six membered aromatic heterocycles pyridine is aromatic … · 50 n.. pyridine pyridine is aromatic...

50

N..Pyridine

Pyridine is aromatic asthere are six delocalizedelectrons in the ring.

Six-membered heterocycles are more closelyrelated to benzene as they are aromatic on thebasis of their p-electron systems without the needfor delocalization of heteroatom lone pairs. Theempirical resonance energy for pyridine is about 28Kcal/mol, only slightly lower than that for benzene.

SIX MEMBERED AROMATIC HETEROCYCLES

51

Pyridine has divalent negatively charged N, which isa stable condition for N. The positive charge isdispersed to carbons around the ring, specifically toC-2 and C-4.

Structure of Pyridine

The net effect is to reduce the p-electron density inthe ring relative to benzene, and as result pyridineis electron deficient compared to benzene.

N 2

34

As a result, unlike benzene pyridine is polarmolecule due to the electronegative nitrogen.

N

53

Six membered heterocycleswith an electronegativeheteroatom are generallyelectron deficient comparedto benzene. Such compoundsare classified as p-deficient.

Electron-withdrawing heteroatoms decreasethe p-electron density at the carbon atomsand are thus p-deficient relative to benzene.

54

Structure of five membered heterocycles

The five-membered aromaticheterocycle ring has a p-electronexcess (six on five atoms), while inbenzene, the p-electron density isone on each ring atom.

Five membered heterocycles with an electronegativeheteroatom are generally electron rich compared tobenzene (six electrons for five carbons). Suchcompounds are classified as p-excessive.

55

36 kcal/mol

29 kcal/mol

22 kcal/mol

16 kcal/mol

The ease with which the lone pairelectron is released is directlyrelated to the electronegativity ofthe heteroatom. Thus the lowerthe electronegativity of theheteroatom, the higher thearomaticity.

The degree of aromatic characterin a five membered ring isdetermined by the ease withwhich the lone pair may bereleased into the delocalizedsystem.

56

57

Aromatic Heterocycles

p- Excessive p- Deficient

This classification is not trivial; there is a vastdifference between the properties of the two typesof aromatic compounds.

58

Reactions of p-deficient heterocyclic aromatic compounds

A hallmark of p-deficient heterocyclic systemsis their low reactivity with electrophilicagents, slower than benzene. For example,pyridine is less reactive than benzene by afactor of 106 when subjected to conditions ofnitration. The reactivity is on the order of thatof nitrobenzene, which is well known torequire much more drastic conditions thanthose for benzene itself.

59

For example, 3-bromopyridine is formed whenpyridine is reacted with bromine in the presence ofoleum (sulfur trioxide in conc. sulfuric acid) at 130°C.

Conversely pyridines are susceptible to nucleophilicattack.

60

The reactivity is greater than that of benzeneand is in roughly the same range as found forbenzenes bearing electron releasing groupssuch as in aniline. The greater electron densityin these rings accounts for this higherreactivity.

A significant feature of the p-excessive ringsystems is that they undergo electrophilicaromatic reactions faster than benzene.

Reactions of p-excessive heterocyclic aromatic compounds

These heterocycles undergo electrophilic aromaticsubstitution reactions much faster than benzeneunder similar conditions. The reasons for this are:

I. The resonance energy of the heterocycles is lessthan that of benzene, i.e. less aromatic thanbenzene.

II. The five-membered aromatic heterocycle ring hasa p-electron excess (six on five atoms), while inbenzene, the p-electron density is one on eachring atom.

61

62

Reaction with bromine requires no Lewis acid andleads to substitution at all four free positions.

no Lewis acid