Heterocyclic Chemistry

Heterocyclic Chemistry

N

OS Chapter 1

Aromaticity

Heterocyclic Chemistry

Aromatic heterocycles

Aromatic heteroyclic compounds are those have a hetroatom in a ring and behave in a manner similar to benzene in some of their properties (i.e. react by electrophilic aromatic substitution) .

Further more, these compounds comply with the general rule proposed by Huckel.

Erich Hückel, a German physical chemist recognized in the early 1930s through MO calculations that cyclic planar molecules with a closed loop of 2,6,10,14,18,22……p-electrons in a fully conjugated system should be aromatic. This finding is called the (4n+2) -electron rule. Conversely, monocyclic planar molecules with 4n -electrons are said to be antiaromatic.

Heterocyclic Chemistry

Hückel’s criteria for aromaticity include:

1. The compound must be cyclic.

2. It must have one p orbital on each atom of the ring.

( for C atoms to have p orbital they must have double bonds, or bear a positive or negative charge i.e. ions)

1. It should be planar or nearly planar so that there is continuous or nearly continuous overlap of all p orbitals.

2. It must have a closed loop of (4n+2) electrons in the cyclic arrangement of p orbitals. Wher n= 0, 1, 2, 3----integral number

Hückel's Rule

Heterocyclic Chemistry

Structures of Pyrrole, Furan, and Thiophene

The double-unsaturated five-membered heterocyles (Pyrrole, furan, and thiophene) are aromatic (Six electrons in a cyclic conjugated system of overlapping p orbitals)

On the other hand, these hetrocycles are considered to be 1,3-butadiene derivatives Cyclopentadiene the carbocylic analog of these compounds does not display the

aromatic behavior. So what is the diffrence between cyclopentadiene and the aromatic 5-memberd heterocycles.

In contast to cycloenadien’s carbon the N, O, or S of the aromatic heterocycles possess at least one electron pair that occupies a p orbital perpendicular to the ring plane. Thus this lone electron pair, or the corresponding p-orbital can participate in the pi system of the conjugated diene. As a rsult these heterocyles fulfill the Huckel’s rule, as they planar and possess six pi electrons with n=1.

Heterocyclic Chemistry

Structures of Pyrrole, Furan, and Thiophene

Heterocyclic Chemistry

Structures of Pyrrole, Furan, and Thiophene

NH O S

Blue electron pair participate in the aromaticityRed electron pair does not participate in aromaticity

However, the extent of aromaticity (as determined by resonance energies, see below) for these compounds is different from that of benzene (which undergoes electrophilic substitution reactions) .Resonance Energies (experimental and theoretical values):

Furan 88 KJmol-1Pyrrole 100 KJmol-1Thiophene 130 KJmol-1Benzene 151 KJmol-1Thus the order of aromatic character of these three heterocycles is as follows:

Thiophene > pyrrole > Furan This order is consistent with the order of the electronegativity values As O is more electronegative than N and S , it provides the two electron necessary for the aromatic sextet less easly, and in consequence furan is less aromatic than pyrrole and thiophene

Element O N S

Electron negativity 3.44 3.04 2.58 For the same reason pyrrole is less aromatic than thiophene which resonance energy is higher than that of furan and pyrrole and about the same as in benzene.Therefore thiophene resemble benzene rather than furan or pyrrole in many o f its reactions but it is more reactive and less stable.

Heterocyclic Chemistry

Pyridine, a Six-Membered Heterocycle

It is a nitrogen-containing heterocyclic analog of benzene Lone pair of electrons on N occupies an sp2 orbital in the plane of

the ring but is not involved in aromaticity.

On the other hand all six-memeberd rings with a heteroatom other than N are not aromatic .

Heterocyclic Chemistry

O

S

4H-Pyran 4H-Thiopyran

All of these compounds have a saturated sp3 hybridized C i.e. no P-orbital at these Cs thus

they are not aromatic

SO

Pyranylium Thiopyranylium

Both of these two ions are aromatic

O

2H-Pyran

Thus pyran and thiopyran are not aromatic compounds. However, the positively charged ions of these compounds are aromatic

since they fulfill Huckel’s criteria for aromaticity

In comparing 5-membered heterocycles with 6-membered hterocycles the latter compounds are more aromatic. Aromatic character

X X

> >

Benzene 6-Memebered heterocycles 5-Memebered heterocycles

Reactivity and Chemical behavior

Consideration of the electron distribution within the π-framework shows that the 5-membered heteroaromatics should be susceptible to electrophilic substitution processes.

Indeed, they undergo electrophilic substiution much more readily than benzene and attack is predominately in the 2-position (due to relative stabilities of intermediates).

Pyrrole is more like furan than benzene Very electron rich and so very reactive to electrophiles (more

reactive than furan) but the presence of the N-H group provides additional scope for reactivity. Hence a more varied and complex chemistry than furan.

Heterocyclic Chemistry

Problem set.1

Q1. Which of the following heterocycles conform to the Hückel rule (4n +2) for aromaticity: (i) furan; (ii) 1H-azepine; (iii) pyrylium perchlorate

Q2. Which of the following compounds (a)–(e) are aromatic? Give your reasons.

Heterocyclic Chemistry

ONH

Furan 1H-Azepine

O

ClO4

Pyranylium perchlorate

N N

N

CH3

(a) (b) (c)