HALOALKANES AND

ORGANOMETALLIC COMPOUNDS
1. Generalities
• Halogenated compounds (halogen derivatives/halides/haloalkanes) have structures similar to
alkanes, in which one or more hydrogen atoms are replaced by one or more halogen atoms.
• A halogenated compound R–X (where X = F, Cl, Br, I) can contain a fluorine, chlorine,
bromine, or iodine atom.
• They can be natural or synthetic and are used in the chemical industry as solvents, plastic
precursors, and in the agrochemical industry as insecticides or pesticides.
1.1 Nomenclature of haloalkanes
According to IUPAC nomenclature, the halogen is considered a substituent attached to the main
alkane chain.
Haloalkanes are named following the rules for alkanes, with the addition of the appropriate
prefix for the halogen: fluoro-, chloro-, bromo-, iodo- (F, Cl, Br, I).
For the common (or trivial) nomenclature of alkyl halides, the name is constructed as follows:
Name of the alkyl group (derived from the corresponding alkane).
Name of the halide (fluoride, chloride, bromide, iodide).
Examples :
1.2 Classification of haloalkanes

Haloalkanes are classified as primary, secondary, or tertiary depending on the nature of the
carbon atom bonded to the halogen.

Examples :
1.3 Physical properties
• Halogenated derivatives have higher boiling points than the corresponding hydrocarbons.
• They are insoluble in water (due to the absence of hydrogen bonding), but miscible with most
organic solvents.
• Haloalkanes containing Br or I atoms are denser than water, while those containing F or Cl may
be lighter.
• The C–X bond is polarized, and halogenated compounds have a non-zero molecular dipole
moment.

Bond CH3-F CH3-Cl CH3-Br CH3-I

Bond Length (Å) 1.39 1.78 1.93 2.14
Bond Strength (kJ/mol) 452 351 293 234
Dipole moment (Debye) 1.847 1.860 1.830 1.636
2. Preparation of haloalkanes
2. 4 From alcohols
• The hydroxyl group of an alcohol is replaced by halogen on reaction with concentrated halogen
acids, phosphorus halides or thionyl chloride

2.5 From aldehydes or ketones

3. Chemical Reactivity of Haloalkane
• The C–X bond is polarized, and the carbon is electron-deficient, carrying a δ+ charge; therefore,
it is susceptible to attack by nucleophilic reagents.
• The neighboring C–H bonds are also influenced by the inductive electron-withdrawing effect of
the halogen and are predisposed to break, releasing an H⁺ ion under the action of a base (labile
hydrogen).

• Halides undergo three main types of reactions:

• Nucleophilic substitution (SN)
• Elimination (E)
• Reactions with metals (formation of organometallic compounds)
3.1 Nucleophilic Substitution Reactions
• The nucleophilic substitution reaction results from the attack of an electron-rich species, called a
"nucleophile," on an electron-poor site.
• The nucleophilic group attaches itself in place of a leaving group, known as a "nucleofuge."

Examples :

• Nucleophilic substitution is represented by two different mechanisms: first-order nucleophilic

substitution (SN1) and second-order nucleophilic substitution (SN2).
3.1.1 Nucleophilic Substitution of Order 1 (SN1)
• The mechanism of the SN1 reaction occurs in two steps :

• During the first step, which is slow, the bond between the carbon atom and the leaving group
breaks, resulting in the formation of a carbocation. The leaving group takes the bonding
electrons from the C–X bond with it.
• In the second step, which is fast, the carbocation combines with the nucleophile to form the
expected product.

Example :
Mecanism:

• It should be noted that the nucleophile can attack from either side of the planar carbocation. This
leads, in the case of an asymmetric carbon, to the formation of enantiomers (a racemic mixture)
• It can be concluded that the SN1 reaction is not stereoselective (and therefore not stereospecific)
• Stereoselective (favors one stereoisomer over others).
• Stereospecific (produces a unique product depending on the configuration of the starting isomer)
• These steps are illustrated in the energy diagram of a first-order nucleophilic substitution (SN1)
reaction below.
• Kinetically, the rate of the overall reaction is
governed by the first, slow step. Notably, the
nucleophilic reactant does not participate in this
step.
• The reaction rate is independent of the nucleophilic
reactant concentration. It depends only on the
substrate concentration.
• The rate law can be written as:

• The SN1 reaction is unimolecular and first-order.

3.1.2 Determinant factors of the SN1 mechanism
a) The Substrate
• The SN1 reaction can only occur if the carbocation formed is stable. This stability is favored by
the presence of any electron-donating effect that helps to stabilize the positive charge on the
carbocation.
Examples :
• Furthermore, steric hindrance has less influence on the SN1 mechanism because the
mechanism of this substitution involves a trigonal carbon, which is sterically less hindered.
As a result, steric hindrance favors the SN1 mechanism.

b) The Base (or Nucleophile)

• The rate of the SN1 substitution does not depend on the concentration of the nucleophile.
• However, the nucleophile must be more reactive than the leaving group.
• When the nucleophile is less reactive, the reaction generally follows an SN1 mechanism.
c) The nucleofuge
• The larger the leaving group, the longer the carbon–leaving group bond (more polarizable), and
the easier its dissociation.

d) The solvent
• A polar protic solvent (water, methanol, etc.) exerts an accelerating effect on the SN1 reaction
because it stabilizes the formed carbocation as well as the leaving group through hydrogen
bonding.
• Polar (It has a high dipole moment)
• Protic (It contains O-H or N-H bonds, which enable it to form hydrogen bonds with other
molecules).
3.1.3 Second-Order Nucleophilic Substitution (SN2)
• The mechanism of an SN2-type reaction occurs in a single step :

• The nucleophile attacks the carbon atom from the side opposite the leaving group (a backside
attack), initiating the formation of a new bond.
• In the transition state, both the nucleophile and the leaving group are partially bonded to the
carbon undergoing substitution.
• As the C–X bond breaks and the X⁻ leaves with its lone pair of electrons, the nucleophile
donates a lone pair to form the new Nu–C bond. This is a concerted reaction.
• These steps are shown in the energy diagram of a second-order nucleophilic substitution (SN2)
below.
• From a kinetic perspective, both the substrate and
the nucleophilic reactant are important in the rate-
determining step of the reaction. The rate depends
on their respective concentrations.

• The reaction is first-order with respect to both the

substrate and the reactant. It is a reaction with an
overall order of two, hence its name SN2, or
bimolecular reaction.
 Example :

• The conversion from the substrate to the substituted product occurs via an inversion of
configuration, known as Walden inversion. If the carbon atom is asymmetric, unlike in an SN1
reaction, only one enantiomer is formed. This makes the reaction stereospecific.
3.1.4 Determinant factors of the SN2 mechanism
a) The Substrate
• Steric hindrance around the substrate interferes with the approach of the nucleophile. This
hindrance increases with the degree of substitution of the substrate.
• The reactivity order for an SN2 mechanism is the reverse of that observed in the SN1
mechanism.
Example :

b) The Base (or Nucleophile)

• SN2 substitution is favored when the nucleophilicity of the reactant is high.

• For example, using a strong nucleophile, typically a strong base such as the hydroxide ion
(–OH) instead of H₂O, accelerates the rate of the SN2 substitution. Moreover, nucleophilicity
increases with the size of the attacking atom.
Example :

c) The nucleofuge

• Just like for SN1, the more polarized a bond is, the easier it is to break.

d) The solvent

• A polar aprotic solvent (such as acetone, DMSO, etc.) has a favorable effect on the SN2 reaction
by promoting the separation of ionic species without solvation of the nucleophile.
Aprotic means it does not contain O-H or N-H bonds, and therefore cannot form hydrogen
bonds with a nucleophile.
3.2 Elimination Reactions
• When a haloalkane has at least one hydrogen atom (on the β carbon) adjacent to the C–X
bond (on the α carbon), the action of a base can lead to a dehydrohalogenation, resulting in
the formation of a double bond.

Example :

• Elimination reactions can occur via two possible mechanisms: first-order elimination reactions
(E1) and second-order elimination reactions (E2).
3.2.1 First-order elimination mechanism (E1)
• The E1 mechanism is a two-step process.

• Step 1: The leaving group detaches from the substrate, and a carbocation is formed through the
heterolytic cleavage of the C–X bond. This is the slow and rate-determining step.
Step 2: This is a fast step in which a hydrogen atom is abstracted from the β carbon of the
carbocation by a base (B⁻). The hydrogen is removed as a proton (H⁺), and the two electrons
from the C–H bond form the π bond of the newly created double bond.
• It is a unimolecular mechanism in which the halogenated compound is the only species involved
in the activated complex.

Example :
• When there are two β-hydrogens that can be eliminated, the one that is removed is the one
leading to the more substituted, and thus more thermodynamically stable, alkene according to
Zaitsev's rule.
• Elimination reactions are regioselective (they favor a specific position in the molecule)
Example :
• E1 is not stereospecific: This is because a carbocation intermediate is formed, allowing free
rotation around the C–C bond. As a result, two alkene isomers (E and Z) can form.

• However, it is stereoselective: The E-isomer predominates, as it is generally more stable due to

less steric hindrance between bulky substituents.

• The E1 mechanism is favored by factors that facilitate the formation of the carbocation
intermediate and increase its stability (tertiary halide, polar solvent, etc.), similar to what
happens in an SN1 reaction.
3.2.2 / Determinant factors of the E1 mechanism

a) The Substrate

• Only tertiary halides, and occasionally secondary halides, undergo an E1 mechanism, typically
in the presence of a weak or moderately weak base at low concentration
b) The nucleofuge

• The reaction strongly depends on the nature of the leaving group. The better the leaving group,
the faster the reaction proceeds.

• The more polarizable the C–X bond is, the easier it breaks. Therefore, the lability of this bond
increases from fluorine to iodine: F < Cl < Br < I.
c) The Base (or Nucleophile)

• The elimination reaction requires the presence of a Brønsted base capable of abstracting a
hydrogen in the β-position.
• Thus, the more basic the nucleophile is (in the Brønsted sense), the more the reaction is favored.
(Examples of weak bases: H₂O, RCO₂⁻…)

d) The solvent
• The rate of the E1 reaction increases with the increase in solvent polarity, as a polar solvent
further stabilizes the carbocation and thus facilitates the first step of the reaction.
• The solvents used for E1 reactions are protic polar solvents (e.g., H2O, ROH...).
3.2.3 Elimination mechanism of second order (E2)
• Like the SN2 mechanism, the E2 mechanism occurs in a single step, and no reaction
intermediate is formed.

• The nucleophile, acting as the base, removes the hydrogen atom attached to the β-carbon.
At the same time, the leaving group departs, and a double bond is formed. This is
therefore a bimolecular mechanism where the base and the substrate are both involved in
the active complex. The rate law for the E2 reaction is the same as for the SN2, which is:
• The elimination of HX is an anti elimination, meaning that the H and X must be on opposite
sides of the C-C bond, in a trans position, with an angle of 180° between them (anti-periplanar
conformation). Therefore, the E2 elimination reaction is stereospecific.

Example: The dehydrobromination of 1-bromo-1,2-diphenylpropane by a base gives: from the

erythro isomer, the Z-alkene; from the threo isomer, the E-alkene.

• The activation energy (Ea) of an E2 elimination reaction is generally higher than that of an SN2
substitution reaction, so energy input (heating) is required.
3.2.3 Determinant factors of the E2 mechanism
a) The Substrate

• The ease of elimination in an E2 mechanism decreases from tertiary halogenoalkanes to primary

halogenoalkanes, but the relative rate variation remains small.
• Elimination is favored if the base is bulky or if the substrate is bulky.
• Indeed, in both cases, the nucleophile has difficulty reaching the carbon bearing the halogen;
however, it can easily reach the hydrogen on the β-carbon (the carbon adjacent to the one
bearing the halogen).

b) The nucleofuge

• The elimination reaction directly depends on how easily the C-X bond breaks, as it must break
easily.
c) The Base (or Nucleophile)

• The attack by the base initiates the reaction process, so a strong base is needed. Experimentally,
it is observed that the rate increases with the strength of the base: for example, NH2− reacts
faster than EtO−, which reacts faster than HO−.

d) The solvent
• An increase in solvent polarity further stabilizes the initial state more than the transition state,
thus increasing the activation energy and reducing the reaction rate. The solvents used for E2
reactions are polar aprotic solvents (e.g., DMF, DMSO).
 4 . Competitive reaction between nucleophilic substitution and elimination.

• The same species can be both nucleophilic and basic (e.g., HO−), and thus it can generate both
nucleophilic substitution and elimination reactions, which are generally competitive.

Three main factors influence this competition, namely:

• Temperature
• The structure and size of the halogenated derivative
• The basicity of the reactant.

4.1 SN1-E1 competition :

• Both reactions occur in the presence of a tertiary halogenoalkane (R-X), with the formation of a
common reaction intermediate, a tertiary carbocation.
• The elimination product is preferentially formed by raising the temperature. Thus, it is primarily
the temperature factor that favors E1 over SN1.

Example :

• An SN1 reaction is observed when 2-bromo-2-methylpropane is dissolved in methanol at low

temperature. However, the presence of 2-methylpropene, resulting from a side elimination, is
also noted.
• This product can be made the major one by applying slight heating and/or adding a small
amount of soda or potash.
4.2 SN2-E2 competition :
• These two reaction mechanisms are always competitive.
• When the R-X is primary and in the presence of the nucleophile EtO−, SN2 is favored.
• To favor E2 over SN2, the temperature must be increased.
• Other factors affecting the product ratio between SN2 and E2 include the basicity and
polarizability of the nucleophile (base).

Example :
Example :

• In the following example, only strong and highly bulky bases will favor an E2 reaction.

• Note also that reactions occurring at a high temperature always favor elimination.
Potassium tert-butoxide is a strong, sterically bulky base. As a result, substitution is more
difficult, and the main reaction is elimination.
Note:
• A strong, weakly polarizable base, such as the amide ion NH2− or an alkoxide ion (particularly
weakly polarizable), leads to an increase in elimination products.
• A weak base, such as the chloride ion Cl− or the ethanoate ion CH3COO−, or a weak and
easily polarizable base, such as I−, Br−, or RS−, increases the percentage of substitution.
5. Reactions with metals (formation of organometallic compounds)

• Halogenated compounds can be converted into organometallic compounds, which are

powerful nucleophiles that allow the elongation of carbon chains.
• These molecules have a polarized carbon-metal bond due to the low electronegativity of the
metal.
• Organomagnesium compounds (RMgX), where X is a halogen such as Cl, Br, or I, are the
most commonly used.
• These compounds, known as Grignard reagents, are named after the French chemist Victor
Grignard, who discovered them and was awarded the Nobel Prize in 1912.
• Organolithium compounds are also used in organic chemistry.
 5.1 Preparation of organomagnesium compounds
• Organomagnesium compounds are prepared from the corresponding halogenoalkanes (R–X)
in the presence of metallic magnesium in an anhydrous solvent, such as diethyl ether or
tetrahydrofuran (THF).

• Organomagnesium compounds are very sensitive to water and must be prepared under strictly
anhydrous conditions.
5. 2 Reactivity of organomagnesium compounds
5. 2. 1 basic properties
Organomagnesium compounds react with compounds that contain labile hydrogen atoms.

Examples :
5. 2. 2 Nucleophilic properties
Organomagnesium compounds are strong carbon nucleophiles, primarily used to form
C–C bonds.
5. 2. 2. 1 Nucleophilic substitution (SN2)
Organomagnesium derivatives react with haloalkanes to form carbon–carbon bonds.

a) With haloalkanes R-X

Mecanism
b) With epoxides
Grignard reagents react with epoxides to extend the carbon chain by two atoms in one step.

Mecanism

The nucleophile attacks the less hindered carbon atom of the epoxide in a stereospecific anti-
addition reaction.
5.2.3 Nucleophilic addition
5.2.3.1 On carbonyl groups
• Organomagnesium compounds react with carbonyl groups to form alcohols of varying classes
after hydrolysis of the intermediate magnesium alkoxide.

a) Aldehydes and ketones

Mecanism
b) Carbon dioxide (CO2)
Grignard reagents react with carbon dioxide to form carboxylic acids.

Mecanism

c) Carboxylic acid derivatives (esters and acid halides)

Reaction with esters or acyl chlorides results in double addition of the organomagnesium reagent,
producing a tertiary alcohol. For example, for an ester :
Mecanism

It is not possible to stop at the intermediate ketone stage under these conditions, as the formed
ketone is more reactive than the starting ester.
5.2.3.2 with nitriles

The C≡N bond is polarized; like in a carbonyl group, the carbon atom of the nitrile group is
electrophilic and can be attacked by a nucleophile such as an organomagnesium compound.