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Mechanisms of organic reactions
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Types of organic reactions
Substitution – an atom (group) of the molecule
is replaced by another
Addition – atoms of a compound are being
attached to a double (triple) bond, which is
accompanied by reduction in bond multiplicity
Elimination – two atoms (groups) are removed
from the molecule
Rearrangement – an atom (group) migrates from
one atom of a molecule to another atom, most
often of the same molecule
Mechanism
Each of these types can proceed by:
Homolytic mechanism – involves formation of
radicals:
A–B  A• + B•
Heterolytic mechanism – involves formation of
ions:
A–B  A+ + :B–
Agent
Radical – possesses an unpaired electron (Cl•)
Ionic:
 A) nucleophilic – possesses an electron pair that can
be introduced into an electron-deficient substrate
i) anions (H–, OH–)
ii) neutral molecules (NH3, HOH)
 B) electrophilic – electron-deficient  accepts an
electron pair when binding to a nucleophile:
i) cations (Br+)
ii) neutral molecules (for example Lewis acids: AlCl3)
Lewis acids and bases
Lewis base: acts as an electron-pair donor; for
example ammonia: •NH
• 3
Lewis acid: can accept a pair of electrons:
AlCl3, FeCl3, ZnCl2 – important in catalysis
(form ions):
CH3–Cl + AlCl3  CH3+ + AlCl4-
Radical substitution
- here: lipid peroxidation
1. Initiation – formation of radicals: H2O  OH• + H•
2. Propagation – radicals attack substrates making new
molecules and new radicals:
HR
O2
CH3CH2R + •OH
CH3CHR  CH3C–O–O•
-H2O
•
fatty acid
CH3CH2R
CH3CHR + CH3C–OOH
•
H R
3. Termination – radical recombines with another and
the reaction is terminated
Nitrotyrosine formation
Nitrotyrosine is being formed in tissue damage
caused by the reactive nitrogen species (RNS)
RNS arise from NO, which is produced by nitric
oxide synthase:
arginine
citrulline
RNS & nitrotyrosine
Electrophilic substitution
Electron-deficient agent attacks the substrate
with a higher electron density; the substrate
retains the original bonding electron pair:
R–X + E+  R–E + X+
Typical for aromatic hydrocarbons
Chlorination, nitration… :
-complex
-complex
Electrophilic substitution using
Lewis acids
Often used in order to incorporate an alkyl:
C6H6
+AlCl4AlCl3 + HCl
Iodination of tyrosine in biochemistry
- at the beginning of the synthesis of T3, T4:
Mesomeric effects
Permanent shift of -bond electrons in compounds
where a double bond neighbours upon an atom (group)
with an electron pair or electron deficiency,
respectively
Positive mesomeric effect (+M) is caused by
atoms/groups that „push“ electrons to neighbouring
atoms:
–NH2, –OH, – SH
Negative mesomeric effect (–M) is caused by
atoms/groups that withdraw electrons of the
neighbouring double/triple bond:
–NO2, –SO3H, –COOH
Electrophilic substitution & M effect
Substituents exhibiting the +M effect: attached to the
benzene ring, facilitate the subsequent substitution,
favouring the ortho, para positions :
Substituents exhibiting the –M effect slow down the
subsequent substitution, favouring the meta position:
Inductive effect
Permanent shift of -bond electrons in the molecule
comprising atoms with different electronegativity:
 – I effect is caused by atoms/groups with high
electronegativity that withdraw electrons of the
neighbouring atoms: – Cl, – NO2:
+

<
+
<
+
-
+I effect is caused by atoms/groups with low electronegativity that increase electron density in their
neighbourhood; metals, alkyls:
Nucleophilic substitution
Electron-rich nucleophile introduces an
electron pair into the substrate; the leaving
atom/group departs with an electron pair:
|Nu– + R–Y  Nu–R + |Y–
+
Nucleophiles: HS–, HO–, Cl–
Electrophilic addition
Typical for alkenes and alkynes
Markovnikov´s rule: the more positive part of the
agent is attached to the carbon atom (of the double
bond) with the greatest number of hydrogens:
cis addition: both new bonds form on the same side of
the alkene
trans addition: new bonds are formed on opposite
sides of the alkene
Nucleophilic addition
In compounds with polar double bonds, such
as C=O, where carbon carries +:
Nucleophiles: water, alcohols
Addition of an alcohol to the carbonyl group
yields a hemiacetal:
hemiacetal
Hemiacetals in biochemistry:
monosaccharides
glucose
Elimination
In most cases, the two atoms/groups are
removed from the neighbouring carbon atoms
and double bond is formed (-elimination)
Dehydration – elimination of water:
2
Dehydration in biochemistry
(in glycolysis)
2-phosphoglycerate
phosphoenolpyruvate
Rearrangement
In biochemistry: often a migration of a hydrogen,
changing the position of a double bond; isomers are
formed
Aldose-ketose isomerization in monosaccharides:
aldose
ketose
in glycolysis (catabolism
of glucose)