1. Mechanisms of organic reactions

2. 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

3. 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–

4. 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)

5. Lewis acids and bases CH3–Cl + AlCl3  CH3+ + AlCl4-
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-
• •

6. 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 CH3CHR CH3C–O–O•
3. Termination – radicals react with each other, forming stable products; thus, the reaction is terminated (by depletion of radicals) H R O2 •
– H2O
fatty acid
CH3CH2R
CH3CHR +
CH3C–OOH • H R

7. 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.

8. Aromatic electrophilic substitution using Lewis acids
Halogenation:
Very often, electrophilic substitution
is used to attach an alkyl to the
benzene ring(Friedel-Crafts alkylation):
benzene carbocation bromobenzene

9. 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:
+I effect is caused by atoms/groups with low electronegativity that increase electron density in their vicinity: metals,
alkyls:
CH CH CH Cl
δ+ < δ+ < δ δ- C H δ+ δ- C
CH3

10. 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

11. 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

12. 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:

13. 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:
Nucleophiles: HS–, HO–, Cl– +
alcohol is produced

14. 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:

15. 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:

16. Nucleophilic addition
In compounds with polar unsaturated bonds, such as C=O:
Nucleophiles – water, alcohols, carbanions – form a covalent bond with the carbon atom of the carbonyl group:
– carbon atom carries +
aldehyde/ketone
used for synthesis of alcohols

17. Hemiacetals
Addition of alcohol to the carbonyl group yields hemiacetal:
As to biochemistry, hemiacetals are formed by monosaccharides:
hemiacetal
glucose
hemiacetals

18. 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:
In biochemistry – e.g. in glycolysis:
– H2O
2-phospho- glycerate
phosphoenol- pyruvate

19. 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-
phosphate
enol form
glyceraldehyd-
3-phosphate