Bromine reaction with benzene derivatives

Cyanide and thiocyanate anions in aqueous solution can be determined as cyanogen bromide after reaction with bromine [686]. The thiocyanate anion can be quantitatively determined in the presence of cyanide by adding an excess of formaldehyde solution to the sample, which converts the cyanide ion to the unreactive cyanohydrin. The detection limits for the cyanide and thiocyanate anions were less than 0.01 ppm with an electron-capture detector. Iodine in acid solution reacts with acetone to form monoiodoacetone, which can be detected at high sensitivity with an electron-capture detector [687]. The reaction is specific for iodine, iodide being determined after oxidation with iodate. The nitrate anion can be determined in aqueous solution after conversion to nitrobenzene by reaction with benzene in the presence of sulfuric acid [688,689]. The detection limit for the nitrate anion was less than 0.1 ppm. The nitrite anion can be determined after oxidation to nitrate with potassium permanganate. Nitrite can be determined directly by alkylation with an alkaline solution of pentafluorobenzyl bromide [690]. The yield of derivative was about 80t.with a detection limit of 0.46 ng in 0.1 ml of aqueous sample. Pentafluorobenzyl p-toluenesulfonate has been used to derivatize carboxylate and phenolate anions and to simultaneously derivatize bromide, iodide, cyanide, thiocyanate, nitrite, nitrate and sulfide in a two-phase system using tetrapentylammonium cWoride as a phase transfer catalyst [691]. Detection limits wer Hi the ppm range. 

The first so-called aromatic compounds to be studied seriously, such as vanillin (derived from vanilla), had two obvious properties. They had a sweet smell and were remarkably stable. This last property was the reef on which many of the early theories of chemical bonding foundered. Consider benzene. Kekule knew that its molecular formula was C H. The only way he could rationalise this formula with the known properties of benzene, was to imagine the six carbon atoms joined in a ring and connected by three alternate double bonds. This is where the trouble started because double bonds are supposed to confer reactivity on an organic molecule benzene is stable. Double bonds can readily be added to for example, they will undergo fast reactions with bromine and sulphuric acid to give simple "addition" compounds. The reagents simply "add" across the double bond. 

The use of acetic anhydride for the acetylation of phenols has been described in some papers [86,87]. Determination of chlorophenols in freshwater, wastewater, and seawater using acetylation and BCD was reported by Abrahamsson and Xie [87]. They compared two derivatization procedures, pentafluorobenzoylation versus acetylation, and concluded that the acetylated derivatives gave better separation on the capillary column. Derivatization using heptafluorobutyryl in combination with GC-BCD [88] involves an extraction of the acidified sample into benzene before derivatization. Another method describes the conversion of eight phenols (phenol, cresols, and xylenols) into corresponding bromophenols after reaction with bromine followed by an analysis using GC-BCD [91 ]. 

Dibromothiophene and also monobromothiophene were both obtained directly from the benzene fraction of coal tar by its reaction with bromine. It is significant that the preparation of bromo derivatives was very soon developed on a multigram scale at the Farbwerke Hoechst AG. From 1 kg of raw benzene fraction, 360 g of pure 2,5-dibromothiophene could be produced together with some monobromothiophene [78]. 

A point in case is provided by the bromination of various monosubstituted benzene derivatives it was realized that substituents with atoms carrying free electron pairs bonded directly to the benzene ring (OH, NH2, etc) gave 0- and p-substituted benzene derivatives. Furthermore, in all cases except of the halogen atoms the reaction rates were higher than with unsubstituted benzene. On the other hand, substituents with double bonds in conjugation with the benzene ring (NO2, CHO, etc.) decreased reaction rates and provided m-substituted benzene derivatives. 

Let us illustrate this with the example of the bromination of monosubstituted benzene derivatives. Observations on the product distributions and relative reaction rates compared with unsubstituted benzene led chemists to conceive the notion of inductive and resonance effects that made it possible to explain" the experimental observations. On an even more quantitative basis, linear free energy relationships of the form of the Hammett equation allowed the estimation of relative rates. It has to be emphasized that inductive and resonance effects were conceived, not from theoretical calculations, but as constructs to order observations. The explanation" is built on analogy, not on any theoretical method. 

The classification of hydrocar bons as aliphatic or ar omatic took place in the 1860s when it was aheady apparent that there was something special about benzene, toluene, and their- derivatives. Their molecular- for-mulas (benzene is CgHg, toluene is CyKj ) indicate that, like alkenes and alkynes, they are unsaturated and should undergo addition reactions. Under conditions in which bromine, for example, reacts rapidly with alkenes and alkynes, however, benzene proved to be inert. Benzene does react with Br-2 in the presence of iron(III) bromide as a catalyst, but even then addition isn t observed. Substitution occurs instead ... 

Reaction of 9-vinylcarbazole with bromine in benzene or ethanol gave the 3,6-dibromo derivative [84AHC(35)83]. Pyridinium bromide perbro-mide gave a 72% yield of the 3-bromo derivative of 2,4-dimethoxycarba-zole. With other reagents mixtures of 3- and 5-bromo-, 3,5- and 3,7-dibromo products were formed. The 5-bromo- and 3,6-dibromo- compounds rearranged quantitatively to the 3- and 3,7-isomers [92JCR(S)2]. 

The bromine atoms in 2,5-dibromo-l,3,4-thiadiazole 54 undergo a palladium-catalyzed Stille reaction with the organostannyl derivative 55 (Equation 7) <1998CEJ2211>. The thiadiazole 54 was co-polymerized with diethynyl benzene 56 (Equation 8) and diethynyl pyrrole in a Sonogashira cross-coupling reaction <2005MM4687>. 

Quinoxalines substituted in the 5- or 6-position generally follow the pattern of reactions expected for substituted benzene derivatives, although recently there have been reports of interesting and unexpected reactions with nucleophiles (see Section III, A,2 and references 85-90). 6-Methylquinoxaline is brominated in the side chain when treated with N-bromosuccinimide in carbon tetrachloride in the presence of azobisiso-butyronitrile, to form 6-bromomethylquinoxaline.182... 

Two excellent reviews <71AHC(13)235, 72IJS(C)(7)6l) have dealt with quantitative aspects of electrophilic substitution on thiophenes. Electrophilic substitution in the thiophene ring appears to proceed in most cases by a mechanism similar to that for the homocyclic benzene substrates. The first step involves the formation of a cr-complex, which is rate determining in most reactions in a few cases the decomposition of this intermediate may be rate determining. Evidence for the similarity of mechanism in the thiophene and benzene series stems from detailed kinetic studies. Thus in protodetritiation of thiophene derivatives in aqueous sulfuric and perchloric acids, a linear correlation between log k and —Ho has been established the slopes are very close to those reported for hydrogen exchanges in benzene derivatives. Likewise, the kinetic profile of the reaction of thiophene derivatives with bromine in acetic acid in the dark is the same as for bromination of benzene derivatives. The activation enthalpies and entropies for bromination of thiophene and mesitylene are very similar. 

The presence of the hydroxyl group in phenols facilitates the substitution of the nuclear hydrogen atoms by halogen the number and position of the substituent atoms varies with the nature of the phenol. This method is an indirect means of identification, as the formation of a substitution derivative is not a characteristic reaction of the phenol group but of the benzene nucleus. Phenol reacts with bromine to give 2,4,6-tribromophenol ... 

Bromination of 14 is achieved by reaction with three equiv of W-bromo-succinimide in boiling benzene under light irradiation. This reaction gives a mixture of the desired tribromide derivative 15a and also the dibromide and tetrabromide derivatives, 15b and 15c respectively (Scheme 9.12). The separation of these compounds is very difficult, and so the mixture is best used without purification for the next step. The experimental procedure is given in Protocol 10. 

As noted above, the first definition of "aromaticity" was in terms of substitution rather than addition. This is certainly true for many benzene derivatives. However, it must be used with some care since thiophene is by most criteria about as "aromatic" as benzene, but when treated with chlorine or bromine it gives an addition product. The latter is, however, the kinetically controlled product, for when heated or treated with base it loses hydrogen halide and gives the 2-halothiophene.20 Compounds such as anthracene and phenanthrene, which are recognized as having considerable resonance stabilization, also undergo addition reactions. 

---