Organic Lab

PDF generated using the open source mwlib toolkit. See http://code.pediapress.com/ for more information.
PDF generated at: Sun, 17 Oct 2010 21:13:17 UTC
Contents
Articles
Melting point 1
Distillation 5
Recrystallization (chemistry) 19
Fragrance extraction 24
Chromatography 28
Hydrocarbon 35
Aldehyde 39
Ketone 45
Amine 50

References
Article Sources and Contributors 58
Image Sources, Licenses and Contributors 60

Article Licenses
License 62
Melting point 1

Melting point
The melting point of a solid is the temperature at which the vapor pressure of the solid and the liquid are equal. At
the melting point the solid and liquid phase exist in equilibrium. When considered as the temperature of the reverse
change from liquid to solid, it is referred to as the freezing point or crystallization point. Because of the ability of
some substances to supercool, the freezing point is not considered to be a characteristic property of a substance.
When the "characteristic freezing point" of a substance is determined, in fact the actual methodology is almost
always "the principle of observing the disappearance rather than the formation of ice", that is, the melting point.[1]

Fundamentals
For most substances, melting and freezing points are approximately
equal. For example, the melting point and freezing point of the element
mercury is 234.32 kelvin (−38.83 °C or −37.89 °F). However, certain
substances possess differing solid-liquid transition temperatures. For
example, agar melts at 85 °C (185 °F) and solidifies from 31 °C to
40 °C (89.6 °F to 104 °F); this process is known as hysteresis.

Certain materials, such as glass, may harden without crystallizing;

these are called amorphous solids. Amorphous materials as well as Melting points (in blue) and boiling points (in
some polymers do not have a true melting point as there is no abrupt pink) of the first eight carboxylic acids (°C)

phase change at any specific temperature. Instead, there is a gradual

change in their viscoelastic properties over a range of temperatures. Such materials are characterized by a glass
transition which occurs at a glass transition temperature which may be roughly defined as the "knee" point of the
material's density vs. temperature graph.

The melting point of ice at 1 atmosphere of pressure is very close [2] to 0 °C (32 °F, 273.15 K), this is also known as
the ice point. In the presence of nucleating substances the freezing point of water is the same as the melting point,
but in the absence of nucleators water can supercool to −42 °C (−43.6 °F, 231 K) before freezing.
Unlike the boiling point, the melting point is relatively insensitive to pressure because the solid/liquid transition
represents only a small change in volume.[3] [4] Melting points are often used to characterize organic and inorganic
compounds and to ascertain their purity. The melting point of a pure substance is always higher and has a smaller
range than the melting point of an impure substance. The more impurity is present, the lower the melting point and
the broader the range. Eventually, a minimum melting point will be reached. The mixing ratio that results in the
lowest possible melting point is known as the eutectic point.
The chemical element with the highest melting point is tungsten, at 3683 K (3410 °C, 6170 °F) making it excellent
for use as filaments in light bulbs. The often-cited carbon does not melt at ambient pressure but sublimes at about
4000 K; a liquid phase only exists above pressures of 10 MPa and estimated 4300–4700 K. Tantalum hafnium
carbide (Ta4HfC5) is a refractory compound with a very high melting point of 4488 K (4215 °C, 7619 °F).[5] At the
other end of the scale, helium does not freeze at all at normal pressure, even at temperatures very close to absolute
zero; pressures over 20 times normal atmospheric pressure are necessary.
Melting point 2

Melting point measurements

Many laboratory techniques exist for the determination of melting points. A Kofler bench is a metal strip with a
temperature gradient (range room temperature to 300 °C). Any substance can be placed on a section of the strip
revealing its thermal behaviour at the temperature at that point. Differential scanning calorimetry gives information
on melting point together with its enthalpy of fusion.
A basic melting point apparatus for the analysis of crystalline solids consists of a oil bath with a transparent window
(most basic design: a Thiele tube) and a simple magnifier. The several grains of a solid are placed in a thin glass tube
and partially immersed in the oil bath. The oil bath is heated (and stirred) and with the aid of the magnifier (and
external light source) melting of the individual crystals at a certain temperature can be observed. In large/small
devices, the sample is placed in a heating block, and optical detection is automated.

Thermodynamics
Not only is heat required to raise the temperature of the solid to the
melting point, but the melting itself requires heat called the heat of
fusion.

Pressure dependence of water melting point

(MPa/K)

From a thermodynamics point of view, at the melting point the change in Gibbs free energy ( ) of the material
is zero, but the enthalpy ( ) and the entropy ( ) of the material are increasing ( ). Melting
phenomenon happens when the Gibbs free energy of the liquid becomes lower than the solid for that material. At
various pressures this happens at a specific temperature. It can also be shown that:

The " "," ", and " " in the above are respectively the temperature at the melting point, change of
entropy of melting, and the change of enthalpy of melting.

Carnelley’s Rule
In organic chemistry Carnelley’s Rule, established in 1882 by Thomas Carnelley, stated that high molecular
symmetry is associated with high melting point.[6] Carnelley based his rule on examination of 15,000 chemical
compounds. For example for three structural isomers with molecular formula C5H12 the melting point increases in
the series isopentane −160 °C (113 K) n-pentane −129.8 °C (143 K) and neopentane −18 °C (255 K). Likewise in
xylenes and also dichlorobenzenes the melting point increases in the order meta, ortho and then para. Pyridine has a
lower symmetry than benzene hence its lower melting point but the melting point again increases with diazine and
triazines. Many cage-like compounds like adamantane and cubane with high symmetry have very high melting
points.
A high melting point results from a high heat of fusion, a low entropy of fusion, or a combination of both. In highly
symmetrical molecules the crystal phase is densely packed with many efficient intermolecular interactions resulting
Melting point 3

in a higher enthalpy change on melting.

Predicting the melting point of substances

An attempt to predict the bulk melting point of crystalline materials was first made in 1910 by Lindemann[7] . The
idea behind the theory was the observation that the average amplitude of thermal vibrations increase with increasing
temperature. Melting initiates when the amplitude of vibration becomes large enough for adjacent atoms to partly
occupy the same space. The Lindemann criterion states that melting is expected when the root mean square
vibration amplitude exceeds a threshold value.
If we assume that all atoms in a crystal vibrate with the same frequency , the average thermal energy can be
estimated using the equipartition theorem to be[8]

where is the atomic mass, is the frequency, is the average vibration amplitude, is the Boltzmann
constant, and is the absolute temperature. If the threshold value of is where is the Lindemann
constant and is the atomic spacing, the melting point is estimated as

Several other expressions for the estimated melting temperature can be obtained depending on the estimate of the
average thermal energy[9] . Another commonly used expression for the Lindemann criterion is[10]

If we use the expression for the Debye frequency for , we have

where is the Debye temperature and is the Planck constant. Values of range from 0.15-0.3 for most
[11]
materials .

Melting point of radioactive materials

The characterization of highly radioactive materials is an important part of the overall optimization strategy for
storage and treatment processes. An important parameter for this optimization is the crystallization temperature of
liquid wastes. The measurement of crystallization temperatures of these materials is a challenging task and has been
solved by the development and deployment of a bespoke imaging system.
The design philosophy of this instrument will be discussed, the approach taken described and the unique problems
encountered during development highlighted. In outline, the instrument consists of:
• A computer controlled unit that allows highly reproducible heating and cooling of a sample. This unit is contained
in a heavily shielded facility
• A vision system that images the sample remotely through the shield window.
• Storage and analysis of the subsequent images.
Results obtained for model solutions will be described and examples from the preliminary studies of highly
radioactive solutions given.
Melting point 4

See also
• Degree of frost
• Freezing-point depression
• List of elements by melting point
• Phases of matter
• Triple point
• Vicat softening point - the determination of the softening point for materials that have no definite melting point.
• Liquidus temperature
• Slip melting point
• Solidus temperature

References
[1] Ramsay, J. A. (1949). "A new method of freezing-point determination for small quantities" (http:/ / jeb. biologists. org/ cgi/ reprint/ 26/ 1/ 57.
pdf). J. Exp. Biol. 26 (1): 57–64. PMID 15406812. .
[2] The melting point of purified water has been measured to be 0.002519 +/- 0.000002 degrees Celsius - see R. Feistel and W. Wagner (2006).
"A New Equation of State for H2O Ice Ih". J. Phys. Chem. Ref. Data 35: 1021–1047. doi:10.1063/1.2183324.
[3] The exact relationship is expressed in the Clausius-Clapeyron relation.
[4] "J10 Heat: Change of aggregate state of substances through change of heat content: Change of aggregate state of substances and the equation
of Clapeyron-Clausius" (http:/ / mpec. sc. mahidol. ac. th/ RADOK/ physmath/ PHYSICS/ j10. htm). . Retrieved 2008-02-19.
[5] hafnium entry at Britannica.com (http:/ / www. britannica. com/ nobel/ micro/ 254_6. html)
[6] Brown, R. J. C. & R. F. C. (June 2000). "Melting Point and Molecular Symmetry". Journal of Chemical Education 77 (6): 724.
doi:10.1021/ed077p724.
[7] Lindemann FA (1910). "The calculation of molecular vibration frequencies". Physik. Z. 11: 609–612.
[8] Sorkin, S., (2003), Point defects, lattice structure, and melting (http:/ / phycomp. technion. ac. il/ ~phsorkin/ thesis/ thesis. html), Thesis,
Technion, Israel.
[9] Solyom, J., (2007), Fundamentals of the physics of solids, Volume 2, Springer.
[10] Hofmann, P., (2008), Solid state physics: an introduction, Wiley-VCH.
[11] Nelson, D. R., (2002), Defects and geometry in condensed matter physics, Cambridge University Press.

External links
• Melting and boiling point tables vol. 1 (http://www.archive.org/details/meltingboilingpo01carnuoft) by
Thomas Carnelley (Harrison, London, 1885-1887)
• Melting and boiling point tables vol. 2 (http://www.archive.org/details/meltingboilingpo02carnuoft) by
Thomas Carnelley (Harrison, London, 1885-1887)
Distillation 5

Distillation
Distillation is a method of separating mixtures based on
differences in their volatilities in a boiling liquid mixture.
Distillation is a unit operation, or a physical separation
process, and not a chemical reaction.
Commercially, distillation has a number of applications. It is
used to separate crude oil into more fractions for specific
uses such as transport, power generation and heating. Water
is distilled to remove impurities, such as salt from seawater.
Air is distilled to separate its components—notably oxygen,
nitrogen, and argon—for industrial use. Distillation of
fermented solutions has been used since ancient times to
produce distilled beverages with a higher alcohol content.
The premises where distillation is carried out, especially
distillation of alcohol, are known as a distillery.

Laboratory display of distillation: 1: A heating device 2: Still

pot 3: Still head 4: Thermometer/Boiling point temperature 5:
Condenser 6: Cooling water in 7: Cooling water out 8:
Distillate/receiving flask 9: Vacuum/gas inlet 10: Still
receiver 11: Heat control 12: Stirrer speed control 13:
Stirrer/heat plate 14: Heating (Oil/sand) bath 15: Stirring
means e.g.(shown), anti-bumping granules or mechanical
[1]
stirrer 16: Cooling bath.
Distillation 6

History
The first clear evidence of distillation comes
from Greek alchemists working in Alexandria
in the first century AD[2] . Distilled water has
been known since at least ca. 200 AD, when
Alexander of Aphrodisias described the
process.[3] Arabs learned the process from the
Egyptians and used it extensively in their
alchemical experiments.

The first clear evidence from the distillation of

alcohol comes from the School of Salerno in the
12th century.[2] [4] Fractional distillation was
developed by Tadeo Alderotti in the 13th
century.[5]
In 1500, German alchemist Hieronymus
Braunschweig published Liber de arte
Distillation apparatus of Zosimus, from Marcelin Berthelot, Collection des
destillandi (The Book of the Art of anciens alchimistes grecs (3 vol., Paris, 1887-1888).
Distillation)[6] the first book solely dedicated to
the subject of distillation, followed in 1512 by a much expanded version. In 1651, John French published The Art of
Distillation [7] the first major English compendium of practice, though it has been claimed[8] that much of it derives
from Braunschweig's work. This includes diagrams with people in them showing the industrial rather than bench
scale of the operation.

As alchemy evolved into the science of

chemistry, vessels called retorts became
used for distillations. Both alembics and
retorts are forms of glassware with long
necks pointing to the side at a downward
angle which acted as air-cooled condensers
to condense the distillate and let it drip
downward for collection. Later, copper
alembics were invented. Riveted joints were
often kept tight by using various mixtures,
for instance a dough made of rye flour.[9]
These alembics often featured a cooling A retort.

system around the beak, using cold water for

instance, which made the condensation of
alcohol more efficient. These were called
pot stills. Today, the retorts and pot stills
have been largely supplanted by more
efficient distillation methods in most
industrial processes. However, the pot still is
still widely used for the elaboration of some Old Ukrainian vodka still
fine alcohols such as cognac, Scotch

whisky, tequila and some vodkas. Pot stills made of various materials (wood, clay, stainless steel) are also used by
bootleggers in various countries. Small pot stills are also sold for the domestic production[10] of flower water or
Distillation 7

essential oils.
Early forms of distillation were batch processes using one vaporization and one condensation. Purity was improved
by further distillation of the condensate. Greater volumes were processed by simply repeating the distillation.
Chemists were reported to carry out as many as 500 to 600 distillations in order to obtain a pure compound[11] .
In the early 19th century the basics of modern techniques including pre-heating and reflux were developed,
particularly by the French[11] , then in 1830 a British Patent was issued to Aeneas Coffey for a whiskey distillation
column[12] , which worked continuously and may be regarded as the archetype of modern petrochemical units. In
1877, Ernest Solvay was granted a U.S. Patent for a tray column for ammonia distillation[13] and the same and
subsequent years saw developments of this theme for oil and spirits.
With the emergence of chemical engineering as a discipline at the end of the 19th century, scientific rather than
empirical methods could be applied. The developing petroleum industry in the early 20th century provided the
impetus for the development of accurate design methods such as the McCabe-Thiele method and the Fenske
equation. The availability of powerful computers has also allowed direct computer simulation of distillation
columns.

Applications of distillation
The application of distillation can roughly be divided in four groups: laboratory scale, industrial distillation,
distillation of herbs for perfumery and medicinals (herbal distillate), and food processing. The latter two are
distinctively different from the former two in that in the processing of beverages, the distillation is not used as a true
purification method but more to transfer all volatiles from the source materials to the distillate.
The main difference between laboratory scale distillation and industrial distillation is that laboratory scale distillation
is often performed batch-wise, whereas industrial distillation often occurs continuously. In batch distillation, the
composition of the source material, the vapors of the distilling compounds and the distillate change during the
distillation. In batch distillation, a still is charged (supplied) with a batch of feed mixture, which is then separated
into its component fractions which are collected sequentially from most volatile to less volatile, with the bottoms
(remaining least or non-volatile fraction) removed at the end. The still can then be recharged and the process
repeated.
In continuous distillation, the source materials, vapors, and distillate are kept at a constant composition by carefully
replenishing the source material and removing fractions from both vapor and liquid in the system. This results in a
better control of the separation process.

Idealized distillation model

The boiling point of a liquid is the temperature at which the vapor pressure of the liquid equals the pressure in the
liquid, enabling bubbles to form without being crushed. A special case is the normal boiling point, where the vapor
pressure of the liquid equals the ambient atmospheric pressure.
It is a common misconception that in a liquid mixture at a given pressure, each component boils at the boiling point
corresponding to the given pressure and the vapors of each component will collect separately and purely. This,
however, does not occur even in an idealized system. Idealized models of distillation are essentially governed by
Raoult's law and Dalton's law, and assume that vapor-liquid equilibria are attained.
Raoult's law assumes that a component contributes to the total vapor pressure of the mixture in proportion to its
percentage of the mixture and its vapor pressure when pure, or succinctly: partial pressure equals mole fraction
multiplied by vapor pressure when pure. If one component changes another component's vapor pressure, or if the
volatility of a component is dependent on its percentage in the mixture, the law will fail.
Dalton's law states that the total vapor pressure is the sum of the vapor pressures of each individual component in the
mixture. When a multi-component liquid is heated, the vapor pressure of each component will rise, thus causing the
Distillation 8

total vapor pressure to rise. When the total vapor pressure reaches the pressure surrounding the liquid, boiling occurs
and liquid turns to gas throughout the bulk of the liquid. Note that a mixture with a given composition has one
boiling point at a given pressure, when the components are mutually soluble.
An implication of one boiling point is that lighter components never cleanly "boil first". At boiling point, all volatile
components boil, but for a component, its percentage in the vapor is the same as its percentage of the total vapor
pressure. Lighter components have a higher partial pressure and thus are concentrated in the vapor, but heavier
volatile components also have a (smaller) partial pressure and necessarily evaporate also, albeit being less
concentrated in the vapor. Indeed, batch distillation and fractionation succeed by varying the composition of the
mixture. In batch distillation, the batch evaporates, which changes its composition; in fractionation, liquid higher in
the fractionation column contains more lights and boils at lower temperatures.
The idealized model is accurate in the case of chemically similar liquids, such as benzene and toluene. In other cases,
severe deviations from Raoult's law and Dalton's law are observed, most famously in the mixture of ethanol and
water. These compounds, when heated together, form an azeotrope, which is a composition with a boiling point
higher or lower than the boiling point of each separate liquid. Virtually all liquids, when mixed and heated, will
display azeotropic behaviour. Although there are computational methods that can be used to estimate the behavior of
a mixture of arbitrary components, the only way to obtain accurate vapor-liquid equilibrium data is by measurement.
It is not possible to completely purify a mixture of components by distillation, as this would require each component
in the mixture to have a zero partial pressure. If ultra-pure products are the goal, then further chemical separation
must be applied. When a binary mixture is evaporated and the other component, e.g. a salt, has zero partial pressure
for practical purposes, the process is simpler and is called evaporation in engineering.

Batch distillation
Heating an ideal mixture of two volatile substances A
and B (with A having the higher volatility, or lower
boiling point) in a batch distillation setup (such as in an
apparatus depicted in the opening figure) until the
mixture is boiling results in a vapor above the liquid
which contains a mixture of A and B. The ratio
between A and B in the vapor will be different from the
ratio in the liquid: the ratio in the liquid will be
determined by how the original mixture was prepared,
A batch still showing the separation of A and B. while the ratio in the vapor will be enriched in the more
volatile compound, A (due to Raoult's Law, see above).
The vapor goes through the condenser and is removed from the system. This in turn means that the ratio of
compounds in the remaining liquid is now different from the initial ratio (i.e. more enriched in B than the starting
liquid).
The result is that the ratio in the liquid mixture is changing, becoming richer in component B. This causes the boiling
point of the mixture to rise, which in turn results in a rise in the temperature in the vapor, which results in a changing
ratio of A : B in the gas phase (as distillation continues, there is an increasing proportion of B in the gas phase). This
results in a slowly changing ratio A : B in the distillate.
If the difference in vapor pressure between the two components A and B is large (generally expressed as the
difference in boiling points), the mixture in the beginning of the distillation is highly enriched in component A, and
when component A has distilled off, the boiling liquid is enriched in component B.
Distillation 9

Continuous distillation
Continuous distillation is an ongoing distillation in which a liquid mixture is continuously (without interruption) fed
into the process and separated fractions are removed continuously as output streams as time passes during the
operation. Continuous distillation produces at least two output fractions, including at least one volatile distillate
fraction, which has boiled and been separately captured as a vapor condensed to a liquid. There is always a bottoms
(or residue) fraction, which is the least volatile residue that has not been separately captured as a condensed vapor.
Continuous distillation differs from batch distillation in the respect that concentrations should not change over time.
Continuous distillation can be run at a steady state for an arbitrary amount of time. For any source material of
specific composition, the main variables that affect the purity of products in continuous distillation are the reflux
ratio and the number of theoretical equilibrium stages (practically, the number of trays or the height of packing).
Reflux is a flow from the condenser back to the column, which generates a recycle that allows a better separation
with a given number of trays. Equilibrium stages are ideal steps where compositions achieve vapor-liquid
equilibrium, repeating the separation process and allowing better separation given a reflux ratio. A column with a
high reflux ratio may have fewer stages, but it refluxes a large amount of liquid, giving a wide column with a large
holdup. Conversely, a column with a low reflux ratio must have a large number of stages, thus requiring a taller
column.

General improvements
Both batch and continuous distillations can be improved by making use of a fractionating column on top of the
distillation flask. The column improves separation by providing a larger surface area for the vapor and condensate to
come into contact. This helps it remain at equilibrium for as long as possible. The column can even consist of small
subsystems ('trays' or 'dishes') which all contain an enriched, boiling liquid mixture, all with their own vapor-liquid
equilibrium.
There are differences between laboratory-scale and industrial-scale fractionating columns, but the principles are the
same. Examples of laboratory-scale fractionating columns (in increasing efficiency) include:
• Air condenser
• Vigreux column (usually laboratory scale only)
• Packed column (packed with glass beads, metal pieces, or other chemically inert material)
• Spinning band distillation system.

Laboratory scale distillation

Laboratory scale distillations are almost exclusively run as batch distillations. The device used in distillation,
sometimes referred to as a still, consists at a minimum of a reboiler or pot in which the source material is heated, a
condenser in which the heated vapour is cooled back to the liquid state, and a receiver in which the concentrated or
purified liquid, called the distillate, is collected. Several laboratory scale techniques for distillation exist (see also
distillation types).

Simple distillation
In simple distillation, all the hot vapors produced are immediately channeled into a condenser that cools and
condenses the vapors. Therefore, the distillate will not be pure - its composition will be identical to the composition
of the vapors at the given temperature and pressure, and can be computed from Raoult's law.
As a result, simple distillation is usually used only to separate liquids whose boiling points differ greatly (rule of
thumb is 25 °C),[14] or to separate liquids from involatile solids or oils. For these cases, the vapor pressures of the
components are usually sufficiently different that Raoult's law may be neglected due to the insignificant contribution
of the less volatile component. In this case, the distillate may be sufficiently pure for its intended purpose.
Distillation 10

Fractional distillation
For many cases, the boiling points of the components in the mixture will be sufficiently close that Raoult's law must
be taken into consideration. Therefore, fractional distillation must be used in order to separate the components well
by repeated vaporization-condensation cycles within a packed fractionating column. This separation, by successive
distillations, is also referred to as rectification [15] .
As the solution to be purified is heated, its vapors rise to the fractionating column. As it rises, it cools, condensing on
the condenser walls and the surfaces of the packing material. Here, the condensate continues to be heated by the
rising hot vapors; it vaporizes once more. However, the composition of the fresh vapors are determined once again
by Raoult's law. Each vaporization-condensation cycle (called a theoretical plate) will yield a purer solution of the
more volatile component.[16] In reality, each cycle at a given temperature does not occur at exactly the same position
in the fractionating column; theoretical plate is thus a concept rather than an accurate description.
More theoretical plates lead to better separations. A spinning band distillation system uses a spinning band of Teflon
or metal to force the rising vapors into close contact with the descending condensate, increasing the number of
theoretical plates.[17]

Steam distillation
Like vacuum distillation, steam distillation is a method for distilling compounds which are heat-sensitive.[18] This
process involves using bubbling steam through a heated mixture of the raw material. By Raoult's law, some of the
target compound will vaporize (in accordance with its partial pressure). The vapor mixture is cooled and condensed,
usually yielding a layer of oil and a layer of water.
Steam distillation of various aromatic herbs and flowers can result in two products; an essential oil as well as a
watery herbal distillate. The essential oils are often used in perfumery and aromatherapy while the watery distillates
have many applications in aromatherapy, food processing and skin care.

Vacuum distillation
Some compounds have very high boiling points. To boil such
compounds, it is often better to lower the pressure at which such
compounds are boiled instead of increasing the temperature. Once
the pressure is lowered to the vapor pressure of the compound (at
the given temperature), boiling and the rest of the distillation
process can commence. This technique is referred to as vacuum
distillation and it is commonly found in the laboratory in the form
of the rotary evaporator.

This technique is also very useful for compounds which boil

beyond their decomposition temperature at atmospheric pressure
and which would therefore be decomposed by any attempt to boil
them under atmospheric pressure.
Molecular distillation is vacuum distillation below the pressure
of 0.01 torr.[19] 0.01 torr is one order of magnitude above high
Dimethyl sulfoxide usually boils at 189 °C. Under a vacuum, where fluids are in the free molecular flow regime, i.e.
vacuum, it distills off into the receiver at only 70 °C. the mean free path of molecules is comparable to the size of the
equipment. The gaseous phase
Distillation 11

no longer exerts significant pressure on the substance to be

evaporated, and consequently, rate of evaporation no longer
depends on pressure. That is, because the continuum
assumptions of fluid dynamics no longer apply, mass
transport is governed by molecular dynamics rather than
fluid dynamics. Thus, a short path between the hot surface
and the cold surface is necessary, typically by suspending a
hot plate covered with a film of feed next to a cold plate with
a clear line of sight in between. Molecular distillation is used
industrially for purification of oils.

Air-sensitive vacuum distillation

Some compounds have high boiling points as well as being
air sensitive. A simple vacuum distillation system as
exemplified above can be used, whereby the vacuum is
replaced with an inert gas after the distillation is complete.
However, this is a less satisfactory system if one desires to
collect fractions under a reduced pressure. To do this a "pig"
adaptor can be added to the end of the condenser, or for
better results or for very air sensitive compounds a Perkin
Perkin triangle distillation setup
triangle apparatus can be used.
1: Stirrer bar/anti-bumping granules 2: Still pot 3:
The Perkin triangle, has means via a series of glass or Teflon Fractionating column 4: Thermometer/Boiling point
temperature 5: Teflon tap 1 6: Cold finger 7: Cooling water
taps to allows fractions to be isolated from the rest of the
out 8: Cooling water in 9: Teflon tap 2 10: Vacuum/gas inlet
still, without the main body of the distillation being removed 11: Teflon tap 3 12: Still receiver
from either the vacuum or heat source, and thus can remain
in a state of reflux. To do this, the sample is first isolated from the vacuum by means of the taps, the vacuum over the
sample is then replaced with an inert gas (such as nitrogen or argon) and can then be stoppered and removed. A fresh
collection vessel can then be added to the system, evacuated and linked back into the distillation system via the taps
to collect a second fraction, and so on, until all fractions have been collected.
Distillation 12

Short path distillation

Short path distillation is a distillation technique that involves the
distillate travelling a short distance, often only a few centimeters, and
is normally done at reduced pressure.[20] A classic example would be a
distillation involving the distillate travelling from one glass bulb to
another, without the need for a condenser separating the two chambers.
This technique is often used for compounds which are unstable at high
temperatures or to purify small amounts of compound. The advantage
is that the heating temperature can be considerably lower (at reduced
pressure) than the boiling point of the liquid at standard pressure, and
the distillate only has to travel a short distance before condensing. A
short path ensures that little compound is lost on the sides of the
apparatus. The Kugelrohr is a kind of a short path distillation apparatus Short path vacuum distillation apparatus with
vertical condenser (cold finger), to minimize the
which often contain multiple chambers to collect distillate fractions.
distillation path; 1: Still pot with stirrer
bar/anti-bumping granules 2: Cold finger - bent
to direct condensate 3: Cooling water out 4:
Other types
cooling water in 5: Vacuum/gas inlet 6: Distillate
• The process of reactive distillation involves using the reaction flask/distillate.

vessel as the still. In this process, the product is usually significantly

lower-boiling than its reactants. As the product is formed from the reactants, it is vaporized and removed from the
reaction mixture. This technique is an example of a continuous vs. a batch process; advantages include less
downtime to charge the reaction vessel with starting material, and less workup.
• Pervaporation is a method for the separation of mixtures of liquids by partial vaporization through a non-porous
membrane.
• Extractive distillation is defined as distillation in the presence of a miscible, high boiling, relatively non-volatile
component, the solvent, that forms no azeotrope with the other components in the mixture.
• Flash evaporation (or partial evaporation) is the partial vaporization that occurs when a saturated liquid stream
undergoes a reduction in pressure by passing through a throttling valve or other throttling device. This process is
one of the simplest unit operations, being equivalent to a distillation with only one equilibrium stage.
• Codistillation is distillation which is performed on mixtures in which the two compounds are not miscible.
The unit process of evaporation may also be called "distillation":
• In rotary evaporation a vacuum distillation apparatus is used to remove bulk solvents from a sample. Typically the
vacuum is generated by a water aspirator or a membrane pump.
• In a kugelrohr a short path distillation apparatus is typically used (generally in combination with a (high) vacuum)
to distill high boiling (> 300 °C) compounds. The apparatus consists of an oven in which the compound to be
distilled is placed, a receiving portion which is outside of the oven, and a means of rotating the sample. The
vacuum is normally generated by using a high vacuum pump.
Other uses:
• Dry distillation or destructive distillation, despite the name, is not truly distillation, but rather a chemical reaction
known as pyrolysis in which solid substances are heated in an inert or reducing atmosphere and any volatile
fractions, containing high-boiling liquids and products of pyrolysis, are collected. The destructive distillation of
wood to give methanol is the root of its common name - wood alcohol.
• Freeze distillation is an analogous method of purification using freezing instead of evaporation. It is not truly
distillation, but a recrystallization where the product is the mother liquor, and does not produce products
equivalent to distillation. This process is used in the production of ice beer and ice wine to increase ethanol and
sugar content, respectively. It is also used to produce applejack. Unlike distillation, freeze distillation concentrates
Distillation 13

poisonous congeners rather than removing them.

Azeotropic distillation
Interactions between the components of the solution create properties unique to the solution, as most processes entail
nonideal mixtures, where Raoult's law does not hold. Such interactions can result in a constant-boiling azeotrope
which behaves as if it were a pure compound (i.e., boils at a single temperature instead of a range). At an azeotrope,
the solution contains the given component in the same proportion as the vapor, so that evaporation does not change
the purity, and distillation does not effect separation. For example, ethyl alcohol and water form an azeotrope of
95.6% at 78.1 °C.
If the azeotrope is not considered sufficiently pure for use, there exist some techniques to break the azeotrope to give
a pure distillate. This set of techniques are known as azeotropic distillation. Some techniques achieve this by
"jumping" over the azeotropic composition (by adding an additional component to create a new azeotrope, or by
varying the pressure). Others work by chemically or physically removing or sequestering the impurity. For example,
to purify ethanol beyond 95%, a drying agent or a (desiccant such as potassium carbonate) can be added to convert
the soluble water into insoluble water of crystallization. Molecular sieves are often used for this purpose as well.
Immiscible liquids, such as water and toluene, easily form azeotropes. Commonly, these azeotropes are referred to as
a low boiling azeotrope because the boiling point of the azeotrope is lower than the boiling point of either pure
component. The temperature and composition of the azeotrope is easily predicted from the vapor pressure of the pure
components, without use of Raoult's law. The azeotrope is easily broken in a distillation set-up by using a
liquid-liquid separator (a decanter) to separate the two liquid layers that are condensed overhead. Only one of the
two liquid layers is refluxed to the distillation set-up.
High boiling azeotropes, such as a 20 weight percent mixture of hydrochloric acid in water, also exist. As implied by
the name, the boiling point of the azeotrope is greater than the boiling point of either pure component.
To break azeotropic distillations and cross distillation boundaries, such as in the DeRosier Problem, it is necessary to
increase the composition of the light key in the distillate.

Breaking an azeotrope with unidirectional pressure manipulation

The boiling points of components in an azeotrope overlap to form a band. By exposing an azeotrope to a vacuum or
positive pressure, it's possible to bias the boiling point of one component away from the other by exploiting the
differing vapour pressure curves of each; the curves may overlap at the azeotropic point, but are unlikely to be
remain identical further along the pressure axis either side of the azeotropic point. When the bias is great enough, the
two boiling points no longer overlap and so the azeotropic band disappears.
This method can remove the need to add other chemicals to a distillation, but it has two potential drawbacks.
Under negative pressure, power for a vacuum source is needed and the reduced boiling points of the distillates
requires that the condenser be run cooler to prevent distillate vapours being lost to the vacuum source. Increased
cooling demands will often require additional energy and possibly new equipment or a change of coolant.
Alternatively, if positive pressures are required, standard glassware can not be used, energy must be used for
pressurization and there is a higher chance of side reactions occurring in the distillation, such as decomposition, due
to the higher temperatures required to effect boiling.
A unidirectional distillation will rely on a pressure change in one direction, either positive or negative.
Distillation 14

Pressure-swing distillation
Pressure-swing distillation is essentially the same as the unidirectional distillation used to break azeotropic mixtures,
but here both positive and negative pressures may be employed.
This has an important impact on the selectivity of the distillation and allows a chemist to optimize a process such
that fewer extremes of pressure and temperature are required and less energy is consumed. This is particularly
important in commercial applications.
Pressure-swing distillation is employed during the industrial purification of ethyl acetate after its catalytic synthesis
from ethanol.

Industrial distillation
Large scale industrial distillation applications include
both batch and continuous fractional, vacuum,
azeotropic, extractive, and steam distillation. The most
widely used industrial applications of continuous,
steady-state fractional distillation are in petroleum
refineries, petrochemical and chemical plants and
natural gas processing plants.

Industrial distillation[15] [21] is typically performed in

large, vertical cylindrical columns known as
distillation towers or distillation columns with
diameters ranging from about 65 centimeters to 16
meters and heights ranging from about 6 meters to 90
meters or more. When the process feed has a diverse
composition, as in distilling crude oil, liquid outlets at
intervals up the column allow for the withdrawal of
different fractions or products having different boiling
points or boiling ranges. The "lightest" products (those
with the lowest boiling point) exit from the top of the
columns and the "heaviest" products (those with the
highest boiling point) exit from the bottom of the
column and are often called the bottoms. Typical industrial distillation towers
Distillation 15

Industrial towers use reflux to achieve a more complete separation of

products. Reflux refers to the portion of the condensed overhead liquid
product from a distillation or fractionation tower that is returned to the
upper part of the tower as shown in the schematic diagram of a typical,
large-scale industrial distillation tower. Inside the tower, the
downflowing reflux liquid provides cooling and condensation of the
upflowing vapors thereby increasing the efficiency of the distillation
tower. The more reflux that is provided for a given number of
theoretical plates, the better the tower's separation of lower boiling
materials from higher boiling materials. Alternatively, the more reflux
that is provided for a given desired separation, the fewer the number of
theoretical plates required.

Such industrial fractionating towers are also used in air separation,

Diagram of a typical industrial distillation tower
producing liquid oxygen, liquid nitrogen, and high purity argon.
Distillation of chlorosilanes also enables the production of high-purity
silicon for use as a semiconductor.
Design and operation of a distillation tower depends on the feed and
desired products. Given a simple, binary component feed, analytical
methods such as the McCabe-Thiele method[15] [22] or the Fenske
equation[15] can be used. For a multi-component feed, simulation
models are used both for design and operation. Moreover, the
efficiencies of the vapor-liquid contact devices (referred to as "plates"
or "trays") used in distillation towers are typically lower than that of a
theoretical 100% efficient equilibrium stage. Hence, a distillation
tower needs more trays than the number of theoretical vapor-liquid
equilibrium stages.

In modern industrial uses, generally a packing material is used in the Section of an industrial distillation tower showing
detail of trays with bubble caps
column instead of trays, especially when low pressure drops across the
column are required, as when operating under vacuum.
Distillation 16

This packing material can either be random dumped packing (1-3"

wide) such as Raschig rings or structured sheet metal. Liquids tend to
wet the surface of the packing and the vapors pass across this wetted
surface, where mass transfer takes place. Unlike conventional tray
distillation in which every tray represents a separate point of
vapor-liquid equilibrium, the vapor-liquid equilibrium curve in a
packed column is continuous. However, when modeling packed
columns, it is useful to compute a number of "theoretical stages" to
denote the separation efficiency of the packed column with respect to
more traditional trays. Differently shaped packings have different
surface areas and void space between packings. Both of these factors
affect packing performance.

Another factor in addition to the packing shape and surface area that
affects the performance of random or structured packing is the liquid
and vapor distribution entering the packed bed. The number of
theoretical stages required to make a given separation is calculated
using a specific vapor to liquid ratio. If the liquid and vapor are not
evenly distributed across the superficial tower area as it enters the
packed bed, the liquid to vapor ratio will not be correct in the packed
bed and the required separation will not be achieved. The packing will
Large-scale, industrial vacuum distillation
[23] appear to not be working properly. The height equivalent of a
column
theoretical plate (HETP) will be greater than expected. The problem is
not the packing itself but the mal-distribution of the fluids entering the
packed bed. Liquid mal-distribution is more frequently the problem than vapor. The design of the liquid distributors
used to introduce the feed and reflux to a packed bed is critical to making the packing perform to it maximum
efficiency. Methods of evaluating the effectiveness of a liquid distributor to evenly distribute the liquid entering a
packed bed can be found in references.[24] [25] Considerable work as been done on this topic by Fractionation
Research, Inc. (commonly known as FRI).[26]

Multi-effect distillation
The goal of multi-effect distillation is to increase the energy efficiency of the process, for use in desalination, or in
some cases one stage in the production of ultrapure water. The number of effects is proportional to the kW·h/m3 of
water recovered figure, and refers to the volume of water recovered per unit of energy compared with single-effect
distillation. One effect is roughly 636 kW·h/m3.
• Multi-stage flash distillation Can achieve more than 20 effects with thermal energy input, as mentioned in the
article.
• Vapor compression evaporation Commercial large-scale units can achieve around 72 effects with electrical
energy input, according to manufacturers.
There are many other types of multi-effect distillation processes, including one referred to as simply multi-effect
distillation (MED), in which multiple chambers, with intervening heat exchangers, are employed.
Distillation 17

Distillation in food processing

Distilled beverages
Carbohydrate-containing plant materials are allowed to ferment, producing a dilute solution of ethanol in the process.
Spirits such as whiskey and rum are prepared by distilling these dilute solutions of ethanol. Components other than
ethanol, including water, esters, and other alcohols, are collected in the condensate, which account for the flavor of
the beverage.

Gallery
Chemistry on its beginnings used retorts as laboratory equipment exclusively for distillation processes.

A simple set-up to distill dry and oxygen-free toluene.

Diagram of an industrial-scale vacuum distillation column as commonly used in oil refineries

A rotary evaporator is able to distill solvents more quickly at lower temperatures through the use of a vacuum.

Distillation using semi-microscale apparatus. The jointless design eliminates the need to fit pieces together. The pear-shaped
flask allows the last drop of residue to be removed, compared with a similarly-sized round-bottom flask The small holdup
volume prevents losses. A pig is used to channel the various distillates into three receiving flasks. If necessary the distillation
can be carried out under vacuum using the vacuum adapter at the pig.

Notes
[1] Laurence M. Harwood, Christopher J. Moody (13 June 1989). Experimental organic chemistry: Principles and Practice (Illustrated ed.).
Oxford: WileyBlackwell. pp. 141–143. ISBN 978-0632020171.
[2] Forbes, Robert James (1970). A short history of the art of distillation: from the beginnings up to the death of Cellier Blumenthal (http:/ /
books. google. com/ books?id=XeqWOkKYn28C). BRILL. ISBN 9789004006171. . Retrieved 29 June 2010.
[3] Taylor, F. Sherwood (1945). "The Evolution of the Still". Annals of Science 5 (3): 186. doi:10.1080/00033794500201451. ISSN 0003-3790.
[4] Sarton, George (1975). Introduction to the history of science. R. E. Krieger Pub. Co.. p. 145.
[5] Holmyard, Eric John (1990). Alchemy. Courier Dover Publications. p. 53.
[6] Magnum Opus Hermetic Sourceworks Series (http:/ / www. alchemywebsite. com/ bookshop/ mohs32. html)
[7] http:/ / www. levity. com/ alchemy/ jfren_ar. html
[8] Industrial Engineering Chemistry (1936) page 677
[9] Sealing Technique (http:/ / www. copper-alembic. com/ manufacturing/ specs_sealing. php), accessed 16 November 2006.
[10] Traditional Alembic Pot Still (http:/ / www. essentialoil. com/ alembic5. html), accessed 16 November 2006.
[11] D. F. Othmer (1982) Distillation - Some Steps in its Development, in W. F. Furter (ed) A Century of Chemical Engineering ISBN
0-306-40895-3
[12] A. Coffey British Patent 5974, 5 August 1830
[13] U.S. Patent 198699 (http:/ / www. google. com/ patents?vid=198699) Improvement in the Ammonia-Soda Manufacture
Distillation 18

[14] ST07 Separation of liquid - liquid mixtures (solutions) (http:/ / www. iupac. org/ didac/ Didac Eng/ Didac05/ Content/ ST07. htm), DIDAC
by IUPAC
[15] Perry, Robert H. and Green, Don W. (1984). Perry's Chemical Engineers' Handbook (6th ed.). McGraw-Hill. ISBN 0-07-049479-7.
[16] Fractional Distillation (http:/ / wulfenite. fandm. edu/ labtech/ fractdistill. htm)
[17] Spinning Band Distillation (http:/ / www. brinstrument. com/ fractional-distillation/ spinning_band_distillation. html) at B/R Instrument
Corporation (accessed 8 September 2006)
[18] Laurence M. Harwood, Christopher J. Moody (1989). Experimental organic chemistry: Principles and Practice (Illustrated ed.). Wiley,
Blackwell. pp. 151–153. ISBN 978-0632020171.
[19] Vogel's 5th ed.
[20] Laurence M. Harwood, Christopher J. Moody (13 June 1989). Experimental organic chemistry: Principles and Practice (Illustrated ed.).
Wiley, Blackwell. pp. 150. ISBN 978-0632020171.
[21] Kister, Henry Z. (1992). Distillation Design (1st ed.). McGraw-Hill. ISBN 0-07-034909-6.
[22] Seader, J. D., and Henley, Ernest J. (1998). Separation Process Principles. New York: Wiley. ISBN 0-471-58626-9.
[23] Energy Institute website page (http:/ / resources. schoolscience. co. uk/ SPE/ knowl/ 4/ 2index. htm?vacuum. html)
[24] Random Packing, Vapor and Liquid Distribution: Liquid and gas distribution in commercial packed towers, Moore, F., Rukovena, F.,
Chemical Plants & Processing, Edition Europe, August 1987, p. 11-15
[25] Spiegel, L (2006). "A new method to assess liquid distributor quality". Chemical Engineering and Processing 45: 1011.
doi:10.1016/j.cep.2006.05.003.
[26] Packed Tower Distributors: Commercial Scale Experiments That Provide Insight on Packed Tower Distributors, Kunesh, J. G., Lahm, L.,
Yanagi, T., Ind. Eng. Chem. Res., 1987, vol. 26, p. 1845-1850 doi:10.1021/ie00069a021 FRI (http:/ / www. fri. org) (click on "Available
Materials" and scroll to "Staff Publications")

Further reading
• Allchin, F. R. (Mar., 1979). "India: The Ancient Home of Distillation?" Man, New Series, Vol. 14, No. 1,
pp. 55–63. Royal Anthropological Institute of Great Britain and Ireland.
• Forbes, R. J. (1970). A Short History of the Art of Distillation from the Beginnings up to the Death of Cellier
Blumenthal (http://books.google.com/?id=XeqWOkKYn28C&printsec=frontcover). BRILL.
ISBN 9004006176.
• Needham, Joseph (1980). Science and Civilisation in China (http://books.google.com/
books?id=JvLroG7r2MYC&printsec=frontcover). Cambridge University Press. ISBN 052108573X.
• Geankoplis, Christie John (2003). Transport Processes and Separation Process Principles (4th ed.). Prentice
Hall. ISBN 013101367X.

External links
• Alcohol distillation (http://www.agcom.purdue.edu/AgCom/Pubs/AE/AE-117.html)
• Case Study: Petroleum Distillation (http://www.members.tripod.com/historycheme/h_distill.html)
• "Binary Vapor-Liquid Equilibrium Data" (http://www.cheric.org/research/kdb/hcvle/hcvle.php) (searchable
database). Chemical Engineering Research Information Center. Retrieved 5 May 2007.
Recrystallization (chemistry) 19

Recrystallization (chemistry)
Recrystallization (see also crystallization) is a physical
process that has meanings in chemistry, metallurgy and
geology.

Chemistry
In chemistry, recrystallization[1] is a procedure for
purifying compounds. The most typical situation is that
a desired "compound A" is contaminated by a small
amount of "impurity B". There are various methods of
purification that may be attempted (see Separation
process), which includes recrystallization. There are Insulin crystals
also different recrystallization techniques that can be
used such as:

Single-solvent recrystallization
Typically, the mixture of "compound A" and "impurity B" are dissolved in the smallest amount of hot solvent to
fully dissolve the mixture, thus making a saturated solution. The solution is then allowed to cool. As the solution
cools the solubility of compounds in solution drops. This results in the desired compound dropping (recrystallizing)
from solution. The slower the rate of cooling, the bigger the crystals formed.
In an ideal situation the solubility product of the impurity, B, is not
exceeded at any temperature. In that case the the solid crystals will
consist of pure A and all the impurity will remain in solution. The solid
crystals are collected by filtration and the filtrate is discarded. If the
→ Solvent added (clear) to compound (orange)
solubility product of the impurity is exceeded, some of the impurity
→ Solvent heated to give saturated compound
will co-precipitate. However, because of the relatively low solution (orange) → Saturated compound
concentration of the impurity, its concentration in the precipitated solution (orange) allowed to cool over time to
crystals will be less than its concentration in the original solid. give crystals (orange) and a saturated solution
(pale-orange).
Repeated recrystallization will result in an ever purer crystalline
precipitate. The purity is checked after each recrystallization by
measuring the melting point, since impurities lower the melting point.
NMR spectroscopy can also be used to check the level of impurity.
Repeated recrystallization results in some loss of material because of
the finite solubility of compound A.

The crystallization process requires an initiation step, such as the

addition of a "seed" crystal. In the laboratory a miniscule fragment of
glass, produced by scratching the side of the glass recrystallization
vessel, may provide the nucleus on which crystals may grow.
Successful recrystallization depends on finding the right solvent. This Crystallization of Ibuprofen in HCl(aq)
is usually a combination of prediction/experience and trial/error. The
compounds must be more soluble at the higher temperature than at the lower temperatures. Any insoluble impurity is
removed by the technique of hot filtration.
Recrystallization (chemistry) 20

Multi-solvent recrystallization
This method is the same as the above but where two (or more) solvents are used. This relies on both "compound A"
and "impurity B" being soluble in a first solvent. A second solvent is slowly added. Either "compound A" or
"impurity B" will be insoluble in this solvent and precipitate, whilst the other of "compound A"/"impurity B" will
remain in solution. Thus the proportion of first and second solvents is critical. Typically the second solvent is added
slowly until one of the compounds begins to crystallize from solution and then the solution is cooled. Heating is not
required for this technique but can be used.

→ Solvent added (clear) to compound (orange)

→ Solvent heated to give saturated compound
solution (orange) → Second solvent (blue) added
to compound solution (orange) to give mixed
solvent system (green) → Mixed solvent system
(green) allowed to cool over time to give crystals
(orange) and a saturated mixed solvent system
(green-blue).

The reverse of this method can be used where a mixture of solvent dissolves both A and B. One of the solvents is
then removed by distillation or by an applied vacuum. This results in a change in the proportions of solvent causing
either "compound A" or "impurity B" to precipitate.

→ First solvent added (clear) to compound

(orange) → Solvent heated to give saturated
compound solution (orange) → Second solvent
(blue) added to compound solution (orange) to
give first mixed solvent system (green) →
Volatile first solvent (clear) is removed (e.g.
evaporation) from first mixed solvent system
(green) to give a second mixed solvent system
(dark-green) → Second mixed solvent system
(dark-green) allowed to cool over time to give
crystals (orange) and a saturated second mixed
solvent system (green-blue).

Hot filtration-recrystallization
Hot filtration[2] can be used to separate "compound A" from both "impurity B" and some "insoluble matter C". This
technique normally uses a single-solvent system as described above. When both "compound A" and "impurity B" are
dissolved in the minimum amount of hot solvent, the solution is filtered to remove "insoluble matter C". This matter
may be anything from a third impurity compound to fragments of broken glass. For a successful procedure, one must
ensure that the filtration apparatus is hot in order to stop the dissolved compounds crystallizing from solution during
filtration, thus forming crystals on the filter paper or funnel.
One way to achieve this is to heat a conical flask containing a small amount of clean solvent on a hot plate. A filter
funnel is rested on the mouth, and hot solvent vapors keep the stem warm. Jacketed filter funnels may also be used.
The filter paper is preferably fluted, rather than folded into a quarter; this allows quicker filtration, thus less
opportunity for the desired compound to cool and crystallize from the solution.
Recrystallization (chemistry) 21

Often it is simpler to do the filtration and recrystallization as two independent and separate steps. That is dissolve
"compound A" and "impurity B" in a suitable solvent at room temperature, filter (to remove insoluble
compound/glass), remove the solvent and then recrystallize using any of the methods listed above.

→ Solvent added (clear) to a mixture of

compound (orange) + insoluble substance
(purple) → Solvent heated to give saturated
compound solution (orange) + insoluble
substance (purple) → Saturated compound
solution (orange) filtered to remove insoluble
substance (purple) → Saturated compound
solution (orange) allowed to cool over time to
give crystals (orange) and a saturated solution
(pale-orange).

Seeding
Crystallization requires an initiation step. This can be spontaneous or can be done by adding a small amount of the
pure compound (a seed crystal)[1] to the saturated solution, or can be done by simply scratching the glass surface to
create a seeding surface for crystal growth. It is thought that even dust particles can act as simple seeds.

Single perfect crystals (for X-ray analysis)

Growing crystals for X-ray crystallography can be quite difficult. For X-ray analysis, single perfect crystals are
required. Typically a small amount (5-100 mg) of pure compound is used, and crystals are allowed to grow very
slowly. Several techniques can be used to grow these perfect crystals:
• Slow evaporation of a single solvent - typically the compound is dissolved in a suitable solvent and the solvent is
allowed to slowly evaporate. Once the solution is saturated crystals can form.

→ Solvent added (clear) to compound (orange) to

give compound solution (orange) → Vessel
sealed but a small hole allows solvent vapour
(clear) to slowly evaporate from compound
solution (orange) over time to give crystals
(orange) and a saturated solution (pale-orange).

• Slow evaporation of a multi-solvent system - the same as above, however as the solvent composition changes due
to evaporation of the more volatile solvent. The compound is more soluble in the volatile solvent, and so the
compound becomes increasingly insoluble in solution and crystallizes.
Recrystallization (chemistry) 22

→ Solvent added (clear) to compound (orange) to

give compound solution (orange) → Second
solvent added (blue) to compound solution
(orange) to give mixed solvent system (green) →
Vessel sealed but a small hole allows solvent
vapour (clear) to slowly evaporate over time to
give crystals (orange) and a saturated mixed
solvent solution (blue-green).

• Slow diffusion - similar to the above. However, a second solvent is allowed to evaporate from one container into
a container holding the compound solution (gas-diffusion). As the solvent composition changes due to an increase
in solvent that is has gas-diffused into solution, the compound become increasingly insoluble in solution and
crystallizes.

→ Solvent added (clear) to compound (orange) in

first vessel to give compound solution (orange)
→ First vessel is placed in a second vessel
contain second solvent (blue). The second vessel
is sealed, the first vessel is also sealed, although a
small hole in the first vessel is present. This hole
allows volatile solvent vapour (blue) to slowly
evaporate from second vessel and condensate
(that is infuse) into the first vessel, to give a
mixed solvent system (green) → Over time this
gives crystals (orange) and a saturated mixed
solvent system (green-blue).

• Interface/slow mixing (often performed in an NMR tube). Similar to the above, but instead of one solvent
gas-diffusing into another, the two solvents mix (diffuse) by liquid-liquid diffusion. Typically a second solvent is
"layered" carefully on top of the solution containing the compound. Over time the two solution mix. As the
solvent composition changes due to diffusion, the compound becomes increasingly insoluble in solution and
crystallizes, usually at the interface.

→ Solvent added (clear) to compound (orange) to

give compound solution (orange) → Second
solvent added (blue) carefully so that the two
solvents do not mix. → The two solvents mix
(diffuse) slowly over time to give crystals
(orange) at solvent interface (green)

• Specialized equipment can be used in the shape of a "H" to perform the above, where one of the vertical line of
the "H" is a tube containing a solution of the compound, and the other vertical line of the "H" is a tube containing
Recrystallization (chemistry) 23

a solvent which the compound is not soluble in, and the horizontal line of the "H" is a tube which joins the two
vertical tubes, which also has a fine glass sinter that restricts the mixing of the two solvents.

→ Solvent added (clear) to compound (orange) to

give a compound solution (orange) → Second
solvent added (blue) to the second tube chamber
→ The two solvents mix slowly over time, the
mixing is slowed by a fine sinter separating the
two solvent chambers, to give crystals (orange) at
solvent interface (green) over time

• Once single perfect crystals have been obtained, it is recommended that the crystals are kept in a sealed vessel
with some of the liquid of crystallisation to prevent the crystal from 'drying out'. Single perfect crystals may
contain solvent of crystallisation in the crystal lattice. Loss of this internal solvent from the crystals can result in
the crystal lattice breaking down, and the crystals turning to powder.

Ice
For ice, recrystallization refers to the growth of larger crystals at the expense of smaller ones. Some biological
antifreeze proteins have been shown to inhibit this process, and the effect may be relevant in freezing-tolerant
organisms.

See also
• Crystal structure
• Crystallization and engineering aspects
• Fractional crystallization (chemistry)
• Laser-heated pedestal growth
• Seed crystal
• Single crystal

References
[1] Laurence M. Harwood, Christopher J. Moody (1989). Experimental organic chemistry: Principles and Practice. Oxford: Blackwell Scientific
Publications. pp. 127–132. ISBN 0632020172.
[2] Laurence M. Harwood, Christopher J. Moody (1989). Experimental organic chemistry: Principles and Practice. Oxford: Blackwell Scientific
Publications. pp. 74. ISBN 0632020172.

Reference books
• Laurence M. Harwood, Christopher J. Moody, Jonathan M. Percy. "Experimental organic chemistry: standard and
microscale" (http://books.google.com/books?id=9mAEtf8zzXYC&lpg=PP1&dq=moody harwood
chemistry&pg=PP1#v=onepage&q=&f=false).
• John Leonard, B. Lygo, Garry Procter. "Advanced practical organic chemistry" (http://books.google.com/
books?id=aP88FuFO5QUC&printsec=frontcover&dq=Advanced+Practical+Inorganic&
source=gbs_similarbooks_s&cad=1#v=onepage&q=&f=false).
Recrystallization (chemistry) 24

Gallery

Single Protein crystal of Lysozyme

Fragrance extraction
Fragrance extraction 25

Fragrance extraction refers to the extraction of

aromatic compounds from raw materials, using
methods such as distillation, solvent extraction,
expression, or enfleurage. The results of the extracts are
either essential oils, absolutes, concretes, or butters,
depending on the amount of waxes in the extracted
product.

To a certain extent, all of these techniques tend to

distort the odour of the aromatic compounds obtained
from the raw materials. Heat, chemical solvents, or
exposure to oxygen in the extraction process denature
the aromatic compounds, either changing their odour
character or rendering them odourless.

Maceration/Solvent extraction
Certain plant materials contain too little volatile oil to
undergo expression, or their chemical components are
too delicate and easily denatured by the high heat used
in steam distillation. Instead, the oils are extracted
using their solvent properties. Copper still from 19th to 20th century Grasse, France for steam
distillation
Organic solvent extraction
Organic solvent extraction is the most common and most economically important technique for extracting aromatics
in the modern perfume industry. Raw materials are submerged and agitated in a solvent that can dissolve the desired
aromatic compounds. Commonly used solvents for maceration/solvent extraction include hexane, and dimethyl
ether.
In organic solvent extraction, aromatic compounds as well as other hydrophobic soluble substances such as wax and
pigments are also obtained. The extract is subjected to vacuum processing, which removes the solvent for re-use.
The process can last anywhere from hours to months. Fragrant compounds for woody and fibrous plant materials are
often obtained in this matter as are all aromatics from animal sources. The technique can also be used to extract
odorants that are too volatile for distillation or easily denatured by heat. The remaining waxy mass is known as a
concrete, which is a mixture of essential oil, waxes, resins, and other lipophilic (oil soluble) plant material, since
these solvents effectively remove all hydrophobic compounds in the raw material. The solvent is then removed by a
lower temperature distillation process and reclaimed for re-use.
Although highly fragrant, concretes are too viscous - even solid - at room temperature to be useful. This is due to the
presence of high-molecular-weight, non-fragrant waxes and resins. Another solvent, often ethyl alcohol, which only
dissolves the fragrant low-molecular weight compounds, must be used to extract the fragrant oil from the concrete.
The alcohol is removed by a second distillation, leaving behind the absolute. These extracts from plants such as
jasmine and rose, are called absolutes.
Due to the low temperatures in this process, the absolute may be more faithful to the original scent of the raw
material, which is subjected to high heat during the distillation process.
Fragrance extraction 26

Supercritical fluid extraction

Supercritical fluid extraction is a relatively new technique for extracting fragrant compounds from a raw material,
which often employs Supercritical CO2 as the extraction solvent. When carbon dioxide is put under high pressure at
slightly above room temperature, a supercritical fluid forms (Under normal pressure CO2 changes directly from a
solid to a gas in a process known as sublimation.) Since CO2 in a non-polar compound has low surface tension and
wets easily, it can be used to extract the typically hydrophobic aromatics from the plant material. This process is
identical to one of the techniques for making decaffeinated coffee.
In supercritical fluid extraction, high pressure carbon dioxide gas (up to 100 atm.) is used as a solvent.Due to the low
heat of process and the relatively unreactive solvent used in the extraction, the fragrant compounds derived often
closely resemble the original odour of the raw material. Like solvent extraction, the CO2 extraction takes place at a
low temperature, extracts a wide range of compounds, and leaves the aromatics unaltered by heat, rendering an
essence more faithful to the original. Since CO2 is gas at normal atmospheric pressure, it also leaves no trace of itself
in the final product, thus allowing one to get the absolute directly without having to deal with a concrete. It is a
low-temperature process, and the solvents are easily removed. Extracts produced using this process are known as
CO2 extracts.

Ethanol extraction
Ethanol extraction is a type of solvent extraction used to extract fragrant compounds directly from dry raw materials,
as well as the impure oils or concrete resulting from organic solvent extraction, expression, or enfluerage. Ethanol
extracts from dry materials are called tinctures, while ethanol washes for purifying oils and concretes are called
absolutes.
The impure substances or oils are mixed with ethanol, which is less hydrophobic than solvents used for organic
extraction, dissolves more of the oxidized aromatic constituents (alcohols, aldehydes, etc.), leaving behind the wax,
fats, and other generally hydrophobic substances. The alcohol is evaporated under low-pressure, leaving behind
absolute. The absolute may be further processed to remove any impurities that are still present from the solvent
extraction.
Ethanol extraction is not used to extract fragrance from fresh plant materials; these contain large quantities of water,
which would also be extracted into the ethanol.

Distillation
Distillation is a common technique for obtaining aromatic compounds from plants, such as orange blossoms and
roses. The raw material is heated and the fragrant compounds are re-collected through condensation of the distilled
vapor. Distilled products, whether through steam or dry distillation are known either as essential oils or ottos.
Today, most common essential oils, such as lavender, peppermint, and eucalyptus, are distilled. Raw plant material,
consisting of the flowers, leaves, wood, bark, roots, seeds, or peel, is put into an alembic (distillation apparatus) over
water,

Steam distillation
Steam from boiling water is passed through the raw material for 60-105 minutes, which drives out most of their
volatile fragrant compounds. The condensate from distillation, which contain both water and the aromatics, is settled
in a Florentine flask. This allows for the easy separation of the fragrant oils from the water as the oil will float to the
top of the distillate where it is removed, leaving behind the watery distillate. The water collected from the
condensate, which retains some of the fragrant compounds and oils from the raw material, is called hydrosol and is
sometimes sold for consumer and commercial use. This method is most commonly used for fresh plant materials
such as flowers, leaves, and stems. Popular hydrosols are rose water, lavender water, and orange blossom water.
Fragrance extraction 27

Many plant hydrosols have unpleasant smells and are therefore not sold.
Most oils are distilled in a single process. One exception is Ylang-ylang (Cananga odorata), which takes 22 hours to
complete distillation. It is fractionally distilled, producing several grades (Ylang-Ylang "extra", I, II, III and
"complete," in which the distillation is run from start to finish with no interruption).

Dry/destructive distillation
Also known as rectification, the raw materials are directly heated in a still without a carrier solvent such as water.
Fragrant compounds that are released from the raw material by the high heat often undergo anhydrous pyrolysis,
which results in the formation of different fragrant compounds, and thus different fragrant notes. This method is used
to obtain fragrant compounds from fossil amber and fragrant woods where an intentional "burned" or "toasted" odour
is desired.

Fractionation distillation
Through the use of a fractionation column, different fractions distilled from a material can be selectively excluded to
manipulated the scent of the final product. Although the product is more expensive, this is sometimes performed to
remove unpleasant or undesirable scents of a material and affords the perfumer more control over their composition
process.

Expression
Expression as a method of frangrance extraction where raw materials are pressed, squeezed or compressed and the
oils are collected. In contemporary times, the only fragrant oils obtained using this method are the peels of fruits in
the citrus family. This is due to the large quantity of oil is present in the peels of these fruits as to make this
extraction method economically feasible. Citrus peel oils are expressed mechanically, or cold-pressed. Due to the
large quantities of oil in citrus peel and the relatively low cost to grow and harvest the raw materials, citrus-fruit oils
are cheaper than most other essential oils. Lemon or sweet orange oils that are obtained as by-products of the
commercial citrus industry are among the cheapest citrus oils.
Expression was mainly used prior to the discovery of distillation, and this is still the case in cultures such as Egypt.
Traditional Egyptian practice involves pressing the plant material, then burying it in unglazed ceramic vessels in the
desert for a period of months to drive out water. The water has a smaller molecular size, so it diffuses through the
ceramic vessels, while the larger essential oils do not. The lotus oil in Tutankhamen's tomb, which retained its scent
after 3000 years sealed in alabaster vessels, was pressed in this manner.

Enfleurage
Enfleurage is a two-step process during which the odour of aromatic materials is absorbed into wax or fat, then
extracted with alcohol. Extraction by enfleurage was commonly used when distillation was not possible because
some fragrant compounds denature through high heat. This technique is not commonly used in modern industry, due
to both its prohibitive cost and the existence of more efficient and effective extraction methods.

See also
• Enfleurage
• Essential oil
• Perfume
• Rose oil
Chromatography 28

Chromatography
Chromatography (from Greek χρῶμα chroma "color" and γράφειν
graphein "to write") is the collective term for a set of laboratory
techniques for the separation of mixtures. It involves passing a mixture
dissolved in a "mobile phase" through a stationary phase, which
separates the analyte to be measured from other molecules in the
mixture based on differential partitioning between the mobile and
stationary phases. Subtle differences in a compound's partition
coefficient result in differential retention on the stationary phase and
thus changing the separation. Pictured is a sophisticated gas chromatography
system. This instrument records concentrations of
Chromatography may be preparative or analytical. The purpose of acrylonitrile in the air at various points
throughout the chemical laboratory.
preparative chromatography is to separate the components of a mixture
for further use (and is thus a form of purification). Analytical
chromatography is done normally with smaller amounts of material and is for measuring the relative proportions of
analytes in a mixture. The two are not mutually exclusive.

History
The history of chromatography begins during the mid-19th century. Chromatography, literally "color writing", was
used—and named— in the first decade of the 20th century, primarily for the separation of plant pigments such as
chlorophyll. New types of chromatography developed during the 1930s and 1940s made the technique useful for
many types of separation process.
Some related techniques were developed during the 19th century (and even before), but the first true chromatography
is usually attributed to Russian botanist Mikhail Semyonovich Tsvet, who used columns of calcium carbonate for
separating plant pigments during the first decade of the 20th century during his research of chlorophyll.
Chromatography became developed substantially as a result of the work of Archer John Porter Martin and Richard
Laurence Millington Synge during the 1940s and 1950s. They established the principles and basic techniques of
partition chromatography, and their work encouraged the rapid development of several types of chromatography
method: paper chromatography, gas chromatography, and what would become known as high performance liquid
chromatography. Since then, the technology has advanced rapidly. Researchers found that the main principles of
Tsvet's chromatography could be applied in many different ways, resulting in the different varieties of
chromatography described below. Simultaneously, advances continually improved the technical performance of
chromatography, allowing the separation of increasingly similar molecules.

Chromatography terms
• The analyte is the substance to be separated during chromatography.
• Analytical chromatography is used to determine the existence and possibly also the concentration of analyte(s)
in a sample.
• A bonded phase is a stationary phase that is covalently bonded to the support particles or to the inside wall of the
column tubing.
• A chromatogram is the visual output of the chromatograph. In the case of an optimal separation, different peaks
or patterns on the chromatogram correspond to different components of the separated mixture.
Chromatography 29

Plotted on the x-axis is the retention time and plotted on the y-axis a signal (for example obtained by a
spectrophotometer, mass spectrometer or a variety of other detectors) corresponding to the response created by
the analytes exiting the system. In the case of an optimal system the signal is proportional to the concentration
of the specific analyte separated.
• A chromatograph is equipment that enables a sophisticated separation e.g. gas chromatographic or liquid
chromatographic separation.
• Chromatography is a physical method of separation in which the components to be separated are distributed
between two phases, one of which is stationary (stationary phase) while the other (the mobile phase) moves in a
definite direction.
• The eluate is the mobile phase leaving the column.
• The eluent is the solvent that will carry the analyte.
• An eluotropic series is a list of solvents ranked according to their eluting power.
• An immobilized phase is a stationary phase which is immobilized on the support particles, or on the inner wall of
the column tubing.
• The mobile phase is the phase which moves in a definite direction. It may be a liquid (LC and CEC), a gas (GC),
or a supercritical fluid (supercritical-fluid chromatography, SFC). The mobile phase consists of the sample being
separated/analyzed and the solvent that moves the sample through the column. In the case of HPLC the mobile
phase consists of a non-polar solvent(s) such as hexane in normal phase or polar solvents in reverse phase
chromotagraphy and the sample being separated. The mobile phase moves through the chromatography column
(the stationary phase) where the sample interacts with the stationary phase and is separated.
• Preparative chromatography is used to purify sufficient quantities of a substance for further use, rather than
analysis.
• The retention time is the characteristic time it takes for a particular analyte to pass through the system (from the
column inlet to the detector) under set conditions. See also: Kovats' retention index
• The sample is the matter analyzed in chromatography. It may consist of a single component or it may be a
mixture of components. When the sample is treated in the course of an analysis, the phase or the phases
containing the analytes of interest is/are referred to as the sample whereas everything out of interest separated
from the sample before or in the course of the analysis is referred to as waste.
• The solute refers to the sample components in partition chromatography.
• The solvent refers to any substance capable of solubilizing other substance, and especially the liquid mobile
phase in LC.
• The stationary phase is the substance which is fixed in place for the chromatography procedure. Examples
include the silica layer in thin layer chromatography
Chromatography 30

Techniques by chromatographic bed shape

Column chromatography
Column chromatography is a separation technique in which the stationary bed is within a tube. The particles of the
solid stationary phase or the support coated with a liquid stationary phase may fill the whole inside volume of the
tube (packed column) or be concentrated on or along the inside tube wall leaving an open, unrestricted path for the
mobile phase in the middle part of the tube (open tubular column). Differences in rates of movement through the
medium are calculated to different retention times of the sample.[1]
In 1978, W. C. Still introduced a modified version of column chromatography called flash column
chromatography (flash).[2] [3] The technique is very similar to the traditional column chromatography, except for
that the solvent is driven through the column by applying positive pressure. This allowed most separations to be
performed in less than 20 minutes, with improved separations compared to the old method. Modern flash
chromatography systems are sold as pre-packed plastic cartridges, and the solvent is pumped through the cartridge.
Systems may also be linked with detectors and fraction collectors providing automation. The introduction of gradient
pumps resulted in quicker separations and less solvent usage.
In expanded bed adsorption, a fluidized bed is used, rather than a solid phase made by a packed bed. This allows
omission of initial clearing steps such as centrifugation and filtration, for culture broths or slurries of broken cells.

Planar chromatography
Planar chromatography is a separation technique in which the stationary phase is present as
or on a plane. The plane can be a paper, serving as such or impregnated by a substance as the
stationary bed (paper chromatography) or a layer of solid particles spread on a support such as
a glass plate (thin layer chromatography). Different compounds in the sample mixture travel
different distances according to how strongly they interact with the stationary phase as
compared to the mobile phase. The specific Retention factor (Rf) of each chemical can be used
to aid in the identification of an unknown substance.

Paper chromatography

Paper chromatography is a technique that involves placing a small dot or line of sample
solution onto a strip of chromatography paper. The paper is placed in a jar containing a
shallow layer of solvent and sealed. As the solvent rises through the paper, it meets the sample
mixture which starts to travel up the paper with the solvent. This paper is made of cellulose, a
polar substance, and the compounds within the mixture travel farther if they are non-polar.
More polar substances bond with the cellulose paper more quickly, and therefore do not travel
as far.

Thin layer
Thin layer chromatography
chromatography is
Thin layer chromatography (TLC) is a widely employed laboratory technique and is similar to used to separate
components of
paper chromatography. However, instead of using a stationary phase of paper, it involves a
chlorophyll
stationary phase of a thin layer of adsorbent like silica gel, alumina, or cellulose on a flat, inert
substrate. Compared to paper, it has the advantage of faster runs, better separations, and the
choice between different adsorbents. For even better resolution and to allow for quantification, high-performance
TLC can be used.
Chromatography 31

Displacement chromatography
The basic principle of displacement chromatography is: A molecule with a high affinity for the chromatography
matrix (the displacer) will compete effectively for binding sites, and thus displace all molecules with lesser
affinities.[4] There are distinct differences between displacement and elution chromatography. In elution mode,
substances typically emerge from a column in narrow, Gaussian peaks. Wide separation of peaks, preferably to
baseline, is desired in order to achieve maximum purification. The speed at which any component of a mixture
travels down the column in elution mode depends on many factors. But for two substances to travel at different
speeds, and thereby be resolved, there must be substantial differences in some interaction between the biomolecules
and the chromatography matrix. Operating parameters are adjusted to maximize the effect of this difference. In many
cases, baseline separation of the peaks can be achieved only with gradient elution and low column loadings. Thus,
two drawbacks to elution mode chromatography, especially at the preparative scale, are operational complexity, due
to gradient solvent pumping, and low throughput, due to low column loadings. Displacement chromatography has
advantages over elution chromatography in that components are resolved into consecutive zones of pure substances
rather than “peaks”. Because the process takes advantage of the nonlinearity of the isotherms, a larger column feed
can be separated on a given column with the purified components recovered at significantly higher concentrations.

Techniques by physical state of mobile phase

Gas chromatography
Gas chromatography (GC), also sometimes known as Gas-Liquid chromatography, (GLC), is a separation technique
in which the mobile phase is a gas. Gas chromatography is always carried out in a column, which is typically
"packed" or "capillary" (see below) .
Gas chromatography (GC) is based on a partition equilibrium of analyte between a solid stationary phase (often a
liquid silicone-based material) and a mobile gas (most often Helium). The stationary phase is adhered to the inside of
a small-diameter glass tube (a capillary column) or a solid matrix inside a larger metal tube (a packed column). It is
widely used in analytical chemistry; though the high temperatures used in GC make it unsuitable for high molecular
weight biopolymers or proteins (heat will denature them), frequently encountered in biochemistry, it is well suited
for use in the petrochemical, environmental monitoring and remediation, and industrial chemical fields. It is also
used extensively in chemistry research.

Liquid chromatography
Liquid chromatography (LC) is a
separation technique in which the
mobile phase is a liquid. Liquid
chromatography can be carried out
either in a column or a plane. Present
day liquid chromatography that
generally utilizes very small packing
particles and a relatively high pressure
is referred to as high performance
liquid chromatography (HPLC).

In the HPLC technique, the sample is

Preparative HPLC apparatus
forced through a column that is packed
Chromatography 32

with irregularly or spherically shaped particles, a porous monolithic layer (stationary phase) or a porous membrane
by a liquid (mobile phase) at high pressure. HPLC is historically divided into two different sub-classes based on the
polarity of the mobile and stationary phases. Methods in which the stationary phase is more polar than the mobile
phase (e.g. toluene as the mobile phase, silica as the stationary phase) are termed normal phase liquid
chromatography (NPLC) and the opposite (e.g. water-methanol mixture as the mobile phase and C18 =
octadecylsilyl as the stationary phase) is termed reversed phase liquid chromatography (RPLC). Ironically the
"normal phase" has fewer applications and RPLC is therefore used considerably more.
Specific techniques which come under this broad heading are listed below. It should also be noted that the following
techniques can also be considered fast protein liquid chromatography if no pressure is used to drive the mobile phase
through the stationary phase. See also Aqueous Normal Phase Chromatography.

Affinity chromatography
Affinity chromatography[5] is based on selective non-covalent interaction between an analyte and specific molecules.
It is very specific, but not very robust. It is often used in biochemistry in the purification of proteins bound to tags.
These fusion proteins are labeled with compounds such as His-tags, biotin or antigens, which bind to the stationary
phase specifically. After purification, some of these tags are usually removed and the pure protein is obtained.
Affinity chromatography often utilizes a biomolecule's affinity for a metal (Zn, Cu, Fe, etc.). Columns are often
manually prepared. Traditional affinity columns are used as a preparative step to flush out unwanted biomolecules.
However, HPLC techniques exist that do utilize affinity chromatogaphy properties. Immobilized Metal Affinity
Chromatography (IMAC) is useful to separate aforementioned molecules based on the relative affinity for the metal
(I.e. Dionex IMAC) . Often these columns can be loaded with different metals to create a column with a targeted
affinity.

Supercritical fluid chromatography

Supercritical fluid chromatography is a separation technique in which the mobile phase is a fluid above and
relatively close to its critical temperature and pressure.

Techniques by separation mechanism

Ion exchange chromatography

Ion exchange chromatography uses ion exchange mechanism to separate analytes. It is usually performed in columns
but can also be useful in planar mode. Ion exchange chromatography uses a charged stationary phase to separate
charged compounds including amino acids, peptides, and proteins. In conventional methods the stationary phase is
an ion exchange resin that carries charged functional groups which interact with oppositely charged groups of the
compound to be retained. Ion exchange chromatography is commonly used to purify proteins using FPLC.

Size-exclusion chromatography
Size-exclusion chromatography (SEC) is also known as gel permeation chromatography (GPC) or gel filtration
chromatography and separates molecules according to their size (or more accurately according to their
hydrodynamic diameter or hydrodynamic volume). Smaller molecules are able to enter the pores of the media and,
therefore, molecules are trapped and removed from the flow of the mobile phase. The average residence time in the
pores depends upon the effective size of the analyte molecules. However, molecules that are larger than the average
pore size of the packing are excluded and thus suffer essentially no retention; such species are the first to be eluted. It
is generally a low-resolution chromatography technique and thus it is often reserved for the final, "polishing" step of
a purification. It is also useful for determining the tertiary structure and quaternary structure of purified proteins,
Chromatography 33

especially since it can be carried out under native solution conditions.

Special techniques

Reversed-phase chromatography
Reversed-phase chromatography is an elution procedure used in liquid chromatography in which the mobile phase is
significantly more polar than the stationary phase.

Two-dimensional chromatography
In some cases, the chemistry within a given column can be insufficient to separate some analytes. It is possible to
direct a series of unresolved peaks onto a second column with different physico-chemical (Chemical classification)
properties. Since the mechanism of retention on this new solid support is different from the first dimensional
separation, it can be possible to separate compounds that are indistinguishable by one-dimensional chromatography.
The sample is spotted at one corner of a square plate,developed, air-dried, then rotated by 90° and usually
redeveloped in a second solvent system.

Fast protein liquid chromatography

Fast protein liquid chromatography (FPLC) is a term applied to several chromatography techniques which are used
to purify proteins. Many of these techniques are identical to those carried out under high performance liquid
chromatography, however use of FPLC techniques are typically for preparing large scale batches of a purified
product.

Countercurrent chromatography
Countercurrent chromatography (CCC) is a type of liquid-liquid chromatography, where both the stationary and
mobile phases are liquids. It involves mixing a solution of liquids, allowing them to settle into layers and then
separating the layers.

Chiral chromatography
Chiral chromatography involves the separation of stereoisomers. In the case of enantiomers, these have no chemical
or physical differences apart from being three-dimensional mirror images. Conventional chromatography or other
separation processes are incapable of separating them. To enable chiral separations to take place, either the mobile
phase or the stationary phase must themselves be made chiral, giving differing affinities between the analytes. Chiral
chromatography HPLC columns (with a chiral stationary phase) in both normal and reversed phase are commercially
available.
Chromatography 34

See also
• Aqueous Normal Phase Chromatography • Chromatography in blood processing
• Flash gas chromatography • Chromatography software
• Multicolumn countercurrent solvent gradient purification (MCSGP) • Van Deemter equation
• Purnell equation

References
[1] IUPAC Nomenclature for Chromatography (http:/ / www. iupac. org/ publications/ pac/ 1993/ pdf/ 6504x0819. pdf) IUPAC
Recommendations 1993, Pure & Appl. Chem., Vol. 65, No. 4, pp.819-872, 1993.
[2] Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43(14), 2923-2925. doi:10.1021/jo00408a041
[3] Laurence M. Harwood, Christopher J. Moody (13 June 1989). Experimental organic chemistry: Principles and Practice (Illustrated ed.).
WileyBlackwell. pp. 180–185. ISBN 9780632020171.
[4] Displacement Chromatography 101 (http:/ / www. sacheminc. com/ industries/ biotechnology/ teaching-tools. html). Sachem, Inc. Austin, TX
78737
[5] Pascal Bailon, George K. Ehrlich, Wen-Jian Fung and Wolfgang Berthold, An Overview of Affinity Chromatography, Humana Press, 2000.
ISBN 978-0-89603-694-9, ISBN 978-1-60327-261-2.

External links
• IUPAC Nomenclature for Chromatography (http://www.iupac.org/publications/pac/1993/pdf/6504x0819.
pdf)
• Chromedia (http://www.chromedia.org) On line database and community for chromatography practitioners
(paid subscription required)
• Library 4 Science: Chrom-Ed Series (http://www.chromatography-online.org/)
• Overlapping Peaks Program - Learning by Simulations (http://www.vias.org/simulations/
simusoft_peakoverlap.html)
• Chromatography Videos - MIT OCW - Digital Lab Techniques Manual (http://ocw.mit.edu/ans7870/
resources/chemvideo/index.htm)
• Chromatography Equations Calculators - MicroSolv Technology Corporation (http://www.mtc-usa.com/
calculators_chrom.asp)
Hydrocarbon 35

Hydrocarbon
In organic chemistry, a hydrocarbon is an organic
compound consisting entirely of hydrogen and carbon.[1]
Hydrocarbons from which one hydrogen atom has been
removed are functional groups, called hydrocarbyls.[2]
Aromatic hydrocarbons (arenes), alkanes, alkenes,
cycloalkanes and alkyne-based compounds are different
types of hydrocarbons.

The majority of hydrocarbons found naturally occur in

crude oil, where decomposed organic matter provides an
abundance of carbon and hydrogen which, when bonded,
can catenate to form seemingly limitless chains.[3] [4]

Types of hydrocarbons
The classifications for hydrocarbons defined by IUPAC
nomenclature of organic chemistry are as follows: Ball-and-stick model of the methane molecule, CH4. Methane is
part of a homologous series known as the alkanes, which contain
1. Saturated hydrocarbons (alkanes) are the simplest of single bonds only.
the hydrocarbon species and are composed entirely of
single bonds and are saturated with hydrogen. The general formula for saturated hydrocarbons is CnH2n+2
(assuming non-cyclic structures).[5] Saturated hydrocarbons are the basis of petroleum fuels and are either found
as linear or branched species. Hydrocarbons with the same molecular formula but different structural formulae are
called structural isomers.[6] As given in the example of 3-methylhexane and its higher homologues, branched
hydrocarbons can be chiral.[7] Chiral saturated hydrocarbons constitute the side chains of biomolecules such as
chlorophyll and tocopherol.[8]
2. Unsaturated hydrocarbons have one or more double or triple bonds between carbon atoms. Those with double
bond are called alkenes. Those with one double bond have the formula CnH2n (assuming non-cyclic structures).[9]
Those containing triple bonds are called alkynes, with general formula CnH2n-2.[10]
3. Cycloalkanes are hydrocarbons containing one or more carbon rings to which hydrogen atoms are attached. The
general formula for a saturated hydrocarbon containing one ring is CnH2n.[11]
4. Aromatic hydrocarbons, also known as arenes, are hydrocarbons that have at least one aromatic ring.
Hydrocarbons can be gases (e.g. methane and propane), liquids (e.g. hexane and benzene), waxes or low melting
solids (e.g. paraffin wax and naphthalene) or polymers (e.g. polyethylene, polypropylene and polystyrene).

General properties
Because of differences in molecular structure, the empirical formula remains different between hydrocarbons; in
linear, or "straight-run" alkanes, alkenes and alkynes, the amount of bonded hydrogen lessens in alkenes and alkynes
due to the "self-bonding" or catenation of carbon preventing entire saturation of the hydrocarbon by the formation of
double or triple bonds.
This inherent ability of hydrocarbons to bond to themselves is referred to as catenation, and allows hydrocarbon to
form more complex molecules, such as cyclohexane, and in rarer cases, arenes such as benzene. This ability comes
from the fact that bond character between carbon atoms is entirely non-polar, in that the distribution of electrons
between the two elements is somewhat even due to the same electronegativity values of the elements (~0.30), and
does not result in the formation of an electrophile.
Hydrocarbon 36

Generally, with catenation comes the loss of the total amount of bonded hydrocarbons and an increase in the amount
of energy required for bond cleavage due to strain exerted upon the molecule; in molecules such as cyclohexane, this
is referred to as ring strain, and occurs due to the "destabilized" spatial electron configuration of the atom.
In simple chemistry, as per valence bond theory, the carbon atom must follow the "4-hydrogen rule", which states
that the maximum number of atoms available to bond with carbon is equal to the number of electrons that are
attracted into the outer shell of carbon. In terms of shells, carbon consists of an incomplete outer shell, which
comprises 4 electrons, and thus has 4 electrons available for covalent or dative bonding.
Hydrocarbons are hydrophobic and are lipids.
Some hydrocarbons also are abundant in the solar system. Lakes of liquid methane and ethane have been found on
Titan, Saturn's largest moon, confirmed by the Cassini-Huygens Mission.[12] Hydrocarbons are also abundant in
nebulae forming Polycyclic Aromatic Hydrocarbons - PAH compounds.

Simple hydrocarbons and their variations

Number of Alkane Alkene Alkyne Cycloalkane Alkadiene

carbon atoms

1 Methane – – – –

2 Ethane Ethene (ethylene) Ethyne (acetylene) – –

3 Propane Propene (propylene) Propyne (methylacetylene) Cyclopropane Propadiene (allene)

4 Butane Butene (butylene) Butyne Cyclobutane Butadiene

5 Pentane Pentene Pentyne Cyclopentane Pentadiene (piperylene)

6 Hexane Hexene Hexyne Cyclohexane Hexadiene

7 Heptane Heptene Heptyne Cycloheptane Heptadiene

8 Octane Octene Octyne Cyclooctane Octadiene

9 Nonane Nonene Nonyne Cyclononane Nonadiene

10 Decane Decene Decyne Cyclodecane Decadiene

Usage
Hydrocarbons are one of the Earth's most important energy resources. The predominant use of hydrocarbons is as a
combustible fuel source. In their solid form, hydrocarbons take the form of asphalt.[13]
Mixtures of volatile hydrocarbons are now used in preference to the chlorofluorocarbons as a propellant for aerosol
sprays, due to chlorofluorocarbon's impact on the ozone layer.
Methane [1C] and ethane [2C] are gaseous at ambient temperatures and cannot be readily liquified by pressure alone.
Propane [3C] is however easily liquified, and exists in 'propane bottles' mostly as a liquid. Butane [4C] is so easily
liquified that it provides a safe, volatile fuel for small pocket lighters. Pentane [5C] is a clear liquid at room
temperature, commonly used in chemistry and industry as a powerful nearly odorless solvent of waxes and high
molecular weight organic compounds, including greases. Hexane [6C] is also a widely used non-polar, non-aromatic
solvent, as well as a significant fraction of common gasoline.
The [6C] through [10C] alkanes, alkenes and isomeric cycloalkanes are the top components of gasoline, naptha, jet
fuel and specialized industrial solvent mixtures. With the progressive addition of carbon units, the simple non-ring
structured hydrocarbons have higher viscosities, lubricating indices, boiling points, solidification temperatures, and
deeper color. At the opposite extreme from [1C] methane lie the heavy tars that remain as the lowest fraction in a
crude oil refining retort. They are collected and widely utilized as roofing compounds, pavement composition, wood
Hydrocarbon 37

preservatives (the creosote series) and as extremely high viscosity sheer-resisting liquids.

Burning hydrocarbons
Hydrocarbons are currently the main source of the world’s electric energy and heat sources (such as home heating)
because of the energy produced when burnt. Often this energy is used directly as heat such as in home heaters, which
use either oil or natural gas. The hydrocarbon is burnt and the heat is used to heat water, which is then circulated. A
similar principle is used to create electric energy in power plants.
Common properties of hydrocarbons are the facts that they produce steam, carbon dioxide and heat during
combustion and that oxygen is required for combustion to take place. The simplest hydrocarbon, methane, burns as
follows:
CH4 + 2 O2 → 2 H2O + CO2 + Energy
Another example of this property is propane:
C3H8 + 5 O2 → 4 H2O + 3 CO2 + Energy
CnH2n+2 + (3n+1)/2 O2 → (n+1) H2O + n CO2 + Energy
Burning of hydrocarbons is an example of exothermic chemical reaction.

Petroleum

Extracted hydrocarbons in a liquid

form are referred to as petroleum
(literally "rock oil") or mineral oil,
whereas hydrocarbons in a gaseous
form are referred to as natural gas.
Petroleum and natural gas are found in
the Earth's subsurface with the tools of
petroleum geology and are a
significant source of fuel and raw
materials for the production of organic
chemicals.

The extraction of liquid hydrocarbon

Oil refineries are key to obtaining hydrocarbons. Crude oil is processed in several stages
fuel from sedimentary basins is
to form desired hydrocarbons, used as fuel and in other products.
integral to modern energy
development. Hydrocarbons are mined
from tar sands and oil shale, and potentially extracted from sedimentary methane hydrates. These reserves require
distillation and upgrading to produce synthetic crude and petroleum.

Oil reserves in sedimentary rocks are the source of hydrocarbons for the energy, transport and petrochemical
industry.
Hydrocarbons are economically important because major fossil fuels such as coal, petroleum and natural gas, and its
derivatives such as plastics, paraffin, waxes, solvents and oils are hydrocarbons. Hydrocarbons — along with NOx
and sunlight – contribute to the formation of tropospheric ozone and greenhouse gases.
Hydrocarbons are abundant in the universe and the hydrocarbons were trapped inside the Earth's mantle during
accretion. They are primordial materials that emerge from great depths to shallower levels in the crust. After
migration of the mantle to the crust, microorganisms invade the hydrocarbon accumulations, feed them and also die
leaving their parts in this context as contaminants, such as biomarkers.
Hydrocarbon 38

See also
• Abiogenic petroleum origin
• Biohydrocarbon
• Energy storage
• Fractional distillation
• Functional group
• Hydrocarbon mixtures
• Hydrocarbons on other planets

References
[1] Silberberg, 620
[2] IUPAC Goldbook hydrocarbyl groups (http:/ / goldbook. iupac. org/ H02891. html)
[3] Clayden, J., Greeves, N., et al. (2001) Organic Chemistry Oxford ISBN 0198503466 p. 21
[4] McMurry, J. (2000). Organic Chemistry 5th ed. Brooks/Cole: Thomson Learning. ISBN 0495118370 pp. 75–81
[5] Silderberg, 623
[6] Silderberg, 625
[7] Silderberg, 627
[8] Meierhenrich, Uwe. Amino Acids and the Asymmetry of Life (http:/ / books. google. com/ books?id=a2J23yPEaBQC& printsec=frontcover).
Springer, 2008. ISBN 978-3-54-076885-2
[9] Silderberg, 628
[10] Silderberg, 631
[11] Silderberg, 625
[12] 'Proof' of methane lakes on Titan (http:/ / news. bbc. co. uk/ 2/ hi/ science/ nature/ 6230381. stm), BBC News, 4 January 2007
[13] Dan Morgan, Lecture ENVIRO 100, University of Washington, 11/5/08

Bibliography
• Silberberg, Martin. Chemistry: The Molecular Nature Of Matter and Change. New York: McGraw-Hill
Companies, 2004. ISBN 0073101699

External links
• The Methane Molecule (http://www.worldofmolecules.com/fuels/methane.htm)
Aldehyde 39

Aldehyde
An aldehyde (pronounced /ˈældɨhaɪd/) is an organic compound containing a
formyl group. This functional group, with the structure R-CHO, consists of a
carbonyl centre bonded to hydrogen and an R group. [1] The group without R
is called the aldehyde group or formyl group. Aldehydes differ from
ketones in that the carbonyl is placed at the end of a carbon skeleton rather
than between two carbon atoms. Aldehydes are common in organic
chemistry. Many fragrances are aldehydes.

Structure and bonding An aldehyde.

R is the group attached to the blue
Aldehydes feature an sp2-hybridized, planar carbon center that is connected
aldehyde group.
by a double bond to oxygen and a single bond to hydrogen. The C-H bond is
not acidic. Owing to resonance stabilization of the conjugate base, an
α-hydrogen in an aldehyde is far more acidic with a pKa near 17, than a C-H
bond in a typical alkane, with a pKa in the 30's. This acidification is attributed
to (i) the electron-withdrawing quality of the formyl center and (ii) the fact
that the conjugate base, an enolate anion, delocalizes its negative charge.
Related to (i), the aldehyde group is somewhat polar.

Aldehydes (except formaldehyde) can exist in either the keto or the enol
tautomer. Keto-enol tautomerism is catalyzed by either acid or base. Usually
the enol is the minority tautomer, but it is more reactive. Formaldehyde, the simplest
aldehyde

Nomenclature

IUPAC names for aldehydes

The common names for aldehydes do not strictly follow official guidelines, such as those recommended by IUPAC
but these rules are useful. IUPAC prescribes the following nomenclature for aldehydes:[2] [3] [4]
1. Acyclic aliphatic aldehydes are named as derivatives of the longest carbon chain containing the aldehyde group.
Thus, HCHO is named as a derivative of methane, and CH3CH2CH2CHO is named as a derivative of butane. The
name is formed by changing the suffix -e of the parent alkane to -al, so that HCHO is named methanal, and
CH3CH2CH2CHO is named butanal.
2. In other cases, such as when a -CHO group is attached to a ring, the suffix -carbaldehyde may be used. Thus,
C6H11CHO is known as cyclohexanecarbaldehyde. If the presence of another functional group demands the use
of a suffix, the aldehyde group is named with the prefix formyl-. This prefix is preferred to methanoyl-.
3. If the compound is a natural product or a carboxylic acid, the prefix oxo- may be used to indicate which carbon
atom is part of the aldehyde group; for example, CHOCH2COOH is named 3-oxopropanoic acid.
4. If replacing the aldehyde group with a carboxyl group (-COOH) would yield a carboxylic acid with a trivial
name, the aldehyde may be named by replacing the suffix -ic acid or -oic acid in this trivial name by -aldehyde.
Aldehyde 40

Etymology
The word aldehyde was coined by Justus von Liebig as a contraction of
the Latin alcohol dehydrogenatus (dehydrogenated alcohol).[5] In the
past, aldehydes were sometimes named after the corresponding
alcohols, for example, vinous aldehyde for acetaldehyde. (Vinous is
from Latin vinum = wine (the traditional source of ethanol), cognate
with vinyl.)

The term formyl group is derived from the Latin and/or Italian word
formica = ant. This word can be recognized in the simplest aldehyde,
formaldehyde (methanal), and in the simplest carboxylic acid, formic
Formic acid
acid (methanoic acid, an acid, but also an aldehyde).

Physical properties and characterization

Aldehydes have properties that are diverse and that depend on the remainder of the molecule. Smaller aldehydes are
more soluble in water, formaldehyde and acetaldehyde completely so. The volatile aldehydes have pungent odors.
Aldehydes degrade in air via the process of autoxidation.
The two aldehydes of greatest importance in industry, formaldehyde and acetaldehyde, have complicated behavior
because of their tendency to oligomerize or polymerize. They also tend to hydrate, forming the geminal diol. The
oligomers/polymers and the hydrates exist in equilibrium with the parent aldehyde.
Aldehydes are readily identified by spectroscopic methods. Using IR spectroscopy, they display a strong νCO band
near 1700 cm−1. In their 1H NMR spectra, the formyl hydrogen center absorbs near δ9, which is a distinctive part of
the spectrum. This signal shows the characteristic coupling to any protons on the alpha carbon.

Applications and occurrence

Important aldehydes and related compounds. From the left: formaldehyde and its trimer, acetaldehyde and its enol, glucose (pyranose form), the
flavorant cinnamaldehyde, the visual pigment retinal, and the vitamin pyridoxal.

Naturally occurring aldehydes

Traces of many aldehydes are found in essential oils and often contribute to their favorable odors, e.g.
cinnamaldehyde, cilantro, and vanillin. Possibly because of the high reactivity of the formyl group, aldehydes are not
common in several of the natural building blocks - amino acids, nucleic acids, lipids. Most sugars, however, are
derivatives of aldehydes. These "aldoses" exist as hemiacetals, a sort of masked form of the parent aldehyde. For
example, in aqueous solution only a tiny fraction of glucose exists as the aldehyde.
Aldehyde 41

Synthesis
There are several methods for preparing aldehydes,[6] but the dominant technology is hydroformylation.[7]
Illustrative is the generation of butyraldehyde by hydroformylation of propene:
H2 + CO + CH3CH=CH2 → CH3CH2CH2CHO

Oxidative routes
Aldehydes are commonly generated by alcohol oxidation. In industry, formaldehyde is produced on a large scale by
oxidation of methanol. Oxygen is the reagent of choice, being "green" and cheap. In the laboratory, more specialized
oxidizing agents are used, but chromium(VI) reagents are popular. Oxidation can be achieved by heating the alcohol
with an acidified solution of potassium dichromate. In this case, excess dichromate will further oxidize the aldehyde
to a carboxylic acid, so either the aldehyde is distilled out as it forms (if volatile) or milder reagents such as PCC are
used.[8]
"O" + CH3(CH2)9OH → CH3(CH2)8CHO + H2O
Oxidation of primary alcohols to form aldehydes and can be achieved under milder, chromium-free conditions by
employing methods or reagents such as IBX acid, Dess-Martin periodinane, Swern oxidation, TEMPO, or the
Oppenauer oxidation.
Another oxidation route significant in industry is the Wacker process, whereby ethylene is oxidized to acetaldehyde
in the presence of copper and palladium catalysts (acetaldehyde is also produced on a large scale by the hydration of
acetylene).

Specialty methods

Reaction name Substrate Comment

Ozonolysis alkene ozonolysis of non-fully-substituted alkenes yield aldehydes upon reductive work-up.

Organic reduction ester Reduction of an ester with diisobutylaluminium hydride (DIBAL-H) or sodium aluminium
hydride

Rosenmund reaction acid chloride or using lithium tri-t-butoxyaluminium hydride (LiAlH(O-t-C4H9)3).

Wittig reaction ketone reagent methoxymethylenetriphenylphosphine in a modified Wittig reaction.

Formylation reactions nucleophilic various reactions for example the Vilsmeier-Haack reaction
arenes

Nef reaction Nitro compound

Zincke reaction pyridines Zincke aldehydes form in a variation

Stephen aldehyde synthesis nitriles reagents tin(II) chloride and hydrochloric acid.

Meyers synthesis oxazine oxazine hydrolysis

McFadyen-Stevens hydrazide is a base-catalyzed thermal decomposition of acylsulfonylhydrazides

reaction
Aldehyde 42

Common reactions
Aldehydes are highly reactive and participate in many reactions.[6] " From the industrial perspective, important
reactions are condensations, e.g. to prepare plasticizers and polyols, and reduction to produce alcohols, especially
"oxo-alcohols." From the biological perspective, the key reactions involve addition of nucleophiles to the formyl
carbon in the formation of imines (oxidative deamination) and hemiacetals (structures of aldose sugars).[6]

Reduction
The" formyl group can be readily reduced to a primary alcohol (-CH2OH). Typically this conversion is accomplished
by catalytic hydrogenation either directly or by transfer hydrogenation. Stoichiometric reductions are also popular, as
can be effected with sodium borohydride.

Oxidation
The formyl group readily oxidizes to the corresponding carboxylic acid (-COOH). The preferred oxidant in industry
is oxygen or air. In the laboratory, popular oxidizing agents include potassium permanganate, nitric acid,
chromium(VI) oxide, and chromic acid. The combination of manganese dioxide, acetic acid and methanol will
convert the aldehyde to a methyl ester.[9]
Another oxidation reaction is the basis of the silver mirror test. In this test, an aldehyde is treated with Tollens'
reagent, which is prepared by adding a drop of sodium hydroxide solution into silver nitrate solution to give a
precipitate of silver(I) oxide, and then adding just enough dilute ammonia solution to redissolve the precipitate in
aqueous ammonia to produce [Ag(NH3)2]+ complex. This reagent will convert aldehydes to carboxylic acids without
attacking carbon-carbon double-bonds. The name silver mirror test arises because this reaction will produce a
precipitate of silver whose presence can be used to test for the presence of an aldehyde.
If the aldehyde cannot form an enolate (e.g., benzaldehyde), addition of strong base induces the Cannizzaro reaction.
This reaction results in disproportionation, producing a mixture of alcohol and carboxylic acid.

Nucleophilic addition reactions

Nucleophiles add readily to the carbonyl group. In the product, the carbonyl carbon becomes sp3 hybridized, being
bonded to the nucleophile, and the oxygen center becomes protonated:
RCHO + Nu- → RCH(Nu)O-
RCH(Nu)O- + H+ → RCH(Nu)OH
In many cases, a water molecule is removed after the addition takes place; in this case, the reaction is classed as an
addition-elimination or addition-condensation reaction. There are many variations of nucleophilic addition reactions.

Oxygen nucleophiles
In the acetalisation reaction, under acidic or basic conditions, an alcohol adds to the carbonyl group and a proton is
transferred to form a hemiacetal. Under acidic conditions, the hemiacetal and the alcohol can further react to form an
acetal and water. Simple hemiacetals are usually unstable, although cyclic ones such as glucose can be stable.
Acetals are stable, but revert to the aldehyde in the presence of acid. Aldehydes can react with water to form
hydrates, R-C(H)(OH)(OH). These diols are stable when strong electron withdrawing groups are present, as in
chloral hydrate. The mechanism of formation is identical to hemiacetal formation.
Aldehyde 43

Nitrogen nucleophiles
In alkylimino-de-oxo-bisubstitution, a primary or secondary amine adds to the carbonyl group and a proton is
transferred from the nitrogen to the oxygen atom to create a carbinolamine. In the case of a primary amine, a water
molecule can be eliminated from the carbinolamine to yield an imine. This reaction is catalyzed by acid.
Hydroxylamine (NH2OH) can also add to the carbonyl group. After the elimination of water, this will result in an
oxime. An ammonia derivative of the form H2NNR2 such as hydrazine (H2NNH2) or 2,4-dinitrophenylhydrazine can
also be the nucleophile and after the elimination of water, this will result in the formation of a hydrazone. This forms
the basis of a test for aldehydes and ketones.

Carbon nucleophiles
The cyano group in HCN can add to the carbonyl group to form cyanohydrins, R-C(H)(OH)(CN). In the Grignard
reaction, a Grignard reagent adds to the group, eventually yielding an alcohol with a substituted group from the
Grignard reagent. Related reactions are the Barbier reaction and the Nozaki-Hiyama-Kishi reaction. In
organostannane addition tin replaces magnesium.
In the aldol reaction, the metal enolates of ketones, esters, amides, and carboxylic acids will add to aldehydes to form
β-hydroxycarbonyl compounds (aldols). Acid or base-catalyzed dehydration will then lead to α,β-unsaturated
carbonyl compounds. The combination of these two steps is known as the aldol condensation. The Prins reaction
occurs when a nucleophilic alkene or alkyne reacts with an aldehyde as electrophile. The product of the Prins
reaction varies with reaction conditions and substrates employed.

More complex reactions

Reaction name Comment

Product

Wolff-Kishner reduction alkane If an aldehyde is converted to a simple hydrazone (RCH=NHNH2) and this is heated with a base such as
KOH, the terminal carbon is fully reduced to a methyl group. The Wolff-Kishner reaction may be
performed as a one-pot reaction, giving the overall conversion RCH=O → RCH3.

Pinacol coupling reaction diol with reducing agents such as magnesium

Wittig reaction alkene reagent an ylide

Takai reaction alkene diorganochromium reagent

Corey-Fuchs reactions alkyne phosphine-dibromomethylene reagent

Ohira–Bestmann reaction alkyne reagent dimethyl (diazomethyl)phosphonate

Johnson-Corey-Chaykovsky epoxide reagent a sulfonium ylide

reaction

Oxo Diels Alder reaction pyran Aldehydes can, typically in the presence of suitable catalysts, serve as partners in cycloaddition
reactions. The aldehyde serves as the dienophile component, giving a pyran or related compound.

Hydroacylation ketone In hydroacylation an aldehyde is added over an alkene to form a ketone.

decarbonylation alkane catalysed by transition metals

Aldehyde 44

Examples of aldehydes
• Methanal (Formaldehyde)
• Ethanal (Acetaldehyde)
• Propanal (Propionaldehyde)
• Butanal (butyraldehyde)
• Benzaldehyde
• Cinnamaldehyde
• Tolualdehyde

Related compounds
Other kinds of organic compounds containing carbonyl groups include
• Dialdehydes
• Ketones
• Carboxylic acids
• Amides

External links
• Aldehyde synthesis - Synthetic protocols [10] from organic-reaction.com

References
[1] IUPAC Gold Book aldehydes (http:/ / goldbook. iupac. org/ A00208. html)
[2] Short Summary of IUPAC Nomenclature of Organic Compounds (http:/ / www. uwc. edu/ dept/ chemistry/ helpful_files/ nomenclature. pdf),
web page, University of Wisconsin Colleges, accessed on line August 4, 2007.
[3] §R-5.6.1, Aldehydes, thioaldehydes, and their analogues, A Guide to IUPAC Nomenclature of Organic Compounds: recommendations 1993
(http:/ / www. acdlabs. com/ iupac/ nomenclature/ 93/ r93_449. htm), IUPAC, Commission on Nomenclature of Organic Chemistry,
Blackwell Scientific, 1993.
[4] §R-5.7.1, Carboxylic acids, A Guide to IUPAC Nomenclature of Organic Compounds: recommendations 1993 (http:/ / www. acdlabs. com/
iupac/ nomenclature/ 93/ r93_480. htm), IUPAC, Commission on Nomenclature of Organic Chemistry, Blackwell Scientific, 1993.
[5] Crosland, Maurice P. (2004), Historical Studies in the Language of Chemistry (http:/ / books. google. com/ books?id=kwQQaltqByAC&
pg=PA297& dq=alcohol+ dehydrogenatus& hl=en& ei=p7dITOPVGJSd4QaN7unkDA& sa=X& oi=book_result& ct=result& resnum=6&
ved=0CEMQ6AEwBQ#v=onepage& q=alcohol dehydrogenatus& f=false), Courier Dover Publications,
[6] Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York:
Wiley-Interscience, ISBN 0-471-72091-7
[7] W." Bertleff, M. Roeper, X. Sava, “Carbonylation” in Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH: Weinheim, 2003. doi:
10.1002/14356007.a05_217.pub2
[8] R. W. Ratcliffe (1988), "Oxidation with the Chromium Trioxide-Pyridine Complex Prepared in situ: 1-Decanal" (http:/ / www. orgsyn. org/
orgsyn/ orgsyn/ prepContent. asp?prep=cv6p0373), Org. Synth., ; Coll. Vol. 6: 373
[9] New methods for the oxidation of aldehydes to carboxylic acids and esters Elias J. Corey, Norman W. Gilman, and B. E. Ganem J. Am.
Chem. Soc. 1968; 90(20) pp 5616 - 5617; doi:10.1021/ja01022a059.
[10] http:/ / www. organic-reaction. com/ synthetic-protocols/ functionals-groups/ aldehyde/
Ketone 45

Ketone

Acetone Ketone group

In organic chemistry, a ketone (pronounced /ˈkiːtoʊn/) is a compound with
the structure RC(=O)R', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group
(C=O) bonded to two other carbon atoms.[1] Acetone is the simplest example of a ketone, and in fact the word ketone
derives its name from Aketon, the German word for acetone.[2]
Ketones differ from aldehydes in that the carbonyl is placed between two carbons rather than at the end of a carbon
skeleton. They are also distinct from other functional groups, such as carboxylic acids, esters and amides, which
have a carbonyl group bonded to a hetero atom.
A ketone that has an α-hydrogen participates in a so-called keto-enol tautomerism. The reaction with a strong base
gives the corresponding enolate, often by deprotonation of the enol.

Nomenclature
According to the rules of IUPAC nomenclature, ketones are named by changing the suffix -e of the parent alkane to
-one. For the most important ketones, however, traditional nonsystematic names are still generally used, for example
acetone and benzophenone. These nonsystematic names are considered retained IUPAC names,[3] although some
introductory chemistry textbooks use names such as 2-propanone instead of acetone, the simplest ketone
(CH3-CO-CH3). The position of the carbonyl group is usually denoted by a number.
Oxo is the IUPAC nomenclature for a ketone functional group. Other prefixes, however, are also used. For some
common chemicals (mainly in biochemistry), "keto" or "oxo" is the term that describes the ketone functional group.
The term "oxo" is used widely through chemistry, for example it also refers to a single oxygen atom coordinated to a
transition metal (a metal oxo).

Structure and properties

Representative ketones, from the left: acetone, a common solvent; oxaloacetate, an intermediate in the metabolism of sugars; acetylacetone in its
(mono) enol form (the enol highlighted in blue); cyclohexanone, precursor to Nylon; muscone, an animal scent; and tetracycline, an antibiotic.

The ketone carbon is often described as "sp2 hybridized," terminology that describes both their electronic and
molecular structure. Ketones are trigonal planar about the ketonic carbon, with C-C-O and C-C-C bond angles of
Ketone 46

approximately 120°.
The carbonyl group is polar as a consequence of the fact that the electronegativity of the oxygen center is greater
than that for carbonyl carbon. Thus, ketones are nucleophilic at oxygen and electrophilic at carbon. Because the
carbonyl group interacts with water by hydrogen bonding, ketones are typically more soluble in water than the
related methylene compounds. Ketones are hydrogen-bond acceptors. Ketones are not usually hydrogen-bond donors
and cannot hydrogen-bond to itself. Because of their inability to serve both as hydrogen-bond donors and acceptors,
ketones tend not to "self-associate" and are more volatile than alcohols and carboxylic acids of comparable
molecular weights. These factors relate to pervasiveness of ketones in perfumery and as solvents.

Classes of ketones
Ketones are classified on the basis of their substituents. One broad classification subdivides ketones into symmetrical
and unsymmetrical derivatives, depending on the equivalency of the two organic substituents attached to the
carbonyl center. Acetone and benzophenone are symmetrical ketones. Acetophenone (C6H5C(O)CH3) is an
unsymmetrical ketone. In the area of stereochemistry, unsymmetrical ketones are known for being prochiral.

Diketones
Many kinds of diketones are known, some with unusual properties. The simplest is biacetyl (CH3C(O)C(O)CH3),
once used as butter-flavoring in popcorn. Acetylacetone (pentane-2,4-dione) is virtually a misnomer (inappropriate
name) because this species exists mainly as the monoenol CH3C(O)CH=C(OH)CH3. Its enolate is a common ligand
in coordination chemistry.

Unsaturated ketones
Ketones containing alkene and alkyne units are often called unsaturated ketones. The most widely used member of
this class of compounds is methyl vinyl ketone, CH3C(O)CH=CH2, which is useful in Robinson annulation reaction.
Lest there be confusion, a ketone itself is a site of unsaturation, that is it can be hydrogenated.

Cyclic ketones
Many ketones are cyclic. The simplest class have the formula (CH2)nCO where n varies from 3 for cyclopropanone
to the teens. Larger derivatives exist. Cyclohexanone, a symmetrical cyclic ketone, is an important intermediate in
the production of nylon. Isophorone, derived from acetone, is an unsaturated, unsymmetrical ketone that is the
precursor to other polymers. Muscone, 3-methylpentadecanone, is an animal pheromone.

Keto-enol tautomerization
Ketones that have at least one alpha-hydrogen, undergo
keto-enol tautomerization; the tautomer is an enol.
Tautomerization may be catalyzed by both acids and
bases. Usually, the keto form is more stable than the
enol. This equilibrium allows ketones to be prepared
via the hydration of alkynes.

Keto-enol tautomerism. 1 is the keto form; 2 is the enol.

Ketone 47

Acidity of ketones
Ketones are far more acidic (pKa ≈ 20) than a regular alkane (pKa ≈ 50). This difference reflects resonance
stabilization of the enolate ion that is formed through dissociation. The relative acidity of the α-hydrogen is
important in the enolization reactions of ketones and other carbonyl compounds. The acidity of the α-hydrogen also
allows ketones and other carbonyl compounds to undergo nucleophilic reactions at that position, with either
stoichiometric and catalytic base.

Characterization

Spectroscopy
Ketones and aldehydes absorb strongly in infra-red spectrum near 1700 cm−1. The exact position of the peak
depends on the substituents.
Whereas 1H NMR spectroscopy is generally not useful for establishing the presence of a ketone, 13C NMR spectra
exhibit signals somewhat downfield of 200 ppm depending on structure. Such signals are typically weak due to the
absence of nuclear Overhauser effects. Since aldehydes resonate at similar chemical shifts, multiple resonance
experiments are employed to definitively distinguish aldehydes and ketones.

Qualitative organic tests

Ketones give positive results in Brady's test, the reaction with 2,4-dinitrophenylhydrazine to give the corresponding
hydrazone. Ketones may be distinguished from aldehydes by giving a negative result with Tollens' reagent. Methyl
ketones give positive results for the iodoform test.

Synthesis
Many methods exist for the preparation of ketones in industrial scale, biology, and in academic laboratories. In
industry, the most important method probably involves oxidation of hydrocarbons, often with air. For example,
billion kilograms of cyclohexanone are produced annually by aerobic oxidation of cyclohexane. Acetone is prepared
by air-oxidation of cumene.
For specialized or small scale organic synthetic applications, ketones are often prepared by oxidation of secondary
alcohols:
R2CH(OH) + O → R2C=O + H2O
Typical strong oxidants (source of "O" in the above reaction) include potassium permanganate or a Cr(VI)
compound. Milder conditions make use of the Dess-Martin periodinane or the Moffatt-Swern methods.
Many other methods have been developed including:
• By geminal halide hydrolysis.
• By hydration of alkynes. Such processes occur via enols and require the presence of an acid and HgSO4.
Subsequent enol-keto tautomerization gives a ketone. This reaction always produces a ketone, even with a
terminal alkyne.
• Aromatic ketones can be prepared in the Friedel-Crafts acylation, the related Houben-Hoesch reaction and the
Fries rearrangement.
• Ozonolysis, and related dihydroxylation/oxidative sequences, cleave alkenes to give aldehydes and/or ketones,
depending on alkene substitution pattern.
• In the Kornblum–DeLaMare rearrangement ketones are prepared from peroxides and base.
• In the Ruzicka cyclization, cyclic ketones are prepared from dicarboxylic acids.
• In the Nef reaction, ketones form by hydrolysis of salts of secondary nitro compounds.
• In the Fukuyama coupling, ketones form from a thioester and an organozinc compound.
Ketone 48

• By the reaction of an acid chloride with organocadmium compounds or organocopper compounds.

• The Dakin-West reaction provides an efficient method for preparation of certain methyl ketones from carboxylic
acids.
• Ketones can also be prepared by the reaction of Grignard reagents with nitriles, followed by hydrolysis.
• By decarboxylation of carboxylic anhydride.
• Ketones can be prepared from haloketones in reductive dehalogenation of halo ketones.

Reactions
Ketones engage in many organic reactions. The most important reactions follow from the susceptibility of the
carbonyl carbon toward nucleophilic addition and the tendency for the enolates to add to electrophiles. Nucleophilic
additions include in approximate order of their generality:
• With water (hydration) gives geminal diols, which are usually not formed in appreciable (or observable) amounts.
• With an acetylide to give the α-hydroxyalkyne.
• With ammonia or a primary amine gives an imine.
• With secondary amine gives an enamine.
• With Grignard and organolithium reagents to give, after aqueous workup, a tertiary alcohol.
• With an alcohols or alkoxides to gives the hemiketal or its conjugate base. With a diol to th ketal. This reaction is
employed to protect ketones.
• With sodium amide resulting in C-C bond cleavage with formation of the amide RCONH2 and the alkane R'H, a
reaction called the Haller-Bauer reaction.[4]
• Electrophilic addition, reaction with an electrophile gives a resonance stabilized cation.
• With phosphonium ylides in the Wittig reaction to give the alkenes
• With thiols to give the thioacetal
• With hydrazine or 1-disubstituted derivatives of hydrazine to give hydrazones.
• With a metal hydride gives a metal alkoxide salt, hydrolysis of which gives the alcohol, an example of ketone
reduction
• With halogens to form α-haloketone, a reaction that proceeds via an enol, see Haloform reaction.
• With heavy water to give a α-deuterated ketone.
• Fragmentation in photochemical Norrish reaction
• Reaction of 1,4-aminodiketones to oxazoles by dehydration in the Robinson-Gabriel synthesis
• In the case of aryl-alkyl ketones, with sulfur and an amine give amides in the Willgerodt reaction.
• With hydroxylamine to produce oximes

Biochemistry
Acetone, acetoacetate and beta-hydroxybutyrate are ketones (or ketone bodies) generated from carbohydrates, fatty
acids and amino acids in humans and most vertebrates. Ketones are elevated in blood after fasting including a night
of sleep, and in both blood and urine in starvation, hypoglycemia due to causes other than hyperinsulinism, various
inborn errors of metabolism, and ketoacidosis (usually due to diabetes mellitus). Although ketoacidosis is
characteristic of decompensated or untreated type 1 diabetes, ketosis or even ketoacidosis can occur in type 2
diabetes in some circumstances as well. Acetoacetate and beta-hydroxybutyrate are an important fuel for many
tissues, especially during fasting and starvation. The brain, in particular, relies heavily on ketone bodies as a
substrate for lipid synthesis and for energy during times of reduced food intake. Ketones have been described as
"magic" in their ability to increase metabolic efficiency, while decreasing production of free radicals, the damaging
byproducts of normal metabolism. Ketone bodies are relevant to neurological diseases such as Alzheimer's and
Parkinson's disease,[5] and the heart and brain operate 25% more efficiently using ketones as a source of energy.[6]
Research has also shown ketones play a role in reducing epileptic seizures with the so-called high-fat, near-zero
Ketone 49

carbohydrate Ketogenic Diet. [7]

Applications
Ketones are produced on massive scales in industry as solvents, polymer precursors, and pharmaceuticals. In terms
of scale, the most important ketones are acetone, methylethyl ketone, and cyclohexanone. They are also common in
biochemistry, but less so than in organic chemistry in general. The combustion of hydrocarbons is an uncontrolled
oxidation process that gives ketones as well as many other types of compounds.

Toxicity
Although it is difficult to generalize on the toxicity of such a broad class of compounds, simple ketones are generally
not highly toxic (for instance, the sugar fructose is a ketone). This characteristic is one reason for their popularity as
solvents. Exceptions to this rule are the unsaturated ketones such as methyl vinyl ketone with LD50 of 7 mg/kg
(oral).

See also
• Diketone

References
[1] IUPAC Gold Book ketones (http:/ / goldbook. iupac. org/ K03386. html)
[2] http:/ / www. etymonline. com/ index. php?term=ketone Online Etymology Dictionary
[3] List of retained IUPAC names retained IUPAC names Link (http:/ / www. acdlabs. com/ iupac/ nomenclature/ 93/ r93_701. htm)
[4] Haller-Bauer Reaction (http:/ / nagoyaren. homeip. net/ chem/ reactions/ 123. htm)
[5] Y. Kashiwaya, T. Takeshima, N. Mori, K. Nakashima, K. Clarke and R. L. Veech (2000). "D-beta -Hydroxybutyrate protects neurons in
models of Alzheimer's and Parkinson's disease" (http:/ / www. pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=25847).
PNAS 97 (10): 5440–5444. doi:10.1073/pnas.97.10.5440. PMID 10805800. PMC 25847.
[6] Y. Kashiwaya, K. Sato, N. Tsuchiya, S. Thomas, D. A. Fell, R. L. Veech and J. V. Passonneau (1994). "Control of glucose utilization in
working perfused rat heart" (http:/ / www. jbc. org/ cgi/ content/ abstract/ 269/ 41/ 25502). J. Biol. Chem. 269 (41): 25502–25514.
PMID 7929251. .
[7] http:/ / www. vanderbilt. edu/ AnS/ psychology/ health_psychology/ ketogenic_diets. htm
Amine 50

Amine
Primary amine Secondary amine Tertiary amine

Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines
are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an
alkyl or aryl group.[1] Important amines include amino acids, biogenic amines, trimethylamine, and aniline; see
Category:Amines for a list of amines. Inorganic derivatives of ammonia are also called amines, such as chloramine
(NClH2).
Compounds with the nitrogen atom attached to a carbonyl of the structure R-C(=O)NR2 are called amides and have
different chemical properties from amines.

Classes of amines

Aliphatic amines
Primary amines arise when one of three hydrogen atoms in ammonia is replaced by an alkyl. Important primary alkyl
amines include methylamine, ethanolamine (2-aminoethanol), and the buffering agent tris). Secondary amines have
two alkyl substituents bound to N together with one hydrogen. Important representatives include dimethylamine and
methylethanolamine. In tertiary amines, all three hydrogen atoms are replaced by organic substituents. Examples
include trimethylamine, a distinctively fishy smell. Cyclic amines are either secondary or tertiary amines. Examples
of cyclic amines include the 3-member ring aziridine and the six-membered ring piperidine. N-methylpiperidine is a
cyclic tertiary amine. It is also possible to have four alkyl substituents on the nitrogen. These compounds are not
amines but are called quaternary ammonium cations, have a charged nitrogen center, and necessarily come with an
anion.

Aromatic amines
Aromatic amines have the nitrogen atom connected to an aromatic ring as in anilines. The aromatic ring decreases
the alkalinity of the amine, depending on its substituents. The presence of an amine group strongly increases the
reactivity of the aromatic ring, due to an electron-donating effect.

Naming conventions
Amines are named in several ways. Typically, the compound is given the prefix "amino-" or the suffix: "-amine."
The prefix "N-" shows substitution on the nitrogen atom. An organic compound with multiple amino groups is called
a diamine, triamine, tetraamine and so forth.
Systematic names for some common amines:

Lower amines are named with the suffix Higher amines have the prefix amino as a functional
-amine. group.

2-aminopentane
methylamine (or sometimes: pent-2-yl-amine or pentane-2-amine)
Amine 51

Physical properties
Hydrogen bonding significantly influences the properties of primary and secondary amines.[2] Thus the boiling point
of amines is higher than those of the corresponding phosphines, but generally lower than those of the corresponding
alcohols. For example, methylamine and ethylamine are gases under standard conditions, whereas the corresponding
methyl alcohol and ethyl alcohols are liquids. Gaseous amines possess a characteristic ammonia smell, liquid amines
have a distinctive "fishy" smell.
Also reflecting their ability to form hydrogen bonds, most aliphatic amines display some solubility in water.
Solubility decreases with the increase in the number of carbon atoms. Aliphatic amines display significant solubility
in organic solvents, especially polar organic solvents. Primary amines react with ketones such as acetone, and most
amines are incompatible with chloroform and carbon tetrachloride.
The aromatic amines, such as aniline, have their lone pair electrons conjugated into the benzene ring, thus their
tendency to engage in hydrogen bonding is diminished. Their boiling points are high and their solubility in water low

Chirality
Amines of the type NHRR' and NRR'R" are chiral: the nitrogen
atom bears four substituents counting the lone pair. The energy
barrier for the inversion of the stereocenter is relatively low, e.g.,
~7 kcal/mol for a trialkylamine. The interconversion of the
stereoisomers has been compared to the inversion of an open
umbrella in to a strong wind. Because of this low barrier, amines
such as NHRR' cannot be resolved optically and NRR'R" can only be resolved when the R, R', and R" groups are
constrained in cyclic structures such as aziridines. Quaternary ammonium salts with four distinct groups on the
nitrogen are capable of exhibiting optical activity.

Properties as bases
Like ammonia, amines are bases. Compared to alkali metal hydroxides, amines are reasonably weak (see table for
examples of conjugate acid Ka values). The basicity of amines depends on:
1. The electronic properties of the substituents (alkyl groups enhance the basicity, aryl groups diminish it).
2. Steric hindrance offered by the groups on nitrogen.
3. The degree of solvation of the protonated amine.
The nitrogen atom features a lone electron pair that can bind H+ to form an ammonium ion R3NH+. The lone
electron pair is represented in this article by a two dots above or next to the N. The water solubility of simple amines
is largely due to hydrogen bonding between protons in the water molecules and these lone electron pairs.
• Inductive effect of alkyl groups
Amine 52

Ions of compound Kb

Ammonia NH3 1.8·10−5 M

Propylamine CH3CH2CH2NH2 4.7·10−4 M

2-Propylamine (CH3)2CHNH2 3.4·10−4 M

Methylamine CH3NH2 4.4·10−4 M

Dimethylamine (CH3)2NH 5.4·10−4 M

Trimethylamine (CH3)3N 5.9·10−5 M

+I effect of alkyl groups raises the energy of the lone pair of electrons, thus elevating the basicity. Thus the
basicity of an amine may be expected to increase with the number of alkyl groups on the amine. However,
there is no strict trend in this regard, as basicity is also governed by other factors mentioned above. Consider
the Kb values of the methyl amines given above. The increase in Kb from methylamine to dimethylamine may
be attributed to +I effect; however, there is a decrease from dimethylamine to trimethyl amine due to the
predominance of steric hindrance offered by the three methyl groups to the approaching Lewis acid.
• Mesomeric effect of aromatic systems

Ions of compound Kb

Ammonia NH3 1.8·10−5 M

Aniline C6H5NH2 3.8·10−10 M

4-Methylaniline 4-CH3C6H4NH2 1.2·10−9 M

2-Nitroaniline 1.5·10−15 M

3-Nitroaniline 2.8·10−13 M

4-Nitroaniline 9.5·10−14 M

-M effect of aromatic ring delocalises the lone pair of electrons on nitrogen into the ring, resulting in decreased
basicity. Substituents on the aromatic ring, and their positions relative to the amine group may also
considerably alter basicity as seen above.
• The degree of solvation of protonated amines:

Ions of compound Maximum number of H-bond

4 Very Soluble in H2O

NH4+

3
RNH3+

2
R2NH2+

1 Least Soluble in H2O

R3NH+

In sterically hindered amines, as in the case of trimethylamine, the protonated form is not well-solvated. For this
reason the parent amine is less basic than expected. In the case of aprotic polar solvents (like DMSO and DMF),
wherein the extent of solvation is not as high as in protic polar solvents (like water and methanol), the basicity of
amines is almost solely governed by the electronic factors within the molecule.
Amine 53

Synthesis

Alkylation
The most industrially significant amines are prepared from ammonia by alkylation with alcohols:
ROH + NH3 → RNH2 + H2O
These reactions require catalysts, specialized apparatus, and additional purification measures since the selectivity can
be problematic. Treatment of Haloalkanes with amines give the corresponding alkyl-substituted amine, with the
release of a halogen acid, which in turn reacts with the amine product or precursor:
RX + 2 R'NH2 → RR'NH + [RR'NH2]X
Such reactions, which are most useful for alkyl iodides and bromides, are rarely employed because the degree of
alkylation is difficult to control.[3]

Reductive routes
Via the process of hydrogenation, nitriles are reduced to amines using hydrogen in the presence of a nickel catalyst.
Reactions are sensitive acidic or alkaline conditions, which can cause hydrolysis of -CN group. LiAlH4 is more
commonly employed for the reduction of nitriles on the laboratory scale. Similarly, LiAlH4 reduces amides to
amines. Many amines are produced from aldehydes and ketones via reductive amination, which can use either
catalytic hydrogenation or stoichiometric reagents.
Aniline and its derivatives are prepared by reduction of the nitroaromatics. In industry, hydrogen is the preferred
reductant, whereas in the laboratory, tin and iron are often employed.

Specialized methods
Many laboratory methods exist for the preparation of amines, many of these methods being rather specialized.

Reaction name Substrate Comment

Gabriel synthesis organohalide reagent: potassium phthalimide

Staudinger reduction Azide This reaction also takes place with a reducing agent such as lithium aluminium hydride.

Schmidt reaction carboxylic acid

Aza-Baylis–Hillman imine Synthesis of allylic amines

reaction

Hofmann degradation amide This reaction is valid for preparation of primary amines only. Gives good yields of primary
amines uncontaminated with other amines.

Hofmann Elimination Quaternary upon treatment with strong base

ammonium salt

Amide reduction amides

Nitrile reduction nitriles

Reduction of nitro nitro compounds can be accomplished with elemental zinc, tin or iron with an acid.
compounds

Amine alkylation haloalkane

Delepine reaction organohalide reagent hexamine

Buchwald-Hartwig aryl halide specific for aryl amines

reaction

Menshutkin reaction tertiary amine reaction product a quaternary ammonium cation

hydroamination alkenes and alkynes

Amine 54

Hofmann-Löffler reaction haloamine

Reactions
The dominant reactivity of amines is their nucleophilicity.[4] Most primary amines are good ligands for metal ions to
give coordination complexes. Amines are alkylated by alkyl halides. Acyl chlorides and acid anhydrides react with
primary and secondary amines to form amides (the "Schotten-Baumann reaction").

Similarly, with sulfonyl chlorides, one obtains sulfonamides. This transformation, known as the Hinsberg reaction, is
a chemical test for the presence of amines.
Because amines are basic, they neutralize acids to form the corresponding ammonium salts R3NH+. When formed
from carboxylic acids and primary and secondary amines, these salts thermally dehydrate to form the corresponding
amides.

Amines react with nitrous acid to give diazonium salts. The alkyl diazonium salts spontaneously decompose by
losing N2 to produce a mixture of alkenes, alkanols or alkyl halides, with alkanols as the major product. This reaction
is of little synthetic importance because the diazonium salt formed is too unstable.
Amine 55

Primary aromatic amines, such as aniline ("phenylamine") form more stable diazonium salts, which can be isolated
in the crystalline form. These species undergo a variety of synthetically useful transformations. With cuprous
cyanide the corresponding nitrile is formed. Arenediazonium ions undergo coupling with electron-rich aromatic
compounds such as a phenol to form an azo compound. These species are widely used as dyes.

Imine formation is an important reaction. Primary amines react with ketones and aldehydes to form imines. In the
case of formaldehyde (R' = H), these products typically exist as cyclic trimers.
RNH2 + R'2C=O → R'2C=NR + H2O
Reduction of the imines gives secondary amines:
R'2C=NR + H2 → R'2CH-NHR
Similarly, secondary amines react with ketones and aldehydes to form enamines:
R2NH + R'(R"CH2)C=O → R"CH=C(NR2)R' + H2O
An amine reaction overview is given below:

Reaction name Reaction product Comment

Amine alkylation amines degree of substitution increases

Schotten-Baumann reaction amides Reagents: acyl chlorides, acid anhydrides

Hinsberg reaction sulfonamides Reagents: sulfonyl chlorides

Amine-carbonyl condensation imines

Organic oxidation nitroso compounds Reagent: peroxymonosulfuric acid

Organic oxidation diazonium salt Reagent: nitrous acid

Zincke reaction Zincke aldehyde reagent pyridinium salts , with primary and secondary amines

Emde degradation tertiary amine reduction of quaternary ammonium cations

Hofmann-Martius rearrangement aryl substituted anilines

Von Braun reaction Organocyanamide By cleavage (tertiary amines only) with cyanogen bromide
Amine 56

Biological activity
Many kinds of biological activity produce amines by breakdown of amino acids. Many natural neurotransmitters like
epinephrine, norepinephrine, dopamine, serotonine, histamine are amines.

Application of amines

Dyes
Primary aromatic amines are used as a starting material for the manufacture of azo dyes. It reacts with nitric(III) acid
to form diazonium salt, which can undergo coupling reaction to form azo compound. As azo-compounds are highly
coloured, they are widely used in dyeing industries, such as:
• Methyl orange
• Direct brown 138
• Sunset yellow FCF
• Ponceau

Drugs
Many drugs are designed to mimic or to interfere with the action of natural amine neurotransmitters, exemplified by
the amine drugs:
• Chlorpheniramine is an antihistamine that helps to relieve allergic disorders due to cold, hay fever, itchy skin,
insect bites and stings.
• Chlorpromazine is a tranquillizer that sedates without inducing sleep. It is used to relieve anxiety, excitement,
restlessness or even mental disorder.
• Ephedrine and Phenylephrine, as amine hydrochlorides, are used as decongestants.
• Amphetamine, Methamphetamine, and Methcathinone are amines that are listed as controlled substances by the
DEA.
• Amitriptyline, Imipramine, Lofepramine and Clomipramine are tricyclic antidepressants and tertiary amines
• Nortriptyline, Desipramine, and Amoxapine are tricyclic antidepressants and secondary amines
• (The tricyclics are grouped by the nature of the final amine group on the side chain.)

Gas treatment
• Aqueous monoethanolamine (MEA), diglycolamine (DGA), diethanolamine (DEA), diisopropanolamine (DIPA)
and methyldiethanolamine (MDEA) are widely used industrially for removing carbon dioxide (CO2) and
hydrogen sulfide (H2S) from natural gas streams and refinery process streams. They may also be used to remove
CO2 from combustion gases / flue gases and may have potential for abatement of greenhouse gases.

Safety
Low molecular weight amines are toxic and some are easily absorbed through the skin. Many higher molecular
weight amines are highly active biologically.
Amine 57

External links
• Primary amine synthesis - Synthetic protocols [5] from organic-reaction.com

See also
• IUPAC nomenclature for the official naming rules for amines. • Acid-base extraction
• Biogenic amine • Amine gas treating
• Imine

References
[1] McMurry, John E. (1992), Organic Chemistry (3rd ed.), Belmont: Wadsworth, ISBN 0-534-16218-5
[2] Lide, D. R., ed. (2005), CRC Handbook of Chemistry and Physics (86th ed.), Boca Raton (FL): CRC Press, ISBN 0-8493-0486-5
[3] Karsten Eller, Erhard Henkes, Roland Rossbacher, Hartmut Höke "Amines, Aliphatic" in Ullmann's Encyclopedia of Industrial Chemistry,
Wiley-VCH, Weinheim, 2005. doi:10.1002/14356007.a02_001
[4] March, Jerry (1992), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (4th ed.), New York: Wiley, ISBN 0-471-60180-2
[5] http:/ / www. organic-reaction. com/ synthetic-protocols/ functionals-groups/ primary-amine/
Article Sources and Contributors 58

Article Sources and Contributors

Melting point  Source: http://en.wikipedia.org/w/index.php?oldid=389435319  Contributors: 13afuse, 5Q5, 8472, Acroterion, Adashiel, Addshore, Ahoerstemeier, Alansohn, Alfio,
AliveFreeHappy, Andonic, Andre Engels, Andres, AnonHat, Antandrus, Art LaPella, Basawala, Bbanerje, Belovedfreak, Benbest, Benjah-bmm27, BesselDekker, Bidabadi, Biscuittin,
Bobblewik, Bobo192, Bomac, BostonMA, Bryan Derksen, Bubba hotep, Bubbachuck, Burn, CJLL Wright, CambridgeBayWeather, Can't sleep, clown will eat me, Capricorn42, Cek,
Chuckiesdad, Clicketyclack, Closedmouth, Complexica, Cryonic07, Curps, D k mackenzie, DARTH SIDIOUS 2, DMacks, Danski14, Datapacrat, David.Monniaux, DeadEyeArrow,
December21st2012Freak, DerHexer, Dinesh smita, Diverman, Dramartistic, Drthomasj, Dusique, El C, Epbr123, Everyking, Excirial, Felix Folio Secundus, Femto, FinalRapture, Fvw, GB fan,
GTBacchus, Gene Nygaard, Gentgeen, Geoffr, Giftlite, Gilgamesh he, Gilliam, Glengarry, Gonzonoir, Gracenotes, Greedysloth, GregorB, Grim23, Gurchzilla, Gwernol, Gzuckier, Harp,
Hayabusa future, HereToHelp, II MusLiM HyBRiD II, IRP, Icairns, Immunize, Iridescent, J.delanoy, JHunterJ, Jackfork, Jawed, JoanneB, Johndburger, Jovianeye, Jpk, JuJube, Julesd, Kaiba,
Kkmurray, Kuru, La goutte de pluie, LeaveSleaves, Lights, Logger9, Lord Pistachio, Magog the Ogre, Marek69, MarkGallagher, Martin Chaplin, Materialscientist, Matt Deres, Mikaey,
Mileystudy, Moogleydog, Mor, Mykhal, NHRHS2010, Nk, Nuggetboy, Nuno Tavares, Olivier, Oxymoron83, Ozzorro, PAR, Pb30, Pepper, Petermr, Pflatau, PhilKnight, Philip Trueman,
Pinethicket, Pizza1512, Pjanini1, Propaniac, R6MaY89, Radagast83, Radiojon, Ranveig, RexNL, Rifleman 82, Rockfang, Romanm, Scipex, Seba5618, Shirik, SiriusAlphaCMa, SmilesALot,
Solid State, State of Love and Trust, Stephenchou0722, Stereotek, StevenDH, THEN WHO WAS PHONE?, Tail, Techman224, The Thing That Should Not Be, Tide rolls, Torris, Touch Of
Light, Tranletuhan, TravisTX, Trelvis, Trevor MacInnis, U.S.Vevek, Ugat, Unara, V.narsikar, V8rik, Van helsing, Vinne2, Waggers, Wavelength, Wioo, Woldo, Zzuuzz, Јованвб, 409
anonymous edits

Distillation  Source: http://en.wikipedia.org/w/index.php?oldid=390719708  Contributors: 10metreh, 16@r, 2D, ABF, Abhisheks.nv, Acm, Agrawal.abhsihek, Alansohn, Alex297cat, Alfred
Barnard, AlphaEta, Anaxial, Andre Engels, Animum, Antonrojo, Araku, Audioiv, Aushulz, Azhura, BUF4Life, Barek, Baristarim, BeastRHIT, Beetstra, BenC7, Betterusername, Big Brother
1984, Bill Owens Photography, Blechnic, Bob, Bobo192, Bongwarrior, Brain40, Bubba hotep, Bwrs, CERminator, CJHackett, COGDEN, Caltas, Canadian-Bacon, Canthusus, Capricorn42, Carl
Henderson, Cblack2, Chem-awb, ChemE50, Chemical Engineer, Childzy, ChillDeity, Chinaranger, Chris fluppy, Cindy Jones1, Closedmouth, Colonies Chris, Cometstyles, Conversion script,
Courcelles, D.c.camero, D3von, DGaw, DMacks, Darrien, David Justin, Dboy stein, Dbroadwell, Dbtfz, DerHexer, Dforest, Distortionmaster20, Dither 56, Dj Capricorn, DocWatson42,
Drbreznjev, Dsmurat, Dvd-junkie, Dwmyers, East of Borschov, Edgar181, ElationAviation, Elo69007, Epbr123, EugeneForrester, Everytime, Exor674, Falcon Kirtaran, Fanghong, FisherQueen,
Fourthgeek, Fraggle81, Freakofnurture, Fri117336, Funandtrvl, Funky Monkey, Fuzheado, Fëaluinix, General Eisenhower, Gentgeen, Giftlite, Gilliam, Glen, GoneAwayNowAndRetired,
GregRM, Gtrmp, Gun Powder Ma, Gunslinger1812, Gurchzilla, H Bruthzoo, H Padleckas, HJ32, Hallenrm, HappyApple, Harland1, Hbackman, Hede2000, Hi878, Homonation, Hooperbloob,
Hugo Dufort, Ike9898, Ioscius, Itub, IvanLanin, Ixfd64, J Di, J.delanoy, J8079s, JForget, JNW, Ja 62, Jacek Kendysz, Jagged 85, JamesBWatson, Jaxl, Jcarroll, Jebba, Jermonian, Jetul,
Jfredrickson, Jfreyre, Jfurr1981, Jguk 2, Joe Rodgers, JoeSmack, Jose77, Joshsteiner, JoshuaZ, Jreferee, Julesd, Juliancolton, Just Another Dan, KVDP, Karlhahn, Kbh3rd, Kdn1982, Kevin
Dorner, Kkolmetz, Knight1993, Knipptang, Konci, Koyaanis Qatsi, Kpjas, Ksyrie, KudzuVine, Kwertii, La goutte de pluie, Lasse Clausen, LeaveSleaves, Leonard G., Lightning, Lihaas, Little
Mountain 5, Llywrch, Lockeownzj00, Lockesdonkey, Loonymonkey, LouisBB, Luna Santin, Lupin, LyleHoward, Lysy, MacGyverMagic, Mahanchian, Malikajumbe, Manager00104, Mandarax,
Markpe, MassimoAr, Masteremoguy, Mat-C, Materialscientist, Mattchess, Mausy5043, Maximus Rex, Maziotis, Mbeychok, Megane, Melchoir, Mentifisto, Merenta, Michael Hardy, Mike
Rosoft, Mike hayes, MiltonT, Mzajac, Nahaj, Naruto1990, Neelix, Neutrality, Neverquick, NewEnglandYankee, News0969, Nicketje666, Nihiltres, Nitin70, Nonexistant User, Nunquam Dormio,
Nuttycoconut, Oasisbob, Oatmeal batman, Oceanconsulting, Ohnoitsjamie, Ojay123, Olivier, Omicronpersei8, Omsco, PaddyM, PamD, Pdcook, Pekinensis, Peko, Pendimethalin, Peyre,
Phantomsteve, Philip Trueman, Phoniexmofo, Physchim62, Piano non troppo, Pinethicket, Pinkadelica, Pinky sl, PoccilScript, Poetaris, Polenth, Polyparadigm, Ponder, Prashanthns, Prodego,
Quadell, Quantockgoblin, Qurozon, Qxz, RA0808, Randy549, Redoubts, Rerooks, Rich Farmbrough, Richard Harvey, Richard Taytor, Ridow, Rifleman 82, Rinroad, Rjwilmsi, Rocco8, Rossami,
Ruy Pugliesi, SMC, Saga City, Sakagewea, Sansri, Sardanaphalus, Sasuke1990, ScAvenger, ScaldingHotSoup, Schaber, SchfiftyThree, Scott14, Scottbogner, Sepideh7, Shalom Yechiel,
SheeEttin, Shoessss, Sikkema, Skarebo, Skier Dude, Slashme, Sm0key82, Snigbrook, Snowolf, Stbalbach, Strontium5, Stuartamccormick, Swadeep.shrivastava, Syncategoremata, Syrthiss, TPK,
Teecorbs, The Thing That Should Not Be, The wub, Thebigboy1, Tomayres, Tommy2010, Torqmaster, Tsemii, Unconcerned, User A1, V8rik, Van helsing, Veinor, Versus22, Vuo, WDavis1911,
Weyes, Wiki Jared 21, Wikipelli, Willking1979, Woland37, Wsloand, Wtmitchell, Zigmar, Zundark, 650 anonymous edits

Recrystallization (chemistry)  Source: http://en.wikipedia.org/w/index.php?oldid=390232178  Contributors: Akirku1, Alxmel, Elbreapoly, Jodie44, Materialscientist, Mrba70, Petergans,
Quantockgoblin, Tide rolls, Wizard191, 24 anonymous edits

Fragrance extraction  Source: http://en.wikipedia.org/w/index.php?oldid=379419449  Contributors: A. B., Brainsik, Calliopejen1, Clicketyclack, Dar-Ape, Edgar181, Fabykot, Foolestroupe,
Hairy Dude, Hikaridranz, Jay32183, Mattchess, Monsterinabox, R'n'B, Razorflame, Seasicksarah, Sensonet, Sjschen, TheMoog, Wrfrancis, 17 anonymous edits

Chromatography  Source: http://en.wikipedia.org/w/index.php?oldid=391257007  Contributors: 194.200.130.xxx, 21655, A8UDI, ABF, Addshore, AdjustShift, Aircorn, Aitias, Alabmouse,
Alansohn, Alksub, Alphachimp, Altenmann, Alteripse, Amplitude101, Anakin101, Andervik, Andre Engels, Andrew Nutter, Anetode, Anna Lincoln, Antandrus, Aranel, Arbitrarily0, ArielGold,
Arthena, Ashlandchemist, Atapattu, AtomicDragon, Aumann, Aznshark4, Aztec project, Azza5678, Bachrach44, Barryaus, Basheez, Bdamokos, Benhart16, Bensaccount, Bluemoose, Bobo192,
Brendan Moody, Bryan Derksen, Bubba hotep, Cacycle, Cadmium, Calmer Waters, Caltas, Can't sleep, clown will eat me, Capricorn42, Carcharoth, CardinalDan, Cathalgarvey, Cenarium,
Ceresbear, Charles Matthews, Chem-awb, ChemGardener, Cherrytree drop, Chris 73, Christopherlin, Ciccone, Clicketyclack, Clone2727, Closedmouth, Cmdrjameson, Cohesion, Cometstyles,
Conversion script, Cpeditorial, Cpichardo, Cquan, Cst17, Custom24, Cyril Washbrook, DMacks, DVD R W, DanMS, Dante Alighieri, Darkblazikenex2, Darry2385, Darth Panda,
Dashinghrishi25, Dawn Bard, Dbfirs, December21st2012Freak, Dekay, Deor, DerHexer, Derek Ross, Dgrant, Diberri, Discospinster, Docmcconl, Doczilla, Dougluce, Dpotter, Dr.Soft,
Drbreznjev, Dureo, Dv3, E0steven, Edgar181, Edward Z. Yang, Edward130603, Edward321, El C, Elektrik Shoos, Elvim, Emilio8, Enviroboy, Epbr123, Erik Holladay, ErikHeidt, Euchiasmus,
Everyking, Excirial, F0i9l, Faithlessthewonderboy, Falcon4196, Faradayplank, Favonian, Fieldday-sunday, Flewis, Flopster2, Foes and rocs, FrancoGG, Frankvangeel, FreplySpang, Fæ, G716,
GAThrawn22, Ganshiba, Gbleem, Gene Nygaard, Gentgeen, Giftlite, Gilliam, Glane23, Graeme Bartlett, Gurch, Gwernol, HJ Mitchell, Hallenrm, Hankwang, Hqb, II MusLiM HyBRiD II, IRP,
IW.HG, Icseaturtles, Iffy, Ike9898, Ilikepie2221, Illnab1024, Invent, Ismarkov, Ixfd64, J Di, J.delanoy, Jacopo Werther, Jaeger5432, James086, Jamesontai, January, Jbbuie, Jecklery, Jeff Dahl,
Jeremiah, Jfdwolff, Jgbundy, Jlapointe, Jmeppley, John254, Jon186, Jossi, KJS77, Kalyan.casturi, Karlhahn, Kbh3rd, Keegan, Keenan Pepper, Keilana, Kelly Martin, Kkmurray, Kku,
KnowledgeOfSelf, Krich, Kristen Eriksen, Kzollman, Lahiru k, Laslovarga, Lcs35, LeilaniLad, Leofer, Lexor, Likaito, Llamadog903, Llywrch, Lord Voldemort, LouisBB, MER-C, Mac Davis,
Madbehemoth, Madpigaaron, Manticore, Martarius, Master2841, Mateo SA, Materialscientist, Mczack26, Meisam.fa, Mentifisto, MichaelJanich, Mihovil, Mikeo, Mild Bill Hiccup, MimirZero,
Mm1972, Mmxx, Mobshar, Modeha, MrOllie, Mxn, Mydearbhava, Naddy, Nagy, Natrij, NeilN, NellieBly, Neno4us, Nils.hoffmann, Ninja247, Nivix, Nmcmillan1512, Nonagonal Spider,
Nono64, Northfox, Norvy, NorwegianBlue, NuclearWarfare, Nunquam Dormio, Obava, Omnipaedista, Onco p53, PDH, PJM, Parkjd08, Parthian Scribe, Pdcook, Peily, Penarc, Pepper, Persian
Poet Gal, Philip Trueman, Phorner87, Physchim62, Pi3832, Pils, Pinethicket, Pjc1190, Porqin, Prodego, Psyche825, Pylze, Quantockgoblin, Quintote, RPlunk2853, Ragesoss, Ranveig,
RedHillian, RedWolf, Redfarmer, Redvers, RexNL, Rich Farmbrough, Richdavi, Richlens, Rifleman 82, Rjwilmsi, Roadnottaken, RobOBrien, RodC, Romanm, Ronhjones, Rstenutz, Rune.welsh,
Russavia, Rustavo, Ryanjunk, Ryulong, SJP, STHayden, Saber girl08, Sachemuser, Sarindam7, SchnitzelMannGreek, Sciurinæ, Seb az86556, Seivad, Senatorpjt, Serephine, Shpakovich,
Sillybilly, Sinistrum, Sjakkalle, Slashme, Smartneddy, Smooth O, Smyth, Snek01, Snowolf, Sodium, Sooty1111, Splash, Stewartadcock, Stokerm, SunCreator, Susanwoh, Synchronism, Tanvir
Ahmmed, Tcncv, Techcae, Tetracube, The Hybrid, The Thing That Should Not Be, TheST, Theresa knott, Thomjakobsen, Thryduulf, Tide rolls, Tim Starling, Tmdgroup, Tony Fox, Tsaalan,
TutterMouse, Ukexpat, Useight, User27091, V8rik, Vale maio, Vanished User 1004, Versus22, Voyagerfan5761, Vrenator, Vsmith, Werdan7, WhatamIdoing, Whispering, WikiLeon,
WilliamMostmans, WillowW, Wimt, Winchelsea, Wk muriithi, Wstraub, Wynott Bymour, Wysprgr2005, Xaosflux, Xenofonos, Xezbeth, YassineMrabet, Youkai no unmei, Zomglmfao,
Zsmith1, Zxcvydfgjkxg, ~K, ‫ملاع بوبحم‬, 1148 anonymous edits

Hydrocarbon  Source: http://en.wikipedia.org/w/index.php?oldid=390115406  Contributors: 05jdunn, A boardley, A8UDI, ABF, AaronThornton, Abjs, Adashiel, Aditya, AdjustShift,
Agatehawk, Ah.starkweather, Aitias, Akonas, Alansohn, Alfio, Alitadepollo, Amorymeltzer, Andrejj, Andres, Andy Dingley, Anirban Chatterje, Anlace, Anonymous101, Antandrus, Antonio
Lopez, Asm79, AtomicDragon, Aushulz, Avatar 06349, AxelBoldt, AxiomShell, Bachrach44, Baiji, Benjah-bmm27, Betterusername, Blueskylab, Bob the Hamster, Bogey97, Bomac, Brandon,
Brumski, Butters0422, CDrecche, Caleb rosenberg, Caltas, Can't sleep, clown will eat me, CaptainVindaloo, Carey Evans, Cburnett, Chadjj, Chamberlain2007, Charleca, CharlotteWebb,
Charlsmells, Chippy92, Chris426, Christian75, Chuunen Baka, Ckatz, ClockworkSoul, Clod2105, Colbuckshot, Collins.mc, Conversion script, Cormallen, Crubins, Crystal whacker, Cubbi,
Cyfal, DMacks, DO11.10, DT Strain, DVD R W, Da monster under your bed, DabMachine, Darklilac, Darry2385, Dcooper, Deadcorpse, DeniseGreen, DerHexer, Diana Ringo, Difu Wu,
Dismas, DoubleBlue, Dragana666, Drummerguy1495, Dysprosia, E Wing, EdTrist, Edgar181, Edivorce, Emily Jensen, Epbr123, Ephemeronium, Eras-mus, Estoy Aquí, Everyking, Exander,
FelisLeo, Flewis, Fluent aphasia, Font, Forstnert, FrYGuY, Fran Rogers, Frankenpuppy, Frehley, Garzo, Gbiten, Gentgeen, GeoGreg, Ghewgill, Giftlite, Gilliam, GoatGuy, Gogo Dodo,
Gromlakh, Gscshoyru, Gutsul, Haham hanuka, Happycool, Hdt83, HenryLi, Horsten, Hydrogen Iodide, Ibby786, Icairns, Insanephantom, Insanity Incarnate, Instinct, Inter, Ixfd64, J.delanoy,
JCraw, JTN, JYOuyang, Jaganath, Jamiesmellshorrible, Jmundo, Joe shabadew, John Sherman, Jonto92, Juan Mussini, Juliancolton, Kandar, Karl-Henner, Kathryn NicDhàna, Kcordina,
Kennita728, Kesac, Ketsuekigata, Kilo-Lima, King of Hearts, Kingpin13, Kkemp, KnowledgeOfSelf, Koavf, Kooldeep, Kotasik, Kuru, Laurinavicius, LeadSongDog, Leigj004, Leroybrownbpj,
LittleOldMe old, Llort, Luk, Luna Santin, MPerel, Mac, Magister Mathematicae, Mani1, Mareino, Martinp23, Materialscientist, Mattguard, Mav, Maz2007, Mbeychok, Mcl-liam, Mhklein, Mike
Rosoft, Mikespedia, Mikez, Minestrone Soup, Miro modo, Mjpieters, Montaced, Mooman0707, Mormegil, Mudgineer, Mushin, Mxn, NJGW, Nomad2u001, Novasource, Nshumeyko, Ntsimp,
NuclearWarfare, Nymph, Oconnell, Ojigiri, Ojs, Otets, Paul-L, Pearn001, Pek-boy.1, Petegallagher311, Peterbmoorman, PhilKnight, Philip Trueman, Pie4all88, Pinethicket, Pit, Ponyo,
Psarianos, Pstanton, Puterno, PvsKllKsVp, Quantumor, R'n'B, R. S. Shaw, RHaworth, RJASE1, Raven4x4x, Readbtweenthelines, Reaper X, Red Director, Rettetast, Rfc1394, Rich Farmbrough,
Roadrunner, Rod57, Rogerd, RoyBoy, Rsrikanth05, SJP, SMC, Sam Korn, Shaddack, Shadowjams, Shadowlynk, Shalom Yechiel, Shiftchange, Shizhao, Silverchemist, Skarebo, Skunkboy74,
SmilesALot, Smjg, Smokefoot, Snowolf, Sonett72, Sore feet, Srkmet92, Supersteve1440, Syrthiss, Tango, Tarquin, Tasc, TeaDrinker, Teamobrayan, Technotaoist, Tenebrous, The Thing That
Should Not Be, The shaggy one, The sock that should not be, Tide rolls, Tiggerjay, Tohd8BohaithuGh1, Tombomp, Torkel.bjornson, Transity, Tslocum, Twirth, Uncle Dick, V8rik, Versageek,
Vespristiano, Vincecate, Viriditas, Vsmith, Wavelength, Wickey-nl, Wiki007wiki, Wikieditor06, Wimt, Winchelsea, WinterSpw, Xezbeth, Xyphy, Yamamoto Ichiro, Yashgaroth, Ybact,
Article Sources and Contributors 59

Yellowmellow45, Yosri, Yyy, Zamias, Zantolak, Zarkov1196, Јованвб, තඹරු විජේසේකර, 672 anonymous edits

Aldehyde  Source: http://en.wikipedia.org/w/index.php?oldid=390159478  Contributors: 130.94.122.xxx, Abhishek Dasgupta, Acather96, Adambiswanger1, Adashiel, Alai, Andy Dingley,
Anthony Appleyard, Arcadian, Beano, Benjah-bmm27, Bensaccount, BokicaK, Bomac, Brockert, Cameron, Chaos, ChemistHans, Delta G, Drphilharmonic, Dynaflow, EconoPhysicist, Edgar181,
Eleventh Guard, Freiddie, Gentgeen, Gikü, Haham hanuka, Harrystein, Hellbus, Hkoala, Imoen, J.Steinbock, Jaconlon, Jclemens, Jeff G., Jklin, Jshadias, Jusjih, Kandar, Keenan Pepper,
Kwamikagami, KyleRGiggs, Lightmouse, Lommer, Looxix, Lupinoid, Materialscientist, Mav, Maximus Rex, Melchoir, Mike2vil, Moonal, Munita Prasad, Nakon, No Guru, Nonagonal Spider,
Nuno Tavares, Nádvorník, OldakQuill, Olin, Onco p53, Papa November, Phydend, Pinethicket, Pisanidavid, Power, Psbsub, Pthag, Rob Hooft, SUL, Shanes, Shoutik, Shultzc, SkyWalker,
Smokefoot, Soul1337, Spacepotato, Steinsky, Suisui, Supernumerary, TangParadise, Tony Sidaway, Trankill34, Trueno Peinado, User A1, V8rik, Vipinhari, Walkerma, Wickey-nl,
Wolfmankurd, Wyatt1021, Yerpo, Ysw1987, Zocky, ~K, 146 anonymous edits

Ketone  Source: http://en.wikipedia.org/w/index.php?oldid=390909237  Contributors: Aitias, Alberrosidus, Alchemical nocturne, AlistairMcMillan, Alteripse, Andres, AnnaFrance, Ato,
AxelBoldt, Azo bob, Basicdesign, Bdesham, Beland, Benjah-bmm27, Bensaccount, BigFatBuddha, Blainster, Bobo192, Bomac, Bragador, Brane.Blokar, Bryan Derksen, Card, ChicXulub,
Christian List, Conversion script, Coolstoryhansel, Cycleskinla, DJamesRock, Djus, EconoPhysicist, Edgar181, Ephemeronium, Espetkov, FreplySpang, Furbo, GODhack, Gentgeen, Gilgamesh,
GoldenGoose100, HistoryStudent113, Husond, Ihope127, Imoen, Imran, InAJar, J.Steinbock, Jackpottle, Jeff G., Jfdwolff, Jhessian Zombie, Joanjoc, Jsindac, Kaygtr, Kglavin, Koavf, Kristen
Eriksen, KsprayDad, Kupirijo, KyleRGiggs, LOL, LOTRrules, Lupinoid, Macellarius, Magnus Manske, Materialscientist, Mav, Mboverload, Mgmei, Michall, Moroboshi, Munita Prasad,
Muu-karhu, Nguyenbaophuong, Nightkey, Nihiltres, Ohito, Ollie holton, Onevalefan, Patho, Paulpjp, Plumbarbacy, Power, PuzzletChung, Quentar, Raymond, Revolutionaryluddite, Richard001,
Rifleman 82, Ron Ritzman, Rsduhamel, Sabbut, SaulPerdomo, Savidan, Shultzc, Silverback, Smokefoot, Sodium, Soroush Mesry, Spellcast, Spookyrunner13, Stone, TangParadise, Tarquin, Tony
Sidaway, Trankill34, User A1, V8rik, Vary, Vladsinger, Walkerma, Whosyourjudas, Wickey-nl, WikHead, Yzalzy, 153 anonymous edits

Amine  Source: http://en.wikipedia.org/w/index.php?oldid=391124937  Contributors: 63.203.101.xxx, Aditya, Agracia3, Alansohn, Anand Karia, Apple2, Beetstra, Benjah-bmm27, Bensaccount,
Betterusername, Bomac, Borb, Brane.Blokar, Cacycle, Chaos, Clarince63, Cmdrjameson, Conversion script, DHN, Deicas, Dmitrybrant, Doczilla, Dolphinling, Drbreznjev, Dreamyshade,
Drphilharmonic, Eblees, EconoPhysicist, Edgar181, Element16, Enigmaman, Exabyte, Filll, Flowerpotman, Frankenpuppy, Freestyle-69, FrozenMan, Gaius Cornelius, GeeJo, Gentgeen,
Geoffrey, Ghiles, Giftlite, Gracenotes, Graham Mills 326, Graham87, Greswik, H Padleckas, Haham hanuka, Havefun, Hellbus, Hobartimus, Hsungmik, Imoen, InfoCan, Isilanes, Ixfd64,
J.Steinbock, JD554, Jackfork, JohnArmagh, Josh Cherry, Kazvorpal, Keenan Pepper, Kokeyokey, Korg, Kupirijo, Kur0, Ling.Nut, Lupinoid, MLauba, MPF, Magister Mathematicae, Magnus
Manske, Majkinetor, Manuel Anastácio, Mbeychok, Meco, Mike2vil, Mikespedia, Mister Matt, Mister1nothing, MrJones, Mullet, Mykhal, Myxoma, Nono64, OldakQuill, Oldsci, Olin, Ondrejsv,
Orangemike, Orchid Righteous, PasswordUsername, Phorse, Piano non troppo, Pion, Pstrous, Qemist, RandomP, Rayleung2709, Rdsmith4, Rettetast, Rich Farmbrough, Rifleman 82, Sai2020,
Sasquatch, Shaddack, Shalom Yechiel, Shootbamboo, SixPurpleFish, Skeptical chymist, Skizzik, Slashme, Sligocki, Slipstream, Smokefoot, Snowolf, Sodium, Someguy1221, Spiff,
SunAquarius129, Superstar.tez, Syvanen, TYW, Tarif Ezaz, Taw, The Thing That Should Not Be, Thrixx, Tlusťa, Tohd8BohaithuGh1, Trankill34, Trees4est, Trevyn, Trioculite, Trusilver, User
A1, UserGoogol, V8rik, Vuo, Webaware, Willems.stijn, Willkehayioff, Wimvandorst, X1987x, Xact, Xasodfuih, ~K, 157 anonymous edits
Image Sources, Licenses and Contributors 60

Image Sources, Licenses and Contributors

Image:Carboxylic.Acids.Melting.&.Boiling.Points.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Carboxylic.Acids.Melting.&.Boiling.Points.jpg  License: Public Domain
 Contributors: Bender235, Kurgus, Rhadamante
Image:Melting curve of water.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Melting_curve_of_water.jpg  License: Public Domain  Contributors: Aushulz, Belfer00, Hnchan01
File:Simple distillation apparatus.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Simple_distillation_apparatus.svg  License: Public Domain  Contributors: User:Quantockgoblin,
User:Slashme
File:Zosimosapparat.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Zosimosapparat.jpg  License: Public Domain  Contributors: Original uploader was Adragoor at sv.wikipedia
File:My retort.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:My_retort.jpg  License: unknown  Contributors: Chatsam, Nk, Toto-tarou
File:UkrainianVodkaStill.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:UkrainianVodkaStill.jpg  License: GNU Free Documentation License  Contributors: User:Knipptang
File:BatchDistill.svg  Source: http://en.wikipedia.org/w/index.php?title=File:BatchDistill.svg  License: Free Art License  Contributors: Original uploader was User A1 at en.wikipedia. Later
version(s) were uploaded by Xyzzy n at en.wikipedia.
File:Vacuum distillation of DMSO at 70C.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Vacuum_distillation_of_DMSO_at_70C.jpg  License: Public Domain  Contributors:
Original uploader was Rifleman 82 at en.wikipedia
File:perkin triangle distillation apparatus.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Perkin_triangle_distillation_apparatus.svg  License: GNU Free Documentation License
 Contributors: User:Slashme
File:short path distillation apparatus.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Short_path_distillation_apparatus.svg  License: Public Domain  Contributors: User:Slashme
File:Colonne distillazione.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Colonne_distillazione.jpg  License: Creative Commons Attribution 3.0  Contributors: User:Luigi Chiesa
File:Distillation Column.png  Source: http://en.wikipedia.org/w/index.php?title=File:Distillation_Column.png  License: GNU Free Documentation License  Contributors: User:mbeychok
File:Bubble Cap Trays.PNG  Source: http://en.wikipedia.org/w/index.php?title=File:Bubble_Cap_Trays.PNG  License: Creative Commons Attribution-Sharealike 2.5  Contributors: User:H
Padleckas
File:Vacuum Column.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Vacuum_Column.jpg  License: GNU Free Documentation License  Contributors: I do not know the name of
the individual who actually took the photograph.
File:Retort-in-operation-early-chemistry.PNG  Source: http://en.wikipedia.org/w/index.php?title=File:Retort-in-operation-early-chemistry.PNG  License: Public Domain  Contributors:
HappyApple, 2 anonymous edits
File:Distillation of dry and oxygen-free toluene.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Distillation_of_dry_and_oxygen-free_toluene.jpg  License: Public Domain
 Contributors: Rifleman 82
File:Vacuum Column.png  Source: http://en.wikipedia.org/w/index.php?title=File:Vacuum_Column.png  License: Public Domain  Contributors: User:Mbeychok
File:Rotavapor.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Rotavapor.jpg  License: unknown  Contributors: Geni
File:Semi-microscale distillation.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Semi-microscale_distillation.jpg  License: Public Domain  Contributors: user:Rifleman_82
Image:Insulincrystals.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Insulincrystals.jpg  License: Public Domain  Contributors: Chrumps, Jurema Oliveira, Photohound
Image:1 solvent recrystallisation.png  Source: http://en.wikipedia.org/w/index.php?title=File:1_solvent_recrystallisation.png  License: Public Domain  Contributors: User:Quantockgoblin
Image:Crystallization Ibuprofen Salt.JPG  Source: http://en.wikipedia.org/w/index.php?title=File:Crystallization_Ibuprofen_Salt.JPG  License: Creative Commons Attribution-Sharealike 2.5
 Contributors: Secretservgy
Image:2 solvent recrystallisation.png  Source: http://en.wikipedia.org/w/index.php?title=File:2_solvent_recrystallisation.png  License: Public Domain  Contributors: User:Quantockgoblin
Image:2 solvent recrystallisation with evaporation.png  Source: http://en.wikipedia.org/w/index.php?title=File:2_solvent_recrystallisation_with_evaporation.png  License: Public Domain
 Contributors: User:Quantockgoblin
Image:Hot-filtration 1 solvent recrystallisation.png  Source: http://en.wikipedia.org/w/index.php?title=File:Hot-filtration_1_solvent_recrystallisation.png  License: Public Domain
 Contributors: User:Quantockgoblin
Image:x-ray crystals - slow evaporation 1 solvent.png  Source: http://en.wikipedia.org/w/index.php?title=File:X-ray_crystals_-_slow_evaporation_1_solvent.png  License: Public Domain
 Contributors: User:Quantockgoblin
Image:x-ray crystals - slow evaporation 2 solvent.png  Source: http://en.wikipedia.org/w/index.php?title=File:X-ray_crystals_-_slow_evaporation_2_solvent.png  License: Public Domain
 Contributors: User:Quantockgoblin
Image:x-ray crystals - slow gas diffusion 2 solvent.png  Source: http://en.wikipedia.org/w/index.php?title=File:X-ray_crystals_-_slow_gas_diffusion_2_solvent.png  License: Public Domain
 Contributors: User:Quantockgoblin
Image:x-ray crystals - slow liquid diffusion.png  Source: http://en.wikipedia.org/w/index.php?title=File:X-ray_crystals_-_slow_liquid_diffusion.png  License: Public Domain  Contributors:
User:Quantockgoblin
Image:x-ray crystals - slow liquid diffusion - H Tube.png  Source: http://en.wikipedia.org/w/index.php?title=File:X-ray_crystals_-_slow_liquid_diffusion_-_H_Tube.png  License: Public
Domain  Contributors: User:Quantockgoblin
Image:Lysozyme_crystal1.JPG  Source: http://en.wikipedia.org/w/index.php?title=File:Lysozyme_crystal1.JPG  License: Creative Commons Attribution-Sharealike 2.0  Contributors: Chrumps,
Lode
Image:Fragonard small perfume distillery.JPG  Source: http://en.wikipedia.org/w/index.php?title=File:Fragonard_small_perfume_distillery.JPG  License: Creative Commons
Attribution-Sharealike 2.5  Contributors: User:BrokenSphere
File:Gas chromatograph.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Gas_chromatograph.jpg  License: Public Domain  Contributors: Linda Bartlett (photographer)
File:Rt 5 9.png  Source: http://en.wikipedia.org/w/index.php?title=File:Rt_5_9.png  License: Public Domain  Contributors: Klaas1978
File:Rt 5 12.png  Source: http://en.wikipedia.org/w/index.php?title=File:Rt_5_12.png  License: Public Domain  Contributors: Klaas1978
File:Chromatography of chlorophyll - Step 7.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Chromatography_of_chlorophyll_-_Step_7.jpg  License: Creative Commons
Attribution-Sharealike 2.5  Contributors: Flo, GeorgHH, Marek M, 1 anonymous edits
File:Preperative HPLC.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Preperative_HPLC.svg  License: Creative Commons Attribution 3.0  Contributors: YassineMrabet
Image:Methane-3D-balls.png  Source: http://en.wikipedia.org/w/index.php?title=File:Methane-3D-balls.png  License: Public Domain  Contributors: Benjah-bmm27
Image:ShellMartinez-refi.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:ShellMartinez-refi.jpg  License: unknown  Contributors: User:Leonard G.
Image:Aldehyde Structural Formulae V.1.png  Source: http://en.wikipedia.org/w/index.php?title=File:Aldehyde_Structural_Formulae_V.1.png  License: Public Domain  Contributors: User:Jü
File:Formaldehyde-2D.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Formaldehyde-2D.svg  License: Public Domain  Contributors: Benjah-bmm27, Wereon
File:Ameisensäure Keilstrich.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Ameisensäure_Keilstrich.svg  License: Public Domain  Contributors: User:NEUROtiker
File:AldehydeGall.png  Source: http://en.wikipedia.org/w/index.php?title=File:AldehydeGall.png  License: Public Domain  Contributors: User:Smokefoot
Image:Ketone-group-2D-skeletal.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Ketone-group-2D-skeletal.svg  License: Public Domain  Contributors: User:Alberrosidus,
User:Benjah-bmm27, User:Vladsinger
file:Aceton.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Aceton.svg  License: Public Domain  Contributors: User:NEUROtiker
file:Acetone-3D-balls.png  Source: http://en.wikipedia.org/w/index.php?title=File:Acetone-3D-balls.png  License: Public Domain  Contributors: Ben Mills
Image:KetoneVarietyPack.png  Source: http://en.wikipedia.org/w/index.php?title=File:KetoneVarietyPack.png  License: Public Domain  Contributors: User:Smokefoot
Image:Keto enol tautomerism.png  Source: http://en.wikipedia.org/w/index.php?title=File:Keto_enol_tautomerism.png  License: unknown  Contributors: V8rik
Image:Primary-amine-2D-general.png  Source: http://en.wikipedia.org/w/index.php?title=File:Primary-amine-2D-general.png  License: Public Domain  Contributors: user:Benjah-bmm27
Image:Secondary-amine-2D-general.png  Source: http://en.wikipedia.org/w/index.php?title=File:Secondary-amine-2D-general.png  License: Public Domain  Contributors: Benjah-bmm27,
Ephemeronium
Image:Amine-2D-general.png  Source: http://en.wikipedia.org/w/index.php?title=File:Amine-2D-general.png  License: Public Domain  Contributors: Benjah-bmm27, Ephemeronium
Image Sources, Licenses and Contributors 61

Image:Methylamine.png  Source: http://en.wikipedia.org/w/index.php?title=File:Methylamine.png  License: GNU Free Documentation License  Contributors: Diberri, Gurch, Jni, Magnus
Manske, Rune.welsh, 2 anonymous edits
Image:2-amino-pentane.png  Source: http://en.wikipedia.org/w/index.php?title=File:2-amino-pentane.png  License: Public Domain  Contributors: User Magnus Manske on en.wikipedia
Image:Inversion of Amine.PNG  Source: http://en.wikipedia.org/w/index.php?title=File:Inversion_of_Amine.PNG  License: Public Domain  Contributors: User:H Padleckas
Image:Amide formation from amine.gif  Source: http://en.wikipedia.org/w/index.php?title=File:Amide_formation_from_amine.gif  License: Public Domain  Contributors: InfoCan, 1
anonymous edits
Image:Amine plus Carboxylic Acid.PNG  Source: http://en.wikipedia.org/w/index.php?title=File:Amine_plus_Carboxylic_Acid.PNG  License: GNU Free Documentation License
 Contributors: User:H Padleckas
Image:Nitrous acid with n-amine.gif  Source: http://en.wikipedia.org/w/index.php?title=File:Nitrous_acid_with_n-amine.gif  License: Public Domain  Contributors: Benjah-bmm27, InfoCan
Image:Aromatic diazonium salt.gif  Source: http://en.wikipedia.org/w/index.php?title=File:Aromatic_diazonium_salt.gif  License: Public Domain  Contributors: InfoCan, Railwayfan2005,
Rhadamante
License 62

License
Creative Commons Attribution-Share Alike 3.0 Unported
http:/ / creativecommons. org/ licenses/ by-sa/ 3. 0/