Dehydration reaction

This article is about chemical reactions resulting in the loss of water from a molecule. For the
removal of water from solvents and reagents, see Desiccation.
In chemistry and the biological sciences, a dehydration reaction is usually defined as a chemical
reaction that involves the loss of a water molecule from the reacting molecule. Dehydration reactions
are a subset of condensation reactions. Because the hydroxyl group (OH) is a poor leaving group,
having a Brnsted acid catalyst often helps by protonating the hydroxyl group to give the better
leaving group, OH2+. The reverse of a dehydration reaction is a hydration reaction. Common
dehydrating agents used in organic synthesis include concentrated sulfuric acid,
concentrated phosphoric acid, hot aluminium oxide and hot ceramic.
Dehydration reactions and dehydration synthesis have the same meaning, and are often used
interchangeably. Two monosaccharides, such as glucose and fructose, can be joined together (to
form sucrose) using dehydration synthesis. The new molecule, consisting of two monosaccharides,
is called a disaccharide.
The process of hydrolysis is the reverse reaction, meaning that the water is recombined with the two
hydroxyl groups and the disaccharide reverts to being monosaccharides.
In the related condensation reaction water is released from two different reactants.

Dehydration reactions [
In organic synthesis, there are many examples of dehydration reaction, for example dehydration of
alcohols or sugars.
Dehydration reactions
Reaction

Equation

Conversion

2 R-OH R-

of alcohols toethers

O-R + H2O

Conversion of

R-CH2-CHOH-R for example the conversion of glycerol to acrolein:[1]

R-CH=CH-R

alcohols toalkenes

+ H2O

or the dehydration of 2-methyl-1-cyclohexanol to

(mainly) 1-methylcyclohexene [2]

Conversion

of carboxylic

RCOO

acidsto acid

anhydrides

(RCO)2
O+
H2 O

Conversion

RCON

of amides to

H2

nitriles

R-CN
+ H2O

Dienol
benzene
rearrangeme
nt
[3][4]

Some dehydration reactions can be mechanistically complex, for instance the reaction of
a sugar (sucrose) with concentrated sulfuric acid:[5] to form carbon as a graphitic foam involves
formation of carbon-carbon bonds.[6] The reaction is driven by the strongly exothermic reaction as
sulfuric acid reacts with water, which produces dangerous sulfuric-acid containing steam, therefore
the experiment should only be performed in a fume-hood or well ventilated area.

Intramolecular Dehydration
A very important reaction by which alcohols can be converted to alkenes
is intramolecular dehydration.
An equation for such a reaction is shown here (and in Example 10-a in your
workbook).
H H
| |
H-C-C-H
| |
H OH

H2SO4

heat

H H
| |
H-C=C-H

+ H2O

In this reaction the alcohol is heated in

the presence of sulfuric acid. The -OH
group on one carbon atom and the
hydrogen atom on an adjacent carbon
atom are split away from the molecule
and are essentially replaced by a double
bond. How concentrated the acid has to
be and how hot the mixture has to be
heated depends on the particular alcohol
that is being dehydrated.
Another important thing to note, something that will become even more important
later, is that since this dehydration occurs within a molecule it is
called intramolecular dehydration. That name is used to distinguish this reaction from
an intermolecular dehydration reaction in which the H- and the -OH come from two
different molecules.

Notice that this is just the opposite of the

reaction in which an alkene is converted
to an alcohol (refer to Example 7-a in your
workbook). The fact that this kind of a
reaction can go in both directions using
the same catalyst, tells you that we are
dealing with anequilibrium reaction.
Because of this, when you start with an alkene and change it into an alcohol, you
should expect to end up with a mixture containing some of the original alkene as
well as some of the alcohol being made. If you start with an alcohol and change it
into an alkene you would expect to have some of the original alcohol remaining in

solution.
You should also realize that the ratio of alkene to alcohol in the resulting solution is
going to depend upon the conditions under which the solution is kept. Conditions
such as the concentration of acid, the temperature of the solution, and even the
abundance of water will affect the equilibrium position and consequently the ratio of
alkene to alcohol in the reaction mixture.

As an aside, let's relate this to the

equilibrium constant expressions that you
worked with last term. In reactions like
this the concentration of water will be low
enough to change considerably as the
reaction takes place. Consequently,
you cannot simply ignore the
concentration of water as we did when
we were dealing with ionic reactions.
Those earlier ionic reactions were taking place in aqueous solution where the
concentration of water was so large (about 55 moles per liter) that the formation or
reaction of water had very little effect upon the position of equilibrium. That is,
the changes in the amount and concentration of water were so small compared to
what was there that they did not influence the equilibrium position very much.
Therefore, we didn't even include it in the equilibrium constant expressions. If you
were to deal with the equilibrium expression of a reaction like this one above,
you would have to take water into account.

As I pointed out earlier, this kind of

dehydration reaction in which you form an
alkene from an alcohol is called
intramolecular dehydration because all of
the atoms for the water molecule came
from the same alcohol molecule. The H
and OH were on adjacent carbon atoms
within the same molecule. This
is intramolecular dehydration.

Phosphodiester bond

Diagram of phosphodiester bonds (PO43) between nucleotides. Which presents Thymine (T) and two molecules
of Adenine (A).

with hydroxyl groups on other molecules

A phosphodiester bond occurs when exactly two of the hydroxyl groups in phosphoric acid react
with hydroxyl groups on other molecules to form two ester bonds.[1]
Phosphodiester bonds are central to all life on Earth,[fn 1] as they make up the backbone of the strands
of nucleic acid. In DNA and RNA, the phosphodiester bond is the linkage between the 3' carbon
atom of one sugar molecule and the 5' carbon atom of another, deoxyribose in DNA and ribose in
RNA. Strong covalent bonds form between the phosphate group and two 5-carbon ring
carbohydrates (pentoses) over twoester bonds.
The phosphate groups in the phosphodiester bond are negatively charged. Because the phosphate
groups have a pKa near 0, they are negatively charged at pH 7[citation needed]. This repulsion forces the
phosphates to take opposite sides of the DNA strands and is neutralized by proteins (histones),
metal ions such as magnesium, and polyamines.
In order for the phosphodiester bond to be formed and the nucleotides to be joined, the tri-phosphate
or di-phosphate forms of the nucleotide building blocks are broken apart to give off energy required
to drive the enzyme-catalyzed reaction. When a single phosphate or two phosphates known

as pyrophosphates break away and catalyze the reaction, the phosphodiester bond is formed. [citation
needed]

Hydrolysis of phosphodiester bonds can be catalyzed by the action of phosphodiesterases which

play an important role in repairing DNA sequences.[citation needed]
In biological systems, the phosphodiester bond between two ribonucleotides can be broken
by alkaline hydrolysis because of the free 2'hydroxyl group.

Enzyme activity
A phosphodiesterase is an enzyme that catalyzes the hydrolysis of phosphodiester bonds, for
instance a bond in a molecule of cyclic AMP or cyclic GMP.
An enzyme that plays an important role in the repair of oxidative DNA damage is the 3'phosphodiesterase.
During the replication of DNA, there is a hole between the phosphates in the backbone left by DNA
polymerase I. DNA ligase is able to form a phosphodiester bond between the nucleotides.

Covalent bond
A covalent bond is a chemical bond that involves the sharing of electron pairs between atoms.( An

atom is the defining structure of an element, which cannot be broken by any chemical
means. A typical atom consists of a nucleus
of protons and neutrons with electrons orbiting this nucleus.)
These electron pairs are known as shared pairs or bonding pairs, and the stable balance of
attractive and repulsive forces between atoms, when they share electrons, is known as covalent
bonding.[1][better source needed] For many molecules, the sharing of electrons allows each atom to attain the
equivalent of a full outer shell, corresponding to a stable electronic configuration.
Covalent bonding includes many kinds of interactions, including -bonding, -bonding, metal-tometal bonding, agostic interactions, bent bonds, and three-center two-electron bonds.[2][3] The
term covalent bonddates from 1939.[4] The prefix co- means jointly, associated in action, partnered to
a lesser degree, etc.; thus a "co-valent bond", in essence, means that the atoms share "valence",
such as is discussed in valence bond theory.
In the molecule H
2, the hydrogen atoms share the two electrons via covalent bonding. [5] Covalency is greatest

between atoms of similar electronegativities. Thus, covalent bonding does not necessarily require

that the two atoms be of the same elements, only that they be of comparable electronegativity.
Covalent bonding that entails sharing of electrons over more than two atoms is said to
be delocalized.

History

Early concepts in covalent bonding arose from this kind of image of the molecule of methane. Covalent bonding
is implied in theLewis structure by indicating electrons shared between atoms.

The term covalence in regard to bonding was first used in 1919 by Irving Langmuir in a Journal of
the American Chemical Society article entitled "The Arrangement of Electrons in Atoms and
Molecules". Langmuir wrote that "we shall denote by the term covalence the number of pairs of
electrons that a given atom shares with its neighbors." [6]
The idea of covalent bonding can be traced several years before 1919 to Gilbert N. Lewis, who in
1916 described the sharing of electron pairs between atoms.[7] He introduced the Lewis

notation or electron dot notation or Lewis dot structure, in which valence electrons (those in the outer
shell) are represented as dots around the atomic symbols. Pairs of electrons located between atoms
represent covalent bonds. Multiple pairs represent multiple bonds, such as double bonds and triple
bonds. An alternative form of representation, not shown here, has bond-forming electron pairs
represented as solid lines.
Lewis proposed that an atom forms enough covalent bonds to form a full (or closed) outer electron
shell. In the methane diagram shown here, the carbon atom has a valence of four and is, therefore,
surrounded by eight electrons (the octet rule), four from the carbon itself and four from the
hydrogens bonded to it. Each hydrogen has a valence of one and is surrounded by two electrons (a
duet rule) its own one electron plus one from the carbon. The numbers of electrons correspond to
full shells in the quantum theory of the atom; the outer shell of a carbon atom is the n=2 shell, which
can hold eight electrons, whereas the outer (and only) shell of a hydrogen atom is the n=1 shell,
which can hold only two.
While the idea of shared electron pairs provides an effective qualitative picture of covalent
bonding, quantum mechanics is needed to understand the nature of these bonds and predict the
structures and properties of simple molecules. Walter Heitler and Fritz London are credited with the
first successful quantum mechanical explanation of a chemical bond (molecular hydrogen) in 1927.
[8]

Their work was based on the valence bond model, which assumes that a chemical bond is formed

when there is good overlap between the atomic orbitals of participating atoms.

Types of covalent bonds

Atomic orbitals (except for s orbitals) have specific directional properties leading to different types of
covalent bonds. Sigma bonds ( bonds) are the strongest covalent bonds and are due to head-on
overlapping of orbitals on two different atoms. A single bond is usually a sigma bond. Pi bonds are
weaker and are due to lateral overlap between p (or d) orbitals. A double bond between two given
atoms consists of one sigma and one pi bond, and a triple bond is one sigma and two pi bonds.
Covalent bonds are also affected by the electronegativity of the connected atoms which determines
the chemical polarity of the bond. Two atoms with equal electronegativity will make nonpolar
covalent bonds such as HH. An unequal relationship creates a polar covalent bond such as with
HCl.

Covalent structures
There are several types of structures for covalent substances, including individual molecules,
molecular structures, macromolecular structures and giant covalent structures. Individual molecules

have strong bonds that hold the atoms together, but there are negligible forces of attraction between
molecules. Such covalent substances are usually gases, for example, HCl, SO 2, CO2, and CH4. In
molecular structures, there are weak forces of attraction. Such covalent substances are low-boilingtemperature liquids (such asethanol), and low-melting-temperature solids (such as iodine and solid
CO2). Macromolecular structures have large numbers of atoms linked by covalent bonds in chains,
including synthetic polymers such as polyethylene and nylon, and biopolymers such
as proteins and starch. Network covalent structures (or giant covalent structures) contain large
numbers of atoms linked in sheets (such as graphite), or 3-dimensional structures (such
as diamond and quartz). These substances have high melting and boiling points, are frequently
brittle, and tend to have high electrical resistivity. Elements that have high electronegativity, and the
ability to form three or four electron pair bonds, often form such large macromolecular structures. [9]

One- and three-electron bonds

Bonds with one or three electrons can be found in radical species, which have an odd number of
electrons. The simplest example of a 1-electron bond is found in the dihydrogen cation, H2+. Oneelectron bonds often have about half the bond energy of a 2-electron bond, and are therefore called
"half bonds". However, there are exceptions: in the case ofdilithium, the bond is actually stronger for
the 1-electron Li2+ than for the 2-electron Li2. This exception can be explained in terms of
hybridization and inner-shell effects.[10]

Comparison of the electronic structure of the three-electron bond to the conventional covalent bond.

The simplest example of three-electron bonding can be found in the helium dimer cation, He2+. It is
considered a "half bond" because it consists of only one shared electron (rather than two); in
molecular orbital terms, the third electron is in an anti-bonding orbital which cancels out half of the
bond formed by the other two electrons. Another example of a molecule containing a 3-electron
bond, in addition to two 2-electron bonds, is nitric oxide, NO. The oxygen molecule, O2 can also be
regarded as having two 3-electron bonds and one 2-electron bond, which accounts for
its paramagnetismand its formal bond order of 2.[11] Chlorine dioxide and its heavier
analogues bromine dioxide and iodine dioxide also contain three-electron bonds.

Molecules with odd-electron bonds are usually highly reactive. These types of bond are only stable
between atoms with similar electronegativities.[11]

Resonance
Main article: Resonance (chemistry)
There are situations whereby a single Lewis structure is insufficient to explain the electron
configuration in a molecule, hence a superposition of structures are needed. The same two atoms in
such molecules can be bonded differently in different structures (a single bond in one, a double bond
in another, or even none at all), resulting in a non-integer bond order. The nitrate ion is one such
example with three equivalent structures. The bond between the nitrogen and each oxygen is a
double bond in one structure and a single bond in the other two, so that the average bond order for
each N-O interaction is (2 + 1 + 1)/3 = 4/3.

Aromaticity
Main article: Aromaticity
In organic chemistry, when a molecule with a planar ring obeys Hckel's rule, where the number of
electrons fit the formula 4n + 2 (where n is an integer), it attains extra stability and symmetry.
In benzene, the prototypical aromatic compound, there are 6 bonding electrons (n = 1, 4n + 2 = 6).
These occupy three delocalized molecular orbitals (molecular orbital theory) or form conjugate
bonds in two resonance structures that linearly combine (valence bond theory), creating a regular
hexagon exhibiting a greater stabilization than the hypothetical 1,3,5-cyclohexatriene.
In the case of heterocyclic aromatics and substituted benzenes, the electronegativity differences
between different parts of the ring may dominate the chemical behaviour of aromatic ring bonds,
which otherwise are equivalent.

Hypervalence
Main article: Hypervalent molecule
Certain molecules such as xenon difluoride and sulfur hexafluoride have higher co-ordination
numbers than would be possible due to strictly covalent bonding according to theoctet rule. This is

explained by the three-center four-electron bond ("3c4e") model in molecular orbital theory and
ionic-covalent resonance in valence bond theory.

Electron-deficiency
Main article: Electron deficiency
In three-center two-electron bonds ("3c2e") three atoms share two electrons in bonding. This type
of bonding occurs in electron deficient compounds like diborane. Each such bond (2 per molecule in
diborane) contains a pair of electrons which connect the boron atoms to each other in a banana
shape, with a proton (nucleus of a hydrogen atom) in the middle of the bond, sharing electrons with
both boron atoms. In certain cluster compounds, so-called four-center two-electron bonds also have
been postulated.

Quantum mechanical description

After the development of quantum mechanics, two basic theories were proposed to provide a
quantum description of chemical bonding: valence bond (VB) theory and molecular orbital (MO)
theory.

Valence bond theory

In 1927, valence bond theory was formulated and it argues that a covalent bond forms when
two valence electrons, in their respective atomic orbitals, work or function to hold two nuclei together,
by virtue of effects of lowering system energies. Building on this theory, the chemist Linus
Pauling published in 1931 what some consider one of the most important papers in the history of
chemistry: "On the Nature of the Chemical Bond". In this paper, elaborating on the works of Lewis,
and the valence bond theory (VB) of Heitler and London, and his own earlier works, Pauling
presented six rules for the shared electron bond, the first three of which were already generally
known:
1. The electron-pair bond forms through the interaction of an unpaired electron on each of
two atoms.
2. The spins of the electrons have to be opposed.
3. Once paired, the two electrons cannot take part in additional bonds.
His last three rules were new:
4. The electron-exchange terms for the bond involve only one wave function from each atom.
5. The available electrons in the lowest energy level form the strongest bonds.

6. Of two orbitals in an atom, the one that can overlap the most with an orbital from another
atom will form the strongest bond, and this bond will tend to lie in the direction of the
concentrated orbital.
Building on this article, Pauling's 1939 textbook: On the Nature of the Chemical
Bond would become what some have called the "Bible" of modern chemistry. This
book helped experimental chemists to understand the impact of quantum theory on
chemistry. However, the later edition in 1959 failed to adequately address the
problems that appeared to be better understood by molecular orbital theory. The
impact of valence theory declined during the 1960s and 1970s as molecular orbital
theory grew in usefulness as it was implemented in large digital computer programs.
Since the 1980s, the more difficult problems, of implementing valence bond theory
into computer programs, have been solved largely, and valence bond theory has
seen a resurgence.

Molecular orbital theory

Main article: Molecular orbital theory
Molecular orbitals were first introduced by Friedrich Hund[12][13] and Robert S. Mulliken[14][15] in
1927 and 1928.[16][17] The linear combination of atomic orbitals or "LCAO" approximation for
molecular orbitals was introduced in 1929 by Sir John Lennard-Jones.[18] Linear
combinations of atomic orbitals (LCAO) can be used to estimate the molecular
orbitals that are formed upon bonding between the molecule's constituent atoms.
Similar to an atomic orbital, a Schrdinger equation, which describes the behavior
of an electron, can be constructed for a molecular orbital as well. Linear
combinations of atomic orbitals, or the sums and differences of the atomic
wavefunctions, provide approximate solutions to the HartreeFock equations which
correspond to the independent-particle approximation of the molecular Schrdinger
equation.
When atomic orbitals interact, the resulting molecular orbital can be of three types:
bonding, antibonding, or nonbonding.
Bonding MOs:
Bonding interactions between atomic orbitals are constructive (in-phase)
interactions.
Bonding MOs are lower in energy than the atomic orbitals that combine to produce
them.
Antibonding MOs:
Antibonding interactions between atomic orbitals are destructive (out-of-phase)
interactions, with a nodal plane where the wavefunction of the antibonding orbital is
zero between the two interacting atoms

Antibonding MOs are higher in energy than the atomic orbitals that combine to
produce them.
Nonbonding MOs:
Nonbonding MOs are the result of no interaction between atomic orbitals because of
lack of compatible symmetries.
Nonbonding MOs will have the same energy as the atomic orbitals of one of the
atoms in the molecule.

Comparison
The two theories differ in the order that the electron configuration of the molecule is
built up.[19] For valence bond theory, the atomic hybrid orbitals are filled first to produce
a full valence configuration of bonding pairs and lone pairs. If several such
configurations exist, a weighted superposition of these configurations is then applied. In
contrast, for molecular orbital theory a weighted superposition of atomic orbitals is
performed first, followed by the filling of the resulting molecular orbitals by
the Aufbau principle.
Either theory has its advantages and uses. As valence bond theory builds the
molecular wavefunction out of localized bonds, it is more suited for the calculation
of bond energiesand the understanding of reaction mechanisms. In particular, valence
bond theory correctly predicts the dissociation of homonuclear diatomic molecules
into separate atoms, while simple molecular orbital theory predicts dissociation into
a mixture of atoms and ions. Molecular orbital theory, with delocalized orbitals that
obey its symmetry, is more suited for the calculation of ionization energies and the
understanding of spectral absorption bands. Molecular orbitals are orthogonal, which
significantly increases feasibility and speed of computer calculations compared to
nonorthogonal valence bond orbitals.
Although the wavefunctions generated by both theories do not agree and do not
match the stabilization energy by experiment, they can be corrected by
configuration interaction.[19] This is done by combining the valence bond covalent
function with the functions describing all possible ionic configurations or by
combining the molecular orbital ground state function with the functions describing
all possible excited states using unoccupied orbitals. It can then be seen that the
simple molecular orbital approach gives too much weight to the ionic structures
while the simple valence bond approach gives too little. This can also be described
as saying that the molecular orbital approach neglects electron correlation while the
valence bond approach overestimates it.[19]
The two approaches are now regarded as complementary, each providing its own
insights into the problem of chemical bonding. Modern calculations in quantum
chemistryusually start from (but ultimately go far beyond) a molecular orbital rather

than a valence bond approach, not because of any intrinsic superiority in the former
but rather because the MO approach is more readily adapted to numerical
computations. However, better valence bond programs are now available.

A molecule is the smallest particle in a

chemical element or compound that has the chemical properties of that
element or compound. Molecules are made up of atom s that are held
together by chemical bonds. These bonds form as a result of the sharing or
exchange of electron s among atoms.
The atoms of certain elements readily bond with other atoms to form
molecules. Examples of such elements are oxygen and chlorine. The atoms
of some elements do not easily bond with other atoms. Examples are neon
and argon.
Molecules can vary greatly in size and complexity. The element helium is a
one-atom molecule. Some molecules consist of two atoms of the same
element. For example, O 2 is the oxygen molecule most commonly found in
the earth's atmosphere; it has two atoms of oxygen. However, under certain
circumstances, oxygen atoms bond into triplets (O 3 ), forming a molecule
known as ozone. Other familiar molecules include water, consisting of two
hydrogen atoms and one oxygen atom (H 2 O), carbon dioxide, consisting of
one carbon atom bonded to two oxygen atoms (CO 2 ), and sulfuric acid,
consisting of two hydrogen atoms, one sulfur atom, and four oxygen atoms
(H 2 SO 4 ).
Some molecules, notably certain proteins, contain hundreds or even
thousands of atoms that join together in chains that can attain considerable
lengths. Liquids containing such molecules sometimes behave strangely. For
example, a liquid may continue to flow out of a flask from which some of it
has been poured, even after the flask is returned to an upright position.
Molecules are always in motion. In solids and liquids, they are packed tightly
together. In asolid , the motion of the molecules can be likened to rapid
vibration. In a liquid, the molecules can move freely among each other, in a
sort of slithering fashion. In a gas , the density of molecules is generally less
than in a liquid or solid of the same chemical compound, and they move
even more freely than in a liquid. For a specific compound in a given state
(solid, liquid, or gas), the speed of molecular motion increases as the
absolute temperature increases.

Sugar

Sugar is the generalized name for sweet, short-chain, soluble carbohydrates, many of which are used in

food. They arecarbohydrates, composed of carbon, hydrogen, and oxygen. There are various types
of sugar derived from different sources. Simple sugars are called monosaccharides and
include glucose (also known as dextrose), fructose andgalactose. The table or granulated sugar
most customarily used as food is sucrose, a disaccharide. (In the body, sucrose hydrolyses into
fructose and glucose.) Other disaccharides include maltose and lactose. Longer chains of sugars
are called oligosaccharides. Chemically-different substances may also have a sweet taste, but are
not classified as sugars. Some are used as lower-calorie food substitutes for sugar described
as artificial sweeteners.
Sugars are found in the tissues of most plants, but are present in sufficient concentrations for
efficient extraction only insugarcane and sugar beet.[citation needed] Sugarcane refers to any of several
species of giant grass in the genusSaccharum that have been cultivated in tropical climates in South
Asia and Southeast Asia since ancient times. A great expansion in its production took place in the
18th century with the establishment of sugar plantations in the West Indies and Americas. This was
the first time that sugar became available to the common people, who had previously had to rely on
honey to sweeten foods. Sugar beet, a cultivated variety of Beta vulgaris, is grown as a root crop in
cooler climates and became a major source of sugar in the 19th century when methods for
extracting the sugar became available. Sugar production and trade have changed the course of
human history in many ways, influencing the formation of colonies, the perpetuation of slavery, the
transition to indentured labour, the migration of peoples, wars between sugar-tradecontrolling
nations in the 19th century, and the ethnic composition and political structure of the New World.

Sucrose: a disaccharide of glucose (left) and fructose(right), important molecules in the body.

Ribose
D-Ribose

Chemical formula

C5H10O5

Ribose is a carbohydrate with the formula C5H10O5; specifically, it is

a pentose monosaccharide (simple sugar) with linear form H(C=O)(CHOH)4H, which has all
the hydroxyl groups on the same side in the Fischer projection.
The term may refer to either of two enantiomers. The term usually indicates D-ribose, which occurs
widely in nature and is discussed here. Its synthetic mirror image, L-ribose, is not found in nature.
D-Ribose

was first reported in 1891 by Emil Fischer. It is a C'-2 carbon epimer of the sugar Darabinose (both isomers of which are named for their source, gum arabic) and ribose itself is named
as a transposition of the name of arabinose.[3]
The ribose -D-ribofuranose forms part of the backbone of RNA. It is related to deoxyribose, which is
found in DNA. Phosphorylatedderivatives of ribose such as ATP and NADH play central roles
in metabolism. cAMP and cGMP, formed from ATP and GTP, serve as secondary messengers in
some signalling pathways.

Structure[edit]
Ribose is an aldopentose (a monosaccharide containing five carbon atoms) that, in its open
chain form, has an aldehyde functional group at one end. In the conventional numbering scheme for
monosaccharides, the carbon atoms are numbered from C1' (in the aldehyde group) to C5'.
The deoxyribose derivative found in DNA differs from ribose by having a hydrogen atom in place of
thehydroxyl group at C2'. This hydroxyl group performs a function in RNA splicing.
Like many monosaccharides, ribose exists in an equilibrium among 5 formsthe linear form H
(C=O)(CHOH)4H and either of the two ring forms: alpha- or beta-ribofuranose (C3'-endo), with a
five-membered ring, and alpha- or beta-ribopyranose (C2'-endo), with a six-membered ring. The
beta-ribopyranose form predominates in aqueous solution.[4]

The D- in the name D-ribose refers to the stereochemistry of the chiral carbon atom farthest away
from the aldehyde group (C4'). InD-ribose, as in all D-sugars, this carbon atom has the same
configuration as in D-glyceraldehyde.

-D-Ribopyranose

-D-Ribopyranose

-D-Ribofuranose

-D-Ribofuranose

Relative abundance of different forms of ribose in solution: -D-ribopyranose (59%), -Dribopyranose (20%), -D-ribofuranose (13%), -D-ribofuranose (7%) and open chain (0.1%). [5]

Deoxyribose
This article is about the naturally-occurring D-form of deoxyribose. For the L-form, see L-deoxyribose.
D-deoxyribose

Names
IUPAC name
2-deoxy-D-ribose

Deoxyribose, or more precisely 2-deoxyribose, is a monosaccharide with idealized formula H

(C=O)(CH2)(CHOH)3H. Its name indicates that it is a deoxy sugar, meaning that it is derived from
the sugar ribose by loss of an oxygen atom. Since the pentose sugars arabinose and ribose only
differ by the stereochemistry at C2, 2-deoxyribose and 2-deoxyarabinose are equivalent, although
the latter term is rarely used because ribose, not arabinose, is the precursor to deoxyribose.

Structure[edit]
Several isomers exist with the formula H(C=O)(CH2)(CHOH)3H, but in deoxyribose all
the hydroxyl groups are on the same side in the Fischer projection. The term "2-deoxyribose" may
refer to either of two enantiomers: the biologically important D-2-deoxyribose and to the rarely
encountered mirror image L-2-deoxyribose.[2] D-2-deoxyribose is a precursor to the nucleic acid DNA.
2-deoxyribose is an aldopentose, that is, a monosaccharide with five carbon atoms and having
an aldehyde functional group.

In aqueous solution, deoxyribose primarily exists as a mixture of three structures: the linear form H
(C=O)(CH2)(CHOH)3H and two ring forms, deoxyribofuranose ("C3-endo"), with a five-membered
ring, and deoxyribopyranose ("C2-endo"), with a six-membered ring. The latter form is predominant
(whereas the C3-endo form is favored for ribose).

Chemical equilibrium of deoxyribose in solution

Biological importance[edit]
As a component of DNA, 2-deoxyribose derivatives have an important role in biology.
[3]

The DNA (deoxyribonucleic acid) molecule, which is the main repository of genetic information in

life, consists of a long chain of deoxyribose-containing units called nucleotides, linked

via phosphate groups. In the standard nucleic acid nomenclature, a DNA nucleotide consists of a
deoxyribose molecule with an organic base (usually adenine, thymine, guanine or cytosine) attached
to the 1 ribose carbon. The 5 hydroxyl of each deoxyribose unit is replaced by a phosphate (forming
a nucleotide) that is attached to the 3 carbon of the deoxyribose in the preceding unit.
The absence of the 2 hydroxyl group in deoxyribose is apparently responsible for the increased
mechanical flexibility of DNA compared to RNA, which allows it to assume the double-helix
conformation, and also (in the eukaryotes) to be compactly coiled within the small cell nucleus. The
double-stranded DNA molecules are also typically much longer than RNA molecules. The backbone
of RNA and DNA are structurally similar, but RNA is single stranded, and made from ribose as
opposed to deoxyribose.
Other biologically important derivatives of deoxyribose include mono-, di-, and triphosphates, as well
as 3-5 cyclic monophosphates.

Cyclic compound
A cyclic compound (ring compound) is a term for a compound in the field of chemistry in which one
or more series of atoms in the compound is connected to form a ring. Rings may vary in size from
three to many atoms, and include examples where all the atoms are carbon (i.e., are carbocycles),
none of the atoms are carbon (inorganic cyclic compounds), or where both carbon and non-carbon
atoms are present (heterocyclic compounds). Depending on the ring size, the bond order of the
individual links between ring atoms, and their arrangements within the rings, carbocyclic and

heterocyclic compounds may be aromatic or non-aromatic, in the latter case, they may vary from
being fullysaturated to having varying numbers of multiple bonds between the ring atoms. Because
of the tremendous diversity allowed, in combination, by the valences of common atoms and their
ability to form rings, the number of possible cyclic structures, even of small size (e.g., <17 total
atoms) numbers in the many billions.

Cyclic compound examples: All-carbon (carbocyclic) and more complex natural cyclic
compounds.

Ingenol, a complex, terpenoid natural product, related to but simpler than the paclitaxel that follows,
which displays a complex ring structure including 3-, 5-, and 7-membered non-aromatic, carbocyclic
rings.

Cycloalkanes, the simplest carbocycles, including cyclopropane, cyclobutane,cyclopentane,

and cyclohexane. Note, elsewhere an organic chemistry shorthand is used where hydrogen atoms are
inferred as present to fill the carbon's valence of 4 (rather than their being shown explicitly).

Paclitaxel, another complex, plant-derivedterpenoid, also a natural product, displaying a complex multiring structure including 4-, 6-, and 8-membered rings (carbocyclic andheterocyclic, aromatic and nonaromatic).

Adding to their complexity and number, closing of atoms into rings may lock particular atoms with
distinct substitution (by functional groups) such that stereochemistry andchirality of the compound
results, including some manifestations that are unique to rings (e.g., configurational isomers). As
well, depending on ring size, the three-dimensional shapes of particular cyclic structurestypically
rings of 5-atoms and largercan vary and interconvert such that conformational isomerism is
displayed. Indeed, the development of this important chemical concept arose, historically, in
reference to cyclic compounds. Finally, cyclic compounds, because of the unique shapes,
reactivities, properties, andbioactivities that they engender, are the largest majority of all molecules
involved in the biochemistry, structure, and function of living organisms, and in the man-made
molecules (e.g., drugs, herbicides, etc.).

Heterocyclic Compounds
Compounds classified as heterocyclic probably constitute the largest and most varied family of
organic compounds. After all, every carbocyclic compound, regardless of structure and
functionality, may in principle be converted into a collection of heterocyclic analogs by replacing
one or more of the ring carbon atoms with a different element. Even if we restrict our
consideration to oxygen, nitrogen and sulfur (the most common heterocyclic elements), the
permutations and combinations of such a replacement are numerous.

Nomenclature
Devising a systematic nomenclature system for heterocyclic compounds presented a formidable
challenge, which has not been uniformly concluded. Many heterocycles, especially amines,
were identified early on, and received trivial names which are still preferred. Some monocyclic
compounds of this kind are shown in the following chart, with the common (trivial) name in bold
and a systematic name based on the Hantzsch-Widman system given beneath it in blue. The
rules for using this system will be given later. For most students, learning these common names
will provide an adequate nomenclature background.

An easy to remember, but limited, nomenclature system makes use of an elemental prefix for
the heteroatom followed by the appropriate carbocyclic name. A short list of some common
prefixes is given in the following table, priority order increasing from right to left. Examples of
this nomenclature are: ethylene oxide = oxacyclopropane, furan = oxacyclopenta-2,4-diene,
pyridine = azabenzene, and morpholine = 1-oxa-4-azacyclohexane.
Element

oxygen

sulfur

selenium

nitrogen

phosphorous

silicon

boron

Valence

II

II

II

III

III

IV

III

Prefix

Oxa

Thia

Selena

Aza

Phospha

Sila

Bora

The Hantzsch-Widman system provides a more systematic method of naming heterocyclic

compounds that is not dependent on prior carbocyclic names. It makes use of the same hetero
atom prefix defined above (dropping the final "a"), followed by a suffix designating ring size and
saturation. As outlined in the following table, each suffix consists of a ring size root (blue) and an
ending intended to designate the degree of unsaturation in the ring. In this respect, it is
important to recognize that the saturated suffix applies only to completely saturated ring
systems, and the unsaturated suffix applies to rings incorporating the maximum number of
non-cumulated double bonds. Systems having a lesser degree of unsaturation require an
appropriate prefix, such as "dihydro"or "tetrahydro".
Ring Size
Suffix
Unsaturated
Saturated

10

irene
irane

ete
etane

ole
olane

ine
inane

epine
epane

ocine
ocane

onine
onane

ecine
ecane

Despite the general systematic structure of the Hantzsch-Widman system, several exceptions
and modifications have been incorporated to accommodate conflicts with prior usage. Some
examples are:
The terminal "e" in the suffix is optional though recommended.
Saturated 3, 4 & 5-membered nitrogen heterocycles should use respectively the
traditional "iridine", "etidine" & "olidine" suffix.
Unsaturated nitrogen 3-membered heterocycles may use the traditional "irine" suffix.
Consistent use of "etine" and "oline" as a suffix for 4 & 5-membered unsaturated
heterocycles is prevented by their former use for similar sized nitrogen heterocycles.
Established use of oxine, azine and silane for other compounds or functions prohibits
their use for pyran, pyridine and silacyclohexane respectively.
Examples of these nomenclature rules are written in blue, both in the previous diagram and that
shown below. Note that when a maximally unsaturated ring includes a saturated atom, its
location may be designated by a "#H " prefix to avoid ambiguity, as in pyran and pyrrole above
and several examples below. When numbering a ring with more than one heteroatom, the

highest priority atom is #1 and continues in the direction that gives the next priority atom the
lowest number.

All the previous examples have been monocyclic compounds. Polycyclic compounds
incorporating one or more heterocyclic rings are well known. A few of these are shown in the
following diagram. As before, common names are in black and systematic names in blue. The
two quinolines illustrate another nuance of heterocyclic nomenclature. Thus, the location of a
fused ring may be indicated by a lowercase letter which designates the edge of the heterocyclic
ring involved in the fusion, as shown by the pyridine ring in the green shaded box.

Heterocyclic rings are found in many naturally occurring compounds. Most notably, they
compose the core structures of mono and polysaccharides, and the four DNA bases that
establish the genetic code. By clicking on the above diagram some other examples of
heterocyclic natural products will be displayed.

Preparation and Reactions

Three-Membered Rings
Oxiranes (epoxides) are the most commonly encountered three-membered heterocycles.
Epoxides are easily prepared by reaction of alkenes with peracids, usually with good
stereospecificity. Because of the high angle strain of the three-membered ring, epoxides are
more reactive that unstrained ethers. Addition reactions proceeding by electrophilic or
nucleophilic opening of the ring constitute the most general reaction class. Example 1 in the
following diagram shows one such transformation, which is interesting due to subsequent
conversion of the addition intermediate into the corresponding thiirane. The initial ring opening
is stereoelectronically directed in a trans-diaxial fashion, the intermediate relaxing to the
diequatorial conformer before cyclizing to a 1,3-oxathiolane intermediate.
Other examples show similar addition reactions to thiiranes and aziridines. The acid-catalyzed
additions in examples 2 and 3, illustrate the influence of substituents on the regioselectivity of
addition. Example 2 reflects the SN2 character of nucleophile (chloride anion) attack on the
protonated aziridine (the less substituted carbon is the site of addition). The phenyl substituent
in example 3 serves to stabilize the developing carbocation to such a degree that SN1 selectivity
is realized. The reduction of thiiranes to alkenes by reaction with phosphite esters (example 6)
is highly stereospecific, and is believed to take place by an initial bonding of phosphorous to
sulfur.

By clicking on the above diagram, four additional example of three-membered heterocycle

reactivity or intermediacy will be displayed. Examples 7 and 8 are thermal reactions in which
both the heteroatom and the strained ring are important factors. The -lactone intermediate
shown in the solvolysis of optically active 2-bromopropanoic acid (example 9) accounts both for
the 1st-order kinetics of this reaction and the retention of configuration in the product. Note that
two inversions of configuration at C-2 result in overall retention. Many examples
of intramolecular interactions, such as example 10, have been documented.
An interesting regioselectivity in the intramolecular ring-opening reactions of disubstituted
epoxides having a pendant -hydroxy substituent has been noted. As illustrated below, acid and

base-catalyzed reactions normally proceed by 5-exo-substitution (reaction 1), yielding a

tetrahydrofuran product. However, if the oxirane has an unsaturated substituent (vinyl or
phenyl), the acid-catalyzed opening occurs at the allylic (or benzylic) carbon (reaction 2) in a 6endo fashion. The -electron system of the substituent assists development of positive charge
at the adjacent oxirane carbon, directing nucleophilic attack to that site.

Four-Membered Rings
Preparation
Several methods of preparing four-membered heterocyclic compounds are shown in the
following diagram. The simple procedure of treating a 3-halo alcohol, thiol or amine with base is
generally effective, but the yields are often mediocre. Dimerization and elimination are common
side reactions, and other functions may compete in the reaction. In the case of example 1,
cyclization to an oxirane competes with thietane formation, but the greater nucleophilicity of
sulfur dominates, especially if a weak base is used. In example 2 both aziridine and azetidine
formation are possible, but only the former is observed. This is a good example of the kinetic
advantage of three-membered ring formation. Example 4 demonstrates that this approach to
azetidine formation works well in the absence of competition. Indeed, the exceptional yield of
this product is attributed to the gem-dimethyl substitution, the Thorpe-Ingold effect, which is
believed to favor coiled chain conformations. The relatively rigid configuration of the substrate in
example 3, favors oxetane formation and prevents an oxirane cyclization from occurring. Finally,
the Paterno-Buchi photocyclizations in examples 5 and 6 are particularly suited to oxetane
formation.

Reactions
Reactions of four-membered heterocycles also show the influence of ring strain. Some
examples are given in the following diagram. Acid-catalysis is a common feature of many ringopening reactions, as shown by examples 1, 2 & 3a. In the thietane reaction (2), the sulfur
undergoes electrophilic chlorination to form a chlorosulfonium intermediate followed by a ringopening chloride ion substitution. Strong nucleophiles will also open the strained ether, as
shown by reaction 3b. Cleavage reactions of -lactones may take place either by acid-catalyzed
acyl exchange, as in 4a, or by alkyl-O rupture by nucleophiles, as in 4b. Example 5 is an
interesting case of intramolecular rearrangement to an ortho-ester. Finally, the -lactam
cleavage of penicillin G (reaction 6) testifies to the enhanced acylating reactivity of this fused
ring system. Most amides are extremely unreactive acylation reagents, thanks to stabilization
by p- resonance. Such electron pair delocalization is diminished in the penicillins, leaving the
nitrogen with a pyramidal configuration and the carbonyl function more reactive toward
nucleophiles.

Five-Membered Rings
Preparation
Commercial preparation of furan proceeds by way of the aldehyde, furfural, which in turn is
generated from pentose containing raw materials like corncobs, as shown in the uppermost
equation below. Similar preparations of pyrrole and thiophene are depicted in the second row
equations. Equation 1 in the third row illustrates a general preparation of substituted furans,
pyrroles and thiophenes from 1,4-dicarbonyl compounds, known as the Paal-Knorr synthesis.
Many other procedures leading to substituted heterocycles of this kind have been devised. Two
of these are shown in reactions 2 and 3. Furan is reduced to tetrahydrofuran by palladiumcatalyzed hydrogenation. This cyclic ether is not only a valuable solvent, but it is readily
converted to 1,4-dihalobutanes or 4-haloalkylsulfonates, which may be used to prepare
pyrrolidine and thiolane.
Dipolar cycloaddition reactions often lead to more complex five-membered heterocycles.

Indole is probably the most important fused ring heterocycle in this class. By clicking on the
above diagram three examples of indole synthesis will be displayed. The first proceeds by an
electrophilic substitution of a nitrogen-activated benzene ring. The second presumably takes
place by formation of a dianionic species in which the ArCH2() unit bonds to the deactivated
carbonyl group. Finally, the Fischer indole synthesis is a remarkable sequence of
tautomerism, sigmatropic rearrangement, nucleophilic addition, and elimination reactions
occurring subsequent to phenylhydrazone formation. This interesting transformation involves
the oxidation of two carbon atoms and the reduction of one carbon and both nitrogen atoms.
Reactions
The chemical reactivity of the saturated members of this class of heterocycles: tetrahydrofuran,
thiolane and pyrrolidine, resemble that of acyclic ethers, sulfides, and 2-amines, and will not be
described here. 1,3-Dioxolanes and dithiolanes are cyclic acetals and thioacetals. These units

are commonly used as protective groups for aldehydes and ketones, and may be hydrolyzed by
the action of aqueous acid.
It is the "aromatic" unsaturated compounds, furan, thiophene and pyrrole that require our
attention. In each case the heteroatom has at least one pair of non-bonding electrons that may
combine with the four -electrons of the double bonds to produce an annulene having
an aromatic sextet of electrons. This is illustrated by the resonance description at the top of the
following diagram. The heteroatom Y becomes sp2-hybridized and acquires a positive charge as
its electron pair is delocalized around the ring. An easily observed consequence of this
delocalization is a change in dipole moment compared with the analogous saturated
heterocycles, which all have strong dipoles with the heteroatom at the negative end. As
expected, the aromatic heterocycles have much smaller dipole moments, or in the case of
pyrrole a large dipole in the opposite direction. An important characteristic of aromaticity is
enhanced thermodynamic stability, and this is usually demonstrated by relative heats of
hydrogenation or heats of combustionmeasurements. By this standard, the three aromatic
heterocycles under examination are stabilized, but to a lesser degree than benzene.
Additional evidence for the aromatic character of pyrrole is found in its exceptionally weak
basicity (pKa ca. 0) and strong acidity (pKa = 15) for a 2-amine. The corresponding values for
the saturated amine pyrrolidine are: basicity 11.2 and acidity 32.

Another characteristic of aromatic systems, of particular importance to chemists, is their pattern

of reactivity with electrophilic reagents. Whereas simple cycloalkenes generally give addition
reactions, aromatic compounds tend to react by substitution. As noted for benzene and its
derivatives, these substitutions take place by an initial electrophile addition, followed by a proton
loss from the "onium" intermediate to regenerate the aromatic ring. The aromatic five-membered
heterocycles all undergo electrophilic substitution, with a general reactivity order: pyrrole >>
furan > thiophene > benzene. Some examples are given in the following diagram. The reaction
conditions show clearly the greater reactivity of furan compared with thiophene. All these
aromatic heterocycles react vigorously with chlorine and bromine, often forming
polyhalogenated products together with polymers. The exceptional reactivity of pyrrole is
evidenced by its reaction with iodine (bottom left equation), and formation of 2-acetylpyrrole by
simply warming it with acetic anhydride (no catalyst).

There is a clear preference for substitution at the 2-position () of the ring, especially for furan
and thiophene. Reactions of pyrrole require careful evaluation, since N-protonation destroys its
aromatic character. Indeed, N-substitution of this 2-amine is often carried out prior to
subsequent reactions. For example, pyrrole reacts with acetic anhydride or acetyl chloride and
triethyl amine to give N-acetylpyrrole. Consequently, the regioselectivity of pyrrole substitution is
variable, as noted by the bottom right equation.
An explanation for the general -selectivity of these substitution reactions is apparent from the
mechanism outlined below. The intermediate formed by electrophile attack at C-2 is stabilized
by charge delocalization to a greater degree than the intermediate from C-3 attack. From
the Hammond postulate we may then infer that the activation energy for substitution at the
former position is less than the latter substitution.

Functional substituents influence the substitution reactions of these heterocycles in much the
same fashion as they do for benzene. Indeed, once one understands the ortho-para and metadirecting character of these substituents, their directing influence on heterocyclic ring
substitution is not difficult to predict. The following diagram shows seven such reactions.
Reactions 1 & 2 are 3-substituted thiophenes, the first by an electron donating substituent and
the second by an electron withdrawing group. The third reaction has two substituents of different
types in the 2 and 5-positions. Finally, examples 4 through 7 illustrate reactions of 1,2- and 1,3oxazole, thiazole and diazole. Note that the basicity of the sp2-hybridized nitrogen in the

diazoles is over a million times greater than that of the apparent sp3-hybridized nitrogen, the
electron pair of which is part of the aromatic electron sextet.

Other possible reactions are suggested by the structural features of these heterocycles. For
example, furan could be considered an enol ether and pyrrole an enamine. Such functions are
known to undergoacid-catalyzed hydrolysis to carbonyl compounds and alcohols or amines.
Since these compounds are also heteroatom substituted dienes, we might anticipate Diels-Alder
cycloaddition reactions with appropriate dienophiles. These possibilities will be illustrated
above by clicking on the diagram. As noted in the upper example, furans may indeed be
hydrolyzed to 1,4-dicarbonyl compounds, but pyrroles and thiophenes behave differently. The
second two examples, shown in the middle, demonstrate typical reactions of furan and pyrrole
with the strong dienophile maleic anhydride. The former participates in a cycloaddition reaction;
however, the pyrrole simply undergoes electrophilic substitution at C-2. Thiophene does not
easily react with this dienophile.
The bottom line of the new diagram illustrates the remarkable influence that additional nitrogen
units have on the hydrolysis of a series of N-acetylazoles in water at 25 C and pH=7. The
pyrrole compound on the left is essentially unreactive, as expected for an amide, but additional
nitrogens markedly increase the rate of hydrolysis. This effect has been put to practical use in
applications of the acylation reagent 1,1'-carbonyldiimidazole (Staab's reagent).
Another facet of heterocyclic chemistry was disclosed in the course of investigations concerning
the action of thiamine (following diagram). As its pyrophosphate derivative, thiamine is a
coenzyme for several biochemical reactions, notably decarboxylations of pyruvic acid to
acetaldehyde and acetoin. Early workers speculated that an "active aldehyde" or acyl carbanion
species was an intermediate in these reactions. Many proposals were made, some involving the
aminopyrimidine moiety, and others, ring-opened hydrolysis derivatives of the thiazole ring, but
none were satisfactory. This puzzle was solved when R. Breslow(Columbia) found that the C-2
hydrogen of thiazolium salts was unexpectedly acidic (pKa ca. 13), forming a relatively stable
ylide conjugate base. As shown, this rationalizes the facile decarboxylation of thiazolium-2carboxylic acids and deuterium exchange at C-2 in neutral heavy water.

Appropriate thiazolium salts catalyze the conversion of aldehydes to acyloins in much the same
way that cyanide ion catalyzes the formation of benzoin from benzaldehyde, the benzoin
condensation. By clicking on the diagram, a new display will show mechanisms for these two
reactions. Note that in both cases an acyl anion equivalent is formed and then adds to a
carbonyl function in the expected manner. The benzoin condensation is limited to aromatic
aldehydes, but the use of thiazolium catalysts has proven broadly effective for aliphatic and
aromatic aldehydes. This approach to acyloins employs milder conditions than the reduction of
esters to enediol intermediates by the action of metallic sodium .

The most important condensed ring system related to these heterocycles is indole. Some
electrophilic substitution reactions of indole are shown in the following diagram. Whether the
indole nitrogen is substituted or not, the favored site of attack is C-3 of the heterocyclic ring.
Bonding of the electrophile at that position permits stabilization of the onium-intermediate by the
nitrogen without disruption of the benzene aromaticity.

Six-Membered Rings
Properties
The chemical reactivity of the saturated members of this class of heterocycles: tetrahydropyran,
thiane and piperidine, resemble that of acyclic ethers, sulfides, and 2-amines, and will not be
described here. 1,3-Dioxanes and dithianes are cyclic acetals and thioacetals. These units are
commonly used as protective groups for aldehydes and ketones, as well as synthetic
intermediates, and may be hydrolyzed by the action of aqueous acid. The reactivity of partially
unsaturated compounds depends on the relationship of the double bond and the heteroatom
(e.g. 3,4-dihydro-2H-pyran is an enol ether).
Fully unsaturated six-membered nitrogen heterocycles, such as pyridine, pyrazine, pyrimidine
and pyridazine, have stable aromatic rings. Oxygen and sulfur analogs are necessarily
positively charged, as in the case of 2,4,6-triphenylpyrylium tetrafluoroborate.

From heat of combustion measurements, the aromatic stabilization energy of pyridine is 21

kcal/mole. The resonance description drawn at the top of the following diagram includes charge
separated structures not normally considered for benzene. The greater electronegativity of
nitrogen (relative to carbon) suggests that such canonical forms may contribute to a significant
degree. Indeed, the larger dipole moment of pyridine compared with piperidine supports this
view. Pyridine and its derivatives are weak bases, reflecting the sp2 hybridization of the nitrogen.
From the polar canonical forms shown here, it should be apparent that electron donating
substituents will increase the basicity of a pyridine, and that substituents on the 2 and 4positions will influence this basicity more than an equivalent 3-substituent. The pKa values given
in the table illustrate a few of these substituent effects. Methyl substituted derivatives have the
common names picoline (methyl pyridines), lutidine (dimethyl pyridines) and collidine (trimethyl
pyridines). The influence of 2-substituents is complex, consisting of steric hindrance and

electrostatic components. 4-Dimethylaminopyridine is a useful catalyst for acylation reactions

carried out in pyridine as a solvent. At first glance, the sp3 hybridized nitrogen might appear to
be the stronger base, but it should be remembered that N,N-dimethylaniline has a pKa slightly
lower than that of pyridine itself. Consequently, the sp2 ring nitrogen is the site at which
protonation occurs.

The diazines pyrazine, pyrimidine and pyridazine are all weaker bases than pyridine due to the
inductive effect of the second nitrogen. However, the order of base strength is unexpected. A
consideration of the polar contributors helps to explain the difference between pyrazine and
pyrimidine, but the basicity of pyridazine seems anomalous. It has been suggested that electron
pair repulsion involving the vicinal nitrogens destabilizes the neutral base relative to its
conjugate acid.
Electrophilic Substitution of Pyridine
Pyridine is a modest base (pKa=5.2). Since the basic unshared electron pair is not part of the
aromatic sextet, as in pyrrole, pyridinium species produced by N-substitution retain the
aromaticity of pyridine. As shown below, N-alkylation and N-acylation products may be prepared
as stable crystalline solids in the absence of water or other reactive nucleophiles. The N-acyl
salts may serve as acyl transfer agents for the preparation of esters and amides. Because of the
stability of the pyridinium cation, it has been used as a moderating component in complexes
with a number of reactive inorganic compounds. Several examples of these stable and easily
handled reagents are shown at the bottom of the diagram. The poly(hydrogen fluoride) salt is a
convenient source of HF for addition to alkenes and conversion of alcohols to alkyl
fluorides, pyridinium chlorochromate (PCC) and its related dichromate analog are versatile
oxidation agents and the tribromide salt is a convenient source of bromine. Similarly, the
reactive compounds sulfur trioxide and diborane are conveniently and safely handled as
pyridine complexes.
Amine oxide derivatives of 3-amines and pyridine are readily prepared by oxidation with
peracids or peroxides, as shown by the upper right equation. Reduction back to the amine can
usually be achieved by treatment with zinc (or other reactive metals) in dilute acid.

From the previous resonance description of pyridine, we expect this aromatic amine to undergo
electrophilic substitution reactions far less easily than does benzene. Furthermore, as depicted
above by clicking on the diagram, the electrophilic reagents and catalysts employed in these
reactions coordinate with the nitrogen electron pair, exacerbating the positive charge at
positions 2,4 & 6 of the pyridine ring. Three examples of the extreme conditions required for
electrophilic substitution are shown on the left. Substituents that block electrophile coordination
with nitrogen or reduce the basicity of the nitrogen facilitate substitution, as demonstrated by the
examples in the blue-shaded box at the lower right, but substitution at C-3 remains dominant.
Activating substituents at other locations also influence the ease and regioselectivity of
substitution. By clicking on the diagram a second time, three examples will shown on the left.
The amine substituent in the upper case directs the substitution to C-2, but the weaker electron
donating methyl substituent in the middle example cannot overcome the tendency for 3substitution. Hydroxyl substituents at C-2 and C-4 tautomerize to pyridones, as shown for the 2isomer at the bottom left.
Pyridine N-oxide undergoes some electrophilic substitutions at C-4 and others at C-3. The
coordinate covalent NO bond may exert a push-pull influence, as illustrated by the two
examples on the right. Although the positively charged nitrogen alone would have a strong
deactivating influence, the negatively charged oxygen can introduce electron density at C-2, C-4
& C-6 by -bonding to the ring nitrogen. This is a controlling factor in the relatively facile
nitration at C-4. However, if the oxygen is bonded to an electrophile such as SO3, the resulting
pyridinium ion will react sluggishly and preferentially at C-3.
The fused ring heterocycles quinoline and isoquinoline provide additional evidence for the
stability of the pyridine ring. Vigorous permanganate oxidation of quinoline results in
predominant attack on the benzene ring; isoquinoline yields products from cleavage of both
rings. Note that naphthalene is oxidized to phthalic acid in a similar manner. By contrast, the
heterocyclic ring in both compounds undergoes preferential catalytic hydrogenation to yield
tetrahydroproducts. Electrophilic nitration, halogenation and sulfonation generally take place at
C-5 and C-8 of the benzene ring, in agreement with the preceding description of similar pyridine
reactions and the kinetically favored substitution of naphthalene at C-1 () rather than C-2 ().

Other Reactions of Pyridine

Thanks to the nitrogen in the ring, pyridine compounds undergo nucleophilic substitution
reactions more easily than equivalent benzene derivatives. In the following diagram, reaction 1
illustrates displacement of a 2-chloro substituent by ethoxide anion. The addition-elimination
mechanism shown for this reaction is helped by nitrogen's ability to support a negative charge. A
similar intermediate may be written for substitution of a 4-halopyridine, but substitution at the 3position is prohibited by the the failure to create an intermediate of this kind. The two
Chichibabin aminations in reactions 2 and 3 are remarkable in that the leaving anion is hydride
(or an equivalent). Hydrogen is often evolved in the course of these reactions. In accord with
this mechanism, quinoline is aminated at both C-2 and C-4.
Addition of strong nucleophiles to N-oxide derivatives of pyridine proceed more rapidly than to
pyridine itself, as demonstrated by reactions 4 and 5. The dihydro-pyridine intermediate easily
loses water or its equivalent by elimination of the OM substituent on nitrogen.

By clicking on the above diagram, five additional examples of base or nucleophile reactions with
substituted pyridine will be displayed. Because the pyridine ring (and to a greater degree the Noxide ring) can support a negative charge, alkyl substituents in the 2- and 4-locations are
activated in the same fashion as by a carbonyl group. Reactions 6 and 7 show alkylation and
condensation reactions resulting from this activation. Reaction 8 is an example of Nalkylpyridone formation by hydroxide addition to an N-alkyl pyridinium cation, followed by mild
oxidation. Birch reduction converts pyridines to dihydropyridines that are bis-enamines and may
be hydrolyzed to 1,5-dicarbonyl compounds. Pyridinium salts undergo a one electron transfer to
generate remarkably stable free radicals. The example shown in reaction 9 is a stable (in the
absence of oxygen), distillable green liquid. Although 3-halopyridines do not undergo additionelimination substitution reactions as do their 2- and 4-isomers, the strong base sodium amide
effects amination by way of a pyridyne intermediate. This is illustrated by reaction 10. It is
interesting that 3-pyridyne is formed in preference to 2-pyridyne. The latter is formed if C-4 is
occupied by an alkyl substituent. The pyridyne intermediate is similar to benzyne.

Some Polycyclic Heterocycles

Heterocyclic structures are found in many natural products. Examples of some nitrogen
compounds, known as alkaloids because of their basic properties, were given in the amine
chapter. Some other examples are displayed in the following diagram. Camptothecin is a
quinoline alkaloid which inhibits the DNA enzyme topoisomerase I. Reserpine is an indole
alkaloid, which has been used for the control of high blood pressure and the treatment of
psychotic behavior. Ajmaline and strychnine are also indole alkaloids, the former being an
antiarrhythmic agent and latter an extremely toxic pesticide. The neurotoxins saxitoxin and
tetrodotoxin both have marine origins and are characterized by guanidiniun moieties. Aflatoxin
B1 is a non-nitrogenous carcinogenic compound produced by the Aspergillus fungus.

Porphyrin is an important cyclic tertrapyrrole that is the core structure of heme and chlorophyll.
These structures will be drawn above by clicking on the diagram.
Derivatives of the simple fused ring heterocycle purine constitute an especially important and
abundant family of natural products. The amino compounds adenine and guanine are two of the
complementary bases that are essential components of DNA. Structures for these compounds
are shown in the following diagram. Xanthine and uric acid are products of the metabolic
oxidation of purines. Uric acid is normally excreted in the urine; an excess serum accumulation
of uric acid may lead to an arthritic condition known as gout.

Examples of common methylated purines will be drawn above by clicking on the diagram.
Caffeine, the best known of these, is a bitter, crystalline alkaloid. It is found in varying quantities,
along with additional alkaloids such as the cardiac stimulants theophylline and theobromine in
the beans, leaves, and fruit of certain plants. Drinks containing caffeine, such as coffee, tea and
some soft drinks are arguably the world's most widely consumed beverages. Caffeine is a
central nervous system stimulant, serving to ward off drowsiness and restore alertness.
Paraxantheine is the chief metabolite of caffeine in the body.
Sulfur heterocycles are found in nature, but to a lesser degree than their nitrogen and oxygen
analogs. Two members of the B-vitamin complex, biotin and thiamine, incorporate such
heterocyclic moieties. These are shown together with other heterocyclic B-vitamins in the
following diagram.

Terthienyl is an interesting thiophene trimer found in the roots of marigolds, where it provides
nemicidal activity. Studies have shown that UV irradiation of terthienyl produces a general
phototoxicity for many organisms. Polymers incorporating thiophene units and fused systems
such as dithienothiophene have interesting electromagnetic properties, and show promise as
organic metal-like conductors and photovoltaic materials. The charge transfer complex formed

by tetrathiofulvalene and tetracyanoquinodimethane has one of the highest electrical

conductivities reported for an organic solid.

Heterocyclic compound
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two
different elements as members of its ring(s).[1]Heterocyclic chemistry is the branch of chemistry
dealing with the synthesis, properties and applications of these heterocycles. In contrast, the rings
ofhomocyclic compounds consist entirely of atoms of the same element.

Pyridine, a heterocyclic compound