Alkylation is achemical reaction that entails transfer of analkyl group. The alkyl group may be transferred as an alkylcarbocation, afree radical, acarbanion, or acarbene (or their equivalents).[1][2]Alkylating agents arereagents for effecting alkylation. Alkyl groups can also be removed in a process known asdealkylation. Alkylating agents are often classified according to theirnucleophilic orelectrophilic character. In oil refining contexts,alkylation refers to a particular alkylation ofisobutane witholefins. For upgrading ofpetroleum, alkylation produces a premium blending stock for gasoline.[3] In medicine, alkylation ofDNA is used inchemotherapy to damage the DNA of cancer cells. Alkylation is accomplished with the class of drugs calledalkylating antineoplastic agents.
Nucleophilic alkylating agents deliver the equivalent of analkylanion (carbanion). The formal "alkyl anion" attacks anelectrophile, forming a newcovalent bond between the alkyl group and the electrophile. The counterion, which is a cation such as lithium, can be removed and washed away in thework-up. Examples include the use oforganometallic compounds such asGrignard (organomagnesium),organolithium,organocopper, andorganosodium reagents. These compounds typically can add to an electron-deficient carbon atom such as at acarbonyl group. Nucleophilic alkylating agents can displacehalide substituents on a carbon atom through theSN2 mechanism. With acatalyst, they also alkylate alkyl andaryl halides, as exemplified bySuzuki couplings.
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.[citation needed]
C-alkylation is a process for the formation of carbon-carbon bonds. The largest example of this takes place in thealkylation units of petrochemical plants, which convert low-molecular-weightalkenes into high octanegasoline components. Electron-rich species such asphenols are also commonly alkylated to produce a variety of products; examples includelinear alkylbenzenes used in the production ofsurfactants likeLAS, or butylated phenols likeBHT, which are used asantioxidants. This can be achieved using either acid catalysts likeAmberlyst, orLewis acids like aluminium.[4] On a laboratory scale theFriedel–Crafts reaction usesalkyl halides, as these are often easier to handle than their corresponding alkenes, which tend to be gasses. The reaction is catalysed byaluminium trichloride. This approach is rarely used industrially as alkyl halides are more expensive than alkenes.[citation needed]
N-, P-, and S-alkylation are important processes for the formation of carbon-nitrogen, carbon-phosphorus, and carbon-sulfur bonds,[citation needed]
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 ongreen chemistry methods involving alkylation of amines with alcohols, the byproduct being water.Hydroamination is another green method for N-alkylation.[citation needed]
In theMenshutkin reaction, atertiary amine is converted into aquaternary ammonium salt by reaction with analkyl halide. Similar reactions occur when tertiary phosphines are treated with alkyl halides, the products being phosphonium salts.
Thiols are readily alkylated to givethioethers via thethiol-ene reaction.[5] The reaction is typically conducted in the presence of a base or using the conjugate base of the thiol. Thioethers undergo alkylation to givesulfonium ions.
Alcohols alkylate to giveethers:
When the alkylating agent is an alkyl halide, the conversion is called theWilliamson 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.[6]
More complex alkylation of a alcohols and phenols involveethoxylation.Ethylene oxide is the alkylating group in this reaction.
In the process calledoxidative addition, low-valent metals often react with alkylating agents to give metal alkyls. This reaction is one step in theCativa process for the synthesis ofacetic acid frommethyl iodide. Manycross coupling reactions proceed via oxidative addition as well.[citation needed]
Electrophilic alkylating agents deliver the equivalent of an alkylcation. Alkyl halides are typical alkylating agents.Trimethyloxonium tetrafluoroborate andtriethyloxonium tetrafluoroborate are particularly strong electrophiles due to their overt positive charge and an inert leaving group (dimethyl ordiethyl ether).Dimethyl sulfate is intermediate in electrophilicity.[citation needed]
Diazomethane is a popularmethylating 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.[8] Use of diazomethane has been significantly reduced by the introduction of the safer and equivalent reagenttrimethylsilyldiazomethane.[9]
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 ofalkylating antineoplastic agents. Somechemical weapons such asmustard 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.[citation needed] Without functional DNA, the functioning of the cell ceases, leading to cell death. Thus, these alkylating agents arecytotoxic.
Electrophilic alkylation usesLewis acids andBrønsted 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 manufactureethyl acetate by the alkylation ofacetic acid byethylene:[10]
Alkylation in biology causesDNA damage. It is the transfer of alkyl groups to thenitrogenous bases. It is caused by alkylating agents such asEMS (Ethyl methanesulfonate). Bifunctional alkyl groups which have two alkyl groups in them cause cross linking in DNA. Alkylation damaged ring nitrogen bases are repaired via thebase excision repair (BER) pathway.[11]
Several commodity chemicals are produced by alkylation. Included are several fundamental benzene-based feedstocks such asethylbenzene (precursor tostyrene),cumene (precursor tophenol andacetone),linear alkylbenzene sulfonates (for detergents).[12]
In a conventionaloil refinery,isobutane is alkylated with low-molecular-weightalkenes (primarily a mixture ofpropene andbutene) in the presence of a Brønsted acid catalyst, which can includesolid acids (zeolites). The catalyst protonates the alkenes (propene, butene) to producecarbocations, which alkylate isobutane. The product, called "alkylate", is composed of a mixture of high-octane, branched-chainparaffinichydrocarbons (mostlyisoheptane andisooctane). Alkylate is a premiumgasoline blending stock because it has exceptional antiknock properties and is clean burning. Alkylate is also a key component ofavgas. By combiningfluid catalytic cracking, polymerization, and alkylation, refineries can obtain a gasoline yield of 70 percent. The widespread use ofsulfuric acid andhydrofluoric acid in refineries poses significant environmental risks.[13]Ionic liquids are used in place of the older generation of strong Bronsted acids.[14][15]
Complementing alkylation reactions are the reverse, dealkylations. Prevalent aredemethylations, which are prevalent in biology, organic synthesis, and other areas, especially formethyl ethers andmethyl amines.[citation needed]
Authority control databases: National |
|---|
