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: NH 3

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:

H R
O2
CH3CH2R + •OH CH3CHR CH3C–O–O•
fatty acid
– H2 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+ < δ+ < δ+ δ-
CH3 CH2 CH2 Cl

+I effect is caused by atoms/groups with low electronegativity that

increase electron density in their vicinity: metals, alkyls:
H δ+ CH3
δ+ δ-
H C CH3 C

H δ+ CH3
 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

hemiacetal

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-phospho- phosphoenol-
glycerate pyruvate
 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 dihydroxyaceton-
enol form glyceraldehyd-
phosphate 3-phosphate