FIVE MEMBERED AROMATIC HETEROCYCLES...the formylation (addition of -CHO) of heterocyclic molecules....
Transcript of FIVE MEMBERED AROMATIC HETEROCYCLES...the formylation (addition of -CHO) of heterocyclic molecules....
63
FIVE MEMBEREDAROMATIC
HETEROCYCLES
64
a-substitution b-substitutionThe Substitution is regioselective to the a position; whenthese positions are occupied, the b-position is substituted.
X = O, S or NH
Electrophilic aromatic substitution reaction of fivemembered aromatic heterocycles
65
WHY?The +ve charge is better resonance stabilized whenthe substitution is at the a-position than at b-position.
A more stable intermediate carbocation having 3resonance forms.
only 2 resonance forms
66
Common reactions of pyrrole, furan, and thiophene
Electrophilic aromatic substitution reaction is easyand is preferred at a-position; also easy at b-position.
The following reaction are common to the three fivemembered aromatic heterocycles.
A. Electrophilic Aromatic Substitution
Z = O, S, NH
67
C. Vilsmeier-Haack reaction
B. Substitution at a-position via a-lithiated Intermediates
Z = O, S, NR
Vilsmeier reaction (Vilsmeier‐Haack reaction) allowsthe formylation (addition of -CHO) of heterocyclicmolecules. The formylating agent, chloroiminiumion, is formed in situ from N,N‐dimethylamide andPOCl3.
68
Z = O, S, NH
Example
Vilsmeier-Haack reaction
69
Mechanism
Chloroiminium ion
70
The reaction of electron rich heterocycles withformaldehyde and primary/secondary amineforming an amino alkylated heterocylcic compoundis called the Mannich reaction.
D. Mannich reaction
Z = O, S, NH
71
Mechanism
R1
N
R2
H
H
OH
Z
N R2
R1H
72
Furans are volatile, fairly stable compounds withpleasant odours. Furan itself is slightly soluble inwater. It is readily available, and its commercialimportance is mainly due to its role as the precursorof the very widely used solvent tetrahydrofuran(THF).
73
By analogy with benzene, furanundergoes reactions with electrophilicreagents, often with substitution.However, it can also react by additionand/or ring-opening depending onreagent and reaction conditions.
Reactions of Furans
74
Electrophilic Aromatic Substitution Reaction
75
HalogenationFuran can be halogenated at a-position. Bromination andiodination are easy to control as only one halogen atomsadds to furan. In the case of chlorination, di-substitution hasbeen known to occur.
O
OCl O
ClCl+
OBr dioxane
- 40 oC
variable yields
Cl2
Br2
76
AcylationAcetyl groups in the presence of phosphoric acid (or a Lewisacid) add at a-position of furans.
In general, position 2 (a-position) is more reactive thanposition 3. When position 2 is blocked, b-acylation canproceed smoothly.
77
n-Butyllithium in hexane metalates furan inthe 2-position, while excess of reagent athigher temperature produces 2,5-dilithiofuran.
Metalation
78
Addition reactionsFurans yield the corresponding tetrahydrofurans bycatalytic hydrogenation.
In some addition reactions, furans behave as 1,3-dienes. For example, furan reacts with bromine inmethanol in the presence of potassium acetate togive 2,5-dimethoxy-2,5-dihydrofuran by a 1,4-addition:
79
Ring-opening reactions
Furans are protonated in the 2-position, and not onthe O-atom, by BRÖNSTED acids:
O
HO
HPOLYMERS
80
Thiophene prefers reactionswith electrophilic reagents.Additions and ring-openingreactions are less importantthan with furan, andsubstitution reactions aredominant.
Some additional reactions, such as oxidationand desulfurization, are due to the presenceof sulfur and are thus confined to thiophenes.
81
Electrophilic substitutions
Thiophene reacts more slowly than furan but fasterthan benzene. Substitution is regioselective in the 2-or in the 2,5-position.
82
Reactions with nucleophilic reagents
83
Thiophenes are oxidized by peroxy acids to givethiophene 1,1 –dioxides:
Oxidation
84
Pyrrole reacts with sodium, sodium hydride or potassium ininert solvents, and with sodium amide in liquid ammonia, togive salt-like compounds:
85
Electrophilic substitution reactions on carbon
Nitration
86
Halogenation