Haloalkane

Tetrafluoroethane (a haloalkane) is a colorless liquid that boils well below room temperature (as seen here) and
can be extracted from common canned air canisters by simply inverting them during use.

The haloalkanes (also known as halogenoalkanes or alkyl halides) are a

group of chemical compounds derived from alkanescontaining one or
more halogens. They are a subset of the general class of halocarbons,
although the distinction is not often made. Haloalkanes are widely used
commercially and, consequently, are known under many chemical and
commercial names. They are used as flame retardants, fire
extinguishants, refrigerants, propellants, solvents, and pharmaceuticals.
Subsequent to the widespread use in commerce, many halocarbons have
also been shown to be serious pollutants and toxins. For example,
the chlorofluorocarbons have been shown to lead to ozone
depletion. Methyl bromide is a controversial fumigant. Only haloalkanes
which contain chlorine, bromine, and iodine are a threat to the ozone layer,
but fluorinated volatile haloalkanes in theory may have activity
as greenhouse gases. Methyl iodide, a naturally occurring substance,
however, does not have ozone-depleting properties and the United States
Environmental Protection Agency has designated the compound a non-
ozone layer depleter. For more information, see Halomethane. Haloalkane
or alkyl halides are the compounds which have the general formula "RX"
where R is an alkyl or substituted alkyl group and X is a halogen (F, Cl, Br,
I).
Haloalkanes have been known for centuries. Chloroethane was produced
synthetically in the 15th century. The systematic synthesis of such
compounds developed in the 19th century in step with the development of
organic chemistry and the understanding of the structure of alkanes.
Methods were developed for the selective formation of C-halogen bonds.
Especially versatile methods included the addition of halogens to
alkenes, hydrohalogenation of alkenes, and the conversion of alcohols to
alkyl halides. These methods are so reliable and so easily implemented
that haloalkanes became cheaply available for use in industrial chemistry
because the halide could be further replaced by other functional groups.
While most haloalkanes are human-produced, non-artificial-source
haloalkanes do occur on Earth, mostly through enzyme-mediated synthesis
by bacteria, fungi, and especially sea macroalgae (seaweeds). More than
1600 halogenated organics have been identified, with bromoalkanes being
the most common haloalkanes. Brominated organics in biology range from
biologically produced methyl bromide to non-alkane aromatics and
unsaturates (indoles, terpenes, acetogenins, and phenols).[1][2] Halogenated
alkanes in land plants are more rare, but do occur, as for example
the fluoroacetate produced as a toxin by at least 40 species of known
plants. Specific dehalogenase enzymes in bacteria which remove halogens
from haloalkanes, are also known.

Classes
From the structural perspective, haloalkanes can be classified according to
the connectivity of the carbon atom to which the halogen is attached. In
primary (1°) haloalkanes, the carbon that carries the halogen atom is only
attached to one other alkyl group. An example is chloroethane (CH
3CH
2Cl). In secondary (2°) haloalkanes, the carbon that carries the halogen
atom has two C–C bonds. In tertiary (3°) haloalkanes, the carbon that
carries the halogen atom has three C–C bonds.
Haloalkanes can also be classified according to the type of halogen on
group 7 responding to a specific halogenoalkane. Haloalkanes containing
carbon bonded to fluorine, chlorine, bromine, and iodine results
in organofluorine, organochlorine, organobromine and organoiodine compo
unds, respectively. Compounds containing more than one kind of halogen
are also possible. Several classes of widely used haloalkanes are classified
in this way chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs)
and hydrofluorocarbons (HFCs). These abbreviations are particularly
common in discussions of the environmental impact of haloalkanes.

Properties
Haloalkanes generally resemble the parent alkanes in being colorless,
relatively odorless, and hydrophobic. The melting and boiling points of
chloro-, bromo-, and iodoalkanes are higher than the analogous alkanes,
scaling with the atomic weight and number of halides. This is due to the
increased strength of the intermolecular forces—from London dispersionto
dipole-dipole interaction because of the increased polarizability.
Thus carbon tetraiodide (CI
4) is a solid whereas carbon tetrachloride (CCl
4) is a liquid. Many fluoroalkanes, however, go against this trend and have
lower melting and boiling points than their nonfluorinated analogues due to
the decreased polarizability of fluorine. For example, methane(CH
4) has a melting point of -182.5 °C whereas tetrafluoromethane has a
melting point of -183.6 °C .
As they contain fewer C–H bonds, halocarbons are less flammable than
alkanes, and some are used in fire extinguishers. Haloalkanes are
better solvents than the corresponding alkanes because of their increased
polarity. Haloalkanes containing halogens other than fluorine are more
reactive than the parent alkanes—it is this reactivity that is the basis of
most controversies. Many are alkylating agents, with primary haloalkanes
and those containing heavier halogens being the most active (fluoroalkanes
do not act as alkylating agents under normal conditions). The ozone-
depleting abilities of the CFCs arises from the photolability of the C–Cl
bond.

Occurrence
Haloalkanes are of wide interest because they are widespread and have
diverse beneficial and detrimental impacts. The oceans are estimated to
release 1-2 million tons of bromomethane annually.[3]
A large number of pharmaceuticals contain halogens, especially fluorine.
An estimated one fifth of pharmaceuticals contain fluorine, including several
of the most widely used drugs.[4] Examples include 5-
fluorouracil, fluoxetine (Prozac), paroxetine (Paxil), ciprofloxacin (Cipro), m
efloquine, and fluconazole. The beneficial effects arise because the C-F
bond is relatively unreactive. Fluorine-substituted ethers are volatile
anesthetics, including the commercial
products methoxyflurane, enflurane, isoflurane, sevoflurane and desflurane
. Fluorocarbon anesthetics reduce the hazard of flammability with diethyl
ether and cyclopropane. Perfluorinated alkanes are used as blood
substitutes.

Teflon structure

Chlorinated or fluorinated alkenes undergo polymerization.

Important halogenated polymers include polyvinyl chloride (PVC),
and polytetrafluoroethene(PTFE, or Teflon). The production of these
materials releases substantial amounts of wastes.

Nomenclature
IUPAC
The formal naming of haloalkanes should follow IUPAC nomenclature,
which put the halogen as a prefix to the alkane. For
example, ethane with brominebecomes bromoethane, methane with
four chlorine groups becomes tetrachloromethane. However, many of these
compounds have already an established trivial name, which is endorsed by
the IUPAC nomenclature, for example chloroform (trichloromethane) and
methylene chloride (dichloromethane). For unambiguity, this article follows
the systematic naming scheme throughout.

Production
Haloalkanes can be produced from virtually all organic precursors. From
the perspective of industry, the most important ones are alkanes and
alkenes.
From alkanes
Main article: Free radical halogenation

Alkanes react with halogens by free radical halogenation. In this reaction a

hydrogen atom is removed from the alkane, then replaced by a halogen
atom by reaction with a diatomic halogen molecule. The reactive
intermediate in this reaction is a free radical and the reaction is called
a radical chain reaction.
Free radical halogenation typically produces a mixture of compounds
mono- or multihalogenated at various positions. It is possible to predict the
results of a halogenation reaction based on bond dissociation energies and
the relative stabilities of the radical intermediates. Another factor to
consider is the probability of reaction at each carbon atom, from a statistical
point of view.
Due to the different dipole moments of the product mixture, it may be
possible to separate them by distillation.
From alkenes and alkynes
" the halogen, In hydrohalogenation, an alkene reacts with a dry
hydrogen halide (HX) like hydrogen chloride (HCl) or hydrogen
bromide (HBr) to form a mono-haloalkane. The double bond of
the alkene is replaced by two new bonds, one with the halogen
and one with the hydrogen atom of the hydrohalic
acid. Markovnikov's rule states that in this reaction, the halogen is
more likely to become attached to the more substituted carbon.
This is an electrophilic addition reaction. Water must be absent
otherwise there will be a side product of a halohydrin. The
reaction is necessarily to be carried out in a dry inert solvent such
as CCl
4 or directly in the gaseous phase. The reaction of alkynes are
similar, with the product being a geminal dihalide; once
again, Markovnikov's rule is followed.
Alkenes also react with halogens (X2) to form haloalkanes with
two neighboring halogen atoms in a halogen addition reaction.
Alkynes react similarly, forming the tetrahalo compounds. This is
sometimes known as "decolorizingsince the reagent X2 is colored
and the product is usually colorless and odorless.

From alcohols
Alcohol undergoes nucleophilic substitution reaction by halogen acid to
give Haloalkanes.Tertiary alkanol reacts with hydrochloric acid directly to
produce tertiary choloroalkane(alkyl chloride), but if primary or secondary
alcohol is used, an activator such as zinc chloride is needed. This reaction
is exploited in the Lucas test.
The most popular conversion is effected by reacting the alcohol with thionyl
chloride (SOCl
2) in the "Darzens halogenation", which is one of the most convenient
laboratory methods because the byproducts are gaseous. Both phosphorus
pentachloride (PCl
5) and phosphorus trichloride (PCl
3) also convert the hydroxyl group to the chloride.

Alcohols may likewise be converted to bromoalkanes using hydrobromic

acid or phosphorus tribromide (PBr3). A catalytic amount of PBr
3 may be used for the transformation using phosphorus and bromine; PBr
3 is formed in situ.

Iodoalkanes may similarly be prepared using

red phosphorus and iodine (equivalent to phosphorus triiodide). The Appel
reaction is also useful for preparing alkyl halides. The reagent is
tetrahalomethane and triphenylphosphine; the co-products
are haloform and triphenylphosphine oxideTwo methods for the synthesis of
haloalkanes from carboxylic acids are the Hunsdiecker reaction and the Kochi reaction.

Biosynthesis
Many chloro and bromoalkanes are formed naturally. The principal
pathways involve the enzymes chloroperoxidase and bromoperoxidase.
By Rydons method
An alcohol on heating with halogen in presence of triphenyl phosphate
produces haloalkanes or alkyl halides.

Reactions
Haloalkanes are reactive towards nucleophiles. They are polar molecules: the carbon to which the
halogen is attached is slightly electropositive where the halogen is slightly electronegative. This
results in an electron deficient (electrophilic) carbon which, inevitably, attracts nucleophiles.

Substitution
Substitution reactions involve the replacement of the halogen with another
molecule—thus leaving saturated hydrocarbons, as well as the
halogenated product. Haloalkanes behave as the R+ synthon, and readily
react with nucleophiles.
Hydrolysis, a reaction in which water breaks a bond, is a good example of
the nucleophilic nature of haloalkanes. The polar bond attracts
a hydroxide ion, OH− (NaOH(aq) being a common source of this ion). This
OH− is a nucleophile with a clearly negative charge, as it has excess
electrons it donates them to the carbon, which results in a covalent bond
between the two. Thus C–X is broken by heterolytic fission resulting in a
halide ion, X−. As can be seen, the OH is now attached to the alkyl group,
creating an alcohol. (Hydrolysis of bromoethane, for example,
yields ethanol). Reaction with ammonia give primary amines.
Chloro- and bromoalkanes are readily substituted by iodide in
the Finkelstein reaction. The iodoalkanes produced easily undergo further
reaction. Sodium iodide is used thus as a catalyst.
Haloalkanes react with ionic nucleophiles
(e.g. cyanide, thiocyanate, azide); the halogen is replaced by the respective
group. This is of great synthetic utility: chloroalkanes are often
inexpensively available. For example, after undergoing substitution
reactions, cyanoalkanes may be hydrolyzed to carboxylic acids, or reduced
to primary amines using lithium aluminium hydride. Azoalkanes may be
reduced to primary amines by the Staudinger reduction or lithium
aluminium hydride. Amines may also be prepared from alkyl halides
in amine alkylation, the Gabriel synthesis and Delepine reaction, by
undergoing nucleophilic substitution with potassium
phthalimide or hexamine respectively, followed by hydrolysis.
In the presence of a base, haloalkanes alkylate alcohols, amines, and thiols
to obtain ethers, N-substituted amines, and thioethers respectively. They
are substituted by Grignard reagents to give magnesium salts and an
extended alkyl compound.
Mechanism
Where the rate-determining step of a nucleophilic substitution reaction is
unimolecular, it is known as an SN1 reaction. In this case, the slowest (thus
rate-determining step) is the heterolysis of a carbon-halogen bond to give a
carbocation and the halide anion. The nucleophile (electron donor) attacks
the carbocation to give the product.
SN1 reactions are associated with the racemization of the compound, as
the trigonal planar carbocation may be attacked from either face. They are
favored mechanism for tertiary haloalkanes, due to the stabilization of the
positive charge on the carbocation by three electron-donating alkyl groups.
They are also preferred where the substituents are sterically bulky,
hindering the SN2 mechanism.
Elimination
Main article: Dehydrohalogenation
Rather than creating a molecule with the halogen substituted with
something else, one can completely eliminate both the halogen and a
nearby hydrogen, thus forming an alkene by dehydrohalogenation. For
example, with bromoethane and sodium hydroxide (NaOH) in ethanol,
the hydroxide ion HO− abstracts a hydrogen atom. Bromide ion is then lost,
resulting in ethylene, H2O and NaBr. Thus, haloalkanes can be converted
to alkenes. Similarly, dihaloalkanes can be converted to alkynes.
In related reactions, 1,2-dibromocompounds are debrominated by zinc dust
to give alkenes and geminal dihalides can react with strong bases to
give carbenes.
Other
Haloalkanes undergo free-radical reactions with elemental magnesium to
give alkylmagnesium compounds: Grignard reagents. Haloalkanes also
react with lithium metal to give organolithium compounds. Both Grignard
reagents and organolithium compounds behave as the R− synthon. Alkali
metals such as sodium and lithium are able to cause haloalkanes to couple
in the Wurtz reaction, giving symmetrical alkanes. Haloalkanes, especially
iodoalkanes, also undergo oxidative addition reactions to
give organometallic compounds.

Applications
Haloalkanes are widely used as synthon equivalents to alkyl cation (R+)
in organic synthesis. They can also participate in a wide variety of other
organic reactions.
Short chain haloalkanes such
as dichloromethane, trichloromethane (chloroform)
and tetrachloromethane are commonly used as hydrophobic solvents in
chemistry. They were formerly very common in industry; however, their use
has been greatly curtailed due to their toxicity and harmful environmental
effects.
Chlorofluorocarbons were used almost universally
as refrigerants and propellants due to their relatively low toxicity and
high heat of vaporization. Starting in the 1980s, as their contribution
to ozone depletion became known, their use was increasingly restricted,
and they have now largely been replaced by HFCs.
Bromochlorodifluoromethane (Halon 1211),
and Bromotrifluoromethane (Halon 1301), as well as others are used in fire
extinguishers. Due to their high ozone depletion potential, production has
ended as of April 6, 1998[5] cost is high, and they are primarily used for
critical applications such as aviation[5] and military.