# Organic Chemistry/Aromatics

\| Aromatics \| Aromatic
reactions\>\>

After understanding the usefulness of unsaturated compound, or
conjugated system, we hope to explore the unique structure of
aromatic compounds,
including why benzene should not be called 1,3,5-cyclohexatriene because
it is more stable than a typical triene, and seemingly unreactive.
Called \"aromatic\" initially because of its fragrance, aromaticity now
refers to the stability of compounds that are considered aromatic, not
only benzene. Any cyclic compound with 4n+2 pi electrons in the system
is aromatic. The stability of aromatic compounds arises because all
bonding orbitals are filled and low in energy.

# History of Aromatics

Early in the 19th century, advances in equipment, technique and
communications resulted in chemists discovering and experimenting with
novel chemical compounds. In the course of their investigations they
stumbled across a different kind of stable compound with the molecular
formula of C~6~H~6~. Unable to visualize what such a compound might look
like, the scientists invented all sorts of models for carbon-to-carbon
bonding \-- many of which were not entirely stable \-- in order to fit
what they had observed to what they expected the C~6~H~6~ compound to
look like.

Benzene (which is the name that was given to the aromatic compound
C~6~H~6~) is probably the most common and industrially important
aromatic compound in wide use today. It was discovered in 1825 by
Michael Faraday, and its commercial production from coal tar (and, later
on, other natural sources) began in earnest about twenty-five years
later. The structure of benzene emerged during the 1860s, the result of
contributions from several chemists, most famously that of
Kekulé.

Scientists of the time did not have the benefit of understanding that
electrons are capable of delocalization, so that all carbon atoms could
share the same π-bond electron configuration equally.
Huckel was the first to
apply the new theory of quantum mechanics to clearly separating σ and π
electrons. He went on to develop a theory of π electron bonding for
benzene, which was the first to explain the electronic origins of
aromaticity.

# Benzene Structure

Benzene is a hexagonal ring of six carbon atoms connected to each other
through one p-orbital per carbon. Its chemical formula is C~6~H~6~, and
its structure is a hexagonal ring of carbons sharing symmetrical bonds,
with all six hydrogen atoms protruding outwards from the carbon ring,
but in the same plane as the ring. The p-orbital system contains 6
electrons, and one way to distribute the electrons yields the following
structure:

:   ![](Benzol.svg "fig:Benzol.svg"){width="45"}

However, another resonance form of benzene is possible, where the single
bonds of the first structure are replaced with double bonds, and the
double bonds with single bonds. These two resonance forms are
co-dominant in benzene. (Other forms, such as a structure with a π bond
connecting opposite carbons, are possible but negligible.) Thus, each
bond in benzene has been experimentally shown to be of equal length and
strength, and each is accounted as approximately a \"1.5\" bond instead
of either a single or double bond alone.

Electron density is shared between carbons, in effect yielding neither a
single nor a double bond, but a sort of one-and-a-half bond between each
of the six carbons. Benzene has a density of negative charge both above
and below the plane formed by the ring structure. Although benzene is
very stable and does not tend to react energetically with most
substances, electrophilic compounds may be attracted to this localized
electron density and such substances may form a bond with the aromatic
benzene ring.

An electron delocalisation ring can be used to show in a single picture
both dominant resonance forms of benzene:

:   ![](Benzene_circle.svg "fig:Benzene_circle.svg"){width="45"}

## Benzene Properties

Benzene is a colorless, flammable liquid with a sweet aroma and
carcinogenic effects. The aromatic properties of benzene make it far
different from other alkenes in many ways.

### Benzene Reactions

:   *Main article:* Aromatic
    reactions

Unlike alkenes, aromatic compounds such as benzene undergo substitution
reactions instead of addition reactions. The most common reaction for
benzene to undergo is electrophilic aromatic substitution (EAS),
although in a few special cases, substituted benzenes can undergo
nucleophilic aromatic substitution.

## Benzene Health Effects

In the body, benzene is metabolized, and benzene exposure may have quite
serious health effects. Breathing in very high levels of benzene can
result in death, while somewhat lower (but still high) levels can cause
drowsiness, dizziness, rapid heart rate, headaches, tremors, confusion,
and unconsciousness. Eating or drinking foods containing high levels of
benzene can cause vomiting, irritation of the stomach, dizziness,
sleepiness, convulsions, rapid heart rate, and even death.

The major effect of benzene from chronic (long-term) exposure is to the
blood. Benzene damages the bone marrow and can cause a decrease in red
blood cells, leading to anemia. It can also cause excessive bleeding and
depress the immune system, increasing the chance of infection. Some
women who breathed high levels of benzene for many months had irregular
menstrual periods and a decrease in the size of their ovaries. It is not
known whether benzene exposure affects the developing fetus in pregnant
women or fertility in men, however animal studies have shown low birth
weights, delayed bone formation, and bone marrow damage when pregnant
animals breathed benzene.

The US Department of Health and Human Services (DHHS) also classifies
benzene as a human carcinogen. Long-term exposure to high levels of
benzene in the air can cause leukemia, a potentially fatal cancer of the
blood-forming organs. In particular, Acute Myeloid Leukemia (AML) may be
caused by benzene.

# Aromaticity

Aromaticity in organic chemistry does not refer to whether or not a
molecule triggers a sensory response from olfactory organs (whether it
\"smells\"), but rather refers to the arrangement of electron bonds in a
cyclic molecule. Many molecules that have a strong odor (such as
diatomic chlorine Cl~2~) are not aromatic in structure \-- odor has
little to do with chemical aromaticity. It was the case, however, that
many of the earliest-known examples of aromatic compounds had
distinctively pleasant smells. This property led to the term
\"aromatic\" for this class of compounds, and hence the property of
having enhanced stability due to delocalized electrons came to be called
\"aromaticity\".

## Definition

Aromaticity is a chemical property in which a conjugated ring of
unsaturated bonds, lone pairs, or empty orbitals exhibit a stabilization
stronger than would be expected by the stabilization of conjugation
alone. It can also be considered a manifestation of cyclic
delocalization and of resonance.

This is usually considered to be because electrons are free to cycle
around circular arrangements of atoms, which are alternately single- and
double-bonded to one another. These bonds may be seen as a hybrid of a
single bond and a double bond, each bond in the ring identical to every
other. This commonly-seen model of aromatic rings was developed by
Kekulé. The model for benzene consists of two resonance forms, which
corresponds to the double and single bonds\' switching positions.
Benzene is a more stable molecule than would be expected of
cyclohexatriene, which is a theoretical molecule.

## Theory

By convention, the double-headed arrow indicates that two structures are
simply hypothetical, since neither can be said to be an accurate
representation of the actual compound. The actual molecule is best
represented by a hybrid (average) of most likely structures, called
resonance forms. A carbon-carbon double bond is shorter in length than a
carbon-carbon single bond, but aromatic compounds are perfectly
geometrical (that is, not lop-sided) because all the carbon-carbon bonds
have the same length. The actual distance between atoms inside an
aromatic molecule is intermediate between that of a single and that of a
double bond.

A better representation than Lewis drawings of double and single bonds
is that of the circular π bond (Armstrong\'s inner cycle), in which the
electron density is evenly distributed through a π bond above and below
the ring. This model more correctly represents the location of electron
density within the aromatic molecule\'s overall structure. The single
bonds are sigma (σ) bonds formed with electrons positioned \"in line\"
between the carbon atoms\' nuclei. Double bonds consist of one \"in
line\" σ bond and another non-linearly arranged bond \-- a π-bond. The
π-bonds are formed from the overlap of atomic p-orbitals simultaneously
above and below the plane of the ring formed by the \"in line\" σ-bonds.

Since they are out of the plane of the atoms, π orbitals can interact
with each other freely, and thereby they become delocalized. This means
that, instead of being tied to one particular atom of carbon, each
electron can be shared by all the carbon atoms in an aromatic ring.
Thus, there are not enough electrons to form double bonds on all the
carbon atoms, but the \"extra\" electrons strengthen all of the bonds of
the ring equally.

## Characteristics

An aromatic compound contains a set of covalently-bound atoms with
specific characteristics:

1.  The molecule has to be cyclic
2.  A delocalized conjugated pi system, most commonly an arrangement of
    alternating single and double bonds (can sometimes include triple
    bonds if the geometry of the molecule permits)
3.  Coplanar structure, with all the contributing atoms in the same
    plane
4.  A number of pi delocalized electrons that is even, but not a
    multiple of 4. (This is known as Hückel\'s (4n+2)Π rule, where,n=
    0,1,2,3 and so on. Permissible numbers of π electrons include 2, 6,
    10, 14, and so on)
5.  Special reactivity in organic reactions such as electrophilic
    aromatic substitution and nucleophilic aromatic substitution

Whereas benzene is aromatic (6 electrons, from 3 double bonds),
cyclobutadiene is not, since the number of π delocalized electrons is 4,
which is not satisfied by any n integer value. The cyclobutadienide (2−)
ion, however, is aromatic (6 electrons). An atom in an aromatic system
can have other electrons that are not part of the system, and are
therefore ignored for the 4n + 2 rule. In furan, the oxygen atom is
sp^2^ hybridized. One lone pair is in the π system and the other in the
plane of the ring (analogous to C-H bond on the other positions). There
are 6 π electrons, so furan is aromatic.

Aromatic molecules typically display enhanced chemical stability,
compared to similar non-aromatic molecules. The circulating (that is,
delocalized) π electrons in an aromatic molecule generate significant
local magnetic fields that can be detected by NMR techniques. NMR
experiments show that protons on the aromatic ring are shifted
substantially further down-field than those on aliphatic carbons. Planar
monocyclic molecules containing 4n π electrons are called anti-aromatic
and are, in general, destabilized. Molecules that could be anti-aromatic
will tend to alter their electronic or conformational structure to avoid
this situation, thereby becoming merely non-aromatic.

Aromatic molecules are able to interact with each other in so-called π-π
stacking: the π systems form two parallel rings overlap in a
\"face-to-face\" orientation. Aromatic molecules are also able to
interact with each other in an \"edge-to-face\" orientation: the slight
positive charge of the substituents on the ring atoms of one molecule
are attracted to the slight negative charge of the aromatic system on
another molecule.

# Monosubstituted Benzenes

Benzene is a very important basic structure which is useful for analysis
and synthesis in most aspects of organic chemistry. The benzene ring
itself is not the most interesting or useful feature of the molecule;
which substitutents and where they are placed on the ring can be
considered the most critical aspect of benzene chemistry in general.

## Effects of Different Substituents

Depending on the type of substituent, atoms or groups of atoms may serve
to make the benzene ring either more reactive or less reactive. If the
atom or group makes the ring more reactive, it is called **activating**,
and if less, then it is called **deactivating**.

Generally, the terms activating and deactivating are in terms of the
reactions that fall into the category of Electrophilic Aromatic
Substitution (EAS). These are the most common forms of reactions with
aromatic rings. Aromatic rings can undergo other types of reactions,
however, and in the case of Nucleophilic Aromatic Substitution, the
activating and deactivating nature of substituents on the rings is
reversed. In EAS, a hydroxyl groups is strongly activating, but in
Nucleophilic Aromatic Substitution, a hydroxyl group is strongly
deactivating. But since EAS is the most common reaction with aromatic
rings, when discussing activation and deactivation, it\'s normally done
in terms of the EAS.

In addition to activating or deactivating, all groups and/or substituent
atoms on a benzene ring are **directing**. An atom or group may
encourage additional atoms or groups to add or not to add to certain
other carbons in relation to the carbon connected to the directing
group. This concept will be further discussed in the next chapter, but
when memorizing the groups below it is helpful to also memorize whether
it is O (ortho), M (meta) or P (para)-directing.

Another factor that heavily influences direction, however, is steric
hindrance. If, for example, you have a tert-butyl substituent on the
ring, despite the fact that it is ortho/para directing, the ortho
positions will be largely blocked by the tert-butyl group and thus
nearly all the product would be para.

## Activating Substituents

Activating substituents make benzene either slightly more reactive or
very much more reactive, depending on the group or atom in question. In
general, if one of the major heteroatoms (nitrogen or oxygen) is
*directly* attached to the carbon ring then the result is probably
activation. This is merely a rule of thumb, and many exceptions exist,
so it is best to memorize the groups listed below instead of counting on
a quick and dirty rule of thumb.

```{=html}
<center>
```
  ----------------------- -------------- ---------------
  **Group**               **Strength**   **Directing**
  -NH~2~, -NHR, -NRR      very strong    ortho/para
  -OH, -O^-^              very strong    ortho/para
  -NHCOCH~3~, -NHCOR      strong         ortho/para
  -OCH~3~, -OR            strong         ortho/para
  -CH~3~, -C~2~H~5~, -R   weak           ortho/para
  -C~6~H~5~               very weak      ortho/para
  ----------------------- -------------- ---------------

```{=html}
</center>
```
## Deactivating Substituents

A deactivating group is a functional group attached to a benzene
molecule that removes electron density from the benzene ring, making
electrophilic aromatic substitution reactions slower and more difficult
than they would be on benzene alone. As discussed above for activating
groups, deactivating groups may also determine the positions (relative
to themselves) on the benzene ring where substitutions take place, so
each deactivating group is listed below along with its directing
characteristic.

```{=html}
<center>
```
  ------------------ -------------- ---------------
  **Group**          **Strength**   **Directing**
  -NR~3~^+^          very strong    meta
  -NO~2~             very strong    meta
  -CF~3~, CCl~3~     very strong    meta
  -CN                strong         meta
  -SO~3~H            strong         meta
  -CO~2~H, -CO~2~R   strong         meta
  -COH, -COR         strong         meta
  -F                 weak           ortho/para
  -Cl                weak           ortho/para
  -Br                weak           ortho/para
                                    
  ------------------ -------------- ---------------

```{=html}
</center>
```
## Activation vs. Deactivation and ortho/para vs. meta directing

So why are some substituents activating or deactivating? Why are some
meta directing and others ortho/para directing? From the above tables,
it seems pretty clear there\'s a relationship.

There are primarily two effects that substituents impart on the ring
that affect these features:

1.  Resonance effects
2.  Inductive effects

### Resonance Effects

Let\'s first look at resonance effects. Resonance effects are the
ability or inability of a substituent to provide electrons to the ring
and enhance its resonance stability. To see this, we must first get a
basic understanding of the mechanism of Electrophilic Aromatic
Subsitution. We\'ll discuss EAS in more detail in the next section, but
some basics are called for here.

!Basic Mechanism of Electrophilic Aromatic
Substitution

As you can see in the image above, the electrophile is attacked by pi
electrons in the ring. The same carbon is now bonded to both the
hydrogen that was bonded to it and the electrophile. This in turn
creates a carbocation on the adjacent carbon, making the ring
non-aromatic. But aromatic rings like to remain aromatic. The
nucleophile which was previously bonded to the electrophile now attacks
the hydrogen, abstracting it from the ring and allowing the pi-bond to
re-form and returning the ring to its aromatic nature.

As we\'ve seen before in some other reactions, when a carbocation is
created as an intermediate, stability of that carbocation is crucial to
the reaction. This is the case in Electrophilic Aromatic Subsitution as
well.

So what is the effect of substituents on the ring?

!Resonance Stability of ortho, para, and meta
attacks.

Let\'s look at the situation above. In this case we have Phenol, a
benzene ring with an -OH (hydroxyl) group attached. When we nitrate the
ring with nitric acid in sulfuric acid (a reaction we\'ll discuss in the
next section), a nitro group is attached to the benzene ring.

There are 3 possible places for the nitro group to attach: An ortho,
meta, or para position. To understand the stability of the carbocation,
we need to look at the resonance structures for a given attack and see
what the results are.

The first resonance structure of the ortho attack results in a positive
charge on the carbon with the hydroxyl group. This happens to be the
most stable of the 3 resonance structures for an ortho attack because
the two negative electron pairs in the oxygen act to stabilize the
positive charge on the carbon. The other two resonance forms leave a
carbon with a hydrogen attached, to hold the positive charge. Hydrogen
can do nothing to stabilize the charge and thus, these are less stable
forms.

In the para attack situation, notice that the second resonance form also
puts a positive charge on the carbon with the hydroxyl group. This
provides for stability just as it does in the case of an ortho attack
and thus, the middle resonance form is very stable.

Finally, in the meta attack situation, all of the resonance forms result
in a positive charge on a carbon with only a hydrogen attached. None of
these is stable, and thus, meta attack with a hydroxyl group attached,
is a very small percentage of the product.

So the electron pairs in the oxygen act to stabilize the ortho and para
attacks.

### Inductive Effects

Now let\'s look at the inductive effects of deactivating substituents.
Let\'s imagine that, instead of a hydroxyl group, we instead have a
carbonyl group attached to the ring in its place. When a carbonyl is
attached, the ring is bonded to a carbon which in turn, is double-bonded
to an oxygen, the double-bonded oxygen is withdrawing electrons and this
inductive effect is felt on the ring, strongly deactivating its pi-bond
nature and putting a positive dipole on the carbon. Looking at the
resonance structures, this carbon, which already has some positive
nature is now given the added resonance of a positive charge, in the
case of ortho and para attacks. Positive plus positive equals more
positive and thus, less stable. There\'s no negative charge or negative
electron pair to stabilize this positive charge.

So in this case, not only is the entire ring less activated, but the
ortho and para attacks result in much more unstable carbocation
resonance forms. Hence, meta is the preferred position, but the overall
reaction is less active than plain benzene.

### Halides as the Exception

Notice that in the list of activating vs. deactivating substituents, the
activating ones are all ortho/para directing. In the deactivating
substituents, all but the halides, are meta directing. Why are halides
an exception?

Because halides are more electronegative than carbon, they induce a
positive dipole on the attached carbon and a negative dipole on their
own atom(inductive effect), and in accordance to the previous logic of
activating/deactivating substituents, deactivate the ring. However,
halides also possess lone pair electrons in their outer shell to share
with the ring, allowing the resonance structures with favored ortho/para
attacks versus meta attacks due to their poor resonance forms. In
essence, although halides do deactivate the ring to some extent, they
provide major resonance contributors due to the availability of their
lone pairs. Resonance structures usually trump the inductive effect.

## Detailed Effects of Substituents

We\'ve discussed some generalities about the effects of substituents and
even some specifics about certain ones, but let\'s look more closely at
the substituents and try to understand the details of what makes them
activating vs. deactivating.

-NH~2~, -NHR, and -NRR are all very strongly activating. Though nitrogen
is more electronegative than carbon, its ability to share a pair of
electrons greatly outweighs its electron withdrawing effect.

-OH and -O^-^ is similar in that it is even more electronegative than
nitrogen, but it has two pairs of electrons to share, which also greatly
outweighs its electron withdrawing effect.

-NHCOCH~3~ and -NHCOR are also strongly activating, but the inductive
effect of the double-bonded oxygen acts to make the nitrogen more
electron withdrawing, so they\'re not quite as activating as the other
-N substituents above.

-OCH~3~ and -OR are also still strongly activating, but less so, because
the electron density is shared on both sides of the oxygen.

-CH~3~ and -R in general provide some electron density sharing, but not
nearly as much as a pair of electrons. Thus their effect is only weakly
felt.

For deactivating groups we have:

-NO~2~, or nitro and -NR~3~^+^. The nitro group is very strongly
deactivating because of its resonance structure. The nitro group has two
resonance forms: O=N^+^-O^-^ and O^-^-N^+^=O. Both of these forms leave
a full positive charge on the nitrogen making it completely unable to
help stabilize the positive carbocation intermediate. The same applies
to -NR~3~^+^.

-CF~3~ and -CCl~3~ both have an inductive electronegative effect of 3
halides, but with no electrons to share with the ring, leaving them also
very strongly deactivating.

-CN has a triple bond between the carbon and nitrogen with a resonance
form of a double bond between the carbon and nitrogen and a positive
charge on the carbon, meaning that between the electronegativity of the
nitrogen and positively charged carbon in the resonance form, it
destabilizes the carbocation and offer no electrons to the ring.

-SO~3~, -COR, -CO~2~R - all of these have electronegative oxygens giving
the carbon a positive partial charge and providing no electrons for
stability on the ring.

-F, -Cl, -Br, all have a similar effect. They are electronegative and
deactivate the ring, but have electrons to share that, to some degree,
makes up for it, allowing the ortho/para direction. But to understand
their effects better, you need to look at them in terms of their
placement on the periodic chart. Florine is the most electronegative
element and it\'s very small and thus very close to the carbon it\'s
bonded to. This gives its electromagnetic influence a stronger
deactivating character. Chlorine is less electronegative, but it\'s also
larger and thus further away from the carbon, making it harder for it to
share its electrons. And so on.

# Polysubstituted Benzenes

Unsubstituted benzene is seldom encountered in nature or in the
laboratory, and you will find in your studies that most often benzene
rings are found as parts of other, more complicated molecules. In order
for benzene to react in most situations, it gains or loses some
functionality dependent on which functional groups are attached.
Although the simplest case is to work with benzene that has only one
functional group, it is also essential to understand the interactions
and competitions between multiple functional groups attached to the same
benzene ring.

When there is more than one substituent present on a benzene ring the
spatial relationship between groups becomes important, which is why the
arene substitution patterns **ortho**, **meta** and **para** were
devised. For example three isomers exist for the molecule cresol because
the methyl group and the hydroxyl group can be placed either next to
each other (*ortho*), one position removed from each other (*meta*) or
two positions removed from each other (*para*). Where each group
attaches is most often a function of which order they were attached in,
due to the activating/deactivating and directing activities of
previously attached groups.

![](Cresol_isomers.PNG "Cresol_isomers.PNG")

## Competition Between Functional Groups

When a ring has more than one functional group, the effects of the
groups are combined and their total effect must be taken into account.
In general, effects are summed. For example, toluene (methylbenzene) is
weakly activated. But p-nitrotoluene has both a methyl group and a nitro
group. The methyl group is weakly activating and the nitro is pretty
strongly deactivating, so overall, the group is very deactivated. In
terms of direction, however, both substitutents agree on the direction.
The methyl group is ortho/para directing. The nitro group occupies the
para position, so the methyl will now want just ortho direction. The
nitro group is meta directing. The positions meta to the nitro are also
ortho to the methyl, so this works out and further substituents will be
almost entirely in the positions ortho to the methyl group.

If two functional groups disagree on direction, the more activating
group is the one that controls direction. That is, if you had
m-nitrotoluene, most of your product would tend to be ortho/para to the
toluene and not meta to the nitro, despite the nitro having a stronger
influence on overall activation.

## Naming Conventions

When a benzene ring has more than one substituent group attached, the
location of all of the groups not directly attached to carbon number one
must be explicitly declared. This is done by listing the number of the
carbon atom where the group is attached, followed by a hyphen and the
group\'s name. The carbon atoms of the benzene ring should be numbered
in order of previously established precedence, i.e., a bromine would
take precedence over a nitro group, which itself would take precedence
over an alcohol or alkane group. The names of the groups should be
listed in alphabetical order, i.e. \"2-methyl-5-nitrobenzaldehyde.\"


------------------------------------------------------------------------

\<\< Dienes \| Aromatics \|
Aromatic
reactions\>\>

