2. Heterocyclic compounds are organic compounds that contain rings
composed of carbon and other atoms – heteroatoms – in natural
heterocyles moustrly nitrogen, sulfur and oxygen.
Heterocycles exist as three-, four-, five- and multi-membered rings.
The stability of heterocyles increases with maximum number of
conjugated double bonds, because the delocalized -bonding
electron pairs form a molecular orbital filled with six electrons and
the compound have the aromatic character.
Heterocyclic Compounds
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18. Pyridine: Bonding and Basicity
Pyridine has a structure similar to that of benzene, except that one CH
unit is replaced by a nitrogen atom. As with benzene, pyridine is a
resonance hybrid of Kekule-type structures .
The orbital pictures for benzene and pyridine are similar. The nitrogen
atom, as with the carbons, is sp2-hybridized, with one electron in a p
orbital perpendicular to the ring plane. Thus, the nitrogen contributes
one electron to the six electrons that form the aromatic pi cloud above
and below the ring plane. On the other hand, the unshared electron
pair on nitrogen lies in the ring plane (as with the C-H bonds) in an sp2
orbital.
19. Because of the similarities in bonding, pyridine resembles benzene in
shape. It is planar, with nearly perfect hexagonal geometry. It is aromatic
and tends to undergo substitution rather than addition reactions.
But the substitution of nitrogen for carbon changes many of the properties.
Like benzene, pyridine is miscible with most organic solvents, but unlike
benzene, pyridine is also completely miscible with water! One explanation
lies in its hydrogen-bonding capability
20. Another reason is that pyridine is much more polar than benzene. The
nitrogen atom is electron-withdrawing compared to carbon; hence, there is
a shift of electrons away from the ring carbons and toward the nitrogen,
making it partially negative and the ring carbons partially positive (Figure
1.1). This polarity enhances the solubility of pyridine in polar solvents like
water, and also increases the boiling point of pyridine (115°C) relative to
benzene (80°C).
Pyridine is weakly basic. It is a much weaker base than aliphatic amines,
mainly because of the different hybridization of the nitrogen (sp2 in pyridine
and sp3 in aliphatic amines). The greater s-character of the orbital
containing the basic nonbonded lone pair (one-third s in pyridine and one-
fourth s in aliphatic amines) means that the unshared electron pair is held
closer to the nitrogen nucleus in pyridine, decreasing its basicity.
21. Pyridine does react with strong acids to form pyridinium salts. For this reason,
pyridine is often used as a scavenger in acid-producing reactions; for example, in
the reaction of thionyl chloride with alcohols.
22. Substitution in Pyridine
Though aromatic, pyridine is very resistant to electrophilic aromatic
substitution and undergoes reaction only under drastic conditions. For
example, nitration or bromination requires high temperatures and strong
acid catalysis.
23. One reason for this sluggishness is that electron withdrawal by the nitrogen
makes the ring partially positive and therefore not receptive to attack by
electrophiles, which are also positive (see Figure 1.1). A second reason is
that, under the acidic conditions for these reactions, most of the pyridine is
protonated and present as the positively charged pyridinium ion, which is
even more unlikely to be attacked by electrophiles than is neutral pyridine.
When substitution does occur, electrophiles attack pyridine mainly at C-3.
The cationic intermediate is least unfavorable in this case, because it does
not put a positive charge on the electron-deficient nitrogen (especially bad
if the nitrogen is protonated).
24. Although resistant to electrophilic substitution, pyridine undergoes
nucleophilic aromatic substitution. The pyridine ring is partially positive (due
to electron withdrawal by the nitrogen) and is therefore susceptible to attack
by nucleophiles. Here are two examples:
25. Pyridine and alkylpyridines are found in coal tar. The monomethyl pyridines
(called picolines) undergo side-chain oxidation to carboxylic. For example, 3-
picoline gives nicotinic acid (or niacin), a vitamin essential in the human diet
to prevent the disease pellagra
Pyridine can be reduced by catalytic hydrogenation to the fully saturated
secondary amine piperidine.
26. Five-Membered Heterocycles: Furan, Pyrrole, and Thiophene
Now let us examine rather different types of heteroaromatic compounds: those with
five-membered rings. Furan, pyrrole, and thiophene are important five-membered
ring heterocycles with one heteroatom.
Numbering begins with the heteroatom and proceeds around the ring.
As drawn, the structures of these heterocycles look as if they ought to be
dienes, but in fact, these ring systems are aromatic; they behave like benzene in
many ways, particularly in their tendency to undergo electrophilic aromatic
substitution. The reasons for this behavior will become clear if we examine the
bonding in these molecules.
27. Electrophilic Substitution in Furan, Pyrrole, and Thiophene
Furan, pyrrole, and thiophene are all much more reactive than benzene
toward electrophilic substitution. Each reacts predominantly at the 2-
position (and, if that position is already substituted, at the 5-position).
Here are typical examples:
28. The reason for predominant attack at C-2 (instead of the other possibility, C-3)
becomes clear if we examine the carbocation intermediate in each case:
Attack at C-2 is preferred because, in the carbocation intermediate, the positive
charge can be delocalized over three atoms, whereas attack at C-3 allows
delocalization of the charge over only two positions.
29. Other Five-Membered Heterocycles: Azoles
It is possible to introduce a second heteroatom (and even a third and fourth) into
fivemembered heterocycles. The most important of these are the azoles, in which
the second heteroatom, located at position 3, is nitrogen.
31. Lipids
Lipids are classified into two broad types:
• those like fats and waxes, which contain ester linkages and can be hydrolyzed
• those like cholesterol and other steroids, which don’t have ester linkages and can’t be
hydrolyzed.
32. Waxes are mixtures of esters of long-chain carboxylic acids with long-chain alcohols. The
carboxylic acid usually has an even number of carbons from 16 through 36, while the
alcohol has an even number of carbons from 24 through 36.
One of the major components of beeswax, for instance, is triacontyl hexadecanoate, the
ester of the C30 alcohol 1-triacontanol and the C16 acid hexadecanoic acid. The waxy
protective coatings on most fruits, berries, leaves, and animal furs have similar structures.
33. Animal fats and vegetable oils are the most widely occurring lipids. Although they appear
different—animal fats like butter and lard are solids, whereas vegetable oils like corn and
peanut oil are liquid—their structures are closely related. Chemically, fats and oils are
triglycerides, or triacylglycerols—triesters of glycerol with three long-chain carboxylic
acids called fatty acids. Animals use fats for long-term energy storage because they are
much less highly oxidized than carbohydrates and provide about six times as much energy
as an equal weight of stored, hydrated glycogen
34. Hydrolysis of a fat or oil with aqueous NaOH yields glycerol and three fatty acids. The
fatty acids are generally unbranched and contain an even number of carbon atoms
between 12 and 20.
If double bonds are present, they have largely, although not entirely, Z, or cis, geometry.
The three fatty acids of a specific triacylglycerol molecule need not be the same, and the
fat or oil from a given source is likely to be a complex mixture of many different
triacylglycerols.
More than 100 different fatty acids are known, and about 40 occur widely.
Palmitic acid (C16) and stearic acid (C18) are the most abundant saturated fatty acids;
oleic and linoleic acids (both C18) are the most abundant unsaturated ones. Oleic acid is
monounsaturated because it has only one double bond, whereas linoleic, linolenic, and
arachidonic acids are polyunsaturated fatty acids because they have more than one
double bond.
36. Table 1.2 Composition of Some Fats and Oils
Table 1.2 lists the approximate composition of fats and oils from different sources.
37. The data in Table 1 .1 show that unsaturated fatty acids generally have lower melting
points than their saturated counter parts, a trend that is also true for triacylglycerols.
Since vegetable oils generally have a higher proportion of unsaturated to saturated fatty
acids than animal fats (Table 1.2), they have lower melting points. The difference is a
consequence of structure.
Saturated fats have a uniform shape that allows them to pack together efficiently in a
crystal lattice. In unsaturated vegetable oils, however, the C=C bonds introduce bends
and kinks into the hydrocarbon chains, making crystal formation
more difficult. The more double bonds there are, the harder it is for the molecules to
crystallize and the lower the melting point of the oil.
38. The C=C bonds in vegetable oils can be reduced by catalytic hydrogenation, typically
carried out at high temperature using a nickel catalyst, to produce saturated solid or
semisolid fats.
Margarine and shortening are produced by hydrogenating soybean, peanut, or
cottonseed oil until the proper consistency is obtained.
Unfortunately, the hydrogenation reaction is accompanied by some cis–trans
isomerization of the double bonds that remain, producing fats with about 10% to
15% trans unsaturated fatty acids. Dietary intake of trans fatty acids increases
cholesterol levels in the blood, thereby increasing the risk of heart problems. The
conversion of linoleic acid into elaidic acid is an example.
39. Chemically, soap is a mixture of the sodium or potassium salts of the long-chain fatty acids
produced by hydrolysis (saponification) of animal fat with alkali.
40. When soaps are dispersed in water, the long hydrocarbon tails cluster together on the
inside of a tangled, hydrophobic ball, while the ionic heads on the surface of the cluster
stick out into the water layer. These spherical clusters, called micelles, are shown
schematically in Figure 1.1. Grease and oil droplets are solubilized in water when they
are coated by the nonpolar, hydrophobic tails of soap molecules in the center of
micelles. Once solubilized, the grease and dirt can be rinsed away.
41. Literature:
1. Organic chemistry (a short course) by David J. Hart, Christofer M. Hadad,
Leslle E. Cralne, Harold Hart, 2011, pp.390-401
2. Organic Chemistry 8th edition by J. McMurry. 2012, pp.1087-1095
