What is benzene

Benzene is a natural organic compound obtained from petroleum .

It is a hydrocarbon which contains only carbon and hydrogen,.

Due to the cyclic continuous pi bonds between the carbon atoms benzene is classed as
an aromatic.

Benzene is a colorless and highly flammable liquid with a sweet smell.

Benzene is highly toxic and also a carcinogen and may cause leukemia.

Benzene has six hydrogen and six carbon atoms and the molecular weight of benzene is
78.11g/mol.

Molecular formula of benzene C6H6

Structure of Benzene

Benzene, C6H6, is a planar molecule containing a ring of six

carbon atoms, each with a hydrogen atom attached. There are
delocalized electrons above and below the plane of the ring.

The six carbon atoms form a perfectly regular hexagon.

All of the carbon-carbon bonds have exactly the same
lengths –somewhere between single and double bonds.
Each C-C bond being 1.39 Å in same length and each
bond angle being 120°.

.
C-C single bond length (1.47 Å) and double (1.34 Å)
 Bond length of C-C in Benzene Ring
How it's possible to have all of the bonds to be the same length if the ring is conjugated
with both single (1.47 Å) and double (1.34 Å), but it is important to note that there are no
distinct single or double bonds within the benzene. Rather, the delocalization of the ring
makes each count as one and a half bonds between the carbons which makes sense
because experimentally we find that the actual bond length is 1.4 Å somewhere in between
a single and double bond. Finally, there are a total of six p-orbital electrons that form the
stabilizing electron clouds above and below the aromatic ring.

The presence of the delocalized electrons makes benzene particularly stable

Benzene resists addition reactions because those reactions would involve breaking the
delocalization and losing that stability.
 Derived of Benzene Structure
Molecular formula: Elemental analysis and molecular wt. determination
show that benzene molecular formula C6H6 and the molecular weight 78.11.
It means that C6H6 is more unsaturated compared to n-hexan C6H14 .

Straight chain structure not possible: Benzene could be constructed as a

straight chain or ring compound having double and triple bond. But
benzene did not behave like alkene or alkynes. It did not decolorized
bromine in CCl4 or cold aqueous potassium permanganate. It did not add
water in the presence of acid
What is the Kekulé structure?

August Kekulé was a German scientist the first to suggest a

sensible structure for benzene in 1865. The carbons are arranged
in a hexagon, and he suggested alternating double and single
bonds between them. Each carbon atom has a
hydrogen attached to it.

Above this short of diagram, each carbon has three bonds leaving
it. Because carbon atoms form four bonds, that means you are a
bond missing - and that must be attached to a hydrogen atom.
Problems with the Kekulé structure in Chemistry

Although the Kekulé structure was a good attempt in its time,

there are serious problems with it.

Because of the three double bonds, One might expect benzene to

have reactions like ethane or any unsaturated alkenes.

But instead of undergoing any addition reaction breaking double

bond of carbon atoms, it usually takes part substitution reactions
by replacing hydrogen atom with something new group or atoms.
Problems with the shape
Benzene is a planar molecule (all the atoms lie in one plane), and that
would also be true of the Kekulé structure. The problem is that C-C single
and double bonds are different lengths.
C-C bond length 0.154nm
C=C bond length 0.134nm

That would mean that the hexagon would be irregular if it had the Kekulé
structure, with alternating shorter and longer sides. In real benzene all the
bonds are exactly the same - intermediate in length between C-C and
C=C at 0.139 nm. Real benzene is a perfectly regular hexagon.
Problems with the stability of benzene

Real benzene is a lot more stable than the Kekulé structure would give it
credit for. Every time you do a thermochemistry calculation based on the
Kekulé structure, you get an answer which is wrong by about 150 kJ mol -1.
This is most easily shown using enthalpy changes of hydrogenation.

Hydrogenation is the addition of hydrogen to something. If, for example,

you hydrogenate ethene you get ethane:
CH2=CH2 + H2 CH3CH3
In order to do a fair comparison with benzene (a ring structure)
we're going to compare it with cyclohexene. Cyclohexene,
C6H10, is a ring of six carbon atoms containing just one C=C.

When hydrogen is added to this, cyclohexane, C6H12, is formed. The "CH"

groups become CH2 and the double bond is replaced by a single one
The structures of cyclohexene and cyclohexane are usually simplified in the
same way that the Kekulé structure for benzene is simplified
by leaving out all the carbons and hydrogens .

In the cyclohexane case, for example, there is a carbon atom at each corner, and
enough hydrogens to make the total bonds on each carbon atom up to four. In this
case, then, each corner represents CH2.
The hydrogenation equation could be written:

The enthalpy change during this reaction is -120 kJ mol -1. In other words, when 1
mole of cyclohexene reacts, 120 kJ of heat energy is evolved.
Where does this heat energy come from? When the reaction happens,
bonds are broken (C=C and H-H) and this costs energy. Other bonds
have to be made, and this releases energy.

Because the bonds made are stronger than those broken, more energy is
released than was used to break the original bonds and so there is a net
evolution of heat energy.

If the ring had two double bonds in it initially (cyclohexa-1,3-diene),

exactly twice as many bonds would have to be broken and exactly twice
as many made. In other words, you would expect the enthalpy change of
hydrogenation of cyclohexa-1,3-diene to be exactly twice that of
cyclohexene - that is, -240 kJ mol-1.
In fact, the enthalpy change is -232 kJ mol-1 - which isn't far off what we
are predicting.
Applying the same argument to the Kekulé structure for benzene (what
might be called cyclohexa-1,3,5-triene), you would expect an enthalpy
change of -360 kJ mol-1, because there are exactly three times as many
bonds being broken and made as in the cyclohexene case. In fact what
you get is -208 kJ mol-1 - not even within distance of the predicted value!

This means that real benzene is about 152 kJ mol-1 more stable than
the Kekulé structure. Because release energy only -208 kJ mol -1
compared to -360 kJ mol-1 .
This is very much easier to see on an enthalpy diagram. Notice that in each case
heat energy is released, and in each case the product is the same (cyclohexane).
That means that all the reactions "fall down" to the same end point. Heavy lines,
solid arrows and bold numbers represent real changes. Predicted changes are
shown by dotted lines and italics.
The most important point to notice is that real benzene is much lower down
the diagram than the Kekulé form predicts. The lower down a substance is,
the more energetically stable it is.

This means that real benzene is about 150 kJ mol -1 more stable than the
Kekulé structure gives it credit for. This increasing stability of benzene is
known as the delocalisation energy or resonance energy of benzene. The
first term (delocalisation energy) is the more commonly used.
Kekule structure:
Kekule's structure was the first suggested structure for Benzene.
In this structure, the Carbons are arranged in a hexagon manner, and it has
been suggested that there exist alternating double and single bonds between
them. According to his proposal Benzene is 1,2,3-cyclohexatriene.
In this, each Carbon atom has a Hydrogen attached to it,
which can be shown in the figure as:
The list of the Limitations of Kekule's structure:
1. According to the prediction made by the Kekule structure, there
should be two ortho isomers of 1,2- dibromobenzene, which
represent the two different bonds present in the benzene structure.
In one isomer the two bromine atoms should be on carbons that are
connected by a double bond as shown in structure. In the other
isomer, the bromines should be on carbons connected by a single
bond as shown in structure . In fact only one Ortho dibrombenzene
could be prepared.
 To overcome this objection Kekule further suggested that
benzene was a mixture of two forms in rapid equilibrium.

2. But in actual practice, only one 1,2-bromobenzene has ever been found,
denoting the fact that all the bonds in benzene are equivalent and form
resonance with each other.
3. According to Kekule's structure benzene contains three double bonds
and hence the chemical properties of benzene should resemble those of
alkene, but alkene is not so stable as Benzene and Benzene forms
substitution compounds easily.
4. Kekule structure predicted that there are two types of bond lengths that
exist in the structure i.e the bond length for the single bonds 1.54A o and
for double bonds 1.34Ao, but actually all the bonds of benzene are
found to be of equal length 1.4Ao . Hence, above are the mentioned list
of the Limitations of Kekule's structure.
5. Kekule structure failed to explain why benzene with three double bonds
did not give addition reaction like other alkens. For examples benzene
did not react with HBr or Br2 in CCl4
 Aromaticity
In 1931, German chemist and physicist Erich Hückel proposed a theory to
help determine if a planar ring molecule would have aromatic properties. His
rule states that if a cyclic, planar molecule has 4n+2 π electrons, it is
considered aromatic. This rule would come to be known as Hückel's Rule.

Four Criteria for Aromaticity

When deciding if a compound is aromatic, go through the following
checklist. If the compound does not meet all the following criteria, it is likely
not aromatic.
1.The molecule is cyclic (a ring of atoms)
2.The molecule is planar (all atoms in the molecule lie in the same plane)
3.The molecule is fully conjugated (p orbitals at every atom in the ring)
4.The molecule has 4n+2 π electrons (n=0 or any positive integer)
 π electrons of Benzene by the Molecular Orbitals structure

The structure of benzene is the best described in terms of modern

Molecular Orbitals theory.
All six carbon atoms in benzene in sp2 hybridized . The sp2 hybrid
orbital overlap with each other and with s orbitals of the six hydrogen
atoms forming C-C and C-H sigma bonds
Since the sigma bond results from the overlap of planner sp2
orbitals, all carbon and hydrogen atoms in benzene lie in the
same plane. All sigma bonds in benzene lie in one plane and all
bond angles e 120 o

Also each carbon atom in benzene possesses an unhybridized

p-orbital containing one electron. These p orbitals are perpendicular
to the plane of sigma bonds. The lateral overlap of theses p orbitals
produces a pie molecular orbital containing six Electrons shown in the
Fig . one half of this pie molecular orbital lies above and one other half
lies below the plane of the sigma bonds.
 Why 4n+2 π Electrons?
According to Hückel's Molecular Orbital Theory, a compound is particularly
stable if all of its bonding molecular orbitals are filled with paired electrons.
This is true of aromatic compounds, meaning they are quite stable. With
aromatic compounds, 2 electrons fill the lowest energy molecular orbital, and 4
electrons fill each subsequent energy level (the number of subsequent energy
levels is denoted by n). This gives a total of 4n+2 π electrons. You can see how
this works with the molecular orbital diagram for the aromatic compound,
benzene, below. Benzene has 6 π electrons. Its first 2 π electrons fill the lowest
energy orbital, and it has 4 π electrons remaining. These 4 fill in the orbitals of
the succeeding energy level.
 How does the 4n+2 Rule Work?

To apply the 4n+2 rule, first count the number of π electrons in

the molecule. Then, set this number equal to 4n+2 and solve for n.
If is 0 or any positive integer (1, 2, 3,...), the rule has been met.
For example, benzene has six π electrons:
4n + 2 = 6
4n = 4
n=1
For benzene, we find that n=1, which is a positive integer, so the
rule is met.
 How Can You Tell Which Electrons are π Electrons?

Perhaps the toughest part of Hückel's Rule is figuring out which electrons in
the compound are actually π electrons. Once this is figured out, the rule is
quite straightforward. π electrons lie in p orbitals. Sp2 hybridized atoms have
1 p orbital each. So if every molecule in the cyclic compound is sp 2
hybridized, this means the molecule is fully conjugated (has 1 p orbital at
each atom), and the electrons in these p orbitals are the π electrons. A simple
way to know if an atom is sp2 hybridized is to see if it has 3 attached atoms
and no lone pairs of electrons.
Each double bond (π bond) always contributes 2 π electrons. Benzene has 3 double
bonds, so it has 6 π electrons.
 Problems
Using the criteria for aromaticity, determine if the following
molecules are aromatic:
 Answers

1.Aromatic - only 1 of S's lone pairs counts as π electrons, so there are 6 π

electrons, n=1
2.Not aromatic - not fully conjugated, top C is sp 3 hybridized
3.Not aromatic - top C is sp2 hybridized, but there are 4 π electrons, n=1/2
4.Aromatic - N is using its 1 p orbital for the electrons in the double bond, so its
lone pair of electrons are not π electrons, there are 6 π electrons, n=1
5.Aromatic - there are 6 π electrons, n=1
6. Not aromatic - all atoms are sp2 hybridized, but only 1 of S's lone
pairs counts as π electrons, so there 8 π electrons, n=1.5
7. Not aromatic - there are 4 π electrons, n=1/2
8. Aromatic - only 1 of N's lone pairs counts as π electrons, so there are
6 π electrons, n=1
9. Not aromatic - not fully conjugated, top C is sp 3 hybridized
10. Aromatic - O is using its 1 p orbital for the elections in the double
bond, so its lone pair of electrons are not π electrons, there are 6 π
electrons, n=1
 What is an Electrophilic Substitution Reaction?

An electrophilic substitution reaction is a chemical reaction in which the

functional group attached to a compound is replaced by an electrophile. The
displaced functional group is typically a hydrogen atom. Electrophilic
substitution reactions generally proceed via a three-step mechanism that involves
the following steps.
•The generation of an electrophile
•The formation of a carbocation (which is an intermediate)
•The removal of a proton from the intermediate
 Electrophilic Aromatic Substitution Mechanism, Step 1: Attack of
The Electrophile (E) By a Pi-bond of The Aromatic Ring

The first step of electrophilic aromatic substitution is attack of the

electrophile (E+) by a pi bond of the aromatic ring. [Note: the identity of the
electrophile E is specific to each reaction, and generation of the active
electrophile is a mechanistic step in itself. We’ll cover the specific reactions
next. This post just covers the general framework for electrophilic aromatic
substitution].
2. Electrophilic Aromatic Substitution Mechanism, Step 2: Deprotonation Of The Tetrahedral Carbon
Regenerates The Pi Bond
 Putting Two Steps Together: The General
Mechanism

Note that attack could have occurred at any one of the six carbons of
benzene and resulted in the same product.
4. The Reaction Energy Diagram of Electrophilic Aromatic Substitution
Electrophilic aromatic substitution has two steps ; attack of electrophile and
deprotonation. There is also a carbocation intermediate.
This means that we should have a “double-peak” reaction energy diagram.
Second, the relative heights of the “peaks” should reflect the rate-limiting step.
What’s the slow step? In other words, which of the two steps has the highest
activation energy?

Electron-donating substitutents increase the rate of reaction (“activating”) and

electron-withdrawing substituents decrease the rate of reaction (deactivating).
Since electron-donating and electron-withdrawing substituents affect the
nucleophilicity of the pi bond (through pi-donation and pi-acceptance) as well
as the stability of the intermediate carbocation, the logical conclusion is that
attack on the electrophile (step 1) is the rate-determining step. Therefore it will
be the higher peak in reaction energy diagram, representing its higher
activation energy.
https://www.masterorganicchemistry.com/2017/11/09/electrophilic-aromatic-substitution-the-mechanism/
Types of Electrophilic Substitution Reactions
The two primary types of electrophilic substitution reactions undergone by
organic compounds are electrophilic aromatic substitution reactions and
electrophilic aliphatic substitution reactions. An illustration describing the
electrophilic substitution of a hydrogen atom (belonging to a benzene molecule)
with a chlorine atom is provided below.

.Here, the chlorine cation acts as an electrophile and replaces a hydrogen

atom in the benzene ring. The products formed in this electrophilic
substitution reaction include a proton and a chlorobenzene molecule.
Amino acids: Characteristics and Classification of amino acids
Amino acids are carboxylic acid in which α-carbon is attached to the amino
group as well as it is attached to R- (alkyl) group. α-carbon means carbon
atom next to the carboxylic group. They are the basic unit of proteins.
Nomenclature of amino acid:
The systematic names and formulas given refer to hypothetical forms in which
amino groups are unprotonated and carboxyl groups are undissociated. This
convention is useful to avoid various nomenclatural problems but should not be
taken to imply that these structures represent an appreciable fraction of the amino-
acid molecules.
Amino Acids
An amino acid is a compound that contains both an amine group (−NH2) and a
carboxyl group (−COOH) in the same molecule. The figure below shows the general
structure of an amino acid. Either structure is considered correct for an amino acid.

Figure 13.1.1: An amino acid is an organic molecule that contains an amine group, a
carbonyl group, and a side chain (R), all bonded to a central carbon atom. Amino acids
can be shown with or without charges. These are equivalent structures .
The amine and carboxyl groups of an amino acid are both covalently bonded to a
central carbon atom. That carbon atom is also bonded to a hydrogen atom and an R
group.
It is this R group which varies from one amino acid to another and is called the amino
acid side chain. The nature of the side chains accounts for the variability in physical and
chemical properties of the different amino acids. Each amino acid is grouped based on
the properties of the side chain. The groups are designated as polar (hydroxylic, sulfur-
containing, amidic) , nonpolar (aliphatic and aromatic), acidic, or basic.
Figure 13.1.2: Five of the twenty biologically relevant amino acids, each having a
distinctive side chain (R). Alanine's side chain is nonpolar, while threonine's is polar.
Tryptophan is one of several amino acids whose side chain is aromatic. Aspartic acid has
an acidic side chain, while lysine has a basic side chain.
What is an isoelectric point and how it is calculated?

The pH at which the net charge on the molecule is zero is defined as the isoelectric
point (pI) of that molecule. Note that the molecule at its pI exists as a zwitterion
with an equal number of positive and negative charges.
• Zwitterion
• Amino acids are typically drawn either with no charges or with a plus
and minus charge as figure below.When an amino acid contains both a
plus and a minus charge in the "backbone", it is called a zwitterion
and has an overall neutral charge. The zwitterion of an amino acid
exists at a pH equal to the isoelectric point. Each amino acid has its
own pI value based on the properties of the amino acid. At pH values
above or below the isoelectric point, the molecule will have a net
charge which depends on its pI value as well as the pH of the solution
in which the amino acid is found.
pI can be easily calculated using the formula, pI = pKa1 + pKa2/ 2 for
molecules with two ionizable groups, while for molecules with more
than two ionizable groups, pI is the average of two pKa values that are
close to each other.
.
The pI of amino acids with acidic side chains
In cases where the side chain is acidic, the pI is at a lower pH because the acidic
side chain will result in an additional -1 charge. Subsequently, the neutral form
arises under conditions of acidity, when the additional -1 charge has been
neutralized. For example, aspartic acid has a pKa3 corresponding to its CH2CO2H
side chain.
The pI of amino acids with acidic side chains
• In case the side chain is basic, the pI is at a higher pH because the acidic side
chain will result in an additional +1 charge. Subsequently, the neutral form arises
under conditions of basicity, when the additional -1 charge has been neutralized.
• Histidine persists in its neutral form between the pH of 6.00 (equivalent to pK a3
for the side chain pyrrole NH group, which corresponds to the equilibrium
between the positive and neutral form) and pH 9.17 (equivalent to pKa 2 of the
amino group which corresponds to the equilibrium between the negative and
neutral forms).
. pI can be easily calculated using the formula, pI = pKa1 + pKa2/ 2 for
molecules with two ionizable groups, while for molecules with more
than two ionizable groups, pI is the average of two pKa values that are
close to each other.
•pH determines the acidity or alkalinity of the solution while pKa determines the strength
of an acid (or base) in the solution.
•pKa is the pH at which there is an equimolar concentration of undissociated acid
and its conjugate base.
•The pH at which the net electric charge on a molecule is zero is known as the isoelectric
point (pI) of the molecule and this species which has an equal number of positive and
negative charges is known as a zwitterion.
•At pH < pI, the amino acid is protonated, hence, positively charged, while at pH > pI, the
amino acid is deprotonated, hence, negatively charged.
•pI can be easily calculated using the formula, for molecules with two ionizable groups,
while for molecules with more than two ionizable groups, pI is the average of two pKa
values that are close to each other.

•At pI value, the protein has no net electrical charge, hence, it is least soluble.
 How does one find an isoelectric point?
Isoelectric point (pI) can be calculated using the formula, pI =( pKa1 + pKa2)/ 2 for
molecules with two ionizable groups (e.g. amino acids like glycine). The pKa1 of the
carboxylic acid group of glycine is 2.34 and pKa2 of the amino group is 9.60,
therefore, pI (glycine) = (2.34+9.60)/2 = 5.94.
However, for molecules with more than two ionizable groups (e.g. arginine), pI is the
average of two pKa values that are close to each other.
Arginine has 3 pKa values: pKa1 (carboxylic acid group) = 2.17, pKa2 (alpha-
ammonium group), = 9.04, pKa3 (guanidium R group) = 12.48. Therefore, pI
(arginine) = (9.04 + 12.48)/2 = 10.76.
Zwitterions
The isoelectric point corresponds to what is known as the zwitterionic form of a
protein. Zwitterion possesses discrete functional groups, each of which carry a
positive or negative charge. A zwitterionic amino acid consists of a negative
carboxylate ion and a positive ammonium ion alongside a charge on their side
chain, which varies between amino acids.
What is the relationship between the pH and pKa of an amino acid?
The pKa for an amino acid is an acid dissociation constant that refers to the equilibrium
between the protonated and deprotonated forms of the backbone amino group,
backbone carboxyl group, and any potential acid/base component of the variable group.
The net charge of the protein is determined by summing the charge of individual amino
acids across the protein.
pKa relates to the equilibrium constant and defines the transition between two structural
forms of an amino acid–protonated and deprotonated. Amino acids possess distinct
pKas for the carbonyl group, amino group, and any functional groups on the side chain
that may be protonated or deprotonated.
There is always one more structure than the number of pKa values for amino acids. For
example, if there were two pKa values, three structures can be discerned. This is
illustrated below using glycine, which has two pKa values – pKa 1 represents the
(de)protonation of the carboxyl group and pKa2 represents the (de)protonation of the
amine group:
When the pH< pKa protonation of the amino and carboxyl groups occurs, resulting in a net
+1 positive charge for glycine. When the pH is increased to a value between the two
pKas(pKa2>pH> pKa1), the carboxyl group is deprotonated while the amino group remains
protonated. This represents the zwitterionic form of the amino acid as it simultaneously
possesses a positive and negative charge.
When the pH> pKa2, the amino group is deprotonated and loses its charge. The amino acid
now carries a net negative charge of -1. The zwitterionic form of the amino acid can exist
at any pH value between pKa1 and pKa2.
 How does the zwitterionic form of an amino acid relate to the pI?
• When the pH is exactly at the pKa value, a buffer arises in which the deprotonated and
protonated amino acids exist in equilibrium. For example, when the pH = 2.34 (pK a of
glycine), the solution comprises of 50% neutral molecules in which the carboxyl is
deprotonated, and 50% positive molecules where the carboxyl is protonated.
• This pH produces the carboxyl buffer zone. If the pH s increased to that of the pK a of
the amino group (9.60), another buffer is produced where there is an equilibration
between the protonated neutral zwitterion and the deprotonated negative amino acid.
• The isoelectric point can, therefore, be approximated by averaging the two pK a values.
More complex amino acids have more than two pK a values due to the presence of
additional pKa values for their side chains.
 Proteins
Proteins are polymers of α-amino acids bonded by peptide linkage. Their
molecular weights range from 5000 to many million. Without protein life
would not be possible. They occur in all living cells in the form of skin,
hair, callus, cartilage, muscles, tendons and ligaments. Proteins hold
together, protect, and provide structure to the body of a multi-celled
organism. In the form of enzymes, hormones, antibodies, and globulins,
they catalyze, regulate, and protect the body chemistry. In the form of
hemoglobin, myoglobin and various lipoproteins, they effect the transport
of oxygen and other substances within an organism.