A​lkylation is the transfer of an alkyl group from one molecule to another.

The alkyl group may

be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene (or their
equivalents).An alkyl group is a piece of a molecule with the general formula CnH2n+1, where n
is the integer depicting the number of carbons linked together. For example, a methyl group (n =
1, CH3) is a fragment of a methane molecule (CH4). Alkylating agents use selective alkylation
by adding the desired aliphatic carbon chain to the previously chosen starting molecule. This is
one of many known chemical syntheses. Alkyl groups can also be removed in a process known
as dealkylation. Alkylating agents are often classified according to their nucleophilic or
electrophilic character.

In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins. For
upgrading of petroleum, alkylation produces a premium blending stock for gasoline.

In medicine, alkylation of DNA is used in chemotherapy to damage the DNA of cancer cells.
Alkylation is accomplished with the class of drugs called alkylating antineoplastic agents.

Typical route for alkylation of benzene with ethylene and ZSM-5 as a heterogeneous catalyst
Nucleophilic alkylating agents:
Nucleophilic alkylating agents deliver the equivalent of an alkyl anion (carbanion). The formal
"alkyl anion" attacks an electrophile, forming a new covalent bond between the alkyl group and
the electrophile. The counterion, which is a cation such as lithium, can be removed and washed
away in the work-up. Examples include the use of organometallic compounds such as Grignard
(organomagnesium), organolithium, organocopper, and organosodium reagents. These
compounds typically can add to an electron-deficient carbon atom such as at a carbonyl group.
Nucleophilic alkylating agents can displace halide substituents on a carbon atom through the
SN2 mechanism. With a catalyst, they also alkylate alkyl and aryl halides, as exemplified by
Suzuki couplings.

The Kumada coupling employs both a nucleophilic alkylation step subsequent to the oxidative
addition of the aryl halide (L = Ligand, Ar = Aryl).
The SN2 mechanism is not available for aryl substituents, where the trajectory to attack the
carbon atom would be inside the ring. Thus only reactions catalyzed by organometallic catalysts
are possible.
C-alkylation:
C-alkylation is a process for the formation of carbon-carbon bonds. For alkylation at carbon, the
electrophilicity of alkyl halides is enhanced by the presence of a Lewis acid such as aluminium
trichloride. Lewis acids are particularly suited for C-alkylation. C-alkylation can also be effected
by alkenes in the presence of acids.
N-and P-alkylation​:
N- and P-alkylation are important processes for the formation of carbon-nitrogen and
carbon-phosphorus bonds.
Amines are readily alkylated. The rate of alkylation follows the order tertiary amine < secondary
amine < primary amine. Typical alkylating agents are alkyl halides. Industry often relies on
green chemistry methods involving alkylation of amines with alcohols, the byproduct being
water. Hydroamination is another green method for N-alkylation.
In the Menshutkin reaction, a tertiary amine is converted into a quaternary ammonium salt by
reaction with an alkyl halide. Similar reactions occur when tertiary phosphines are treated with
alkyl halides, the products being phosphonium salts.
S-alkylation:
Thiols are readily alkylated to give thioethers.[3] The reaction is typically conducted in the
presence of a base or using the conjugate base of the thiol. Thioethers undergo alkylation to
give sulfonium ions.
O-alkylation​:
Alcohols alkylate to give ethers:
ROH + R'X → ROR'
When the alkylating agent is an alkyl halide, the conversion is called the Williamson ether
synthesis. Alcohols are also good alkylating agents in the presence of suitable acid catalysts.
For example, most methyl amines are prepared by alkylation of ammonia with methanol. The
alkylation of phenols is particularly straightforward since it is subject to fewer competing
reactions.More complex alkylation of a alcohols and phenols involve ethoxylation. Ethylene
oxide is the alkylating group in this reaction.
Oxidative addition to metals:
In the process called oxidative addition, low-valent metals often react with alkylating agents to
give metal alkyls. This reaction is one step in the Cativa process for the synthesis of acetic acid
from methyl iodide. Many cross coupling reactions proceed via oxidative addition as well.
Electrophilic alkylating agents:
Electrophilic alkylating agents deliver the equivalent of an alkyl cation. Alkyl halides are typical
alkylating agents. Trimethyloxonium tetrafluoroborate and triethyloxonium tetrafluoroborate are
particularly strong electrophiles due to their overt positive charge and an inert leaving group
(dimethyl or diethyl ether). Dimethyl sulfate is intermediate in electrophilicity.Triethyloxonium
tetrafluoroborate is one of the most electrophilic alkylating agents.
Hazards:
Electrophilic, soluble alkylating agents are often toxic due to their tendency to alkylate DNA.
This mechanism of toxicity is relevant to the function of anti-cancer drugs in the form of
alkylating antineoplastic agents. Some chemical weapons such as mustard gas function as
alkylating agents. Alkylated DNA either does not coil or uncoil properly, or cannot be processed
by information-decoding enzymes.
Catalysts:
Friedel-Crafts alkylation of benzene is often catalyzed by aluminium trichloride.
Electrophilic alkylations use Lewis acids and Brønsted acids, sometimes both. Classically, Lewis
acids, e.g., aluminium trichloride, are employed when the alkyl halide are used. Brønsted acids
are used when alkylating with olefins. Typical catalysts are zeolites, i.e. solid acid catalysts, and
sulfuric acid. Silicotungstic acid is used to manufacture ethyl acetate by the alkylation of acetic
acid by ethylene.
[C2H4 + CH3CO2H → CH3CO2C2H5]
Commodity chemicals:
Several commodity chemicals are produced by alkylation. Included are several fundamental
benzene-based feedstocks such as ethylbenzene (precursor to styrene), cumene (precursor to
phenol and acetone), linear alkylbenzene sulfonates (for detergents).Sodium dodecylbenzene,
obtained by alkylation of benzene with dodecene, is a precursor to linear alkylbenzene sulfonate
detergents.
Oil refining:
Typical acid-catalyzed route to 2,4-dimethylpentane.
In a conventional oil refinery, isobutane is alkylated with low-molecular-weight alkenes (primarily
a mixture of propene and butene) in the presence of a Brønsted acid catalyst, which can include
solid acids (zeolites). The catalyst protonates the alkenes (propene, butene) to produce
carbocations, which alkylate isobutane. The product, called "alkylate", is composed of a mixture
of high-octane, branched-chain paraffinic hydrocarbons (mostly isoheptane and isooctane).
Alkylate is a premium gasoline blending stock because it has exceptional antiknock properties
and is clean burning. Alkylate is also a key component of avgas. By combining fluid catalytic
cracking, polymerization, and alkylation refineries can obtain a gasoline yield of 70 percent. The
widespread use of sulfuric acid and hydrofluoric acid in refineries poses significant
environmental risks.