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Halogeno-compounds
A.
Introduction
Alkyl halides are compounds in which halogen(s) (fluorine, chlorine, bromine and iodine)
attach(es) to an alkane.
For examples: CH3Cl, CH3CH2Br,
Polyhalides are halogeno-compounds in which more than one halogen group attach on the
organic molecule.
For examples: CH2ClCH2Cl, CH2Cl2 and CHCl3 etc.
Alkyl halides are classified into:
Aryl halides are compounds in which halogen(s) attach(es) the phenyl group (C6H5-).
For examples:
B.
Nomenclature of halogeno-compounds
Alkanes bearing halogen substitutents are named, in IUPAC system, haloalkanes, for examples:
C.
Physical properties
Most of the halides have very low solubility in water but they are miscible with each other and
with other relatively non-polar solvents, CH2Cl2, CHCl3 and CCl4 which are often used as
solvents for non-polar and moderately polar organic compounds.
D.
Preparation of halides
i.
From alkanes
Alkanes or cycloalkanes undergo free radical substitution reactions when they react with
halogens.
If all the hydrogens of an alkane or a cycloalkane are equivalent, the reaction will
be very useful.
Usually, bromination of alkanes is a more selective in free radical reactions.
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ii.
iii.
From alkenes
a.
Alkyl halides can be prepared from alkenes by addition of hydrogen halides,
HX.
Hydrogen halides can be added to alkenes in Markovnikov fashion in the
absence of peroxides and in an anti-Markovnikov way in the present of
peroxides.
b.
Benzylic halides can be prepared in a similar way.
c.
vic-dihalides can be prepared by addition of halogen to alkenes.
From alkynes
a.
vinylic halides can be prepared by addition of one molar equivalent of hydrogen
to an alkyne.
b.
gem-dihalides can be prepared by addition of two molar equivalent of hydrogen
halides to an alkyne.
gem-dihalides can also be prepared by the reaction of a ketone with PCl5.
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E.
iv.
From arenes (aromatic compounds e.g. benzene, toluene, naphthalene)
Aryl halides can be prepared by treating arenes with bromine or chlorine in the
presence of FeX3 as catalyst.
v.
From alcohols
Alcohols react with a variety of reagents to yield alkyl halides. The most commonly
used reagents are hydrogen halide, phosphorus tribromide (PBr3) and thionyl chloride
(SOCl2).
Reaction mechanisms of alkyl halides
In most reactions of alkyl halides, the nucleophilic substitution reactions occur frequently.
In this type of reactions, a nucleophile, a spieces with an unshared pair of electron, reacts with
halide (called the substrate) by replacing the halogen substitutent. Because the reaction is
initiated by a nucleophile, it is called a nucleophilic substitution reaction.
However, if the some specific conditions of the reaction are provided elimination reaction will
occur instead of nucleophilic substitution reaction.
Nu:- + R-X
Nu-R + X-
or Nu: + R-X
Nu-R+ + X-
for examples:
F.
SN2 : bimolecular nucleophilic substitution
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The mechanism is a one-step mechanism. There is no intermediate. The reaction
proceeds through a single transition state.
The transition state is one in which both the nucleophile and the leaving group (halogen
group in this case) are partially bonded to the carbon undergoing attack. Since this
transition state involves both the nucleophile (hydroxide ion) and the substrate (methyl
chloride), this mechanism accounts for the second-order reaction kinetics.
Rate = k
G.
SN1 : unimolecular nucleophilic substitution
∆Η = -9kcal/mol
The hydroxide ion does not involve in the rate-controlling step, so the reaction is unimolecular.
This reaction mechanism is called SN1.
mechanism
The first step requires heterolytic cleavage of carbon-chlorine bond and no other bond is
formed, so it should be highly endothermic and have high activation energy.
energy
Classwork:
reaction pathway
It should be noted that vinylic halides, ary halides are generally unreactive in SN1 and
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SN2 reactions, why?
H.
Reactions of halogeno-compounds
i.
Reactions with amines / ammonia
The reactions are of very limited synthetic applications because multiple alkylations
occur.
Multiple alkylations can be minimized by using a large excess of ammonia. (Why?)
For example:
A much better method for preparing a primary amine from an alkyl halide is first to
convert the alkyl halide to an alkyl azides (R-N3) by a nucleophilic substitution reaction.
Alkyl azides are explosive and low-molecular weight alkyl azides should not be isolated
but should be kept in solution.
ii.
Reactions with cyanides
iii.
Reduction of alkyl halides
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Most alkyl halides react with Zn and aqueous acid to produce alkanes.
iv.
Friedel-Craft alkylation
v.
Hydrolysis
Hydrolysis is a reaction with water (sometime OH-, alkaline hydrolysis or H+, acidic
hydrolysis) and produces pH change in the reaction mixture.
General reaction
R-X + H2O
ROH + HX
Reaction of 2-chloro-2-methylpropane with water rapidly produces 2-methyl-2-propanol.
The product is the result of substitution of chloride by the hydroxyl group of water.
Experimental data show that the rate of hydrolysis depends only on the substrate
(2-chloro-2-methylpropane), but not the nucleophile (water). The reaction is thus first
order. Of the reasonable mechanistic possibilities that we introduced initially, only the
two-step dissociation-addition sequence is consistent with an SN1 designation.
In contrast to the reaction of 2-chloro-2-methylpropane considered above, chloroethane
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does not react rapidly with neutral water. However, if sodium hydroxide is added to the
reaction mixture, hydrolysis proceeds to give ethanol.
CH3CH2Cl + H2O Æ no/slow reaction
(1)
CH3CH2Cl + OH- Æ CH3CH2OH + Cl-
fast
(2)
The rate of hydrolysis depends on the concentrations of both haloalkane and hydroxide
in the reaction. Therefore the kinetics is second order; first order w.r.t. each reactant.
A one step, concerted mechanism is proposed for this reaction and designated as SN2
mechanism.
Halobenzene also carries out hydrolysis, but the conditions should be more violent
(temperature at 350oC).
Cl
OH
+ NaOH
I.
+ NaCl
Stereochemistry of Nucleophilic substitution reactions of alkyl halides
i.
of SN1 reaction
For achiral substrate, as the reaction mechanism involved a carbocation, we consider
the attacking of the carbocation as follow:
There exist two ways of attack but the results are the same.
However, for the case that the substrate is chiral, a very different result may be
obtained. For example,
ii.
As the substrate is a chiral molecule, the nucleophile has the same chance to attack on
both sides of the carbocation, therefore, two products are produced. But more important
is that they are mirror reflection of each other. A mixture in which the substances are
mirror reflection of each other, that means, produce the same but opposite effect on
plane-polarized light, is called racemic mixture.
of SN2 reactions:
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In such reaction mechanism, inversion of configuration is resulted. The fact that SN2
reactions result in inversion can be rationalized on a very simple basis. Approach from
the side opposite the leaving group minimizes steric interactions between entering
nucleophie, leaving group and the other three groups bonded to the central carbon atom.
When can visualize a process whereby the molecule inverts like an umbrella turning
inside out.
A clever experiment used to demonstrate inversion in the SN2 process is the reaction of
2-iodooctane with iodide-128 ion. When optically active 2-iodooctane is allowed to
react with iodide-128 in acetone solvent, the substrate slowly loses optical activity.
How do these experimental results support an inversion process in SN2 reaction?
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J.
Uses of halogeno-compounds
i. As raw materials of PVC and PTFE
Poly(vinylchloride) or polychloroethene is made from the polymerization of its monomer
chloroethene (vinyl chloride).
The polar bond C-Cl results in considerable intermolecular attraction between the polymer
chains, making PVC a fairly strong material. It is used among other thing for coating
fabrics, for covering wires and cables and for making Gramophone records.
One of the most important uses of fluorocarbons, e.g. tetrafluoroethene, is the making of
poly(tetrafluoroethene) PTFE which frequently sold under the trade name "Fluon" or
"Teflon". PTFE, like other fully-fluorinated hydrocarbons, is very unreactive and resists
almost all corrosive chemicals. Therefore, it is used for values, seals and gaskets in
chemical plants and laboratories. It is also an excellent electrical insulator and is used for
wire coverings. PTFE has an extremely low coefficient of friction and has anti-stick
properties, so thin layer of it are coated on the cooking surface of non-stick sauce-pans and
on the running surface of skis.
ii. As solvents in dry-cleaning
Chlorinated hydrocarbons tend to be very good solvents for non-polar materials. For
example, dichloromethane will partially dissolve old paint and is therefore used as a
paint-stripper. Fluorochlorocarbons have intermediate solvent properties and have many
applications where a moderate solvent is needed, for example in cleaning and degreasing
machinery and electronic circuits. 1,1,2-trichloro-1,2,2-trifluoroethane, a liquid that boils at
48oC; it is also used for dry cleaning delicate materials such as suede or fur.
iii. As refrigerants
Dichlorodifluoromethane has a boiling point of -30oC, which makes it a useful refrigerant
fluid. In the refrigerator, the fluid is liquefied by compression then vaporized by sudden
expansion, which gives a cooling effect. Dichlorodifluoromethane is particularly useful
because it is unreactive so it does not corrode the machinery, and it is non-toxic so there is
no danger from possible leaks.
iv. As aerosol propellants
Dichlorodifluoromethane is also suitable for the use as an aerosol propellants. It is a liquid
in the aerosol can, when the value is opened some of it vaporizes, carrying with it the active
components, e.g. insecticide, paint, hair lacquer, etc.
v. As anaesthetics
It was known that the substitution of chlorine atoms into an alkyl chain gave it anaesthetic
properties, but also made it toxic. Therefore scientists looked for other halogen. They found
fluorine. As the stability of C-F bond, so non-toxic, and non-flammability of haloalkanes
make 2-bromo-2-chloro-1,1,1-trifluoroethane a good anaesthetic which is still widely used
in hospitals today.
vi. As fire extinguishing materials
Halons (special names of haloalkanes) are liquids that do not burn. They are made from
carbon and chlorine, bromine or fluorine. Two examples of this use are BCF and BTM.