Mechanisms of organic reactions
mirka.rovenska@lfmotol.cuni.cz
Types of organic reactions
Substitution – an atom (group) of the molecule is replaced by another
atom (group)
Addition – π-bond of a compound serves to create two new covalent
bonds that join the two reactants together
Elimination – two atoms (groups) are removed from a molecule which is
thus cleft into two products
Rearrangement – atoms and bonds are rearranged within the molecule;
thus, isomeric compound is formed
Mechanism
A reaction can proceed by:
homolytic mechanism – each fragment possesses one of the bonding
electrons; thus, radicals are formed:
A–B  A• + B•
heterolytic mechanism – one of the fragments retains both the bonding
electrons; thus, ions are formed:
A–B  A+ + :B–
Agents
Radical – possess an unpaired electron (Cl•)
Ionic:
A) nucleophilic – possess 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  bind to substrate centres with
a higher electron density:
• i) cations (Br+)
• ii) neutral molecules (for example Lewis acids: AlCl3)
Lewis acids and bases
••
Lewis base: acts as an electron-pair donor; e.g. ammonia: NH3
Lewis acid: can accept a pair of electrons; e.g.: AlCl3, FeCl3, ZnCl2. These
compounds – important catalysts: generate ions that can initiate a reaction:
CH3–Cl + AlCl3  CH3+ + AlCl4-
Radical substitution
- here: lipid peroxidation:
1. Initiation – formation of radicals: H2O  OH• + H•
2. Propagation – radicals attack neutral molecules generating new molecules
and new radicals:
CH3CH2R + •OH
fatty acid
– H2 O
CH3CHR
O2
•
H R
CH3C–O–O•
CH3CH2R
CH3CHR
•
+
CH3C–OOH
H R
3. Termination – radicals react with each other, forming stable products; thus,
the reaction is terminated (by depletion of radicals)
Electrophilic substitution
An electron-deficient agent reacts with an electron-rich substrate; the
substrate retains the bonding electron pair, a cation (proton) is
removed:
R–X + E+  R–E + X+
Typical of aromatic hydrocarbons:
chlorination
nitration etc.
Aromatic electrophilic substitution using
Lewis acids
Halogenation:
benzene
carbocation
bromobenzene
Very often, electrophilic substitution is used
to attach an alkyl to the benzene ring
(Friedel-Crafts alkylation):
Inductive effect
Permanent shift of -bond electrons in the molecule composed of atoms
with different electronegativity:
– I effect is caused by atoms/groups with high electronegativity that
withdraw electrons from the neighbouring atoms: – Cl, –C=O, –NO2:
δ+
<
CH3
δ+
CH2
<
δ+
δ-
CH2
Cl
+I effect is caused by atoms/groups with low electronegativity that
increase electron density in their vicinity: metals, alkyls:
H δ+
δ+
H
C
δ-
H δ+
CH3
CH3
CH3
C
Mesomeric effects
Permanent shift of electron density along the -bonds (i.e. in compounds
with unsaturated bonds, most often in aromatic hydrocarbons)
Positive mesomeric effect (+M) is caused by atoms/groups with lone
electron pair(s) that donate π electrons to the system: –NH2, –OH,
halogens
Negative mesomeric effect (–M) is caused by atoms/groups that
withdraw π electrons from the system: –NO2, –SO3H, –C=O
Activating/deactivating groups
If inductive and mesomeric effects are contradictory, then the stronger
one predominates
Consequently, the group bound to the aromatic ring is:
activating – donates electrons to the aromatic ring, thus facilitating
the electrophilic substitution:
• a) +M > – I… –OH, –NH2
• b) only +I…alkyls
deactivating – withdraws electrons from the aromatic ring, thus
making the electrophilic substitution slower:
• a) –M and –I… –C=O, –NO2
• b) – I > +M…halogens
Electrophilic substitution & M, I-effects
Substituents exhibiting the +M or +I effect (activating groups, halogens)
attached to the benzene ring direct next substituent to the ortho, para
positions:
Substituents exhibiting the –M and – I effect (–CHO, –NO2) direct the
next substituent to the meta position:
Nucleophilic substitution
Electron-rich nucleophile introduces an electron pair into the substrate;
the leaving atom/group retains the originally bonding electron pair:
|Nu– + R–Y  Nu–R + |Y–
This reaction is typical of haloalkanes:
+
alcohol is produced
Nucleophiles: HS–, HO–, Cl–
Radical addition
Again: initiation (creation of radicals), propagation (radicals attack neutral
molecules, producing more and more radicals), termination (radicals react
with each other, forming a stable product; the chain reaction is terminated)
E.g.: polymerization of ethylene using dibenzoyl peroxide as an initiator:
Electrophilic addition
An electrophile forms a covalent bond by attacking an electron-rich
unsaturated C=C bond
Typical of alkenes and alkynes
Markovnikov´s rule: the more positive part of the agent (hydrogen in the
example below) becomes attached to the carbon atom (of the double
bond) with the greatest number of hydrogens:
Nucleophilic addition
In compounds with polar unsaturated bonds, such as C=O:
– carbon atom carries +
Nucleophiles – water, alcohols, carbanions – form a covalent bond with
the carbon atom of the carbonyl group:
aldehyde/ketone
used for synthesis
of alcohols
Hemiacetals
Addition of alcohol to the carbonyl group yields hemiacetal:
hemiacetal
As to biochemistry, hemiacetals are formed by monosaccharides:
hemiacetals
glucose
Elimination
In most cases, the two atoms/groups are removed from the neighbouring
carbon atoms and a double bond is formed (-elimination)
Elimination of water = dehydration – used to prepare alkenes:
– H2O
In biochemistry – e.g. in glycolysis:
2-phosphoglycerate
phosphoenolpyruvate
Rearrangement
In biochemistry: often migration of a hydrogen atom, changing the
position of the double bond
Keto-enol tautomerism of carbonyl compounds: equilibrium between a
keto form and an enol form:
E.g.: isomerisation of monosaccharides occurs via enol form:
glucose
(keto form)
enol form
fructose
dihydroxyacetonphosphate
enol form
glyceraldehyd3-phosphate