Bromination of furans

An examination of the products formed by bromination of furan disclosed only addition. These were very unstable and could not be isolated but NMR analyses showed that both 2,5-dibromo-2,5-dihydrofuran (cis and trans) and 2,3-dibromo-2,3-dihydrofuran (trans only) were formed. Eventually only 2-bromofuran is left, but whether the additions are side equilibria or genuine stages on the way to the substitution product is not yet known.148... 

Bromination of pyrrole with bromine gives mainly the thermodynamically more stable 3-bromo derivative, which is produced from the 2-isomer, formed initially under kinetic control, through isomerization catalyzed by the reaction product HBr. If N-bromosuccinimide is used for bromination, no HBr is produced and the 2-isomer dominates (8IJOC222I). Bromination of furan gave cis- and frans-2,5,-dibromo-2,5-dihydrofurans (isolated as the dimethoxy derivatives) in a ratio of 3 I (67BCJ130). A spectroscopic study carried out at low temperature (- 50°C) confirmed this ratio and also showed that 20% of trans-2,3-dibro-mo-2,3-dihydrofuran was formed (75CC875). It is not known whether these adducts (which demonstrate the competition between 1,4- and 1,2-addition) are intermediates along the pathway for bromine substitution, or whether they are produced in a separate equilibrium as is the case for bromination of benzo[6]furan. 

Af-Bromosuccinimide has also been used for the bromination of furan derivatives e.g., 2-furoic ester is converted into the 5-bromo derivative (15% yield) but furan itself resiniiies. 

Determine the mechanism of bromination of furan at C2, assuming that it proceeds via Brh... 

The oxidative reaction of furan with bromine in methanol solution or an electrochemical process using sodium bromide produces 2,5-dimethoxy-2,5-dihydrofuran (19), which is a cycHc acetal of maleic dialdehyde. The double bond in (19) can be easily hydrogenated to produce the corresponding succindialdehyde derivative. Both products find appHcation in photography and as embalming materials, as well as other uses. 

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

Furan reacts vigorously with chlorine and bromine at room temperature to give poly-halogenated products. Low temperature (-40 °C) reaction of furan with chlorine in dichloromethane yields mainly 2-chlorofuran and reaction of furan with dioxane dibromide at 0 °C affords 2-bromofuran in good yield. 2-Iodofuran is obtained by treatment of 2-furoic acid with iodine and potassium iodide in aqueous sodium hydroxide. 

The 2,5-dialkoxy-2,5-dihydrofurans can be obtained by electrolytic oxidation of furan in alcoholic ammonium bromide or by bromine oxidation of furan in the appropriate alcohol. ... 

Using these assumptions and conventions, Imoto and co-workers have correlated a number of series of reactions of thiophenes and furans. The reactions studied are the acid-base equilibria pK values) and the acid catalyzed methylations (thiophenes only) of thiophene-and furan-carboxylic acids and the alkaline hydrolyses of their ethyl esters the side-chain bromination of the a-acetylthiophenes, and the a-mercuration of thiophenes and the polarographic half-wave potentials of the methyl esters of thiophene- and furan-carboxylic acids and of nitrothiophenes. The pK values were determined and the ester hydrolyses studied for all three substitution orientations in the thiophene series. For the 4-R-2-Y and 5-R-2-Y series, the p-values do not appear significantly different and the data could probably be combined into a single series unfortunately, however, no limits of accuracy are reported for the p-values, and some of the raw data are not readily available so recalculation is not easily possible. For the 5-R-3-Y series the p-values deviate considerably from the other values however, whereas they are higher for the pK values, they are lower for the ester hydrolyses, and it is possible that the differences are neither systematic nor significant. 

Quaternary ammonium tribromides in methanol-dichloromethane did not brominate the furan ring of 3-methyl-8//-cyclohepta[/>]furan-8-one. Instead, the 7-bromo derivative was formed (92BCJ295). 

Bromination of 4//-furo[3,2-b]indole (50) occurred at the 2-position and was assisted by prior N-benzylation with the 4-benzoyl compound a 61% yield of the 2-bromo derivative was obtained. Thus, a-attack in the furan moiety predominates (78JHC123). When the pyrazolofuran (51) was treated with one molar equivalent of bromine, a mixture of the 2-bromo... 

Treatment of 6-(2 -furanyl)imidazo[2,l-b]thiazole (65) with bromine in chloroform gave rise to products of bromination of both furan and imidazole moieties (80MI1). In the unsubstituted imidazothiazole, bromination in dimethylformamide at 80°C, or in dichloromethane at 0°C, occurred in the 5-position. Even when there are such reactive groups as 2 -furanyl or... 

Aromatic bromine compounds can be formed and transformed during various thermal processes, like aromatic chlorine compounds (ref. 22). Brominated dibenzodioxins and -furans and mixed brominated/chlorinated compounds have been detected in trace levels in the fly ash of a municipal waste incinerator (ref. 23).Chlorine is generally abundant compared to the bromine of typical municipal waste the chlorine vs. bromine ratio is in the range of 250 1. 

Anodic hydroxylation/methoxylation of furans has an exact chemical counterpart in the well-known bromine/methanol reaction, and the choice of method is not always easily made. One can compare the two methods particularly easily in syntheses of the flavoring component, the pyrone maltol 121, from the furan 122 since one group used the electrolytic method299 and another the chemical method.300... 

A divergent protocol for a solid-phase synthesis of 3-substituted 2,5-biarylfurans was reported. Thus, reaction of furan zincate A with polymer bound aryl bromide or iodide provides resin intermediates 61. Subsequent bromination-Suzuki coupling reaction followed by further transformations gives rise to structurally diverse 2,3,5-trisubstituted furans 68 in good overall yields and chemical purities <00TL5447>. 

In a similar manner, bromine has been employed as an oxidant for glucose to calcium gluconate [132] and for the methoxylation of furan [133] (Eq. 11). 

A number of N-brominated and N-chlorinated heterocycles also provide sources of electrophilic bromine. Examples include 1-chlorobenzotriazole (82JOC4895 87JOC173 88CHE36) and various HBr and Br2 adducts of pyridines, or pyridine perbromides [84SC939 85JAP(K)60/87264], Polymer-supported reagents of this type include 1-cyclohexylpyridinium perbromide linked to polystyrene, effective for the bromination of 1-methylindole, benzo[fc]furan, and benzo[6]thiophene (89T7869). 

The presence of at least one electron-withdrawing group in the furan ring makes monobromination a much more viable process. Considerable study has been made of the bromination of 2-acylfurans, especially in the presence of Lewis acid catalysts. A kinetic study of the bromination of 2-formylfuran in aqueous medium showed that the reaction is first order in each reactant and pH-independent, and influenced by bromide ion concentration (83MI1). In contrast to the analogous acylthiophenes and acylselenophenes, 2-acetylfuran was hydrolyzed when treated with bromine in the presence of sodium acetate (81SC29). 

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