In organic chemistry, an aryl halide (also known as haloarene) is an aromatic compound in which one or more hydrogen atoms, directly bonded to an aromatic ring are replaced by a halide. The haloarene are different from haloalkanes because they exhibit many differences in methods of preparation and properties. The most important members are the aryl chlorides, but the class of compounds is so broad that there are many derivatives and applications.
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. [1]
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: [2]
Monochlorination of benzene is accompanied by formation of the dichlorobenzene derivatives. [1] 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. [3] For alkylbenzene derivatives, e.g. toluene, the alkyl positions tend to be halogenated by free radical conditions, whereas ring halogenation is favored in the presence of Lewis acids. [4] The decolouration of bromine water by electron-rich arenes is used in the bromine test.
The oxychlorination of benzene has been well investigated, motivated by the avoidance of HCl as a coproduct in the direct halogenation: [1]
This technology is not widely used however.
The Gatterman reaction can also be used to convert diazonium salts to chlorobenzenes using using copper-based reagents. Owing to high cost of diazonium salts, this method is reserved for specialty chlorides.
The main aryl bromides produced commercially are tetrabromophthalic anhydride, decabromodiphenyl ether, and tetrabromobisphenol-A. These materials are used as flame retardants. They are produced by direct bromination of phenols 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 using copper-based reagents. Owing to high cost of diazonium salts, this method is reserved for specialty bromides.
Aryl fluorides are used as synthetic intermediates, e.g. for the preparation of pharmaceuticals, pesticides, and liquid crystals. [5] The conversion of diazonium salts 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: [6]
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 Grignard reagents, but they much more expensive than the lighter, less reactive aryl chlorides and bromides.
Aryl iodides can be prepared by treating diazonium salts with iodide salts. [7] Electron-rich arenes such as anilines and dimethoxy derivatives react directly with iodine. [8]
Aryl lithium and aryl Grignard reagents 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, [9] aryl lithium and Grignard reagents are produced from aryl halides.
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. There are also many halobenzene derivatives.
Halopyridines are based on the aromatic compound pyridine. [10] This includes chloropyridines and bromopyridines. Chloropyridines are important intermediates to pharmaceuticals and agrochemicals.
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. [1]
The thyroxin hormone T3 is an aryl iodide. Its biosynthetic precursor T4 is one of the most prescribed medications. A tetraiodide, T4, is produced by electrophilic iodination of tyrosine derivative. [11] Synthetic T4 is one of the most heavily prescribed medicines in the U.S.. [12]
Many chlorinated and brominated aromatic compounds are produced by marine organisms. The chloride and bromide in ocean waters are the source of the halogens. Various peroxidase enzymes (e.g., bromoperoxidase catalyze the reactions. Numerous are derivatives of electron-rich rings found in tyrosine, tryptophan, and various pyrroles. Some of these natural aryl halides exhibit useful medicinal properties. [13] [14]
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 pm, respectively. [15]
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. [16] A 2018 paper indicates that this situation may actually be rather common, occurring in systems that were previously assumed to proceed via SNAr mechanisms. [17]
Aryl halides often react via the intermediacy of benzynes. Chlorobenzene and sodium amide react in liquid ammonia to give aniline by this pathway.
Aryl halides react with metals, generally lithium or magnesium, to give more 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 phenyl lithium from bromobenzene using butyl lithium (BuLi):
Direct formation of Grignard reagents, 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.
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.
Chlorobenzene was once the precursor to phenol, which is now made by oxidation of cumene. At high temperatures, aryl groups react with ammonia to give anilines. [1]
Rhodococcus phenolicus is a bacterium that degrade dichlorobenzene as sole carbon sources. [18]
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. [1] Triphenylphosphine is produced from chlorobenzene:
Aryl bromides are widely used as fire-retardants. The most prominent member is tetrabromobisphenol-A, which is prepared by direct bromination of the diphenol. [19]
In chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine.
Bromine is a chemical element; it has symbol Br and atomic number 35. It is a volatile red-brown liquid at room temperature that evaporates readily to form a similarly coloured vapour. Its properties are intermediate between those of chlorine and iodine. Isolated independently by two chemists, Carl Jacob Löwig and Antoine Jérôme Balard, its name was derived from the Ancient Greek βρῶμος (bromos) meaning "stench", referring to its sharp and pungent smell.
The halogens are a group in the periodic table consisting of six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), and the radioactive elements astatine (At) and tennessine (Ts), though some authors would exclude tennessine as its chemistry is unknown and is theoretically expected to be more like that of gallium. In the modern IUPAC nomenclature, this group is known as group 17.
The haloalkanes are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely used commercially. They are used as flame retardants, fire extinguishants, refrigerants, propellants, solvents, and pharmaceuticals. Subsequent to the widespread use in commerce, many halocarbons have also been shown to be serious pollutants and toxins. For example, the chlorofluorocarbons have been shown to lead to ozone depletion. Methyl bromide is a controversial fumigant. Only haloalkanes that contain chlorine, bromine, and iodine are a threat to the ozone layer, but fluorinated volatile haloalkanes in theory may have activity as greenhouse 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, see Halomethane. 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.
In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, drugs. This kind of conversion is in fact so common that a comprehensive overview is challenging. This article mainly deals with halogenation using elemental halogens. Halides are also commonly introduced using salts of the halides and halogen acids. Many specialized reagents exist for and introducing halogens into diverse substrates, e.g. thionyl chloride.
In organic chemistry, an acyl halide is a chemical compound derived from an oxoacid by replacing a hydroxyl group with a halide group.
The Stille reaction is a chemical reaction widely used in organic synthesis. The reaction involves the coupling of two organic groups, one of which is carried as an organotin compound (also known as organostannanes). A variety of organic electrophiles provide the other coupling partner. The Stille reaction is one of many palladium-catalyzed coupling reactions.
The Sandmeyer reaction is a chemical reaction used to synthesize aryl halides from aryl diazonium salts using copper salts as reagents or catalysts. It is an example of a radical-nucleophilic aromatic substitution. The Sandmeyer reaction provides a method through which one can perform unique transformations on benzene, such as halogenation, cyanation, trifluoromethylation, and hydroxylation.
n-Butyllithium C4H9Li (abbreviated n-BuLi) is an organolithium reagent. It is widely used as a polymerization initiator in the production of elastomers such as polybutadiene or styrene-butadiene-styrene (SBS). Also, it is broadly employed as a strong base (superbase) in the synthesis of organic compounds as in the pharmaceutical industry.
Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group [R−N+≡N]X− where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide.
Thiophenol is an organosulfur compound with the formula C6H5SH, sometimes abbreviated as PhSH. This foul-smelling colorless liquid is the simplest aromatic thiol. The chemical structures of thiophenol and its derivatives are analogous to phenols. An exception is the oxygen atom in the hydroxyl group (-OH) bonded to the aromatic ring is replaced by a sulfur atom. The prefix thio- implies a sulfur-containing compound and when used before a root word name for a compound which would normally contain an oxygen atom, in the case of 'thiol' that the alcohol oxygen atom is replaced by a sulfur atom.
The Finkelstein reaction, named after the German chemist Hans Finkelstein, is an SN2 reaction that involves the exchange of one halogen atom for another. It is an equilibrium reaction, but the reaction can be driven to completion by exploiting the differential solubility of halide salts, or by using a large excess of the halide salt.
Bromobenzenes are a group of aryl bromides/halobenzenes consisting of one or more bromine atoms as substituents on a benzene core. They have the formula C6H6–nBrn, where n = 1–6 is the number of bromine atoms. Depending on the number of bromine substituents, there may be several constitutional isomers possible.
Organozinc chemistry is the study of the physical properties, synthesis, and reactions of organozinc compounds, which are organometallic compounds that contain carbon (C) to zinc (Zn) chemical bonds.
In inorganic chemistry, sulfonyl halide groups occur when a sulfonyl functional group is singly bonded to a halogen atom. They have the general formula RSO2X, where X is a halogen. The stability of sulfonyl halides decreases in the order fluorides > chlorides > bromides > iodides, all four types being well known. The sulfonyl chlorides and fluorides are of dominant importance in this series.
Organocopper chemistry is the study of the physical properties, reactions, and synthesis of organocopper compounds, which are organometallic compounds containing a carbon to copper chemical bond. They are reagents in organic chemistry.
The Balz–Schiemann reaction is a chemical reaction in which a primary aromatic amine is transformed to an aryl fluoride via a diazonium tetrafluoroborate intermediate. This reaction is a traditional route to fluorobenzene and some related derivatives, including 4-fluorobenzoic acid.
A cyanogen halide is a molecule consisting of cyanide and a halogen. Cyanogen halides are chemically classified as pseudohalogens.
Trifluoromethylation in organic chemistry describes any organic reaction that introduces a trifluoromethyl group in an organic compound. Trifluoromethylated compounds are of some importance in pharmaceutical industry and agrochemicals. Several notable pharmaceutical compounds have a trifluoromethyl group incorporated: fluoxetine, mefloquine, Leflunomide, nulitamide, dutasteride, bicalutamide, aprepitant, celecoxib, fipronil, fluazinam, penthiopyrad, picoxystrobin, fluridone, norflurazon, sorafenib and triflurazin. A relevant agrochemical is trifluralin. The development of synthetic methods for adding trifluoromethyl groups to chemical compounds is actively pursued in academic research.
In organometallic chemistry, metal–halogen exchange is a fundamental reaction that converts an organic halide into an organometallic product. The reaction commonly involves the use of electropositive metals and organochlorides, bromides, and iodides. Particularly well-developed is the use of metal–halogen exchange for the preparation of organolithium compounds.