as a heterogeneous catalyst]]
Alkylation is a chemical reaction that entails transfer of an
alkyl group. The alkyl group may be transferred as an alkyl
carbocation, a
free radical, a
carbanion, or a
carbene (or their equivalents).
[March Jerry; (1985). Advanced Organic Chemistry reactions, mechanisms and structure (3rd ed.). New York: John Wiley & Sons, inc. ] Alkylating agents are
for effecting alkylation. 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
alkene. 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.
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 reagent,
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
Catalysis, they also alkylate alkyl and
Aryl group halides, as exemplified by
.
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.
Alkylation by carbon electrophiles
C-alkylation
C-alkylation is a process for the formation of carbon-carbon bonds. The largest example of this takes place in the
of petrochemical plants, which convert low-molecular-weight
alkenes into high octane
gasoline components. Electron-rich species such as
are also commonly alkylated to produce a variety of products; examples include linear alkylbenzenes used in the production of
surfactants like LAS, or butylated phenols like BHT, which are used as
. This can be achieved using either acid catalysts like
Amberlyst, or
like aluminium.
On a laboratory scale the Friedel–Crafts reaction uses
, as these are often easier to handle than their corresponding alkenes, which tend to be gasses. The reaction is catalysed by aluminium trichloride. This approach is rarely used industrially as alkyl halides are more expensive than alkenes.
N-,P-, S- alkylation
N-, P-, and S-alkylation are important processes for the formation of carbon-nitrogen, carbon-phosphorus, and carbon-sulfur 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.
are readily alkylated to give via the thiol-ene reaction.
O-alkylation
Alcohols alkylate to give
:
- R-OH + R'-X -> R-O-R'
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.
- Ph-O- + Me2-SO4 -> Ph-O-Me + Me-SO4-
- (with as a spectator ion)
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.
Methylation with diazomethane
Diazomethane is a popular methylating agent in the laboratory, but it is too hazardous (explosive gas with a high acute toxicity) to be employed on an industrial scale without special precautions.
Use of diazomethane has been significantly reduced by the introduction of the safer and equivalent reagent trimethylsilyldiazomethane.
Hazards
Electrophilic, soluble alkylating agents are often toxic and carcinogenic, 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 (sulfide of dichloroethyl) function as alkylating agents. Alkylated DNA either does not coil or uncoil properly, or cannot be processed by information-decoding enzymes.
Catalysts
Electrophilic alkylation uses
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
In biology
Alkylation in biology causes
DNA damage. It is the transfer of alkyl groups to the nitrogenous bases. It is caused by alkylating agents such as EMS (Ethyl Methyl Sulphonate). Bifunctional alkyl groups which have two alkyl groups in them cause cross linking in DNA. Alkylation damaged ring nitrogen bases are repaired via the Base Excision Repair (BER) pathway.
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).
Gasoline production
In a conventional
oil refinery,
isobutane is alkylated with low-molecular-weight
(primarily a mixture of
propene and
butene) in the presence of a Brønsted acid catalyst, which can include
(zeolites). The catalyst protonates the alkenes (propene, butene) to produce
, which alkylate isobutane. The product, called "alkylate", is composed of a mixture of high-
octane, branched-chain
alkane (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.
[Michael Röper, Eugen Gehrer, Thomas Narbeshuber, Wolfgang Siegel "Acylation and Alkylation" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2000. ] are used in place of the older generation of strong Bronsted acids.
Dealkylation
Complementing alkylation reactions are the reverse, dealkylations. Prevalent are
, which are prevalent in biology, organic synthesis, and other areas, especially for
and
.
See also
External links
