# 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}
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  ----------------------- -------------- ---------------
  **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
  ----------------------- -------------- ---------------

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## 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.

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  ------------------ -------------- ---------------
  **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

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

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## 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\>\>


# Organic Chemistry/Aromatic reactions

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\<\< Aromatics \| Aromatic
reactions \| Ketones and
aldehydes\>\>

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The lack of reactivity of arenes is notable when compared to the
reactivities of typical compounds containing multiple conjugated double
bonds. For example, 1,3,5-hexatriene is much more reactive than hexane,
hexene, or any hexadiene. Benzene is much less reactive than any of
these. Any of the alkenes will be readily converted to alcohols in the
presence of a dilute aqueous solution of H~2~SO~4~, but benzene is
inert. Similarly, alkenes react readily with halogens and hydrogen
halides *by addition* to give alkyl halides, whereas halogens react with
benzene *by substitution* and only in the presence of a catalyst.
KMnO~4~ or chromic acid solutions (typically CrO~3~ or K~2~Cr~2~O~7~)
cleave the double bonds of alkenes, giving ketones or carboxylic acids,
but do not react at all with benzene. Because of the stability of
aromatic compounds, however, reactions involving these have extremely
high activation energies, for passage to the transition state
necessarily requires disruption of the aromatic system, resulting in a
temporary loss of aromatic stabilization energy. Instead of reacting by
addition and elimination, as nonaromatic compounds often do, benzene and
its derivatives usually react by electrophilic aromatic substitution.

# Redox

## Birch reduction

The **Birch reduction**[^1] is the reduction of aromatic compounds by
sodium in liquid ammonia. It is attributed to the chemist Arthur
Birch. The reaction product is a
1,4-cyclohexadiene. The metal can also be lithium or potassium and the
hydrogen atoms are supplied by an alcohol such as ethanol or
tert-butanol.

!Birch reduction of aromatic
rings

The first step of a Birch reduction is a one-electron reduction of the
aromatic ring to a radical anion. Sodium is oxidized to the sodium ion
Na^+^. This intermediate is able to dimerize to the dianion. In the
presence of an alcohol the second intermediate is a free radical which
takes up another electron to form the carbanion. This carbanion
abstracts a proton from the alcohol to form the cyclohexadiene.
center\|Birch reduction reaction
mechanism

In the presence of an alkyl halide, the carbanion can also engage in
nucleophilic substitution with carbon-carbon bond formation. In
substituted aromatics an electron withdrawing substituent such as a
carboxylic acid stabilizes a carbanion and the least-substituted alkene
is generated. With an electron donating substituent, the opposite effect
occurs. The non-conjugated 1,4-addition product is preferred over the
conjugated 1,3-diene which is explicable by the principle of least
motion. Experimental alkali
metal alternatives that are safer to handle, such as the M-SG reducing
agent, also exist.

## Oxidation of Benzene in the Human Body

Because benzene is nonpolar, it cannot be passed in urine, and will
remain in the body until oxidized. Benzene itself is not dangerous to
health, but in order to be passed, it is oxidized by cytochrome P-450 in
the liver. This produces benzene oxide, a highly teratogenic and
carcinogenic compound. Benzene has been replaced by toluene as an
industrial solvent, because toluene can be oxidized to benzoic acid,
which is mostly harmless to health, and is quickly passed. The
decomposition of benzoic acid into benzene and carbon dioxide in soda
pop has become an issue recently.

# Nucleophilic Aromatic Substitution

A nucleophilic substitution is a substitution reaction in organic
chemistry in which the nucleophile displaces a good leaving group, such
as a halide on an aromatic ring. In order to understand this type of
reaction, it is important to recognize which chemical groups are good
leaving groups and which are not.

## Leaving Groups

A leaving group can probably most simply be described as an atom or
molecule that detaches from an organic molecule. The ability for a
functional group to leave is called *lability*. Leaving groups affect
the intrinsic reactivity of the molecule as a whole, but only until,
quite naturally, they actually leave.

The lower the p*K*~a~ of the conjugate acid for a given leaving group,
the better that leaving group is at actually leaving. This is because
such groups can easily stabilize any developing negative charge and
without stabilization, a leaving group will actually become a
nucleophile causing the reaction to cycle pointlessly between attached
and detached forms. (This explains why a strong base is nearly always a
poor leaving group.)

In room temperature water, the sequence of lability is:

-   *Less lability*
-   amine/amide (NH~2~^-^)
-   alkoxy/alkoxide (RO^-^)
-   hydroxyl/hydroxide (HO^-^)
-   carboxylate (RCOO^-^)
-   fluoro/fluoride (F^-^)
-   water (H~2~O)
-   chloro/chloride (Cl^-^)
-   bromo/bromide (Br^-^)
-   iodo/iodide (I^-^)
-   azide (N~3~^-^)
-   thiocyanate (SCN^-^)
-   nitro/nitrite (NO~2~)
-   cyano/cyanide (CN^-^)
-   *Greater Lability*

## Rate of Reaction

The better a leaving group, the faster a nucleophilic reaction will
occur. This is demonstrated by comparisons of the kinetics between
halogenalkanes, where the bromides dissociate more quickly than the
chlorides, but the iodides dissociate more rapidly than either of the
other two. This is because the bond between the halogen and its nearest
carbon must be broken at some point for a nucleophilic substitution to
take place. A bond between iodine and carbon is far more polarizable
than a bond between carbon and chlorine, for example, due to iodine\'s
relatively large size and relatively large number of ionizable
electrons. The fact that water is a far better leaving group than
hydroxide also has the important consequence that the rate of a reaction
in which hydroxide leaves is increased dramatically by the presence of
an acid, for hydroxide is then protonated to water, a much weaker
nucleophile.

## Types of Reactions

There are three nucleophilic substitution mechanisms commonly
encountered with aromatic systems, the SNAr (addition-elimination)
mechanism, the benzyne mechanism and the free radical SRN1 mechanism.
The most important of these is the SNAr mechanism, where electron
withdrawing groups activate the ring towards nucleophilic attack, for
example if there are nitro functional groups positioned ortho or para to
the halide leaving group. It is not generally necessary to discuss these
types in detail within the context of an introductory organic chemistry
course.

# Electrophilic Aromatic Substitution

**Electrophiles** are particles with a deficiency of electrons.
Therefore they are likely to react with substances that have excess
electrons. Aromatic compounds have increased electron density in the
form of delocalized π-orbitals.

## Step 1: Formation of a π-complex

At first, the electrophile interacts with the delocalized orbitals of
the aromatic ring and a π-complex is formed.

![](Electrophilic_substitution_pi_complex.png "Electrophilic_substitution_pi_complex.png")

No chemical bonds are formed at this stage. Evidence of the formation of
a π-complex as an intermediate state has been found for some reactions,
but not for all, since the chemical interaction in π-complexes is very
weak.

## Step 2: Formation of a σ-complex

After the π-complex is formed, in the presence of an electron acceptor
another complex is formed - the σ-complex. It is a cationic species, an
intermediate that lacks aromatic properties, but its four π-electrons
are delocalized across the ring, which stabilizes the cation somewhat,
sometimes allowing its isolation. An example would be the salt mesityl
fluoroborate, which is stable at low temperatures, and is prepared by
the reaction of mesitylene (1,3,5-trimethylbenzene) with fluoroboric
acid (BF~3~/HF); the cation of this salt is protonated mesitylene.
σ-complexes are also known as *Wheland intermediates*.

## Step 3: Formation of a Substituted product

At the next stage the σ-complex decomposes, freeing a hydrogen cation
and forming the product of substitution.

![](Electrophilic_substitutiom_sigma_complex.png "Electrophilic_substitutiom_sigma_complex.png")

### Electrophilic aromatic halogenation

!Electrophilic aromatic substitution of
benzene{width="450"}
Another important reaction of benzene is the electrophilic substitution
of halides, a specific type of electrophilic aromatic substitution.
These reactions are very useful for adding substituents to an aromatic
system. The rates of the reactions increase with the electrophilicity of
the halogen: hence, fluorination in this manner is too rapid and
exothermic to be practical, whereas iodine requires the most vigorous
conditions. Chlorination and bromination are the most often practiced in
the lab of the four possible halogenations. Halobenzenes are used for
pesticides, as well as the precursors to other products. Many COX-2
inhibitors contain halobenzene subunits.

Some highly activated aromatic compounds, such as phenol and aniline,
are reactive enough to undergo halogenation without a catalyst, but for
typical benzene derivatives (and benzene itself), the reactions are
extremely slow at room temperature in the absence of a catalyst.
Usually, Lewis acids are used as catalysts, which work by helping to
polarize the halogen-halogen bond, thus decreasing the electron density
around one halogen atom, making it more electrophilic. The most common
catalysts used are either Fe or Al, or their respective chlorides and
bromides (+3 oxidation state). Iron(III) bromide and iron(III) chloride
lose their catalytic activity if they are hydrolyzed by any moisture
present, including atmospheric water vapor. Therefore, they are
generated *in situ* by adding iron fillings to bromine or chlorine.
Iodination is carried out under different conditions: periodic acid is
often used as a catalyst. Under these conditions, the I^+^ ion is
formed, which is sufficiently electrophilic to attack the ring.
Iodination can also be accomplished using a diazonium reaction.
Fluorination is most often done using this technique, as the use of
fluorine gas is inconvenient and often fragments organic compounds.

Halogenation of aromatic compounds differs from the additions to alkenes
or the free-radical halogenations of alkanes, which do not require Lewis
acid catalysts. The formation of the arenium ion results in the
temporary loss of aromaticity, the overall result being that the
reaction\'s activation energy is higher than those of halogenations of
aliphatic compounds.

Halogenation of phenols is faster in polar solvents due to the
dissociation of phenol, because the phenoxide (-O^-^) group is more
strongly activating than hydroxyl itself.

### Electrophilic aromatic sulfonation

Aromatic sulfonation is an organic reaction in which a hydrogen atom on
an arene is replaced by a sulfonic acid functional group in an
electrophilic aromatic substitution.

The electrophile of such a reaction is sulfur trioxide (SO~3~), which
can be released from oleum (also known as fuming sulfuric acid),
essentially sulfuric acid in which gaseous sulfur trioxide has been
dissolved.

In contrast to aromatic nitration and other electrophilic aromatic
substitutions, aromatic sulfonation is reversible. Sulfonation takes
place in strongly acidic conditions, and desulfonation can occur on
heating with a trace of acid. This also means that thermodynamic, rather
than kinetic, control can be achieved at high temperatures. Hence,
directive effects are not expected to play a key role in determining the
proportions of isomeric products of high-temperature sulfonation.

Aromatic sulfonic acids can be intermediates in the preparation of dyes
and many pharmaceuticals. Sulfonation of aniline produces
p-aminobenzenesulfonic acid or sulfanilic acid, which is a zwitterionic
compound with an unusually high melting point. The amide of this
compound and related compounds form a large group of sulfa drugs (a type
of antibiotic).

Overall reaction: ArH + SO~3~ → ArSO~3~H

### Electrophilic aromatic nitration

Nitration occurs with aromatic organic compounds via an electrophilic
substitution mechanism involving the attack of the electron-rich benzene
ring by the nitronium (nitryl) ion. Benzene is commonly nitrated by
refluxing with a mixture of concentrated sulfuric acid and concentrated
nitric acid at 50°C. The sulfuric acid is regenerated and hence acts as
a catalyst.

Selectivity is always a challenge in nitrations. Fluorenone nitration is
selective and yields a tri-nitro compound or tetra-nitro compound by
tweaking reaction conditions just slightly. Another example of
trinitration can be found in the synthesis of phloroglucinol. Other
nitration reagents include nitronium tetrafluoroborate which is a true
nitronium salt. This compound can be prepared from hydrogen fluoride,
nitric acid and boron trifluoride. Aromatic nitro compounds are
important intermediates for anilines; the latter may be readily prepared
by action of a reducing agent.

Overall reaction: ArH + HNO~3~ → ArNO~2~ + H~2~O

### Friedel-Crafts alkylation

!Friedel-Crafts alkylation of benzene with methyl
chloride{width="400"}

The Friedel-Crafts reactions, discovered by French alkaloid chemist
Charles Friedel and his American partner, James Crafts, in 1877, is
either the alkylation or acylation of aromatic compounds catalyzed by a
Lewis acid. They are very useful in the lab for formation of
carbon-carbon bonds between an aromatic nucleus and a side chain.

#### Source of electrophile

Friedel-Crafts alkylation is an example of electrophilic substitution in
aromatic compounds. The electrophile is formed in the reaction of an
alkyl halide with a Lewis acid. The Lewis acid polarizes the alkyl
halide molecule, causing the hydrocarbon part of it to bear a positive
charge and thus become more electrophilic.

CH~3~---Cl + AlCl~3~ → CH~3~^+^ + AlCl~4~^−^

or

CH~3~Cl + AlCl~3~ → CH~3~^δ+^Cl^+^Al^−^Cl~3~

(The carbon atom has a slight excess of positive charge, as the
electronegative chlorine atom draws electron density towards itself. The
chlorine atom has a positive charge, as it has formed a sub-ordinate
bond with the aluminium atom. In effect, the Cl atom has lost an
electron, while the Al atom has gained an electron. Therefore, the Al
atom has a negative charge.)

#### Mechanism of alkylation

The polarized, electrophilic molecule then seeks to saturate its
electron deficiency and forms a π-complex with the aromatic compound
that is rich in π-electrons. Formation a π-complex does not lead to loss
of aromaticity. The aromaticity is lost however in the σ-complex that is
the next stage of reaction. The positive charge in the σ-complex is
evenly distributed across the benzene ring.

C~6~H~6~ + CH~3~^+^ → C~6~H~6~^+^Br → C~6~H~5~Br + H^+^

The σ-complex C~6~H~6~^+^Br can be separated (it is stable at low
temperatures), while the π-complex can not.

#### Restrictions

-   Deactivating functional groups, such as nitro (-NO~2~), usually
    prevent the reaction from occurring at any appreciable rate, so it
    is possible to use solvents such as nitrobenzene for Friedel-Crafts
    alkylation.

```{=html}
<!-- -->
```
-   Primary and secondary carbocations are much less stable than
    tertiary cations, so rearrangement typically occurs when one
    attempts to introduce primary and secondary alkyl groups onto the
    ring. Hence, Friedel-Crafts alkylation using n-butyl chloride
    generates the n-butylium cation, which rearranges to the t-butyl
    cation, which is far more stable, and the product is exclusively the
    t-butyl derivative. This may, in some cases, be circumvented through
    use of a weaker Lewis acid.

```{=html}
<!-- -->
```
-   The Friedel-Crafts reaction can not be used to alkylate compounds
    which are sensitive to acids, including many heterocycles.

```{=html}
<!-- -->
```
-   Another factor that restricts the use of Friedel-Crafts alkylation
    is polyalkylation. Since alkyl groups have an activating influence,
    substituted aromatic compounds alkylate more easily than the
    original compounds, so that the attempted methylation of benzene to
    give toluene often gives significant amounts of xylene and
    mesitylene. The usual workaround is to acylate first (see the
    following sections) and then reduce the carbonyl group to an alkyl
    group.

### Friedel-Crafts acylation

!Friedel-Crafts acylation of benzene by acetyl
chloride{width="300"}

Friedel-Crafts acylation, like Friedel-Crafts alkylation, is a classic
example of electrophilic substitution.

#### Source of electrophile

Reacting with Lewis acids, anhydrides and chloranhydrides of acids
become strongly polarized and often form acylium cations.

RCOCl + AlCl~3~ → RC^+^O + AlCl~4~^-^

#### Mechanism of acylation

The mechanism of acylation is very similar to that of alkylation.

C~6~H~6~ + RC^+^O → C~6~H~6~---CO---R + H^+^

The ketone that is formed then forms a complex with aluminum chloride,
reducing its catalytic activity.

C~6~H~6~---CO---R + AlCl~3~ → C~6~H~6~---C^+^(R)---O---Al^−^Cl~3~

Therefore, a much greater amount of catalyst is required for acylation
than for alkylation.

#### Restrictions

-   Although no isomerisation of cations happens, due to the reasonance
    stabilization provided by the acylium ion, certain cations may lose
    CO and alkylation will occur instead of acylation. For example, an
    attempt to add pivalyl (neopentanoyl) to an aromatic ring will
    result in loss of CO from the cation, which then results in the
    t-butyl derivative being formed.
-   Acidophobic aromatic compounds, such as many heterocycles can\'t
    exist in the presence of both Lewis acids and anhydrides.
-   Formyl chloride is unstable and cannot be used to introduce the
    formyl group onto a ring through Friedel-Crafts acylation. Instead,
    the Gattermann-Koch reaction is often used.

#### Applications

Friedel-Crafts acylation is used, for example, in the synthesis of
anthraquinone from benzene and phtalic anhydride.

In laboratory synthesis Friedel-Crafts acylation is often used instead
of alkylation in cases where alkylation is difficult or impossible, such
as synthesis of monosubstituted alkylbenzenes.

# External links

-   reduction of o-anisic acid to
    2-heptyl-2-hexenone in Organic
    Syntheses
    Article
-   reduction of naphthalene to
    1,4,5,8-Tetrahydronaphthalene (isotetralin) in Organic
    Syntheses
    Article.
-   reduction of o-xylene to
    1,2-Dimethyl-1,4-cyclohexadiene in Organic
    Syntheses
    Article
-   reduction of benzoic acid to
    2,5-Cyclohexadiene-1-carboxylic acid in Organic
    Syntheses
    Article

# References

```{=html}
<references/>
```
```{=html}
<div style="text-align: center;">
```
\<\< Aromatics \| Aromatic
reactions \| Ketones and
aldehydes\>\>

```{=html}
</div>
```

[^1]: \* A. J. Birch, J. Chem. Soc. **1944**, 430.


# Organic Chemistry/Ketones and aldehydes

Aldehydes (![](Aldehyde2.png "Aldehyde2.png"){width="50"}) and ketones
(![](Ketone-general.svg "Ketone-general.svg"){width="50"}) are both
carbonyl compounds. They are organic compounds in which the carbonyl
carbon is connected to conyl carbon satisfied by a H atom, while a
ketone has both its vacancies satisfied by carbon.

## Naming Aldehydes and Ketones

**Ketones** are named by replacing the**-e** in the alkane name with
**-one**. The **carbon chain** is numbered so that the ketone carbon,
called **the carbonyl group**, gets the lowest number. For example,
![](Butanone-structure-skeletal.png "Butanone-structure-skeletal.png"){width="50"}
would be named 2-butanone because the root structure is butane and the
ketone group is on the number two carbon.

Alternatively, functional class nomenclature of ketones is also
recognized by IUPAC, which is done by naming the substituents attached
to the carbonyl group in alphabetical order, ending with the word
ketone. The above example of 2-butanone can also be named ethyl methyl
ketone using this method.

If two ketone groups are on the same structure, the ending **-dione**
would be added to the alkane name, such as heptane-2,5-dione.

**Aldehydes** replace the**-e** ending of an alkane with **-al** for an
aldehyde. Since an aldehyde is always at the carbon that is numbered
one, a number designation is not needed. For example, the aldehyde of
pentane would simply be pentanal.

The **-CH=O group of aldehydes** is known as a formyl group. When a
formyl group is attached to a ring, the ring name is followed by the
suffix **\"carbaldehyde\"**. For example, a hexane ring with a formyl
group is named cyclohexanecarbaldehyde.

## Boiling Points and Bond Angles

**Aldehyde and ketone** polarity is characterized by the high dipole
moments of their carbonyl group, which makes them rather polar
molecules. They are more polar than alkenes and ethers, though because
they lack hydrogen, they cannot participate in hydrogen bonding like
alcohols, thus making their relative boiling points higher than alkenes
and ethers, yet lower than alcohols.

Typical bond angles between the carbonyl group and its substituents show
minor deviations from the trigonal planar angles of 120 degrees, with a
slightly higher bond angle between the O=C-R bond than the R-C-R bond on
the carbonyl carbon (with R being any substituent).

## Preparing Aldehydes and Ketones

### Preparing Aldehydes

#### Partial oxidation of primary alcohols to aldehydes

This reaction uses pyridinium chlorochromate (PCC) in the absence of
water (if water is present the alcohol will be oxidized further to a
carboxylic acid). ![](alcohol-aldehyde.PNG "alcohol-aldehyde.PNG")

#### From fatty acids

`<chem>`{=html}Ca(COOH)2 -\>\[\\Delta\] HCHO + CaCO3 `</chem>`{=html}

`<chem>`{=html}(CH3COO)2Ca -\>\[\\Delta\] CH3COCH3 +
CaCO3`</chem>`{=html}

`<chem>`{=html}(CH3COO)2Ca + (HCOO)2Ca -\> CH3CHO`</chem>`{=html}

#### Stephen reduction

`<chem>`{=html}R-CN + SnCl2 + HCl -\> R-CH=NH2+Cl- -\>\[H\^+/H_2O\]
R-CHO `</chem>`{=html}

Here sulfur is used as a poisoner so that aldehyde formed doesn\'t get
oxidised to the carboxylic acid. See the Wikipedia
article for more detail.

#### Rosenmund reaction

`<chem>`{=html}R-COCl + Pd + BaSO4 + S -\> R-CHO`</chem>`{=html}

(For solvent xylene is used)

### Preparing Ketones

#### From Grignard reagents

`<chem>`{=html}RCOOR\' + R\'MgX -\>RCOR + R\'OH`</chem>`{=html}

`                    R'            R'      OH  `\
`                    |             |       |`

`<chem>`{=html}RC=O + R\'MgX -\> R-CO-MgX -\> R-C-OH +
Mg-X`</chem>`{=html}

`|                   |             |  `\
`O-R'                OR'           OR'`

#### From nitriles

RCN + R\'MgX \-\-\--\> RCOR\'(after hydrolysis) HCN does not react with
RMgX as HCN has acidic hydrogen which results in RH being formed.

#### From gem dihalides

RCCl~2~R + strong base \-\-\--\> RCOR

#### Oppenaur oxidation

Reagent is Aluminium tert. butoxide solvent is acetone

ROH + ACETONE \-\-\--\> Ketone + isopropyl alcohol this oxidation does
not affect double bonds in this oxidation ketone act as a oxidizing
agent this is exact opposite to merrwine pondroff reduction

#### Friedel-Crafts acylation of aromatic compounds

An aromatic ring reacts with a carboxylic acid chlorine (RCOCl) in the
presence of AlCl~3~ to form an aryl ketone of the form ArCOR.

#### Oxidation of secondary alcohols to ketones

A secondary alcohol can be oxidised into a ketone using acidified
potassium dichromate(VI) and heating under reflux.

The orange dichromate(VI) ion, Cr2O72-, is reduced to the green Cr3+(aq)
ion.

### Ozonolysis of alkenes

It is a reaction in which the double bond is completely broken and the
alkene molecule converted into two smaller molecules.

!A generalized scheme of
ozonolysis{width="350"}
Ozonolysis (cleavage \"by ozone) is carried out in two stages: first,
addition of ozone to the double bond to form an ozonide ; and second,
hydrolysis of the ozonide to yield the cleavage products.

Ozone gas is passed into a solution of the alkene in some inert solvent
like carbon tetrachloride; evaporation of the solvent leaves the ozonide
as a viscous oil. This unstable, explosive compound is not purified, but
is treated directly with water, generally in the presence of a reducing
agent. If oxidising reagent is used, aldehyde or ketone if oxidisable
can further oxidise into carboxylic acid which is not the case with
reducing agents

In the cleavage products a doubly-bonded oxygen is found attached to
each of the originally doubly-bonded carbons.

The function of the reducing agent, which is frequently zinc dust, is to
prevent formation of hydrogen peroxide, which would otherwise react with
the aldehydes and ketones. (Aldehydes, RCHO, are often converted into
acids,rCOOH, for ease of isolation.)

##### Mechanism

The alkene and ozone form an intermediate molozonide in a 1,3-dipolar
cycloaddition. Next, the molozonide reverts to its corresponding
carbonyl oxide (also called the Criegee intermediate or Criegee
zwitterion) and aldehyde or ketone in a retro-1,3-dipolar cycloaddition.
The oxide and aldehyde or ketone react again in a 1,3-dipolar
cycloaddition or produce a relatively stable ozonide intermediate (a
trioxolane) !The reaction mechanism of
ozonolysis.{width="600"}

### Hydration of alkynes

Water is added to an alkyne in a strong acid. The strong acid used is
sulfuric acid and mercuric acid.

## Keto-enol tautomerism

In the presence of an acid (H+) or a base (OH-), the aldehyde or ketone
will form an equilibrium with enols, in which the double bond of the
carbonyl group migrates to form double bond between the carbonyl and the
alpha (α) carbon.

In the presence of an acid, protonation of the oxygen group will occur,
and water will abstract an alpha (α) hydrogen.

In the presence of a base, deprotonation of the alpha hydrogen will
occur, and a hydrogen from water will be abstracted by the carbonyl
oxygen.

This is an important feature of ketone and aldehydes, and is known as
the *keto-enolic tautomery* or *keto-enol tautomerism*, i.e. the
equilibrium of carbonyl compounds between two forms.

It must be stressed that the *keto* and the *enol* forms are **two
distinct compounds**, not isomers. They are known as tautomers of each
other. The presence of α-hydrogen is necessary for this equilibrium:
those compounds not possessing it are called *non-enolizable* ketones.

!Mechanism of enol-keto
tautomerism

## Reactions of Aldehydes and Ketones

### Reactions with the carbonyl carbon

Since aldehydes and ketones contain a polar carbonyl group, the
partially positive carbon atom can act as an electrophile. Strong and
weak nucleophiles are able to attack this carbonyl carbon, resulting in
a net addition to the molecule.

#### Nucleophilic addition

With cyanide, nucleophilic addition occur to give a hydroxynitrile:

RR\'C=O + CN^-^ + H^+^ → RR\'COHCN

e.g. propanone → 2-hydroxymethylpropanonitrile

### Reactions with the carbonyl oxygen

The partially negative oxygen can act as a nucleophile, or be attacked
by electrophiles.

### Oxidation

Using a strong oxidizing agent such as the Tollens\' Reagent (Ag~2~O in
aqueous ammonia) acidified dichromate, Benedict\'s/Fehling\'s reagent
(essentially alkaline Cu^+2^); aldehydes but not ketones may be oxidized
into carboxylic acids. This is one way to test for the presence of an
aldehyde in a sample compound: an aldehyde will become a carboxylic acid
when reacted with Tollens\' reagent, but a ketone will not react. when
aldehydes react with fehling solution a red precipitate is obtained (due
to formation of Cu~2~O) .

## Inductive Effect and Greek letter assignment

The carbonyl group is very electron withdrawing, and adjacent carbons
are effected by induction. Using the carbonyl group as a reference,
adjacent carbons are named using Greek letters in order of closeness to
the carbonyl group. Alpha (α) carbons are directly attached to the
carbonyl group, beta (β) carbons are connected to alpha carbons, gamma
(γ) to beta (β), and so on.

Due to the inductive effect of the partial positive especially prone to
removal.

id:Kimia Organik/Keton dan
aldehida


# Organic Chemistry/Carboxylic acids

A carboxylic acid is characterized by the presence of the *carboxyl
group* -COOH. The chemical reactivity of carboxylic acids is dominated
by the very positive carbon, and the resonance stabilization that is
possible should the group lose a proton. These two factors contribute
both to acidity and to the group\'s dominant chemical reaction:
nucleophilic substitution.

# Preparation

1\) from alkenes

`       R-CH=CHR + KMnO`~`4`~` + OH`^`-`^` + Heat----> 2RCOOH`\
`       `

2\) from ROH

`       RCH`~`2`~`OH + OXIDIZING AGENT ----> RCOOH`

Aliphatic carboxylic acids are formed from primary alcohols or aldehydes
by reflux with potassium dichromate (VI) acidified with sulphuric acid.

3\) from toluene etc.

`       toluene + KMnO`~`4`~` ----> benzoic acid  `

Alkyl benzenes (methyl benzene, ethyl benzene, etc) react with potassium
manganate (VII) to form benzoic acid. All alkyl benzenes give the same
product, because all but one alkyl carbon is lost.

No acidification is needed. The reaction is refluxed and generates KOH.
The benzoic acid is worked up by adding a proton source (such as HCl).

4\) from methyl ketones

`       RCOCH`~`3`~` + NaOH + I-I ----> RCOO`^`-`^` + CHI`~`3`~

5\) from Grignard reagents

`       RMgX + O=C=O ----> RCOOMgX `\
`       RCOOMgX + HOH ----> RCOOH + MgX(OH)`

# Properties

## Nomenclature

The systematic IUPAC nomenclature for carboxylic acids requires the
longest carbon chain of the molecule to be identified and the -e of
alkane name to be replaced with -oic acid.

The traditional names of many carboxylic acids are still in common use.

  formula           IUPAC name               traditional name
  ----------------- ------------------------ ------------------
  HCOOH             methanoic acid           formic acid
  CH~3~-COOH        ethanoic acid            acetic acid
  CH~3~CH~2~-COOH   propanoic acid           propionic acid
  CH~2~=CH-COOH     propenoic acid           acrylic acid
  CF~3~-COOH        trifluoroethanoic acid

  : **Nomenclature of carboxylic acids**

The systematic approach for naming dicarboxylic acids (alkanes with
carboxylic acids on either end) is the same as for carboxylic acids,
except that the suffix is -dioic acid. Common name Nomenclature of
dicarboxylic acids is aided by the acronym OMSGAP (Om\'s Gap), where
each letter stands for the first letter of the first seven names for
each dicarboxylic acid, starting from the simplest.

  formula                              IUPAC name          traditional name
  ------------------------------------ ------------------- ------------------
  HOOCCOOH                             Ethanedioic acid    Oxalic acid
  HOOCCH~2~-COOH                       propanedioic acid   Malonic acid
  HOOCCH~2~CH~2~-COOH                  butanedioic acid    Succinic acid
  HOOCCH~2~CH~2~CH~2~-COOH             pentanedioic acid   Glutaric acid
  HOOCCH~2~CH~2~CH~2~CH~2~-COOH        hexanedioic acid    Adipic acid
  HOOCCH~2~CH~2~CH~2~CH~2~CH~2~-COOH   heptanedioic acid   Pimelic acid

  : **Nomenclature of dicarboxylic acids**

## Acidity

Most carboxylic acids are weak acids. To quantify the acidities we need
to know the pKa values: The pH above which the acids start showing
mostly acidic behaviour: Ethanoic acid: 4.8 Phenol: 10.0 Ethanol: 15.9
Water: 15.7

  acid                     formula           *pK*~a~
  ------------------------ ----------------- ---------
  methanoic acid           H-COOH            3.75
  ethanoic acid            CH~3~-COOH        4.75
  propanoic acid           CH~3~CH~2~-COOH   4.87
  propenoic acid           CH2=CH-COOH       4.25
  benzoic acid             C~6~H~5~-COOH     4.19
  trifluoroethanoic acid   CF~3~-COOH        0.3
  phenol                   C~6~H~5~-OH       10.0
  ethanol                  CH~3~CH~2~-OH     15.9
  water                    H~2~O             15.7

  : **Acidity of carboxylic acids in water**

Data from CRC Handbook of Chemistry & Physics, 64th edition, 1984
D-167-8 Except <http://en.wikipedia.org/wiki/Trifluoroacetic_acid>

Clearly, the carboxylic acids are remarkably acidic for organic
molecules. Somehow, the release of the H^+^ ion is favoured by the
structure. Two arguments: The O-H bond is polarised by the removal of
electrons to the carbonyl oxygen. The ion is stabilised by resonance:
the carbonyl oxygen can accept the charge from the other oxygen. The
acid strength of carboxylic acid are strongly modulated by the moiety
attached to the carboxyl. Electron-donor moiety decrease the acid
strength, whereas strong electron-withdrawing groups increase it.

# Reactions

## Acid Chloride Formation

Carboxylic acids are converted to acid chlorides by a range of reagents:
SOCl~2~, PCl~5~ or PCl~3~ are the usual reagents. Other products are HCl
& SO~2~, HCl & POCl~3~ and H~3~PO~3~ respectively. The conditions must
be dry, as water will hydrolyse the acid chloride in a vigorous
reaction. Hydrolysis forms the original carboxylic acid.

CH~3~COOH + SOCl~2~ → CH~3~COCl + HCl + SO~2~

C~6~H~5~COOH + PCl~5~ → C~6~H~5~COCl + HCl + POCl~3~

3 CH~3~CH~2~COOH + PCl~3~ → 3 CH~3~CH~2~COCl + H~3~PO~3~

## Esterification

Alcohols will react with acid chlorides or carboxylic acids to form
esters. This reaction is catalyzed by acidic or basic conditions. See
alcohol notes.

C~6~H~5~COCl + CH~3~CH~2~OH → C~6~H~5~COOCH~2~CH~3~ + HCl

With carboxylic acids, the condensation reaction is an unfavourable
equilibrium, promoted by using non-aqueous solvent (if any) and a
dehydrating agent such as sulfuric acid (non-nucleophilic), catalyzing
the reaction).

CH~3~COOH + CH~3~CH~2~CH~2~OH = CH~3~COOCH~2~CH~2~CH~3~ + H~2~O

!Ethanoic Acid reacts with Propanol to form Propyl
Ethanoate

Reversing the reaction is simply a matter of refluxing the ester with
plenty of aqueous acid. This hydrolysis produces the carboxylic acid and
the alcohol.

C~6~H~5~COOCH~3~ + H2O → C~6~H~5~COOH + CH~3~OH

Alternatively, the reflux is done with aqueous alkali. The salt of the
carboxylic acid is produced. This latter process is called
\'saponification\' because when fats are hydrolysed in this way, their
salts are useful as soap.

## Anhydrides

See acid anhydride.

## Amides

Conceptually, an amide is formed by reacting an acid (an
electrophile) with an amine
compound (a nucleophile),
releasing water.

RCOOH + H~2~NR\' → RCONHR\' + H~2~O

However, the acid-base reaction is much faster, which yields the
non-electrophilic carboxylate and the non-nucleophilic ammonium, and no
further reaction takes place.

RCOOH + H~2~NR\' → RCOO^-^ + H~3~NR\'^+^

To get around this, a variety of coupling reagents have been developed
that first react with the acid or carboxylate to form an active acyl
compound, which is basic enough to deprotonate an ammonium and
electrophilic enough to react with the free base of the amine. A common
coupling agent is
dicyclohexylcarbodiimide,
or DCC, which is very toxic.

## Acid Decarboxylation

On heating with sodalime (NaOH/CaO solid mix) carboxylic acids lose
their --COOH group and produce a small alkane plus sodium carbonate:

CH~3~CH~2~COOH + 2 NaOH →CH~3~CH~3~ + Na~2~CO~3~ + H~2~O

Note how a carbon is lost from the main chain. The product of the
reaction may be easier to identify than the original acid, helping us to
find the structure.

## Ethanoic anhydride

Industrially, ethanoic anhydride is used as a less costly and reactive
alternative to ethanoyl chloride. It forms esters and can be hydrolysed
in very similar ways, but yields a second ethanoic acid molecule, not
HCl The structure is formed from two ethanoic acid molecules...

## Polyester

Polyester can be made by reacting a diol (ethane-1,2-diol) with a
dicarboxylic acids (benzene-1,4-dicarboxylic acid). n HO-CH~2~CH~2~-OH +
n HOOC-C~6~H~4~-COOH → (-O-CH~2~CH~2~-O-OC-C~6~H~4~-CO-)n + n H~2~O
Polyester makes reasonable fibres, it is quite inflexible so it does not
crease easily; but for clothing it is usually combined with cotton for
comfort. The plastic is not light-sensitive, so it is often used for net
curtains. Film, bottles and other moulded products are made from
polyester.

## Distinguishing carboxylic acids from phenols

Although carboxylic acids are acidic, they can be distinguished from
phenol because: Only carboxylic acids will react with carbonates and
hydrogencarbonates to form CO2

2 CH~3~COOH + Na~2~CO~3~ → 2 CH~3~COONa + H~2~O + CO~2~

C~6~H~5~COOH + NaHCO~3~ → C~6~H~5~COONa + H~2~O + CO~2~

Some phenols react with FeCl~3~ solution, giving a characteristic purple
colour.

***Note***: Click on the following icon to go back to the contents page.
![](Go_To_Organic_Chemistry_Contents.png "Go_To_Organic_Chemistry_Contents.png")


# Organic Chemistry/Carboxylic acid derivatives

The carboxyl group (abbreviated -CO~2~H or -COOH) is one of the most
widely occurring functional groups in chemistry as well as biochemistry.
The carboxyl group of a large family of related compounds called Acyl
compounds or **Carboxylic Acid Derivatives**.

All the reactions and compounds covered in this section will yield
Carboxylic Acids on hydrolysis, and thus are known as Carboxylic Acid
Derivatives. Hydrolysis is one example of *Nucleophilic Acyl
Substitution*, which is a very important two step mechanism that is
common in all reactions that will be covered here.

## Structure

This group of compounds also contains a carbonyl group, but now there is
an electronegative atom (oxygen, nitrogen, or a halogen) attached to the
carbonyl carbon. This difference in structure leads to a major change in
reactivity.

## Nomenclature

The systematic IUPAC nomenclature for carboxylic acid derivatives is
different for the various compounds which are in this vast category, but
each is based upon the name of the carboxylic acid closest to the
derivative in structure. Each type is discussed individually below.

### Acyl Groups

Acyl groups are named by stripping the *-ic acid* of the corresponding
carboxylic acid and replacing it with *-yl*.

> **EXAMPLE:**\
> CH~3~COOH = *acetic acid*\
> CH~3~CO-R = *acetyl-R*

### Acyl Halides

Simply add the name of the attached halide to the end of the acyl group.

> **EXAMPLE:**\
> CH~3~COOH = *acetic acid*\
> CH~3~COBr = *acetyl bromide*

### Carboxylic Acid Anhydrides

A carboxylic acid anhydride (\[RC=O\]O\[O=CR\]) is a carboxylic acid
(COOH) that has an acyl group (RC=O) attached to its oxygen instead of a
hydrogen. If both acyl groups are the same, then it is simply the name
of the carboxylic acid with the word *acid* replaced with *anhydride*.
If the acyl groups are different, then they are named in alphabetical
order in the same way, with *anhydride* replacing *acid*.

> **EXAMPLE:**\
> CH~3~COOH = *acetic acid*\
> CH~3~CO-O-OCCH~3~ = *Ethanoic Anhydride*

### Esters

Esters are created when the hydrogen on a carboxylic acid is replaced by
an alkyl group. Esters are known for their pleseant, fruity smell and
taste, and they are often found in both natural and artificial flavors.
Esters (RCOOR^1^) are named as *alkyl alkanoates*. The alkyl group
directly attached to the oxygen is named first, followed by the acyl
group, with *-ate* replacing *-yl* of the acyl group.

> **EXAMPLE:**\
> CH~3~COOH = *acetic acid*\
> CH~3~COOCH~2~CH~2~CH~2~CH~3~ = *acetyl butanoate*

> cooh 1 cooh 1 2-ethan oic acid

### Amides

Amides which have an amino group (-NH~2~) attached to a carbonyl group
(RC=O) are named by replacing the *-oic acid* or *-ic acid* of the
corresponding carboxylic acid with *-amide*.

> **EXAMPLE:**\
> CH~3~COOH = *acetic acid*\
> CH~3~CONH~2~ = *acetamide*

### Nitriles

Nitriles (RCN) can be viewed a nitrogen analogue of a carbonyl and are
known for their strong electron withdrawing nature and toxicity.
Nitriles are named by adding the suffix *-nitrile* to the longest
hydrocarbon chain (including the carbon of the cyano group). It can also
be named by replacing the *-ic acid* or *-oic acid* of their
corresponding carboxylic acids with *-onitrile*. Functional class IUPAC
nomenclature may also be used in the form of *alkyl cyanides*.

> **EXAMPLE:**\
> CH~3~CH~2~CH~2~CH~2~CN = *pentanenitrile* or *butyl cyanide*

## Structure and Reactivity

Stability and reactivity have an inverse relationship, which means that
the more stable a compound, generally the less reactive - and vice
versa. Since acyl halides are the least stable group listed above, it
makes sense that they can be chemically changed to the other types.
Since the amides are the most stable type listed above, it should
logically follow that they cannot easily changed into the other molecule
types, and this is indeed the case.

The stability of any type of carboxylic acid derivative is generally
determined by the ability of its functional group to donate electrons to
the rest of the molecule. In essence, the *more electronegative* the
atom or group attached to carbonyl group, the *less stable* the
molecule. This readily explains the fact that the acyl halides are the
most reactive, because halides are generally quite electronegative. It
also explains why acid anhydrides are unstable; with two carbonyl groups
so close together the oxygen in between them cannot stabilize both by
resonance - it can\'t *loan* electrons to both carbonyls.

The following derivative types are ordered in decreasing reactivity (the
first is the most reactive):

> Acyl Halides **(CO-X)** \> Acyl Anhydrides **(-CO-O-OCR)** \> Acyl
> Thioester **(-CO-SR)** \> Acyl Esters **(-CO-OR)** \> Acyl Amides
> **(-CO-NR~2~)**

As mentioned before, any substance in the preceding list can be readily
transformed into a substance to its right; that is, the more reactive
derivative types (acyl halides) can be directly transformed into less
reactive derivative types (esters and amides). Every type can be made
directly from carboxylic acid (hence the name of this subsection) but
carboxylic acid can also be made from any of these types.

## Reactions of Carboxylic Acids and Their Derivatives

### Carboxylic Acids

1\) As acids:

`  RCO`~`2`~`H + NaOH ----> RCO`~`2`~^`-`^`Na`^`+`^` + H`~`2`~`O`\
`  RCO`~`2`~`H + NaHCO`~`3`~` ----> RCO`~`2`~^`-`^`Na`^`+`^` + H`~`2`~`O + CO`~`2`~

2\) Reduction:

`  RCO`~`2`~`H + LiAlH`~`4`~` --- (1) Et`~`2`~`O -- (2) H`~`2`~`O ----> RCH`~`2`~`OH`

2a) Fukyama reduction: Pd and Et3SiH COOH-\>CHO

3\) Conversion to acyl chlorides:

`  RCO`~`2`~`H -----SOCl`~`2`~` or PCl`~`5`~` ----> RCOCl`

4\) Conversion to esters (Fischer esterfication):

`  RCOOH + R'-OH  <--- HA --->  RCOOR' + H`~`2`~`O`

5\) Conversion to amides:

`  RCO`~`2`~`H -----SOCl`~`2`~` or PCl`~`5`~` ----> RCOCl + NH`~`3`~` <------> RCOO`^`-`^`NH`~`4`~^`+`^` --- heat ---> R-CONH`~`2`~` + H`~`2`~`O`

6\) Decarboxylation: (Note: you need a doubly-bonded oxygen (carbonyl)
two carbons away or two carboxylic acid groups attached to a same carbon
atom for this reaction to work)

`   Note: Decarboxylation by heating can only occur for ẞ-keto acids or 1,1-dicarboxylic acids`\
`  RCOCH`~`2`~`COOH  --- heat ---> R-COCH`~`3`~` + CO`~`2`~\
`  HOCOCH`~`2`~`COOH --- heat ---> CH`~`3`~`COOH + CO`~`2`~

7)R-COOH + R-OH \-\-\-\-\-\-\-\--R-COOR + H2O

### Acyl Chlorides

1\) Conversion to acids:

`  R-COCl + H`~`2`~`O ----> R-COOH + HCl`

2\) Conversion to anhydrides:

`  R-COCl + R'COO`^`-`^` ----> R-CO-O-COR' + Cl`^`-`^

3\) Conversion to esters:

`  R-COCl + R'-OH --- pyridine ---> R-COOR' + Cl`^`-`^` + pyr-H`^`+`^

4\) Conversion to amides:

`  R-COCl + R'NHR" (excess) ---> R-CONR'R" + R'NH`~`2`~`R"Cl`

R\' and/or R\" may be H

5\) Conversion to ketones:

Friedel-Crafts acylation

`  R-COCl + C`~`6`~`H`~`6`~` --- AlCl`~`3`~` ---> C`~`6`~`H`~`5`~`-COR`

Reaction of Dialkylcuprates (also known as a Gilman reagent)

`  R-COCl + R'`~`2`~`CuLi ----> R-CO-R'`

6\) Conversion to aldehydes:

`  R-COCl + LiAlH[OC(CH`~`3`~`)`~`3`~`]`~`3`~` --- (1) Et`~`2`~`O  (2) H`~`2`~`O ---> R-CHO`

### Acid Anhydrides

1\) Conversion to acids:

`  (R-CO)`~`2`~`-O + H`~`2`~`O ----> 2 R-COOH`

2\) Conversion to esters:

`  (R-CO)`~`2`~`-O + R'OH ----> R-COOR' + R-COOH`

3\) Conversion to amides:

`  (R-CO)`~`2`~`-O + H-N-(R'R") ----> R-CON-(R'R") + R-COOH`

R\' and/or R\" may be H.

4\) Conversion to aryl ketones (Friedel-Crafts acylation):

`  (R-CO)`~`2`~`-O + C`~`6`~`H`~`6`~` --- AlCl`~`3`~` C`~`6`~`H`~`5`~`-COR + R-COOH`

### Esters

1\) Hydrolysis:

`   R-COOR' + H`~`2`~`O <--- HA --->  R-COOH + R'-OH`\
`   R-COOR' + OH`^`-`^` ----> RCOO`^`-`^` + R'-OH`

2\) Transesterification (conversion to other esters):

`   R-COOR' + R"-OH <--- HA ---> R-COO-R" + R'-OH`

3\) Conversion to amides:

`   R-COOR' + HN-(R"R"') ----> R-CON-(R"R"') + R'-OH`

R\" and/or R\"\' may be H

4\) Reaction with Grignard reagents:

`  R-COOR' + 2 R"MgX --- Et`~`2`~`O ---> R-C-R"`~`2`~`OMgX + R'OMgX ---> H`~`3`~`O`^`+`^`  R-C-R"`~`2`~`OH`

The intermediate and final product is a tetrahedral carbon with two R\"
attached directly to the carbon along with R and OH/OMgX

X = halogen.

5\) Reduction:

`  R-COOR' + LiAlH`~`4`~` --- (1) Et`~`2`~`O (2) H`~`2`~`O ---> R-CH`~`2`~`OH + R'-OH`

### Amides

1\) Hydrolysis:

`  R-CON(R'R") + H`~`3`~`O`^`+`^`  --- H`~`2`~`O ---> R-COOH + R'-N`^`+`^`H`~`2`~`R"`\
`  R-CON(R'R") + OH`^`-`^`  --- H`~`2`~`O ---> R-COO`^`-`^` + R'-NHR"`

R,R\' and/or R\" may be H.

2\) Dehydration (conversion to nitriles):

`  R-CONH`~`2`~`  --- P`~`4`~`O`~`10`~`, heat, (-H`~`2`~`O) ---> R-CN`

### Nitriles

1\) Hydrolysis:

`  R-CN --- H`~`3`~`O`^`+`^`,heat ---> RCOOH`\
`  R-CN --- OH`^`-`^`,H`~`2`~`O,heat ---> RCOO`^`-`^

2\) Reduction to aldehyde:

`  R-CN --- (1) (`*`i`*`-Bu)`~`2`~`AlH (2) H`~`2`~`O ---> R-COH`

(*i*-Bu)~2~AlH = DIBAL-H

3\) Conversion to ketone (by Grignard or organolithium reagents):

`  R-CN + R"-M --- (1) Et`~`2`~`O (2) H`~`3`~`O`^`+`^` ---> R-COR"`

M = MgBr (Grignard reagent) or Li (organolithium reagent)

### Mechanisms

A common motif in reactions dealing with carboxylic acid derivatives is
the tetrahedral intermediate. The carbonyl group is highly polar, with
the carbon having a low electron density, and the oxygen having a high
electron density. With an acid catalyst, a H+ is added to the oxygen of
the carbonyl group, increasing the positive charge at the carbon atom. A
nucleophile can then attack the carbonyl, creating a tetrahedral
intermediate.

For example, in Fischer esterification, the mechanism can be outlined
thus: 1) H+ is added to carbonyl oxygen 2) Oxygen atom of the alcohol
adds to the carbonyl carbon 3) Proton transfer from alcohol oxygen to
carboxyl oxygen 4) Water molecule ejected from tetrahedral intermediate,
double bond forms, recreating the carbonyl 5) H+ is removed from
carbonyl oxygen(very important for the base reduction of acids)


# Organic Chemistry/Questions and Discussions

Name the reagent used to distinguish the following pair Carboxylic and
ethanol Alkyne and alkene Butan-1-yne and Butan-2-yne

## Q1

**What is more acidic, cyclopentadiene or penta-1,4-diene? What is the
application of Huckel\'s rule here?**

### Discussion

In this context acidity is the ability to lose a proton.We will decide
the acidity on the basis of the stability of the resulting carbanion
\[Why did we emphasize the word \"context\" here? How else can a
molecule behave as an acid?\]\[Why is it that a carbanion is formed?\]
\[How did we relate stability of carbanion with acidity here?\]

Also, the number of carbons in both the compounds are same and are of a
similar structure.It is only now that we can compare the stability of
their conjugate bases \[What are they?\] \[carbanions we were talking
about in this case\...\]

So, first we decide what is the most acidic hydrogen in both the
molecules. In the straight chain carbon molecule, the two hydrogens
attached to the central carbon are more acidic than the rest of the
hydrogens. This is for a specific reason.Once any of the hydrogen is
extracted by a base, the central carbon should acquire a negative
charge.Instead,the molecule is represented by a resonance hybrid of two
degenerate \[equivalent\] resonance structures with a negative charge on
the terminal carbons and a third one with the negative charge on the
central carbon. This is a stabilizing factor of the carbanion. The
presence of this stabilizing factor makes the two hydrogens in the
original molecule acidic.

\[What exactly are we talking about here? What is the conjugate base
whose stability we discussed?\]

In the cyclic molecule, the same thing applies. We again have a molecule
which is represented by resonating structures.But the speciality is that
it has six pi electrons and is cyclic.In other words, by Huckel\'s rule
we find that the cyclopentadiene anion is aromatic. Aromaticity is a
better stabilizing factor than simple resonance. Hence the
cyclopentadiene molecule is the more acidic than the straight chain
molecule. Remember that the comparison could be made only because they
are similar molecules.

What is the smallest aromatic species? Is penta-1,4-diene hydrolyzed by
water? Is cyclopentadiene hydrolyzed by water? How do you relate these
observations to what we just discussed above?

### Additional Questions

#### Nucleophillicity and basicity

Proton is a lewis acid.It\'s also an electrophile. Consider hydroxide
ions- OH-(- indicates negative charge) They are nucleophiles. They are
Lewis bases as well.What property makes them nucleophiles and what
property makes them bases? Still another question: Give an example of a
strong base but a weak nucleophile. What gives the molecule these
characteristics?

#### A corrosive phenol

Which phenol has a boiling point of 132 to 134 degree Celsius and is
corrosive in nature? Dark orange in colour?

#### Answers

#### A little variation

What if the linear chain is hex-1,5-diene? Does aromaticity still
dominate?

#### Answers

If it\'s linear it cannot be aromatic, although it can still contain a
delocalised p-system.


# Organic Chemistry/Introduction to reactions

![](Go_To_Organic_Chemistry_Contents_.png "Go_To_Organic_Chemistry_Contents_.png")
\> Introduction to reactions

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

![](Go_To_Organic_Chemistry_Contents_.png "Go_To_Organic_Chemistry_Contents_.png")
\> Introduction to reactions

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

## Specific Reactions

1.  Polar and radical
    reactions

2.  Redox
    reactions

3.  Carbocations
4.  Hydroboration/oxidation
5.  Free-radical
    halogenation

6.  Rearrangement
    reactions
7.  Pericyclic
    reactions
8.  Diels-Alder
    reaction

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