Hydrohalogenation
Encyclopedia
A hydrohalogenation reaction is the electrophilic addition
of hydrohalic acids like hydrogen chloride
or hydrogen bromide
to alkene
s to yield the corresponding haloalkane
s.
If the two carbon atoms at the double bond are linked to a different number of hydrogen atoms, the halogen is found preferentially at the carbon with fewer hydrogen substituents, an observation known as Markovnikov's rule
. This is due to the abstraction of a hydrogen atom by the alkene
from the acid
(HX) to form the most stable carbocation
(relative stability: 3°>2°>1°>methyl), as well as generating a halogen anion.
The subsequent reaction proceeds by an SN1 mechanism due to the presence of the electrophilic carbocation
and a nucleophilic halide
anion, thus resulting in the final product.
A simple example of a hydrochlorination is that of indene
with hydrochloric acid
gas (no solvent):
s, HBr adds to a given alkene
in an anti-Markovnikov addition fashion. This is because the reaction proceeds through the most stable carbon radical
intermediate (relative stability: 3° > 2° > 1°>methyl) instead of a carbocation
. The mechanism for this reaction is similar to a chain reaction
such as free radical halogenation
in which the peroxide promotes the formation of the bromide
radical
. Therefore, in the presence of peroxide
s, HBr adds so that the bromine
atom is added to the carbon bearing the most numerous hydrogen substituents and hydrogen atoms will add to carbons bearing less hydrogen substituents. However, this process is restricted to addition of HBr.
No other hydrogen halide
behaves in the manner described above, this can be explained by a survey of the different hydrohalic acids: HF (hydrogen fluoride
), HCl (hydrogen chloride
— more commonly known by the aqueous species hydrochloric acid
), and HI (hydrogen iodide
).
The hydrogen-fluorine
bond is simply too strong and therefore no fluorine
radicals
can be generated in the propagation step. Hydrogen chloride
will react in a manner that is so slow that it is essentially synthetically useless. This is because the hydrogen-chlorine
bond is strong and thus the second step of the reaction would be extremely slow due to the heat required (it is an endothermic
reaction). Due to the weakness of the carbon-iodine
bond necessary to complete the first step of the propagation phase, insufficient heat is released to proceed through the reaction successfully.
With Michael acceptors the addition is also anti-Markovnikov because now a nucleophilic X- reacts in a nucleophilic conjugate addition
for example in the reaction of HCl with acrolein
.
or alumina to H-Cl (or H-Br) in dichloromethane
increases the rate of reaction making it an easy one to carry out .
Electrophilic addition
In organic chemistry, an electrophilic addition reaction is an addition reaction where, in a chemical compound, a π bond is broken and two new σ bonds are formed...
of hydrohalic acids like hydrogen chloride
Hydrogen chloride
The compound hydrogen chloride has the formula HCl. At room temperature, it is a colorless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric humidity. Hydrogen chloride gas and hydrochloric acid are important in technology and industry...
or hydrogen bromide
Hydrogen bromide
Hydrogen bromide is the diatomic molecule HBr. HBr is a gas at standard conditions. Hydrobromic acid forms upon dissolving HBr in water. Conversely, HBr can be liberated from hydrobromic acid solutions with the addition of a dehydration agent, but not by distillation. Hydrogen bromide and...
to alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
s to yield the corresponding haloalkane
Haloalkane
The haloalkanes are a group of chemical compounds derived from alkanes containing 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...
s.
If the two carbon atoms at the double bond are linked to a different number of hydrogen atoms, the halogen is found preferentially at the carbon with fewer hydrogen substituents, an observation known as Markovnikov's rule
Markovnikov's rule
In organic chemistry, Markovnikov's rule or Markownikoff's rule is an observation based on Zaitsev's rule. It was formulated by the Russian chemist Vladimir Vasilevich Markovnikov in 1870....
. This is due to the abstraction of a hydrogen atom by the alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
from the acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
(HX) to form the most stable carbocation
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
(relative stability: 3°>2°>1°>methyl), as well as generating a halogen anion.
The subsequent reaction proceeds by an SN1 mechanism due to the presence of the electrophilic carbocation
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
and a nucleophilic halide
Halide
A halide is a binary compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound. Many salts are halides...
anion, thus resulting in the final product.
A simple example of a hydrochlorination is that of indene
Indene
Indene is a flammable polycyclic hydrocarbon with chemical formula C9H8. It is composed of a benzene ring fused with a cyclopentene ring. This aromatic liquid is colorless although samples often are pale yellow...
with hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
gas (no solvent):
Anti-Markovnikov addition
In the presence of peroxidePeroxide
A peroxide is a compound containing an oxygen–oxygen single bond or the peroxide anion .The O−O group is called the peroxide group or peroxo group. In contrast to oxide ions, the oxygen atoms in the peroxide ion have an oxidation state of −1.The simplest stable peroxide is hydrogen peroxide...
s, HBr adds to a given alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
in an anti-Markovnikov addition fashion. This is because the reaction proceeds through the most stable carbon radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
intermediate (relative stability: 3° > 2° > 1°>methyl) instead of a carbocation
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
. The mechanism for this reaction is similar to a chain reaction
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....
such as free radical halogenation
Free radical halogenation
In organic chemistry, free-radical halogenation is a type of halogenation. This chemical reaction is typical of alkanes and alkyl-substituted aromatics under application of heat or UV light. The reaction is used for the industrial synthesis of chloroform , dichloromethane , and hexachlorobutadiene...
in which the peroxide promotes the formation of the bromide
Bromide
A bromide is a chemical compound containing bromide ion, that is bromine atom with effective charge of −1. The class name can include ionic compounds such as caesium bromide or covalent compounds such as sulfur dibromide.-Natural occurrence:...
radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
. Therefore, in the presence of peroxide
Peroxide
A peroxide is a compound containing an oxygen–oxygen single bond or the peroxide anion .The O−O group is called the peroxide group or peroxo group. In contrast to oxide ions, the oxygen atoms in the peroxide ion have an oxidation state of −1.The simplest stable peroxide is hydrogen peroxide...
s, HBr adds so that the bromine
Bromine
Bromine ") 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...
atom is added to the carbon bearing the most numerous hydrogen substituents and hydrogen atoms will add to carbons bearing less hydrogen substituents. However, this process is restricted to addition of HBr.
No other hydrogen halide
Hydrogen halide
Hydrogen halides are acids resulting from the chemical reaction of hydrogen with one of the halogen elements , which are found in Group 17 of the periodic table. Astatine is not included in the list because it is very rare, unstable and not found as the acid in substantial quantities...
behaves in the manner described above, this can be explained by a survey of the different hydrohalic acids: HF (hydrogen fluoride
Hydrogen fluoride
Hydrogen fluoride is a chemical compound with the formula HF. This colorless gas is the principal industrial source of fluorine, often in the aqueous form as hydrofluoric acid, and thus is the precursor to many important compounds including pharmaceuticals and polymers . HF is widely used in the...
), HCl (hydrogen chloride
Hydrogen chloride
The compound hydrogen chloride has the formula HCl. At room temperature, it is a colorless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric humidity. Hydrogen chloride gas and hydrochloric acid are important in technology and industry...
— more commonly known by the aqueous species hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
), and HI (hydrogen iodide
Hydrogen iodide
Hydrogen iodide is a diatomic molecule. Aqueous solutions of HI are known as iohydroic acid or hydroiodic acid, a strong acid. Gas and aqueous solution are interconvertible...
).
The hydrogen-fluorine
Fluorine
Fluorine 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...
bond is simply too strong and therefore no fluorine
Fluorine
Fluorine 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...
radicals
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
can be generated in the propagation step. Hydrogen chloride
Hydrogen chloride
The compound hydrogen chloride has the formula HCl. At room temperature, it is a colorless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric humidity. Hydrogen chloride gas and hydrochloric acid are important in technology and industry...
will react in a manner that is so slow that it is essentially synthetically useless. This is because the hydrogen-chlorine
Chlorine
Chlorine 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...
bond is strong and thus the second step of the reaction would be extremely slow due to the heat required (it is an endothermic
Endothermic
In 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,...
reaction). Due to the weakness of the carbon-iodine
Iodine
Iodine 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....
bond necessary to complete the first step of the propagation phase, insufficient heat is released to proceed through the reaction successfully.
With Michael acceptors the addition is also anti-Markovnikov because now a nucleophilic X- reacts in a nucleophilic conjugate addition
Nucleophilic conjugate addition
Nucleophilic conjugate addition is a type of organic reaction. Ordinary nucleophilic additions or 1,2-nucleophilic additions deal mostly with additions to carbonyl compounds. Simple alkene compounds do not show 1,2 reactivity due to lack of polarity, unless the alkene is activated with special...
for example in the reaction of HCl with acrolein
Acrolein
Acrolein is the simplest unsaturated aldehyde. It is produced widely but is most often immediately reacted with other products due to its instability and toxicity...
.
Scope
Recent research has found that adding silica gelSilica gel
Silica gel is a granular, vitreous, porous form of silica made synthetically from sodium silicate. Despite its name, silica gel is a solid. It is a naturally occurring mineral that is purified and processed into either granular or beaded form...
or alumina to H-Cl (or H-Br) in dichloromethane
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...
increases the rate of reaction making it an easy one to carry out .