O OHN
O ON
O
H
H
N O
CH3 O
EtO2C
CH3 OH
EtO2C
CH3 O
EtO2C NO
CH3 O
EtO2C NOH
Na+ - HOAc H+ +
- H2O
+
+ OAc-
+ HOAc
+ NaOAc
OAc-
The Hantzsch pyrrole synthesis• The Hantzsch pyrrole synthesis, named for
Arthur Rudolf Hantzsch, is the chemical reaction of β-ketoesters (1) with ammonia (or primary amines) and α-haloketones (2) to give substituted pyrroles (3).
• Note: direct reaction of β-ketoesters (1) with α-haloketones (2) gives furan [Fiest-Benary furan synthesis], and this can be a troublesome side reaction.
The Hantzsch pyrrole synthesis
CH3 O
EtO2C
RNH2CH3 NH
EtO2C
R
CH3O
Cl
N CH3CH3
EtO2C
R
CH3 NH
EtO2C
R
+
+
Reactions of Pyrrole
Substitution at nitrogen, A) Metallation of Pyrrole
N -
N
MgBr
NH
NH
N
LiNH
NaNH2, or KNH2, NH3 liq
Na+ (K+)or Na, or K
EtMgBr / ether
RLi
ionic
covalent
covalent
B) Formation of N-substituted pyrrole
N
K+
-
N
MgBr
N
Me
N
Me
MeI/ NH3 Liq
MeI/ HMPA
hexamethylphosphorousamide
95%
98%
Electrophilic Substitution (position 2 and 5)
The aromatic five-membered heterocycles all undergo electrophilic substitution, with a general reactivity order:
pyrrole >> furan > thiophene > benzene
Diels-Alder Reactions of pyrrolePyrroles normally do not undergo DA reactions, Exception
N
O
OEt
CO2Me
CO2MeN
CO2Et
CO2Me
CO2Me
+
N-Ethoxycarbonylpyrrole Dimethyl acetylenedicarboxylate