Organobromine chemistry

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Organobromine chemistry is the study of the synthesis and properties of organobromine compounds, also called organobromides, [1] which are organic compounds that contain carbon bonded to bromine. The most pervasive is the naturally produced bromomethane.

Contents

One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.

A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact.

General properties

Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. [2]

Carbon–halogen bond strengths, or bond dissociation energies are of 115, 83.7, 72.1, and 57.6 kcal/mol for bonded to fluorine, chlorine, bromine, or iodine, respectively. [3]

The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.

Synthetic methods

From bromine

Alkenes reliably add bromine without catalysis to give the vicinal dibromides:

RCH=CH2 + Br2 → RCHBrCH2Br

Aromatic compounds undergo bromination simultaneously with evolution of hydrogen bromide. Catalysts such as AlBr3 or FeBr3 are needed for the reaction to happen on aromatic rings. Chlorine-based catalysts (FeCl3, AlCl3) could be used, but yield would drop slightly as dihalogens(BrCl) could form. The reaction details following the usual patterns of electrophilic aromatic substitution:

RC6H5 + Br2 → RC6H4Br + HBr

A prominent application of this reaction is the production of tetrabromobisphenol-A from bisphenol-A.

Free-radical substitution with bromine is commonly used to prepare organobromine compounds. Carbonyl-containing, benzylic, allylic substrates are especially prone to this reactions. For example, the commercially significant bromoacetic acid is generated directly from acetic acid and bromine in the presence of phosphorus tribromide catalyst:

CH3CO2H + Br2 → BrCH2CO2H + HBr

Bromine also converts fluoroform to bromotrifluoromethane.

From hydrogen bromide

Hydrogen bromide adds across double bonds to give alkyl bromides, following the Markovnikov rule:

RCH=CH2 + HBr → RCHBrCH3

Under free radical conditions, the direction of the addition can be reversed. Free-radical addition is used commercially for the synthesis of 1-bromoalkanes, precursors to tertiary amines and quaternary ammonium salts. 2-Phenethyl bromide (C6H5CH2CH2Br) is produced via this route from styrene.

Hydrogen bromide can also be used to convert alcohols to alkyl bromides. This reaction, that must be done under low temperature conditions, is employed in the industrial synthesis of allyl bromide:

HOCH2CH=CH2 + HBr → BrCH2CH=CH2 + H2O

Methyl bromide, another fumigant, is generated from methanol and hydrogen bromide.

From bromide salts

Bromide ions, as provided by salts like sodium bromide, function as a nucleophiles in the formation of organobromine compounds by displacement. [4]

An example of this salt mediated bromide displacement is the use of Copper(II) bromide on ketones: [5] [6]

R-CO-CH2-R' + 2 CuBr2 → R-CO-CHBr-R' + 2 CuBr + HBr

Applications

Structure of three industrially significant organobromine compounds. From left: ethylene bromide, bromoacetic acid, and tetrabromobisphenol-A. ImpCBr.png
Structure of three industrially significant organobromine compounds. From left: ethylene bromide, bromoacetic acid, and tetrabromobisphenol-A.

Fire-retardants

Organobromine compounds are widely used as fire-retardants. [7] The most prominent member is tetrabromobisphenol-A (4,4'-(1-methylethylidene)bis-(2,6-di-bromophenol), see figure). It and tetrabromophthalic anhydride are precursors to polymers wherein the backbone features covalent carbon-bromine bonds. Other fire retardants, such as hexabromocyclododecane and the bromodiphenyl ethers, are additives and are not chemically attached to the material they protect. The use of organobromine fire-retardants is growing but is also controversial because they are persistent pollutants.

Fumigants and biocides

Ethylene bromide, obtained by addition of bromine to ethylene, was once of commercial significance as a component of leaded gasoline. It was also a popular fumigant in agriculture, displacing 1,2-dibromo-3-chloropropane ("DBCP"). Both applications are declining owing to environmental and health considerations. Methyl bromide is also an effective fumigant, but its production and use are controlled by the Montreal Protocol. Growing in use are organobromine biocides used in water treatment. Representative agents include bromoform and dibromodimethylhydantoin (“DBDMH”). [7] Some herbicides, such as bromoxynil, contain also bromine moieties. Like other halogenated pesticides, bromoxynil is subject to reductive dehalogenation under anaerobic conditions, and can be debrominated by organisms originally isolated for their ability to reductively dechlorinate phenolic compounds. [8]

Dyes

Many dyes contain carbon-bromine bonds. The naturally occurring Tyrian purple (6,6’-dibromoindigo) was a valued dye before the development of the synthetic dye industry in the late 19th century. Several brominated anthroquinone derivatives are used commercially. Bromothymol blue is a popular indicator in analytical chemistry.

Pharmaceuticals

Commercially available organobromine pharmaceuticals include the vasodilator nicergoline, the sedative brotizolam, the anticancer agent pipobroman, and the antiseptic merbromin. Otherwise, organobromine compounds are rarely pharmaceutically useful, in contrast to the situation for organofluorine compounds. Several drugs are produced as the bromide (or equivalents, hydrobromide) salts, but in such cases bromide serves as an innocuous counterion of no biological significance. [7]

Designer drugs

Organobromine compounds such as 4-bromomethcathinone have appeared on the designer drug market alongside other halogenated amphetamines and cathinones in an attempt to circumvent existing drug laws.[ citation needed ]

In nature

Organobromine compounds are the most common organohalides in nature. Even though the concentration of bromide is only 0.3% of that for chloride in sea water, organobromine compounds are more prevalent in marine organisms than organochlorine derivatives. Their abundance reflects the easy oxidation of bromide to the equivalent of Br+, a potent electrophile. The enzyme vanadium bromoperoxidase, one of a larger family of bromoperoxidases, catalyzes this reaction in the marine environment. [9] The oceans are estimated to release 1–2 million tons of bromoform and 56,000 tons of bromomethane annually. [10] Red algae, such as the edible Asparagopsis taxiformis , eaten in Hawaii as "limu kohu", concentrate organobromine and organoiodine compounds in "vesicle cells"; 95% of the essential volatile oil of Asparagopsis, prepared by drying the seaweed in a vacuum and condensing using dry ice, is organohalogen compounds, of which bromoform comprises 80% by weight. [11] Bromoform, produced by several algae, is a known toxin, though the small amounts present in edible algae do not appear to pose human harm. [12]

Some of these organobromine compounds are employed in a form of interspecies "chemical warfare". In mammals, eosinophil peroxidase, important for defense against multicellular parasites, uses bromide ion in preference to chloride ion. 5-Bromouracil and 3-Bromo-tyrosine have been identified in human white blood cells as products of myeloperoxidase-induced halogenation on invading pathogens. [13]

Structure of some naturally-occurring organobromine compounds. From left: bromoform, a brominated bisphenol, dibromoindigo (Tyrian purple), and the antifeedant tambjamine B. NatCBr.png
Structure of some naturally-occurring organobromine compounds. From left: bromoform, a brominated bisphenol, dibromoindigo (Tyrian purple), and the antifeedant tambjamine B.

In addition to conventional brominated natural products, a variety of organobromine compounds result from the biodegradation of fire-retardants. Metabolites include methoxylated and hydroxylated aryl bromides as well as brominated dioxin derivatives. Such compounds are considered persistent organic pollutants and have been found in mammals.

Safety

Alkyl bromine compounds are often alkylating agents and the brominated aromatic derivatives are implicated as hormone disruptors. Of the commonly produced compounds, ethylene dibromide is of greatest concern as it is both highly toxic and highly carcinogenic.

See also

Related Research Articles

<span class="mw-page-title-main">Bromine</span> Chemical element, symbol Br and atomic number 35

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.

<span class="mw-page-title-main">Haloalkane</span> Group of chemical compounds derived from alkanes containing one or more halogens

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, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species replaces a functional group within another electron-deficient molecule. The molecule that contains the electrophile and the leaving functional group is called the substrate.

<span class="mw-page-title-main">1,2-Dibromoethane</span> Chemical compound

1,2-Dibromoethane, also known as ethylene dibromide (EDB), is an organobromine compound with the chemical formula C
2
H
4
Br
2
. Although trace amounts occur naturally in the ocean, where it is probably formed by algae and kelp, it is mainly synthetic. It is a dense colorless liquid with a faint, sweet odor, detectable at 10 ppm, and is a widely used and sometimes-controversial fumigant. The combustion of 1,2-dibromoethane produces hydrogen bromide gas that is significantly corrosive.

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 aryl halide 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.

<span class="mw-page-title-main">Hydrogen bromide</span> Chemical compound

Hydrogen bromide is the inorganic compound with the formula HBr. It is a hydrogen halide consisting of hydrogen and bromine. A colorless gas, it dissolves in water, forming hydrobromic acid, which is saturated at 68.85% HBr by weight at room temperature. Aqueous solutions that are 47.6% HBr by mass form a constant-boiling azeotrope mixture that boils at 124.3 °C (255.7 °F). Boiling less concentrated solutions releases H2O until the constant-boiling mixture composition is reached.

Organochlorine chemistry is concerned with the properties of organochlorine compounds, or organochlorides, organic compounds containing at least one covalently bonded atom of chlorine. The chloroalkane class includes common examples. The wide structural variety and divergent chemical properties of organochlorides lead to a broad range of names, applications, and properties. Organochlorine compounds have wide use in many applications, though some are of profound environmental concern, with TCDD being one of the most notorious.

A bromide ion is the negatively charged form (Br) of the element bromine, a member of the halogens group on the periodic table. Most bromides are colorless. Bromides have many practical roles, being found in anticonvulsants, flame-retardant materials, and cell stains. Although uncommon, chronic toxicity from bromide can result in bromism, a syndrome with multiple neurological symptoms. Bromide toxicity can also cause a type of skin eruption, see potassium bromide. The bromide ion has an ionic radius of 196 pm.

<span class="mw-page-title-main">Carbon tetrabromide</span> Chemical compound

Carbon tetrabromide, CBr4, also known as tetrabromomethane, is a bromide of carbon. Both names are acceptable under IUPAC nomenclature.

<span class="mw-page-title-main">1-Bromobutane</span> Chemical compound

1-Bromobutane is the organobromine compound with the formula CH3(CH2)3Br. It is a colorless liquid, although impure samples appear yellowish. It is insoluble in water, but soluble in organic solvents. It is primarily used as a source of the butyl group in organic synthesis. It is one of several isomers of butyl bromide.

Cyanogen bromide is the inorganic compound with the formula (CN)Br or BrCN. It is a colorless solid that is widely used to modify biopolymers, fragment proteins and peptides, and synthesize other compounds. The compound is classified as a pseudohalogen.

<span class="mw-page-title-main">Hypobromous acid</span> Chemical compound

Hypobromous acid is a weak, unstable acid with chemical formula of HOBr. It is mainly produced and handled in an aqueous solution. It is generated both biologically and commercially as a disinfectant. Salts of hypobromite are rarely isolated as solids.

<span class="mw-page-title-main">Vanadium bromoperoxidase</span>

Vanadium bromoperoxidases are a kind of enzymes called haloperoxidases. Its primary function is to remove hydrogen peroxide which is produced during photosynthesis from in or around the cell. By producing hypobromous acid (HOBr) a secondary reaction with dissolved organic matter, what results is the bromination of organic compounds that are associated with the defense of the organism. These enzymes produce the bulk of natural organobromine compounds in the world.

Tin(II) bromide is a chemical compound of tin and bromine with a chemical formula of SnBr2. Tin is in the +2 oxidation state. The stability of tin compounds in this oxidation state is attributed to the inert pair effect.

Bromine compounds are compounds containing the element bromine (Br). These compounds usually form the -1, +1, +3 and +5 oxidation states. Bromine is intermediate in reactivity between chlorine and iodine, and is one of the most reactive elements. Bond energies to bromine tend to be lower than those to chlorine but higher than those to iodine, and bromine is a weaker oxidising agent than chlorine but a stronger one than iodine. This can be seen from the standard electrode potentials of the X2/X couples (F, +2.866 V; Cl, +1.395 V; Br, +1.087 V; I, +0.615 V; At, approximately +0.3 V). Bromination often leads to higher oxidation states than iodination but lower or equal oxidation states to chlorination. Bromine tends to react with compounds including M–M, M–H, or M–C bonds to form M–Br bonds.

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<span class="mw-page-title-main">Bromide peroxidase</span> Family of enzymes

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Tetrabromo-<i>o</i>-xylene Chemical compound

α,α,α',α'-Tetrabromo-o-xylene is an organobromine compound with the formula C6H4(CHBr2)2. Three isomers of α,α,α',α'-Tetrabromoxylene exist, but the ortho derivative is most widely studied. It is an off-white solid. The compound is prepared by the photochemical reaction of o-xylene with elemental bromine:

References

  1. Matson, Michael; Orbaek, Alvin W. (2013-06-04). "Chapter 12: The Main Groups § (Re)Active Singles: The Group 17 Halogens § Briny bromine". Inorganic Chemistry For Dummies. John Wiley & Sons. ISBN   9781118228821 . Retrieved 12 November 2016. Because [bromine is] found in seawater, marine animals developed techniques for converting it to other forms; for example, organobromides (compounds with carbon and bromine) are made by sponges, corals, seaweed, and even some mammals.
  2. Saikia, Indranirekha; Borah, Arun Jyoti; Phukan, Prodeep (2016). "Use of Bromine and Bromo-Organic Compounds in Organic Synthesis". Chemical Reviews. 116 (12): 6837–7042. doi:10.1021/acs.chemrev.5b00400. PMID   27199233.
  3. Blanksby SJ, Ellison GB (April 2003). "Bond dissociation energies of organic molecules". Acc. Chem. Res. 36 (4): 255–63. CiteSeerX   10.1.1.616.3043 . doi:10.1021/ar020230d. PMID   12693923.
  4. James S. Nowick, Guido Lutterbach, “Sodium Bromide” in Encyclopedia of Reagents for Organic Synthesis John Wiley & Sons, 2001. doi : 10.1002/047084289X.rs054
  5. L. Carroll King; G. Kenneth Ostrum (1964). "Selective Bromination with Copper(II) Bromide". The Journal of Organic Chemistry. 29 (12): 3459–3461. doi:10.1021/jo01035a003.
  6. Dennis P. Bauer; Roger S. Macomber (1975). "Iodide catalysis of oxidations with dimethyl sulfoxide. Convenient two-step synthesis of .alpha. diketones from .alpha.-methylene ketones". The Journal of Organic Chemistry. 40 (13): 1990–1992. doi:10.1021/jo00901a027.
  7. 1 2 3 David Ioffe, Arieh Kampf “Bromine, Organic Compounds” in Kirk-Othmer Encyclopedia of Chemical Technology 2002 by John Wiley & Sons. doi : 10.1002/0471238961.0218151325150606.a01.
  8. Cupples, A. M., R. A. Sanford, and G. K. Sims. 2005. Dehalogenation of Bromoxynil (3,5-Dibromo-4-Hydroxybenzonitrile) and Ioxynil (3,5-Diiodino-4-Hydroxybenzonitrile) by Desulfitobacterium chlororespirans. Appl. Env. Micro. 71(7):3741-3746.
  9. Jayme N. Carter-Franklin, Alison Butler "Vanadium Bromoperoxidase-Catalyzed Biosynthesis of Halogenated Marine Natural Products" Journal of the American Chemical Society 2004, volume 126, 15060-15066. doi : 10.1021/ja047925p
  10. Gordon W. Gribble "The diversity of naturally occurring organobromine compounds" Chemical Society Reviews, 1999, volume 28, pages 335 – 346. doi : 10.1039/a900201d
  11. Rhoda A. Marshall, John T.G. Hamilton , M.J. Dring, D.B. Harper. Do vesicle cells of the red alga Asparagopsis (Falkenbergia stage) play a role in bromocarbon production? Chemosphere 52 (2003) 471–475.
  12. Agency for Toxic substances and Disease Registry. Bromoform and Dibromochloromethane. Aug 2005. URL: https://wwwn.cdc.gov/TSP/PHS/PHSLanding.aspx?id=711&tid=128
  13. Gordon W. Gribble (1998). "Naturally Occurring Organohalogen Compounds". Acc. Chem. Res. 31 (3): 141–152. doi:10.1021/ar9701777.