Organobromine chemistry
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.
One prominent application of synthetic organobromine compounds is the use of
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
Carbon–
The reactivity of organobromine compounds resembles but is intermediate between the reactivity of
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
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
- 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.
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
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
R-CO-CH2-R' + 2 CuBr2 → R-CO-CHBr-R' + 2 CuBr + HBr
Applications
Fire-retardants
Organobromine compounds are widely used as fire-retardants.
Fumigants and biocides
Dyes
Many dyes contain carbon-bromine bonds. The naturally occurring
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
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]
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
- Organofluorine compounds
- Organochlorine compounds
- Organoiodine compounds
References
- 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.
- PMID 27199233.
- PMID 12693923.
- .
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- ^ .
- ^ 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.
- doi:10.1039/a900201d
- ^ 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.
- ^ 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
- .