In organic chemistry, an aryl halide (also known as a haloarene) is an aromatic compound in which one or more hydrogen atoms directly bonded to an aromatic ring are replaced by a halide ion (such as fluorine F −, chlorine Cl−1,−3,−5, bromine Br−1, or iodine I−). Aryl halides are distinct from Haloalkane (alkyl halides) due to significant differences in their methods of preparation, chemical reactivity, and physical properties. The most common and important members of this class are aryl chlorides, but the group encompasses a wide range of derivatives with diverse applications in organic synthesis, pharmaceuticals, and materials science.
Classification according to halide
Aryl fluorides
Aryl fluorides are used as synthetic intermediates, e.g. for the preparation of pharmaceuticals, pesticides, and liquid crystals.
The conversion of
is a well established route to aryl fluorides. Thus, anilines are precursors to aryl fluorides. In the classic Schiemann reaction, tetrafluoroborate is the fluoride donor:
In some cases, the fluoride salt is used:
Many commercial aryl fluorides are produced from aryl chlorides by the Halex process. The method is often used for aryl chlorides also bearing electron-withdrawing groups. Illustrative is the synthesis of 2-fluoronitrobenzene from 2-nitrochlorobenzene:[.]
Aryl chlorides
Aryl chlorides are the aryl halides produced on the largest scale commercially: 150,000 tons/y in the US alone (1994). Production levels are decreasing owing to environmental concerns. Chlorobenzenes are used mainly as solvents.
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Friedel-Crafts halogenation or "direct chlorination" is the main synthesis route. Lewis acids, e.g. iron(III) chloride, catalyze the reactions. The most abundantly produced aryl halide, chlorobenzene, is produced by this route:
Monochlorination of benzene is accompanied by formation of the dichlorobenzene derivatives.[ Arenes with electron donating groups react with halogens even in the absence of Lewis acids. For example, phenols and anilines react quickly with chlorine and bromine water to give multihalogenated products. Many detailed laboratory procedures are available.]
The oxychlorination of benzene has been well investigated, motivated by the avoidance of HCl as a coproduct in the direct halogenation:
This technology is not widely used however.
The Gatterman reaction can also be used to convert diazonium salts to chlorobenzenes using copper-based reagents. Owing to high cost of , this method is reserved for specialty chlorides.
Aryl bromides
The main aryl bromides produced commercially are tetrabromophthalic anhydride, decabromodiphenyl ether, and tetrabromobisphenol-A. These materials are used as . They are produced by direct bromination of and aryl ethers. Phthalic anhydride is poorly reactive toward bromine, necessitating the use of acidic media.
The Gatterman reaction can also be used to convert diazonium salts to bromobenzenes using copper-based reagents. Owing to high cost of , this method is reserved for specialty bromides.
Aryl iodides
Synthetic aryl iodides are used as X-ray contrast agents, but otherwise these compounds are not produced on a large scale. Aryl iodides are "easy" substrates for many reactions such as cross-coupling reactions and conversion to , but they are much more expensive than the lighter, less reactive aryl chlorides and bromides.
Aryl iodides can be prepared by treating diazonium salts with iodide salts.
Aryl lithium and aryl react with iodine to give the aryl halide:
This method is applicable to the preparation of all aryl halides. One limitation is that most, but not all,
Classification according to aryl group
Halobenzenes and halobenzene derivatives
Although the term aryl halide includes halogenated derivatives of any aromatic compound, it commonly refers to halobenzenes, which are specifically halogenated derivatives of benzene. Groups of halobenzenes include fluorobenzenes, chlorobenzenes, bromobenzenes, and iodobenzenes, as well as mixed halobenzenes containing at least two different types of halogens bonded to the same benzene ring. There are also many halobenzene derivatives.
Halopyridines
Halopyridines are based on the aromatic compound pyridine.
Halogenated naphthalenes
Halogenated naphthalenes are based on naphthalene. Polychlorinated naphthalenes were used extensively from the 1930s to 1950s in cable and capacitor production, due to their insulating, hydrophobic, and flame retardant properties, but they have since been phased out for this use due to toxicity, environmental persistence, and introduction of new materials.
Aryl halides in nature
The triiodothyronine (T3) and thyroxine (T4) are aryl iodides. A tetraiodide, T4 is by electrophilic iodination of tyrosine derivative.
Many chlorinated and brominated aromatic compounds are produced by marine organisms. Chloride and bromide ions in ocean waters are the source of the halogens. Various peroxidase (e.g., bromoperoxidase) catalyze the formation of these natural aryl chlorides and bromides. Numerous are derivatives of electron-rich rings found in tyrosine, tryptophan, and various pyrroles. Some of these natural aryl halides exhibit useful medicinal properties.
Structural trends
The C-X distances for aryl halides follow the expected trend. These distances for fluorobenzene, chlorobenzene, bromobenzene, and methyl 4-iodobenzoate are 135.6(4), 173.90(23), 189.8(1), and 209.9 picometer, respectively.
Reactions
Substitution
Unlike typical alkyl halides, aryl halides typically do not participate in conventional substitution reactions. Aryl halides with electron-withdrawing groups in the ortho and para positions, can undergo SNAr reactions. For example, 2,4-dinitrochlorobenzene reacts in basic solution to give a phenol.
Unlike in most other substitution reactions, fluoride is the best leaving group, and iodide the worst.
Benzyne
When treated with strong base, some aryl halides often react via the intermediacy of . Benzyne is an intermediate in the reaction of chlorobenzene with strongly basic reagents such as potassium amide, even at −33 °C. It is also implicated in the conversion of chlorobenzene to phenol using sodium hydroxide, which requires high temperatures.
Organometallic reagent formation
Aryl halides react with metals, generally lithium or magnesium, to give organometallic derivatives that function as sources of aryl anions. By the metal–halogen exchange reaction, aryl halides are converted to aryl lithium compounds. Illustrative is the preparation of phenyllithium from bromobenzene using N-Butyllithium ( n-BuLi):
- C6H5Br + BuLi → C6H5Li + BuBr
Direct formation of , by adding the magnesium to the aryl halide in an ethereal solution, works well if the aromatic ring is not significantly deactivated by electron-withdrawing groups.
Other reactions
The halides can be displaced by strong nucleophiles via reactions involving radical anions. Alternatively aryl halides, especially the bromides and iodides, undergo oxidative addition, and thus are subject to Buchwald–Hartwig amination-type reactions.
Biodegradation
Rhodococcus phenolicus is a bacterium that degrades dichlorobenzene as sole carbon sources.
Applications
The aryl halides produced on the largest scale are chlorobenzene and the isomers of dichlorobenzene. One major but discontinued application was the use of chlorobenzene as a solvent for dispersing the herbicide Lasso. Overall, production of aryl chlorides (also naphthyl derivatives) has been declining since the 1980s, in part due to environmental concerns.
- 3 C6H5Cl + PCl3 + 6 Na → P(C6H5)3 + 6 NaCl
Some prominent herbicides are aryl chlorides.
2,4-Dichlorophenoxyacetic acid structure numbered.svg|2,4-D
Dicamba.svg|Dicamba
DDT.svg|DDT
pentachlorophenol.svg|Pentachlorophenol
Several chlorobenzene derivatives are used as and dyes..[K. Hunger. W. Herbst "Pigments, Organic" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2012. ]
Aryl bromides are widely used as fire-retardants. A prominent member is tetrabromobisphenol-A, which is prepared by direct bromination of the diphenol.
