organohalogen compound

Introduction

 any of a class of organic compounds (organic compound) that contain at least one halogen (halogen element) ( fluorine [F], chlorine [Cl], bromine [Br], or iodine [I]) bonded to carbon. They are subdivided into alkyl, vinylic, aryl, and acyl halides. In alkyl halides all four bonds to the carbon that bears the halogen are single bonds; in vinylic halides the carbon that bears the halogen is doubly bonded to another carbon; in aryl halides the halogen-bearing carbon is part of an aromatic ring; and in acyl halides (also called acid halides (acid halide)) the halogen-bearing carbon is doubly bonded to oxygen. Examples of the four types are shown here.

      It is the type of carbon to which the halogen is directly bonded that is primarily responsible for the characteristic properties of each class. Thus, the carbon that bears the halogen in allyl chloride (CH₂=CHCH₂Cl) is singly bonded to each of its attached atoms, which makes the compound an alkyl halide even though a double bond is present elsewhere in the chain. For the same reason, benzyl chloride (C₆H₅CH₂Cl) is an alkyl halide, not an aryl halide, even though a benzene ring is present.

      Organohalogen compounds differ widely in chemical reactivity, depending on the halogen and the class to which they belong, and they may even differ within a class. A halogen substituent is considered a functional group, and the transformations of organohalogen compounds rank among the most important in organic chemistry. Many organohalogen compounds, especially organochlorine compounds, are important industrial chemicals; they are used as solvents and pesticides (pesticide) and as intermediates in the preparation of dyes (dye), drugs (drug), and synthetic polymers (polymer). More than 2,000 organohalogen compounds have been identified as naturally occurring materials and are produced by various plants (plant), fungi (fungus), bacteria, and marine organisms. A variety of synthetic methods to introduce halogens into organic molecules are available, and organic halogen compounds may be converted to other functional-group (functional group) classes by reliable methods.

      This article discusses alkyl, vinylic, and aryl halides; for more information about acyl halides, see acid halide and carboxylic acid.

nomenclature

      Two types of IUPAC nomenclature are used when naming organohalogen compounds: substitutive and functional class. In substitutive nomenclature the prefix fluoro-, chloro-, bromo-, or iodo- is added to the name of the hydrocarbon framework along with a number (called a locant) identifying the carbon to which the halogen is attached. Substituents, including the halogen, are listed in alphabetical order. Examples of substitutive nomenclature are given here.

      Two separate words are used when naming alkyl halides by functional class nomenclature. The first word is the IUPAC name of the alkyl group (for an explanation of IUPAC nomenclature, see hydrocarbon), and the second is the word fluoride, chloride, bromide, or iodide—depending on the halogen. The alkyl group chain is numbered beginning at the carbon to which the halogen is attached.

      Some chlorinated hydrocarbons are known by common names of long standing. These include CH₂Cl₂ ( methylene chloride), CHCl₃ ( chloroform), CCl₄ ( carbon tetrachloride), CH₂=CHCl ( vinyl chloride), and CH₂=CCl₂ ( vinylidene chloride).

Carbon-halogen bond strengths and reactivity

      Among the various classes of organohalogen compounds, aryl halides have the strongest carbon-halogen bonds and alkyl halides the weakest, as, for example, in the following series of organochlorine compounds. (The bond dissociation energy is the amount of energy needed to break a given bond of a molecule in the gaseous phase.)

      There is a rough correlation between bond strength and the rates of reaction of organohalogen compounds; for example, the stronger the carbon-halogen bond, the slower the rate of reaction. Many of the most common and useful reactions of alkyl halides, when applied to vinylic or aryl halides, occur too slowly to be practical.

Alkyl halides

Structure and physical properties

      Alkyl halides (RX, where R is an alkyl group and X is F, Cl, Br, or I) are classified as primary, secondary, or tertiary according to the degree of substitution at the carbon to which the halogen is attached. In a primary alkyl halide, the carbon that bears the halogen is directly bonded to one other carbon, in a secondary alkyl halide to two, and in a tertiary alkyl halide to three.

      The methods used to prepare alkyl halides and the reactions that alkyl halides undergo frequently depend on whether the alkyl halide is primary, secondary, or tertiary.

       Selected properties of ethyl halides (CH3CH2X)A halogen substituent draws the electrons (electron) in the C−X bond toward itself, giving the carbon a partial positive charge (δ+) and the halogen a partial negative charge (δ-). The presence of the resulting polar covalent bond makes most alkyl halides polar compounds. Because the bond dipole (the measure of the separation of charge) of a C−X bond is the product of a charge term (largest for fluorine and smallest for iodine) and a distance term (smallest for fluorine and largest for iodine), the molecular dipole moments of alkyl halides do not vary much from one halogen to another. Selected properties of ethyl halides (CH3CH2X)

      The most important reactions of organohalogen compounds involve breaking the carbon-halogen bond by processes in which the halogen retains both of the electrons from the original bond and is lost as a negatively charged ion (X⁻). Consistent with the order of carbon-halogen bond strengths, in which the bond to fluorine is the strongest and the bond to iodine the weakest of the carbon-halogen bonds, fluorides are normally observed to be the least reactive of the alkyl halides and iodides the most reactive.

      The boiling points (boiling point) of ethyl halides increase as the atomic number of the halogen increases. With increasing atomic number the halogen becomes more polarizable, meaning that the electric field associated with the atom is more easily distorted by the presence of nearby electric fields. Fluorine is the least polarizable of the halogens and iodine the most polarizable. An increased polarizability is associated with stronger intermolecular attractive forces of the London dispersion type (see chemical bonding: Intermolecular forces (chemical bonding)) and therefore with an increased boiling point.

      Multiple halogen substitution tends to increase the boiling point: CH₃Cl boils at −24 °C (−11 °F), CH₂Cl₂ at 40 °C (104 °F), CHCl₃ at 61 °C (142 °F), and CCl₄ at 77 °C (171 °F). Multiple fluorine substitution is an exception, however: CH₃CH₂F boils at −32 °C (−26 °F), CH₃CHF₂ at −25 °C (−13 °F), CH₃CF₃ at −47 °C (−53 °F), and CF₃CF₃ at −78 °C (−108 °F). By reducing the molecular polarizability, multiple fluorine substitution weakens the strength of dispersion forces between molecules. In the liquid state these weakened intermolecular attractive forces are reflected in unusually low boiling points, and in the solid state they are responsible for the novel properties of fluorocarbon polymers.

      The densities of alkyl halides are related to intermolecular attractive forces and tend to parallel boiling points, alkyl fluorides being the least dense and alkyl iodides the most dense. In general, alkyl fluorides and chlorides are less dense than water, and bromides and iodides are more dense than water. Alkyl halides are not soluble in water.

Natural occurrence

      Estimates place the amount of chloromethane (methyl chloride) (methyl chloride; CH₃Cl) that results from natural biological processes at more than five million tons (five billion kilograms) per year. Most of this is produced in the oceans by marine algae and kelp, but terrestrial organisms—especially fungi (fungus)—also contribute. Smaller quantities (less than 250,000 tons per year) enter the atmosphere as a result of volcanic emissions, forest fires, and human activity. Ocean-living organisms are a source of bromomethane (methyl bromide) (CH₃Br) and iodomethane (CH₃I). More than 50 organohalogen compounds, including CHBr₃, CHBrClI, BrCH₂CH₂I, CH₂I₂, Br₂CHCH=O, I₂CHCO₂H, and (Cl₃C)₂C=O, have been identified as being present in the Hawaiian red seaweed Asparagopsis taxiformis. Virtually every marine plant that has been assayed has been found to produce organohalogen compounds, many of which have quite complicated structures.

      Several naturally occurring halogen-containing substances have pharmaceutical applications. An example is the antibiotic chloramphenicol produced by Streptomyces venezuelae.

      Fluorine-containing natural products are relatively rare, the most prominent examples being ω-fluoro fatty acids (fatty acid). (The prefix ω indicates that the substitution occurs at the end of a chain.) Fluoroacetic acid, FCH₂CO₂H, occurs in the South African plant Dichapetalum cymosum and is quite toxic. A related Dichapetalum species contains 16-fluorohexadecanoic acid, FCH₂(CH₂)₁₄CO₂H, which is also poisonous when ingested, because of its subsequent metabolic conversion to fluoroacetic acid.

Synthesis

      Alkyl halides are prepared by three main methods.

      The first is the reaction of an alcohol with a hydrogen halide, as in the following synthesis of 1-bromobutane.

      The second method is addition of a hydrogen halide to an alkene (olefin); e.g.,

      The third method is free- radical halogenation of an alkane (paraffin hydrocarbon); e.g.,

      Each of these three methods suffers from certain features that limit its generality. Consequently, the particular method chosen depends on the structure of the desired alkyl halide.

      Vicinal dihalides, compounds that have halogens on adjacent carbons, are prepared by the reaction between a halogen and an alkene. The simplest example is the reaction between ethylene and chlorine to give 1,2-dichloroethane (ethylene dichloride). 1,2-Dichloroethane leads all other organohalogen compounds in terms of its annual production, which averages nearly 20 million tons globally per year. Most of this material is converted to vinyl chloride and then to polyvinyl chloride, or PVC.

      The methods described above are best suited for preparing alkyl chlorides and bromides. Alkyl fluorides and iodides are normally made from the corresponding chloride or bromide by nucleophilic substitution (see below Reactions (organohalogen compound)).

      Among one-carbon organohalogen compounds, chloromethane is important as the starting material for the preparation of dichlorodimethylsilane, (CH₃)₂SiCl₂, from which silicone polymers are produced. The main method for the synthesis of chloromethane is the reaction of methanol with hydrogen chloride:

      A second method, the high-temperature gas-phase chlorination of methane, contributes about one-third of the annual chloromethane production.

      Dichloromethane (methylene chloride), used as a solvent, a paint remover, and aerosol propellant, is prepared by chlorination of chloromethane, and trichloromethane (chloroform) is prepared by chlorination of dichloromethane.

      Production of a large number of other one- or two-carbon organohalogen compounds has either been curtailed or eliminated because of the hazards they present with regard to ozone depletion, global warming, carcinogenicity (carcinogen), or toxicity. One example is the group of compounds called chlorofluorocarbons (chlorofluorocarbon), or CFCs. A typical CFC is dichlorodifluoromethane (CCl₂F₂; also known as CFC-12). Chlorofluorocarbons were introduced in the 1930s as safe, stable, nontoxic refrigerant gases and shortly thereafter became the standard materials for this purpose. In the 1970s, however, research by American chemists F. Sherwood Rowland (Rowland, F. Sherwood) and Mario Molina (Molina, Mario) and by Dutch chemist Paul Crutzen (Crutzen, Paul), who shared the 1995 Nobel Prize for Chemistry, indicated that CFCs were involved in the thinning of the ozone layer in Antarctica. Being very stable gases, CFCs diffuse through the atmosphere and into the stratosphere (the atmospheric region that is approximately 10 to 50 km [6 to 30 miles] above the Earth's surface), where ultraviolet radiation induces their dissociation by carbon-chlorine bond cleavage. The products of this cleavage are a chlorine atom and a chlorodifluoromethyl radical. (A free radical is a species that has one or more unpaired electrons.)

      With respect to ozone depletion, the chlorine atom is the more important product of this dissociation. The chlorine atom reacts with atmospheric ozone, abstracting an oxygen atom to form chlorine monoxide:

      At this point, one chlorine atom has reacted with one ozone molecule. However, a sequence of several steps follows in which chlorine monoxide reacts further to cleave a second molecule of ozone while regenerating a chlorine atom. This chlorine atom can then react with another ozone molecule to continue the process, eventually causing the destruction of thousands of ozone molecules.

      Because ozone is an important absorber of ultraviolet radiation, any decrease in the stratospheric concentration of ozone carries with it an increased risk of skin cancer. In 1987 the United Nations Environment Programme drafted the Montreal Protocol on Substances That Deplete the Ozone Layer, under which most of the world's industrialized nations agreed in 1990 to phase out all uses of CFCs by the year 2000. Later amendments to the Montreal Protocol have allowed developed countries to continue to produce and use certain CFCs, including chloromethane, but they are expected to phase out their dependence on these chemicals by 2030.

      In addition to CFCs, which are sources of chlorine atoms, sources of bromine atoms are ozone depleters. Bromomethane ( methyl bromide) is an example, and it was scheduled to be phased out by 2005; however, developed countries have been granted permission to negotiate annual exemptions. In 2006 the global production of bromomethane was capped at 13,000 metric tons—a 20 percent reduction from the previous year. Less-developed countries are expected to phase out their use of bromomethane by 2015. Most of the atmospheric bromomethane arises from biological processes that occur in the oceans, but about one-quarter results from the bromomethane used each year as a soil fumigant for agricultural purposes.

Reactions (chemical reaction)

      A useful property of alkyl halides is the ease with which they may be converted to other classes of compounds. The three most important reactions of alkyl halides are nucleophilic substitution, elimination, and conversion to organomagnesium compounds.

Nucleophilic substitution

      Nucleophilic substitution, which can be represented by the following general equation, permits the halogen to be replaced by oxygen, sulfur, nitrogen, or another carbon.

      The source of the negatively charged nucleophile Y⁻ is normally an ionic sodium or a potassium salt (Na⁺Y⁻or K⁺Y⁻). A specific example of a nucleophilic substitution is the reaction of sodium hydroxide and benzyl chloride:

      The relative order of alkyl halide reactivity is governed by the carbon-halogen bond strength. Alkyl iodides have the weakest carbon-halogen bond and react at the fastest rate. Alkyl fluorides have the strongest carbon-halogen bond and react so slowly as to rarely undergo nucleophilic substitutions.

      Various families of organic compounds (organic compound) can be prepared by the appropriate choice of nucleophile. These include ethers (ether) (ROR′), esters (ester) (RCOOR′), nitriles (nitrile) (RCN), and sulfides (sulfide) (RSR′):

      Alkyl fluorides are normally prepared by fluoride acting as a nucleophile toward an alkyl chloride, bromide, or iodide—e.g., NaF + RX → RF + NaX. While the reaction is reversible in principle, the greater strength of the carbon-fluorine bond causes the alkyl fluoride to predominate over the alkyl chloride, bromide, or iodide. Alkyl iodides can be prepared from alkyl chlorides and alkyl bromides by reaction with a solution of sodium iodide (NaI) in acetone (CH₃COCH₃). In this case the reaction proceeds in the direction shown because neither sodium chloride (NaCl) nor sodium bromide (NaBr) is soluble in acetone; precipitation of sodium chloride or sodium bromide from the reaction mixture causes the position of equilibrium to shift to the right.

      Chemists generally agree that the reactions of alkyl halides described to this point take place through a mechanism in which the nucleophile approaches the alkyl halide from the side opposite the bond to the leaving group. Substitution occurs in a single step by way of a transition state (a high-energy, unstable, nonisolable structure) in which the carbon being attacked is partially bonded to both the nucleophile and the leaving group. Any one-step process involving two species is defined as bimolecular, and this reaction mechanism is termed S_N2 (substitution-nucleophilic-bimolecular).

      The rate of bimolecular nucleophilic substitution strongly depends on the structure of the alkyl halide and is believed to be governed by the degree of crowding at the carbon undergoing nucleophilic attack. Methyl halides (CH₃X) react at the fastest rate. Primary alkyl halides (RCH₂X) react faster than secondary alkyl halides (RR′CHX), which in turn react faster than tertiary alkyl halides (RR′R″CX). When the substituents R, R′, and R″ are small—e.g., R = R′ = R″ = H in CH₃X—the transition state is not very crowded, and the nucleophile displaces the leaving group from carbon rapidly. Successive replacement of R, R′, and R″ by alkyl groups increasingly hinders the approach of the nucleophile to carbon, makes the transition state more crowded, and slows the rate. The blocking of access to a reactive site by nearby groups is referred to as steric hindrance.

      Tertiary alkyl halides are so sterically hindered that, when they undergo nucleophilic substitution, they do so by a mechanism other than S_N2. A two-step mechanism is believed to be followed, the first step of which is slower than the second and determines the overall rate of the reaction.

      Because the rate-determining (slow) step involves only one molecule, the mechanism is described as unimolecular, and the term S_N1 (substitution-nucleophilic-unimolecular) is applied. The species formed in the slow step contains a positively charged, electron-deficient carbon and is called a carbocation. Carbocations are unstable and react rapidly with substances such as nucleophiles that have unshared electrons available for bond formation.

Elimination (elimination reaction)

      When the attacking species is a strong base such as hydroxide (⁻OH) or alkoxide (⁻OR), nucleophilic substitutions carried out for synthetic objectives are practical only when the alkyl halide is primary. The principal reaction observed when a strong base reacts with a secondary or tertiary alkyl halide is elimination (elimination reaction), as in the attack of sodium methoxide on 2-chloro-2-methylpropane.

      Elimination competes with substitution because the negatively charged ion, in this case methoxide (⁻OCH₃), can either attack carbon (act as a nucleophile) or remove a proton (act as a base). The bonding changes that accompany elimination are often represented using curved-arrow notation to track the movement of electron pairs.

      Elimination of alkyl halides in the manner described is believed to occur in a single step and is given the mechanistic symbol E2, which stands for elimination-bimolecular. Elimination always accompanies nucleophilic substitution and is the chief limitation on efficient synthetic applications of nucleophilic substitution. By using a sufficiently strong base, it is usually possible to cause elimination to predominate over substitution, and dehydrohalogenation of alkyl halides by the E2 mechanism is one of the main methods by which alkenes are prepared (see hydrocarbon).

Preparation of Grignard reagents (Grignard reagent)

      Many metals (metal), especially those of Groups 1 and 2, reduce alkyl halides, converting the carbon-halogen bond to a carbon-metal bond. (Substances that contain a carbon-metal bond are referred to as organometallic compounds (organometallic compound).) The most generally useful organometallic compounds are those of magnesium (Mg), formulated as alkylmagnesium halides, RMgX.

      Organomagnesium compounds, called Grignard reagents (Grignard reagent), are versatile in synthetic organic chemistry. These highly reactive substances are normally prepared and stored in inert solvents, especially diethyl ether (ethyl ether) (CH₃CH₂OCH₂CH₃), until used. The preparation of Grignard reagents is of broad scope. The organohalogen compound may be an alkyl, alkenyl, or aryl halide; if it is an alkyl halide, it may be primary, secondary, or tertiary. It may be an iodide (most reactive toward reduction by magnesium), bromide, or chloride. Even alkyl fluorides, which normally do not react with magnesium, can be converted to Grignard reagents by using a specially prepared highly reactive form of the metal.

      The most useful reaction of Grignard reagents is their reaction with aldehydes (aldehyde) and ketones (ketone) to form alcohols (alcohol). Grignard reagents react with formaldehyde to give primary alcohols having one more carbon atom than the alkyl halide from which the Grignard reagent was derived. Aldehydes give secondary alcohols, while ketones yield tertiary alcohols. Alcohols can also be prepared by the reaction of Grignard reagents with epoxides or esters (for more information about these reactions, see alcohol and phenol).

Vinylic halides

Natural occurrence

      Vinylic chlorides and bromides constitute a diverse class of marine natural products. For example, the following compounds have all been isolated from the volatile oil of Chondrococcus hornemanni, a red seaweed found in the Pacific Ocean. (In line formulas such as the following, a carbon atom is assumed to be at every intersection of two lines and at the end of each line, unless otherwise labeled, with hydrogen atoms attached as necessary to each carbon.)

Preparation

      The two major methods for preparing vinylic halides are dehydrohalogenation of a dihalide and addition of a hydrogen halide to an alkyne.

Dehydrohalogenation of a dihalide

      Treatment of a geminal dihalide (both halogens on the same carbon) or a vicinal dihalide (halogens on adjacent carbons) with a base such as sodium ethoxide (NaOCH₂CH₃) yields a vinylic halide.

      The vinylic halide prepared in greatest amount as an industrial chemical is vinyl chloride (CH₂=CHCl). It is prepared from 1,2-dichloroethane (ethylene chloride) (ClCH₂CH₂Cl).

Addition (addition reaction) of a hydrogen halide to an alkyne

      When a hydrogen halide adds to the carbon-carbon triple bond of an alkyne, addition of the first molecule is faster than the second, and a vinylic halide can be isolated.

      Chloroprene, the monomer used in the formation of the elastomer neoprene, is prepared from vinylacetylene by this reaction.

      Certain vinylic halides are prepared by methods that are not applicable in general but are unique to the individual substance. tetrafluoroethylene (CF₂=CF₂), for example, is prepared by heating chlorodifluoromethane (ClCHF₂) at temperatures of 600–750 °C (1,100–1,400 °F). Tetrafluoroethylene is the monomer from which the polymer polytetrafluoroethylene (PTFE; familiarly known by its trade name, Teflon) is prepared.

Reactions

      Vinylic halides differ from alkyl halides in being essentially unreactive toward nucleophilic substitution. They do undergo elimination reactions similar to alkyl halides, although at slower rates, and they normally require very strong bases such as sodium amide (NaNH₂).

      Vinylic halides may be converted to Grignard reagents (Grignard reagent) by reaction with magnesium, and these reagents undergo the same types of reaction as those derived from alkyl halides.

      Vinylic halides resemble alkenes in that they undergo addition to their double bond. An example is the addition of hydrogen chloride to vinyl chloride to yield 1,1-dichloroethane. The product is a geminal dihalide (both halogens are bonded to the same carbon).

       polymerization of certain vinylic halides yields materials of economic value. Among synthetic polymers, the annual production of polyvinyl chloride, or PVC, is second only to that of polyethylene.

      Polyvinyl chloride is used in siding for houses, shingles, gutters and downspouts, floor tiles, and pipes and fittings. The copolymer of vinyl chloride and vinylidene chloride (CH₂=CCl₂), called saran, has properties that make it a useful self-clinging transparent wrapping material.

      Polymerization of tetrafluoroethylene gives a carbon chain that bears only fluorine substituents. Its strong carbon-fluorine bonds make polytetrafluoroethylene relatively inert toward both thermal and chemical degradation. The weakness of the attractive forces between fluorocarbon chains and other molecules causes the polymer to have a low coefficient of friction, making it well suited for nonstick coatings.

Aryl halides

Natural occurrence

      Many organohalogen compounds in which the halogen is directly attached to a benzenoid ring occur naturally. Unlike alkyl and vinylic halides, for which marine origins are the most common, aryl halides are found in a variety of sources. l- thyroxine, for example, is an iodine-containing amino acid secreted by the thyroid gland that acts as a regulator of metabolism. At one time, natural l-thyroxine extracted from the thyroids of animals was used to treat patients with thyroxine deficiencies, but today almost all of the l-thyroxine used to treat thyroid disorders is synthetic.

      The sex pheromone of the lone star tick, Amblyomma americanum, is 2,6-dichlorophenol, and 2,6-dibromophenol has been isolated from the acorn worm, Balanoglossus biminiensis.

      Several halogen-containing aromatic compounds (aromatic compound), while not natural products in the customary sense of the word, have become widely dispersed in the environment. The most familiar example is 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, or DDT.

      DDT was introduced in the early 1940s and soon became both the agricultural insecticide of choice and the principal means of combating disease-bearing insects (insect). One of the advantages of DDT is that it is a persistent insecticide, meaning that it is only slowly degraded by natural processes and survives for a long time after its initial application. DDT proved so effective in increasing crop yields and controlling insect-borne diseases such as malaria that Paul Müller (Müller, Paul Hermann), the Swiss chemist who developed the insecticide, was awarded the Nobel Prize for Physiology or Medicine in 1948. Studies in the 1960s, however, revealed that DDT accumulated in the fatty tissue of fishes, birds (bird), and other animals (animal) and that the DDT levels increased in moving up the food chain. High DDT levels in birds were associated with fragile eggshells and reproductive abnormalities. Potential harm to wildlife and humans, along with the fact that many insects had become resistant to DDT, prompted the U.S. Environmental Protection Agency (EPA) to impose in 1972 an almost complete ban on its use.

      A second chlorine-containing aromatic compound that is widespread in the environment is 2,3,7,8-tetrachlorodibenzo-p-dioxin (known simply as dioxin).

      Dioxin is formed in small amounts as a by-product in the synthesis of the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), in chlorine-based bleaching processes during paper production, and whenever organic material burns in the presence of a source of chloride ion Cl⁻, as in forest fires (forest fire), for example. It is a very stable compound and gradually accumulates in the environment. Because dioxin is exceedingly toxic, carcinogenic (carcinogen), and teratogenic to test animals, regulations designed to limit further environmental contamination have been implemented.

      A group of aryl halides called polychlorinated biphenyls (polychlorinated biphenyl) (PCBs) were formerly prepared on a large scale for use as heat-transfer mediums and insulating materials in transformers (transformer) and other electrical equipment. Many of the problems associated with DDT and dioxin as environmental pollutants apply to PCBs as well, and PCB production was banned by the EPA in 1979.

Preparation

      Aryl halides are prepared by two major methods: halogenation of the aromatic ring and reactions involving diazonium salts (diazonium salt).

Halogenation

      Treatment of a compound that contains an aromatic ring with chlorine or bromine in the presence of a catalyst, typically iron (Fe) or an iron(III) halide (FeX₃), brings about electrophilic aromatic substitution of one of the ring hydrogen atoms by the halogen.

      Certain highly reactive aromatic compounds, especially derivatives of phenol (C₆H₅OH) and aniline (C₆H₅NH₂), undergo halogenation of the ring rapidly, even in the absence of a catalyst.

      The reaction of benzene with fluorine is difficult to control and gives a mixture of polyfluorinated derivatives of cyclohexane (C₆H₁₂). Dehydrofluorination of these compounds in the presence of strong bases yields fluorinated derivatives of benzene. Direct iodination of aromatic rings requires specialized reagents and is not often carried out.

Diazonium (diazonium salt) ions

      Aryl diazonium ions (ArN⁺≡N, where Ar denotes an aromatic ring) are especially useful starting materials for preparing aryl halides, because they provide access to aryl halides as well as to phenols and nitriles (nitrile). Aryl diazonium ions are prepared by diazotization, a procedure in which a primary aromatic amine (ArNH₂) is treated with a source of nitrous acid (HNO₂). Typically this involves adding sodium nitrite (NaNO₂) to an aqueous acidic solution containing the amine.

      Once formed, the aryl diazonium ion is converted to an aryl chloride or bromide by heating the ion in the presence of the appropriate copper(I) salt. Aryl iodides are prepared by adding potassium iodide to the solution of the aryl diazonium ion.

      Aryl fluorides are prepared by converting the aryl diazonium ion to its corresponding fluoroborate salt and then isolating and heating the aryl diazonium fluoroborate.

Reactions

      A halogen substituent on an aromatic ring can be a functional group (i.e., the site of chemical reactivity) itself, or it can influence the course of reactions that involve other parts of the molecule. The latter of these effects is seen in electrophilic aromatic substitution of aryl halides. When present as a substituent on an aromatic ring, a halogen deactivates the ring toward electrophilic aromatic substitution (i.e., makes it less reactive than benzene) and directs incoming substituents to positions ortho and para to itself.

      When the halogen acts as a functional group, aryl halides are less reactive than alkyl halides and more closely resemble vinylic halides in their reactivity. Nucleophilic aromatic substitution is a practical synthetic reaction only when the aryl halide bears a strongly electron-attracting substituent, such as a nitro group NO₂, at a position ortho or para to the halogen, as in 1-chloro-4-nitrobenzene:

      Additional nitro groups make the aryl halide even more reactive. 1-Chloro-2,4-dinitrobenzene, for example, reacts with sodium methoxide in methanol at 50 °C (120 °F) more than 30,000 times faster than does 1-chloro-4-nitrobenzene.

      Nucleophilic aromatic substitution of nitro-substituted aryl halides probably proceeds by attachment of the nucleophile to the aromatic ring in a step that precedes loss of the halide leaving group. This nucleophilic addition step is facilitated by the presence of the electron-attracting nitro group. The negatively charged intermediate formed by nucleophilic addition then rapidly expels the halide ion to form the observed product.

      Unlike other nucleophilic substitutions of organohalogen compounds, the relative rates do not parallel carbon-halogen bond strengths. Aryl chlorides, bromides, and iodides are similar in reactivity to one another, an observation that provides the experimental basis for the belief that the carbon-halogen bond is not broken until after the slow step of the mechanism. Aryl chlorides, bromides, and iodides are all far less reactive than aryl fluorides, consistent with the formation of the negatively charged intermediate shown in the slow step. The highly electronegative fluorine substituent stabilizes this intermediate much more than do the other halogens and causes it to be formed faster.

      The low reactivity of simple aryl halides toward nucleophilic substitution is illustrated by the observation that temperatures on the order of 350 °C (660 °F) are required in order to convert chlorobenzene to phenol by reaction with sodium hydroxide. Furthermore, the reaction has been shown to proceed by a mechanism different from conventional nucleophilic substitution pathways. It proceeds in two stages, the first of which is an elimination in which a formal triple bond is incorporated into the ring to give a benzyne intermediate. In the second stage of the mechanism, a hydroxide ion and a proton add to the benzyne intermediate to give the product.

      The involvement of benzynelike intermediates, called arynes, has been demonstrated in numerous reactions of aryl halides with strong bases.

      Aryl halides (ArX), especially bromides and iodides, are converted to Grignard reagents (ArMgX) by reaction with magnesium. These arylmagnesium halides are similar in reactivity and in their applications to alkylmagnesium halides.

Francis A. Carey

Additional Reading

Basic works on organic chemistry that discuss organohalogen compounds include D.R. Bloch, Organic Chemistry Demystified (2006); and K. Peter C. Vollhard and Neil E. Schore, Organic Chemistry: Structure and Function, 5th ed. (2007). Organohalogen compounds feature prominently in texts devoted to specific reaction mechanisms, most notably S.R. Hartshorn, Aliphatic Nucleophilic Substitution (1973); and William H. Saunders, Jr., and Anthony F. Cockerill, Mechanisms of Elimination Reactions (1973). The unique properties of organofluorine compounds are described in R.D. Chambers, Fluorine in Organic Chemistry, 2nd ed. (2003).Francis A. Carey

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