In
organic chemistryOrganic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
,
free-radical halogenation is a type of
halogenationHalogenation is a chemical reaction that incorporates a halogen atom into a molecule in substitution of hydrogen atom. Halogenation takes place in the gas phase. There are four types of halogenation: fluorination, chlorination, bromination, and iodination...
. This
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
is typical of
alkaneAlkanes are chemical compounds that consist only of hydrogen and carbon atoms and are bonded exclusively by single bonds without any cycles...
s and alkyl-substituted aromatics under application of heat or UV light. The reaction is used for the industrial synthesis of
chloroformChloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
(CHCl
3),
dichloromethaneDichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...
(CH
2Cl
2), and
hexachlorobutadieneHexachlorobutadiene, Cl2C=CC=CCl2, is a colorless liquid at room temperature that has an odor similar to that of turpentine. It is a chlorinated aliphatic diene with niche applications but is most commonly used as a solvent for other chlorine-containing compounds.-Synthesis:Hexachlorobutadiene, or...
. It proceeds by a free-radical chain mechanism.
General mechanism
The chain mechanism is as follows, using the chlorination of
methaneMethane is a chemical compound with the chemical formula . It is the simplest alkane, the principal component of natural gas, and probably the most abundant organic compound on earth. The relative abundance of methane makes it an attractive fuel...
as a typical example:
- 1. Initiation
In chemistry, initiation is a chemical reaction that triggers one or more secondary reactions. Often the initiation reaction generates a reactive intermediate from a stable molecule which is then involved in secondary reactions. In polymerisation, initiation is followed by a chain reaction and...
: Splitting or homolysisIn general it means breakdown to equal pieces There are separate meanings for the word in chemistry and biology.-Homolysis in chemistry:...
of a chlorine molecule to form two chlorine atoms, initiated by ultraviolet radiation or sunlight. A chlorine atom has an unpaired electron and acts as a free radical.
- 2. chain propagation
Chain propagation is a process in which a reactive intermediate is continuously regenerated during the course of a chemical reaction. In polymerization reaction, the reactive end-groups of a polymer chain react in each propagation step with a new monomer molecule transferring the reactive group to...
(two steps): a hydrogen atom is pulled off from methane leaving a 1˚ methyl radical. The methyl radical then pulls a Cl· from Cl2.
- This results in the desired product plus another chlorine radical. This radical will then go on to take part in another propagation reaction causing a chain reaction
A chain reaction is a sequence of reactions where a reactive product or by-product causes additional reactions to take place. In a chain reaction, positive feedback leads to a self-amplifying chain of events....
. If there is sufficient chlorine, other products such as CH2Cl2 may be formed.
- 3. chain termination
Chain termination is any chemical reaction that ceases the formation of reactive intermediates in a chain propagation step in the course of a polymerization, effectively bringing it to a halt.- Mechanisms of Termination :...
: recombination of two free radicals:
- The last possibility in the termination step will result in an impurity in the final mixture; notably this results in an organic molecule with a longer carbon chain than the reactants.
The net reaction is:
In the case of methane or ethane, all the hydrogen atoms are equivalent and thus have an equal chance of being replaced. This leads to what is known as a
statistical product distribution. For
propanePropane is a three-carbon alkane with the molecular formula , normally a gas, but compressible to a transportable liquid. A by-product of natural gas processing and petroleum refining, it is commonly used as a fuel for engines, oxy-gas torches, barbecues, portable stoves, and residential central...
and higher alkanes, the hydrogen atoms which form part of CH
2 (or CH) groups are preferentially replaced.
The reactivity of the different halogens varies considerably. The relative rates are:
fluorineFluorine is the chemical element with atomic number 9, represented by the symbol F. It is the lightest element of the halogen column of the periodic table and has a single stable isotope, fluorine-19. At standard pressure and temperature, fluorine is a pale yellow gas composed of diatomic...
(108) >
chlorineChlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...
(1) >
bromineBromine ") is a chemical element with the symbol Br, an atomic number of 35, and an atomic mass of 79.904. It is in the halogen element group. The element was isolated independently by two chemists, Carl Jacob Löwig and Antoine Jerome Balard, in 1825–1826...
(7×10
−11) >
iodineIodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
(2×10
−22). Hence the reaction of
alkaneAlkanes are chemical compounds that consist only of hydrogen and carbon atoms and are bonded exclusively by single bonds without any cycles...
s with fluorine is difficult to control, that with chlorine is moderate to fast, that with bromine is slow and requires high levels of UV irradiation while the reaction with iodine is practically non-existent and
thermodynamicallyThermodynamics is a physical science that studies the effects on material bodies, and on radiation in regions of space, of transfer of heat and of work done on or by the bodies or radiation...
unfavorable.
A common method in organic synthesis employing
N-bromosuccinimideN-Bromosuccinimide or NBS is a chemical reagent which is used in radical substitution and electrophilic addition reactions in organic chemistry. NBS can be considered a convenient source of cationic bromine.-Preparation:...
, which can undergo
homolysisIn general it means breakdown to equal pieces There are separate meanings for the word in chemistry and biology.-Homolysis in chemistry:...
to yield a bromine radical and is a free-radical halogenation variant, is the
Wohl-Ziegler reactionThe Wohl-Ziegler reactionis a chemical reaction that involves the allylic or benzylic bromination of hydrocarbons using an N-bromoimide and a radical initiator.Best yields are achieved with N-bromosuccinimide in carbon tetrachloride solvent...
.
Control of halogenation
- Halogenation often does not stop at monosubstititution. Depending on reaction conditions the chlorination of methane yields dichloromethane
Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...
, chloroformChloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
and carbon tetrachlorideCarbon tetrachloride, also known by many other names is the organic compound with the formula CCl4. It was formerly widely used in fire extinguishers, as a precursor to refrigerants, and as a cleaning agent...
.
- In most hydrocarbon
In organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons from which one hydrogen atom has been removed are functional groups, called hydrocarbyls....
s more than one possible product exists depending on which hydrogen is replaced. ButaneButane is a gas with the formula C4H10 that is an alkane with four carbon atoms. The term may refer to any of two structural isomers, or to a mixture of them: in the IUPAC nomenclature, however, butane refers only to the unbranched n-butane isomer; the other one being called "methylpropane" or...
(CH3-CH2-CH2-CH3), for example, can be chlorinated at the "1" position to give 1-chlorobutane (CH3-CH2-CH2-CH2Cl) or at the "2" position to give 2-chlorobutane (CH3-CH2-CHCl-CH3). The product distribution depends on relative reaction rates: in this case the "2" position of butane reacts faster and 2-chlorobutane is the major product.
- Chlorination is generally less selective than bromination. Fluorination is not only even less selective than chlorination, but also highly exothermic
In thermodynamics, the term exothermic describes a process or reaction that releases energy from the system, usually in the form of heat, but also in the form of light , electricity , or sound...
and care must be taken to prevent an explosion or a runaway reaction. This relationship is often used as a demonstration of the reactivity–selectivity principleIn chemistry the reactivity–selectivity principle or RSP states that a more reactive chemical compound or reactive intermediate is less selective in chemical reactions. In this context selectivity represents the ratio of reaction rates....
and can be explained with the aid of the Hammond postulate. A bromine radical is not very reactive and the transition stateThe transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate. At this point, assuming a perfectly irreversible reaction, colliding reactant molecules will always...
for proton abstraction has much radical character and is reached late. The reactive chlorine radical develops a transition state resembling the reactant with little radical character. When the alkyl radical is fully formed in the transition state it can benefit fully from any resonance stabilization present thereby maximizing selectivity.
- We can also look at the bond dissociation energies
In chemistry, bond-dissociation energy or D0, is one measure of the bond strength in a chemical bond. It is defined as the standard enthalpy change when a bond is cleaved by homolysis, with reactants and products of the homolysis reaction at 0 K...
(BDE's) to understand the selectivity of bromination. The BDE of a bond is the energy required to break it by homolytic cleavage, and these values can be used to determine if a reaction or step in a reaction is exothermicIn thermodynamics, the term exothermic describes a process or reaction that releases energy from the system, usually in the form of heat, but also in the form of light , electricity , or sound...
or endothermicIn thermodynamics, the word endothermic describes a process or reaction in which the system absorbs energy from the surroundings in the form of heat. Its etymology stems from the prefix endo- and the Greek word thermasi,...
. In a chain reaction step of a Br radical reacting with a hydrogen on a secondary carbon to cleave the H-C bond requires 397 kJ/mol and an H-Br is formed. We can look at the BDE of H-Br (=366 kJ/mol) and subtract this value from 397 kJ/mol to get +31 kJ/mol. This positive value tells us that this step in the reaction requires energy (endothermic) and the reactants are more stable than the products. Comparing this with the same situation of a Cl radical we see that this step is exothermic (397 kJ/mol - 431 kJ/mol = -20 kJ/mol). From these values we can conclude that in bromination it is more important that the most stable radical (tertiary) be formed during this step and thus it is more selective than chlorination. This is because less energy is required to form the H-Br and tertiary radical (380 kJ/mol - 366 kJ/mol = +14 kJ/mol). This value is 17 kJ/mol less than the secondary radical formation. Iodine does not even participate in free-radical halogenation because the entire reaction is endothermic.
- It is possible to predict the product distribution of different monochloro derivatives resulting from the chlorination of an alkane with non-equivalent hydrogens . From experimentation it has been determined that the relative rates of chlorination to primary, secondary, and tertiary positions are 1, 3.8, and 5 respectively (this ratio is used in the example following this paragraph). This corresponds with alkyl radical
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
stability: tertiary radical species are more stable than secondary radical species, and secondary radical species are more stable than primary radical species—thus any single chlorination will favor substitution at the most substituted carbon. Because of this trend, the percentages of each product formed from the parent radical can be estimated with relatively high accuracy. For example, 2-methyl butane ((CH3)2CHCH2CH3) exhibits the following results:
- -For clarity, the unique hydrogens will be labeled as follows:
- a=(CH3)2 (primary), b=CH (tertiary), c=CH2 (secondary), d=CH3 (also primary)
- -Applying the aforementioned substitution ratios in the formula: ([number of hydrogens]*[ratio factor])/[(primary hydrogens*1) + (secondary hydrogens*3.8) + (tertiary hydrogens*5)]
- a:6 X 1 = 6 a= 6/21.6 = 28%
- b:1 X 5 = 5 b= 5/21.6 = 23%
- c:2 X 3.8 = 7.6 c= 7.6/21.6 = 35%
- d:3 X 1 = 3 d= 3/21.6 = 14%
- Denominator total for this species = 6 + 5 + 7.6 + 3 = 21.6
Because all six "a" hydrogens, both "c" hydrogens, and the three "d" hydrogens are chemically equivalent with the others in their three classifications (i.e., any "a" hydrogen is equivalent with any other "a" hydrogen), these rates accurately reflect where a single chlorination may take place for 2-methyl butane. The single tertiary hydrogen "b" is nearly as susceptible as the six, primary "a" hydrogens, and almost doubly susceptible as any of the three, also-primary "d" hydrogens, illustrating the radical stability differences between tertiary and primary hydrogens (the secondary "c" hydrogens also follow the radical stability order as previously mentioned).
Free-radical iodination is usually not possible because iodine is too unreactive to form a radical. For the other halogens, free-radical halogenation generally proceeds in the following order:
- Carbons with one or more aryl
In the context of organic molecules, aryl refers to any functional group or substituent derived from an aromatic ring, be it phenyl, naphthyl, thienyl, indolyl, etc....
substituents (benzylic positions) react faster than:
- Carbons with three alkyl substituents (tertiary positions), which react faster than:
- Carbons with two alkyl substituents (secondary positions), which react faster than:
- Carbons with one or zero substituents (primary positions)
OxygenOxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
is a halogenation
inhibitorA reaction inhibitor is a substance that decreases the rate of, or prevents, a chemical reaction.-Inhibition of a catalyst:An inhibitor can reduce the effectiveness of a catalyst in a catalysed reaction...
.
An example of radical bromination of
tolueneToluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...
is given below :
This reaction takes place
on waterOn water reactions are a group of organic reactions that take place as an emulsion in water and that exhibit an unusual reaction rate acceleration compared to the same reaction in an organic solvent or compared to the corresponding dry media reaction. This effect has been known for many years but...
instead of an organic solvent and the bromine is obtained by oxidation of
hydrobromic acidHydrobromic acid is a strong acid formed by dissolving the diatomic molecule hydrogen bromide in water. "Constant boiling" hydrobromic acid is an aqueous solution that distills at 124.3 °C and contains 47.6% HBr by weight, which is 8.89 mol/L. Hydrobromic acid has a pKa of −9, making it a...
with
hydrogen peroxideHydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
. An
incandescent light bulbThe incandescent light bulb, incandescent lamp or incandescent light globe makes light by heating a metal filament wire to a high temperature until it glows. The hot filament is protected from air by a glass bulb that is filled with inert gas or evacuated. In a halogen lamp, a chemical process...
is sufficient for bromine radical generation.