Haloalkanes can be produced from virtually all organic precursors. From the perspective of industry, the most important ones are alkanes and alkenes.
From alkanes 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. Free radical halogenation typically produces a mixture of compounds mono- or multihalogenated at various positions.
From alkenes and alkynes In
hydrohalogenation, an
alkene reacts with a dry hydrogen halide (HX)
electrophile like
hydrogen chloride () or
hydrogen bromide () 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 under normal conditions, hydrogen is attached to the unsaturated carbon with the most hydrogen substituents. The rule is violated when neighboring functional groups
polarize the multiple bond, or in certain additions of hydrogen bromide (addition in the presence of
peroxides and the
Wohl-Ziegler reaction) which occur by a free-radical mechanism. 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 "decolorizing" the halogen, since the reagent X2 is colored and the product is usually colorless and odorless.
From alcohols Alcohol can be converted to haloalkanes. Direct reaction with a
hydrohalic acid rarely gives a pure product, instead generating
ethers. However, some exceptions are known: ionic liquids suppress the formation or promote the cleavage of ethers,
hydrochloric acid converts tertiary alcohols to chloroalkanes, and primary and
secondary alcohols convert similarly in the presence of a
Lewis acid activator, such as
zinc chloride. The latter is exploited in the
Lucas test. In the laboratory, more active deoxygenating and halogenating agents combine with base to effect the conversion. In the "
Darzens halogenation",
thionyl chloride () with
pyridine converts less reactive alcohols to chlorides. Both
phosphorus pentachloride () and
phosphorus trichloride () function similarly, and alcohols convert to bromoalkanes under
hydrobromic acid or
phosphorus tribromide (PBr3). The heavier halogens do not require preformed reagents: A catalytic amount of may be used for the transformation using phosphorus and bromine; is formed
in situ. Iodoalkanes may similarly be prepared using red
phosphorus and
iodine (equivalent to
phosphorus triiodide). One family of
named reactions relies on the
deoxygenating effect of
triphenylphosphine. In the
Appel reaction, the reagent is tetrahalomethane and
triphenylphosphine; the co-products are
haloform and
triphenylphosphine oxide. In the
Mitsunobu reaction, the reagents are any
nucleophile, triphenylphosphine, and a
diazodicarboxylate; the coproducts are triphenylphosphine oxide and a
hydrazodiamide.
From carboxylic acids Two methods for the synthesis of haloalkanes from
carboxylic acids are
Hunsdiecker reaction and
Kochi reaction.
Biosynthesis Many chloro- and bromoalkanes are formed naturally. The principal pathways involve the enzymes
chloroperoxidase and
bromoperoxidase.
From amines by Sandmeyer's Method Primary aromatic
amines yield
diazonium ions in a solution of
sodium nitrite. Upon heating this solution with copper(I) chloride, the diazonium group is replaced by -Cl. This is a comparatively easy method to make aryl halides as the gaseous product can be separated easily from aryl halide. When an iodide is to be made, copper chloride is not needed. Addition of
potassium iodide with gentle shaking produces the haloalkane. ==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). Reactions 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 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 alkanes using
lithium aluminium hydride. Azoalkanes may be reduced to primary amines by
Staudinger reduction or
lithium aluminium hydride. Amines may also be prepared from alkyl halides in
amine alkylation,
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 reagent to give magnesium salts and an extended alkyl compound.
Elimination In
dehydrohalogenation reactions, the halogen and an adjacent proton are removed from halocarbons, thus forming an
alkene. For example, with
bromoethane and sodium hydroxide (NaOH) in
ethanol, the hydroxide ion HO− abstracts a hydrogen atom. A
Bromide ion is then lost, resulting in
ethene, 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 alkyl-magnesium compound:
Grignard reagent. 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
Wurtz reaction, giving symmetrical alkanes. Haloalkanes, especially iodoalkanes, also undergo
oxidative addition reactions to give
organometallic compounds. ==Applications==