Haloalkane

Thehaloalkanes(also known ashalogenoalkanesoralkyl halides) arealkanescontaining one or morehalogensubstituents.They are a subset of the general class ofhalocarbons,although the distinction is not often made. Haloalkanes are widely used commercially. They are used asflame retardants,fire extinguishants,refrigerants,propellants,solvents,andpharmaceuticals.Subsequent to the widespread use in commerce, many halocarbons have also been shown to be seriouspollutantsand toxins. For example, thechlorofluorocarbonshave been shown to lead toozone depletion.Methyl bromideis a controversial fumigant. Only haloalkanes that contain chlorine, bromine, and iodine are a threat to theozone layer,but fluorinated volatile haloalkanes in theory may have activity asgreenhouse gases.Methyl iodide,a naturally occurring substance, however, does not have ozone-depleting properties and the United States Environmental Protection Agency has designated the compound a non-ozone layer depleter. For more information, seeHalomethane.Haloalkane or alkyl halides are the compounds which have the general formula "RX" where R is an alkyl or substituted alkyl group and X is a halogen (F, Cl, Br, I).

Tetrafluoroethane(a haloalkane) is a colorless liquid that boils well below room temperature (as seen here) and can be extracted from commoncanned aircanisters by simply inverting them during use.

Haloalkanes have been known for centuries.Chloroethanewas produced in the 15th century. The systematic synthesis of such compounds developed in the 19th century in step with the development of organic chemistry and the understanding of the structure of alkanes. Methods were developed for the selective formation of C-halogen bonds. Especially versatile methods included the addition of halogens to alkenes,hydrohalogenationof alkenes, and the conversion ofalcoholsto alkyl halides. These methods are so reliable and so easily implemented that haloalkanes became cheaply available for use in industrial chemistry because the halide could be further replaced by other functional groups.

While many haloalkanes are human-produced, substantial amounts are biogenic.

Classes

From the structural perspective, haloalkanes can be classified according to the connectivity of the carbon atom to which the halogen is attached. In primary (1°) haloalkanes, thecarbonthat carries the halogen atom is only attached to one other alkyl group. An example ischloroethane(CH
₃CH
₂Cl). In secondary (2°) haloalkanes, the carbon that carries the halogen atom has two C–C bonds. In tertiary (3°) haloalkanes, the carbon that carries the halogen atom has three C–C bonds.

Haloalkanes can also be classified according to the type of halogen on group 17 responding to a specific halogenoalkane. Haloalkanes containing carbon bonded tofluorine,chlorine,bromine,andiodineresults inorganofluorine,organochlorine,organobromineandorganoiodinecompounds, respectively. Compounds containing more than one kind of halogen are also possible. Several classes of widely used haloalkanes are classified in this waychlorofluorocarbons(CFCs),hydrochlorofluorocarbons(HCFCs) andhydrofluorocarbons(HFCs). These abbreviations are particularly common in discussions of the environmental impact of haloalkanes.

Properties

Haloalkanes generally resemble the parent alkanes in being colorless, relatively odorless, and hydrophobic. The melting and boiling points of chloro-, bromo-, and iodoalkanes are higher than the analogous alkanes, scaling with the atomic weight and number of halides. This effect is due to the increased strength of theintermolecular forces—fromLondon dispersionto dipole-dipole interaction because of the increased polarizability. Thustetraiodomethane(CI
₄) is a solid whereastetrachloromethane(CCl
₄) is a liquid. Many fluoroalkanes, however, go against this trend and have lower melting and boiling points than their nonfluorinated analogues due to the decreased polarizability of fluorine. For example,methane(CH
₄) has a melting point of −182.5 °C whereastetrafluoromethane(CF
₄) has a melting point of −183.6 °C.

As they contain fewer C–H bonds, haloalkanes are less flammable than alkanes, and some are used in fire extinguishers. Haloalkanes are bettersolventsthan the corresponding alkanes because of their increased polarity. Haloalkanes containing halogens other than fluorine are more reactive than the parent alkanes—it is this reactivity that is the basis of most controversies. Many arealkylating agents,with primary haloalkanes and those containing heavier halogens being the most active (fluoroalkanes do not act as alkylating agents under normal conditions). The ozone-depleting abilities of the CFCs arises from thephotolabilityof the C–Cl bond.

Natural occurrence

An estimated 4,100,000,000 kg ofchloromethaneare produced annually by natural sources.The oceans are estimated to release 1 to 2 million tons ofbromomethaneannually.

Nomenclature

IUPAC

The formal naming of haloalkanes should followIUPAC nomenclature,which put the halogen as aprefixto the alkane. For example,ethanewithbrominebecomesbromoethane,methanewith fourchlorinegroups becomestetrachloromethane.However, many of these compounds have already an established trivial name, which is endorsed by the IUPAC nomenclature, for examplechloroform(trichloromethane) and methylene chloride (dichloromethane). But nowadays, IUPAC nomenclature is used. To reduce confusion this article follows the systematic naming scheme throughout.

Production

Haloalkanes can be produced from virtually all organic precursors. From the perspective of industry, the most important ones are alkanes and alkenes.

From alkanes

Main article:Free radical halogenation

Alkanes react with halogens byfree radical halogenation.In this reaction a hydrogen atom is removed from the alkane, then replaced by a halogen atom by reaction with a diatomic halogen molecule. Free radical halogenation typically produces a mixture of compounds mono- or multihalogenated at various positions.

From alkenes and alkynes

Inhydrohalogenation,analkenereacts with a dry hydrogen halide (HX)electrophilelikehydrogen chloride(HCl) orhydrogen bromide(HBr) to form a mono-haloalkane. The double bond of the alkene is replaced by two new bonds, one with the halogen and one with the hydrogen atom of the hydrohalic acid.Markovnikov's rulestates that under normal conditions, hydrogen is attached to the unsaturated carbon with the most hydrogen substituents. The rule is violated when neighboring functional groupspolarizethe multiple bond, or in certain additions of hydrogen bromide (addition in the presence ofperoxidesand theWohl-Ziegler reaction) which occur by a free-radical mechanism.

Alkenes also react with halogens (X₂) to form haloalkanes with two neighboring halogen atoms in ahalogen addition reaction.Alkynes react similarly, forming the tetrahalo compounds. This is sometimes known as "decolorizing" the halogen, since the reagent X₂is colored and the product is usually colorless and odorless.

From alcohols

Alcoholcan be converted to haloalkanes. Direct reaction with ahydrohalic acidrarely gives a pure product, instead generatingethers.However, some exceptions are known: ionic liquids suppress the formation or promote the cleavage of ethers,hydrochloric acidconverts tertiary alcohols to choloroalkanes, and primary andsecondary alcoholsconvert similarly in the presence of aLewis acidactivator, such aszinc chloride.The latter is exploited in theLucas test.

In the laboratory, more active deoxygenating and halogenating agents combine with base to effect the conversion. In the "Darzens halogenation",thionyl chloride(SOCl
₂) withpyridineconverts less reactive alcohols to chlorides. Bothphosphorus pentachloride(PCl
₅) andphosphorus trichloride(PCl
₃) function similarly, and alcohols convert to bromoalkanes underhydrobromic acidorphosphorus tribromide(PBr₃). The heavier halogens do not require preformed reagents: A catalytic amount ofPBr
₃may be used for the transformation using phosphorus and bromine;PBr
₃is formedin situ.Iodoalkanes may similarly be prepared using redphosphorusandiodine(equivalent tophosphorus triiodide).

One family ofnamed reactionsrelies on thedeoxygenatingeffect oftriphenylphosphine.In theAppel reaction,the reagent is tetrahalomethane andtriphenylphosphine;the co-products arehaloformandtriphenylphosphine oxide.In theMitsunobu reaction,the reagents are anynucleophile,triphenylphosphine, and adiazodicarboxylate;the coproducts are triphenyl­phosphine oxide and ahydrazodiamide.

From carboxylic acids

Two methods for the synthesis of haloalkanes fromcarboxylic acidsareHunsdiecker reactionandKochi reaction.

Biosynthesis

Many chloro- and bromoalkanes are formed naturally. The principal pathways involve the enzymeschloroperoxidaseandbromoperoxidase.

From amines by Sandmeyer's Method

Further information:Sandmeyer reaction

Primary aromaticaminesyielddiazoniumions in a solution ofsodium nitrite.Upon heating this solution with copper(I) chloride, the diazonium group is replaced by -Cl. This is a comparatively easy method to make aryl halides as the gaseous product can be separated easily from aryl halide.

When an iodide is to be made, copper chloride is not needed. Addition ofpotassium iodidewith gentle shaking produces the haloalkane.

Reactions

Haloalkanes are reactive towardsnucleophiles.They arepolarmolecules: the carbon to which the halogen is attached is slightlyelectropositivewhere the halogen is slightlyelectronegative.This results in anelectron deficient(electrophilic) carbon which, inevitably, attractsnucleophiles.

Substitution

Substitution reactionsinvolve the replacement of the halogen with another molecule—thus leavingsaturated hydrocarbons,as well as the halogenated product. Haloalkanes behave as the R⁺synthon,and readily react with nucleophiles.

Hydrolysis,a reaction in whichwaterbreaks a bond, is a good example of the nucleophilic nature of haloalkanes. The polar bond attracts ahydroxideion, OH⁻(NaOH_(aq)being a common source of this ion). This OH⁻is a nucleophile with a clearly negative charge, as it has excess electrons it donates them to the carbon, which results in acovalentbond between the two. Thus C–X is broken byheterolytic fissionresulting in a halide ion, X⁻.As can be seen, the OH is now attached to the alkyl group, creating analcohol.(Hydrolysis of bromoethane, for example, yieldsethanol). Reactions with ammonia give primary amines.

Chloro- and bromoalkanes are readily substituted by iodide in theFinkelstein reaction.The iodoalkanes produced easily undergo further reaction.Sodium iodideis used as acatalyst.

Haloalkanes react with ionic nucleophiles (e.g.cyanide,thiocyanate,azide); the halogen is replaced by the respective group. This is of great synthetic utility: chloroalkanes are often inexpensively available. For example, after undergoing substitution reactions, cyanoalkanes may be hydrolyzed to carboxylic acids, or reduced to primary amines usinglithium aluminium hydride.Azoalkanes may be reduced to primary amines byStaudinger reductionorlithium aluminium hydride.Amines may also be prepared from alkyl halides inamine alkylation,Gabriel synthesisandDelepine reaction,by undergoing nucleophilic substitution withpotassium phthalimideorhexaminerespectively, followed by hydrolysis.

In the presence of a base, haloalkanesalkylatealcohols, amines, and thiols to obtainethers,N-substituted amines, and thioethers respectively. They are substituted byGrignard reagentto give magnesium salts and an extended alkyl compound.

Elimination

Main article:Dehydrohalogenation

Indehydrohalogenationreactions, the halogen and an adjacent proton are removed from halocarbons, thus forming analkene.For example, withbromoethaneand sodium hydroxide (NaOH) inethanol,the hydroxide ion HO⁻abstracts a hydrogen atom. ABromideion is then lost, resulting inethene,H₂O and NaBr. Thus, haloalkanes can be converted to alkenes. Similarly, dihaloalkanes can be converted toalkynes.

In related reactions, 1,2-dibromocompounds are debrominated byzincdust to give alkenes andgeminaldihalides can react with strong bases to givecarbenes.

Other

Haloalkanes undergo free-radical reactions with elemental magnesium to give alkyl-magnesium compound:Grignard reagent.Haloalkanes also react withlithiummetal to giveorganolithium compounds.Both Grignard reagents and organolithium compounds behave as the R⁻synthon. Alkali metals such assodiumandlithiumare able to cause haloalkanes to couple inWurtz reaction,giving symmetrical alkanes. Haloalkanes, especially iodoalkanes, also undergooxidative additionreactions to giveorganometallic compounds.

Applications

Teflon structure

Chlorinated or fluorinated alkenes undergo polymerization. Important halogenated polymers includepolyvinyl chloride(PVC), andpolytetrafluoroethene(PTFE, or teflon).

Alkyl fluorides

An estimated one fifth of pharmaceuticals contain fluorine, including several of the top drugs. Most of these compounds are alkyl fluorides.Examples include5-fluorouracil,flunitrazepam(Rohypnol),fluoxetine(Prozac),paroxetine(Paxil),ciprofloxacin(Cipro),mefloquineandfluconazole.Fluorine-substitutedethersarevolatile anesthetics,including the commercial productsmethoxyflurane,enflurane,isoflurane,sevofluraneanddesflurane.

Alkyl chlorides

Some low molecular weight chlorinated hydrocarbons such aschloroform,dichloromethane,dichloroethene,andtrichloroethaneare useful solvents. Several million tons of chlorinated methanes are produced annually. Chloromethane is a precursor tochlorosilanesandsilicones.Chlorodifluoromethane(CHClF₂) is used to make teflon.

Alkyl bromides

Large scale applications of alkyl bromides exploit their toxicity, which also limits their usefulness.Methyl bromideis also an effective fumigant, but its production and use are controversial.

Alkyl iodides

No large scale applications are known for alkyl iodides.Methyl iodideis a popular methylating agent inorganic synthesis.

Chlorofluorocarbons

Chlorofluorocarbonswere used almost universally asrefrigerantsandpropellantsdue to their relatively low toxicity and highheat of vaporization.Starting in the 1980s, as their contribution toozone depletionbecame known, their use was increasingly restricted, and they have now largely been replaced by HFCs.

Environmental considerations

Nature produces massive amounts of chloromethane and bromomethane. Most concern focuses on anthropogenic sources, which are potential toxins, even carcinogens. Similarly, great interest has been shown in remediation of man made halocarbons such as those produced on large scale, such as dry cleaning fluids. Volatile halocarbons degrade photochemically because the carbon-halogen bond can be labile. Some microorganisms dehalogenate halocarbons. While this behavior is intriguing, the rates of remediation are generally very slow.

Safety

Asalkylating agents,haloalkanes are potential carcinogens. The more reactive members of this large class of compounds generally pose greater risk, e.g.carbon tetrachloride.

External links

• Media related toHaloalkanesat Wikimedia Commons