mechanisms of organic reactions [email protected]
TRANSCRIPT
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
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
CH3CH2R
- here: lipid peroxidation:
– H2O
O2
CH3C–OOH•
R
H R
CH3CHR +
fatty acid
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:
Very often, electrophilic substitution is usedto attach an alkyl to the benzene ring(Friedel-Crafts alkylation):
benzene carbocation bromobenzene
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:
CHδ+ δ-
H δ+
H δ+
C
CH3
CH3
CH3
CH3 CH2 CH2 Clδ+ < δ+ < δ+ δ-
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:
Nucleophiles: HS–, HO–, Cl–
+
alcohol is produced
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 bondTypical of alkenes and alkynesMarkovnikov´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:
Nucleophiles – water, alcohols, carbanions – form a covalent bond with the carbon atom of the carbonyl group:
used for synthesisof alcohols
– carbon atom carries +
aldehyde/ketone
Hemiacetals
glucose
hemiacetals
hemiacetal
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:
2-phospho-glycerate
phosphoenol-pyruvate
– H2O
Rearrangement
In biochemistry: often migration of a hydrogen atom, changing the position of the double bondKeto-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-
phosphateglyceraldehyd-3-phosphate
enol form